Research indicates that the giant sequoia, a serotinous conifer and the world's most massive tree species, is positively associated with high-severity fire for effective reproduction. However, land managers hypothesize that portions of giant sequoia groves could be lost in large crown fire areas due to a lack of regeneration, extensive montane chaparral cover, and long distances to the nearest surviving sequoia seed trees. Based on these hypotheses, rollbacks of environmental laws to facilitate intensive logging and tree plantation establishment are now proposed in giant sequoia groves on national forests and national parks, in the name of wildfire management and reforestation. Yet existing research is sparse, particularly regarding postfire sequoia regeneration that reaches the size of small trees (≥ 140 cm tall), which are most likely to survive to maturity. We investigated this issue in 62 field plots within the largest high-severity fire patches in Redwood Mountain Grove, Sequoia, and Kings Canyon National Parks, four years post-fire. These patches are dominated by crown fire but also include areas of high-intensity surface fire. At four years post-fire, we found sequoia regeneration density (mean = 19,478/ha) that was more than 21 times higher than initial modeling projected. Within the high-severity fire category, we found no correlation between fire severity or percent montane chaparral cover and giant sequoia small tree density, but found the percentage of all sequoia regeneration comprised by small trees is significantly higher in crown fire areas. The mean distance to the nearest live sequoia is now significantly shorter than reported at one year post-fire, suggesting that some live sequoias were not recognized as still living in initial evaluations. Our findings indicate that giant sequoia regeneration is thriving in large high-severity fire areas dominated by crown fire.
Anorexia nervosa (AN) is a severe psychiatric disorder (ED) with high mortality, marked functional impairment, and substantial phenotypical heterogeneity. Despite extensive research, treatment outcomes remain poor, and it is unclear why some individuals improve while others follow more persistent and severe courses. Existing diagnostic subtypes show limited value in predicting illness trajectory or treatment response. This study examined the distinct AN phenotypes which emerged within a treatment-seeking sample and considered how these differ in their response to standard treatment. Using data from the TRIANGLE study, latent profile analysis was used to identify phenotypic subgroups of adult patients with AN or atypical AN admitted to hospital for intensive care (n = 382), based on a variety of anthropometric and clinical variables. Following profile allocation, separate linear mixed model analyses (n = 370) examined differences between groups and over time (18 months) in depression, anxiety, and stress symptoms, work and social impairment, body mass index (BMI), and ED psychopathology. A four-profile solution best fit the data. Profiles differed in illness duration and symptom severity. One profile with long illness duration (mean ± standard deviation = 9 ± 7 years) and high symptom severity, a long-duration group (21 ± 11 years) with moderate severity, and two short-duration groups (4 ± 3 and 5 ± 3 years), one with high and one with comparatively lower severity, respectively. The high-severity, shorter-duration profile showed significant improvement across all variables over the 18-month follow-up period, whereas the highest-severity, longer-duration profile showed significant improvement on all variables except ED psychopathology. Where improvements were observed in both high-severity profiles, the magnitude of change was generally greater in the longer-duration profile, except for BMI, where it was equal and work and social impairment, where the shorter-duration profile showed greater improvement. In contrast, the lower-severity profiles showed significant improvements only in BMI and work and social impairment, which were smaller in magnitude than those observed in the high-severity profiles. Subtyping and treatment planning for AN must recognise that prognosis is shaped by multiple interacting factors rather than any single indicator and incorporate psychological, social, and functional complexity. Anorexia Nervosa (AN) is a complex mental disorder with heterogeneous symptom presentations. Recovery rates are suboptimal, and it is unclear which factors predict symptom remission in the shorter and longer term. The hypothesis that illness duration might contribute to explaining symptom severity has been proposed and has received some empirical support. However, it is becoming apparent that a more complex array of individual and clinical characteristics might better explain treatment response. In this study, we used a large dataset to examine the possibility of different, distinct presentations of AN. Using a data-driven approach, participants were grouped based on illness duration, body mass index, depression and anxiety symptoms, social and work functioning, autism traits, and eating disorder behaviours. Follow-up data were considered to examine the symptom trajectories of the different groups following standard treatment for AN. The results indicated the presence of four different groups in this dataset, defined by differences in symptom severity and illness duration. One group with long illness duration (9 years) and high severity, a very long-duration group (21 years) with moderate severity, and two shorter-duration groups with an average duration of 4 and 5 years, one with high and one with comparatively lower severity, respectively. The groups differed in their response to standard treatment; individuals with initially higher impairment showed the highest symptom improvement. The findings highlight that a single indicator, such as weight or length of illness, is not enough to subtype AN and predict prognosis. Treatment planning should consider different factors such as psychopathology, illness duration, and social impairments.
