Global climate change has increased the frequency and intensity of extreme weather events, significantly impacting the net primary productivity (NPP) of vegetation. Understanding the relationship between NPP and extreme climate events in ecologically sensitive areas is essential for effective ecological strategies. This study analyzed the spatiotemporal distribution characteristics of net primary productivity (NPP) from 2000 to 2022 and its response to extreme climate conditions. Utilizing the flexible space-temporal DAta fusion (FSDAF), the study integrated MODIS and Landsat data from 2000 to 2022 to generate a high-resolution NDVI dataset (30 m, 16-day). The NPP was estimated using the Carnegie-Ames-Stanford approach (CASA) model. We also evaluated the effects of 13 extreme climate indices (ECIs) on NPP in the Gaoligong Mountains. The results showed that (1) annual NPP exhibited an upward trend (slope = 1.5), with the most significant increase occuring in January (slope = 0.35, p < 0.001); (2) the climate in the study area has displayed a clear warming trend, with significant increases in extreme temperature indices (TXx, TNx, TN90p, TX90p, TMAXmean, and TMINmean, p < 0.001), while extreme precipitation indices (RX1day, RX5day), showd a relatively small trend of change and not significant; (3) At the seasonal scale, the responses of NPP to ECIs varied significantly among different vegetation types. The correlations between NPP and ECIs were markedly stronger in spring and autumn than in summer and winter, with temperature-related indices showing the strongest explanatory power for variations in NPP. (4)The response of NPP to extreme temperatures and precipitation is primarily characterized by a lag effect, typically delayed by 1-2 months, and is observed across different vegetation types. (5) extreme temperatures, particularly TX90p, TXx, TMAXmean, and DTR, are the key climatic factors affecting NPP. These results offer insights into the impact of climate extremes on NPP, which can inform future ecological management strategies.
This study examines the influence of convectively coupled equatorial waves (CCEWs) on extreme rainfall over the west coast of India across all seasons. The results show that CCEWs substantially amplify extreme rainfall, with Rossby waves exerting the strongest impact, followed by Mixed Rossby-Gravity (MRG) and Kevin waves. Overall, these waves enhance land rainfall extremes by about 20-60 %, while amplification over adjacent oceanic regions can exceed 150 %. Wave activity associated with Kelvin and Rossby waves remains relatively uniform throughout the year, whereas MRG waves exhibit pronounced seasonality, peaking during June-September. During summer, the enhancement in extreme rainfall linked to MRG waves is comparable to that of Rossby waves, while in winter the influence of all wave types is largely confined to the southernmost part of India. The amplification of rainfall primarily arises from wave-induced increases in moisture convergence and the subsequent development of deep convective systems, further supported by strong interactions between the dynamical waves and the orography of the Western Ghats. The waves are not only instrumental in magnifying extreme rainfall but also in increasing its probability, with Rossby and MRG waves playing a major role in this process, while Kelvin wave's effect is insignificant. The study observes that the devastating extreme rainfall events over the southwest coast in 2018, 2019, and 2024 are linked to strong wave activity. These findings provide new insight into the mechanisms that intensify rainfall extremes over the west coast of India and highlight the potential for improving extreme rainfall forecasts using the predictable nature of equatorial wave activity.
