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As many business activities-especially those associated with the energy-intensive industries-continue to be major sources of greenhouse gas emissions, and hence significantly contributing to global warming, there is a perceived need to identify ways to make business activities eventually carbon neutral. This paper explores the implications of a changing climate for the global tourism business and its intertwining global aviation industry that operates in a self-regulatory environment. Adopting a bibliometric analysis of the literature in the domain of global tourism and climate change (772 articles), the paper reveals the underlying sustainability issues that entail unsustainable energy consumption. The aviation industry as a significant source of carbon emission within the sector is then examined by analyzing the top 20 largest commercial airlines in the world with respect to its ongoing mitigating measures in meeting the Paris Agreement targets. While self-regulatory initiatives are taken to adopt Sustainable Aviation Fuels (SAF) as alternative fuel production and consumption for drastically reducing carbon emission, voluntary alignment and commitment to long-term targets remain inconsistent. A concerted strategic approach to building up complementary sustainable infrastructures among the global network of airports based in various international tourist destination cities to enable a measurable reduction in carbon emission is necessary to achieve a transformational adaptation of a business sector that is of essence to the recovery of the global economy while attempting to tackle climate change in a post-COVID-19 era., (© The Author(s), under exclusive licence to Springer Japan KK, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In recent decades, gender-fair language (GFL) has drawn considerable attention in educational settings. The field of English language teaching (ELT) likewise has contributed to this development, with gender issues receiving significant focus. The current study adds to this evolving conversation by investigating ELT practitioners' perspectives on using the third-person singular pronoun they in academic writing (AW). This area has received little attention in the literature on gender diversity in ELT, particularly in restrictive and conservative societies such as the Philippines. Using a survey with 64 English language teachers from Philippine universities, 15 of whom participated in follow-up email interviews, the study explores what these teachers think about using singular they in AW. The study likewise examines the ways these teachers include the use of singular they in their AW teaching practice. The findings demonstrate that the teachers have positive views on using singular they in AW and, in fact, find it necessary for promoting gender inclusivity and equality. However, some teachers also report their own traditional, conservative knowledge and beliefs, and possible resistance from stakeholders as challenges that need to be faced when integrating singular they in AW as a component of GFL practice. Sa nakalipas na mga dekada, ang 'gender-fair language' (GFL) ay nakakuha ng malaking atensyon sa mga espasyo ng pagtuturo. Nakapag-ambag din sa debelopment nito ang larang ng pagtuturo ng wikang Ingles o English language teaching (ELT), kung saan karamihan ay nagtuon sa isyu ng kasarian. Ang kasalukuyang pag-aaral ay paglahok sa nabanggit na yumayabong na talastasan, sa pamamagitan ng pagsiyasat sa perspektiba ng mga praktisyoner ng ELT sa paggamit ng panghalip pang-isahan na nasa ikatlong panauhan na they sa akademikong pagsulat o 'academic writing' (AW). Batay sa mga literatura hinggil sa 'gender diversity' sa ELT, kakaunti pa ang nagsagawa ng pag-aaral sa erya na ito, partikular na sa mga mahihigpit at konserbatibong lipunan tulad ng Pilipinas. Sa pagsasagawa ng sarbey sa 64 na guro ng wikang Ingles mula sa mga unibersidad sa Pilipinas, kung saan 15 sa kanila ay lumahok sa follow-up na interbyu sa email, sinisiyasat ng pag-aaral kung ano ang pagtingin ng mga guro sa paggamit ng pang-isahang they sa AW. Sinusuri din sa pag-aaral ang pamamaraan ng mga guro sa kung paano isinasama sa pagtuturo ng AW ang paggamit ng pang-isahang they. Natuklasan sa pag-aaral na mayroong positibong pananaw ang mga guro sa paggamit ng pang-isahang they sa AW at, sa katunayan, nakita nila ang pangangailangan nito sa pagsusulong ng 'gender inclusivity' at 'equality.' Gayunman, ilan sa mga guro ay ibinahagi rin ang kanilang sariling tradisyonal, konserbatibong kaalaman at mga paniniwala, at ang posibilidad ng resistans mula sa mga stakeholder bilang hamon na kailangan harapin kapag isinama ang pang-isahang they sa AW bilang bahagi ng praktika ng GFL. PLAIN LANGUAGE SUMMARY: Gender-fair language (GFL) has sparked interest in schools during the last few decades, and issues concerning the use of GFL have been emphasized in English language teaching (ELT). This study investigates ELT teachers' perspectives on utilizing the third-person singular pronoun they in academic writing (AW), an area in the literature that has received little attention, particularly in conservative countries such as the Philippines. The current study looks specifically at what these teachers believe about using singular they in AW and how they incorporate it into their AW teaching practice. The findings indicate that the teachers favor the use of singular they in AW to promote gender equality and inclusivity. When introducing singular they in AW as part of GFL practice, however, some teachers identify their own conservative knowledge and values, as well as stakeholder resistance, as barriers. [ABSTRACT FROM AUTHOR]

This study explores the potential of green finance as a strategic method to addressing climate change mitigation in China's blockchain industry. This research methodically analyzes a large dataset collected from many sources across the period between 1999 and 2020. Using a mixed approach of quantitative research and qualitative case studies, this study delves into the tangled web of relationships between alternative finance sources for green initiatives and the use of blockchain technology to promote more environmentally friendly business practices. The results provide light on how green finance and blockchain technologies might work together to boost China's climate change mitigation efforts, revealing fresh insights into the possible synergies and obstacles that erupt from this intersection. In response to the worsening climate problem, there is a pressing need for unconventional methods of financing that can lead holistic sustainable growth. Concurrently, blockchain technology's disruptive potential reverberates across numerous sectors. However, research on blockchain's potential for combating climate change, especially in conjunction with green funding systems, is still in its infancy. Intrinsic interest has motivated this study, which provides a new viewpoint on paths that might transform climate change mitigation in China by mapping the unexplored territory at the intersection of the green finance and blockchain sectors. This research hopes that by examining this interface, it will shed light on the hidden opportunities presented by the combination of green financing and blockchain innovation, allowing for more well-informed and effective decisions to be made in support of environmentally sustainable futures., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Accurate detection of homologous recombination deficiency (HRD) in cancer patients is paramount in clinical applications, as HRD confers sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. With the advances in genome sequencing technology, mutational profiling on a genome-wide scale has become readily accessible, and our knowledge of the genomic consequences of HRD has been greatly expanded and refined. Here, we review the recent advances in HRD detection methods. We examine the copy number and structural alterations that often accompany the genome instability that results from HRD, describe the advantages of mutational signature-based methods that do not rely on specific gene mutations, and review some of the existing algorithms used for HRD detection. We also discuss the choice of sequencing platforms (panel, exome, or whole-genome) and catalog the HRD detection assays used in key PARP inhibitor trials. [ABSTRACT FROM AUTHOR]

Plant disease forecasting models, driven by concurrent data and advanced technologies, are reliable tools for accurate prediction of disease outbreaks in achieving sustainable and productive agricultural systems. Optimal integration of Internet of Things (IoTs), machine learning (ML) techniques and artificial intelligence (AI), further augment the capabilities of these models in empowering farmers with proactive disease control measures towards modern agriculture manifested by efficient resource management, reduced diseases and higher crop yields. This article summarizes the role of disease forecasting models in crop management, emphasizing the advancements and applications of AI and ML in disease prediction, challenges and future directions in the field via (a) The technological foundations and need for validation testing of models, (b) The advancements in disease forecasting with the importance of high-quality publicly available data and (c) The challenges and future directions for the development of transparent and interpretable open-source AI models. Further improvement of these models needs investment in continuous innovative research with collaboration and data sharing among agricultural stakeholders. [ABSTRACT FROM AUTHOR]

