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Introduction: Respiratory syncytial virus (RSV) is a common, highly contagious pathogen and a leading cause of serious illness among infants and older adults. While existing scientific evidence has predominantly focused on the epidemiology and disease burden of RSV in infants, data in older adults remain limited in some countries, including those in Southeast Asia (SEA) and the Middle East and North Africa (MENA) region. Here, we outline the key challenges for understanding the burden of RSV in older adults in SEA and the MENA region and we propose opportunities for improving understanding and eventually reducing the impact of RSV. Main Findings and Conclusions: A key challenge identified by the expert group, particularly in older adults, is a lack of awareness (among healthcare professionals, policy makers, and the public) of RSV burden and the associated risks for severe outcomes. This is often confounded by the complexities of underdiagnosis, surveillance limitations, and comorbidities. To address these issues, we suggest medical education initiatives for physicians in SEA and the MENA region to better understand the need to protect older adults from RSV, and encourage more widespread routine testing to better understand the burden of RSV. We also recommend surveillance studies in these regions to provide comprehensive and accurate epidemiological data on RSV in older adults. Finally, in the absence of current surveillance data in these regions, we propose extrapolating existing global data and local pediatric data to inform the likely burden of RSV in older adults. A graphical abstract is available with this article. [ABSTRACT FROM AUTHOR]

Ba1 − xSrxMg2 − yZnyV2O8 compounds, abbreviated as BSMZVO@xy (x = 0.0–0.2 and y = 0.02), were synthesized with tetragonal structures. The microstructure, molecular structure, and polarization mechanism were investigated using X‐ray diffraction, electronic microscopy, Raman spectroscopy, and vector network analyzer. The sintering temperatures (<900°C) and microwave dielectric properties of BSMZVO are significantly impacted by (Sr/Zn)2+ substitution and TiO2 mixing. The BSMZVO@xy (x = 0.15 and y = 0.02) exhibited encouraging εr (12.4–12.7), Q × f (40 054–40 973 GHz), and temperature coefficient of resonance frequency (τf ∼ −5.2 to 0.0 ppm/°C) after sintering at 860°C/4 h and 800°C/4 h. For the first time, TiO2 was added to enhance the density and Q × f value without degrading τf. The 0.25 wt.% TiO2 resulted in optimum εr of 13.4, Q × f of 43 636 GHz, and τf of +1.8 ppm/°C after sintering at 760°C/4 h. The improved quality factor (Q × f) is linked to the Raman A1g mode and relative density. [ABSTRACT FROM AUTHOR]

Background: Despite promising outcomes of treatment with anti-programmed cell death (PD)-1/PD-ligand (L)1 agents in combination with platinum-doublet chemotherapy (PDC) in the first-line setting, a significant unmet medical need remains in patients with PD-L1-unselected non-small cell lung cancer (NSCLC). Methods: This multicenter, open-label, phase 1b study comprising dose-confirmation and dose-expansion parts investigated the combination of spartalizumab and various PDC regimens, with or without canakinumab, in treatment-naïve patients with PD-L1-unselected, metastatic NSCLC. The primary objectives were to determine maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of spartalizumab, with or without canakinumab, in combination with PDC in the dose-confirmation part and antitumor activity of spartalizumab in the dose-expansion part. Results: The MTD/RDE of spartalizumab was 300 mg every 3 weeks (Q3W) when administered with either gemcitabine (1250 mg/m2)/cisplatin (75 mg/m2) (group A; no dose-limiting toxicities [DLTs]), pemetrexed (500 mg/m2)/cisplatin (group B; 2 DLTs: grade 2 posterior reversible encephalopathy syndrome and grade 4 hyponatremia), or paclitaxel (200 mg/m2)/carboplatin area under the curve 6 min*mg/mL (group C; 1 DLT: grade 4 neutropenic colitis). The RDE of canakinumab combined with spartalizumab and pemetrexed/cisplatin (group E; no DLTs) was 200 mg Q3W (no dose-expansion part was initiated). No new safety signals were identified. In groups A, B, C, and E, the overall response rates were 57.6%, 55.3%, 51.5%, and 57.1%, respectively. Group B compared with other groups had the longest median progression-free survival (10.4 months vs. 6.2–7.5 months), overall survival (29.7 months vs. 16.1–21.0 months), and duration of response (30.1 months vs. 6.0-8.2 months). Conclusions: The combination of spartalizumab and PDC, with or without canakinumab, was well tolerated across treatment groups. The antitumor activity across treatment groups was comparable with that of pembrolizumab and pemetrexed combination. Canakinumab did not appear to improve the antitumor activity when combined with spartalizumab, pemetrexed and cisplatin. Trial registration: The trial was registered in Clinicaltrials.gov with identifier no. NCT03064854. Date of Registration: 06 February 2017. Highlights: A significant unmet medical need still exists in patients with PD-L1-unselected NSCLC due to the limited efficacy of immune checkpoint inhibitors and the lack of a well-defined, effective treatment approach. Spartalizumab in combination with platinum doublet chemotherapy (PDC), with/without canakinumab, was well tolerated across treatment groups. Spartalizumab plus PDC, with/without canakinumab, showed the antitumor activity in this clinical setting. Addition of canakinumab did not appear to improve the antitumor activity of the combination of spartalizumab with pemetrexed plus cisplatin. [ABSTRACT FROM AUTHOR]

FOXG1 syndrome is a rare neurodevelopmental disorder of the telencephalon, for which there is no cure. Underlying heterozygous pathogenic variants in the Forkhead Box G1 (FOXG1) gene with resulting impaired or loss of FOXG1 function lead to severe neurological impairments. Here, we report a patient with a de novo pathogenic single nucleotide deletion c.946del (p.Leu316Cysfs*10) of the FOXG1 gene that causes a premature protein truncation. To study this variant in vivo, we generated and characterized Foxg1 c946del mice that recapitulate hallmarks of the human disorder. Accordingly, heterozygous Foxg1 c946del mice display neurological symptoms with aberrant neuronal networks and increased seizure susceptibility. Gene expression profiling identified increased oligodendrocyte- and myelination-related gene clusters. Specifically, we showed that expression of the c946del mutant and of other pathogenic FOXG1 variants correlated with overexpression of proteolipid protein 1 (Plp1), a gene linked to white matter disorders. Postnatal administration of Plp1-targeting antisense oligonucleotides (ASOs) in Foxg1 c946del mice improved neurological deficits. Our data suggest Plp1 as a new target for therapeutic strategies mitigating disease phenotypes in FOXG1 syndrome patients. [ABSTRACT FROM AUTHOR]

Introduction: Spontaneous pneumomediastinum with pneumopericardium is an uncommon clinical entity. Case Study: Here, we report the case of a 23-year-old male with asthma who presented with acute chest pain and shortness of breath after an episode of coughing and sneezing. CT scans of the chest and neck revealed pneumomediastinum and pneumopericardium with extensive subcutaneous emphysema extending into the axilla and neck. Results: The patient was admitted for observation and analgesia. No other interventions were administered. Interval scans performed on day five of the admission demonstrated an interval reduction in the degree of air within the mediastinum, pericardium and subcutaneous tissues, and the patient was subsequently discharged home. Conclusion: This case outlines the presentation, diagnosis, and management of concurrent spontaneous pneumomediastinum and pneumopericardium. [ABSTRACT FROM AUTHOR]

Introduction: Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma. Methods: In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants. Results: Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4–6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice. Conclusions: In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy. [ABSTRACT FROM AUTHOR]

