Loss of biochemical response at any time worsens outcomes in UDCA-treated patients with primary biliary cholangitis.

Background & Aims: Biochemical response to ursodeoxycholic acid (UDCA) therapy is associated with good prognosis in people living with primary biliary cholangitis (PBC). Biochemical response is typically assessed early in disease and it is not known what proportion of patients lose previously attained biochemical response, nor whether this impacts long-term liver transplant (LT)-free survival. Methods: We identified all UDCA-treated patients with PBC from the Canadian Network for Autoimmune Liver disease with biochemical measurements at 1 year, and evaluated their liver biochemistry over time. Inadequate biochemical response was defined as serum alkaline phosphatase ≥1.67x the upper limit of normal or abnormal serum total bilirubin at 1 year of UDCA therapy and all time points thereafter. Multistate Markov models were used to estimate transition rates between biochemical response states and from each state to LT or death. Results were validated in an external cohort (GLOBAL PBC registry). Results: A total of 823 patients from eight centers were included. Mean age at diagnosis was 53 years, 91% were female, 33% had inadequate biochemical response to UDCA at 1 year (n = 269). Patients who retained initial adequate response had lower rates of LT or death compared to patients who subsequently lost response (relative rate 0.102, 95% CI 0.047-0.223). Patients who regained adequate response had lower rates than patients who did not (0.016, 95% CI 0.001-0.568), and patients who lost response once more (0.010, 95% CI 0.001-0.340). Patients who regained adequate response for a third time also had lower rates than patients who did not (0.151, 95% CI 0.040-0.566). Analyses in the GLOBAL PBC registry (n = 2,237) validated these results. Conclusion: Loss of biochemical response at any time is associated with heightened risks of LT or death in people living with PBC. Achievement of biochemical response is an important goal throughout follow-up, regardless of biochemical response profile early in therapy. Impact and implications: Early biochemical response to ursodeoxycholic acid is associated with good prognosis in patients with primary biliary cholangitis (PBC). Our work demonstrates that patients with PBC transition between biochemical response states over time, and that these transitions correspond with changes in risk of liver transplantation or death. Clinicians should re-evaluate risk and optimize treatment decisions for patients with PBC throughout follow-up, regardless of early biochemical response to therapy.

Clinical Phenotyping for Prognosis and Immunotherapy Guidance in Bacterial Sepsis and COVID-19.

OBJECTIVES: It is suggested that sepsis may be classified into four clinical phenotypes, using an algorithm employing 29 admission parameters. We applied a simplified phenotyping algorithm among patients with bacterial sepsis and severe COVID-19 and assessed characteristics and outcomes of the derived phenotypes. DESIGN: Retrospective analysis of data from prospective clinical studies. SETTING: Greek ICUs and Internal Medicine departments. PATIENTS AND INTERVENTIONS: We analyzed 1498 patients, 620 with bacterial sepsis and 878 with severe COVID-19. We implemented a six-parameter algorithm (creatinine, lactate, aspartate transaminase, bilirubin, C-reactive protein, and international normalized ratio) to classify patients with bacterial sepsis intro previously defined phenotypes. Patients with severe COVID-19, included in two open-label immunotherapy trials were subsequently classified. Heterogeneity of treatment effect of anakinra was assessed. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS: The algorithm validated the presence of the four phenotypes across the cohort of bacterial sepsis and the individual studies included in this cohort. Phenotype α represented younger patients with low risk of death, ß was associated with high comorbidity burden, and δ with the highest mortality. Phenotype assignment was independently associated with outcome, even after adjustment for Charlson Comorbidity Index. Phenotype distribution and outcomes in severe COVID-19 followed a similar pattern. CONCLUSIONS: A simplified algorithm successfully identified previously derived phenotypes of bacterial sepsis, which were predictive of outcome. This classification may apply to patients with severe COVID-19 with prognostic implications.