The triangular fibrocartilaginous complex is made of multiple components, of which the palmar and dorsal radioulnar ligaments play an important role in distal radioulnar joint stability. The ulnar wrist ligaments may be injured during forearm and wrist trauma. There are several aspects of triangular fibrocartilaginous complex management that are still open to debate. The aim of the present study was to review the current concepts and discuss emerging trends to better elucidate and treat this important ligament complex. Level of evidence: V [ABSTRACT FROM AUTHOR]

Integrated reporting (IR) represents a cutting-edge model for sustainability reporting. Despite gaining traction in several countries, its acceptance in China remains limited, with research exploring its implementation within the Chinese context being notably sparse. Whether IR is a universally applicable reporting approach is under debate, but the context is deemed to influence the universality of IR adoption. Regrettably, context-specific research, especially concerning emerging markets such as China, is noticeably absent. This paper endeavours to address this gap, responding to the requests of IR scholars by examining the suitability of IR for China through a thorough consideration of wide-ranging national-level factors. A conceptual model, rooted in institutional theory, is presented to theorize the feasibility and necessity of IR in particular nations. To achieve the objectives of this study, a contextual analysis, comprising political, economic, social, and technological (PEST) analysis, coupled with content analysis, is employed. The PEST analysis evaluates factors uniquely relevant to the local Chinese environment, including cultural, economic, political, legal, international, social, and environmental aspects. Concurrently, content analysis is used to assess the alignment of Chinese firms' corporate reports with the International Integrated Reporting Framework (IIRF) for the years 2012 and 2020. The findings suggest that in the Chinese context, IR is both feasible and necessary, affirming its applicability within the country. This research offers guidance for future studies similar to ours and serves as a roadmap for further IR research within China. The implications of this study will be of interest to both practitioners and regulatory bodies. [ABSTRACT FROM AUTHOR]

Objective: To establish a practical risk stratification system (RSS) based on ultrasonography (US) and clinical characteristics for predicting soft tissue masses (STMs) malignancy. Methods: This retrospective multicenter study included patients with STMs who underwent US and pathological examinations between April 2018 and April 2023. Chi-square tests and multivariable logistic regression analyses were performed to assess the association of US and clinical characteristics with the malignancy of STMs in the training set. The RSS was constructed based on the scores of risk factors and validated externally. Results: The training and validation sets included 1027 STMs (mean age, 50.90 ± 16.64, 442 benign and 585 malignant) and 120 STMs (mean age, 51.93 ± 17.90, 69 benign and 51 malignant), respectively. The RSS was constructed based on three clinical characteristics (age, duration, and history of malignancy) and six US characteristics (size, shape, margin, echogenicity, bone invasion, and vascularity). STMs were assigned to six categories in the RSS, including no abnormal findings, benign, probably benign (fitted probabilities [FP] for malignancy: 0.001–0.008), low suspicion (FP: 0.008–0.365), moderate suspicion (FP: 0.189–0.911), and high suspicion (FP: 0.798–0.999) for malignancy. The RSS displayed good diagnostic performance in the training and validation sets with area under the receiver operating characteristic curve (AUC) values of 0.883 and 0.849, respectively. Conclusion: The practical RSS based on US and clinical characteristics could be useful for predicting STM malignancy, thereby providing the benefit of timely treatment strategy management to STM patients. Critical relevance statement: With the help of the RSS, better communication between radiologists and clinicians can be realized, thus facilitating tumor management. Key Points: There is no recognized grading system for STM management. A stratification system based on US and clinical features was built. The system realized great communication between radiologists and clinicians in tumor management. [ABSTRACT FROM AUTHOR]

Non-enzymatic spontaneous deamination of 5-methylcytosine, producing thymine, is the proposed etiology of cancer mutational signature 1, which is the most predominant signature in all cancers. Here, the proposed mutational process was reconstituted using synthetic DNA and purified proteins. First, single-stranded DNA containing 5-methylcytosine at CpG context was incubated at an elevated temperature to accelerate spontaneous DNA damage. Then, the DNA was treated with uracil DNA glycosylase to remove uracil residues that were formed by deamination of cytosine. The resulting DNA was then used as a template for DNA synthesis by yeast DNA polymerase δ. The DNA products were analyzed by next-generation DNA sequencing, and mutation frequencies were quantified. The observed mutations after this process were exclusively C>T mutations at CpG context, which was very similar to signature 1. When 5-methylcytosine modification and uracil DNA glycosylase were both omitted, C>T mutations were produced on C residues in all sequence contexts, but these mutations were diminished by uracil DNA glycosylase-treatment. These results indicate that the CpG>TpG mutations were produced by the deamination of 5-methylcytosine. Additional mutations, mainly C>G, were introduced by yeast DNA polymerase ζ on the heat-damaged DNA, indicating that G residues of the templates were also damaged. However, the damage on G residues was not converted to mutations with DNA polymerase δ or ε. [ABSTRACT FROM AUTHOR]

Urban heat islands can jeopardize urban inhabitants, but the installation of green roofs (GRs) and walls (GWs) can contribute to mitigating urban overheating. The present study provides novel indices to easily predict the spatial median variation in air temperature at pedestrian heights related to the application of GR- and GW-based scenarios during the hottest hours of a typical summer day by varying the building height (BH), coverage percentage, and leaf area index. The indices are meant to be applied to built areas with 0.3–0.4 urban density in the Mediterranean climate and are derived from regression models fed with the outputs of 281 simulations of three urban areas developed and run in ENVI-met software. The developed models are all highly significant. The GR model shows that mitigation is influenced by all three parameters, and it can estimate mitigation with a root mean square error of 0.05 °C. Compared with the other parameters, the GW models revealed that the BH did not influence the decrease in air temperature. The green façade and living wall (LW) indices predict mitigation with errors of 0.04 °C and 0.05 °C, respectively. However, for the LW model, further parameters should be considered to improve its reliability. [ABSTRACT FROM AUTHOR]