Sustainable agricultural development not only addresses global food insecurity but may also alleviate poverty by enriching the lives of millions of smallholder farmers. Improving the sustainability and profitability of agriculture where smallholders are dominant creates profound impacts because small landholding farmers produce approximately 70–80% of the global food. The need for a thorough understanding of the factors affecting farmers' adoption of agricultural technologies and practices has been identified from extant literature as an important research gap. Responding to the research gap and need, this study examined the challenges that prevent farm households from adopting improved farming practices and/or technologies in Banteay Meanchey and Battambang provinces in Northwest Cambodia. A total of 524 rice producing farm household representatives were randomly selected from a household database maintained by the local government authorities. A mixed methods approach was used in the study including semi-structured interviews followed by in-depth interviews, field observations, and literature review. Farmers were found to be confronted with a range of challenges and concerns, including soil degradation, weeds, diseases, insect pests, high production costs, flooding, droughts, changing rainfall pattern, and unreliable rainfall distribution. The research findings demonstrate that improved crop production practices (e.g., adopting mechanised direct seeding methods of crop establishment, maintaining and improving soil health through crop residue retention, growing cover crops, etc.) and better resource use efficiency (e.g., reducing seeding rates to less than 100 kg/ha, being more strategic in the use of integrated nutrient, weed, and pest management strategies, etc.) can be a starting point for sustainable intensification of rice production. This transition towards intensifying paddy production sustainably may become even more effective through a clear understanding of local contexts, farm household characteristics, available resources, and the farm management practices and constraints. We observed that farmers and their associations have yet to be fully recognised as partners and actors in Cambodia. Instead, they tend to be viewed as beneficiaries and recipients of improved practices and technologies. We, therefore, propose that farmers and their associations be acknowledged and included in a process of co-creation of knowledge-practices. Such partnerships will enable the inclusion of factors (e.g., production costs, production risks, complexity and practicability of implementations, product market and prices, etc.) shown to influence farmers' adoption of innovative farming practices and technologies. The original contribution of this article is a real-world account of the constraints and limitations experienced by smallholder rice farmers in Cambodia, which are connected to future research and development priorities in the region. [ABSTRACT FROM AUTHOR]

Heat stress poses a significant environmental challenge that profoundly impacts wheat productivity. It disrupts vital physiological processes such as photosynthesis, by impeding the functionality of the photosynthetic apparatus and compromising plasma membrane stability, thereby detrimentally affecting grain development in wheat. The scarcity of identified marker trait associations pertinent to thermotolerance presents a formidable obstacle in the development of marker-assisted selection strategies against heat stress. To address this, wheat accessions were systematically exposed to both normal and heat stress conditions and phenotypic data were collected on physiological traits including proline content, canopy temperature depression, cell membrane injury, photosynthetic rate, transpiration rate (at vegetative and reproductive stage and 'stay-green'. Principal component analysis elucidated the most significant contributors being proline content, transpiration rate, and canopy temperature depression, which exhibited a synergistic relationship with grain yield. Remarkably, cluster analysis delineated the wheat accessions into four discrete groups based on physiological attributes. Moreover, to explore the relationship between physiological traits and DNA markers, 158 wheat accessions were genotyped with 186 SSRs. Allelic frequency and polymorphic information content value were found to be highest on genome A (4.94 and 0.688), chromosome 1A (5.00 and 0.712), and marker Xgwm44 (13.0 and 0.916). Population structure, principal coordinate analysis and cluster analysis also partitioned the wheat accessions into four subpopulations based on genotypic data, highlighting their genetic homogeneity. Population diversity and presence of linkage disequilibrium established the suitability of population for association mapping. Additionally, linkage disequilibrium decay was most pronounced within a 15–20 cM region on chromosome 1A. Association mapping revealed highly significant marker trait associations at Bonferroni correction P < 0.00027. Markers Xwmc418 (located on chromosome 3D) and Xgwm233 (chromosome 7A) demonstrated associations with transpiration rate, while marker Xgwm494 (chromosome 3A) exhibited an association with photosynthetic rates at both vegetative and reproductive stages under heat stress conditions. Additionally, markers Xwmc201 (chromosome 6A) and Xcfa2129 (chromosome 1A) displayed robust associations with canopy temperature depression, while markers Xbarc163 (chromosome 4B) and Xbarc49 (chromosome 5A) were strongly associated with cell membrane injury at both stages. Notably, marker Xbarc49 (chromosome 5A) exhibited a significant association with the 'stay-green' trait under heat stress conditions. These results offers the potential utility in marker-assisted selection, gene pyramiding and genomic selection models to predict performance of wheat accession under heat stress conditions. [ABSTRACT FROM AUTHOR]

Background: The identification of cancer driver genes from sequencing data has been crucial in deepening our understanding of tumor biology and expanding targeted therapy options. However, apart from the most commonly altered genes, the mechanisms underlying the contribution of other mutations to cancer acquisition remain understudied. Leveraging on our whole-exome sequencing of the largest Asian lung adenocarcinoma (LUAD) cohort (n = 302), we now functionally assess the mechanistic role of a novel driver, PARP4. Methods: In vitro and in vivo tumorigenicity assays were used to study the functional effects of PARP4 loss and mutation in multiple lung cancer cell lines. Interactomics analysis by quantitative mass spectrometry was conducted to identify PARP4's interaction partners. Transcriptomic data from cell lines and patient tumors were used to investigate splicing alterations. Results: PARP4 depletion or mutation (I1039T) promotes the tumorigenicity of KRAS- or EGFR-driven lung cancer cells. Disruption of the vault complex, with which PARP4 is commonly associated, did not alter tumorigenicity, indicating that PARP4's tumor suppressive activity is mediated independently. The splicing regulator hnRNPM is a potentially novel PARP4 interaction partner, the loss of which likewise promotes tumor formation. hnRNPM loss results in splicing perturbations, with a propensity for dysregulated intronic splicing that was similarly observed in PARP4 knockdown cells and in LUAD cohort patients with PARP4 copy number loss. Conclusions: PARP4 is a novel modulator of lung adenocarcinoma, where its tumor suppressive activity is mediated not through the vault complex—unlike conventionally thought, but in association with its novel interaction partner hnRNPM, thus suggesting a role for splicing dysregulation in LUAD tumorigenesis. [ABSTRACT FROM AUTHOR]

Introduction: Deep learning (DL) models predicting biomarker expression in images of hematoxylin and eosin (H&E)-stained tissues can improve access to multi-marker immunophenotyping, crucial for therapeutic monitoring, biomarker discovery, and personalized treatment development. Conventionally, these models are trained on ground truth cell labels derived from IHC-stained tissue sections adjacent to H&Estained ones, which might be less accurate than labels from the same section. Although many such DL models have been developed, the impact of ground truth cell label derivation methods on their performance has not been studied. Methodology: In this study, we assess the impact of cell label derivation on H&E model performance, with CD3+ T-cells in lung cancer tissues as a proof-ofconcept. We compare two Pix2Pix generative adversarial network (P2P-GAN)- based virtual staining models: one trained with cell labels obtained from the same tissue section as the H&E-stained section (the 'same-section' model) and one trained on cell labels from an adjacent tissue section (the 'serial-section' model). Results: We show that the same-section model exhibited significantly improved prediction performance compared to the 'serial-section' model. Furthermore, the same-section model outperformed the serial-section model in stratifying lung cancer patients within a public lung cancer cohort based on survival outcomes, demonstrating its potential clinical utility. Discussion: Collectively, our findings suggest that employing ground truth cell labels obtained through the same-section approach boosts immunophenotyping DL solutions. [ABSTRACT FROM AUTHOR]

Rationale: The term "pre–chronic obstructive pulmonary disease" ("pre-COPD") refers to individuals at high risk of developing COPD who do not meet conventional spirometric criteria for airflow obstruction. New approaches to identifying these individuals are needed, particularly in younger populations. Objectives: To determine whether lung function thresholds and respiratory symptoms can be used to identify individuals at risk of developing COPD. Methods: The Tasmanian Longitudinal Health Study comprises a population-based cohort first studied in 1968 (at age 7 yr). Respiratory symptoms, pre- and post-bronchodilator (BD) spirometry, diffusing capacity, and static lung volumes were measured in a subgroup at age 45, and the incidence of COPD was assessed at age 53. For each lung function measure, z-scores were calculated using Global Lung Function Initiative references. The optimal threshold for best discrimination of COPD incidence was determined by the unweighted Youden index. Measurements and Main Results: Among 801 participants who did not have COPD at age 45, the optimal threshold for COPD incidence by age 53 was pre-BD FEV1/FVC z-score less than −1.264, corresponding to the lowest 10th percentile. Those below this threshold had a 36-fold increased risk of developing COPD over an 8-year follow-up period (risk ratio, 35.8; 95% confidence interval, 8.88 to 144), corresponding to a risk difference of 16.4% (95% confidence interval, 3.7 to 67.4). The sensitivity was 88%, and the specificity was 87%. Positive and negative likelihood ratios were 6.79 and 0.14, respectively. Respiratory symptoms, post-BD spirometry, diffusing capacity, and static lung volumes did not improve on the classification achieved by pre-BD FEV1/FVC alone. Conclusions: This is the first study, to our knowledge, to evaluate the discriminatory accuracy of spirometry, diffusing capacity, and static lung volume thresholds for COPD incidence in middle-aged adults. Our findings support the inclusion of pre-BD spirometry in the physiological definition of pre-COPD and indicate that pre-BD FEV1/FVC at the 10th percentile accurately identifies individuals at high risk of developing COPD in community-based settings. [ABSTRACT FROM AUTHOR]

