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Hung-Hsiang Huang,1,* Chi-Jie Lu,2– 4,* Mao-Jhen Jhou,4 Tzu-Chi Liu,4 Chih-Te Yang,5 Shang-Ju Hsieh,1 Wen-Jen Yang,6 Hsiao-Chun Chang,1 Ming-Shu Chen7 1Department of Urology, Surgery, Far Eastern Memorial Hospital, New Taipei City, 220, Taiwan; 2Artificial Intelligence Development Center, Fu Jen Catholic University, New Taipei City, 242, Taiwan; 3Department of Information Management, Fu Jen Catholic University, New Taipei City, 242, Taiwan; 4Graduate Institute of Business Administration, Fu Jen Catholic University, New Taipei City, 242, Taiwan; 5Department of Business Administration, Tamkang University, New Taipei City, 251, Taiwan; 6Health Screening Center, Chi Hsin Clinic, Taipei City, 104, Taiwan; 7Department of Healthcare Administration, Asia Eastern University of Science and Technology, New Taipei City, 220, Taiwan*These authors contributed equally to this workCorrespondence: Ming-Shu Chen; Hsiao-Chun Chang, Email tree1013@mail.gmail.com; liberalcsc@gmail.comPurpose: Approximately 20% of couples face infertility challenges and struggle to conceive naturally. Despite advances in artificial reproduction, its success hinges on sperm quality. Our previous study used five machine learning (ML) algorithms, random forest, stochastic gradient boosting, least absolute shrinkage and selection operator regression, ridge regression, and extreme gradient boosting, to model health data from 1375 Taiwanese males and identified ten risk factors affecting sperm count.Methods: We employed the CART algorithm to generate decision trees using identified risk factors to predict healthy sperm counts. Four error metrics, SMAPE, RAE, RRSE, and RMSE, were used to evaluate the decision trees. We identified the top five decision trees based on their low errors and discussed in detail the tree with the least error.Results: The decision tree featuring the least error, comprising BMI, UA, ST, T-Cho/HDL-C ratio, and BUN, corroborated the negative impacts of metabolic syndrome, particularly high BMI, on sperm count, while emphasizing the link between good sleep and male fertility. Our study also sheds light on the potentially significant influence of high BUN on spermatogenesis. Two novel risk factors, T-Cho/HDL-C and UA, warrant further investigation.Conclusion: The ML algorithm established a predictive model for healthcare personnel to assess low sperm counts. Refinement of the model using additional data is crucial for improved precision. The risk factors identified offer avenues for future investigations.Keywords: sperm count, metabolic syndrome, sleep time, food metabolite, decision tree

Flavonoids from mulberry leave (FML) are natural flavonoids, and Candida tropicalis (CT) is yeast like microbe. In this study, forty-eight male calves were selected with born weight (40.5±0.7 kg) and 20±2 days age, divided into 4 groups randomly. FML was supplemented in a dairy calf starter at 2 g/d per calf before weaning, or 4 g/d per calf after weaning (FML group), while CT was added in a dairy calf starter at 1 g/d per calf (CT group). Our results showed that FML could be used to enhance body weight (BW) of calves through enhancing apparent digestibility of ether extract (EE) of the diet, and increased the levels of serum growth hormone (GH) and insulin-like growth factors 1 (IGF-1) in calves after the age of 56 days. CT enhanced the BW of calves before weaning through increasing the apparent digestibility of neutral detergent fiber (NDF) of the diet, and elevated the apparent digestibility of EE of the diet of calves after weaning through increasing the level of serum IGF-1 in calves. Furthermore, the mixture of FML and CT plays a synergistic role in enhancing growth, improving feed intake and nutriment digestibility. In conclusion, FML and CT could be used as additives to increase growth and nutrient digestibility in calves.

Alexander W Jackson,1,* Prashant Chandrasekharan,2,* Jian Shi,3 Steven P Rannard,4 Quan Liu,5 Chang-Tong Yang,6 Tao He1,7 1Institute of Chemical and Engineering Sciences (ICES), 2Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science Technology and Research (A* STAR), 3Department of Biological Science, National University of Singapore, Singapore; 4Department of Chemistry, University of Liverpool, Liverpool, United Kingdom; 5School of Chemical and Biomedical Engineering, 6Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 7School of Chemistry and Chemical Engineering, HeFei University of Technology, Anhui, People’s Republic of China *These authors contributed equally to this work Abstract: Branched copolymer nanoparticles (Dh =20–35 nm) possessing 1,4,7, 10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid macrocycles within their cores have been synthesized and applied as magnetic resonance imaging (MRI) nanosized contrast agents in vivo. These nanoparticles have been generated from novel functional monomers via reversible addition–fragmentation chain transfer polymerization. The process is very robust and synthetically straightforward. Chelation with gadolinium and preliminary in vivo experiments have demonstrated promising characteristics as MRI contrast agents with prolonged blood retention time, good biocompatibility, and an intravascular distribution. The ability of these nanoparticles to perfuse and passively target tumor cells through the enhanced permeability and retention effect is also demonstrated. These novel highly functional nanoparticle platforms have succinimidyl ester-activated benzoate functionalities within their corona, which make them suitable for future peptide conjugation and subsequent active cell-targeted MRI or the conjugation of fluorophores for bimodal imaging. We have also demonstrated that these branched copolymer nanoparticles are able to noncovalently encapsulate hydrophobic guest molecules, which could allow simultaneous bioimaging and drug delivery. Keywords: branched copolymer nanoparticles, gadolinium chelate, MRI, RAFT polymerization

Chih-Hao Chang,1 Kuo-Chien Tsao,2,3 Han-Chung Hu,1,4 Chung-Chi Huang,1,4 Kuo-Chin Kao,1,4 Ning-Hung Chen,1,4 Cheng-Ta Yang,1,4 Ying-Huang Tsai,4,5 Meng-Jer Hsieh4,51Department of Pulmonary and Critical Care Medicine, Linkou Chang-Gung Memorial Hospital, Chang-Gung Medical Foundation, Chang-Gung University College of Medicine, Taoyuan, Taiwan; 2Department of Laboratory Medicine, Linkou Chang-Gung Memorial Hospital, Chang-Gung Medical Foundation; 3Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan; 4Department of Respiratory Therapy, Chang-Gung University, Taoyuan, Taiwan; 5Department of Pulmonary and Critical Care Medicine, Chiayi Chang-Gung Memorial Hospital, Chang-Gung Medical Foundation, Puzi City, TaiwanBackground: Viral and bacterial infections are the most common causes of chronic obstructive pulmonary disease (COPD) exacerbations. Whether serum inflammatory markers can differentiate bacterial from virus infection in patients with COPD exacerbation requiring emergency department (ED) visits remains controversial.Methods: Viral culture and polymerase chain reaction (PCR) were used to identify the viruses in the oropharynx of patients with COPD exacerbations. The bacteria were identified by the semiquantitative culture of the expectorated sputum. The peripheral blood white blood cell (WBC) counts, serum C-reactive protein (CRP), procalcitonin (PCT), and clinical symptoms were compared among patients with different types of infections.Results: Viruses were isolated from 16 (22.2%) of the 72 patients enrolled. The most commonly identified viruses were parainfluenza type 3, influenza A, and rhinovirus. A total of 30 (41.7%) patients had positive bacterial cultures, with the most commonly found bacteria being Haemophilus influenzae and Haemophilus parainfluenzae. Five patients (6.9%) had both positive sputum cultures and virus identification. The WBC, CRP, and PCT levels of the bacteria-positive and bacteria-negative groups were not statistically different. Multivariate analysis showed that patients with increased sputum volumes during the COPD exacerbations had higher risks of recurrent exacerbations in the 1-year period following the first exacerbation.Conclusion: WBC, CRP, or PCT could not differentiate between bacterial and viral infections in patients with COPD exacerbation requiring ED visits. Those with increased sputum during a COPD exacerbation had higher risks for recurrent exacerbations.Keywords: chronic obstructive pulmonary disease, bacterial infection, virus, CRP