Fatal traffic crashes are a rare yet catastrophically consequential event in real-world crash data, typically constituting less than 1% of total records. This extreme class imbalance poses a fundamental challenge for machine learning-based severity prediction, as standard algorithms tend to ignore the minority class in favor of maximizing overall accuracy. This study investigates whether modern deep tabular learning architectures (TabNet, FT-Transformer) offer consistent advantages over the traditional gradient boosting method XGBoost in predicting fatal crashes under conditions of extreme class imbalance. The analysis is conducted on 5,676 traffic crashes recorded in Batman province of Türkiye between 2013 and 2022, with a fatal crash rate of only 0.8%. Methodologically, a leakage-controlled design was implemented through ex-ante variable selection, structured missing value handling, and SMOTE-based balancing applied exclusively to the training set. Model performance was evaluated not only with decomposition metrics such as ROC-AUC, but also with PR-AUC, Recall@K/Lift, and cost-sensitive analyses, which are more meaningful for imbalanced data. The results show that FT-Transformer achieved the strongest performance with ROC-AUC = 0.820 (vs. XGBoost: 0.752, TabNet: 0.760) and PR-AUC = 0.031 (approximately 3.9× above the random baseline of 0.008). It captured approximately 44% of fatal crashes in the riskiest 10% of cases, providing a ≈ 4.4-fold lift compared to random selection. Calibration analyses revealed that FT-Transformer produced more reliable risk scores: in the predicted probability band of 0.5-0.8, its observed positive rate reached the 8-15% range, representing a 4-7× elevation above the near-zero rates (0-2%) recorded for XGBoost and TabNet across the same probability range. These findings indicate that transformer-based tabular architectures offer consistent statistical, operational, and cost-sensitive advantages under extreme imbalance, supporting their use as decision-support tools in traffic safety management. To examine the generalizability of the framework beyond a single jurisdiction and a single time window, the analysis is complemented by (i) a temporal hold-out within Batman (training on 2013-2020, testing on 2021-2022) and (ii) external benchmarking on an independent publicly available rare-event crash corpus (n = 12,316; fatal rate = 1.28%) [61, 62]; the architectural ranking and rank-based operational gains are reproduced in both regimes.
Do-not-attempt-resuscitation (DNAR) orders are commonly issued for patients of advanced age in the setting of severe illness with an anticipated risk of mortality. However, DNAR orders are also observed among extremely elderly patients who are not critically ill at admission. The characteristics and outcomes of such patients remain poorly understood. This study aimed to characterize these patients and to examine the association between DNAR status and discharge outcomes. We retrospectively analyzed non-critically ill (National Early Warning Score [NEWS] of 4 or less) hospitalized patients aged 85 years or older admitted to a university hospital in Japan between 2022 and 2024 using electronic medical record data. Patients with and without DNAR orders were compared in terms of age, sex, activities of daily living (ADL), disease severity (NEWS), primary diagnoses, comorbidities, laboratory data, and discharge outcomes using univariable analyses. A Fine‒Gray competing-risk model examined the association between DNAR orders and transfer to post-acute care facilities, with discharge to home and death as competing events. Among the 1,230 eligible patients, 72 (5.9%) had DNAR orders. Patients with DNAR orders were older, had lower ADL, and had higher NEWS at admission. Primary diagnoses and comorbidities showed no consistent pattern between the two groups. Laboratory findings at admission showed lower hemoglobin and albumin levels and higher C-reactive protein levels in the DNAR group. Patients with DNAR orders were less likely to be discharged home, more likely to be transferred to post-acute care facilities or die in hospital, and had longer hospital stays. DNAR orders were associated with a higher probability of transfer to post-acute facilities (subdistribution hazard ratio 2.11; 95% confidence interval 1.21-3.69). Among non-critically ill extremely elderly hospitalized patients, those with DNAR orders were older, had lower ADL, and had higher disease severity. The presence of DNAR orders was associated with unfavorable discharge outcomes independent of age, ADL, and disease severity.
To summarize current evidence on endometriosis in adolescents and postmenopausal women and to compare age-specific clinical characteristics, diagnostic approaches, and management strategies. A narrative review was conducted following SWiM principles. A comprehensive search of PubMed, MEDLINE, Web of Science, Scopus, Embase, and the Cochrane Library was performed from database inception to December 2024. Studies reporting clinical or diagnostic data in adolescents or postmenopausal women with endometriosis were included. A total of 64 studies were analyzed (41 adolescent, 23 postmenopausal). Adolescent endometriosis is typically characterized by pelvic pain, reported in 40-55% of cases, with peritoneal lesions being the most common form. Recurrence rates range from 20 to 30%, and diagnostic laparoscopy remains central to evaluation. In contrast, postmenopausal endometriosis often presents with less specific symptoms, including gastrointestinal complaints, while pelvic pain is less frequently reported (18-25%). Recurrence appears lower (3-8%), although this may be influenced by differences in follow-up. Imaging modalities are more commonly used for diagnosis in postmenopausal women, particularly to exclude malignancy. Pathophysiological mechanisms differ between groups, with estrogen-dependent inflammation predominating in adolescents and local estrogen production contributing to disease persistence in postmenopausal women. Endometriosis demonstrates age-related differences in clinical presentation, diagnosis, and underlying mechanisms. Recognition of these variations may support more tailored diagnostic and management approaches across the reproductive lifespan.