Food‐derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non‐gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non‐gastrointestinal diseases via the gut‐liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut‐liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non‐alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut‐liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate natural language processing (NLP) methods to infer metastatic sites from radiology reports. METHODS: A set of 4,522 computed tomography (CT) reports of 550 patients with 14 types of cancer was used to fine-tune four clinical large language models (LLMs) for multilabel classification of metastatic sites. We also developed an NLP information extraction (IE) system (on the basis of named entity recognition, assertion status detection, and relation extraction) for comparison. Model performances were measured by F1 scores on test and three external validation sets. The best model was used to facilitate analysis of metastatic frequencies in a cohort study of 6,555 patients with 53,838 CT reports. RESULTS: The RadBERT, BioBERT, GatorTron-base, and GatorTron-medium LLMs achieved F1 scores of 0.84, 0.87, 0.89, and 0.91, respectively, on the test set. The IE system performed best, achieving an F1 score of 0.93. F1 scores of the IE system by individual cancer type ranged from 0.89 to 0.96. The IE system attained F1 scores of 0.89, 0.83, and 0.81, respectively, on external validation sets including additional cancer types, positron emission tomography-CT ,and magnetic resonance imaging scans, respectively. In our cohort study, we found that for colorectal cancer, liver-only metastases were higher in de novo stage IV versus recurrent patients (29.7% v 12.2%; P <.001). Conversely, lung-only metastases were more frequent in recurrent versus de novo stage IV patients (17.2% v 7.3%; P <.001). CONCLUSION: We developed an IE system that accurately infers metastatic sites in multiple primary cancers from radiology reports. It has explainable methods and performs better than some clinical LLMs. The inferred metastatic phenotypes could enhance cancer research databases and clinical trial matching, and identify potential patients for oligometastatic interventions. Ever thought of using NLP to extract sites of metastases from radiology reports? Read this paper. [ABSTRACT FROM AUTHOR]

Background: Ex-ante identification of the last year in life facilitates a proactive palliative approach. Machine learning models trained on electronic health records (EHR) demonstrate promising performance in cancer prognostication. However, gaps in literature include incomplete reporting of model performance, inadequate alignment of model formulation with implementation use-case, and insufficient explainability hindering trust and adoption in clinical settings. Hence, we aim to develop an explainable machine learning EHR-based model that prompts palliative care processes by predicting for 365-day mortality risk among patients with advanced cancer within an outpatient setting. Methods: Our cohort consisted of 5,926 adults diagnosed with Stage 3 or 4 solid organ cancer between July 1, 2017, and June 30, 2020 and receiving ambulatory cancer care within a tertiary center. The classification problem was modelled using Extreme Gradient Boosting (XGBoost) and aligned to our envisioned use-case: "Given a prediction point that corresponds to an outpatient cancer encounter, predict for mortality within 365-days from prediction point, using EHR data up to 365-days prior." The model was trained with 75% of the dataset (n = 39,416 outpatient encounters) and validated on a 25% hold-out dataset (n = 13,122 outpatient encounters). To explain model outputs, we used Shapley Additive Explanations (SHAP) values. Clinical characteristics, laboratory tests and treatment data were used to train the model. Performance was evaluated using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC), while model calibration was assessed using the Brier score. Results: In total, 17,149 of the 52,538 prediction points (32.6%) had a mortality event within the 365-day prediction window. The model demonstrated an AUROC of 0.861 (95% CI 0.856–0.867) and AUPRC of 0.771. The Brier score was 0.147, indicating slight overestimations of mortality risk. Explanatory diagrams utilizing SHAP values allowed visualization of feature impacts on predictions at both the global and individual levels. Conclusion: Our machine learning model demonstrated good discrimination and precision-recall in predicting 365-day mortality risk among individuals with advanced cancer. It has the potential to provide personalized mortality predictions and facilitate earlier integration of palliative care. [ABSTRACT FROM AUTHOR]

Forty wheat samples of ten wheat varieties harvested from optimal or late sowings in 2019 and 2020 were evaluated for nutrient composition. This included crude protein (CP), starch, amino acids, minerals, phytate-phosphorus (phytate-P) and non-starch polysaccharides (NSPs). The objective was to investigate the impact of high temperature on wheat grain quality as a feedstuff for broiler chickens. Growth performance and economic impact of such changes were predicted by the Emmans, Fisher and Gous broiler growth model. On average, 2019 was 1 °C hotter than 2020 during the growing season (Narrabri, NSW 2390, Australia). The wheat harvested in 2019 had higher concentrations of CP, phytate-P, total P and calcium. In 2019, late sowing increased average protein concentrations from 166.6 to 190.2 g/kg, decreased starch concentration from 726 to 708 g/kg and increased total NSPs from 693 to 73.9 g/kg. Unlike the 2019 harvest, the late sowing in 2020 had no impact on CP concentrations in almost all wheat varieties. The 2019 varieties had higher concentrations of 16 assessed amino acids (p < 0.001) compared to the 2020 harvest. The largest difference was in lysine (19.2%), and the smallest difference was in proline (11.1%). It was predicted that broiler diets formulated from 2019 wheat varieties would have better efficiency of feed conversion with an advantage of 2.53% (1.539 versus 1.579) than 2020 varieties to 35 days post-hatch. This would translate to a cost saving of approximately AUD 16.45 per tonne of feed, much of which would represent additional profit. [ABSTRACT FROM AUTHOR]

Cotton (Gossypium hirsutum L.) is a significant fiber crop. Being a major contributor to the textile industry requires continuous care and attention. Cotton is subjected to various biotic and abiotic constraints. Among these, biotic factors including cotton leaf curl virus (CLCuV) are dominant. CLCuV is a notorious disease of cotton and is acquired, carried, and transmitted by the whitefly (Bemisia tabaci). A cotton plant affected with CLCuVmay show a wide range of symptoms such as yellowing of leaves, thickening of veins, upward or downward curling, formation of enations, and stunted growth. Though there aremany efforts to protect the crop from CLCuV, long-term results are not yet obtained as CLCuV strains are capable of mutating and overcoming plant resistance. However, systemic-induced resistance using a gene-based approach remained effective until new virulent strains of CLCuV (like Cotton Leaf Curl Burewala Virus and others) came into existence. Disease control by biological means and the development of CLCuV-resistant cotton varieties are in progress. In this review, we first discussed in detail the evolution of cotton and CLCuV strains, the transmission mechanism of CLCuV, the genetic architecture of CLCuV vectors, and the use of pathogen and nonpathogen-based approaches to control CLCuD. Next, we delineate the uses of cutting-edge technologies like genome editing (with a special focus on CRISPR-Cas), next-generation technologies, and their application in cotton genomics and speed breeding to develop CLCuD resistant cotton germplasm in a short time. Finally, we delve into the current obstacles related to cotton genome editing and explore forthcoming pathways for enhancing precision in genome editing through the utilization of advanced genome editing technologies. These endeavors aim to enhance cotton's resilience against CLCuD. [ABSTRACT FROM AUTHOR]

