Fine-scale movement response of juvenile brown trout to hydropeaking.

Juvenile fish are known to be the most impacted during hydropeaking events due to stranding or uncontrolled drift resulting from changes to water depth and flow velocity. To shed light on their response to such hydraulic alterations, we coupled flume experiments with image-based fish tracking and quantified the fine-scale movement behavior of wild (n = 30) and hatchery-reared (n = 38) brown trout (Salmo trutta) parr. We exposed fish to two distinct hydropeaking treatments in a laterally inclined (14 %) flume section stocked with real cobbles to create refuge and heterogeneous hydraulic conditions. Fish were individually acclimated (20 min) to baseflow (Q = 1.6 L s-1) and then exposed to three consecutive hydropeaking events, reaching peakflows tenfold larger than baseflow (Q = 16 L s-1). We found that, within just minutes, fish exhibited fine-scale movement responses to cope with the change of hydrodynamic conditions. Fish moved perpendicular to the main flow direction to shallow areas as these became submerged during discharge increase, holding position at low velocity zones. This resulted in a significant difference (p < 0.001) in lateral occupancy of the experimental section between baseflow and peakflow. During peakflow, fish occupied specific positions around cobbles and exhibited swimming behaviors, including bow-riding and entraining, that allowed them to hold position while likely minimizing energy expenditure. As a result, swimming distance reduced 60-70 % compared to baseflow. During the decrease in discharge following peakflow, fish abandoned areas falling dry by moving laterally. In the treatment with the larger down-ramping rate, the time to initiate relocation was lower while the relocation speed was higher. This study shows that, for the conditions investigated here, brown trout parr is capable of swiftly deploying multiple behavioral responses to navigate rapid changes in hydrodynamic conditions. These findings can be incorporated into habitat modeling and improve our capacity to inform hydropeaking mitigation efforts.

Polyoxometalate inhibition of SOX2-mediated tamoxifen resistance in breast cancer.

BACKGROUND: Increased cancer stem cell (CSC) content and SOX2 overexpression are common features in the development of resistance to therapy in hormone-dependent breast cancer, which remains an important clinical challenge. SOX2 has potential as biomarker of resistance to treatment and as therapeutic target, but targeting transcription factors is also challenging. Here, we examine the potential inhibitory effect of different polyoxometalate (POM) derivatives on SOX2 transcription factor in tamoxifen-resistant breast cancer cells. METHODS: Various POM derivatives were synthesised and characterised by infrared spectra, powder X-ray diffraction pattern and nuclear magnetic resonance spectroscopy. Estrogen receptor (ER) positive breast cancer cells, and their counterparts, which have developed resistance to the hormone therapy tamoxifen, were treated with POMs and their consequences assessed by gel retardation and chromatin immunoprecipitation to determine SOX2 binding to DNA. Effects on proliferation, migration, invasion and tumorigenicity were monitored and quantified using microscopy, clone formation, transwell, wound healing assays, flow cytometry and in vivo chick chorioallantoic membrane (CAM) models. Generation of lentiviral stable gene silencing and gene knock-out using CRISPR-Cas9 genome editing were applied to validate the inhibitory effects of the selected POM. Cancer stem cell subpopulations were quantified by mammosphere formation assays, ALDEFLUOR activity and CD44/CD24 stainings. Flow cytometry and western blotting were used to measure reactive oxygen species (ROS) and apoptosis. RESULTS: POMs blocked in vitro binding activity of endogenous SOX2. [P2W18O62]6- (PW) Wells-Dawson-type anion was the most effective at inhibiting proliferation in various cell line models of tamoxifen resistance. 10 µM PW also reduced cancer cell migration and invasion, as well as SNAI2 expression levels. Treatment of tamoxifen-resistant cells with PW impaired tumour formation by reducing CSC content, in a SOX2-dependent manner, which led to stem cell depletion in vivo. Mechanistically, PW induced formation of reactive oxygen species (ROS) and inhibited Bcl-2, leading to the death of tamoxifen-resistant cells. PW-treated tamoxifen-resistant cells showed restored sensitivity to tamoxifen. CONCLUSIONS: Together, these observations highlight the potential use of PW as a SOX2 inhibitor and the therapeutic relevance of targeting SOX2 to treat tamoxifen-resistant breast cancer.