Artisanal and small-scale gold mining (ASGM) is the largest anthropogenic source of atmospheric mercury (Hg) globally, yet residential airborne Hg data and associated health impacts remain scarce in urban ASGM settings. The Atrato River basin combines intense ASGM activity with fish-dependent communities, making it a priority region for exposure assessment. We assessed (i) seasonal airborne elemental Hg (THg-Air) in urban Quibdo (QO) and rural Negua (NA); (ii) urinary total Hg (THg-U), hair total Hg (THg-Hair), and hair methylmercury (MeHg-Hair); and (iii) the relative contributions of inhalation and diet using correlation and multiple linear regression. Airborne Hg was monitored at 68 sites across dry and rainy seasons (n = 4,608 readings). Biomarkers were analyzed in 127 residents (QO: n = 77; NA: n = 50). Mean THg-Air in QO exceeded international guidelines at 64% of sites (8.40 and 7.85 μg/m3 in dry and rainy seasons), with gold-shop peaks >50 μg/m3, whereas NA levels were ∼100-fold lower. THg-U was significantly higher in QO (10.66 vs. 3.25 μg/L, p<0.05), and 40% exceeded biomonitoring thresholds. MeHg accounted for ∼80% of hair Hg, reflecting dietary fish exposure. THg-Air correlated strongly with THg-U (r = 0.73-0.88), while hair biomarkers correlated with fish intake (r ≈ 0.47). Sex was the dominant hair-biomarker predictor (β ≈ 0.38), and occupational effects on THg-U emerged only through interaction terms. QO ranks among the most airborne-mercury-contaminated urban environments globally. Dual exposure pathways-inhalation of elemental Hg and dietary MeHg-affect workers and the general population respectively. Multi-matrix biomonitoring is essential, and urgent regulatory action is needed to protect vulnerable communities.
Understanding ecosystems functioning under frequent climatic perturbations is central to predicting ecosystem stability. While studies suggest that stable ecosystems can buffer against climate extremes, there is no agreement on whether this stability arises from their resistance (ability to absorb shock) to perturbations, resilience (capacity to recover) towards disturbances, or a combination of both. Using annual net primary productivity (NPP) and Standardized Precipitation Evapotranspiration Index (SPEI) and aridity index (AI), we investigated the (i) spatiotemporal changes of NPP, (ii) correlation between NPP, SPEI and AI, and (iii) resistance and resilience of meadow steppe, typical steppe, steppe desert, and desert steppe in Inner Mongolia from 2000-2019. Despite substantial interannual variability, all grassland types showed an upward trend in NPP, ranging from 1.21 g C m-2 yr-1 in desert steppe to 4.54 g C m-2 yr-1 in meadow steppe. The highest NPP (g C m-2 yr-1) was observed in meadow steppe (251), followed by typical steppe (160), steppe desert (95), and desert steppe (83). NPP increased significantly with increasing SPEI values across all grassland types, and with rising AI in steppe desert and desert steppe. Partial correlation analysis controlling for CO2 confirmed that NPP remained significantly and positively correlated with precipitation across all grassland types. Species richness ranged between 9 and 14 in meadow steppe, 7 and 17 in typical steppe and 5-10 in steppe desert. The measured NPP showed an increasing trend with rising species richness across these three grassland types, demonstrating a positive diversity-productivity relationship. Vegetation exhibited lower (higher) resistance against dry (wet) climatic conditions and higher (lower) resilience towards dry (wet) climatic conditions for all grasslands except for desert steppe. Typical steppe, meadow steppe and steppe desert are susceptible to extreme dry climate as these grasslands showed lower resistance against extreme dry climate. However, the higher resilience of these grasslands after extreme dry climate highlights that they recover faster after dry conditions compared to the recovery after wet conditions. The observed increase in vegetation productivity and differing stability has practical implications for pastoralists, landscape managers, and conservationists for grassland management. The demonstrated positive diversity-productivity relationship suggests maintaining greater species richness could buffer productivity losses during climate extremes, while the NPP-AI correlations in steppe desert and desert steppe offer early warning indicators for drought preparedness.