Enhancing Unmanned Aerial Vehicle Security: A Zero-Knowledge Proof Approach with Zero-Knowledge Succinct Non-Interactive Arguments of Knowledge for Authentication and Location Proof.

UAVs are increasingly being used in various domains, from personal and commercial applications to military operations. Ensuring the security and trustworthiness of UAV communications is crucial, and blockchain technology has been explored as a solution. However, privacy remains a challenge, especially in public blockchains. In this work, we propose a novel approach utilizing zero-knowledge proof techniques, specifically zk-SNARKs, which are non-interactive cryptographic proofs. This approach allows UAVs to prove their authenticity or location without disclosing sensitive information. We generated zk-SNARK proofs using the Zokrates tool on a Raspberry Pi, simulating a drone environment, and analyzed power consumption and CPU utilization. The results are promising, especially in the case of larger drones with higher battery capacities. Ethereum was chosen as the public blockchain platform, with smart contracts developed in Solidity and tested on the Sepolia testnet using Remix IDE. This novel proposed approach paves the way for a new path of research in the UAV area.

Clinical Phenotyping for Prognosis and Immunotherapy Guidance in Bacterial Sepsis and COVID-19.

OBJECTIVES: It is suggested that sepsis may be classified into four clinical phenotypes, using an algorithm employing 29 admission parameters. We applied a simplified phenotyping algorithm among patients with bacterial sepsis and severe COVID-19 and assessed characteristics and outcomes of the derived phenotypes. DESIGN: Retrospective analysis of data from prospective clinical studies. SETTING: Greek ICUs and Internal Medicine departments. PATIENTS AND INTERVENTIONS: We analyzed 1498 patients, 620 with bacterial sepsis and 878 with severe COVID-19. We implemented a six-parameter algorithm (creatinine, lactate, aspartate transaminase, bilirubin, C-reactive protein, and international normalized ratio) to classify patients with bacterial sepsis intro previously defined phenotypes. Patients with severe COVID-19, included in two open-label immunotherapy trials were subsequently classified. Heterogeneity of treatment effect of anakinra was assessed. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS: The algorithm validated the presence of the four phenotypes across the cohort of bacterial sepsis and the individual studies included in this cohort. Phenotype α represented younger patients with low risk of death, ß was associated with high comorbidity burden, and δ with the highest mortality. Phenotype assignment was independently associated with outcome, even after adjustment for Charlson Comorbidity Index. Phenotype distribution and outcomes in severe COVID-19 followed a similar pattern. CONCLUSIONS: A simplified algorithm successfully identified previously derived phenotypes of bacterial sepsis, which were predictive of outcome. This classification may apply to patients with severe COVID-19 with prognostic implications.

Can limb length discrepancies be corrected with the Masquelet technique? A technical trick.

Masquelet technique is a well-established procedure for reconstruction of bone defects secondary to such causes as infections, non-unions, tumors or open fractures with bone loss. The management of limb length discrepancies following bone defects has been well established using bone transport and remains the preferred choice amongst reconstruction surgeons. One of the criticisms of the Masquelet technique has been its limitation to address limb length discrepancies. We describe a technique for the correction of limb length discrepancies using the Masquelet technique.

Vortex inverted pin beams: mitigation of scintillations in strong atmospheric turbulence.

We recently introduced a new class of optical beams with a Bessel-like transverse profile and increasing beam width during propagation, akin to an "inverted pin." Owing to their specially engineered distribution, these beams have shown remarkable performance in atmospheric turbulence. Specifically, inverted pin beams (PBs) were found to have a reduced scintillation index as compared to collimated or focused Gaussian beams as well as other types of pin beams especially in moderate to strong turbulence. In this work, we demonstrate that inverted pin beams carrying orbital angular momentum (OAM) can further suppress intensity scintillations in moderate to strong irradiance fluctuation conditions. Our results can be useful in improving the performance and link availability of free-space optical communication systems.