The adsorption of n-alkanes onto Brønsted-acid sites is a key step in the catalytic cracking of alkanes. Employing configurational-bias Monte Carlo simulations, we have investigated how the ratio of equilibrium adsorption constants for central C-C bonds relative to terminal bonds of n-alkanes (i.e., the adsorption selectivity ratio) in Brønsted-acid zeolites is influenced by the Si/Al ratio and the Al distribution. A new computational approach was implemented, and the developed force field was validated by a comprehensive comparison between simulation results and experimental data for a number of Brønsted-acid zeolites. While the adsorption selectivity seems to be relatively insensitive to the Si/Al ratio, our results reveal that the Al distribution plays a crucial role in determining the adsorption selectivity. Changes in the Al distribution result in a change of as much as 2-fold in the adsorption selectivity ratio for n-hexane. The selectivity generally shows larger variations with respect to Al distribution in zeolites with a larger Si/Al ratio. The two factors identified by this work that substantially influence the selectivity ratio are the siting of Al atoms among T-sites and their spatial proximity, and an atomic-level understanding of each of these effects was achieved. The siting of Al atoms at more or less selective T-sites significantly influences the overall selectivity ratio, and Al atoms in close proximity can synergistically enhance the adsorption of central C-C bonds, leading to a higher selectivity ratio relative to isolated Al atoms. We anticipate that these results will have important implications for future large-scale computational screenings and the development of advanced synthesis approaches to target certain Al distributions in zeolites.

Casein kinase II (CK2) inhibitors suppress cancer cell growth. In this study, we examined the inhibitory effects of a novel CK2 inhibitor, hematein, on tumor growth in a murine xenograft model. We found that in lung cancer cells, hematein inhibited cancer

BACKGROUND: Few studies have investigated the effects of care models that combine interdisciplinary care with nutrition consultation, depression management, and fall prevention in older persons with hip fracture. The purpose of this study was to compare the effects of a comprehensive care program with those of interdisciplinary care and usual care for elderly patients with hip fracture. METHODS: A randomized experimental trial was used to explore outcomes for 299 elderly patients with hip fracture receiving three treatment care models: interdisciplinary care (n = 101), comprehensive care (n = 99), and usual care (n = 99). Interdisciplinary care included geriatric consultation, continuous rehabilitation, and discharge planning with post-hospital services. Comprehensive care consisted of interdisciplinary care plus nutrition consultation, depression management, and fall prevention. Usual care included only in-hospital rehabilitation without geriatric consultation, in-home rehabilitation, and home environmental assessment. RESULTS: Participants in the comprehensive care group had better self-care ability (odds ratio, OR = 3.19, p < .01) and less risk of depression (OR = 0.48, p < .01) than those who received usual care. The comprehensive care group had less risk of depression (OR = 0.51, p < .05) and of malnutrition (OR = 0.48, p < .05) than the interdisciplinary care group during the first year following discharge. Older persons with hip fracture benefitted more from the comprehensive care program than from interdisciplinary care and usual care. CONCLUSIONS: Older persons with hip fracture benefitted more from comprehensive care including interdisciplinary care and nutrition consultation, depression management, and fall prevention than simply interdisciplinary care. [ABSTRACT FROM AUTHOR]

Background: Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), shows superior lung cancer treatment efficacy. However, osimertinib-induced severe hypersensitivity, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), is frequently observed in Asian populations and hinders cancer treatment., Objective: We investigated the genetic HLA predisposition and immune pathomechanism of osimertinib-induced hypersensitivity., Methods: We enrolled 17 patients with osimertinib-induced delayed hypersensitivity (7 with severe SJS/TEN and 10 with mild maculopapular exanthema [MPE]), 98 osimertinib-tolerant subjects, and 2123 general population controls. HLA genotyping, drug-induced lymphocyte activation test (LAT), and surface plasmon resonance (SPR) assay were performed., Results: HLA-B*51:02 was present in 83.3% of osimertinib-induced SJS/TEN patients but only in 3.3% of the general population controls (P = 2.8×10 -7 , Pc=6.9×10 -6 , odds ratio [OR]=146), and 0% of osimertinib-tolerant controls (P = 6.5×10 -8 , Pc=1.6×10 -6 , OR=707). The association of HLA-B*51:01 and HLA-A*24:02 with osimertinib-induced MPE patients, rather than with osimertinib-tolerant subjects (P = 0.002, OR=15.7 for HLA-B*51:01; P = 0.003, OR=9.5 for HLA-A*24:02), was identified as a phenotype-specific association. Granulysin-the SJS/TEN-specific cytotoxic protein-was significantly higher in SJS/TEN patients' plasma (39.8±4.5 ng/ml, P<0.001) and in in vitro LAT (sensitivity=83.3%, P<0.01) compared to the tolerant controls. Patients with osimertinib-induced hypersensitivity appeared to tolerate alternative EGFR-TKIs. SPR results also confirmed that HLA-B*51:02 protein has a higher binding affinity for osimertinib and lower or no affinity for other EGFR-TKIs., Conclusions: HLA-B*51:02 frequently occurs in Asian populations and is strongly associated with osimertinib-induced SJS/TEN. Our findings suggest HLA-B*51:02 screening as a preemptive test to reduce osimertinib-induced severe hypersensitivity., (Copyright © 2024. Published by Elsevier Inc.)

Background: Non-alcoholic fatty liver diseases (NAFLDs)/non-alcoholic steatohepatitis (NASH) are the most common liver disorders among patients with type 2 diabetes. Newer classes of glucose-lowering agents (GLAs), such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is), have been shown to improve liver-related biomarkers. However, their effects on the development of NAFLD/NASH remain inconclusive., Methods: A nested case-control study was conducted using Taiwan's National Health Insurance Research Database for 2011-2018. Patients aged ≥ 40 years, diagnosed with type 2 diabetes, having stable non-insulin GLA use, and without NAFLD/NASH history were included. Patients with incident NAFLD/NASH were matched up to 10 randomly sampled controls based on individual's age, gender, cohort entry date, type 2 diabetes diagnosis date, and disease risk score. Conditional logistic regression analyses were employed to estimate the association between liver risk and treatment exposure. Dose-response analysis was also performed., Results: There were 621,438 study patients included for analysis. During 1.8 years of median follow-up, the incidence of NAFLD/NASH was 2.7 per 1000 person-years. After matching, 5,730 incident NAFLD cases (mean age: 57.6 years, male: 53.2%) and 45,070 controls (57.7 years, 52.7%) were identified. Using GLP-1RAs or SGLT2is was associated with an insignificantly lower NAFLD/NASH risk (i.e., odds ratios [95% CIs]: 0.84 [0.46-1.52] and 0.85 [0.63-1.14], respectively) and increased cumulative SGLT2i doses were significantly associated with a reduced NAFLD/NASH risk (0.61 [0.38-0.97])., Conclusion: GLP-1RA and SGLT2i therapies in type 2 diabetes patients might prevent NAFLD/NASH development, with a significantly lower risk related to greater treatment exposure., (© 2024. The Author(s).)