There are significant gaps in knowledge regarding the epidemiology, management, and outcomes of patients presenting to the emergency department (ED) with vaginal bleeding. This was a retrospective, successional cross-sectional study using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) examining all adult patients presenting to EDs with vaginal bleeding from 2011-2019. Patients were stratified by age, race/ethnicity, and pregnancy status. Main outcomes were ultimate outcome severity, presenting vital signs, and diagnostic tests performed. We defined high-severity outcome as any patient who was dead on arrival, died in the ED, or during that hospitalization; any patient admitted to the intensive care or stepdown units or to the cardiac catheterization lab or the operating room; or patients transferred to a non-psychiatric hospital. Moderate severity was defined as any patient admitted to floor-level care, held in observation, or transferred to a psychiatric hospital. We defined low-severity outcome as any patient discharged home. Patients presenting with a chief complaint of vaginal bleeding comprised 1.3% (95% CI, 1.2-1.4%,) of all ED visits, representing 14,620,933 total encounters. Of these patients, 53.0% (95% CI, 49.4-56.7%) were identified as pregnant. There was a lower prevalence of White patients presenting with this complaint compared to White patients presenting with any chief complaint (45.6% [95% CI, 41.9-49.4] vs 60.3% [95% CI, 57.7-62.8%]), with a reciprocal higher prevalence of Hispanic patients (21.1% [95% CI,17.7-24.5%] vs 13.2% [95% CI, 11.7-14.8%]). The majority of patients (88.1%, 95% CI, 86.1-90%) were classified as having a low-severity outcome, 10.3% (95% CI, 8.5-12.1%) were classified as moderate-severity, and 1.6% (95% CI,1.0-2.2%) as high-severity. Patients who were ultimately classified with high-severity outcomes had significantly higher shock indices at presentation and shorter wait times than patients with low-severity outcomes (0.75 [95% CI, 0.72-0.78] vs 0.68 [95% CI, 0.67-0.69], and 23.4 minutes [95% CI, 17.1-29.8] vs 41.7 minutes [95% CI, 37.1-46.4], respectively), despite no difference in median Emergency Severity Index triage score (2.5 [IQR 2.1-2.8] v 2.6 [IQR 2.2-2.9]). A quarter of patients (24.3% [95% CI, 20.8-27.7%]) received a pelvic exam: there were no significant differences in pelvic exam rate by age, pregnancy status, race/ethnicity, or ultimate outcome severity. Although most patients presenting to EDs with vaginal bleeding are discharged home, current triage models do not appear to appropriately risk-stratify higher risk patients. Disparities in presentation exist.
Background/Objectives: Endoscopic retrograde cholangiopancreatography (ERCP) requires deep sedation, which is increasingly provided by anaesthetists using propofol-based regimens. However, real-world data on the incidence and predictors of anaesthesia-related adverse events (AEs) in this setting remain limited. The objective of this study was to assess the frequency, predictors, and clinical significance of adverse events during anaesthetist-delivered sedation for ERCP, based on a propofol regimen. Methods: We conducted a retrospective single-centre cohort study including 388 consecutive adult patients who underwent ERCP with propofol-based sedation administered by an anaesthetist. Adverse events were classified into three tiers: Tier 1 (any adverse physiological events, including haemodynamic and respiratory threshold crossings), Tier 2 (clinically significant events requiring pharmacological intervention-the primary regression outcome), and Tier 3 (high-severity outcomes, reported descriptively). Independent predictors of Tier 2 events were identified using multivariable logistic regression. Results: Adverse physiological events occurred in 220 patients (56.7%), the majority of which were minor and self-limiting. Clinically significant events requiring active pharmacological intervention occurred in 108 patients (27.8%), with vasopressor-treated hypotension as the predominant component (88 patients, 22.7%). All bradycardia episodes required atropine administration (34 patients, 8.8%), while desaturation was largely self-limiting, with advanced airway management required in only three patients (0.8%). High-severity outcomes were rare (9 patients, 2.3%). In multivariable logistic regression predicting clinically significant adverse events, propofol dose (OR 1.20 per 10 mg, 95% CI 1.14-1.25, p < 0.001), ASA physical status (OR 1.63, 95% CI 1.07-2.49, p = 0.024), age (OR 1.04 per year, 95% CI 1.01-1.07, p = 0.007), and ketamine use, confounded by indication (OR 2.18, 95% CI 1.14-4.14, p = 0.018) were independent predictors. Model fit was good (Nagelkerke R2 = 0.43). Conclusions: Adverse events are frequent when defined using inclusive criteria, but are predominantly minor in severity. Propofol dose is the principal modifiable risk factor, demonstrating a consistent dose-response relationship across multiple adverse outcomes. ASA physical status and age further identify patients at increased risk of clinically significant events requiring intervention. Ketamine use was associated with increased odds of adverse events; however, this association is likely confounded by indication and should not be interpreted as a direct causal effect. These findings support stepwise propofol titration guided by clinical sedation assessment, with avoidance of anticipatory dosing particularly in older patients and those with higher ASA scores, and highlight the safety of anaesthetist-led sedation in this setting.