This study analyzed whether extended molecular profiling can predict the development of epidermal growth factor receptor (EGFR) gene T790M mutation, which is the most frequent resistance alteration in non‐small cell lung cancer (NSCLC) after treatment with the first‐/second‐generation (1G/2G) EGFR inhibitors (tyrosine kinase inhibitors [TKIs]), but only weakly associated with clinical characteristics. Whole exome sequencing (WES) was performed on pretreatment tumor tissue with matched normal samples from NSCLC patients with (n = 25, detected in tissue or blood rebiopsies) or without (n = 14, negative tissue rebiopsies only) subsequent EGFR p.T790M mutation after treatment with 1G/2G EGFR TKI. Several complex genetic biomarkers were assessed using bioinformatic methods. After treatment with first‐line afatinib (44%) or erlotinib/gefitinib (56%), median progression‐free survival and overall survival were 12.1 and 33.7 months, respectively. Clinical and tumor genetic characteristics, including age (median, 66 years), sex (74% female), smoking (69% never/light smokers), EGFR mutation type (72% exon 19 deletions), and TP53 mutations (41%) were not significantly associated with T790M mutation (p > 0.05). By contrast, complex biomarkers including tumor mutational burden, the clock‐like mutation signature SBS1 + 5, tumor ploidy, and markers of subclonality including mutant‐allele tumor heterogeneity, subclonal copy number changes, and median tumor‐adjusted variant allele frequency were significantly higher at baseline in tumors with subsequent T790M mutation (all p < 0.05). Each marker alone could predict subsequent development of T790M with an area under the curve (AUC) of 0.72–0.77, but the small number of cases did not allow confirmation of better performance for biomarker combinations in leave‐one‐out cross‐validated logistic regression (AUC 0.69, 95% confidence interval: 0.50–0.87). Extended molecular profiling with WES at initial diagnosis reveals several complex biomarkers associated with subsequent development of T790M resistance mutation in NSCLC patients receiving first‐/second‐generation TKIs as the first‐line therapy. Larger prospective studies will be necessary to define a forecasting model. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Plant Science. It discusses the adaptation of plants to waterlogging and hypoxia, which are challenges caused by climate change and extreme weather events. The editorial highlights the physiological, molecular, and management strategies that plants employ to cope with these conditions. It also emphasizes the need for further research and practical applications to help farmers mitigate the negative effects of waterlogging. The document includes references to various studies that explore the impact of waterlogging on plant growth and yield, as well as potential solutions for improving crop resilience. [Extracted from the article]

Background: Cotton is a strategically important fibre crop for global textile industry. It profoundly impacts several countries' industrial and agricultural sectors. Sustainable cotton production is continuously threatened by the unpredictable changes in climate, specifically high temperatures. Breeding heat-tolerant, high-yielding cotton cultivars with wide adaptability to be grown in the regions with rising temperatures is one of the primary objectives of modern cotton breeding programmes. Therefore, the main objective of the current study is to figure out the effective breeding approach to imparting heat tolerance as well as the judicious utilization of commercially significant and stress-tolerant attributes in cotton breeding. Initially, the two most notable heat-susceptible (FH-115 and NIAB Kiran) and tolerant (IUB-13 and GH-Mubarak) cotton cultivars were spotted to develop filial and backcross populations to accomplish the preceding study objectives. The heat tolerant cultivars were screened on the basis of various morphological (seed cotton yield per plant, ginning turnout percentage), physiological (pollen viability, cell membrane thermostability) and biochemical (peroxidase activity, proline content, hydrogen peroxide content) parameters. Results: The results clearly exhibited that heat stress consequently had a detrimental impact on every studied plant trait, as revealed by the ability of crossing and their backcross populations to tolerate high temperatures. However, when considering overall yield, biochemical, and physiological traits, the IUB-13 × FH-115 cross went over particularly well at both normal and high temperature conditions. Moreover, overall seed cotton yield per plant exhibited a positive correlation with both pollen viability and antioxidant levels (POD activity and proline content). Conclusions: Selection from segregation population and criteria involving pollen viability and antioxidant levels concluded to be an effective strategy for the screening of heat-tolerant cotton germplasms. Therefore, understanding acquired from this study can assist breeders identifying traits that should be prioritized in order to develop climate resilient cotton cultivars. [ABSTRACT FROM AUTHOR]

Background: Specialist palliative care is often provided late in the patient's disease trajectory in response to uncontrolled symptoms. Shifting from this reactionary illness-stress paradigm to a proactive health-wellness approach, the ENABLE (Educate, Nurture, Advise, Before Life Ends) telehealth model aims to enhance the coping, stress and symptom management, self-care, and advance care planning skills of patients with advanced cancers and their caregivers. The ENABLE model has been culturally adapted to Singapore (ENABLE-SG) and pilot-tested. A hybrid type 1 effectiveness-implementation design will be used to evaluate the effectiveness of ENABLE-SG while collecting real-world implementation data. Methods: This single-centre, assessor-blind, wait-list (immediately vs. 6 months) randomized controlled trial will recruit 300 adult patients within 60 days of an advanced cancer diagnosis and their family caregivers from the National Cancer Centre of Singapore. ENABLE-SG comprises structured psychoeducational sessions with a telehealth coach, covering essential topics of early palliative care. Participants will be assessed at baseline and every 3 months until patient's death, 12 months (caregivers), or end of study (patients). The primary outcome is patient quality of life 6 months after baseline. Secondary patient-reported outcomes include mood, coping, palliative care concerns, and health status. Secondary caregiver-reported outcomes include caregiver quality of life, mood, coping, and care satisfaction. Mixed-effects regression modelling for repeated measurements will be used. To assess the effectiveness of ENABLE-SG versus usual care, patient and caregiver outcomes at 6 months will be compared. To compare earlier versus delayed ENABLE-SG, patient and caregiver outcomes at 12 months will be compared. Within the hybrid type 1 effectiveness-implementation design, implementation outcomes will be evaluated in both the early and delayed groups. Acceptability, adoption, appropriateness, and feasibility will be assessed using a feedback survey and semi-structured interviews with a purposive sample of patients, caregivers, and healthcare providers. Transcribed interviews will be analysed thematically. Other implementation outcomes of penetration, fidelity, and cost will be assessed using records of study-related processes and summarized using descriptive statistics. A cost-effectiveness analysis will also be conducted. Discussion: This study will assess both effectiveness and implementation of ENABLE-SG. Insights into implementation processes can facilitate model expansion and upscaling. Trial registration: Registered prospectively on ClinicalTrials.gov, NCT06044441. Registered on 21/09/2023. [ABSTRACT FROM AUTHOR]

Background: Body temperature (BT) is routinely measured and can be controlled in critical care settings. BT can impact patient outcome, but the relationship between BT and mortality has not been well-established. Methods: A retrospective cohort study was conducted based on the MIMIC-IV (N = 43,537) and eICU (N = 75,184) datasets. The primary outcome and exposure variables were hospital mortality and first 48-h median BT, respectively. Generalized additive models were used to model the associations between exposures and outcomes, while adjusting for patient age, sex, APS-III, SOFA, and Charlson comorbidity scores, temperature gap, as well as ventilation, vasopressor, steroids, and dialysis usage. We conducted subgroup analysis according to ICU setting, diagnoses, and demographics. Results: Optimal BT was 37 °C for the general ICU and subgroup populations. A 10% increase in the proportion of time that BT was within the 36–38 °C range was associated with reduced hospital mortality risk in both MIMIC-IV (OR 0.91; 95% CI 0.90–0.93) and eICU (OR 0.86; 95% CI 0.85–0.87). On the other hand, a 10% increase in the proportion of time when BT < 36 °C was associated with increased mortality risk in both MIMIC-IV (OR 1.08; 95% CI 1.06–1.10) and eICU (OR 1.18; 95% CI 1.16–1.19). Similarly, a 10% increase in the proportion of time when BT > 38 °C was associated with increased mortality risk in both MIMIC-IV (OR 1.09; 95% CI 1.07–1.12) and eICU (OR 1.09; 95% CI 1.08–1.11). All patient subgroups tested consistently showed an optimal temperature within the 36–38 °C range. Conclusions: A BT of 37 °C is associated with the lowest mortality risk among ICU patients. Further studies to explore the causal relationship between the optimal BT and mortality should be conducted and may help with establishing guidelines for active BT management in critical care settings. [ABSTRACT FROM AUTHOR]

