Evaluating individualized treatment effect predictions: A model-based perspective on discrimination and calibration assessment.

In recent years, there has been a growing interest in the prediction of individualized treatment effects. While there is a rapidly growing literature on the development of such models, there is little literature on the evaluation of their performance. In this paper, we aim to facilitate the validation of prediction models for individualized treatment effects. The estimands of interest are defined based on the potential outcomes framework, which facilitates a comparison of existing and novel measures. In particular, we examine existing measures of discrimination for benefit (variations of the c-for-benefit), and propose model-based extensions to the treatment effect setting for discrimination and calibration metrics that have a strong basis in outcome risk prediction. The main focus is on randomized trial data with binary endpoints and on models that provide individualized treatment effect predictions and potential outcome predictions. We use simulated data to provide insight into the characteristics of the examined discrimination and calibration statistics under consideration, and further illustrate all methods in a trial of acute ischemic stroke treatment. The results show that the proposed model-based statistics had the best characteristics in terms of bias and accuracy. While resampling methods adjusted for the optimism of performance estimates in the development data, they had a high variance across replications that limited their accuracy. Therefore, individualized treatment effect models are best validated in independent data. To aid implementation, a software implementation of the proposed methods was made available in R.

Robust interaction of ZnO and TiO2 nanoparticles with layered graphitic carbon nitride for enhanced photocatalytic oxidative desulfurization of fuel oil: mechanism, performance and stability.

Sulfur compounds in fuel such as thiophene, benzothiophene and dibenzothiophene are the primary source of SO x emissions, leading to environmental pollution and acid rain. In this study, we synthesized a layered oxygen-doped graphitic carbon nitride (OCN) structure and integrated ZnO and TiO2 nanoparticles onto the OCN surface through a microwave-assisted sol-gel method. The X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) results confirmed a robust interaction between the ZnO and TiO2 nanoparticles and the oxygen-doped g-C3N4 (OCN) surface, as indicated by the formation of C-N-Ti and C-O-Ti bonds. This interaction notably improved the optoelectronic properties of the ZnO-TiO2/OCN composite, yielding increased visible light absorption, reduced charge recombination rate, and enhanced separation and transfer of photogenerated electron-hole pairs. The oxygen doping into the CN network could alter the band structure and expand the absorption range of visible light. The ZnO-TiO2/OCN photocatalyst demonstrated remarkable desulfurization capabilities, converting 99.19% of dibenzothiophene (DBT) to dibenzothiophene sulfone (DBT-O2) at 25 °C, and eliminating 92.13% of DBT from real-world fuel oil samples. We conducted in-depth analysis of the factors impacting the redox process of DBT, including the ZnO ratio, initial DBT concentration, catalyst dosage, stability, and O/S molar ratio. Radical trapping experiments established that ˙O2 -, ˙OH and h+ radicals significantly influence the reaction rate. The obtained results indicated that the ZnO-TiO2/OCN photocatalyst represents a promising tool for future fuel oil desulfurization applications.

Suicide risk among young people who use drugs in Hanoi, Vietnam: Prevalence and related factors.

AIM: Adolescents and young adults are vulnerable to suicidality, especially those at high risk such as young people who use drugs (YPUD). This study aimed to assess the prevalence and related factors of suicide risk among this population. METHODS: We conducted a descriptive, cross-sectional study on YPUD aged 16-24 in the community in Hanoi, Vietnam. Data on socio-demographic characteristics, drug use, and adverse childhood experiences were collected using face-to-face questionnaires by research assistants. YPUD were screened by psychiatrists for depression, psychotic symptoms, and suicide risk, using the MINI questionnaire. RESULTS: Three hundred-seven YPUD (250 males, 57 females) participated in the study; of those, 86 (28.0%) were at risk of suicide. Gender (female), adverse childhood experiences, depression, and psychosis were relevant factors. CONCLUSION: The prevalence of suicide risk among young people using drugs was high. Therefore, suicide risk should be screened and monitored in the clinical assessment of this population. In addition, the intervention efforts to detect and intervene in adverse events during childhood may be one way to prevent mental health and suicide in later life.