Pediatric sepsis is a leading cause of global morbidity and mortality, yet high-resolution, granular subnational assessments remain scarce. Chile and Mexico are the only countries in Latin America that possess robust vital registration systems and open access databases with marginal levels of missing cases. This offers a unique opportunity to quantify the subnational burden of pediatric sepsis, identify healthcare system constrictions, and guide targeted public health interventions. This retrospective longitudinal study analyzed official hospital discharge and non-fetal death records of pediatrics (< 10 years old) from Chile and Mexico between 2014 and 2024. Age-standardized incidence (ASIR) and mortality (ASMR) rates, standardized ratios, and the mortality-to-incidence ratio (MIR), were calculated to assess mortality relative to subnational hospital output. A novel dynamic risk stratification matrix was developed to classify ICD-10 sepsis-related causes into four risk/severity quadrants based on year-specific ASIR and MIR indicators. A total of 656,234 discharges and 2,035 deaths in Chile, and 964,452 discharges and 77,252 deaths in Mexico were analyzed. Subnational trends were highly heterogeneous. Chile exhibited a predominantly low pediatric MIR (median < 1%) with isolated hotspots with significant structural deviations to the North. High-severity sepsis causes in Chile were relatively rare. Conversely, Mexico displayed an alarmingly high MIR (median 7.2%), with systemic persistency in States such as Chiapas and Nuevo León. Strikingly, high-severity causes in Mexico (e.g., unspecified septicaemia, bacterial meningitis) were highly frequent, accounting for 88-97% of pediatric sepsis deaths. Furthermore, systemic instances of code-specific MIR > 1.0 in Mexico suggest significant health system fragmentation and decoupling of hospital discharge from vital statistic registries. Pediatric sepsis in Latin America encompasses distinct realities, ranging from localized critical care gaps to high-lethality persistency. One-size-fits-all national policies may be inadequate. These findings advocate for precision public health, urging the deployment of decentralized, data-driven interventions and specialized resource allocation based on high-risk subnational hotspot identification.
Wildfire activity is increasingly characterized by larger fire events and a greater prevalence of high-severity burns, driven by climate change, land-use change, and prolonged fire suppression. These shifts are altering post-fire vegetation dynamics, yet uncertainty remains regarding how early post-fire plant responses vary with burn severity and pre-fire occurrence of invasive plants under contemporary fire conditions. Given limited capacity for post-fire monitoring and restoration across increasingly large fire-affected landscapes, identifying factors associated with early post-fire vegetation responses is critical for prioritizing surveillance and supporting invasive plant management through early detection and rapid response (EDRR) programs. The 46,000 ha McKay Creek Wildfire in interior British Columbia, Canada, provided an opportunity to examine how burn severity, topography, and pre-fire occurrence of invasive plants (based on mapped infestation extent) influence early post-fire vegetation composition across diverse ecosystems. We predicted that both high burn severity and pre-fire occurrence of invasive plants would be associated with increased non-native plant cover following wildfire. Vegetation cover was recorded by species and grouped by native status (native or non-native), and life cycle (annual, biennial, perennial), on 80 plots stratified by burn severity and pre-fire occurrence of invasive plants. Two years post-fire, vegetation cover was dominated by bare ground across all plots, while native plant cover exceeded non-native cover under all conditions. At the broad status-group level (native vs. non-native), post-fire vegetation cover did not differ meaningfully across burn severity classes or between areas with and without documented pre-fire occurrence of invasive plants. Instead, elevation was the strongest driver of early post-fire vegetation patterns, with native cover increasing and non-native cover and bare ground decreasing at higher elevations. When vegetation was disaggregated by status and life cycle, non-native annual cover was higher in high-severity burns and at lower elevations, and non-native perennial cover increased with elevation. At a time when wildfires are increasing in size, frequency, and intensity, and resources for recovery are limited, this study provides region-specific insights to support prioritization of early post-fire restoration activities such as monitoring, prevention and management of invasive plants, and planting of native species. La actividad de los fuegos de vegetación se está caracterizando por eventos de incendio cada vez más grandes y una mayor prevalencia de quemas de alta severidad, conducidas por el cambio climático, cambios en el uso de la tierra, y una prolongada era de supresión de