Efficacy and safety of palliative treatment in patients with autoimmune liver disease-associated hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: Autoimmune liver diseases (AILD) are rare causes hepatocellular carcinoma (HCC), and data on the efficacy and tolerability of anti-tumor therapies are scarce. This pan-European study aimed to assess outcomes in AILD-HCC patients treated with tyrosine kinase inhibitors (TKIs) or transarterial chemoembolization (TACE) compared with patients with more common HCC etiologies, including viral, alcoholic or non-alcoholic fatty liver disease. MATERIALS AND METHODS: 107 patients with HCC-AILD (AIH:55; PBC:52) treated at 13 European centres between 1996 and 2020 were included. 65 received TACE and 28 received TKI therapy. 43 (66 %) were female (median age 73 years) with HCC tumor stage BCLC A (34 %), B (46 %), C (9 %) or D (11 %). For each treatment type, propensity score matching was used to match AILD to non-AILD-HCC on a 1:1 basis, yielding in a final cohort of 130 TACE and 56 TKI patients for comparative analyses of median overall survival (mOS) and treatment tolerability. RESULTS: HCC-AILD patients showed comparable mOS to controls for both TACE (19.5 vs. 22.1 months, p = 0.9) and TKI (15.4 vs. 15.1 months, p = 0.5). Adverse events were less frequent in AILD-HCC patients than controls (33 % % vs. 62 %, p = 0.003). For TKIs, there were no significant differences in adverse events (73% vs. 86%, p = 0.2) or interruption rates (44% vs. 36 %, p = 0.7). CONCLUSIONS: In summary, this study demonstrates comparable mOS for AILD-HCC patients undergoing local and systemic treatments, with better tolerability than HCC of other causes. TKIs remain important therapeutic options for AILD-HCC patients, particularly given their exclusion from recent immunotherapy trials.

Revision Anterior Cruciate Ligament Reconstruction in Pediatric and Adolescent Patients Yields Low Rates of Graft Failure and Good Functional Scores, but Low Rates of Return to Sport: A Systematic Review.

PURPOSE: To evaluate outcomes after revision anterior cruciate ligament reconstruction (ACLR) in pediatric and adolescent patients in terms of graft failure rate and functional patient outcomes. METHODS: A systematic review of Cochrane, Embase, Scopus, Ovid, and PubMed databases was performed for all original clinical studies that reported outcomes of pediatric and adolescent patients undergoing revision ACLR. Non-English studies and studies not reporting both graft failure rates and an additional outcome measure were excluded. We evaluated patient demographics, injury mechanisms, surgical technique characteristics, concomitant injuries, failure rates, patient-reported outcome measures (PROMs), complications, and return to sports rates. Risk of bias (ROB) was assessed with the methodological index for nonrandomized studies (MINORS). RESULTS: Five studies with a total of 239 knees in 234 patients were included. Failure of the revision ACLR ranged from 9% to 21%. Return to previous level of activity ranged between 27% and 68%. PROMs were variable, with good Lysholm Knee Scoring Scale score (range 84.5-93.7), moderate Tegner Activity Score (range 5.5-9.0), and good International Knee Documentation Committee knee scores (range 79.9-80.0). Allograft was used in 48% of revisions, followed by bone patellar tendon bone autograft in 34%, and hamstrings (HS) autograft in 14%. Meniscus injury and cartilage injury was present in 53.1% to 92.5% and 5.5% to 59.4% of knees, respectively. Gwet's AC1 coefficient was 0.89, indicating a high degree of interrater reliability. The average MINORS score was 6, and heterogeneity was low (I2 = 9%). The included studies did not present with sufficient detail to disaggregate clinical outcomes by patient sex. CONCLUSIONS: Revision ACLR yields a graft failure ranging from 9 to 20%. Revision patients experience good PROMs but low rates of return to preinjury level of sport. Further, revision ACLR was associated with high rates of intra-articular damage and relatively low rates of meniscal repair at the time of second surgery. LEVEL OF EVIDENCE: Level IV, systematic review of level IV evidence.