Synthesis and characterisation of copper(I) complexes with relevance to intramolecular Ullmann O,S-arylation.

Copper-catalysed intramolecular Ullman arylation has been frequently used to synthesise benzoxazoles and benzothiazoles. Despite widespread use, investigations into the mechanism and speciation of copper-containing complexes relevant to the catalytic pathway have remained relatively limited. Accordingly, this study aims to elucidate the structural details of potential copper(I) intermediates through the analysis of their solid-state structures using X-ray crystallography, while also investigating the reactivities of these complexes. Five novel copper complexes are reported which are formed prior to the aryl halide activation step and feature distinct aggregation modes based on either Cu4N4O4C4 or Cu4N4S4C4 clusters.

A Comprehensive Strategy for Metabolites Profiling of Flowers and Leaves from Camellia tienii, an Endemic Golden Tea of Vietnam.

Golden camellia is defined as a species of the Camellia genus with yellow flowers, which have long been used as a medicine, food, and cosmetic in many Asian countries. To date, more than 50 golden camellia species are considered endemic in Vietnam; however, more information is needed about its chemical constituents and biological activity. This work aims to unveil the potential of Camellia tienii Ninh, a golden camellia species, as an herbal beverage by examining the presence and abundance of chemical components in flowers and leaves. A comprehensive strategy has been developed using both liquid and gas chromatography coupled with mass spectrometry. Specifically, LC-MS-based widely targeted analyses were opted to characterize 158 polar metabolites belonging mainly to flavonoids, catechins, and amino acids classes, and an untargeted approach using GC-MS annotated 42 major volatile compounds such as terpenes and fatty acids. The extensive profile revealed by these techniques could help understand the significant discrimination between two organs. C. tienii flowers accumulated more flavonoids, amino acids, and fatty acids, while leaves contain more terpenes, suggesting different pharmacological properties of these materials. Overall, this pipeline can be applied for other Camellia species and valorization of these valuable resources for health benefits purposes.

Modifications of surgical techniques in laparoscopic percutaneous extraperitoneal closure of inguinal ring for childhood inguinal hernia to achieve zero recurrence and zero subcutaneous stitch granuloma.

PURPOSE: To present our technical modifications of single incision laparoscopic percutaneous extraperitoneal closure (SILPEC) of the internal inguinal ring (IIR) for pediatric inguinal hernia (PIH). METHODS: The prospectively collected data of all children diagnosed with PIH undergoing SILPEC at our center from 2016 to 2023 were reviewed and divided into two groups for result comparison: Group A: before and Group B: after the implementation of full modifications. Our modifications included using a nonabsorbable monofilament suture, creating a peritoneal thermal injury at the internal inguinal ring (IIR), employing a cannula to ensure the suture at the IIR ligates only the peritoneum, and double ligation of the IIR in selected cases. RESULTS: 1755 patients in group A and in group B (1 month to 14 years old) were enrolled. There were no significant differences regarding baseline patient characteristics between the two groups. At a median follow-up of 40 months, the rate of recurrent CIH and subcutaneous stitch granuloma (SSG) was 2.3% and 1.5% in group A vs. 0% and 0% in group B (p < 0.001). There were no hydroceles, no ascended or atrophic testis. CONCLUSIONS: Our SILPEC technical modifications can achieve zero recurrence and zero SSG for PIH.

Age-dependent heterogeneity in the antigenic effects of mutations to influenza hemagglutinin.

Human influenza virus evolves to escape neutralization by polyclonal antibodies. However, we have a limited understanding of how the antigenic effects of viral mutations vary across the human population and how this heterogeneity affects virus evolution. Here, we use deep mutational scanning to map how mutations to the hemagglutinin (HA) proteins of two H3N2 strains, A/Hong Kong/45/2019 and A/Perth/16/2009, affect neutralization by serum from individuals of a variety of ages. The effects of HA mutations on serum neutralization differ across age groups in ways that can be partially rationalized in terms of exposure histories. Mutations that were fixed in influenza variants after 2020 cause greater escape from sera from younger individuals compared with adults. Overall, these results demonstrate that influenza faces distinct antigenic selection regimes from different age groups and suggest approaches to understand how this heterogeneous selection shapes viral evolution.