fuegos. Estos cambios están alterando la dinámica de la vegetación en el post-fuego, y aún así, la incertidumbre permanece sobre cómo las respuestas de las plantas en el post fuego temprano varían con la severidad de la quema y con la ocurrencia de plantas invasoras en el período previo al fuego en las actuales condiciones de los incendios. Dada la limitada capacidad para monitorear en el post fuego y en la restauración a través de grandes paisajes afectados por fuegos, la identificación de factores asociados con la respuesta inicial de las plantas en el post fuego temprano es crítico para priorizar la vigilancia y el soporte del manejo de plantas invasoras a través de programas de rápida detección y respuesta rápida (EDRR). Las 46 mil ha del incendio de McKay Creek en el interior de la Columbia Británica, proveen de una oportunidad para examinar cómo la severidad de ese incendio, la topografía del lugar, y la existencia, previa al fuego, de especies invasoras (basados en mapas de extensión de la infestación), influencian la composición de la vegetación en el post fuego temprano y a través de diversos ecosistemas. Nuestra predicción fue que tanto la severidad de las quemas y la pre-ocurrencia de plantas invasoras, podría asociarse con un incremento en la cobertura de plantas invasoras (no nativas) en el post fuego temprano. La cobertura de la vegetación fue registrada por especies y agrupadas por su estatus (Nativas y No-nativas) y ciclo de vida (anuales, bienales, y perennes), en 80 parcelas estratificadas por la severidad del fuego y la existencia previa de plantas invasoras. Dos años luego del incendio, la cobertura vegetal fue dominada por el suelo desnudo en todas las parcelas, mientras que la cobertura de plantas nativas excedió a la de no-nativas bajo todas las condiciones. A nivel de estatus amplio (entre grupos de nativas vs. no-nativas) la cobertura post fuego no difirió significativamente entre las clases de severidad o entre áreas documentadas previamente con existencias o no de especies invasoras. En cambio, la elevación del terreno fue el factor conducente más importante de los patrones de vegetación encontrados en el post fuego, con una cobertura creciente de plantas nativas y un decrecimiento tanto de plantas no nativas como de suelo desnudo a mayores elevaciones. Cuando la vegetación fue desagregada por estatus y ciclos de vida, la cobertura de anuales no-nativas fue mayor en quemas de alta severidad y a bajas elevaciones, y la cobertura de plantas perennes no-nativas se incrementó con la elevación. Cuando los incendios de vegetación se incrementan en tamaño, frecuencia, e intensidad, y los recursos para la recuperación de la vegetación son limitados, este estudio provee de percepciones específicas de valor regional para priorizar actividades de restauración post fuego como el monitoreo, prevención, y manejo de plantas invasoras, y la plantación de especies nativas.
Cancer pharmacotherapy has shifted to outpatient settings, making community pharmacists essential for ensuring medication safety. Although community pharmacist prescription audits are important, evidence regarding the clinical significance of their prescription audits for oral anticancer agents remains limited. This study aimed to analyze the content of inquiries regarding oral anticancer drugs and clarify the details of prescription audits conducted by community pharmacists. This single-institution retrospective a descriptive observational study included all records of inquiries regarding oral anticancer drugs submitted from community pharmacies to the National Cancer Center Hospital East between September 2023 and March 2025. Inquiry content was categorized based on treatment efficacy and safety concerns, while the level of pharmacist intervention was assessed based on the severity of the medication error and the clinical value of the pharmacist service. As the purpose of this study is to investigate prescription audits by community pharmacies, interventions unrelated to prescription auditing, such as telephone follow-ups or tracing reports, were excluded. During the study period, 184,688 prescriptions were issued, of which 384 inquiries (0.2%) involved oral anticancer agents and were included in the analysis. Prescription modifications occurred in 295 cases (77%). The most common inquiry categories were incorrect treatment duration (23%), adjustment for leftover medication (20%), and dosage errors (16%). Overall, 49% of cases were classified as potentially lethal, serious, or significant medication-order errors, and 49% were assessed as having a value of service of significant or higher. High-severity and high-value interventions most frequently involved errors in treatment duration and dosage. Prescription inquiries regarding oral anticancer agents frequently identified clinically significant prescribing issues, and community pharmacists provided high-value interventions. These findings indicate that community pharmacists play a crucial role in conducting high-quality prescription audits and enhancing the safety of outpatient cancer drug therapy.