Somatic hypermutation in cancer has gained momentum with the increased use of tumour mutation burden as a biomarker for immune checkpoint inhibitors. Spontaneous deamination of 5-methylcytosine to thymine at CpG dinucleotides is one of the most ubiquitous endogenous mutational processes in normal and cancer cells. Here, we performed a systematic investigation of somatic CpG hypermutation at a pan-cancer level. We studied 30,191 cancer patients and 103 cancer types and developed an algorithm to identify somatic CpG hypermutation. Across cancer types, we observed the highest prevalence in paediatric leukaemia (3.5%), paediatric high-grade glioma (1.7%), and colorectal cancer (1%). We discovered germline variants and somatic mutations in the mismatch repair complex MutSα (MSH2 - MSH6) as genetic drivers of somatic CpG hypermutation in cancer, which frequently converged on CpG sites and TP53 driver mutations. We further observe an association between somatic CpG hypermutation and response to immune checkpoint inhibitors. Overall, our study identified novel cancer types that display somatic CpG hypermutation, strong association with MutSα-deficiency, and potential utility in cancer immunotherapy. Synopsis: Systematic analysis of mutation rates in 30,191 cancer patients across 103 cancer types revealed a somatic CpG hypermutator phenotype, associated with MSH2/MSH6 deficiency, an increase in TP53 hotspot mutations, and associated improved response to immune checkpoint inhibitors. A subset of hypermutated tumours is characterised by an extreme rate of C > T substitutions at CpG dinucleotides. Somatic CpG hypermutation is associated with mismatch repair deficiency. Somatic CpG hypermutation is most common in pediatric leukaemia, pediatric gliomas, and colorectal cancer. Somatic CpG hypermutation converges on mutational hotspots in TP53. Somatic CpG hypermutation is associated with improved response to immune checkpoint inhibitors. Systematic analysis of mutation rates in 30,191 cancer patients across 103 cancer types revealed a somatic CpG hypermutator phenotype, associated with MSH2/MSH6 deficiency, an increase in TP53 hotspot mutations and associated improved response to immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Fintech is an industry that uses technology to enhance and automate financial services. Fintech firms use software, mobile apps, and digital technologies to provide financial services that are faster, more efficient, and more accessible than those provided by traditional banks and financial institutions. Fintech companies take care of processes such as lending, payment processing, personal finance, and insurance, among other financial services. A data breach refers to a security liability when unapproved individuals gain access to or pilfer susceptible data. Data breaches pose a significant financial, reputational, and legal liability for companies. In 2017, Equifax suffered a data breach that revealed the personal information of over 143 million customers. Combining federated learning (FL) and blockchain can provide financial institutions with additional insurance and safeguards. Blockchain technology can provide a transparent and secure platform for FL, allowing financial institutions to collaborate on machine learning (ML) models while maintaining the confidentiality and integrity of their data. Utilizing blockchain technology, FL can provide an immutable and auditable record of all transactions and data exchanges. This can ensure that all parties adhere to the protocols and standards agreed upon for data sharing and collaboration. We propose the implementation of an FL framework that uses multiple ML models to protect consumers against fraudulent transactions through blockchain. The framework is intended to preserve customer privacy because it does not mandate the exchange of private customer data between participating institutions. Each bank trains its local models using data from its consumers, which are then combined on a centralised federated server to produce a unified global model. Data is neither stored nor exchanged between institutions, while models are trained on each institution's data. [ABSTRACT FROM AUTHOR]

Pseudolesions in bone and muscle are encountered mostly incidentally in routine imaging studies, especially due to the recent advancements on many different imaging modalities. These lesions can be categorized into the following categories: normal variants; congenital; iatrogenic; degenerative; and postoperative. In this review, we discuss the many different radiological characteristics of musculoskeletal pseudolesions that appear on imaging, which can prevent non-essential additional studies. [ABSTRACT FROM AUTHOR]

Mutational signatures refer to distinct patterns of DNA mutations that occur in a specific context or under certain conditions. It is a powerful tool to describe cancer etiology. We conducted a study to show cancer heterogeneity and cancer specificity from the aspect of mutational signatures through collinearity analysis and machine learning techniques. Through thorough training and independent validation, our results show that while the majority of the mutational signatures are distinct, similarities between certain mutational signature pairs can be observed through both mutation patterns and mutational signature abundance. The observation can potentially assist to determine the etiology of yet elusive mutational signatures. Further analysis using machine learning approaches demonstrated moderate mutational signature cancer specificity. Skin cancer among all cancer types demonstrated the strongest mutational signature specificity. [ABSTRACT FROM AUTHOR]

The primary aim of this study is to examine the influence of the technological acceptance model on customer engagement. An additional aim of this study is to examine the mediating effect of customer satisfaction in the relationship between the technology acceptance model and customer engagement. The present study gathered primary data from users of retail banking services in specific metropolitan areas in India. The participants were chosen based on their considerable expertise in utilizing online, digital, and mobile banking platforms and their substantial knowledge of implementing advanced e-banking strategies. The application of confirmatory factor analysis investigated measurement validity. The study's findings indicate a significant correlation between emotional and rational engagement, mediated via perceived usefulness. Additionally, the study revealed that the relationship between perceived usefulness and emotional engagement is mediated by customer satisfaction. Furthermore, it can be observed that this factor entirely mediates the relationship between transaction cost and emotional engagement. The study's findings suggest that customer satisfaction is a complete mediator in the association between transaction cost and rational engagement. The results of this study make a valuable contribution to the current body of literature on the technological acceptance model, customer satisfaction, and customer engagement. [ABSTRACT FROM AUTHOR]

While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for detection of molecular residual disease (MRD), its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read-level, achieving an error rate of 4.2 × 10−7, which is about two orders of magnitude lower than a read-centric de-noising method. The application of AccuScan to MRD demonstrated analytical sensitivity down to 10−6 circulating variant allele frequency at 99% sample-level specificity. AccuScan showed 90% landmark sensitivity (within 6 weeks after surgery) and 100% specificity for predicting relapse in colorectal cancer. It also showed 67% sensitivity and 100% specificity in esophageal cancer using samples collected within one week after surgery. When AccuScan was applied to monitor immunotherapy in melanoma patients, the circulating tumor DNA (ctDNA) levels and dynamic profiles were consistent with clinical outcomes. Overall, AccuScan provides a highly accurate WGS solution for MRD detection, empowering ctDNA detection at parts per million range without requiring high sample input or personalized reagents. Synopsis: A novel approach, named AccuScan, was developed for molecular residual disease (MRD) detection and immunotherapy monitoring. This technology uses whole genome sequencing (WGS) with single-read error correction for circulating tumor DNA (ctDNA) analysis. AccuScan reduced WGS error rate to less than 5 × 10−7, enabling an ultralow limit of detection for circulating tumor variant allele frequency down to the parts-per-million (PPM) range. When applied to MRD detection, AccuScan achieved 90% landmark sensitivity and 100% specificity in post-surgical colorectal cancer patients. AccuScan showed high sensitivity and specificity for MRD detection in esophageal cancer and for immunotherapy monitoring in melanoma patients. AccuScan established a simple, white blood cell-free workflow for tumor-specific variant identification and tumor-informed MRD detection. A novel approach, named AccuScan, was developed for molecular residual disease (MRD) detection and immunotherapy monitoring. This technology uses whole genome sequencing (WGS) with single-read error correction for circulating tumor DNA (ctDNA) analysis. [ABSTRACT FROM AUTHOR]

Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer. Synopsis: Collecting duct carcinoma (CDC) is an aggressive kidney cancer without effective treatment. Our study not only enhanced our scientific understanding of the oncogenic alterations prevalent in Asian CDC, but has also identified cell-cycle machinery as a potential target for therapeutic intervention. Mutations in KRAS hotspot and TP53 were predominantly identified in Asian CDC patients, shedding light on the genetic landscape of this cancer. Aristolochic acid (AA) mutational signature was identified in CDC tumors, providing valuable insights for cancer prevention strategies. Dysregulation of cell-cycle machinery was observed in both Caucasian and Asian CDC patients, indicating similar disease pathobiology. We have established a CDC patient-derived xenograft (PDX) and cell line models to facilitate drug screening and testing. Through our screening efforts, we have identified and validated a CDK9 inhibitor, LDC000067, which specifically inhibited CDC tumor growth and improved overall survival. Collecting duct carcinoma (CDC) is an aggressive kidney cancer without effective treatment. Our study not only enhanced our scientific understanding of the oncogenic alterations prevalent in Asian CDC, but has also identified cell-cycle machinery as a potential target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Rationale: Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of cancer death worldwide. To reduce incidence and improve survival rates, a deeper understanding of lung premalignancy and the multistep process of tumorigenesis is essential, allowing timely and effective intervention before cancer development. Objectives: To summarize existing information, identify knowledge gaps, formulate research questions, prioritize potential research topics, and propose strategies for future investigations into the premalignant progression in the lung. Methods: An international multidisciplinary team of basic, translational, and clinical scientists reviewed available data to develop and refine research questions pertaining to the transformation of premalignant lung lesions to advanced lung cancer. Results: This research statement identifies significant gaps in knowledge and proposes potential research questions aimed at expanding our understanding of the mechanisms underlying the progression of premalignant lung lesions to lung cancer in an effort to explore potential innovative modalities to intercept lung cancer at its nascent stages. Conclusions: The identified gaps in knowledge about the biological mechanisms of premalignant progression in the lung, together with ongoing challenges in screening, detection, and early intervention, highlight the critical need to prioritize research in this domain. Such focused investigations are essential to devise effective preventive strategies that may ultimately decrease lung cancer incidence and improve patient outcomes. [ABSTRACT FROM AUTHOR]

In this review paper, we present a thorough investigation into the role of pavement technologies in advancing urban sustainability. Our analysis traverses the historical evolution of these technologies, meticulously evaluating their socio-economic and environmental impacts, with a particular emphasis on their role in mitigating the urban heat island effect. The evaluation of pavement types and variables influencing pavement performance to be used in the multi-criteria decision-making (MCDM) framework to choose the optimal pavement application are at the heart of our research. Which serves to assess a spectrum of pavement options, revealing insights into the most effective and sustainable practices. By highlighting both the existing challenges and potential innovative solutions within the field, this paper aims to offer a directional compass for future urban planning and infrastructural advancements. This review not only synthesizes the current state of knowledge but also aims to chart a course for future exploration, emphasizing the critical need for innovative and environmentally sensitive pavement technologies in the creation of resilient and sustainable urban environments. [ABSTRACT FROM AUTHOR]

Background: Health disparities have been highlighted among patient with prostate adenocarcinoma (PRAD) due to ethnicity. Mexican men present a more aggressive disease than other patients resulting in less favorable treatment outcome. We aimed to identify the mutational landscape which could help to reduce the health disparities among minority groups and generate the first genomics exploratory study of PRAD in Mexican patients. Methods: Paraffin-embedded formalin-fixed tumoral tissue from 20 Mexican patients with early-stage PRAD treated at The Instituto Nacional de Cancerología, Mexico City from 2017 to 2019 were analyzed. Tumoral DNA was prepared for whole exome sequencing, the resulting files were mapped against h19 using BWA-MEM. Strelka2 and Lancet packages were used to identify single nucleotide variants (SNV) and insertions or deletions. FACETS was used to determine somatic copy number alterations (SCNA). Cancer Genome Interpreter web interface was used to determine the clinical relevance of variants. Results: Patients were in an early clinical stage and had a mean age of 59.55 years (standard deviation [SD]: 7.1 years) with 90% of them having a Gleason Score of 7. Follow-up time was 48.50 months (SD: 32.77) with recurrences and progression in 30% and 15% of the patients, respectively. NUP98 (20%), CSMD3 (15%) and FAT1 (15%) were the genes most frequently affected by SNV; ARAF (75%) and ZNF419 (70%) were the most frequently affected by losses and gains SNCA's. One quarter of the patients had mutations useful as biomarkers for the use of PARP inhibitors, they comprise mutations in BRCA, RAD54L and ATM. SBS05, DBS03 and ID08 were the most common mutational signatures present in this cohort. No associations with recurrence or progression were identified. Conclusions: This pilot study reveals the mutational landscape of early-stage prostate adenocarcinoma in Mexican men, providing a first approach to understand the mutational patterns and actionable mutations in early prostate cancer can inform personalized treatment approaches and reduce the underrepresentation in genomic cancer studies. [ABSTRACT FROM AUTHOR]

Background: Deletions and partial losses of chromosome 7 (chr7) are frequent in acute myeloid leukemia (AML) and are linked to dismal outcome. However, the genomic landscape and prognostic impact of concomitant genetic aberrations remain incompletely understood. Methods: To discover genetic lesions in adult AML patients with aberrations of chromosome 7 [abn(7)], 60 paired diagnostic/remission samples were investigated by whole-exome sequencing in the exploration cohort. Subsequently, a gene panel including 66 genes and a SNP backbone for copy-number variation detection was designed and applied to the remaining samples of the validation cohort. In total, 519 patients were investigated, of which 415 received intensive induction treatment, typically containing a combination of cytarabine and anthracyclines. Results: In the exploration cohort, the most frequently mutated gene was TP53 (33%), followed by epigenetic regulators (DNMT3A, KMT2C, IDH2) and signaling genes (NRAS, PTPN11). Thirty percent of 519 patients harbored ≥ 1 mutation in genes located in commonly deleted regions of chr7—most frequently affecting KMT2C (16%) and EZH2 (10%). KMT2C mutations were often subclonal and enriched in patients with del(7q), de novo or core-binding factor AML (45%). Cancer cell fraction analysis and reconstruction of mutation acquisition identified TP53 mutations as mainly disease-initiating events, while del(7q) or −7 appeared as subclonal events in one-third of cases. Multivariable analysis identified five genetic lesions with significant prognostic impact in intensively treated AML patients with abn(7). Mutations in TP53 and PTPN11 (11%) showed the strongest association with worse overall survival (OS, TP53: hazard ratio [HR], 2.53 [95% CI 1.66–3.86]; P < 0.001; PTPN11: HR, 2.24 [95% CI 1.56–3.22]; P < 0.001) and relapse-free survival (RFS, TP53: HR, 2.3 [95% CI 1.25–4.26]; P = 0.008; PTPN11: HR, 2.32 [95% CI 1.33–4.04]; P = 0.003). By contrast, IDH2-mutated patients (9%) displayed prolonged OS (HR, 0.51 [95% CI 0.30–0.88]; P = 0.0015) and durable responses (RFS: HR, 0.5 [95% CI 0.26–0.96]; P = 0.036). Conclusion: This work unraveled formerly underestimated genetic lesions and provides a comprehensive overview of the spectrum of recurrent gene mutations and their clinical relevance in AML with abn(7). KMT2C mutations are among the most frequent gene mutations in this heterogeneous AML subgroup and warrant further functional investigation. [ABSTRACT FROM AUTHOR]