Among the lead-free piezoceramics, (1 − x)BiFeO 3 − x BaTiO3 (BF-BT) is considered a promising candidate for high-temperature piezoelectric materials owing to its high Curie temperature ( T C > 4 0 0 ∘ C) and good electromechanical properties. In this work, the hydrothermal synthesis method was used to prepare the precursor powders of BiFeO3 and BaTiO3, and then the mixed powder compacts with the chemical composition of 0.7BF–0.3BT were sintered under pressureless conditions. The influence of the hydrothermal reaction times (12–24 h) of BiFeO3 on the structures and electric properties of the sintered ceramics was instigated. First, all the samples synthesized with the tetragonal BaTiO3 and BiFeO3 powders were identified with relatively stable dielectric properties. As the hydrothermal reaction time to synthesize BiFeO3 increased, the dielectric properties as well as the temperature stability of the 0.7BiFeO3–0.3BaTiO3 ceramics also improved. At the condition of a hydrothermal reaction time of 24 h, the sample obtained possesses both the lowest temperature coefficient of dielectric constant (T k ε = 1. 5 3 × 1 0 − 2 / ∘ C between RT and 3 0 0 ∘ C) and the highest Curie temperature ( T C = 4 7 1 ∘ C at 100 kHz). Moreover, at high temperatures, it exhibits a higher AC impedance than others. The calculating result based on the resistive constant-phase-element model (R-CPE) circuit model showed that the grain boundary of the 0.7BF–0.3BT ceramics contributes more resistance to the conductivity at high temperatures. In summary, the hydrothermal reaction proved to be a useful way that achieves the preparation of single-phase 0.7BF–0.3BT ceramics with improved electrical properties. [ABSTRACT FROM AUTHOR]

Neurotrophic tyrosine kinase (NTRK) fusions involving NTRK1, NTRK2, and NTRK3 were found in a broad range of solid tumors as driver gene variants. However, the prevalence of NTRK fusions in Chinese solid tumor patients is rarely reported. Based on the next-generation sequencing data from 10,194 Chinese solid tumor patients, we identified approximately 0.4% (40/10,194) of Chinese solid tumor patients with NTRK fusion. NTRK fusions were most frequently detected in soft tissue sarcoma (3.0%), especially in the fibrosarcoma subtype (12.7%). A total of 29 NTRK fusion patterns were identified, of which 11 were rarely reported. NTRK fusion mostly co-occurred with TP53 (38%), CDKN2A (23%), and ACVR2A (18%) and rarely with NTRK amplification (5.0%) and single nucleotide variants (2.5%). DNA-based NTRK fusion sequencing exhibited a higher detection rate than pan-TRK immunohistochemistry (100% vs. 87.5%). Two patients with NTRK fusions showed clinical responses to larotrectinib, supporting the effective response of NTRK fusion patients to TRK inhibitors. [ABSTRACT FROM AUTHOR]

The Ni-rich layered oxide cathode has shown high energy density, proper rate capability, and longevity of the rechargeable battery, while poor stability and capacity fading are assumed to be its common cons. To address this obstacle, prospective cathode materials are synthesized by integrating the lithium transition metal oxides with an artificial cathode electrolyte interphase (CEI) layer. Herein, plasma-enhanced atomic layer deposition (PEALD) is employed to coat the LiNi0.8Mn0.1Co0.1O2 (NMC811) electrode with Al2O3 and MoO3. The combined results from morphological examinations revealed the formation of uniform Al2O3 and MoO3 sheets after 200 cycles of PEALD coating. Consistent results from the XRD analysis demonstrate that Al2O3 and MoO3 artificial CEIs can reduce Li–Ni mixing. The cyclic voltammetry tests show the oxidation–reduction kinetic. The modified NMC811 structures with Al2O3 and MoO3 represent a remarkable improvement in terms of capacity retention. The coated cathode with Al2O3 clearly outperforms the modified configuration with MoO3 concerning ionic conductivity, charge/discharge reversibility, and capacity retention. The promising results obtained in this study open the possibility of synthesizing Ni-rich cathodes with enhanced electrochemical performance. [ABSTRACT FROM AUTHOR]

High temperature has seriously impacted the production of wheat in many countries. We examined four wheat cultivars (PBW343, Berkurt, Janz, and Attila) under heat stress (35/25 °C) and control treatments (23/15 °C) for 3 days at the meiosis and anthesis stages to evaluate the response and recovery of the four cultivars to heat stress and the relationship between photosynthetic parameters related to heat tolerance. Photosynthetic activity in all cultivars declined in plants that were treated at 35 °C, even for only 1 d compared with control plants. However, the differences among the four cultivars were obvious in net photosynthetic rate (Pn). At meiosis, the reduction of Pn in Berkut and PBW343 was lower and could nearly fully recover after 3 d of recovery and showed higher heat tolerance characteristics. The highest reduction in Pn occurred in Janz, which did not recover completely after 3 d of recovery. The same trend was observed at the anthesis stage, but Pn in all cultivars could not fully recover. Taking transpiration rate (Tr), stomatal conductance (gs), intercellular CO2 concentration (Ci), and limitation of stomatal conductance (Ls) into account, results suggested the decline in Pn under heat stress was mainly caused by non-stomatal restriction. In parallel with the decline in Pn, the maximum photochemical efficiency (Fv/Fm) decreased. In addition, both the maximum rate of net photosynthesis (Pmax) and the light saturation point declined after heat stress in all cultivars. However, the relevant photosynthetic parameters of PBW343 and Berkut recovered more quickly at both the meiotic and flowering stages. In summary, there were significant differences in the adaptability of different cultivars to high temperatures, with Berkut and PBW343 being more adaptable to heat stress than Janz and Attila. These may be used as valuable resources for further studies in breeding to understand the physiological mechanisms of heat sensitivity. This paper provides detailed information on the ecophysiological responses of wheat under heat stress. [ABSTRACT FROM AUTHOR]

This document is a reply to Dr. Divo and Dr. Celli's correspondence regarding a study on pre-chronic obstructive lung disease (pre-COPD). The authors clarify that their study is the first to provide discriminatory accuracy estimates for a range of physiological abnormalities for pre-COPD. They explain that their intention was to evaluate and compare the discriminatory accuracy of individual physiological measures over a range of thresholds, which was an important step before adding physiological variables to their model. The authors acknowledge the importance of developing validated risk prediction models and advocate for evaluating the pre-COPD concept more broadly at a population level. They also address concerns about the lack of validation in their study and discuss the inclusion of symptoms in the diagnosis of COPD. Overall, they believe that their discriminatory accuracy analysis is novel and distinct from previously published work, but they welcome discussion and debate to advance the pre-COPD concept. [Extracted from the article]

Neurotrophic tyrosine kinase (NTRK) fusions involving NTRK1, NTRK2, and NTRK3 were found in a broad range of solid tumors as driver gene variants. However, the prevalence of NTRK fusions in Chinese solid tumor patients is rarely reported. Based on the next-generation sequencing data from 10,194 Chinese solid tumor patients, we identified approximately 0.4% (40/10,194) of Chinese solid tumor patients with NTRK fusion. NTRK fusions were most frequently detected in soft tissue sarcoma (3.0%), especially in the fibrosarcoma subtype (12.7%). A total of 29 NTRK fusion patterns were identified, of which 11 were rarely reported. NTRK fusion mostly co-occurred with TP53 (38%), CDKN2A (23%), and ACVR2A (18%) and rarely with NTRK amplification (5.0%) and single nucleotide variants (2.5%). DNA-based NTRK fusion sequencing exhibited a higher detection rate than pan-TRK immunohistochemistry (100% vs. 87.5%). Two patients with NTRK fusions showed clinical responses to larotrectinib, supporting the effective response of NTRK fusion patients to TRK inhibitors. [ABSTRACT FROM AUTHOR]