An international study presenting a federated learning AI platform for pediatric brain tumors.

While multiple factors impact disease, artificial intelligence (AI) studies in medicine often use small, non-diverse patient cohorts due to data sharing and privacy issues. Federated learning (FL) has emerged as a solution, enabling training across hospitals without direct data sharing. Here, we present FL-PedBrain, an FL platform for pediatric posterior fossa brain tumors, and evaluate its performance on a diverse, realistic, multi-center cohort. Pediatric brain tumors were targeted due to the scarcity of such datasets, even in tertiary care hospitals. Our platform orchestrates federated training for joint tumor classification and segmentation across 19 international sites. FL-PedBrain exhibits less than a 1.5% decrease in classification and a 3% reduction in segmentation performance compared to centralized data training. FL boosts segmentation performance by 20 to 30% on three external, out-of-network sites. Finally, we explore the sources of data heterogeneity and examine FL robustness in real-world scenarios with data imbalances.

Inspiratory Muscle Training for Lung Transplant Candidates and Recipients.

OBJECTIVES: Inspiratory muscle training is used in rehabilitation to exercise respiratory muscles in various conditions associated with limited ventilatory reserve. In this review, we investigated inspiratory muscle training in lung transplant candidates and recipients. MATERIALS AND METHODS: We searched 5 primary databases from inception through April 2024. Two key word entries, "lung transplantation" and "inspiratory muscle training," were matched using the Boolean operator AND. No filters were applied for document type, age, sex, publication date, language, and subject. RESULTS AND CONCLUSIONS: The searched databases returned 119 citations. Seven articles that considered 64 patients (47% female) were included in the final analysis, with 1 study involving a pediatric patient. Lung transplant recipients used a threshold trainer at 15% to 60% of maximal inspiratory pressure and mostly exercised twice daily for 10 to 15 minutes per session. Lung transplant candidates exercised at 30% to >50% of maximal inspiratory pressure twice daily, performing 30 to 60 inspirations or for 15 minutes. The highest inspiratory muscle strength was observed in a series of adult lung transplant recipients whose mean value improved by 31.8 ± 14.6 cmH2O versus baseline after treatment. To the same extent, the highest value of maximal inspiratory pressure was detected in a pediatric patient who scored 180 cmH2O after training. Overall, participants obtained improvements in lung function (forced expiratory volume in 1 second, forced vital capacity), functional performance, dyspnea intensity, and exercise tolerance. Inspiratory muscle training is easy to perform and can be done at home without specific supervision (in adults) before or after a lung transplant. Nevertheless, additional rigorous investigations should aim to replicate the positive effects reported in the present review.

Pre-pregnancy substance use and first trimester cardiovascular health among nulliparous pregnant people: The nuMoM2b Study.

BACKGROUND: Suboptimal pre-pregnancy health, including substance use and cardiovascular risk factors, is associated with higher risks of maternal-foetal morbidity and mortality. OBJECTIVE: To determine if pre-pregnancy substance use is associated with early pregnancy cardiovascular health (CVH). It is hypothesised that pre-pregnancy use of substances is associated with worse CVH in the first trimester of pregnancy. METHODS: This is a secondary analysis from the 2010-2015 United States nuMoM2b cohort (n = 9895). Pre-pregnancy alcohol, tobacco, marijuana, and illicit substance use were assessed through questionnaires. Latent class analysis categorised participants based on their 3-month pre-pregnancy or ever(*) substance use: (1) Illicit substances*, marijuana*, and alcohol use (n = 1234); (2) marijuana* and alcohol use (n = 2066); (3) tobacco and alcohol use (n = 636); and (4) alcohol only use (n = 3194). The referent group reported no pre-pregnancy substance use (n = 2765). First trimester CVH score from 0 (least healthy) to 100 (most healthy) was calculated using a modified American Heart Association Life's Essential 8 framework and included body mass index (BMI), blood pressure, blood glucose, non-HDL cholesterol, diet, sleep, and physical activity. Multiple linear regression evaluated the relationship between pre-pregnancy substance use classes and CVH scores. RESULTS: CVH score varied by class: No substance use (mean: 65, SD: ±1.3), illicit substances*, marijuana*, and alcohol use (68 ± 1.3), marijuana* and alcohol use (67 ± 1.3), tobacco and alcohol use (62 ± 1.4), and alcohol only use (67 ± 1.3). In adjusted models, those who used tobacco and alcohol compared to the no substance use class had a lower CVH score (-2.82); other classes had scores ranging from 1.81 to 2.44 points higher than the no substance use class. Individual CVH component scores followed similar patterns. CONCLUSIONS: All groups, but most markedly those who used tobacco and alcohol prior to pregnancy, began pregnancy with only moderate CVH and may benefit from CVH promotion efforts along with substance use treatment.