The aim of this study was to systemically evaluate how different pyrolysis temperatures (400, 550, and 700 °C) and particle sizes (1–2 mm and 63–75 µm) were influenced biochar evolution, made from urban pruning waste, during pyrolysis process and to establish their relationships with biochar potential for removal of lead (Pb), cadmium (Cd), and manganese (Mn) from real municipal solid waste landfill leachate. The effects of pH (2–7), contact time (30–300 min) and adsorbent dosage (0.1–5 g L−1) on heavy metals removal were also examined. The results showed that physicochemical properties of biochar were greatly influenced by pyrolysis temperature. Particle size, however, showed little influence on biochar characteristics (p > 0.05). The yield, volatile matter, hydrogen and oxygen contents, and surface functional groups decreased consistently with increasing pyrolysis temperature. An increase in the pH, electrical conductivity, ash, fixed carbon, and specific surface area values was also found. In biochar samples formed at high temperatures (i.e., 550 and 700 °C), Fourier transform infrared spectroscopy-FTIR studies confirmed the increase in aromaticity. Field emission scanning electron microscopy-FESEM images showed differences in the microporous structure and lower size pores at higher temperatures. Biochar pyrolyzed at 700 °C with a particle size of 63–75 µm (i.e., Lv700-63) showed the highest removal efficiency performance. Pb and Cd ions were completely removed (100%) by 0.2 g L−1 Lv700-63 at 7.0 pH and contact times of 120 and 90 min, respectively. The maximum percentage removal of Mn was 86.20% at optimum conditions of 0.2 g L−1 Lv700-63 dosage, 7.0 pH, and 180 min contact time. The findings suggests that the surface complexation, π-electron coordination, and cation exchange were the dominant mechanisms for the Pb, Cd, and Mn removal onto Lv700-63. [ABSTRACT FROM AUTHOR]

The tumor microenvironment demonstrates great immunophenotypic heterogeneity, which has been leveraged in traditional immune-hot/cold tumor categorization based on the abundance of intra-tumoral immune cells. By incorporating the spatial immune contexture, the tumor immunophenotype was further elaborated into immune-inflamed, immune-excluded, and immune-desert. However, the mechanisms underlying these different immune phenotypes are yet to be comprehensively elucidated. In this review, we discuss how tumor cells and the tumor microenvironment interact collectively to shape the immune landscape from the perspectives of tumor cells, immune cells, the extracellular matrix, and cancer metabolism, and we summarize potential therapeutic options according to distinct immunophenotypes for personalized precision medicine. [ABSTRACT FROM AUTHOR]

Background: The accuracy of traditional knee MR imaging in diagnosing anterior cruciate ligament tears, especially partial tears, is relatively low, which may lead to misdiagnosis and missed diagnosis. This study aimed to assess the diagnostic performance of a novel imaging method, high-resolution oblique coronal MRI at an optimal flexed-knee Angle, for ACL tears. Methods: 50 healthy volunteers were scanned with a scan-assisted device for the optimal flexion angle of ACL. For 92 knee trauma patients selected strictly according to inclusion and exclusion criteria, conventional extended-knee scans (control group) and high-resolution oblique coronal scans based on the optimal flexed-knee angle (experimental group) were conducted. Two observers rated ACL visibility blindly on a 5-point scale. Arthroscopy-defined outcomes determined diagnostic metrics for each method and sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. Results: The average optimal flexion angle for healthy volunteers was approximately 30° (30.3° ± 5.0°). Imaging demonstrated complete visualization of the ACL in 96.7% of images in the experimental group versus 12.0% in the control group. The diagnostic indicators of the experimental group surpassed those of the control group: sensitivity (94.9% vs. 76.3%), specificity (97.0% vs. 81.8%), positive predictive value (98.2% vs. 88.2%), negative predictive value(91.4% vs. 65.9%), and accuracy (95.7% vs. 78.3%). ROC analysis indicated superior diagnostic performance in the experimental group, with an AUC of 0.945 compared with 0.776 for the control group (p < 0.0001). Conclusions: High-resolution oblique coronal imaging at the optimal 30° flexed-knee angle improved ACL visualization and diagnostic performance compared with conventional techniques. [ABSTRACT FROM AUTHOR]

In recent years, the emerging phenomenon of ferroptosis has garnered significant attention as a distinctive mode of programmed cell death. Distinguished by its reliance on iron and dependence on reactive oxygen species (ROS), ferroptosis has emerged as a subject of extensive investigation. Mechanistically, this intricate process involves perturbations in iron homeostasis, dampening of system Xc-activity, morphological dynamics within mitochondria, and the onset of lipid peroxidation. Additionally, the concomitant phenomenon of ferritinophagy, the autophagic degradation of ferritin, assumes a pivotal role by facilitating the liberation of iron ions from ferritin, thereby advancing the progression of ferroptosis. This discussion thoroughly examines the detailed cell structures and basic processes behind ferroptosis and ferritinophagy. Moreover, it scrutinizes the intricate web of regulators that orchestrate these processes and examines their intricate interplay within the context of joint disorders. Against the backdrop of an annual increase in cases of osteoarthritis, rheumatoid arthritis, and gout, these narrative sheds light on the intriguing crossroads of pathophysiology by dissecting the intricate interrelationships between joint diseases, ferroptosis, and ferritinophagy. The newfound insights contribute fresh perspectives and promising therapeutic avenues, potentially revolutionizing the landscape of joint disease management. [ABSTRACT FROM AUTHOR]

The contributions of the tourism sector and its development to economic growth are widely recognized across the economies. However, development in this sector also has its impacts on environmental quality and sustainability. In addition, elevated economic policy uncertainty also has repercussions on the environment. The objective of this study is to examine the impact of international tourism on environmental sustainability while considering EPU, renewable energy consumption (REC), and service sector output (SSO) in the model estimated based on panel data from 17 economies. Having the heteroskedasticity and autocorrelation issues in the panel data, the author used multiple econometric methods (pooled OLS with Drisk/Kraay standard errors (DKSEs), GLS, PCSE, and quantile regressions) to examine the relationship between international tourism and environmental sustainability. DKSEs address the common issue of heteroskedasticity and GLS also accounts for both heteroskedasticity and autocorrelation. PCSE method corrects these errors. Finally, quantile regression estimates the relationships between variables at different points of the distribution. The results show that international tourism and EPU adversely impact environmental quality and sustainability by increasing GHG emissions. The findings show that increased GHG emissions from international tourism and EPU harm environmental sustainability. Furthermore, SSO and REC significantly reduce GHG emissions and enhance sustainability. Nevertheless, the tourism sector should adopt sustainable practices like using eco-friendly lodging, conserving energy and water, and utilizing renewable energy (RE) to reduce negative environmental impacts. Conserving biodiversity and regional cultures while minimizing waste and resource use is also essential. Tourists should embrace eco-friendly practices such as choosing green hotels, conserving energy and water, and supporting environmental causes while adhering to regulations to reduce emissions. The study recommends establishing uniform trade laws that support green technology and RE to reduce EPU. The findings stress the need for international collaboration to promote eco-friendly tourist practices and minimize the sector's environmental impact. [ABSTRACT FROM AUTHOR]