PNPLA3 I148 M genetic variant in autoimmune hepatitis characterises advanced disease at diagnosis and reduced survival free of cirrhotic events and liver-related mortality.

Background: Autoimmune hepatitis (AIH) is a relatively rare autoimmune disease with a strong genetic background. The patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148 M (rs738409 C/G) variant has been associated with hepatic inflammation and fibrosis in chronic hepatic diseases beyond metabolic dysfunction-associated steatotic liver disease (MASLD). Aim: Our aim was to investigate the significance of PNPLA3 I148 M variant in AIH. Method: Two hundred AIH patients, followed in our centre, were evaluated while 100 healthy subjects served as controls. Genotyping was performed with allelic discrimination end-point polymerase chain reaction (PCR). Results: The I148 M variant was present in 95/200 (47.5 %) AIH patients compared to 47/100 (47 %) healthy controls (p = 1.000). Patients with GG/CG genotypes were more likely to present with decompensated cirrhosis at diagnosis (GG/CG 6.3 % vs. CC 1 %, p = 0.039). Comorbidity with cardiometabolic risk factors and concurrence of MASLD was similar across genotypes. Simple steatosis was present in 37/186 (19.9 %) and steatohepatitis in 14/186 (7.5 %) patients with available liver biopsy without correlation with PNPLA3 genotype. Fibrosis stage and grade of inflammation were not correlated with any genotype. Response to treatment was also independent of the presence of the I148 M variant, even though a longer time was needed to achieve complete biochemical response in those carrying the GG/CG genotypes (p = 0.07). On Kaplan Meier analysis homozygosity for the G allele corelated with reduced survival free of decompensation (p = 0.006), cirrhotic events (decompensation, liver transplantation, hepatocellular carcinoma; p = 0.001) and liver-related death or liver transplantation (p = 0.011) in treated patients. Conclusions: The PNPLA3 I148 M variant in AIH patients is associated with increased risk of advanced disease at diagnosis and reduced survival free of cirrhotic events and liver-related death or liver transplantation, regardless of the presence of MASLD. This signifies a potential role for the PNPLA3 I148 M variant as a new AIH biomarker allowing to identify patients at increased risk of disease progression.

Donanemab, another anti-Alzheimer's drug with risk and uncertain benefit.

Based on "reducing amyloid plaques in the brain", the U.S. Food and Drug Administration has granted accelerated and full approval for two monoclonal anti-Alzheimer's antibodies, aducanumab and lecanemab, respectively. Approval of a third antibody, donanemab, is pending. Moreover, lecanemab and donanemab are claimed to cause delay in the cognitive decline that characterizes the disease. We believe that these findings are subject to misinterpretation and statistical bias. Donanemab is claimed to cause removal of up to 86 % of cerebral amyloid and 36 % delay in cognitive decline compared to placebo. In reality, these are very small changes on an absolute scale and arguably less than what can be achieved with cholinesterase inhibitor/memantine therapy. Moreover, the "removal" of amyloid, based on the reduced accumulation of amyloid-PET tracer, most likely also reflects therapy-related tissue damage. This would also correlate with the minimal clinical effect, the increased frequency of amyloid-related imaging abnormalities, and the accelerated loss of brain volume in treated compared to placebo patients observed with these antibodies. We recommend halting approvals of anti-AD antibodies until these issues are fully understood to ensure that antibody treatment does not cause more harm than benefit to patients.

NanoConstruct: A web application builder of ellipsoidal nanoparticles for the investigation of their crystal growth, stability, and the calculation of atomistic descriptors.