Sepsis is a leading cause of morbidity and mortality in critically ill children, yet heterogeneous immune responses complicate the development of targeted therapies and the host immune factors driving sepsis pathobiology remain unclear. We integrated deep immune phenotyping, plasma proteomics, single-cell transcriptomics, and phosphoflow cytometry in a prospective cohort of 88 critically ill children to elucidate the mechanisms underlying immune heterogeneity. Unsupervised clustering of plasma cytokines identified three immunologic subgroups, including a high-severity group ("Group C") characterized by hypercytokinemia driven by IL-6 and IFN-γ. Group C exhibited distinct alterations in immune cell frequency and activation, with a strong association between hyperinflammatory cytokine signaling and lymphocyte dysfunction. Single-cell RNA sequencing revealed transcriptional signatures of T cell activation and metabolic stress, with suppression of a lymphoid protective gene program across CD8⁺ T cell subsets. Despite increased expression of activation markers, T cell receptor repertoire analysis revealed no dominant clonotypes, consistent with bystander activation. Phosphoflow cytometry demonstrated baseline STAT1/STAT3 hyperactivation in Group C CD8⁺ T cells, which failed to respond to αCD3/αCD28/αCD49d stimulation. These findings define an IL‑6/IFN‑γ-driven endotype of T cell dysfunction in pediatric sepsis and highlight the JAK/STAT axis as a rational target for immunomodulatory therapy. K12HD047349, K23GM159013, K08AI135091, R01HD095976, Thrasher Research Foundation, Burroughs Wellcome Fund CAMS, Immune Deficiency Foundation, Primary Immune Deficiency Treatment Consortium, Barbara Brodsky Foundation, CHOP Research Institute.
Robotic cholecystectomy has gained increased adoption as an alternative to conventional laparoscopic cholecystectomy. However, evidence regarding its operative efficiency and conversion to open surgery remains incomplete, particularly when comparing elective and urgent cases. We conducted a retrospective cohort study of 350 consecutive patients who underwent minimally invasive cholecystectomy at a level I trauma center. Procedures were categorized by surgical approach (laparoscopic or robotic) and operative indication (elective or urgent). The World Society of Emergency Surgery grading system was used to classify disease severity. Among 350 patients, 184 underwent laparoscopic cholecystectomy and 166 underwent robotic cholecystectomy. In elective cases, operative time was comparable between robotic and laparoscopic approaches (93.0 versus 91.0 min, P = 0.748). No conversions to open surgery occurred in elective cases for either approach. In urgent cases, operative time increased compared with elective procedures in both groups. Conversion occurred more frequently in laparoscopic urgent operations (3.7%) compared with robotic urgent operations (1.9%). Conversions occurred almost exclusively in grade D diseases. For elective cholecystectomy, robotic and laparoscopic approaches demonstrate comparable operative efficiency with no conversions. In urgent cholecystectomy, the robotic approach achieved similar operative time and a lower conversion frequency. These findings support the use of robotic cholecystectomy as an effective alternative for both elective and urgent gallbladder disease, with potential benefit in high-severity urgent cases.
Late-onset neonatal sepsis (LOS) requires early recognition to reduce mortality and morbidity, but clinical signs are often nonspecific. We introduced a nurse-driven red-flag-based sepsis bundle in our Level IV NICU in 2021. We assessed its performance in detecting culture-positive LOS by stratifying the severity of illness. This retrospective observational study included infants 3 days and older who were evaluated for sepsis. Cases were stratified into Green (lowest severity), Amber, Yellow, or Red (highest severity) categories according to clinical and laboratory criteria. We assessed bundle performance by calculating sensitivity, specificity, predictive values, and the area under the receiver operating characteristic curve (AUROC) relative to the Green reference group. Of the 142 evaluated sepsis episodes, the bundle was used in 123 (86.6%). Sensitivity was robust across the severity groups: 85.1% for Amber, 73.7% for Yellow, and 90.0% for Red. However, the specificity was uniformly poor at 13.0%, and the AUROC values remained <0.52 across all categories. Although the bundle consistently identified high-severity cases, it frequently over-identified low-risk infants. The nurse-driven sepsis bundle demonstrated high sensitivity for severe LOS, ensuring no critical cases were missed, but lacked discriminative ability due to poor specificity. Integrating additional objective markers and validated diagnostic tools may enhance the specificity and clinical utility of LOS evaluations while supporting nursing autonomy in sepsis recognition. A video abstract summarizing this study is available as supplemental digital content.