Despite optimal lipoprotein cholesterol control, patients with chronic coronary syndrome (CCS) exhibit substantial residual cardiovascular risk. Lipoprotein(a) (Lp[a]) is an independent cardiovascular risk factor, primarily determined by genetic variation within the LPA gene. To evaluate the association between the LPA polymorphisms rs10455872 and rs3798220, plasma Lp(a) concentrations-including extreme phenotypes-and clinical and coronary anatomical characteristics in patients with CCS. A total of 390 patients with CCS undergoing genetic evaluation for suspected inherited dyslipidemia were included. Lp(a) concentrations were measured using standardized assays, and the LPA polymorphisms rs10455872 and rs3798220 were genotyped. Associations with Lp(a) levels, clinical events, and coronary anatomical complexity were assessed using linear, logistic, ordinal, and negative binomial regression models. Both polymorphisms were robustly and independently associated with higher Lp(a) concentrations under dominant and additive genetic models (P < .001). The combined LPA genetic burden explained approximately 28% of the variability in Lp(a) levels. Extreme Lp(a) phenotypes were significantly more frequent among risk allele carriers. However, neither Lp(a) levels, extreme phenotypes, nor LPA genetic burden were independently associated with coronary events, multivessel disease, or coronary anatomical complexity (number of stents) after multivariable adjustment. Negative binomial models incorporating disease duration confirmed the lack of association with recurrent ischemic events. In patients with CCS, common LPA gene variants strongly determine plasma Lp(a) concentrations, including extreme phenotypes, but are not associated with the anatomical extent of coronary artery disease. These findings suggest that Lp(a) plays a predominant role in early disease stages rather than in established coronary anatomy.
Diffusion models have demonstrated remarkable performance on vision generation tasks. However, the high computational complexity hinders its wide application on edge devices. Quantization has emerged as a promising technique for inference acceleration and memory reduction. However, existing quantization methods do not generalize well under extremely low-bit (2-4 bit) quantization. Directly applying these methods will cause severe performance degradation. We identify that the existing quantization framework suffers from the outlier-unfriendly quantizer design, suboptimal initialization, and optimization strategy. We present MPQ-DMv2, an improved Mixed Precision Quantization framework for extremely low-bit Diffusion Models. For the quantization perspective, the imbalanced distribution caused by salient outliers is quantization-unfriendly for uniform quantizer. We propose Flexible Z-Order Residual Mixed Quantization that utilizes an efficient binary residual branch for flexible quant steps to handle salient error. For the optimization framework, we theoretically analyzed the convergence and optimality of the LoRA module and propose Object-Oriented Low-Rank Initialization to use prior quantization error for informative initialization. We then propose Memory-based Temporal Relation Distillation to construct an online time-aware pixel queue for long-term denoising temporal information distillation, which ensures the overall temporal consistency between quantized and full-precision model. Comprehensive experiments on various generation tasks show that our MPQ-DMv2 surpasses current SOTA methods by a great margin on different architectures, especially under extremely low-bit widths.