NanoConstruct is a state-of-the-art computational tool that enables a) the digital construction of ellipsoidal neutral energy minimized nanoparticles (NPs) in vacuum through its graphical user-friendly interface, and b) the calculation of NPs atomistic descriptors. It allows the user to select NP's shape and size by inserting its ellipsoidal axes and rotation angle while the NP material is selected by uploading its Crystallography Information File (CIF). To investigate the stability of materials not yet synthesised, NanoConstruct allows the substitution of the chemical elements of an already synthesized material with chemical elements that belong into the same group and neighbouring rows of the periodic table. The process is divided into three stages: 1) digital construction of the unit cell, 2) digital construction of NP using geometry rules and keeping its stoichiometry and 3) energy minimization of the geometrically constructed NP and calculation of its atomistic descriptors. In this study, NanoConstruct was applied for the investigation of the crystal growth of Zirconia (ZrO2) NPs when in the rutile form. The most stable configuration and the crystal growth route were identified, showing a preferential direction for the crystal growth of ZrO2 in its rutile form. NanoConstruct is freely available through the Enalos Cloud Platform (https://enaloscloud.novamechanics.com/riskgone/nanoconstruct/).

Statistical mechanics and pressure of composite multimoded weakly nonlinear optical systems.

Statistical mechanics can provide a versatile theoretical framework for investigating the collective dynamics of weakly nonlinear-wave settings that can be utterly complex to describe otherwise. In optics, composite systems arise due to interactions between different frequencies and polarizations. The purpose of this work is to develop a thermodynamic theory that takes into account the synergistic action of multiple components. We find that the type of the nonlinearity involved can have important implications in the thermalization process and, hence, can lead to different thermal equilibrium conditions. Importantly, we derive closed-form expressions for the actual optomechanical pressure that is exerted on the system. In particular, the total optomechanical pressure is the sum of the partial pressures due to each component. Our results can be applied to a variety of weakly nonlinear optical settings such as multimode fibers, bulk waveguides, photonic lattices, and coupled microresonators. We present two specific examples, where two colors interact in a one-waveguide array with either a cubic or quadratic nonlinearity.

Arthroscopic Patella Realignment for Children And Adolescents: A Single Incision Technique.

Management of patellofemoral conditions in children and adolescents can be extremely challenging. Apart from the patellofemoral instability patients, there are several other disorders that can cause significant morbidity, patellofemoral maltracking, patellar tilt, and Hoffa's fat pad impingement syndrome are common problems that may not respond to nonoperative management. Understanding the exact pathology and apply the appropriate management is critical for successful outcome. Identification of novel surgical interventions that can provide symptom relief in a safe manner is important. This technical note describes a surgical technique for patella realignment in young patients that combines safety, simplicity, and reproducibility.

Dalton's law of partial optical thermodynamic pressures in highly multimoded nonlinear photonic systems.

We show that in highly multimoded nonlinear photonic systems, the optical thermodynamic pressures emerging from different species of the optical field obey Dalton's law of partial pressures. In multimode settings, the optical thermodynamic pressure is defined as the conjugate to the extensive variable associated with the system's total number of modes and is directly related to the actual electrodynamic radiation forces exerted at the physical boundaries of the system. Here, we extend this notion to photonic configuration supporting different species of the optical field. Under thermal equilibrium conditions, we formally derive an equation that establishes a direct link between the partial thermodynamic pressures and the electrodynamic radiation pressures exerted by each polarization species. Our theoretical framework provides a straightforward approach for quantifying the total radiation pressures through the system's thermodynamic variables without invoking the Maxwell stress tensor formalism. In essence, we show that the total electrodynamic pressure in such arrangements can be obtained in an effortless manner from initial excitation conditions, thus avoiding time-consuming simulations of the utterly complex multimode dynamics. To illustrate the validity of our results, we carry out numerical simulations in multimoded nonlinear optical structures supporting two polarization species and demonstrate excellent agreement with the Maxwell stress tensor method.

In silico assessment of nanoparticle toxicity powered by the Enalos Cloud Platform: Integrating automated machine learning and synthetic data for enhanced nanosafety evaluation.