The efficacy of nitrogenous additives in deconstructing the lignin macromolecule is conventionally attributed to physical interactions. However, this macroscopic adsorption-centric model frequently overlooks the kinetic contributions of chemical lability at the molecular level. Here, we introduce a mechanistic decoupling strategy using melamine as an inert structural probe to benchmark against hydrolytically labile urea and dicyandiamide. We report an affinity-efficiency inversion: Urea, despite having the weakest theoretical binding energy, achieves the highest bulk delignification (~95%), surpassing the apparent physical ceiling (~85%) constrained by non-covalent interactions. This chemical override is driven by in situ generated nucleophiles acting as chemical etchants, amplified by localized structural relaxation to induce extensive depolymerization. Conversely, the inert melamine system operates via a distinct surface masking pathway. Rather than a kinetic limitation, the observed physical limit represents a thermodynamic complexation ceiling, where melamine leverages its superior affinity to form stable supramolecular complexes that passivate residual lignin. Mass balance analysis reveals a functional equivalence: surface passivation compensates for lower bulk purity, enabling the masking pathway to match the enzymatic glucose recovery of the high-severity erosion pathway. Our findings shift design principles for nitrogenous additives from maximizing solubility to tailoring specific erosion or masking functionalities, offering divergent structural engineering routes for highly monodisperse lignin nanospheres or functionalized supramolecular biocomposites.
To identify molecular biomarkers associated with chronic liver failure (CLF) progression to acute-on-chronic liver failure (ACLF). RNA-seq data from 8 CLF patients-stratified into high-severity (G, ACLF with total bilirubin ≥171 μmol/L) and low-severity (L, stable CLF with total bilirubin <171 μmol/L) groups-along with 4 healthy controls were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify disease-associated gene modules. A total of 3112 differentially expressed genes (DEGs) were identified, with KEGG analysis showing enrichment in innate immune pathways. Metabolomic profiling revealed 63 differentially expressed metabolites (DEMs), with four bile acids-Glycochenodeoxycholic acid, Glycocholic acid, Glycodeoxycholic acid, and Lithocholic acid-identified as key metabolites in bile acid biosynthesis pathways. Strong negative correlations were observed between these hydrophobic bile acids and 33 hub genes. Bile acid metabolism dysregulation and associated hub genes may contribute to CLF severity progression, warranting validation in larger cohorts.
Metal-organic frameworks (MOFs) are promising platforms for drug delivery due to their high porosity, tunable chemistry, and controlled release capabilities. However, their clinical translation is limited by insufficient safety data, particularly regarding the toxicity of organic linkers that may leach or degrade under physiological conditions. Experimental evaluation of linker biocompatibility across the vast MOF design space is impractical, creating a critical bottleneck for biomedical applications. Here, we present an integrated machine learning framework for systematic toxicity assessment of MOF organic linkers. Using acute toxicity data from the TOXRIC database, we trained four complementary modeling architectures: a directed message-passing graph neural network (Chemprop), a transformer-based SMILES model (ChemBERTa-2), a Random Forest using Morgan fingerprints, and a Support Vector Machine based on physicochemical descriptors. Across 5-fold stratified cross-validation, all models demonstrated strong predictive performance, achieving micro F1 scores up to ∼0.87, and microaveraged ROC-AUC values between ∼0.95 and 0.96, indicating robust discrimination despite substantial class imbalance. The trained models were applied to a large hypothetical MOF linker library, and ensemble predictions were used to improve robustness and reduce model-specific bias. Applicability-domain analysis based on chemical space overlap and nearest-neighbor similarity confirmed that predictions remained within well-supported regions of chemical space. To enable mechanistic interpretability, we integrated graph-based SHAP analysis with a SHAP-weighted Morgan fingerprint representation, allowing systematic identification of molecular substructures driving high-severity toxicity predictions. The most influential motifs showed strong agreement with independently documented toxic scaffolds, including polycyclic aromatic hydrocarbons. Together, this framework provides a scalable, accurate, and interpretable approach for prioritizing safe MOF linkers and guiding experimental screening toward candidates with favorable safety profiles.