Impact of Different Red Blood Cell Storage Solutions and Conditions on Cell Function and Viability: A Systematic Review.

Red blood cell (RBC) storage solutions have evolved significantly over the past decades to optimize the preservation of cell viability and functionality during hypothermic storage. This comprehensive review provides an in-depth analysis of the effects of various storage solutions and conditions on critical RBC parameters during refrigerated preservation. A wide range of solutions, from basic formulations such as phosphate-buffered saline (PBS), to advanced additive solutions (ASs), like AS-7 and phosphate, adenine, glucose, guanosine, saline, and mannitol (PAGGSM), are systematically compared in terms of their ability to maintain key indicators of RBC integrity, including adenosine triphosphate (ATP) levels, morphology, and hemolysis. Optimal RBC storage requires a delicate balance of pH buffering, metabolic support, oxidative damage prevention, and osmotic regulation. While the latest alkaline solutions enable up to 8 weeks of storage, some degree of metabolic and morphological deterioration remains inevitable. The impacts of critical storage conditions, such as the holding temperature, oxygenation, anticoagulants, irradiation, and processing methods, on the accumulation of storage lesions are also thoroughly investigated. Personalized RBC storage solutions, tailored to individual donor characteristics, represent a promising avenue for minimizing storage lesions and enhancing transfusion outcomes. Further research integrating omics profiling with customized preservation media is necessary to maximize post-transfusion RBC survival and functions. The continued optimization of RBC storage practices will not only enhance transfusion efficacy but also enable blood banking to better meet evolving clinical needs.

A first-principles prediction of novel Janus ZrGeZ3H (Z = N, P, and As) monolayers: Raman active modes, piezoelectric responses, electronic properties, and carrier mobility.

In this article, an attempt is made to explore new materials for applications in piezoelectric and electronic devices. Based on density functional theory calculation, we construct three Janus ZrGeZ3H (Z = N, P, and As) monolayers and study their stability, piezoelectricity, Raman response, and carrier mobility. The results from phonon dispersion spectra, ab initio molecular dynamics simulation, and elastic coefficients confirm the structural, thermal, and mechanical stability of these proposed structures. The ZrGeZ3H monolayers are indirect band gap semiconductors with favourable band gap energy of 1.15 and 1.00 eV for the ZrGeP3H and ZrGeAs3H, respectively, from Heyd-Scuseria-Ernzerhof functional method. It is found that the Janus ZrGeZ3H monolayers possess both in-plane and out-of-plane piezoelectric coefficients, revealing that they are potential piezoelectric candidates. In addition, the carrier mobilities of electrons and holes along transport directions are anisotropic. Notably, the ZrGeP3H and ZrGeAs3H monolayers have high electron mobility of 3639.20 and 3408.37 cm2 V-1 s-1, respectively. Our findings suggest the potential application of the Janus ZrGeZ3H monolayers in the piezoelectric and electronic fields.

Biogenic fabrication of a gold nanoparticle sensor for detection of Fe3+ ions using a smartphone and machine learning.

In recent years, smartphones have been integrated into rapid colorimetric sensors for heavy metal ions, but challenges persist in accuracy and efficiency. Our study introduces a novel approach to utilize biogenic gold nanoparticle (AuNP) sensors in conjunction with designing a lightbox with a color reference and machine learning for detection of Fe3+ ions in water. AuNPs were synthesized using the aqueous extract of Eleutherine bulbosa leaf as reductants and stabilizing agents. Physicochemical analyses revealed diverse AuNP shapes and sizes with an average size of 19.8 nm, with a crystalline structure confirmed via SAED and XRD techniques. AuNPs exhibited high sensitivity and selectivity in detection of Fe3+ ions through UV-vis spectroscopy and smartphones, relying on nanoparticle aggregation. To enhance image quality, we developed a lightbox and implemented a reference color value for standardization, significantly improving performance of machine learning algorithms. Our method achieved approximately 6.7% higher evaluation metrics (R 2 = 0.8780) compared to non-normalized approaches (R 2 = 0.8207). This work presented a promising tool for quantitative Fe3+ ion analysis in water.