Background: Zorifertinib (AZD3759), an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with high blood-brain barrier penetration capability, demonstrated promising intracranial and systemic antitumor activity in phase 1 and 2 studies in central nervous system (CNS)-metastatic patients., Methods: In this phase 3 EVEREST trial (ClinicalTrials.gov: NCT03653546), patients with EGFR-sensitizing mutations, advanced treatment-naive non-small cell lung cancer (NSCLC), and non-irradiated symptomatic or asymptomatic CNS metastases were randomized (1:1) to zorifertinib or first-generation EGFR-TKI (gefitinib or erlotinib; control). The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival (PFS) per RECIST1.1., Findings: Overall, 439 patients were randomized (zorifertinib n = 220; control n = 219). Most patients had the EGFR L858R mutation (55%) or >3 CNS lesions (54%). Median PFS was significantly longer with zorifertinib versus control (9.6 versus 6.9 months; hazard ratio [HR], 0.719; 95% confidence interval [CI], 0.580-0.893; p = 0.0024). Zorifertinib significantly prolonged intracranial PFS versus control (BICR per modified RECIST1.1: HR, 0.467; 95% CI, 0.352-0.619; investigator per RANO-BM: HR, 0.627; 95% CI, 0.466-0.844). Overall survival (OS) was immature; the estimated median OS was 37.3 months with zorifertinib and 31.8 months with control (HR, 0.833; 95% CI, 0.524-1.283) in patients subsequently treated with third-generation EGFR-TKIs. Safety profiles were consistent with previously reported data for zorifertinib., Conclusions: Zorifertinib significantly improved systemic and intracranial PFS versus first-generation EGFR-TKIs; adverse events were manageable. Sequential use of zorifertinib and third-generation EGFR-TKIs showed the potential to prolong patients' survival. The results favor zorifertinib as a novel, well-validated first-line option for CNS-metastatic patients with EGFR-mutant NSCLC., Funding: This work was funded by Alpha Biopharma (Jiangsu) Co., Ltd., China., Competing Interests: Declaration of interests Q.Z. declares lecture and presentation fees from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi. S.L. declares grants or contracts from AstraZeneca, Hutchison, BMS, Hengrui, BeiGene, Roche, and Hansoh; consulting fees from AstraZeneca, Pfizer, Boehringer Ingelheim, Hutchison Medipharma, Simcere, Zai Lab, GenomiCare, Yuhan, prlME Oncology, Menarini, InventisBio, and Roche; lecture and presentation fees from AstraZeneca, Roche, Hansoh, and Hengrui Therapeutics; participation on a data safety monitoring board or advisory board for Roche, Regeneron, AstraZeneca, and Xcovery Holdings; and a leadership or fiduciary role in the Chinese Lung Cancer Associate and CSCO. Z. Wang is an employee of Alpha Biopharma (Jiangsu) and declares no stock ownership in the company. M.-J.A. declares consulting fees from AstraZeneca, Amgen, Merck, Takeda, BMS, ONO, Roche, Daiichi-Sankyo, Janssen, Alpha Pharmaceuticals, Yuhan, Arcus Biosciences, Eutilex, and VORONOI and lecture and presentation fees from AstraZeneca, Amgen, Merck, Takeda, BMS, ONO, Roche, Daiichi-Sankyo, Janssen, and Yuhan. Y.-L.W. declares consulting services for AstraZeneca, Boehringer Ingelheim, Novartis, and Takeda; lecture and presentation fees from AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi; and grants or contracts from AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, and Roche., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The urgent need for affordable and rapid detection methodologies for foodborne pathogens, particularly Escherichia coli (E. coli), highlights the importance of developing efficient and widely accessible diagnostic systems. Dark field microscopy, although effective, requires specific isolation of the target bacteria which can be hindered by the high cost of producing specialized antibodies. Alternatively, M13 bacteriophage, which naturally targets E. coli, offers a cost-efficient option with well-established techniques for its display and modification. Nevertheless, its filamentous structure with a large length-diameter ratio contributes to nonspecific binding and low separation efficiency, posing significant challenges. Consequently, refining M13 phage methodologies and their integration with advanced microscopy techniques stands as a critical pathway to improve detection specificity and efficiency in food safety diagnostics., Methods: We employed a dual-plasmid strategy to generate a truncated M13 phage (tM13). This engineered tM13 incorporates two key genetic modifications: a partial mutation at the N-terminus of pIII and biotinylation at the hydrophobic end of pVIII. These alterations enable efficient attachment of tM13 to diverse E. coli strains, facilitating rapid magnetic separation. For detection, we additionally implemented a convolutional neural network (CNN)-based algorithm for precise identification and quantification of bacterial cells using dark field microscopy., Results: The results obtained from spike-in and clinical sample analyses demonstrated the accuracy, high sensitivity (with a detection limit of 10 CFU/μL), and time-saving nature (30 min) of our tM13-based immunomagnetic enrichment approach combined with AI-enabled analytics, thereby supporting its potential to facilitate the identification of diverse E. coli strains in complex samples., Conclusion: The study established a rapid and accurate detection strategy for E. coli utilizing truncated M13 phages as capture probes, along with a dark field microscopy detection platform that integrates an image processing model and convolutional neural network., (© 2024. The Author(s).)

Objective: We aim to investigate the interplay between mentalization, brain microstructure, and psychological resilience as potential protective factors against mental illness., Method: Four hundred and twenty-six participants (mean age 40.12±16.95; 202 males, 224 females), without psychiatric or neurological history, completed assessments: Dissociative Process Scale (DPS), Peace of Mind (PoM), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Resilience Scale for Adults (RSA), and Magnetic Resonance Imaging (MRI) structures with selected regions of interest, and Diffusion Tensor Imaging (DTI) maps from various tracts in the right hemisphere and connection to the frontal areas, including anterior thalamic radiation (ATR), Cingulum (hippocampus) (CH), Corticospinal tract (CST), Superior longitudinal fasciculus (SLF), Inferior fronto-occipital fasciculus (IFOF), and Uncinate fasciculus (UF) were analyzed., Results: Two clusters, representing hypomentalization (HypoM) and hypermentalization (HyperM), were identified based on DPS, CPSS, and RFQ responses. One-way ANOVA showed no significant age or gender differences between clusters. The HypoM group exhibited lower PoM scores, higher BDI and BAI scores, and lower RSA scores (ps< 0.05). Structural brain metric comparison showed significant differences in GMV in the right caudal middle frontal gyrus (rcMFG), right superior frontal gyrus (rsFG), and right frontal pole (rFP) between groups. In addition, the HyperM individuals with a higher risk of depression and a higher ratio of intrapersonal to interpersonal factors of resilience were found with reduced GMV on the rcMFG. Additionally, analyses of DTI metrics revealed significant differences between two groups in rATR and rSLF in terms of fractional anisotropy (FA) values; rATR, rCST, rUF, rSLF, rCH and rIFOF in terms of mean diffusivity (MD) values, and radial diffusivity (RD) (corrected p = 0.05). Moreover, the positive correlation between different domains of resilience and white matter (WM) integrity implied further enhancement of intrapersonal or interpersonal resilience factors that are different for people with different mentalization., Conclusions: The findings underscore the importance of considering both intrapersonal and interpersonal factors in understanding the interactions between psychological resilience and mental health conditions relevant to brain mechanisms., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Before 2019, the Minimum Data Set (MDS) and Outcome and Assessment Information Set (OASIS) had incongruent response categories for rating cognitive impairment and activities of daily living (ADLs), hindering direct comparisons between nursing facilities and home health. We devised rule-based algorithms to compare cognitive impairment and ADL limitations between these 2 care settings among people with Alzheimer's disease and Alzheimer's disease-related dementias (ADRD)., Design: A retrospective cohort study., Setting and Participants: Included fee-for-service Medicare beneficiaries (2013-2018) transitioning from nursing facilities to home health, with 1-year of continuous enrollment, aged ≥65 years, diagnosed ADRD, and with complete MDS discharge and OASIS admission assessments (N = 398,496)., Methods: We identified target phenotypes using the Cognitive Function Scale (CFS) and ADL items from the MDS discharge assessment as reference standards. We compared 6 OASIS-based algorithms for cognitive impairment and 1 for each ADL limitation by estimating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)., Results: The average age was 83.5 (SD = 7.5) years and 82.3% transitioned from nursing to home health within 3 days. In the MDS discharge assessment, 42.2% had moderate-to-severe cognitive impairment. ADL limitations ranged from 71.4% for feeding to 97.8% for bathing. Compared with the moderate-to-severe cognitive impairment (CFS ≥3) on the MDS, the OASIS cognitive assessment indicating "considerable assistance to total dependence in routine situations" had 24% sensitivity, 94% specificity, 75% PPV, and 63% NPV. The ADL limitation algorithms exhibited high sensitivities (>96%) and PPVs (>94%) except for feeding (Sensitivity: 82%; PPV: 74%). Despite the short time frame between the 2 assessments, the OASIS admission assessment showed a higher prevalence of ADL limitations than the MDS discharge assessment., Conclusions and Implications: We highlighted differences in patient function between post-acute care settings. Our algorithms can help researchers, clinicians, and policymakers standardize patient-centered outcomes for comparative effectiveness research or quality initiatives., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Genomic alterations after resistance to osimertinib therapy in advanced T790M-mutated non-small cell lung cancer (NSCLC) are complex and poorly understood. In this study, we aimed to detect these genomic alternations via comprehensive next-generation sequencing (NGS) of tissue and liquid biopsies., Patients and Methods: From September 2020 to June 2021, 31 stage IIIB/IV T790M-mutated NSCLC patients who exhibited progressive disease after osimertinib therapy and provided written informed consent were recruited. Liquid and tissue biopsy samples for NGS testing were collected from 31 and 18 patients, respectively. Eighteen study patients had paired NGS data from tissue and liquid biopsies., Results: With respect to the T790M mutation status, the preservation and loss rates were 33% and 67%, respectively, in both liquid and tissue biopsy samples. Five patients (16.1%) had the C797S mutation (4 liquid samples and 1 tissue sample). Two (6.5%) had MET mutations, 3 (9.7%) had BRAF-V600E mutations, and 1 (3.2%) had a KRAS-G12C mutation. Among the 18 patients who underwent tissue rebiopsies, those with preserved T790M mutation had significantly longer progression-free survival (PFS) with osimertinib therapy than those with T790M mutation loss (10.8 vs. 5.0 months, P = 0.045). Among all patients, those with T790M mutation loss in liquid biopsy samples had longer PFS after osimertinib therapy (10.8 vs. 7.5 months, P = 0.209) and postprogression survival (17.7 vs. 9.6 months, P = 0.132) than those with preserved T790M mutation based on liquid biopsies., Conclusions: NGS using either tissue or liquid biopsy samples from advanced T790M-mutated NSCLC patients with acquired resistance to osimertinib therapy can detect various genomic alternations. Future studies focusing on subsequent tailored therapies on the basis of NGS results are warranted., (© 2024. The Author(s).)