The rapid advance of nanotechnology has led to the development and widespread application of nanomaterials, raising concerns regarding their potential adverse effects on human health and the environment. Traditional (experimental) methods for assessing the nanoparticles (NPs) safety are time-consuming, expensive, and resource-intensive, and raise ethical concerns due to their reliance on animals. To address these challenges, we propose an in silico workflow that serves as an alternative or complementary approach to conventional hazard and risk assessment strategies, which incorporates state-of-the-art computational methodologies. In this study we present an automated machine learning (autoML) scheme that employs dose-response toxicity data for silver (Ag), titanium dioxide (TiO2), and copper oxide (CuO) NPs. This model is further enriched with atomistic descriptors to capture the NPs' underlying structural properties. To overcome the issue of limited data availability, synthetic data generation techniques are used. These techniques help in broadening the dataset, thus improving the representation of different NP classes. A key aspect of this approach is a novel three-step applicability domain method (which includes the development of a local similarity approach) that enhances user confidence in the results by evaluating the prediction's reliability. We anticipate that this approach will significantly expedite the nanosafety assessment process enabling regulation to keep pace with innovation, and will provide valuable insights for the design and development of safe and sustainable NPs. The ML model developed in this study is made available to the scientific community as an easy-to-use web-service through the Enalos Cloud Platform (www.enaloscloud.novamechanics.com/sabydoma/safenanoscope/), facilitating broader access and collaborative advancements in nanosafety.

The Sociodemographic Factors Related to Disability of Applicants of Welfare Benefits in Greece: A Cross-Sectional Survey Based on the World Health Organization Disability Assessment Schedule (WHODAS) 2.0.

INTRODUCTION: The aim of the present study was to report on the prevalence of disability and its association with sociodemographic factors among welfare benefit applicants in Greece. The study also compared the disability scores between different health conditions using the WHODAS 2.0 (12-item version), a biopsychosocial-model-based measure. METHODS: The Greek WHODAS 2.0, 12-item version, was administered by interview. A three-member medical committee assessed the medical records of the applicants and assigned a disability percentage based on the biomedical measure of disability percentage determination (Barema scale). RESULTS: The majority of the participants were female (56.65%). Certain health conditions were presented more frequently among welfare benefit applicants (mental health disorders and neoplasms). The domains with the highest rate of difficulty were the "participation" and "life activities" domains. Significant differences were found between WHODAS 2.0 and Barema scores for all eight different health condition categories. The factorial ANOVA (8x2) showed a significant interaction effect between health condition category and gender with respect to the WHODAS 2.0 score (F = 19.033, p <.001, η2 = 0.13). The WHODAS 2.0 score was negatively correlated to gender, years of studies, and marital status and positively correlated to age, working status, and the Barema score. The results revealed that male participants with a partner who were younger, had more studies, were actively working, and had a lower Barema score would have lower WHODAS scores. CONCLUSION: Sociodemographic characteristics of welfare benefit applicants are associated with disability levels based on WHODAS 2.0. Certain health conditions, like mental health or neuromusculoskeletal conditions, are associated with higher disability scores. There are differences between the biopsychosocial and the biomedical approaches to disability assessment. The implementation of WHODAS 2.0 may contribute to a better understanding of the lived experience of patients and is a feasible and efficient tool. Combining biomedical and biopsychosocial approaches may enhance the procedures of disability assessment and help in the development of policies that support people with disabilities.

Real-World Data and Evidence in Lung Cancer: A Review of Recent Developments.

Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects of cancer treatments in real-world settings. The distinction between RWD and data derived from randomized clinical trials lies in the method of data collection, as RWD by definition are obtained at the point of care. Experimental designs resembling those used in traditional clinical trials can be utilized to generate RWD, thus offering multiple benefits including increased efficiency and a more equitable balance between internal and external validity. Real-world data can be utilized in the field of pharmacovigilance to facilitate the understanding of disease progression and to formulate external control groups. By utilizing prospectively collected RWD, it is feasible to conduct pragmatic clinical trials (PCTs) that can provide evidence to support randomized study designs and extend clinical research to the patient's point of care. To ensure the quality of real-world studies, it is crucial to implement auditable data abstraction methods and develop new incentives to capture clinically relevant data electronically at the point of care. The treatment landscape is constantly evolving, with the integration of front-line immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, affecting subsequent treatment lines. Real-world effectiveness and safety in underrepresented populations, such as the elderly and patients with poor performance status (PS), hepatitis, or human immunodeficiency virus, are still largely unexplored. Similarly, the cost-effectiveness and sustainability of these innovative agents are important considerations in the real world.