Background: Cancer predisposition is most often studied in the context of single cancers. However, inherited cancer predispositions can also give rise to multiple primary cancers. Yet, there is a paucity of studies on genetic predisposition in multiple primary cancers, especially those outside of well-defined cancer predisposition syndromes. This study aimed to identify germline variants associated with dual primary cancers of the breast and lung. Methods: Exome sequencing was performed on germline DNA from 55 Singapore patients (52 [95%] never-smokers) with dual primaries in the breast and lung, confirmed by histopathology. Using two large control cohorts: the local SG10K_Health (n = 9770) and gnomAD non-cancer East Asians (n = 9626); and two additional local case cohorts of early-onset or familial breast cancer (n = 290), and lung cancer (n = 209), variants were assessed for pathogenicity in accordance with ACMG/AMP guidelines. In particular, comparisons were made with known pathogenic or likely pathogenic variants in the ClinVar database, pathogenicity predictions were obtained from in silico prediction software, and case–control association analyses were performed. Results: Altogether, we identified 19 pathogenic or likely pathogenic variants from 16 genes, detected in 17 of 55 (31%) patients. Six of the 19 variants were identified using ClinVar, while 13 variants were classified pathogenic or likely pathogenic using ACMG/AMP guidelines. The 16 genes include well-known cancer predisposition genes such as BRCA2, TP53, and RAD51D; but also lesser known cancer genes EXT2, WWOX, GATA2, and GPC3. Most of these genes are involved in DNA damage repair, reaffirming the role of impaired DNA repair mechanisms in the development of multiple malignancies. These variants warrant further investigations in additional populations. Conclusions: We have identified both known and novel variants significantly enriched in patients with primary breast and lung malignancies, expanding the body of known cancer predisposition variants for both breast and lung cancer. These variants are mostly from genes involved in DNA repair, affirming the role of impaired DNA repair in the predisposition and development of multiple cancers. [ABSTRACT FROM AUTHOR]

Rationale: Asthma is a heterogeneous condition, and longitudinal phenotyping may provide new insights into the origins and outcomes of the disease. Objectives: We aimed to characterize the longitudinal phenotypes of asthma between the first and sixth decades of life in a population-based cohort study. Methods: Respiratory questionnaires were collected at seven time points in the TAHS (Tasmanian Longitudinal Health Study) when participants were aged 7, 13, 18, 32, 43, 50, and 53 years. Current-asthma and ever-asthma status was determined at each time point, and group-based trajectory modeling was used to characterize distinct longitudinal phenotypes. Linear and logistic regression models were fitted to investigate associations of the longitudinal phenotypes with childhood factors and adult outcomes. Measurements and Main Results: Of 8,583 original participants, 1,506 had reported ever asthma. Five longitudinal asthma phenotypes were identified: early-onset adolescent-remitting (40%), early-onset adult-remitting (11%), early-onset persistent (9%), late-onset remitting (13%), and late-onset persistent (27%). All phenotypes were associated with chronic obstructive pulmonary disease at age 53 years, except for late-onset remitting asthma (odds ratios: early-onset adolescent-remitting, 2.00 [95% confidence interval (CI), 1.13-3.56]; early-onset adult-remitting, 3.61 [95% CI, 1.30-10.02]; early-onset persistent, 8.73 [95% CI, 4.10-18.55]; and late-onset persistent, 6.69 [95% CI, 3.81-11.73]). Late-onset persistent asthma was associated with the greatest comorbidity at age 53 years, with increased risk of mental health disorders and cardiovascular risk factors. Conclusions: Five longitudinal asthma phenotypes were identified between the first and sixth decades of life, including two novel remitting phenotypes. We found differential effects of these phenotypes on risk of chronic obstructive pulmonary disease and nonrespiratory comorbidities in middle age. [ABSTRACT FROM AUTHOR]

Climate change has affected the food supply chain and raised serious food concerns for humans and animals worldwide. The present investigation aimed to assess the effect of environmental factors along with three different levels of cutting (i.e., cutting 1, 2, and 3 at the vegetative, budding, and flowering stages, respectively) and spacing (i.e., 21, 23, and 26 cm) on quinoa biomass and quality to select the most suitable accessions. This experiment was repeated for two years using a split–split plot experimental design. The cutting × genotype × year and cutting × space × genotype interactions were significant for most quinoa morphological traits (except for leaf area and intermodal distance), where the maximum growth in number of leaves/plant (NoL), plant height (PH), fresh weight (FW), number of branches/plant (Br), and dry weight (DW) were observed during the second growing season. Cutting and spacing levels also showed significant effects on morphological and quality traits of quinoa. Among the different levels of cutting and spacing, cutting level 3 and spacing level 2 were more effective across both years at gaining maximum biomass and quality traits such as crude fat (CF) and crude protein (CP). According to the MGIDI, only two accessions (R3 and R9) fared better in both growing seasons, and selected accessions had positive morphological and quality traits. There were moderately significant negative correlations between PH, NoL, LA, FW, and DW and anti-quality traits such as neutral detergent fiber (NDF) and acid detergent fiber (ADF), indicating that an increase in biomass decreased the concentrations of ADF and NDF in both stem and leaves. A comparison with oat accessions (G3 and G7) revealed that quinoa has higher CP and CF and lower NDF than oats in both stems and leaves (except for ADF). In conclusion, the combination of cutting level 3 and spacing level 2 (23 cm) is more suitable to obtain high-quality quinoa forage with maximum biomass production. Furthermore, the MGIDI is a useful tool for breeders to select genotypes based on their mean performance, stability, and desired traits. [ABSTRACT FROM AUTHOR]

Lead (Pb) and nickel (Ni) are serious soil pollutants that adversely affect plant growth and development and need to be removed through phytoremediation. The present study aimed to assess the morphological indices of Albizia lebbeck (L.) (Benth.) in relation to anatomical modifications for survival under both Pb and Ni stress. The seedlings of A. lebbeck were established and then subjected to four different concentrations, viz. 0 mM, 25 mM, 50 mM and 75 mM, of Pb and Ni for 14 days in two phases. Morphological traits such as shoot length (70.93%), fresh weight (79.27%), dry weight (83.9%), number of root hairs (65.7%), number of leaves per plant (67.4%) and number of leaflets per plant greatly reduced under Pb or Ni stress. Surprisingly, root length increased rather than decreased with the increase in Pb or Ni concentrations, along with an increase in leaflet width, leaflet length and leaflet area. Moreover, root cortical cell area, metaxylem area and phloem area decreased at 75 mM of Pb and Ni while epidermal thickness and cell area increased. Stem epidermal thickness, cell area and phloem area significantly decreased with the consistent increase in metaxylem area and cortical region thickness under both Pb and Ni stress. Leaf anatomical traits such as midrib thickness, abaxial epidermal thickness and stomatal density and adaxial epidermal thickness and stomatal area significantly increased with increasing Pb or Ni stress. Correlation analysis revealed close relations among morphological and anatomical traits (such as root length with cortical region thickness) for better plant survival under Pb or Ni stress, and a PCA-biplot further verified these correlation analyses. Cluster analyses demonstrated the associations among the morphological and anatomical traits based on different stress levels. Furthermore, we found that the longer exposure (from phase 1 to phase 2) of heavy metals stress is more dangerous for plant survival and can ultimately lead to plant death. Moreover, our results also confirmed that Ni is more harmful or dangerous to plants than Pb at high and moderate concentrations. The anatomical modifications ensured the survival of A. lebbeck in extreme heavy metals stress and therefore unlocked its potential to be used as a natural source of phytoremediation. We also recommend that the genetic potential of A. lebbeck associated with its survival under heavy metal stress be investigated. [ABSTRACT FROM AUTHOR]