Introduction: The primary analysis (median follow-up 34.9 mo across all arms) of the phase 3 POSEIDON study revealed a statistically significant overall survival (OS) improvement with first-line tremelimumab plus durvalumab and chemotherapy (T+D+CT) versus CT in patients with EGFR and ALK wild-type metastatic NSCLC (mNSCLC). D+CT had a trend for OS improvement versus CT that did not reach statistical significance. This article reports prespecified OS analyses after long-term follow-up (median >5 y)., Methods: A total of 1013 patients were randomized (1:1:1) to T+D+CT, D+CT, or CT, stratified by tumor cell programmed cell death ligand-1 (PD-L1) expression (≥50% versus <50%), disease stage (IVA versus IVB), and tumor histologic type (squamous versus nonsquamous). Serious adverse events were collected during follow-up., Results: After a median follow-up of 63.4 months across all arms, T+D+CT had sustained OS benefit versus CT (hazard ratio [HR] = 0.76, 95% confidence interval [CI]: 0.64-0.89; 5-y OS: 15.7% versus 6.8%). OS improvement with D+CT versus CT (HR = 0.84, 95% CI: 0.72-1.00; 5-y OS: 13.0%) was consistent with the primary analysis. OS benefit with T+D+CT versus CT remained more pronounced in nonsquamous (HR = 0.69, 95% CI: 0.56-0.85) versus squamous (HR = 0.85, 95% CI: 0.65-1.10) mNSCLC. OS benefit with T+D+CT versus CT was still evident regardless of PD-L1 expression, including patients with PD-L1 tumor cell less than 1%, and remained evident in STK11-mutant (nonsquamous), KEAP1-mutant, and KRAS-mutant (nonsquamous) mNSCLC. No new safety signals were identified., Conclusions: After a median follow-up of more than 5 years, T+D+CT had durable long-term OS benefit versus CT, supporting its use as first-line treatment in mNSCLC, including in patient subgroups with harder-to-treat disease., Competing Interests: Disclosure Peters has received grants (paid to institution) from Amgen, Arcus, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, F. Hoffmann-La Roche/Genentech, GlaxoSmithKline, iTeos, Merck Sharp & Dohme, Merck Serono, Mirati, PharmaMar, Promontory Therapeutics, and Seattle Genetics; has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events (paid to institution) from AiCME, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, ecancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Foundation Medicine, GlaxoSmithKline, Illumina, Imedex, Ipsen, Medscape, Merck Sharp & Dohme, Mirati, MJH Life Sciences, Novartis, Peerview, Pfizer, RTP, and Takeda; and has participation on a data safety monitoring board or advisory board (payment to institution) for AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, BerGenBio, Biocartis, Bioinvent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Fishawack, Foundation Medicine, F-Star, Genzyme, Gilead, GlaxoSmithKline, Hutchmed, Illumina, Imedex, Incyte, Ipsen, IQVIA, iTeos, Janssen, Medscape, Medtoday, Merck Sharp & Dohme, Merck Serono, Merrimack, Mirati, MJH Life Sciences, Novartis, Novocure, Nykode Therapeutics, OncologyEducation, Peerview, Pharma Mar, Pfizer, Promontory Therapeutics, Regeneron, RMEI, RTP, Sanofi, Seattle Genetics, and Takeda. Cho reports receiving research funding from MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp., GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Oncology, CJ Bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio Therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph Therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center, and Vertical Bio AG; receiving royalties from Champions Oncology, Crown Bioscience, Imagen, and PearlRiver Bio GmbH; receiving consulting fees from Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, CJ, CureLogen, Cyrus Therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, Merck Sharp & Dohme, Janssen, Medpacto, Blueprint Medicines, RandBio, and Hanmi; receiving payment or honoraria for presentations from ASCO, AstraZeneca, Guardant, Roche, ESMO, International Association for the Study of Lung Cancer, Korean Cancer Association, Korean Society of Medical Oncology, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, Merck Sharp & Dohme, The Chinese Thoracic Oncology Society, and Pfizer; having scientific advisory board participation for Kanaph Therapeutics Inc., Bridgebio Therapeutics, Cyrus Therapeutics, Guardant Health, Oscotec Inc., J INTS Bio, Therapex Co., Ltd., Gilead, and Amgen; having membership of the board of directors for J INTS BIO; having stock ownership in TheraCanVac Inc., Gencurix Inc., Bridgebio Therapeutics, Kanaph Therapeutics Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp., and J INTS BIO; having employment with Yonsei University Health System; and being a founder of DAAN Biotherapeutics. Alatorre-Alexander has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, and Roche; received support for attending meetings and/or travel from AstraZeneca, Merck Sharp & Dohme, and Roche; and participated on a data safety monitoring board or advisory board for Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, and Roche. Geater has received research funding (paid to institution) from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, and Roche; received honoraria from AstraZeneca and Boehringer Ingelheim; and performed an advisory role for Merck Sharp & Dohme and Pfizer. Laktionov has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events for AstraZeneca, Biocad, Bristol-Myers Squibb, Merck Sharp & Dohme, and Roche AG, and has participated on a data safety monitoring board or advisory board for AstraZeneca, Biocad, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, and Roche AG. Kim has received grants (paid to institution) from Yuhan and support for attending an investigator meeting from AstraZeneca. Hussein has received consulting fees from IntegraConnect, Coherus Biosciences, Athenex, Karyopharm Therapeutics, Bristol-Myers Squibb, AstraZeneca, Mirati Therapeutics, Exelixis, Biopharma, Oncocyte, Aptitude Health, IntrinsiQ, GIntrinsiQ, National Community Oncology Dispensing Association, Integra PrescisionQ, AbbVie, and CTI BioPharma Corp. Araujo has received grants from Lilly, Boehringer, Merck Sharp & Dohme, Bristol-Myers Squibb, Roche, Pfizer, AstraZeneca, Novartis, and Merck; consulting fees from Merck Sharp & Dohme, Roche, AstraZeneca, Bristol-Myers Squibb, Lilly, Illumina, and Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, Boehringer, Merck, Roche, Pfizer, and Lilly; and support for attending meetings and/or travel from Daiichi Sankyo, Bristol-Myers Squibb, and AstraZeneca. Saito has received grants from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, and ONO Pharmaceutical, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, ONO Pharmaceutical, and Pfizer. Reinmuth has received consulting fees from Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck Sharp & Dohme, and Pfizer; received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck Sharp & Dohme, Pfizer, Sanofi, and Takeda; received support for attending meetings and/or travel from Janssen, Sanofi, and Takeda; and participated on a data safety monitoring board or advisory board for Symphogen. Lowery, Mann, Stewart, and Jiang are employees of, and own stocks in, AstraZeneca. Garon has received grants paid to their institution from ABL-Bio, AstraZeneca, Bristol-Myers Squibb, Daiichi Sanko, Dynavax Technologies, Eli Lilly, EMD Serono, Genentech, Gilead, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Neon, and Novartis; consulting fees paid to their institution from AbbVie, ABL-Bio, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dracen Pharmaceuticals, EMD Serono, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, Xilio, and Zymeworks; and support for attending meetings and/or travel from A2 Bio and Novartis. Mok reports receiving grants paid to their institution from AstraZeneca, Bristol-Myers Squibb, G1 Therapeutics, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, and Xcovery; consulting fees from AbbVie Inc., ACEA Pharma, Adagene, Alpha Biopharma Co., Ltd., Amgen, Amoy Diagnostics Co., AVEO Pharmaceuticals, Inc., Bayer Healthcare Pharmaceuticals Ltd., BeiGene, Berry Oncology, Boehringer Ingelheim, Blueprint Medicines Corporation, Bristol-Myers Squibb, Bowtie Life Insurance Company Limited, Bridge Biotherapeutics Inc., Covidien LP, C4 Therapeutics Inc., Cirina Ltd., CStone Pharmaceuticals, Curio Science, D3 Bio Ltd., Da Volterra, Daiichi Sankyo, Eisai, Elevation Oncology, F. Hoffmann-La Roche Ltd./Genentech, Fishawack Facilitate Ltd., G1 Therapeutics Inc., geneDecode Co., Ltd., Gilead Sciences, Inc., GLG’s Healthcare, Gritstone Oncology, Inc., Guardant Health, Hengrui Therapeutics Inc., HutchMed, Ignyta, Inc., Illumina Inc., Incyte Corporation, Inivata, IQVIA, Janssen, Lakeshore Biotech Ltd., Lilly, Lunit USA, Inc., Loxo-Oncology, Lucence Health Inc., Medscape LLC/WebMD, Medtronic, Merck Serono, Merck Sharp & Dohme, Mirati Therapeutics Inc., MiRXES, MoreHealth, Novartis, Novocure GmbH, Omega Therapeutics Inc., OrigiMed, OSE Immunotherapeutics, PeerVoice, Pfizer, PrIME Oncology, Prenetics, Puma Biotechnology Inc., Qiming Development (HK) Ltd., Regeneron Pharmaceuticals Inc., Roche Pharmaceuticals/Diagnostics/Foundation One, Sanofi-Aventis, SFJ Pharmaceutical Ltd., Simcere of America Inc., Synergy Research, Summit Therapeutics Sub, Inc., Takeda Pharmaceuticals HK Ltd., Tigermed, Vertex Pharmaceuticals, Virtus Medical Group, XENCOR, Inc., and Yuhan Corporation; receiving payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from ACEA Pharma, Alpha Biopharma Co. Ltd., Amgen, Amoy Diagnostics Co. Ltd., AstraZeneca (before January 1, 2019), BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Daz Group, Fishawack Facilitate Ltd., InMed Medical Communications, Janssen Pharmaceutica NV, Jiahui Holdings Co. Ltd., LiangYiHui Healthcare, Lilly, Lucence Health Inc., MD Health Brazil, Medscape LLC, Merck Pharmaceuticals HK Ltd., Merck Sharp & Dohme, MiRXES, Novartis, OrigiMed Co. Ltd., P. Permanyer SL, PeerVoice, Physicians’ Education Resource, Pfizer, PrIME Oncology, Research to Practice, Roche Pharmaceuticals/Diagnostics/Foundation One, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co. Ltd., Taiho Pharmaceutical Co. Ltd., Takeda Oncology, and Touch Independent Medical Education Ltd.; receiving support for attending meetings and/or travel from Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, Merck Sharp & Dohme (paid to institution), Novartis, Roche (paid to self and institution), AstraZeneca, Daiichi Sankyo, MiRXES, AbbVie, Zai Lab, and Liangyihui (paid to self); having participation on a data safety monitoring board or advisory board for AbbVie Inc., ACEA Pharma, Amgen, AstraZeneca, Berry Oncology, Blueprint Medicines Corporation, Boehringer Ingelheim, Bowtie Life Insurance Co., Ltd., Bristol-Myers Squibb, C4 Therapeutics Inc., Covidien LP, CStone Pharmaceuticals, Curio Science, D3 Bio Ltd., Daiichi Sankyo Inc., Eisai, Fishawack Facilitate Ltd., G1 Therapeutics Inc., Gilead Sciences Inc., Gritstone Oncology Inc., Guardant Health, geneDecode Co. Ltd. (uncompensated), Hengrui Therapeutics Inc., HutchMed, Ignyta Inc., Incyte Corporation, Imagene AI Ltd., Inivata, IQVIA, Janssen, Lakeshore Biotech, Lilly, Loxo-Oncology Inc., Lunit Inc., Merck Serono, Merck Sharp & Dohme, Mirati Therapeutics Inc., MiRXES Group, Novartis, OrigiMed, Pfizer, Puma Biotechnology Inc., Roche/Genentech, Regeneron Pharmaceuticals Inc., Sanofi-Aventis R&D, SFJ Pharmaceutical, Simcere of America Inc., Simcere Zaiming, Inc., Takeda, Vertex Pharmaceuticals, Virtus Medical Group, XENCOR, Inc., and Yuhan Corporation; having leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, with AstraZeneca PLC, HutchMed, and Aurora; and having stock or stock options in AstraZeneca, Aurora Tele-Oncology Ltd., Biolidics Ltd., HutchMed, Prenetics, D3 Bio, Lunit, Bowtie Life Insurance, Lakeshore Biotech Ltd., Loxo-oncology, Virtus Medical Group, and Phanes Therapeutics, Inc. Johnson has received research funding paid to their institution from AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Calithera Biosciences, Carisma Therapeutics, Corvus Pharmaceutical, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Kadmon Pharmaceuticals, Kartos Therapeutics, Loxo-Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, Y-mAbs Therapeutics, Bristol-Myers Squibb, Checkpoint Therapeutics, City of Hope National Medical Center, Jounce Therapeutics, Mythic Therapeutics, RasCal Therapeutics, WindMIL Therapeutics, ArriVent BioPharma, Bayer, LockBody Therapeutics, and Taiho Oncology; and receiving consulting fees paid to their institution from AbbVie, Amgen, Arrivent, Alentis Therapeutics, AstraZeneca, Bristol-Myers Squibb, D3 Bio Limited, Daiichi Sankyo, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Hookipa Biotech, Janssen, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Pyramid Biosciences, Revolution Medicines, Sanofi-Aventis, SeaGen, Takeda Pharmaceuticals, VBL Therapeutics, Arcus Biosciences, Immunocore, Jazz Pharmaceuticals, Synthekine, Boehringer Ingelheim, Gilead Sciences, Normunity, Lilly, Novocure, and Pfizer. The remaining authors delcare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