Sepsis remains a leading cause of mortality in intensive care units (ICUs) globally; however, the effectiveness of conventional prognostic scoring systems varies across healthcare settings and patient populations. This study aimed to evaluate the comparative discriminative ability of the Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Charlson Comorbidity Index (CCI) in predicting 28-day mortality among critically ill septic patients. We conducted a retrospective observational study involving 392 consecutive adult patients diagnosed with sepsis according to the Sepsis-3 criteria, who were admitted to the ICU of a tertiary pulmonary care center in Serbia from January 2017 to December 2020. APACHE II scores were derived from the worst physiological values recorded within the first 24 hours of ICU admission; SOFA scores reflected the highest total score assessed during the same period; and CCI was calculated based on comorbidities present at admission. Discriminative performance was evaluated using receiver operating characteristic curve analysis. The overall 28-day mortality rate was 51.3%, which increased to 68.1% in patients with septic shock, with pneumonia being the source of infection in 97.4% of cases. APACHE II demonstrated the highest area under the curve (AUC) in the overall sepsis cohort (0.692, 95% CI 0.643-0.747), followed by SOFA (0.682, 95% CI 0.629-0.735) and CCI (0.667, 95% CI 0.613-0.720). In patients with septic shock, SOFA (AUC 0.671, 95% CI 0.561-0.782) and APACHE II (AUC 0.646, 95% CI 0.539-0.754) significantly outperformed CCI (AUC 0.423, 95% CI 0.302-0.543; p=0.006 and p=0.013, respectively), with no statistically significant difference between SOFA and APACHE II (p=0.828). Optimal cut-off values were identified as SOFA ≥8, APACHE II ≥21, and CCI ≥4, with corresponding sensitivities of 59.7%, 67.7%, and 56.2%, respectively. Both APACHE II and SOFA exhibited modest and comparable discriminative abilities for mortality prediction in this high-severity population, while CCI demonstrated limited utility in cases of septic shock. These findings underscore the continued relevance of conventional scoring systems and highlight the necessity for population-specific validation in high-acuity settings.
This review develops a region-specific Multi-Criteria Decision Analysis (MCDA)-based screening framework for evaluating food-processing residues for biochar applications, offering a transparent and replicable decision-support tool for policymakers and bioeconomy stakeholders in Turkey and beyond. Using Turkey as a region-specific case context, ten underutilized residues-boza fermentation residue, tarhana fines, rosehip seed cake, mulberry syrup press-cake, carob syrup pulp residue, pumpkin seed oil cake, saffron floral by-products, fig-jam seed fraction, lupin brining sediment, and date syrup filter cake-were compiled from the literature and characterized in terms of moisture, ash, organic fractions, higher heating value, and macro-mineral composition. Drawing on thermochemical fundamentals, the review synthesizes how these traits influence biochar properties relevant to fuel use, soil amendment, pollutant adsorption, anaerobic digestion (AD) enhancement, and composite materials, and qualitatively links residue groups to suitable conversion windows such as hydrothermal carbonization and low- or high-severity slow pyrolysis. To convert this information into a transparent screening tool, all indicators were normalized via min-max transformation and aggregated into four mechanistic proxies capturing fuel quality, nutrient release, an adsorption-oriented screening proxy, and AD compatibility. A Simple Additive Weighting (SAW) method was then used to calculate 0-1 suitability scores and 0-100 indices for five application domains: fuel, soil amendment, adsorption/remediation, AD enhancement, and composite/material use. Under the selected criteria and weighting assumptions, rosehip seed cake, pumpkin seed oil cake, carob syrup pulp residue, and fig-jam seed fraction emerged as comparatively high-priority feedstocks, whereas saffron floral by-products and lupin brining sediment showed consistently low relative suitability. By linking feedstock chemistry to application-oriented screening scores, the framework supports rapid comparison of residue-to-application pathways while acknowledging that rankings may evolve as additional performance data, logistical constraints, or alternative weighting scenarios are incorporated.
Potato common scab, a disease caused by the pathogenic Streptomyces species, produces cork lesions on tubers, leading to significant reductions in marketable yield and crop quality worldwide. Although the established correlation between soil physicochemical properties and microbial communities with disease severity, the interactive effects of these factors remain to be fully understood. In this study, we conducted a comprehensive, multi-year investigation of 124 potato fields in South Korea. This investigation was undertaken to elucidate the combined influence of soil properties and microbial communities on the development of common scab disease. An analysis of the soil physicochemical characteristics was conducted in conjunction with high-throughput 16s rRNA and ITS amplicon sequencing. The application of random forest modeling, based on soil physicochemical properties, exhibited a moderate predictive accuracy. Consistent with this, the importance feature of individual variables remained low, suggesting complex interactions among soil factors. The analysis of microbial communities revealed taxa that described a correlation with severity levels, thus distinguishing between distinct severity groups. Rhodanobacteraceae and Mortierellaceae were identified as indicators of low-severity fields, whereas Sphingomonadaceae, Chaetomiaceae, and Cystofilobasidiaceae were associated with high-severity fields. Despite the identification of several severity-associated soil and microbial features, no predominant factor explaining common scab severity was detected. This finding suggests that disease development is influenced by complex interactions among soil physicochemical conditions and microbial communities rather than by a single dominant driver.