Source and propagation modelling scenarios for environmental impact assessment: Model verificationa).

Evaluation of possible effects of underwater sound on aquatic life requires quantification of the sound field. A marine sound source and propagation modelling workshop took place in June 2022, whose objectives were to facilitate the evaluation of source and propagation models and to identify relevant metrics for environmental impact assessment. The scope of the workshop included model verification (model-model comparison) and model validation (model-measurement comparison) for multiple sources, including airguns, a low-frequency multi-beam echo sounder, and a surface vessel. Several verification scenarios were specified for the workshop; these are described herein.

Prognostic Significance of Hemodynamics in Patients With Transposition of the Great Arteries and Systemic Right Ventricle.

BACKGROUND: Patients with transposition of the great arteries (TGA) and systemic right ventricle often confront significant adverse cardiac events. The prognostic significance of invasive hemodynamic parameters in this context remains uncertain. Our hypothesis is that the aortic pulsatility index and hemodynamic profiling utilizing invasive measures provide prognostic insights for patients with TGA and a systemic right ventricle. METHODS: This retrospective multicenter cohort study encompasses adults with TGA and a systemic right ventricle who underwent cardiac catheterization. Data collection, spanning from 1994 to 2020, encompasses clinical and hemodynamic parameters, including measured and calculated values such as pulmonary capillary wedge pressure, aortic pulsatility index, and cardiac index. Pulmonary capillary wedge pressure and cardiac index values were used to establish 4 distinct hemodynamic profiles. A pulmonary capillary wedge pressure of ≥15 mm Hg indicated congestion, termed wet, while a cardiac index <2.2 L/min per m2 signified inadequate perfusion, labeled cold. The primary outcome comprised a composite of all-cause death, heart transplantation, or the requirement for mechanical circulatory support. RESULTS: Of 1721 patients with TGA, 242 individuals with available invasive hemodynamic data were included. The median follow-up duration after cardiac catheterization was 11.4 (interquartile range, 7.5-15.9) years, with a mean age of 38.5±10.8 years at the time of cardiac catheterization. Among hemodynamic parameters, an aortic pulsatility index <1.5 emerged as a robust predictor of the primary outcome, with adjusted hazard ratios of 5.90 (95% CI, 3.01-11.62; P<0.001). Among the identified 4 hemodynamic profiles, the cold/wet profile was associated with the highest risk for the primary outcome, with an adjusted hazard ratio of 3.83 (95% CI, 1.63-9.02; P<0.001). CONCLUSIONS: A low aortic pulsatility index (<1.5) and the cold/wet hemodynamic profile are linked with an elevated risk of adverse long-term cardiac outcomes in patients with TGA and systemic right ventricle.

Pumping the Breaks on Acantholytic Skin Disorders: Targeting Calcium Pumps, Desmosomes, and Downstream Signaling in Darier, Hailey-Hailey, and Grover Disease.

Acantholytic skin disorders, by definition, compromise intercellular adhesion between epidermal keratinocytes. The root cause of blistering in these diseases traces back to direct disruption of adhesive cell-cell junctions, exemplified by autoantibody-mediated attack on desmosomes in pemphigus. However, genetic acantholytic disorders originate from more indirect mechanisms. Darier disease and Hailey-Hailey disease arise from mutations in the endoplasmic reticulum calcium pump, SERCA2, and the Golgi calcium/manganese pump, SPCA1, respectively. Though the disease-causing mutations have been known for nearly 25 years, the mechanistic linkage between dysregulation of intracellular ion stores and weakening of cell-cell junctions at the plasma membrane remains puzzling. The molecular underpinnings of a related idiopathic disorder, Grover disease, are even less understood. Due to an incomplete understanding of acantholytic pathology at the molecular level, these disorders lack proven, targeted treatment options, leaving patients with the significant physical and psychological burdens of chronic skin blistering, infections, and pain. This article aims to review what is known at the molecular, cellular, and clinical levels regarding these under-studied disorders and to highlight knowledge gaps and promising ongoing research. Armed with this knowledge, our goal is to aid investigators in defining essential questions about disease pathogenesis and to accelerate progress toward novel therapeutic strategies.