Human herpesvirus 6 (HHV-6) is a latent beta-herpesvirus with potential transfusion-transmissible relevance, particularly in immunocompromised recipients. Data on HHV-6 viremia among Sudanese blood donors are extremely limited. This study aimed to determine the molecular prevalence of HHV-6 DNA among blood donors in Kassala, Sudan. A descriptive cross-sectional study was conducted at Kassala Teaching Hospital. Only male donors were included due to extremely low female donation rates in this setting. Whole-blood samples (n = 180) were screened for HHV-6 DNA using real-time PCR, followed by multiplex PCR for genotyping attempts. Due to the small number of positive cases, comparisons were considered exploratory and descriptive. HHV-6 DNA was detected in 2.78% (5/180) of donors. No significant associations were found between HHV-6 positivity and age group, region, or ABO/Rh blood groups. Hematological parameters showed no significant differences between HHV-6-positive and negative donors. Genotyping was unsuccessful for all positive samples, likely due to the high cycle threshold (Ct) values (38.7-39.9), indicating low viral DNA levels. HHV-6 viremia was infrequent among blood donors in Kassala. Given the very small number of positive cases (n = 5), failed genotyping, and lack of serological confirmation, these findings are exploratory and preliminary. Larger multicenter studies with more sensitive methods are needed.
Fusarium stalk rot (FSR), caused by Fusarium verticillioides, is a major disease affecting maize production. Currently, chemical control serves as the primary management strategy, and our preliminary studies have demonstrated that fludioxonil exhibits excellent antifungal activity against F. verticillioides. However, the resistance risk and potential resistance mechanisms have not been fully established. In this study, we investigated four resistant laboratory isolates of F. verticillioides that had fludioxonil EC50 values ranging from 43.3 to 53.7 μg/mL. Evaluation of their biological characteristics indicated a significant fitness cost resulting from both reduced mycelial growth and impaired pathogenicity. In addition, the isolates were extremely sensitive to osmotic stress induced by NaCl, KCl, mannitol, and glucose, suggesting a decline in their environmental adaptability. Meanwhile, molecular analysis revealed that all isolates carried a G298D substitution in FvHIK1, but little evidence of altered expression. Molecular docking analysis indicated that the G298D mutation changed the minimum binding energy from -5.6 to -5.3 kcal/mol. Cross-resistance experiments revealed no correlation between fludioxonil and other fungicides with unrelated modes of action such as tebuconazole, prochloraz, azoxystrobin, or fluazinam, confirming a fludioxonil-specific mechanism of resistance. Taken together with the extreme sensitivity to osmotic stress, it is likely that the G298D in FvHIK1 caused the high levels of fludioxonil resistance observed in the current study. The absence of cross-resistance indicates that tebuconazole, prochloraz, azoxystrobin, and fluazinam remain viable options for F. verticillioides control if this type of resistance arose in the field, and that rotation could help prevent fludioxonil resistance emergence.
Functionality appreciation, valuing the body for what it can do, is a central aspect of positive body image. The Functionality Appreciation Scale (FAS) is widely used to assess this construct; however, its item-level properties have not been examined using item response theory. This study applied a graded response model to evaluate item discrimination, difficulty, and measurement precision, and to assess differential item functioning across gender. Participants were 386 adults aged 18-39 (Mage = 27.54, SD = 5.58) from English-speaking countries. Confirmatory factor analysis supported a unidimensional FAS structure. Graded response model analyses indicated strong item discrimination (α = 2.79-4.08) and appropriate difficulty thresholds, with items varying in sensitivity across levels of functionality appreciation. Test information functions demonstrated optimal precision in the moderate range (approximately -2 to +1 SD), with lower precision at extreme levels of the latent trait. Differential item functioning analyses revealed no significant gender differences, supporting measurement invariance across gender. These findings provide detailed item-level evidence supporting the reliability and utility of the FAS in community samples. Highly discriminating items may be especially sensitive to differences in functionality appreciation; however, caution is warranted when interpreting scores at the extremes of the latent trait, particularly in non-clinical samples. Future research should examine FAS performance across broader demographic, cultural, and clinical populations and explore refinements to improve measurement precision at extreme trait levels. Overall, the FAS appears to be a robust and informative measure of functionality appreciation. These findings further support its application within positive body image and well-being research.