Tropoelastin modulates systemic and local tissue responses to enhance wound healing.

Wound healing is facilitated by biomaterials-based grafts and substantially impacted by orchestrated inflammatory responses that are essential to the normal repair process. Tropoelastin (TE) based materials are known to shorten the period for wound repair but the mechanism of anti-inflammatory performance is not known. To explore this, we compared the performance of the gold standard Integra Dermal Regeneration Template (Integra), polyglycerol sebacate (PGS), and TE blended with PGS, in a murine full-thickness cutaneous wound healing study. Systemically, blending with TE favorably increased the F4/80+ macrophage population by day 7 in the spleen and contemporaneously induced elevated plasma levels of anti-inflammatory IL-10. In contrast, the PGS graft without TE prompted prolonged inflammation, as evidenced by splenomegaly and greater splenic granulocyte and monocyte fractions at day 14. Locally, the inclusion of TE in the graft led to increased anti-inflammatory M2 macrophages and CD4+T cells at the wound site, and a rise in Foxp3+ regulatory T cells in the wound bed by day 7. We conclude that the TE-incorporated skin graft delivers a pro-healing environment by modulating systemic and local tissue responses. STATEMENT OF SIGNIFICANCE: Tropoelastin (TE) has shown significant benefits in promoting the repair and regeneration of damaged human tissues. In this study, we show that TE promotes an anti-inflammatory environment that facilitates cutaneous wound healing. In a mouse model, we find that inserting a TE-containing material into a full-thickness wound results in defined, pro-healing local and systemic tissue responses. These findings advance our understanding of TE's restorative value in tissue engineering and regenerative medicine, and pave the way for clinical applications.

Clinical implementation of artificial-intelligence-assisted detection of breast cancer metastases in sentinel lymph nodes: the CONFIDENT-B single-center, non-randomized clinical trial.

Pathologists' assessment of sentinel lymph nodes (SNs) for breast cancer (BC) metastases is a treatment-guiding yet labor-intensive and costly task because of the performance of immunohistochemistry (IHC) in morphologically negative cases. This non-randomized, single-center clinical trial (International Standard Randomized Controlled Trial Number:14323711) assessed the efficacy of an artificial intelligence (AI)-assisted workflow for detecting BC metastases in SNs while maintaining diagnostic safety standards. From September 2022 to May 2023, 190 SN specimens were consecutively enrolled and allocated biweekly to the intervention arm (n = 100) or control arm (n = 90). In both arms, digital whole-slide images of hematoxylin-eosin sections of SN specimens were assessed by an expert pathologist, who was assisted by the 'Metastasis Detection' app (Visiopharm) in the intervention arm. Our primary endpoint showed a significantly reduced adjusted relative risk of IHC use (0.680, 95% confidence interval: 0.347-0.878) for AI-assisted pathologists, with subsequent cost savings of ~3,000 €. Secondary endpoints showed significant time reductions and up to 30% improved sensitivity for AI-assisted pathologists. This trial demonstrates the safety and potential for cost and time savings of AI assistance.

Algae-constructed wetland integrated system for wastewater treatment: A review.

Integrating algae into constructed wetlands (CWs) enhances wastewater treatment, although the results vary. This review evaluates the role of algae in CWs and the performance of different algae-CW (A-CW) configurations based on literature and meta-analysis. Algae considerably improve N removal, although their impact on other parameters varies. Statistical analysis revealed that 70 % of studies report improved treatment efficiencies with A-CWs, achieving average removal rates of 75 % for chemical oxygen demand (COD), 74 % for total nitrogen and ammonium nitrogen, and 79 % for total phosphorus (TP). This review identifies hydraulic retention times, which average 3.1 days, and their varied impact on treatment efficacy. Mixed-effects models showed a slight increase in COD and TP removal efficiencies of 0.6 % every ten days in the A-CWs. Future research should focus on robust experimental designs, adequate algal storage and separation techniques, and advanced modeling to optimize the treatment potential of algae in CWs.