Cancer initiates as a consequence of genomic mutations and its subsequent progression relies in part on increased production of ribosomes to maintain high levels of protein synthesis for unchecked cell growth. Recently, cytidine deaminases have been uncovered as sources of mutagenesis in cancer. In an attempt to form a connection between these 2 cancer driving processes, we interrogated the cytidine deaminase family of proteins for potential roles in human ribosome biogenesis. We identified and validated APOBEC3A and APOBEC4 as novel ribosome biogenesis factors through our laboratory's established screening platform for the discovery of regulators of nucleolar function in MCF10A cells. Through siRNA depletion experiments, we highlight APOBEC3A's requirement in making ribosomes and specific role within the processing and maturation steps that form the large subunit 5.8S and 28S ribosomal (r)RNAs. We demonstrate that a subset of APOBEC3A resides within the nucleolus and associates with critical ribosome biogenesis factors. Mechanistic insight was revealed by transient overexpression of both wild-type and a catalytically dead mutated APOBEC3A, which both increase cell growth and protein synthesis. Through an innovative nuclear RNA sequencing methodology, we identify only modest predicted APOBEC3A C-to-U target sites on the pre-rRNA and pre-mRNAs. Our work reveals a potential direct role for APOBEC3A in ribosome biogenesis likely independent of its editing function. More broadly, we found an additional function of APOBEC3A in cancer pathology through its function in ribosome biogenesis, expanding its relevance as a target for cancer therapeutics. Cancer initiation is driven by mutations and progression relies on increased protein synthesis, enabled in part by increased production of ribosomes. This study links both processes by showing that cytidine deaminase APOBEC3A, a source of cancer-initiating mutations, also contributes to cancer progression by promoting ribosome biogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Infection with SARS-CoV-2 virus may result in long COVID, a syndrome characterized by symptoms such as dyspnea, cardiac abnormalities, cognitive impairment, and fatigue. One potential explanation for these symptoms is hypocortisolism. Objective: To evaluate the prevalence of hypocortisolism in patients with a history of COVID-19 pneumonia. Methods: Cross-sectional study of patients who were aged ≥18 years and had a 3-month history of radiography-confirmed COVID-19 pneumonia. Exclusion criteria included current or previous treatment with glucocorticoids and use of an oral contraceptive. Adrenal function was evaluated using a low dose (1ug) corticotropin stimulation test (CST). Serum cortisol levels were measured at 0, 30, and 60 minutes, and baseline plasma ACTH was also measured. Results: Of the 41 patients enrolled, the median age was 62 years, 17 (42%) were female, and all 41 (100%) had severe pneumonia at baseline. Eleven patients (27%) had hypocortisolism, as evidenced by peak cortisol of less than 402.81 nmol/l after low dose (1 μg) CST. Of these 11 patients, 10 (91%) had secondary hypocortisolism (median ACTH 6.27 pmol/L, range 4.98–9.95 pmol/L) and one had primary hypocortisolism (mean ACTH 32.78 pmol/L). Six of the 11 patients with hypocortisolism (54.5%) reported symptoms of persistent fatigue and 5 (45.5%) required regular glucocorticoid replacement. Conclusions: Our results suggest that hypocortisolism, predominantly caused by pituitary disruption, may emerge after SARS-CoV-2 infection and should be considered in patients with a history of COVID-19 pneumonia with or without clinical hypocortisolism. [ABSTRACT FROM AUTHOR]

Developing markets are using sustainable development potential to reach zero-carbon goals. Due to the limitation of natural resources, companies need to use environmentally friendly manufacturing to develop a circular economy (CE). Green finance (GF) and the CE are linked in a systematic and complex approach; therefore, it was essential to employ the coupling coordination-level framework to explain their relationship and feedback. Any study linking green financing and CE together has been found. The objective of this research is to explore this twofold domain and determine its main characteristics. To address this objective, a comprehensive review of the literature was conducted, supplemented by a bibliometric analysis. The results confirm that GF has the potential to help society, sustainability, and the prevention to climate shifts, investing in the CE. There are many hurdles to overcome, including inadequate knowledge about CE and GF, ambiguous definitions, a lack of coherence between legal frameworks on CE and green financing, unclear laws, and a lack of financially viable motivation for investors and financial institutions that are ready to promote in sustainability. This study explores CE and GF domains. Managers may readily increase their understanding of methods, strategies, and technical solutions beneficial to assist their operations toward a green economy depending on various CE and GF elements. Finally, based on a categorization of GF types, the assessment identifies future investment potential consequences of green financing in the CE. [ABSTRACT FROM AUTHOR]

The rates at which mutations accumulate across human cell types vary. To identify causes of this variation, mutations are often decomposed into a combination of the single-base substitution (SBS) "signatures" observed in germline, soma, and tumors, with the idea that each signature corresponds to one or a small number of underlying mutagenic processes. Two such signatures turn out to be ubiquitous across cell types: SBS signature 1, which consists primarily of transitions at methylated CpG sites thought to be caused by spontaneous deamination, and the more diffuse SBS signature 5, which is of unknown etiology. In cancers, the number of mutations attributed to these 2 signatures accumulates linearly with age of diagnosis, and thus the signatures have been termed "clock-like." To better understand this clock-like behavior, we develop a mathematical model that includes DNA replication errors, unrepaired damage, and damage repaired incorrectly. We show that mutational signatures can exhibit clock-like behavior because cell divisions occur at a constant rate and/or because damage rates remain constant over time, and that these distinct sources can be teased apart by comparing cell lineages that divide at different rates. With this goal in mind, we analyze the rate of accumulation of mutations in multiple cell types, including soma as well as male and female germline. We find no detectable increase in SBS signature 1 mutations in neurons and only a very weak increase in mutations assigned to the female germline, but a significant increase with time in rapidly dividing cells, suggesting that SBS signature 1 is driven by rounds of DNA replication occurring at a relatively fixed rate. In contrast, SBS signature 5 increases with time in all cell types, including postmitotic ones, indicating that it accumulates independently of cell divisions; this observation points to errors in DNA repair as the key underlying mechanism. Thus, the 2 "clock-like" signatures observed across cell types likely have distinct origins, one set by rates of cell division, the other by damage rates. The rate at which DNA mutations accumulate varies substantially across cell types and tissues in the human body, but the origin of these differences is not well understood. This study develops a model to interpret "clock-like" mutation accumulation in humans, showing that the rate of accumulation depends on underlying processes of DNA damage, repair and replication. [ABSTRACT FROM AUTHOR]

Background: IDH1-wildtype glioblastoma multiforme (IDHwt-GBM) is a highly heterogeneous and aggressive brain tumour characterised by a dismal prognosis and significant challenges in accurately predicting patient outcomes. To address these issues and personalise treatment approaches, we aimed to develop and validate robust multiomics molecular subtypes of IDHwt-GBM. Through this, we sought to uncover the distinct molecular signatures underlying these subtypes, paving the way for improved diagnosis and targeted therapy for this challenging disease. Methods: To identify stable molecular subtypes among 184 IDHwt-GBM patients from TCGA, we used the consensus clustering method to consolidate the results from ten advanced multiomics clustering approaches based on mRNA, lncRNA, and mutation data. We developed subtype prediction models using the PAM and machine learning algorithms based on mRNA and MRI data for enhanced clinical utility. These models were validated in five independent datasets, and an online interactive system was created. We conducted a comprehensive assessment of the clinical impact, drug treatment response, and molecular associations of the IDHwt-GBM subtypes. Results: In the TCGA cohort, two molecular subtypes, class 1 and class 2, were identified through multiomics clustering of IDHwt-GBM patients. There was a significant difference in survival between Class 1 and Class 2 patients, with a hazard ratio (HR) of 1.68 [1.15–2.47]. This difference was validated in other datasets (CGGA: HR = 1.75[1.04, 2.94]; CPTAC: HR = 1.79[1.09–2.91]; GALSS: HR = 1.66[1.09–2.54]; UCSF: HR = 1.33[1.00–1.77]; UPENN HR = 1.29[1.04–1.58]). Additionally, class 2 was more sensitive to treatment with radiotherapy combined with temozolomide, and this sensitivity was validated in the GLASS cohort. Correspondingly, class 2 and class 1 exhibited significant differences in mutation patterns, enriched pathways, programmed cell death (PCD), and the tumour immune microenvironment. Class 2 had more mutation signatures associated with defective DNA mismatch repair (P = 0.0021). Enriched pathways of differentially expressed genes in class 1 and class 2 (P-adjust < 0.05) were mainly related to ferroptosis, the PD-1 checkpoint pathway, the JAK-STAT signalling pathway, and other programmed cell death and immune-related pathways. The different cell death modes and immune microenvironments were validated across multiple datasets. Finally, our developed survival prediction model, which integrates molecular subtypes, age, and sex, demonstrated clinical benefits based on the decision curve in the test set. We deployed the molecular subtyping prediction model and survival prediction model online, allowing interactive use and facilitating user convenience. Conclusions: Molecular subtypes were identified and verified through multiomics clustering in IDHwt-GBM patients. These subtypes are linked to specific mutation patterns, the immune microenvironment, prognoses, and treatment responses. [ABSTRACT FROM AUTHOR]