This review explores the critical role of machine learning (ML) in enhancing microalgae bioprocesses for sustainable biofuel production. It addresses both technical and economic challenges in commercializing microalgal biofuels and examines how ML can optimize various stages, including identification, classification, cultivation, harvesting, drying, and conversion to biofuels. This review also highlights the integration of ML with technologies such as the Internet of Things (IoT) for real-time monitoring and management of bioprocesses. It discusses the adaptability and flexibility of ML in the context of microalgae biotechnology, focusing on diverse algorithms such as Artificial Neural Networks, Support Vector Machines, Decision Trees, and Random Forests, while emphasizing the importance of data collection and preparation. Additionally, current ML applications in microalgae biofuel production are reviewed, including strain selection, growth optimization, system monitoring, and lipid extraction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: Epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors (TKIs) are standard first-line therapy for EGFR -mutant, metastatic non-small cell lung cancer (NSCLC); however, most patients experience disease progression. We report results from the randomized, double-blind, phase III KEYNOTE-789 study of pemetrexed and platinum-based chemotherapy with or without pembrolizumab for TKI-resistant, EGFR -mutant, metastatic nonsquamous NSCLC (ClinicalTrials.gov identifier: NCT03515837)., Methods: Adults with pathologically confirmed stage IV nonsquamous NSCLC, documented DEL19 or L858R EGFR mutation, and progression after EGFR-TKI treatment were randomly assigned 1:1 to 35 cycles of pembrolizumab 200 mg or placebo once every 3 weeks plus four cycles of pemetrexed and carboplatin or cisplatin once every 3 weeks and then maintenance pemetrexed. Dual primary end points were progression-free survival (PFS) and overall survival (OS). Final PFS testing was completed at the second interim analysis (IA2; data cutoff, December 3, 2021); OS was tested at final analysis (FA; data cutoff, January 17, 2023). Efficacy boundaries were one-sided P = .0117 for PFS and OS., Results: Four hundred ninety-two patients were randomly assigned to pembrolizumab plus chemotherapy (n = 245) or placebo plus chemotherapy (n = 247). At IA2, the median PFS was 5.6 months for pembrolizumab plus chemotherapy versus 5.5 months for placebo plus chemotherapy (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.97]; P = .0122). At FA, the median OS was 15.9 versus 14.7 months, respectively (HR, 0.84 [95% CI, 0.69 to 1.02]; P = .0362). Grade ≥3 treatment-related adverse events occurred in 43.7% of pembrolizumab plus chemotherapy recipients versus 38.6% of placebo plus chemotherapy recipients., Conclusion: Addition of pembrolizumab to chemotherapy in patients with TKI-resistant, EGFR -mutant, metastatic nonsquamous NSCLC did not significantly prolong PFS or OS versus placebo plus chemotherapy in KEYNOTE-789.