Application of low-density polyethylene (LDPE) passive samplers for monitoring PAHs in groundwater.

Equilibrium passive sampling continues to find increasing use for performing in situ assessments and monitoring of hydrophobic organic compounds (HOCs). Although this method has been successfully used in several field studies including open surface waters and sediments, comparatively, their use in groundwater has been very limited. In this study, low-density polyethylene (LDPE) passive samplers were deployed for 80 days in three groundwater wells contaminated with polycyclic aromatic hydrocarbons (PAHs). Prior to deployment, LDPE was loaded with performance reference compounds (PRCs) consisting of deuterated PAHs and their release used to ascertain system equilibrium. Within the 80-day deployment period, LDPE-groundwater equilibrium was confirmed for PAHs with molecular weights (MWs) in the range of 178 to 228 (i.e. anthracene, chrysene). Measured freely dissolved concentrations (Cw) were between one to three orders of magnitude lower than the total filtered concentrations (Ctotal) in the studied wells. The sum of PAHs (ΣPAHs) measured based on Cw and Ctotal were 2.05, 0.07 and 29.2 µg L-1 and 197, 59.7 and 1010 µg L-1, at wells 1, 2 and 3, respectively. A separate dataset, comprising long-term (2010 to 2022) concentrations of PAHs in total (i.e., unfiltered) groundwater, is also presented to provide insight into PAH contamination levels at the assessed groundwater wells based on conventional measurement. Estimated in situ LDPE daily clearance volumes (2.34 to 27.56 Ld-1) for the target analytes were far less than the daily turnover of ground water (144 to 348 Ld-1) encountered in the wells eliminating the possibility of depletive sampling of the groundwater by the passive samplers. These results represent the first published study on the practical application of equilibrium passive sampling using LDPE for monitoring and quantitatively assessing PAHs in groundwater. Also, this work demonstrates that LDPEs are a useful tool for measuring the Cw of PAHs in groundwater, a critical contaminant in many ecological and human health risk assessments.

High-intensity resistance training and collagen supplementation improve patellar tendon adaptations in professional female soccer athletes.

We investigated whether 10 weeks of pre-season soccer training (including high-intensity resistance exercise) with hydrolysed collagen (COL) supplementation would confer greater changes in patellar tendon (PT) mechanical and material properties compared with placebo (PLA) in professional female soccer athletes. Eleven athletes from the first team squad of a Football Association Women's Championship soccer club volunteered to participate in this study (age, 25.7 ± 4.2 years; height, 1.68 ± 0.04 m; mass, 64.0 ± 4.6 kg). Participants were pair-matched for baseline knee extensor maximum isometric voluntary contraction torque, age, height and mass and were randomly assigned to the COL group (n = 6) or PLA group (n = 5). Participants were given 30 g COL or energy-matched (36.5 g maltodextrin and 8.4 g fructose) PLA, plus 500 mg vitamin C before each training session, which consisted of high-intensity lower-limb resistance exercise, plyometric or pitch-based exercise 3 days/week for 10 weeks during the pre-season period. We assessed knee extensor maximum isometric voluntary contraction torque and PT properties using isokinetic dynamometry and ultrasonography before and after the intervention. The PT stiffness [COL, +15.4% ± 3.1% (d = 0.81) vs. PLA, +4.6% ± 3.0% (d = 0.32), P = 0.002] and Young's modulus [COL, +14.2% ± 4.0% (d = 0.65) vs. PLA, +3.4% ± 2.8% (d = 0.15), P = 0.004] increased more in COL than in PLA. There was a main effect of training on PT cross-sectional area (P = 0.027), but no interaction effect (P = 0.934). To conclude, 10 weeks of pre-season soccer training (incorporating high-intensity resistance exercise) with 30 g COL increased PT stiffness and Young's modulus more than training alone in professional female soccer athletes. This has positive implications for improving athletic performance and mitigating injury risk.