Harnessing Maxwell's demon to establish a macroscale concentration gradient.

Maxwell's demon describes a thought experiment in which a 'demon' regulates the flow of particles between two adjoining spaces, establishing a potential gradient without appearing to do work. This seeming paradox led to the understanding that sorting entails thermodynamic work, a foundational concept of information theory. In the past centuries, many systems analogous to Maxwell's demon have been introduced in the form of molecular information, molecular pumps and ratchets. Here we report a functional example of a Maxwell's demon that pumps material over centimetres, whereas previous examples operated on a molecular scale. In our system, this demon drives directional transport of o-fluoroazobenzene between the arms of a U-tube apparatus upon light irradiation, transiting through an aqueous membrane containing a coordination cage. The concentration gradient thus obtained is further harnessed to drive naphthalene transport in the opposite direction.

In vitro anti-leukemia, antioxidant, and anti-inflammatory properties of Lantana camara.

It has been demonstrated that Lantana camara possesses several therapeutic properties that can be used to treat various human diseases, including dermatological and gastrointestinal conditions, tetanus, malaria, and tumours. In this investigation, every collected part of L. camara was extracted with absolute methanol to examine its antioxidant capacity using the DPPH assay and its anti-leukemia activity on two AML cell lines, MOLM-13 and MV4-11. In addition, anti-inflammatory effectiveness was evaluated. The results show that extracts from various sections of L. camara have a significant ability to neutralize free radicals, as indicated by their EC50 values. Most of the extracts had values less than 100 µg/ml, with the flower extract having an even lower value of less than 50 µg/ml. Experiments on two AML cell lines showed that the anti-leukemia effects of the extracts were remarkable, with the most potent impact belonging to the root extract (IC50 was 9.78 ± 0.61 and 12.48 ± 1.69 for MOLM-13 and MV4-11 cell lines). The antitumor effect of the extracts was determined to be time- and dose-dependent and did not correlate with antioxidant capacity. Furthermore, when BJ cells were exposed to L. camara root and leaf extracts, their migratory potential was dramatically reduced compared to untreated cells. The extracts demonstrated potential anti-inflammatory capabilities by lowering NO production in LPS-induced BJ cells.

Imputation accuracy and carrier frequency of deleterious recessive defects in Australian dairy cattle.

Widespread genotyping has enabled the identification of putative recessive mutations that affect fertility through early embryonic fetal loss, or compromise neonate or calf viability. The use of artificial insemination in the global dairy population can rapidly spread these harmful mutations, and testing for multiple mutations can become relatively expensive if not all tests are available on the same SNP panel. However, it is possible to provide heifer and cow predicted carrier status to farmers at no additional cost if the animals are genotyped with a standard SNP panel. Additionally, for defects where the causal mutation is unknown, but a haplotype of markers has been associated with the defect, the carrier status can be predicted based on that haplotype. The aims of this study were 3-fold: 1) to determine the accuracy of imputation of putative causal mutations for recessive deleterious conditions in Australian dairy cattle, 2) to impute carrier status for known recessive deleterious conditions in all genotyped Australian Holstein, Jersey and Red breed cows, and 3) to determine the changes in carrier frequencies across time for these recessive deleterious mutations. We used the F1 statistic, combining precision and recall, to assess the accuracy of carrier status prediction. We showed that known deleterious mutations can be accurately imputed in Australian Holstein and Jersey cattle that are not directly genotyped for the causal mutation, with F1 ranging between 0.88 and 0.99. For recessive deleterious conditions not included on the standard Australian SNP panel, carrier status could be predicted using a marker haplotype, with F1 ranging from 0.91 to 0.92. Most putative causals and haplotypes were either stable with a low carrier percentage or had a declining carrier percentage. However, several recessive mutations showed a relatively high or increasing percentage, highlighting the importance of detecting carriers to reduce the number of at risk matings. Furthermore, the high carrier percentage of the recently identified Bovine Lymphocyte Intestinal Retention Defect (BLIRD) mutation emphasizes the importance of detection of novel mutations.