Context: Cost-conscious care is critical for healthcare sustainability but evidence suggests that most doctors do not consider cost in their clinical decision making. A critical step in changing this is understanding the barriers to encouraging behaviours and attitudes related to cost-conscious care. We therefore conducted a qualitative study to address the research question: what factors influence consideration of cost in emergency medicine (ED) clinical decision making? Methods: This was a qualitative focus group study using patient vignettes to explore attitudes towards cost-conscious clinical decision making. Participants were Year 4 and Year 5 medical students from Singapore, a country with a fee-for-service healthcare system. After a data-driven initial data analysis, and to make sense of a multitude of factors impacting on cost conscious care, we selected Fishbein's integrative model of behavioural prediction to underpin secondary data analysis. Results: Via four focus groups with 21 participants, we identified five main themes relevant to the integrative model of behavioural prediction. These were: attitudes towards considering cost when managing a patient (e.g., "better safe than sorry"); normative beliefs (e.g., doing what others do, perceptions of patient wishes); efficacy beliefs (e.g., no authority to take decisions or challenge); skills and knowledge (e.g., little knowledge of costs), and environmental constraints (e.g., the nature of the healthcare system). Discussion: Medical students do not consider cost in their clinical decision making due to numerous factors, of which lack of knowledge of costs is but one. While some of the factors identified reflect those found in previous studies with residents and fully-trained staff, and in other contexts, theory driven analysis added value in that it facilitated a richer exploration of why students do not consider cost in clinical decision making. Our findings provide insight to inform how best to engage and empower educators and learners in teaching and learning about cost-conscious care. [ABSTRACT FROM AUTHOR]

Polypropylene film is the most important organic dielectric in capacitor technology; however, applications such as power electronic devices require more miniaturized capacitors and thinner dielectric films. The commercial biaxially oriented polypropylene film is losing the advantage of its high breakdown strength as it becomes thinner. This work carefully studies the breakdown strength of the film between 1 and 5 microns. The breakdown strength drops rapidly and hardly ensures that the capacitor reaches a volumetric energy density of 2 J/cm3. Differential scanning calorimetry, X-ray, and SEM analyses showed that this phenomenon has nothing to do with the crystallographic orientation and crystallinity of the film but is closely related to the non-uniform fibers and many voids produced by overstretching the film. Measures must be taken to avoid their premature breakdown due to high local electric fields. An improvement below 5 microns will maintain a high energy density and the important application of polypropylene films in capacitors. Without destroying the physical properties of commercial films, this work employs the ALD oxide coating scheme to augment the dielectric strength of a BOPP in the thickness range below 5 μm, especially its high temperature performance. Therefore, the problem of the reduction in dielectric strength and energy density caused by BOPP thinning can be alleviated. [ABSTRACT FROM AUTHOR]

Single-agent checkpoint inhibitor (CPI) activity in Epstein-Barr Virus (EBV) related nasopharyngeal carcinoma (NPC) is limited. Dual CPI shows increased activity in solid cancers. In this single-arm phase II trial (NCT03097939), 40 patients with recurrent/metastatic EBV-positive NPC who failed prior chemotherapy receive nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. Primary outcome of best overall response rate (BOR) and secondary outcomes (progression-free survival [PFS], clinical benefit rate, adverse events, duration of response, time to progression, overall survival [OS]) are reported. The BOR is 38% with median PFS and OS of 5.3 and 19.5 months, respectively. This regimen is well-tolerated and treatment-related adverse events requiring discontinuation are low. Biomarker analysis shows no correlation of outcomes to PD-L1 expression or tumor mutation burden. While the BOR does not meet pre-planned estimates, patients with low plasma EBV-DNA titre (<7800 IU/ml) trend to better response and PFS. Deep immunophenotyping of pre- and on-treatment tumor biopsies demonstrate early activation of the adaptive immune response, with T-cell cytotoxicity seen in responders prior to any clinically evident response. Immune-subpopulation profiling also identifies specific PD-1 and CTLA-4 expressing CD8 subpopulations that predict for response to combined immune checkpoint blockade in NPC. Dual PD-1 and CTLA-4 checkpoint blockade has proven effective in several cancer types. Here the authors report the results of a clinical trial of anti-PD1 (nivolumab) and anti-CTLA4 (ipilimumab) in patients with recurrent/metastatic EBV-positive nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Image retargeting aims to resize a photograph without distorting its content. Recent solutions leverage generative adversarial networks (GANs) to learn an image's internal distribution. Patches are then replicated and generated to fill the target aspect ratio to preserve the internal distribution. Although these approaches are somewhat successful, they do not have a sense of image semantics or the image's contents, causing semantic errors during generation (e.g., a person with two heads). Our model addresses this by allowing user intervention. The users can preserve the objects they desire through user-defined masks. Our model enforces the masked object to appear at the user-defined location. It also utilizes a de-association regularizer to loosen the association of the selected object with its surroundings. Our method prevents object distortion and enables the user to remove or relocate the object from the input image while allowing the user to set its target size. [ABSTRACT FROM AUTHOR]

Background: The extent to which biomarkers of asthma activity persist in spontaneous asthma remission and whether such markers are associated with future respiratory outcomes remained unclear. We investigated the association between sub‐clinical inflammation in adults with spontaneous asthma remission and future asthma relapse and lung function decline. Methods: The Tasmanian Longitudinal Health Study is a population‐based cohort (n = 8583). Biomarkers of systemic inflammation were measured on participants at age 45, and latent profile analysis was used to identify cytokine profiles. Bronchial hyperresponsiveness (BHR) and nitric oxide products in exhaled breath condensate (EBC NOx) were measured at age 50. Participants with spontaneous asthma remission at ages 45 (n = 466) and 50 (n = 318) were re‐evaluated at age 53, and associations between baseline inflammatory biomarkers and subsequent asthma relapse and lung function decline were assessed. Results: We identified three cytokine profiles in adults with spontaneous asthma remission: average (34%), Th2‐high (42%) and Th2‐low (24%). Compared to the average profile, a Th2‐high profile was associated with accelerated decline in post‐BD FEV1/FVC (MD −0.18% predicted per‐year; 95% CI −0.33, −0.02), while a Th2‐low profile was associated with accelerated decline in both post‐BD FEV1 (−0.41%; −0.75, −0.06) and post‐BD FVC (−0.31%; −0.62, 0.01). BHR and high TNF‐α during spontaneous remission were associated with an increased risk of asthma relapse. In contrast, we found no evidence of association between EBC NOx and either asthma relapse or lung function decline. Conclusion: BHR and serum inflammatory cytokines have prognostic value in adults with spontaneous asthma remission. At‐risk individuals with BHR, Th2‐high or Th2‐low cytokine profiles may benefit from closer monitoring and on‐going follow‐up. [ABSTRACT FROM AUTHOR]

Profiling tumors at single-cell resolution provides an opportunity to understand complexities underpinning lymph-node metastases in head and neck squamous-cell carcinoma. Single-cell RNAseq (scRNAseq) analysis of cancer-cell trajectories identifies a subpopulation of pre-metastatic cells, driven by actionable pathways including AXL and AURK. Blocking these two proteins blunts tumor invasion in patient-derived cultures. Furthermore, scRNAseq analyses of tumor-infiltrating CD8 + T-lymphocytes show two distinct trajectories to T-cell dysfunction, corroborated by their clonal architecture based on single-cell T-cell receptor sequencing. By determining key modulators of these trajectories, followed by validation using external datasets and functional experiments, we uncover a role for SOX4 in mediating T-cell exhaustion. Finally, interactome analyses between pre-metastatic tumor cells and CD8 + T-lymphocytes uncover a putative role for the Midkine pathway in immune-modulation and this is confirmed by scRNAseq of tumors from humanized mice. Aside from specific findings, this study demonstrates the importance of tumor heterogeneity analyses in identifying key vulnerabilities during early metastasis. The molecular mechanisms underlying lymph-node metastasis in head and neck squamous-cell carcinoma remain to be investigated. Here, the authors perform single-cell RNA sequencing of cancer cells and CD8 + T cells and suggest potential mechanisms of immune evasion during early metastasis. [ABSTRACT FROM AUTHOR]