The deep-sea supergiant isopod is renowned for surviving over 5 years without food, which is a crucial adaptive trait for megafauna inhabiting extreme environments. Here, morphological, physiological, and genomic comparisons of deep-sea isopods reveal a dual adaptive strategy underlying this trait: a distended, food-retentive stomach that enables episodic hyperphagia and a markedly reduced basal metabolic rate (BMR). Notably, central to this adaptation is the ancient horizontal acquisition of the microbial energy metabolism-related gene ND1, which thereafter achieved significant dosage enhancement via post-transfer duplication and ultra-high expression that is specifically regulated by histone acetylation at its promoter. Functional assays in transgenic zebrafish, nematodes, and cell lines demonstrate that ND1 reduces BMR by downregulating endogenous energy-production genes and thus extends starvation survival under cold-induced metabolic suppression. These findings uncover an exceptional evolutionary strategy whereby deep-sea megafauna co-opts and epigenetically optimizes exogenous microbial genes to reconcile the metabolic conflict between energy-demanding gigantism and extreme energy limitation.
Variability in the clinical presentation of patients with type 2 diabetes (T2D) is high and underlines the need for more personalized patient care. This nationwide study aimed to describe characteristics, treatment patterns, and disease progression of Finnish patients with T2D (N = 302,987), and to identify patient clusters with distinct progression patterns based on the occurrence of diabetes-related complications. The study included all adult patients with incident T2D in Finland between 2010 and 2019. Data were collected from national health and social care registers, data lakes, and a private healthcare provider between 1996 and 2021. Patient clusters were identified based on disease progression, defined by the occurrence of 22 pre-defined end-points, using likelihood-based growth mixture modeling. Five patient clusters with stable (C1; n = 133,951), mild (C2; n = 52,819), moderate (C3, n = 43,488), rapid (C4; n = 10,159), and extremely rapid progression (C5; n = 1973) were identified. The mean number of end-point complications per patient at baseline ranged from 0.2 to 2.3 across clusters and remained stable in C1-C3 over the first 5 years. In C5, the number increased to 5.5 and 7.2 during the first and third follow-up years, respectively, with a similar but more modest annual increase observed in C4. Cardiovascular complications increased more rapidly in C5 and C4 than C1-C3. T2D medication use was more common in milder clusters, whereas 31.4% and 48.2% of patients in C4 and C5, respectively, had no T2D medication. The rate of certain infections and values of creatinine, hemoglobin, and erythrocytes, increased with cluster severity. Diagnosis of several other new conditions, particularly cardiovascular complications, at or soon after incident T2D diagnosis predicts poor prognosis. The results further support a comprehensive approach in diabetes care, including evaluation and treatment of cardiovascular diseases alongside glycemic control. It is well known that people with type 2 diabetes can experience the disease in different ways, with wide variation in symptoms and disease progression. To support more personalized care, clinically useful tools that can predict how the disease will develop are needed. The researchers analyzed nationwide health register data from Finland, including all patients who received their first diagnosis of type 2 diabetes between 2010 and 2019. Their goal was to group patients into clusters with different long-term disease progression patterns, based on the development of diabetes-related complications after diagnosis. In total, the study included 302,987 patients with type 2 diabetes. These patients were divided into five clusters showing either stable (cluster 1), mild (cluster 2), moderate (cluster 3), rapid (cluster 4), or extremely rapid (cluster 5) disease progression. Further analysis showed that having additional conditions diagnosed at, or shortly after, the onset of diabetes was linked to a worse prognosis. Notably, 18.6% of patients did not purchase any diabetes medication during the follow-up period. This proportion was particularly high in patients allocated to cluster 4 (31.4%) and cluster 5 (48.2%). This study shows that patients with type 2 diabetes can be classified into meaningful groups with different progression patterns. This approach may help clinicians make timely and cost-effective decisions, focusing resources on patients most likely to benefit from early and intensive treatment.