Wildfires are reversing decades of air quality improvements across much of the US. Expanded use of prescribed fire is a primary proposed solution, but air quality trade-offs-more initial smoke for less smoke later-remain poorly quantified. Using two decades of satellite-derived measurements of fire severity and smoke particulate matter across California, we assessed the causal effect of low-severity wildfire, a proxy for prescribed burning, on subsequent wildfire activity and air quality. We found that low-severity fire reduced the probability of very-high-severity wildfire by 92%, with reductions lasting a decade and extending 5 kilometers from treated locations. Reduced future smoke far outweighed the smoke produced during treatment, with benefit-cost ratios exceeding five after a decade. Sustained treatment of 500,000 acres annually would reduce cumulative smoke fine particulate matter (PM2.5) by about 10% after a decade.
Large-scale outbreaks of infectious diseases, often spread through person-to-person contact, have historically caused significant morbidity and mortality. In this study, we develop a two-layer SIR (Susceptible-Infected-Recovered) model that accounts for individual mobility within and between populations. We explore two complementary approaches to disease mitigation: (i) an optimal control framework and (ii) an evolutionary behavior model. The optimal control approach minimizes the disease burden by coordinating three controls: travel restrictions, social distancing, and antiviral treatment, guided by predefined cost functions. In contrast, the behavioral model captures adaptive individual responses based on infection prevalence, interpopulation infection disparities, and socioeconomic trade-offs, following evolutionary game theory. We find that for high-severity epidemics, combining travel restrictions with social distancing significantly reduces infection peaks and total cases, while these measures become less effective for lower-severity outbreaks. Across all scenarios, a combined control strategy is most effective. However, a key finding is that antiviral treatment alone can rival the effectiveness of combined travel and distancing measures, offering a streamlined alternative when the societal costs of nonpharmaceutical interventions are prohibitive. Furthermore, optimally coordinated policies consistently outperform adaptive behavioral responses, yielding a significant reduction in the population.
To evaluate the association between Social Determinants of Health (SDOH), Social Capital (SC), and dental caries experience according to severity in 12-year-old children from a rural Peruvian community. A cross-sectional study was conducted with 61 schoolchildren and their families in Pampacolca, Arequipa - Peru. DMFT index (decayed, missing, and filled teeth) was assessed via clinical examination (kappa = 0.90). SDOH and SC were evaluated through household interviews with parents, using a survey based on the National Census and the short version of the Adapted Social Capital Assessment Tool (SASCAT), respectively. Data were analyzed using Spearman's correlation and the coefficient of determination (R2). The mean DMFT score was 5.25 ± 2.94. SDOH explained 3.99% of the variance in caries experience overall (p > 0.05). Significant associations were found when stratified by severity: in children with low severity (DMFT≤3), maternal education showed a significant correlation (r = -0.632, p = 0.007), explaining 39.9% of the variance. In children with high severity (DMFT≥5), limited access to health services was the most relevant factor (r = -0.605, p = 0.001), explaining 36.6% of the variance. Regarding social capital, only Cognitive SC showed a significant correlation (r = 0.494, p = 0.044), explaining 24.4% of the variance in the low-severity group. The findings suggest that SDOH and specific dimensions of SC are associated with dental caries, with effects varying by disease severity. While limited access to health services was linked to greater caries experience in high-severity cases, higher maternal education and cognitive social capital appeared to be associated with lower caries experience in children with lower severity. These results highlight the importance of context-specific social interventions.
Patient behavioral events, defined as physically aggressive behaviors, are common experiences of healthcare workers. Most research focuses on direct experiences of high severity but low frequency (acute) events and less is known about indirect experiences of frequent (chronic) low- and high-severity events, especially in a pediatric setting. This study examines pediatric healthcare workers' primary (directly targeted) and secondary (witnessed/heard about) experiences with patient behavioral events, and associations with stress-related outcomes, work attitudes, and work behaviors. Three children's hospitals (academic medical centers and free-standing hospitals) in the Midwest and South, United States, participated in the anonymous, cross-sectional survey. Of 2918 invited bedside healthcare workers (≥18 years), 521 responded. Respondents included nurses, ancillary staff, providers, and technicians/assistants (mean age = 37.76 years), predominantly female and white. The survey measured primary/secondary patient behavioral events, stress-related outcomes (work pressure, emotional demands, burnout), work attitudes (job satisfaction, engagement, hospital attachment), and work behaviors (withdrawal, turnover intentions). Patient behavioral event frequency correlated positively with stress-related outcomes, negatively with work attitudes, and positively with most of the work withdrawal behaviors, for both primary and secondary events. Nurses and those in emergency departments or behavioral health units reported the highest frequencies of events. Patient behavioral events are associated with pediatric healthcare professionals' well-being and work outcomes, whether they are directly targeted or witnessed/heard about. Attending to the psychological effects of patient behavioral events for targets and their coworkers may be a key element in pediatric personnel retention.