Inside the Black Box of Deliberate Practice: How do Coaches Coach to Improve Trauma Triage.

INTRODUCTION: Deliberate practice, goal-oriented training with feedback from a coach, is a common tool for improving physicians' performance. However, little is known about how coaches foster performance improvement. METHODS: A content analysis of video-recorded training sessions was performed to analyze the coaches' behaviors during a pilot randomized trial of deliberate practice in trauma triage. The intervention consisted of three video-conference sessions during which trial physicians, under the supervision of a coach, played a customized video game designed to review trauma triage principles. A multidisciplinary team specified tasks (e.g., create collaborative learning environment) that coaches should complete, and suggested 19 coaching strategies (e.g., encourage culture of error) to allow execution of these tasks. Two independent raters translated those strategies into a coding framework and applied it deductively to the recorded sessions. The frequencies of the coaching strategies were summarized, and tested for variation across coaches and time. RESULTS: Thirty physicians received the intervention across two 1-mo blocks. Most (28 [93%]) completed three sessions, each covering two (interquartile range 1-2) triage principles. Coaches used coaching strategies 18 (interquartile range 14.5-22) times per triage principle, using some often (2-3 times/principle) and others infrequently (<1 time/principle). The three coaches used similar numbers (20 versus 16 versus 18.5, P = 0.07) and types of strategies. However, use increased over time (16.8 [Block 1] versus 20 [Block 2] P = 0.018). CONCLUSIONS: Coaches used 19 coaching strategies to deliver this deliberate practice intervention, with behavior that evolved over time. Future trials should isolate the most potent strategies and should assess the best method of standardizing coaching.

Vascular Placental Pathology and Cardiac Structure in Stillborn Fetuses.

OBJECTIVE: Adverse pregnancy outcomes, including preterm birth and preeclampsia, are associated with worse cardiovascular outcomes for offspring. Examination of the placenta is important for understanding how the prenatal period shapes long-term cardiovascular health. We sought to investigate the association between placental vascular malperfusion and fetal cardiac structure. STUDY DESIGN: Data obtained from the Stillbirth Collaborative Research Network included stillbirths with placental pathology and autopsy. Stillbirths were classified in two ways: based on severity of placental maternal vascular malperfusion (MVM) and based on cause of death (MVM, fetal vascular malperfusion (FVM), or acute infection/controls). Organ weight and heart measures were standardized by gestational age (GA) and compared across groups. RESULTS: We included 329 stillbirths in the analysis by MVM severity and 76 in the analysis by cause of death (COD). While z-scores for most organ weights/heart measures were smaller when COD was attributed to MVM as compared with FVM or controls, heart weight and brain weight z-score did not differ by COD (p>0.05). In analyses accounting for body size, the difference between heart and body weight z-score was -0.05 (SD: 0.53) among those with MVM as a COD and -0.20 (SD: 0.95) among those with severe MVM. Right and left ventricle thicknesses and tricuspid, pulmonary, mitral, and aortic valve circumferences were consistently as expected or larger than expected for GA and body weight. In analysis investigating severity of MVM, those with the most severe MVM had heart measures that were as expected or larger than expected for body weight while those with only mild to moderate MVM had heart measures that were generally small relative to body weight. CONCLUSION: When assessed as COD or based on severity, MVM was associated with heart measures that were as expected or larger than expected for GA and body weight, indicating that possible heart sparing.

Structural basis for CCR6 modulation by allosteric antagonists.