The current study examines the strategic use of "Jayu" (freedom or liberty) in South Korean politics, with a focus on President Yoon Suk Yeol's administration, where it symbolizes conservative ideologies and political identity. Employing Natural Language Processing, time-series analysis, and visualization techniques, the research analyzes presidential speeches to explore Yoon's marked emphasis on Jayu, indicative of a strong conservative allegiance. The findings reveal a significant association between the utilization of Jayu and conservative strategies, underscoring its crucial role in Yoon's political strategy and its function in garnering support from conservative factions within a polarized political context. Yoon's discourse, characterized by an extensive use of Jayu, fosters polarization and partisanship, moving away from inclusive dialog. This study illuminates the role of symbolic language in political communication and identity formation, providing insights into the interplay between rhetoric and ideological positions in the intricate political landscape of South Korea. [ABSTRACT FROM AUTHOR]

APOBEC-induced mutations occur in 50% of sequenced human tumors, with APOBEC3A (A3A) being a major contributor to mutagenesis in breast cancer cells. The mechanisms that cause A3A activation and mutagenesis in breast cancers are still unknown. Here, we describe factors that influence basal A3A mRNA transcript levels in breast cancer cells. We found that basal A3A mRNA correlates with A3A protein levels and predicts the amount of APOBEC signature mutations in a panel of breast cancer cell lines, indicating that increased basal transcription may be one mechanism leading to breast cancer mutagenesis. We also show that alteration of ERBB2 expression can drive A3A mRNA levels, suggesting the enrichment of the APOBEC mutation signature in Her2-enriched breast cancer could in part result from elevated A3A transcription. Hierarchical clustering of transcripts in primary breast cancers determined that A3A mRNA was co-expressed with other genes functioning in viral restriction and interferon responses. However, reduction of STAT signaling via inhibitors or shRNA in breast cancer cell lines had only minor impact on A3A abundance. Analysis of single cell RNA-seq from primary tumors indicated that A3A mRNA was highest in infiltrating immune cells within the tumor, indicating that correlations of A3A with STAT signaling in primary tumors may be result from higher immune infiltrates and are not reflective of STAT signaling controlling A3A expression in breast cancer cells. Analysis of ATAC-seq data in multiple breast cancer cell lines identified two transcription factor sites in the APOBEC3A promoter region that could promote A3A transcription. We determined that Rel-A, and Bach1, which have binding sites in these peaks, elevated basal A3A expression. Our findings highlight a complex and variable set of transcriptional activators for A3A in breast cancer cells. Author summary: The protein APOBEC3A (A3A) is a major cause of mutations in breast cancers by changing cytidines in single-stranded DNA to uridine. The amount of A3A transcript is elevated specifically in cancer cells containing A3A-induced mutations, suggesting that up-regulation of A3A transcription may be an underlying cause of cancer mutations. However, little is known about the factors that influence A3A transcript level in breast cancer. Here, we identify three different proteins that impact A3A transcription: Her2, Rel-A and Bach1. Her2 activation is a common oncogenic event in some breast cancer subtypes and likely alters transcription of a variety of genes, including APOBEC3A, through enhanced signaling pathways or cell stress signaling. Contrastingly, Rel-A and Bach1 are transcription factors that we provide evidence that likely impact A3A transcription by binding the A3A promoter. Additionally, we found that correlations between A3A expression and canonical A3A transcriptional regulators, STAT1 and STAT2, in primary tumors stems from immune cells infiltrating into the tumor instead of direct transcriptional regulation in breast cancer cells. Our results demonstrate that A3A transcriptional regulation is highly complex with multiple factors and inputs potentially leading to an increase in mutations. [ABSTRACT FROM AUTHOR]

Flooding is the most frequent type of natural disaster, inducing devastating damage at large and small spatial scales. Flood exposure analysis is a critical part of flood risk assessment. While most studies analyze the exposure elements separately, it is crucial to perform a multi-parameter exposure analysis and consider different types of flood zones to gain a comprehensive understanding of the impact and make informed mitigation decisions. This research analyzes the population, properties, and road networks potentially exposed to the 100, 200, and 500-year flood events at the county level in the State of Iowa using geospatial analytics. We also propose a flood exposure index at the county level using fuzzy overlay analysis to help find the most impacted county. During flooding, results indicate that the county-level percentage of displaced population, impacted properties, and road length can reach up to 46%, 41%, and 40%, respectively. We found that the most exposed buildings and roads are laid in residential areas. Also, 25% of the counties are designated as very high-exposure areas. This study can help many stakeholders identify vulnerable areas and ensure equitable distribution of investments and resources toward flood mitigation projects. [ABSTRACT FROM AUTHOR]

We evaluated the prognostic value of hypoalbuminemia in context of various biomarkers at baseline, including clinical, genomic, transcriptomic, and blood-based markers, in patients with metastatic melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anti-CTLA-4 combination therapy (n = 178). An independent validation cohort (n = 79) was used to validate the performance of hypoalbuminemia compared to serum LDH (lactate dehydrogenase) levels. Pre-treatment hypoalbuminemia emerged as the strongest predictor of poor outcome for both OS (HR = 4.01, 95% CI 2.10–7.67, Cox P = 2.63e−05) and PFS (HR = 3.72, 95% CI 2.06–6.73, Cox P = 1.38e−05) in univariate analysis. In multivariate analysis, the association of hypoalbuminemia with PFS was independent of serum LDH, IFN-γ signature expression, TMB, age, ECOG PS, treatment line, treatment type (combination or monotherapy), brain and liver metastasis (HR = 2.76, 95% CI 1.24–6.13, Cox P = 0.0131). Our validation cohort confirmed the prognostic power of hypoalbuminemia for OS (HR = 1.98, 95% CI 1.16–3.38; Cox P = 0.0127) and was complementary to serum LDH in analyses for both OS (LDH-adjusted HR = 2.12, 95% CI 1.2–3.72, Cox P = 0.00925) and PFS (LDH-adjusted HR = 1.91, 95% CI 1.08–3.38, Cox P = 0.0261). In conclusion, pretreatment hypoalbuminemia was a powerful predictor of outcome in ICI in melanoma and showed remarkable complementarity to previously established biomarkers, including high LDH. [ABSTRACT FROM AUTHOR]