Editorial Commentary: Waiting at Least 1 Month After an Intra-articular Corticosteroid Injection for Performing a Knee, Shoulder, and Hip Arthroscopy Could Minimize the Risk for Postoperative Infection: Platelet-Rich Plasma Is an Alternative.

An intra-articular corticosteroid is associated with a higher risk of joint infection. Identifying the necessary time interval from the injection to the arthroscopic procedure that does not impose an additional risk of infection is critical for the safety of our patients. Increasing evidence suggests that there is a high risk of infection at the first 4 weeks after the injection, but it seems that this risk declines to normal levels after that period. Interestingly, this time interval of 4 weeks is comparable between knee, shoulder, and hip injection and subsequent arthroscopy. A delay of an arthroscopic intervention at any joint for at least 4 weeks is recommended. Finally, platelet-rich plasma (PRP) is equally effective as corticosteroids in terms of pain management and anti-inflammatory response, with the advantage of promoting healing. PRP may also be associated with a lower risk of postoperative infection in patients undergoing arthroscopy, representing a biologic alternative.

ASCOT: A web tool for the digital construction of energy minimized Ag, CuO, TiO2 spherical nanoparticles and calculation of their atomistic descriptors.

ASCOT (an acronym derived from Ag-Silver, Copper Oxide, Titanium Oxide) is a user-friendly web tool for digital construction of electrically neutral, energy-minimized spherical nanoparticles (NPs) of Ag, CuO, and TiO2 (both Anatase and Rutile forms) in vacuum, integrated into the Enalos Cloud Platform (https://www.enaloscloud.novamechanics.com/sabydoma/ascot/). ASCOT calculates critical atomistic descriptors such as average potential energy per atom, average coordination number, common neighbour parameter (used for structural classification in simulations of crystalline phases), and hexatic order parameter (which measures how closely the local environment around a particle resembles perfect hexatic symmetry) for both core (over 4 Å from the surface) and shell (within 4 Å of the surface) regions of the NPs. These atomistic descriptors assist in predicting the most stable NP size based on lowest per atom energy and serve as inputs for developing machine learning models to predict the toxicity of these nanomaterials. ASCOT's automated backend requires minimal user input in order to construct the digital NPs: inputs needed are the material type (Ag, CuO, TiO2-Anatase, TiO2-Rutile), target diameter, a Force-Field from a pre-validated list, and the energy minimization parameters, with the tool providing a set of default values for novice users.

Artificial Intelligence-Based Treatment Decisions: A New Era for NSCLC.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality among women and men, in developed countries, despite the public health interventions including tobacco-free campaigns, screening and early detection methods, recent therapeutic advances, and ongoing intense research on novel antineoplastic modalities. Targeting oncogenic driver mutations and immune checkpoint inhibition has indeed revolutionized NSCLC treatment, yet there still remains the unmet need for robust and standardized predictive biomarkers to accurately inform clinical decisions. Artificial intelligence (AI) represents the computer-based science concerned with large datasets for complex problem-solving. Its concept has brought a paradigm shift in oncology considering its immense potential for improved diagnosis, treatment guidance, and prognosis. In this review, we present the current state of AI-driven applications on NSCLC management, with a particular focus on radiomics and pathomics, and critically discuss both the existing limitations and future directions in this field. The thoracic oncology community should not be discouraged by the likely long road of AI implementation into daily clinical practice, as its transformative impact on personalized treatment approaches is undeniable.