The 2023 consensus from the Taiwanese Dermatological Association (TDA) and Taiwan Lung Cancer Society (TLCS) addresses the management of tyrosine kinase inhibitor (TKI)-induced skin toxicities in non-small cell lung cancer (NSCLC). Providing a comprehensive overview, the consensus reflects recent advances in understanding causes and developmental processes of TKI-related skin toxicities. Aimed at guiding clinicians in Taiwan, the consensus integrates new treatment perspectives while incorporating experiences from local dermatology experts. Recommendations underwent a voting process, achieving consensus when 75% or more of experts agreed, leading to their inclusion. Approved by over 90% of participants, the recommended treatment algorithms for major skin toxicities offer valuable insights for clinicians managing TKI-associated effects in NSCLC patients., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

In practical visual search fields, observers often encounter errors that result from an unknown number of targets, which may induce reduced accuracy and speed. Our current study addresses the potential enhancement of collaborative search efficiency as a dyad to mitigate such incurred search costs. Utilizing the capacity coefficient, we evaluated search efficiency and explored the interplay of task difficulty and termination rule in collaborative visual search. Our prediction that collaborative benefits increased with elevated task difficulty was not supported in Experiment 1, where participants were tasked with judging the presence of any target. In contrast, Experiment 2 demonstrated that dyads exhibited greater search efficiency during exhaustive searches for multiple targets with elevated task difficulty. Notably, our findings indicated an advantage in dyad searches compared to baseline predictions from individual searches. Our results underscored the significance of task difficulty and termination rules in leveraging human resources for improved collaborative visual search performance., (© 2024. The Psychonomic Society, Inc.)

This study aims to explore the mechanisms of the inhibitory effect of kaempferol on the invasion and metastasis of gastric cancer (GC) cells through network pharmacology prediction and experimental verification. It identifies core targets via PPI network analysis and finds that kaempferol binds to these targets well. In vitro experiments showed that kaempferol could inhibit the proliferation, colony formation, migration and invasion of GC cells. Western blotting indicated kaempferol may reduce AKT and GSK3β phosphorylation, leading to lower expression of invasion-related genes SRC, MMP9, CXCR4, KDR, and MMP2. Overall, kaempferol may prevent migration and invasion of GC cells via the AKT/GSK3β signaling pathway.

Introduction: Although angiotensin receptor-neprilysin inhibitor (ARNI) has shown promise in patients with heart failure and reduced ejection fraction (HFrEF), the treatment effect in HFrEF patients with end-stage renal disease (ESRD) undergoing dialysis is uncertain. This study aimed to examine the real-world effects of ARNI vs. angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in this subpopulation., Methods: This multi-institutional, retrospective study identified 349 HFrEF patients with ESRD on dialysis, who initiated either ARNI or ACEI/ARB therapy. Efficacy outcomes included rates of hospitalization for heart failure (HHF) and mortality, as well as changes in echocardiographic parameters. Safety outcomes encompassed hypotension and hyperkalemia. Treatment effects were assessed using Cox proportional hazards models, with additional sensitivity analyses for robustness., Results: Out of 349 patients screened, 89 were included in the final analysis (42 in the ARNI group and 47 in the ACEI/ARB group). After 1 year of treatment, echocardiographic measures between the two groups were comparable. The primary composite rate of HHF or mortality was 20.6 events per 100 patient-years in the ARNI group and 26.1 in the ACEI/ARB group; the adjusted hazard ratio was 0.98 (95% CI: 0.28-3.43, P  = 0.97). Their safety outcomes did not differ significantly. Sensitivity analyses, including repetitive sampling, propensity score matching, and extended follow-up, corroborated these findings., Conclusion: ARNI has proven effective in treating HFrEF patients; however, significant benefits were not observed in these patients with ESRD undergoing dialysis compared with ACEI/ARB in this real-world cohort. Future research employing a more extended follow-up period, larger sample size, or randomized design is warranted to investigate the treatment effects in this subpopulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Yang, Huang, Yang, Toh, Chang, Su, Lin, Wang, Wang and Liao.)

In situ-forming biocompatible hydrogels have great potential in various medical applications. Here, we introduce a pH-responsive, self-healable, and biocompatible hydrogel for cell scaffolds and the development of a tumor spheroid phantom for magnetic resonance imaging. The hydrogel (pMAD) was synthesized via amino-yne click chemistry between poly(2-methacryloyloxyethyl phosphorylcholine- co -2-aminoethylmethacrylamide) and dialkyne polyethylene glycol. Rheology analysis, compressive mechanical testing, and gravimetric analysis were employed to investigate the gelation time, mechanical properties, equilibrium swelling, and degradability of pMAD hydrogels. The reversible enamine and imine bond mechanisms leading to the sol-to-gel transition in acidic conditions (pH ≤ 5) were observed. The pMAD hydrogel demonstrated potential as a cellular scaffold, exhibiting high viability and NIH-3T3 fibroblast cell encapsulation under mild conditions (37 °C, pH 7.4). Additionally, the pMAD hydrogel also demonstrated the capability for in vitro magnetic resonance imaging of glioblastoma tumor spheroids based on the chemical exchange saturation transfer effect. Given its advantages, the pMAD hydrogel emerges as a promising material for diverse biomedical applications, including cell carriers, bioimaging, and therapeutic agent delivery.