Introduction: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease requiring multimodal treatment approaches. KINDLE-Asia, as part of a real world global study, evaluated treatment patterns and associated survival outcomes in stage III NSCLC in Asia. Methods: Retrospective data from 57 centers in patients with stage III NSCLC diagnosed between January 2013 and December 2017 were analyzed. Median progression free survival (mPFS) and median overall survival (mOS) estimates with two sided 95% confidence interval (CI) were determined by applying the Kaplan-Meier survival analysis. Results: Of the total 1874 patients (median age: 63.0 years [24 to 92]) enrolled in the Asia subset, 74.8% were men, 54.7% had stage IIIA disease, 55.7% had adenocarcinoma, 34.3% had epidermal growth factor receptor mutations (EGFRm) and 50.3% had programmed death-ligand 1 (PD-L1) expression (i.e. PD-L1 =1%). Of the 31 treatment approaches as initial therapy, concurrent chemoradiotherapy (CRT) was the most frequent (29.3%), followed by chemotherapy (14.8%), sequential CRT (9.5%), and radiotherapy (8.5%). Targeted therapy alone was used in 81 patients of the overall population. For the Asia cohort, the mPFS and mOS were 12.8 months (95% CI, 12.2-13.7) and 42.3 months (95% CI, 38.1-46.8), respectively. Stage IIIA disease, Eastern Cooperative Oncology Group =1, age =65 years, adenocarcinoma histology and surgery/concurrent CRT as initial therapy correlated with better mOS (p < 0.05). Conclusions: The results demonstrate diverse treatment patterns and survival outcomes in the Asian region. The high prevalence of EGFRm and PD-L1 expression in stage III NSCLC in Asia suggests the need for expanding access to molecular testing for guiding treatment strategies with tyrosine kinase inhibitors and immunotherapies in this region. [ABSTRACT FROM AUTHOR]

Pendimethalin herbicide toxicity to rice plants and barnyard grass invasion have increasingly affected the productivity of direct-seeded rice (DSR) in the fields. Whether and how to promote DSR productivity and sustain weed management depend on the appropriate pre-emergence herbicide application rate to minimise its toxicity in the rice ecosystem. Pot experiments were conducted to determine the effects of pendimethalin rates (1.5, 1.75, 2.0 kg a.i. ha−1, two control treatments include the untreated control and the treated control with 1.5 kg a.i. ha−1 S-metolachlor) on barnyard grass (Echinochloa crus-galli (L.) Beaux) and their potential toxicity risk to photosynthetic performances of rice (Topaz and Sen pidao). All the pendimethalin treatments provided excellent control of barnyard grass. Among the treatments, 1.5, 1.75, 2.0 kg a.i. ha−1 pendimethalin and 1.5 kg a.i. ha−1 S-metolachlor (treated control) decreased leaf area of barnyard grass significantly by 38.9, 49.6, 49.6 and 46.2%, respectively, compared with the untreated control at 40 days after sowing (DAS). The above-ground biomass of barnyard grass significantly decreased by 40% (1.48 g plant−1) with 2.0 kg a.i. ha−1 pendimethalin and by 46.2% (1.33 g plant−1) when 1.5 kg a.i. ha−1S-metolachlor was applied at 40 DAS compared with the untreated pots. Higher pendimethalin rates increased toxicity in Topaz and Sen pidao varieties, and 2.0 kg a.i. ha−1 pendimethalin significantly reduced effective quantum yield (light-adapted) of photosystem (PS) II by 18% (0.58) and 19% (0.52), respectively, compared with the untreated control. Application of 2.0 kg a.i. ha−1 pendimethalin rate significantly decreased the maximum quantum yield (dark-adapted) of Sen pidao (0.66) compared with 1.5 kg a.i. ha−1 pendimethalin (0.68) including the untreated control. All pendimethalin treatments suppressed above-ground biomass at 55 DAS, but above-ground biomass of barnyard grass significantly decreased by 59.9% when 2.0 kg a.i. ha−1 pendimethalin was applied compared with the untreated control. Although application of 1.5 kg a.i. ha−1 pendimethalin rates reduced the effective quantum yield (light-adapted) of photosystem II of Sen pidao (0.55) by a small percentage (8%) than Topaz (0.65), it was non-toxic for both varieties compared with 2.0 kg a.i. ha−1 pendimethalin. Therefore, the use of 1.5 kg a.i. ha−1 pendimethalin can be used for effective weed management in the direct seeding of rice at an early growth stage. [ABSTRACT FROM AUTHOR]

Background: Persons with advanced cancer may participate in Phase 1 clinical trials – first-in-human trials that are conducted with the main objectives of safety and dosing. The motivations for participation are not well understood and may include hope for cure. Aim: To explore the perspectives of persons with advanced cancer in order to understand the motivations for participating in Phase 1 clinical trials, experiences while being on trial and views on palliative care provision. Design: Qualitative study with a constructivist stance, using thematic analysis based upon the grounded theory approach. Setting/participants: 20 persons with advanced cancer who were participating in a Phase 1 clinical trial. Results: Many participants described how Phase 1 clinical trial participation was their last hope, as they were cognisant of their advanced disease. Information-seeking needs differed – some needed comprehensive information while others relied on the doctor's recommendation. Participants experienced varied negative and positive physical and psycho-emotional concerns, and needed to draw on multiple sources of support such as family, friends and healthcare professionals. Some could list potential benefits of palliative care but felt they did not require it yet. The overarching theme was hope and positive thinking as a way of coping. Conclusions: The concepts of hope as a way of coping and the supportive presence of healthcare professionals could be weaved into a future model of palliative care to improve the illness journey for patients considering Phase 1 clinical trial participation and other persons with advanced cancer. [ABSTRACT FROM AUTHOR]

Real-world outcomes of chemo-antiangiogenesis versus chemo-immunotherapy combinations in EGFR-mutant advanced non-small cell lung cancer patients after failure of EGFR-TKI therapy. Chemotherapy Plus Immunotherapy Versus Chemotherapy Plus Bevacizumab Versus Chemotherapy Alone in EGFR-Mutant NSCLC After Progression on Osimertinib. Keywords: EGFR mutation; lung cancer; immunotherapy; non-small cell lung cancer EN EGFR mutation lung cancer immunotherapy non-small cell lung cancer 117 120 4 03/08/23 20230201 NES 230201 1. [Extracted from the article]

Insect pests are a serious problem for rice farmers in Cambodia, threatening livelihoods and food security. To protect their yields, farmers are dependent on broad-spectrum pesticides, which has led to a pesticide 'lock-in' scenario. Our study aimed to better understand farmers' current pest management practices and the underlying knowledge and attitudes driving these behaviours. We surveyed rice farming households (n = 168) from five different villages in Battambang Province, Cambodia. Survey respondents considered insect pests to be the most significant cause of yield loss. Respondents depended solely on chemical insecticides to manage insect pests. Combinations of agronomic and pesticide application practices contributed to pesticide dependency, including high seeding rate, insecticide timing and application rate. Additionally, 77% of respondents misidentified the beneficial lady beetle, Micraspis discolor, as a pest. Respondents indicated a desire for education and training on pest and beneficial arthropod identification, safe pesticide use, and improved cropping practices. We suggest critical areas for education and training are damage thresholds of local pests, the role of natural enemies, and improved awareness of pesticide toxicity and exposure. Promoting local knowledge sharing to engage and empower farmers to make informed decisions about their own pest management can forge a pathway away from pesticide dependency. [ABSTRACT FROM AUTHOR]

Opinion statement: While cisplatin-based adjuvant chemotherapy has been the standard of care for the past two decades, the recent introduction of immunotherapy has heralded an important milestone in the adjuvant landscape of early-stage non-small cell lung cancer (NSCLC). The landmark approval of adjuvant atezolizumab based on disease-free survival (DFS) benefit in IMpower010 was swiftly followed by the recent data for use of adjuvant pembrolizumab in PEARLS/KEYNOTE-091, and similar trials involving other immune checkpoint inhibitors are eagerly anticipated. Although both atezolizumab and pembrolizumab demonstrated a significant DFS benefit in the intention-to-treat population, key subgroup analyses have raised questions about the role of predictive biomarkers such as PD-L1 expression and EGFR-mutation status. In this review, we examine the data from the two important trials (IMpower010 and PEARLS/KEYNOTE-091), discuss the controversies surrounding adjuvant immunotherapy including appropriate endpoints, biomarker selection and highlight key considerations in oncogene-driven NSCLC. Finally, we propose future directions including the impact of neoadjuvant therapy on developments in the adjuvant immunotherapy paradigm and role of minimal residual disease (MRD). [ABSTRACT FROM AUTHOR]