Phenotyping chronic respiratory diseases with airways obstruction.

Given the high prevalence of asthma-chronic obstructive pulmonary disease overlap (ACO) in Vietnam, there is an urgent need to establish a simplified strategy for categorising patients as either having asthma or chronic obstructive pulmonary disease (COPD). This classification would streamline the application of treatment recommendations outlined by the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD).Patients with obstructive lung function were classified as having COPD, asthma, or ACO based on GINA/GOLD guidelines. We hypothesised that ACO-like asthma (ACO-A) would present with positive skin prick tests (SPTs) or early onset of symptoms without a history of tuberculosis (TB), while those with ACO-like COPD (ACO-B) would exhibit negative SPTs and late onset of symptoms and/or a history of TB.Among 235 patients, the prevalence of asthma, ACO-A, ACO-B, and COPD was respectively 21%, 22%, 17%, and 40%. Allergic history, rhinitis, and childhood asthma were associated with ACO-A, while high cumulative smoking was correlated with ACO-B. Socio-economic and demographic parameters, medical history, clinical features, smoking habits, lung function, and para-clinical investigations significantly differed between "all asthma" (i.e., individuals with asthma combined with ACO-A) and "all COPD" (i.e., individuals with COPD combined with ACO-B).Based on SPTs, history of TB, and onset age, ACO patients may be defined as people with asthma or COPD..

Near-Infrared Ratiometric Fluorescent Probe for Detecting Endogenous Cu2+ in the Brain.

Copper participates in a range of critical functions in the nervous system and human brain. Disturbances in brain copper content is strongly associated with neurological diseases. For example, changes in the level and distribution of copper are reported in neuroblastoma, Alzheimer's disease, and Lewy body disorders, such as Parkinson disease and dementia with Lewy bodies (DLB). There is a need for more sensitive techniques to measure intracellular copper levels to have a better understanding of the role of copper homeostasis in neuronal disorders. Here, we report a reaction-based near-infrared (NIR) ratiometric fluorescent probe CyCu1 for imaging Cu2+ in biological samples. High stability and selectivity of CyCu1 enabled the probe to be deployed as a sensor in a range of systems, including SH-SY5Y cells and neuroblastoma tumors. Furthermore, it can be used in plant cells, reporting on copper added to Arabidopsis roots. We also used CyCu1 to explore Cu2+ levels and distribution in post-mortem brain tissues from patients with DLB. We found significant decreases in Cu2+ content in the cytoplasm, neurons, and extraneuronal space in the degenerating substantia nigra in DLB compared with healthy age-matched control tissues. These findings enhance our understanding of Cu2+ dysregulation in Lewy body disorders. Our probe also shows promise as a photoacoustic imaging agent, with potential for applications in bimodal imaging.

[Bilateral vestibulopathy and sensorineural hearing loss in necrobiotic xanthogranuloma, multiple myeloma and amiloidosis]. / Dvustoronnyaya vestibulopatiya i sensonevral'naya tugoukhost' u patsienta s nekroticheskoi ksantogranulemoi, mnozhestvennoi mielomoi i amiloidozom.

This article describes a rare case of necrotic xanthogranuloma in a 46-year-old patient who presented with the development of periorbital xanthelasms, progressive bilateral sensorineural hearing loss and bilateral vestibulopathy, followed by multiple myeloma and amyloidosis. For several years, the patient underwent standard rehabilitation for chronic sensorineural hearing loss and was fitted with a hearing aid. During hospitalisation for exacerbation of chronic bronchitis, monoclonal gammopathy was identified, and later, after careful examination and repeated biopsies, necrotic xanthogranuloma, multiple myeloma and AL-amyloidosis were confirmed. Targeted immunochemotherapy resulted in improvement of hearing and significant recovery of the vestibuloocular reflex bilaterally.