Bioelectronic devices benefit from materials that have tissue-like levels of softness and good conductive coupling to biological structures. Conventional conjugated polyelectrolyte complexes such as poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT/PSS) have favorable levels of mixed ionic-electronic conductivity, but have high elastic stiffness, typically reflected in Young's moduli in the GPa range. Soft ionic conductors, such as ionogels, offer extreme deformability but generally lack the semiconducting mixed ionic-electronic transport required for signal transduction and amplification. Here, we report the first room-temperature liquid semiconducting block copolymer (L-SBCP) that functions as an organic electrochemical transistor (OECT) and enables solvent-free processing. The synthesis of L-SBCP involves the covalent linkage of two unlike polymers: a π-conjugated block bearing glycol side chains and a PEGMEMA bottlebrush acrylic block. This architecture combines mixed ionic-electronic conductivity with the mechanical properties of a viscoelastic liquid. The result is a phase-stable, free-flowing single-component material with a deformability comparable to that of biological cells (1-100 Pa) and a substrate-limited stretchability of 800%. Its liquid rheology supports direct injection and vacuum filling of microchannels without additives or thermal processing. The L-SBCP exhibits p-type accumulation-mode behavior in an organic electrochemical transistor (OECT), with a threshold voltage of +0.08 V, comparable to that of state-of-the-art soft semiconductors. Importantly, L-SBCP supports robust cell viability (>97%). The cellular compatibility opens opportunities for bioelectronic signal amplification at cell-material interfaces enabled by a semiconducting material with cell-scale softness. By uniting biorelevant softness, extreme deformability, electronic performance, and solvent-free processability, L-SBCP establishes a new material composition and form factor for semiconducting polymers and bioelectronic devices.
Sequence-unrelated but structurally similar (SUSS) effector families represent a distinctive evolutionary strategy among plant pathogen virulence proteins. Within families such as MAX, LARS and RALPH effectors, individual proteins maintain nearly identical three-dimensional folds despite minimal sequence identities, whilst targeting functionally diverse host cellular processes. This decoupling of structural conservation from functional specificity challenges traditional precepts of the classic structure-function paradigm and reveals how pathogen effectors exploit stable protein scaffolds as platforms for rapid functional diversification through extreme sequence variation. Comparative structural analyses suggest that surface frustration, regions of local energetic instability essential for fold flexibility, may be conserved across SUSS family members despite sequence divergence. This conservation creates potential vulnerabilities that could be exploited for resistance engineering. Rather than targeting individual effector-host interactions, frustration-guided design of molecular sponges, synthetic integrated domains or proteome degradation warheads could potentially neutralise entire SUSS effector families. This review explores the mechanisms of functionalisation by SUSS effectors and suggests strategies combining structural genomics, surface frustration analysis and AI-driven protein design for developing broad-spectrum resistance against major classes of plant pathogen effectors.
Research is needed to develop more accurate readmission prediction models that identify patients at the highest risk of readmission after their initial pneumonia hospitalization. Improving prediction accuracy will support the implementation of more effective, personalized interventions to lower readmission rates. Published models tend to rely on traditional methods or advanced machine learning models that exclude continuous variables, overlooking opportunities to uncover nonlinear relationships and interactions. In response, we used electronic medical record (EMR) data, including continuous variables such as vitals, alongside more advanced machine learning (ML) models. Using EMR data from a single academic medical center, we identified adults with initial pneumonia admissions between April 2018 and February 2024. We predicted 30-day readmission using eXtreme Gradient Boosting (XGBoost) and deep neural networks, and compared their performance with that of traditional logistic regression. We identified 2,752 patients admitted with pneumonia during the study period (mean age = 70.0 years, 49.1% female). The 30-day readmission rate was 9.9%. The average AUROC for our ML models ranged from 0.62 to 0.64, and AUPRC was 0.15 to 0.16, comparable to traditional logistic regression (0.63 and 0.17, respectively). Previously underemphasized predictors included drug abuse and BUN values. Using more advanced machine learning models and continuous variables yielded similar performance to logistic regression models. However, we identified previously understated predictors of readmission after pneumonia hospitalization. Future efforts should focus on gathering important data not readily available in EMR, such as social determinants of health, to potentially enhance the models.