This letter to the editor relates to the study entitled "Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study", which was recently published by Peng et al . Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer. The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects, so it is crucial to identify safe and effective drugs to inhibit viral replication., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: This study quantifies the longitudinal economic burden for a wide spectrum of incident complications, metabolic syndrome (MS)-related risk factors, and comorbidities in patients with MS., Methods: This retrospective study utilized linked data from the 2013 National Health Interview Survey and the 2012-2021 National Health Insurance Research Database to identify MS individuals and their characteristics. The incidence rate of each complication was calculated as the number of complication events in the study period divided by the total person-years during follow-up. The healthcare costs of complications were analyzed using a generalized estimating equation model to determine the cost impact of complications after adjustment for patients' characteristics. Sensitivity analyses on variables with high missing rates (i.e., cause of death, body mass index) were performed., Results: Among 837 identified MS individuals over 8.28 (± 1.35) years of follow-up, the most frequent complications were microvascular diseases (incidence rate for nephropathy/retinopathy/neuropathy: 6.49/2.64/2.08 events per 100 person-years), followed by cardiovascular diseases (2.47), peripheral vascular diseases (2.01), and cancers (1.53). Death was the costliest event (event-year cost per person: USD 16,429) and cancers were the most expensive complications (USD 9,127-11,083 for non-MS- and MS-related cancers). Developing non-MS/MS-related cancers, cardiovascular diseases, and obesity-related medical conditions increased annual costs by 273% (95% CI: 181-397%)/175% (105-269%), 159% (118-207%), and 140% (84-214%), respectively. Microvascular diseases had the lowest cost impact on annual costs (i.e., 27% [17-39%]/27% [11-46%]/24% [11-37%] increases for nephropathy/neuropathy/retinopathy, respectively). Having existing comorbidities increased annual costs by 20% (osteoarthritis) to 108% (depression). Having morbid obesity (i.e., body mass index ≥ 35 kg/m 2 ) increased annual costs by 58% (30-91%)., Conclusions: The economic burden from costly incident complications (i.e., cardiovascular diseases, peripheral vascular diseases, cancers), MS-related risk factors (i.e., morbid obesity), and comorbidities (i.e., depression) highlight the urgent need for early intervention to prevent MS and its progression. The comprehensive cost estimates reported in this study can facilitate the parameterization of economic analyses to identify cost-effective interventions for these patients., (© 2024. The Author(s).)

Objective: To adapt risk prediction equations for myocardial infarction (MI), stroke, and heart failure (HF) among patients with type 2 diabetes in real-world settings using cross-institutional electronic health records (EHRs) in Taiwan., Methods: The EHRs from two medical centers, National Cheng Kung University Hospital (NCKUH; 11,740 patients) and National Taiwan University Hospital (NTUH; 20,313 patients), were analyzed using the common data model approach. Risk equations for MI, stroke, and HF from UKPDS-OM2, RECODe, and CHIME models were adapted for external validation and recalibration. External validation was assessed by (1) discrimination, evaluated by the area under the receiver operating characteristic curve (AUROC) and (2) calibration, evaluated by calibration slopes and intercepts and the Greenwood-Nam-D'Agostino (GND) test. Recalibration was conducted for unsatisfactory calibration (p-value of GND test < 0.05) by adjusting the baseline hazards of original equations to address variations in patients' cardiovascular risks across institutions., Results: The CHIME risk equations had acceptable discrimination (AUROC: 0.71-0.79) and better calibration than that for UKPDS-OM2 and RECODe, although the calibration remained unsatisfactory. After recalibration, the calibration slopes/intercepts of the CHIME-MI, CHIME-stroke, and CHIME-HF risk equations were 0.9848/- 0.0008, 1.1003/- 0.0046, and 0.9436/0.0063 in the NCKUH population and 1.1060/- 0.0011, 0.8714/0.0030, and 1.0476/- 0.0016 in the NTUH population, respectively. All the recalibrated risk equations showed satisfactory calibration (p-values of GND tests ≥ 0.05)., Conclusions: We provide valid risk prediction equations for MI, stroke, and HF outcomes in Taiwanese type 2 diabetes populations. A framework for adapting risk equations across institutions is also proposed., (© 2024. The Author(s).)

Vitamin D deficiency is common in patients with inflammatory bowel disease (IBD). In this study, we aimed to evaluate the prevalence and risk factors of vitamin D deficiency in a Taiwanese IBD cohort. Vitamin D levels were checked in adult patients with IBD who were treated at Changhua Christian Hospital, a medical center in central Taiwan, from January 2017 to December 2023. The risk factors for vitamin D deficiency were evaluated. 106 adult IBD patients were included, including 20 patients with Crohn's disease and 86 with ulcerative colitis. The median age at diagnosis was 39.2 years. The mean vitamin D level was 22.2 ± 8 ng/mL. Forty-five patients (42.5%) had vitamin D deficiency (vitamin D level < 20 ng/mL). Comparing patients with normal vitamin D levels and those with vitamin D deficiency after multivariate adjustment, female sex and early age at diagnosis were identified as statistically significant risk factors. We found a prevalence of 42.5% of vitamin D deficiency in the Taiwanese IBD population. Understanding this issue is essential for teaching patients and doctors about vitamin D deficiency screening and improving patient outcomes., (© 2024. The Author(s).)

Importance: Underutilization of guideline-directed medical therapy for heart failure with reduced ejection fraction is a major cause of poor outcomes. For many American Indian patients receiving care through the Indian Health Service, access to care, especially cardiology care, is limited, contributing to poor uptake of recommended therapy., Objective: To examine whether a telehealth model in which guideline-directed medical therapy is initiated and titrated over the phone with remote telemonitoring using a home blood pressure cuff improves guideline-directed medical therapy use (eg, drug classes and dosage) in patients with heart failure with reduced ejection fraction in Navajo Nation., Design, Setting, and Participants: The Heart Failure Optimization at Home to Improve Outcomes (Hózhó) randomized clinical trial was a stepped-wedge, pragmatic comparative effectiveness trial conducted from February to August 2023. Patients 18 years and older with a diagnosis of heart failure with reduced ejection fraction receiving care at 2 Indian Health Service facilities in rural Navajo Nation (defined as having primary care physician with 1 clinical visit and 1 prescription filled in the last 12 months) were enrolled. Patients were randomized to the telehealth care model or usual care in a stepped-wedge fashion, with 5 time points (30-day intervals) until all patients crossed over into the intervention. Data analyses were completed in January 2024., Intervention: A phone-based telehealth model in which guideline-directed medical therapy is initiated and titrated at home, using remote telemonitoring with a home blood pressure cuff., Main Outcomes and Measures: The primary outcome was an increase in the number of guideline-directed classes of drugs filled from the pharmacy at 30 days postrandomization., Results: Of 103 enrolled American Indian patients, 42 (40.8%) were female, and the median (IQR) age was 65 (53-77) years. The median (IQR) left ventricular ejection fraction was 32% (24%-36%). The primary outcome occurred significantly more in the intervention group (66.2% vs 13.1%), thus increasing uptake of guideline-directed classes of drugs by 53% (odds ratio, 12.99; 95% CI, 6.87-24.53; P < .001). The number of patients needed to receive the telehealth intervention to result in an increase of guideline-directed drug classes was 1.88., Conclusions and Relevance: In this heart failure trial in Navajo Nation, a telephone-based strategy of remote initiation and titration for outpatients with heart failure with reduced ejection fraction led to improved rates of guideline-directed medical therapy at 30 days compared with usual care. This low-cost strategy could be expanded to other rural settings where access to care is limited., Trial Registration: ClinicalTrials.gov Identifier: NCT05792085.