The CC chemokine receptor 6 (CCR6) is a potential target for chronic inflammatory diseases. Previously, we reported an active CCR6 structure in complex with its cognate chemokine CCL20, revealing the molecular basis of CCR6 activation. Here, we present two inactive CCR6 structures in ternary complexes with different allosteric antagonists, CCR6/SQA1/OXM1 and CCR6/SQA1/OXM2. The oxomorpholine analogues, OXM1 and OXM2 are highly selective CCR6 antagonists which bind to an extracellular pocket and disrupt the receptor activation network. An energetically favoured U-shaped conformation in solution that resembles the bound form is observed for the active analogues. SQA1 is a squaramide derivative with close-in analogues reported as antagonists of chemokine receptors including CCR6. SQA1 binds to an intracellular pocket which overlaps with the G protein site, stabilizing a closed pocket that is a hallmark of inactive GPCRs. Minimal communication between the two allosteric pockets is observed, in contrast to the prevalent allosteric cooperativity model of GPCRs. This work highlights the versatility of GPCR antagonism by small molecules, complementing previous knowledge of CCR6 activation, and sheds light on drug discovery targeting CCR6.

Association of post-operative ctDNA detection with outcomes of patients with early breast cancers.

BACKGROUND: In early breast cancer (EBC) patients, we aimed to determine whether circulating tumor DNA (ctDNA) analysis following primary surgery, before systemic therapy, identified molecular residual disease and was associated with risk of relapse and relapse-free survival (RFS). METHODS: Plasma was collected, retrospectively, before surgery, 1-14 weeks post-operatively, and before adjuvant therapy, and in a subset of patients after adjuvant therapy. A personalized, tumor-informed, multiplex PCR next generation sequencing assay (Signatera™) was used for ctDNA detection and quantification. The primary objective was to compare RFS and distant recurrence-free survival (DRFS) in patients with detected versus non-detected ctDNA. RESULTS: A total of 48 patients with EBC (median age 50.5 years) [34 hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-), 5 HER2+, 9 triple-negative breast cancer) were included. ctDNA was detected in 64.5% (20/31) of patients before surgery, and 35.4% (17/48) after surgery. ctDNA detection before surgery was associated with tumor grade (P = 0.019), ctDNA detection after surgery was associated with receptor subtype (P = 0.01). Patients with ctDNA detected after surgery had worse DRFS [hazard ratio = 5.5, 95% confidence interval (CI) 1.1-28.5, P = 0.04]. RFS in patients with ctDNA detected after surgery was worse than in those with lack of ctDNA detection, although not statistically significant (hazard ratio = 3.7, 95% CI 0.9-15.7, P = 0.073). Patients with ctDNA detected preoperatively or post-operatively had a trend towards worse RFS (hazard ratio = 7.8, 95% CI 0.9-63.7, P = 0.05) and DRFS (hazard ratio = 6.8, 95% CI 0.8-57, P = 0.07) compared with those with ctDNA undetected at both timepoints. ctDNA detection anticipated clinical relapse with a median lead time of 16 months. CONCLUSIONS: In patients with treatment-naive EBC, ctDNA is detectable after surgery. The absence of ctDNA at a single post-surgical timepoint is associated with improved DRFS, supporting the development of future trials studying de-escalation of systemic therapy.

Acute care of cyclic vomiting syndrome and cannabinoid hyperemesis syndrome in the home and emergency department for: Special supplement/proceedings of 3rd international symposium.

BACKGROUND: Cyclic vomiting syndrome (CVS) and cannabinoid hyperemesis syndrome (CHS) are both characterized by episodic, acute transitions from asymptomatic states to highly symptomatic states of nausea, repetitive vomiting, and often severe abdominal pain. Patients with CVS and CHS face significant challenges to abort or mitigate episodes at home and often require emergency department (ED)-based care. PURPOSE: This paper reviews the current treatment approach to abort acute CVS and CHS episodes at home and in ED settings. Multiple pharmacologic and nonpharmacologic interventions have been demonstrated to potentially abort CVS or CHS episodes. Systemic pharmacologic agents often used as abortive therapy include triptans, antiemetics, anxiolytics, NK-1 receptor antagonists, antipsychotics, sedatives in general, and various analgesic / anti-inflammatory medications. Nonsystemic, nonpharmacologic approaches include reducing external stimuli (quiet room, dim lights, etc.), and hot water bathing or the application of topical capsaicin cream. More research is needed to develop evidence-based, individualized abortive treatment plans, as well as to determine whether the abortive treatment for CVS requires a fundamentally different approach than for CHS. When home-based approaches fail, all patients with CVS or CHS should receive nonjudgmental, informed, and compassionate care in the ED to abort their episode. Patients with more severe forms of CVS/CHS who require more frequent ED utilization should develop care plans with their ED to assure predictable and effective treatment.