Climate change intensifies temperature extremes, increasing daily variations between high and low temperatures (intraday temperature variation). These variations can influence environmental exposures, such as ambient air pollution and pollen, and indoor behaviors, including heating use, potentially elevating asthma exacerbation risk. Neighborhood context may modify these effects, particularly in disinvested or racially segregated areas where adaptive capacity is limited. We conducted a case-crossover study using conditional logistic regressions to estimate associations between intraday temperature variation and asthma exacerbations among children in Philadelphia, PA (2011-2016). Cases were identified from electronic health records at the Children's Hospital of Philadelphia. Analyses were stratified by season: Spring/Summer (March-August) and Fall/Winter (October-February). We assessed nonlinear and lagged (up to 7 days) effects, defining reference thresholds as 4 °F for Spring/Summer and 3 °F for Fall/Winter. Models were further stratified by present-day racialized economic segregation and historical redlining. In Spring/Summer, greater intraday temperature variation on lag day 4 was associated with increased odds of asthma exacerbation (OR = 1.20, 95% CI: 1.08-1.34). In Fall/Winter, greater variation was associated with decreased odds (OR = 0.81, 95% CI: 0.68-0.98). No statistically significant effect modification was observed by segregation or redlining. Intraday temperature variation was associated with pediatric asthma exacerbations, with stronger adverse effects during warmer months. These findings highlight the importance of addressing temperature variation in public health and clinical strategies aimed at protecting children with asthma in a changing climate.
Penile agenesis is an extremely rare congenital anomaly that poses major challenges for urological reconstruction. The appendix, due to its consistent vascular supply and mobility, represents a promising option for complex urethral reconstructions. This case report describes a 10-year-old boy with penile agenesis who initially underwent perineal urethrostomy and colostomy, followed by neophalloplasty using a scrotal flap and Vantris injections to enhance neophallus volume. Later, urethral reconstruction was performed using a pedicled appendiceal graft harvested robotically and implanted into the neophallus with microsurgical precision, preserving vascularity. The procedure was successful, and the patient is awaiting the next stage for urethral anastomosis. This study presents a minimally invasive technique employing the appendix as a neourethra, combining functional and aesthetic outcomes in the challenging context of penile agenesis.
Opioids are traditionally prescribed for postoperative pain management following arthroscopic glenoid labrum repair in young patients. Injudicious use has contributed to rising rates of dependence and overdose, and subsequent interest in opioid-sparing strategies. This study compared the efficacy of multimodal non-opioid to opioid-containing regimens for postoperative pain control in young patients undergoing arthroscopic labral repair. A single-center, prospective, randomized controlled trial was conducted from February 2023 to December 2025. Opioid-naive patients between 15 and 25 years of age undergoing an arthroscopic labrum repair were randomized into standard postoperative pain protocol group, prescribed 5 oxycodone 5 mg tablets, or the experimental non-opioid group. All patients received an interscalene nerve block. Demographics, comorbidities, daily morphine milligram equivalents (MME) consumed and visual analog scale (VAS) pain scores for 14 postoperative days, and pain control satisfaction were collected. Analysis was by intention-to-treat (ITT), representing randomization groups, and as-treated (AT), grouped by consumption or non-consumption of opioids. A mixed model estimated differences in outcomes while accounting for variability to assess postoperative VAS and MME. A total of 34 patients were included in this analysis (ITT: 17 experimental, 17 control) with mean age of 17.8 years (standard deviation 3.9), 24% female, 82% with labral tears secondary to sports injury, and mean number of anchors used of 4.1 (+ 1.7). Only 1 experimental patient requested oxycodone postoperatively. A total of 29 patients (85.29%) did not consume any postoperative opioids, including 16 (94.12%) in the experimental group and 13 (76.47%) in the control group. In ITT, mean total MME consumption was low in both groups (experimental 4.0 vs control 2.4), with no significant differences in daily MME use, VAS pain scores, or satisfaction with pain control (P>.05). By day 14, 88.24% of patients reported being "very satisfied" with their pain management. This study found no significant differences in postoperative opioid consumption, VAS pain scores, or patient satisfaction between opioid-containing and non-opioid regimens following arthroscopic labral repair. Overall opioid use was extremely low across both groups. These findings support the viability of non-opioid regimens in this patient population.