This study delves into expressing primary emotions anger, happiness, sadness, and fear through drawings. Moving beyond the well-researched color-emotion link, it explores under-examined aspects like spatial concepts and drawing styles. Employing Python and OpenCV for objective analysis, we make a breakthrough by converting subjective perceptions into measurable data through 728 digital images from 182 university students. For the prominent color chosen for each emotion, the majority of participants chose red for anger (73.11%), yellow for happiness (17.8%), blue for sadness (51.1%), and black for fear (40.7%). Happiness led with the highest saturation (68.52%) and brightness (75.44%) percentages, while fear recorded the lowest in both categories (47.33% saturation, 48.78% brightness). Fear, however, topped in color fill percentage (35.49%), with happiness at the lowest (25.14%). Tangible imagery prevailed (71.43-83.52%), with abstract styles peaking in fear representations (28.57%). Facial expressions were a common element (41.76-49.45%). The study achieved an 81.3% predictive accuracy for anger, higher than the 71.3% overall average. Future research can build on these results by improving technological methods to quantify more aspects of drawing content. Investigating a more comprehensive array of emotions and examining factors influencing emotional drawing styles will further our understanding of visual-emotional communication., (© 2024. The Author(s).)

Osimertinib has demonstrated efficacy in patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC) in clinical trials. However, real-world data on its effectiveness remain scarce. Taiwanese patients with T790M-positive locally advanced or metastatic NSCLC and progressive disease following treatment with at least one EGFR tyrosine kinase inhibitor (TKI) were enrolled from the osimertinib early access program. Of the 419 patients (mean age, 63 years; female, 67%), 53% were heavily pretreated (≥ third-line [3L]), making osimertinib a fourth-line (4L) intervention. The median progression-free survival (PFS) was 10.5 months (95% confidence interval [CI]: 8.95-11.41); the 18-month PFS rate was 26.5%. The median overall survival (OS) was 19.0 months (95% CI: 16.30-20.95); the 24-month OS rate was 40.9%. The objective response rate was 32.46%, and the disease control rate was 86.38%. The median time to treatment discontinuation of osimertinib monotherapy was 11.9 months (95% CI: 10.49-13.11). Subgroup analyses of median PFS and OS in the chemotherapy combination group vs. the osimertinib monotherapy group yielded no difference. Central nervous system (CNS) metastasis, number of prior lines of therapy, and types of initial EGFR-TKIs did not significantly impact outcomes. The median PFS values were 9.0 (95% CI: 5.18-11.34) and 10.9 (95% CI: 9.18-11.90) months with and without CNS metastasis, respectively, and 10.8 (95% CI: 8.59-12.69), 13.6 (95% CI: 10.89-16.3), and 9.2 (95% CI: 7.8-10.62) months for second-line (2L), 3L, and ≥4L therapy, respectively. In patients who received osimertinib as 2L therapy, the median PFS values in response to prior afatinib, erlotinib and gefitinib treatment were 11.2 (95% CI: 4.85-4.79), 10.5 (95% CI: 8.59-20.26) and 8.7 (95% CI: 7.21-16.79) months, respectively. Overall, real-world data from Taiwan support the clinical benefits of osimertinib in EGFR T790M -positive NSCLC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Charcoal-burning has become a predominant method of suicide in many East-Asian countries since the 1990s. Aims: To explore charcoal-burning suicide trends from 1996 to 2020 in Taiwan. Methods: Joinpoint regression models were applied to identify suicide trends over the study period. Decompositional analyses quantified the contributions of age, sex, suicide method, and area of residence to suicide rate trends, accounting for age and geographical distribution of the general population, with a focus on charcoal-burning suicide. Results: There were three stages of suicide rate trends: increasing (1996-2006), descending (2006-2011), and levelling-off (2011-2020). Suicide by charcoal-burning accounted for 70% of the increasing suicide rates between 1996 and 2006 and 50% of the decreasing rates in the descending stage (2011-2020). During the levelling-off stage, suicide by charcoal-burning continued to decrease, albeit slowly. During the descending stage, there was a partial "substitution" of jumping for charcoal-burning. During the levelling-off stage, suicide by hanging partially "substituted" for suicide by charcoal-burning. Limitations: The variables included were limited by data availability. Conclusions: Charcoal-burning remains the second most common method of suicide in Taiwan today. Charcoal-burning has been partially replaced in the last 10 years by jumping and hanging. Monitoring suicide methods and trends is essential for suicide prevention interventions.

Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis. Twenty-one patients (29.2%) received atezolizumab and fifty-one (70.8%) received durvalumab. Objective response (OR) and disease control (DC) rates of 59.7% and 73.6%, respectively, were observed with first-line ICI plus chemotherapy. The median progression-free survival (PFS) was 6.63 months (95% confidence interval (CI), 5.25-8.02), and the median overall survival (OS) was 16.07 months (95% CI, 15.12-17.0) in all study patients. A high neutrophil-to-lymphocyte ratio (NLR; >4) and a high serum lactate dehydrogenase (LDH) concentration (>260 UL) were identified as independent unfavorable factors associated with shorter OS in the multivariate analysis. Regarding safety, neutropenia was the most common grade 3 treatment-related adverse event (AE), but no treatment-related deaths occurred in the study patients. First-line anti-PD-L1 ICIs combined with chemotherapy are effective and safe for male extensive-stage SCLC patients. Further therapeutic strategies may need to be developed for patients with unfavorable outcomes (e.g., baseline high NLR and serum LDH level).

Herein, we developed a gold nanoparticle (GNP)-mediated barcode qPCR strategy with a sensitivity for a single virus particle per reaction for the detection of influenza virus H3N2. The analysis of the results for pure virus and real virus samples show that GNP-mediated barcode qPCR is ∼16 times more sensitive than conventional qPCR, demonstrating the potential to reduce false negatives and improve early diagnosis of viral infections.

Longitudinal data, while often limited, contain valuable insights into features impacting clinical outcomes. To predict the progression of chronic kidney disease (CKD) in patients with metabolic syndrome, particularly those transitioning from stage 3a to 3b, where data are scarce, utilizing feature ensemble techniques can be advantageous. It can effectively identify crucial risk factors, influencing CKD progression, thereby enhancing model performance. Machine learning (ML) methods have gained popularity due to their ability to perform feature selection and handle complex feature interactions more effectively than traditional approaches. However, different ML methods yield varying feature importance information. This study proposes a multiphase hybrid risk factor evaluation scheme to consider the diverse feature information generated by ML methods. The scheme incorporates variable ensemble rules (VERs) to combine feature importance information, thereby aiding in the identification of important features influencing CKD progression and supporting clinical decision making. In the proposed scheme, we employ six ML models-Lasso, RF, MARS, LightGBM, XGBoost, and CatBoost-each renowned for its distinct feature selection mechanisms and widespread usage in clinical studies. By implementing our proposed scheme, thirteen features affecting CKD progression are identified, and a promising AUC score of 0.883 can be achieved when constructing a model with them.

Systemic exposure to starch-coated iron oxide nanoparticles (IONPs) can stimulate antitumor T cell responses, even when little IONP is retained within the tumor. Here, we demonstrate in mouse models of metastatic breast cancer that IONPs can alter the host immune landscape, leading to systemic immune-mediated disease suppression. We report that a single intravenous injection of IONPs can inhibit primary tumor growth, suppress metastases, and extend survival. Gene expression analysis revealed the activation of Toll-like receptor (TLR) pathways involving signaling via Toll/Interleukin-1 receptor domain-containing adaptor-inducing IFN-β (TRIF), a TLR pathway adaptor protein. Requisite participation of TRIF in suppressing tumor progression was demonstrated with histopathologic evidence of upregulated IFN-regulatory factor 3 (IRF3), a downstream protein, and confirmed in a TRIF knockout syngeneic mouse model of metastatic breast cancer. Neither starch-coated polystyrene nanoparticles lacking iron, nor iron-containing dextran-coated parenteral iron replacement agent, induced significant antitumor effects, suggesting a dependence on the type of IONP formulation. Analysis of multiple independent clinical databases supports a hypothesis that upregulation of TLR3 and IRF3 correlates with increased overall survival among breast cancer patients. Taken together, these data support a compelling rationale to re-examine IONP formulations as harboring anticancer immune (nano)adjuvant properties to generate a therapeutic benefit without requiring uptake by cancer cells.