An audacious approach to conservation.

New digital and sensor technology provides a huge opportunity to revolutionise conservation, but we lack a plan for deploying the technologies effectively. I argue that environmental research should be concentrated at a small number of 'super-sites' and that the concentrated knowledge from super-sites should be used to develop holistic ecosystem models. These, in turn, should be morphed into digital twin ecosystems by live connecting them with automated environmental monitoring programmes. Data-driven simulations can then help select pathways to achieve locally determined conservation goals, and digital twins could revise and adapt those decisions in real-time. This technology-heavy vision for 'smart conservation' provides a map toward a future defined by more flexible, more responsive, and more efficient management of natural environments.

Creation of a predictive calculator to determine adequacy of occlusion of the woven endobridge (WEB) device in intracranial aneurysms-A retrospective analysis of the WorldWide WEB Consortium database.

BACKGROUND: Endovascular treatment with the woven endobridge (WEB) device has been widely utilized for managing intracranial aneurysms. However, predicting the probability of achieving adequate occlusion (Raymond-Roy classification 1 or 2) remains challenging. OBJECTIVE: Our study sought to develop and validate a predictive calculator for adequate occlusion using the WEB device via data from a large multi-institutional retrospective cohort. METHODS: We used data from the WorldWide WEB Consortium, encompassing 356 patients from 30 centers across North America, South America, and Europe. Bivariate and multivariate regression analyses were performed on a variety of demographic and clinical factors, from which predictive factors were selected. Calibration and validation were conducted, with variance inflation factor (VIF) parameters checked for collinearity. RESULTS: A total of 356 patients were included: 124 (34.8%) were male, 108 (30.3%) were elderly (≥65 years), and 118 (33.1%) were current smokers. Mean maximum aneurysm diameter was 7.09 mm (SD 2.71), with 112 (31.5%) having a daughter sac. In the multivariate regression, increasing aneurysm neck size (OR 0.706 [95% CI: 0.535-0.929], p = 0.13) and partial aneurysm thrombosis (OR 0.135 [95% CI: 0.024-0.681], p = 0.016) were found to be the only statistically significant variables associated with poorer likelihood of achieving occlusion. The predictive calculator shows a c-statistic of 0.744. Hosmer-Lemeshow goodness-of-fit test indicated a satisfactory model fit with a p-value of 0.431. The calculator is available at: https://neurodx.shinyapps.io/WEBDEVICE/. CONCLUSION: The predictive calculator offers a substantial contribution to the clinical toolkit for estimating the likelihood of adequate intracranial aneurysm occlusion by WEB device embolization.

Highly Selective O-Phenylene Bisurea Catalysts for ROP: Stabilization of Oxyanion Transition State by a Semiflexible Hydrogen Bond Pocket.

Organocatalyzed ring-opening polymerization (ROP) is a versatile technique for synthesizing biodegradable polymers, including polyesters and polycarbonates. We introduce o-phenylene bisurea (OPBU) (di)anions as a novel class of organocatalysts that are fast, easily tunable, mildly basic, and exceptionally selective. These catalysts surpass previous generations, such as thiourea, urea, and TBD, in selectivity (kp/ktr) by 8 to 120 times. OPBU catalysts facilitate the ROP of various monomers, achieving high conversions (>95%) in seconds to minutes, producing polymers with precise molecular weights and very low dispersities (D ≈ 1.01). This performance nearly matches the ideal distribution expected from living polymerization (Poisson distribution). Density functional theory (DFT) calculations reveal that the catalysts stabilize the oxyanion transition state via a hydrogen bond pocket similar to the "oxyanion hole" in enzymatic catalysis. Both experimental and theoretical analyses highlight the critical role of the semirigid o-phenylene linker in creating a hydrogen bond pocket that is tight yet flexible enough to accommodate the oxyanion transition state effectively. These new insights have provided a new class of organic catalysts whose accessibility, moderate basicity, excellent solubility, and unparalleled selectivity and tunability open up new opportunities for controlled polymer synthesis.