Objective: This study aims to develop a nomogram integrating inflammation (NLR), Prognostic Nutritional Index (PNI), and EBV DNA (tumor burden) to achieve personalized treatment and prediction for stage IVA NPC. Furthermore, it endeavors to pinpoint specific subgroups that may derive significant benefits from S-1 adjuvant chemotherapy. Methods: A total of 834 patients diagnosed with stage IVA NPC were enrolled in this study and randomly allocated into training and validation cohorts. Multivariate Cox analyses were conducted to identify independent prognostic factors for constructing the nomogram. The predictive and clinical utility of the nomogram was assessed through measures including the AUC, calibration curve, DCA, and C-indexes. IPTW was employed to balance baseline characteristics across the population. Kaplan-Meier analysis and log-rank tests were utilized to evaluate the prognostic value. Results: In our study, we examined the clinical features of 557 individuals from the training cohort and 277 from the validation cohort. The median follow-up period was 50.1 and 49.7 months, respectively. For the overall cohort, the median follow-up duration was 53.8 months. The training and validation sets showed 3-year OS rates of 87.7% and 82.5%, respectively. Meanwhile, the 3-year DMFS rates were 95.9% and 84.3%, respectively. We created a nomogram that combined PNI, NRI, and EBV DNA, resulting in high prediction accuracy. Risk stratification demonstrated substantial variations in DMFS and OS between the high and low risk groups. Patients in the high-risk group benefited significantly from the IC + CCRT + S-1 treatment. In contrast, IC + CCRT demonstrated non-inferior 3-year DMFS and OS compared to IC + CCRT + S-1 in the low-risk population, indicating the possibility of reducing treatment intensity. Conclusions: In conclusion, our nomogram integrating NLR, PNI, and EBV DNA offers precise prognostication for stage IVA NPC. S-1 adjuvant chemotherapy provides notable benefits for high-risk patients, while treatment intensity reduction may be feasible for low-risk individuals. [ABSTRACT FROM AUTHOR]

Background: Indonesia is currently facing a significant problem of air pollution caused by vehicle emissions, which severely impacts both health and the economy. With the depletion of natural resources, the cost of gasoline is on the rise. Purpose: To address this issue, a study was conducted to investigate consumer behavior and their awareness of environmental sustainability when purchasing electric vehicles. Design/methodology/approach: A purposive sampling method was used, and the survey was conducted on 140 individuals who own fossil fuel-powered vehicles. The research utilized Smart PLS for data processing. Findings/Result: The results confirmed two hypotheses and refuted two based on prior research.Conclusion: Findings indicate environmental awareness, but barriers to EV adoption persist. Originality/value (State of the art): Adds new evidence on EV purchase decisions in emerging markets. [ABSTRACT FROM AUTHOR]

A young patient presented with fever for two days and a week later from onset of fever, patient noticed a blurring of vision in both the eyes. Hemogram showed a platelet count of 108,000/μL. Dengue fever was diagnosed based on dengue serology (positive for immunoglobulin IgM). Fundus fluorescein angiography (FFA) showed bilateral dilated, tortuous vessels with retinal hemorrhages and capillary occlusion suggestive of retinal vasculopathy. Patient was treated with a course of oral steroids for five days and symptomatic improvement in visual symptoms was noted. Ocular involvement in dengue is diverse and tends to occur five to seven days after onset of fever during the nadir of thrombocytopenia. Overall, dengue-related ocular complications have a good prognosis. [ABSTRACT FROM AUTHOR]

Background: Accurate differentiation of extremity soft-tissue tumors (ESTTs) is important for treatment planning. Purpose: To develop and validate an ultrasound (US) image-based radiomics signature to predict ESTTs malignancy. Material and Methods: A dataset of US images from 108 ESTTs were retrospectively enrolled and divided into the training cohort (78 ESTTs) and validation cohort (30 ESTTs). A total of 1037 radiomics features were extracted from each US image. The most useful predictive radiomics features were selected by the maximum relevance and minimum redundancy method, least absolute shrinkage, and selection operator algorithm in the training cohort. A US-based radiomics signature was built based on these selected radiomics features. In addition, a conventional radiologic model based on the US features from the interpretation of two experienced radiologists was developed by a multivariate logistic regression algorithm. The diagnostic performances of the selected radiomics features, the US-based radiomics signature, and the conventional radiologic model for differentiating ESTTs were evaluated and compared in the validation cohort. Results: In the validation cohort, the area under the curve (AUC), sensitivity, and specificity of the US-based radiomics signature for predicting ESTTs malignancy were 0.866, 84.2%, and 81.8%, respectively. The US-based radiomics signature had better diagnostic predictability for predicting ESTT malignancy than the best single radiomics feature and the conventional radiologic model (AUC = 0.866 vs. 0.719 vs. 0.681 for the validation cohort, all P <0.05). Conclusion: The US-based radiomics signature could provide a potential imaging biomarker to accurately predict ESTT malignancy. [ABSTRACT FROM AUTHOR]

Although colorectal cancer (CRC) remains the second leading cause of cancer-related death in the United States, the overall incidence and mortality from the disease have declined in recent decades. In contrast, there has been a steady increase in the incidence of CRC in individuals under 50 years of age. Hereditary syndromes contribute disproportionately to early onset CRC (EOCRC). These include microsatellite instability high (MSI+) tumors arising in patients with Lynch Syndrome. However, most EOCRCs are not associated with familial syndromes or MSI+ genotypes. Comprehensive genomic profiling has provided the basis of improved more personalized treatments for older CRC patients. However, less is known about the basis of sporadic EOCRC. To define the genomic landscape of EOCRC we used DNA content flow sorting to isolate diploid and aneuploid tumor fractions from 21 non-hereditary cases. We then generated whole exome mutational profiles for each case and whole genome copy number, telomere length, and EGFR immunohistochemistry (IHC) analyses on subsets of samples. These results discriminate the molecular features of diploid and aneuploid EOCRC and provide a basis for larger population-based studies and the development of effective strategies to monitor and treat this emerging disease. [ABSTRACT FROM AUTHOR]

Background: The integration of transcriptomic, proteomic, druggable genetic and metabolomic association studies facilitated a comprehensive investigation of molecular features and shared pathways for cancers' development and progression. Methods: Comprehensive approaches consisting of transcriptome-wide association studies (TWAS), proteome-wide association studies (PWAS), summary-data-based Mendelian randomization (SMR) and MR were performed to identify genes significantly associated with cancers. The results identified in above analyzes were subsequently involved in phenotype scanning and enrichment analyzes to explore the possible health effects and shared pathways. Additionally, we also conducted MR analysis to investigate metabolic pathways related to cancers. Results: Totally 24 genes (18 transcriptomic, 1 proteomic and 5 druggable genetic) showed significant associations with cancers risk. All genes identified in multiple methods were mainly enriched in nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Additionally, biosynthesis of ubiquinol and urate were found to play an important role in gastrointestinal tumors. Conclusions: A set of putatively causal genes and pathways relevant to cancers were identified in this study, shedding light on the shared biological processes for tumorigenesis and providing compelling genetic evidence to prioritize anti-cancer drugs development. [ABSTRACT FROM AUTHOR]