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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.)

Background: Cigarette smoking is associated with nasopharyngeal cancer (NPC) risk. Whether quitting reduces the risk is unclear. We investigated the associations of NPC with duration of and age at quitting in an endemic region., Methods: We investigated the associations between NPC and quitting in a multicenter case-control study in Hong Kong with 676 newly diagnosed NPC cases and 1,285 hospital controls between 2014 and 2017, using a computer-assisted self-administered questionnaire. Multivariable unconditional logistic regression yielded adjusted odds ratios (AORs) of NPC by quitting status, duration and age of quitting, combinations of duration and age of quitting, and quitting to smoking duration ratio, compared with current smoking., Results: Quitting (AOR: 0.72; 95% CI: 0.53-0.98) and never smoking (0.73, 0.56-0.95) were associated with lower NPC risk. NPC risk decreased with (i) longer quitting duration ( p < 0.01), reaching significance after 11-20 (0.62, 0.39-0.99) and 21+ years (0.54, 0.31-0.92) of quitting; (ii) younger quitting age ( p = 0.01), reaching significance for quitting at <25 years (0.49, 0.24-0.97); and (iii) higher quitting to smoking duration ratio ( p < 0.01), reaching significance when the ratio reached 1 (0.60, 0.39-0.93). Quitting younger (age <25) appeared to confer larger reductions (49% for ≤10 years of quitting, 50% for 11+ years) in NPC risk than quitting at older ages (25+) regardless of quitting duration (16% for ≤10 years, 39% for 11+ years)., Conclusions: We have shown longer duration and younger age of quitting were associated with lower NPC risk, with dose-response relations. Our findings support including smoking as a cause of NPC. Stronger tobacco control measures and quitting services are needed to prevent NPC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Mai, Ngan, Ng, Lin, Kwong, Chiang, Yuen, Ng, Ip, Chan, Lee, Lung, Ho and Lam.)

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]

Background: We investigated the relationship of Epstein-Barr virus viral capsid antigen (EBV VCA-IgA) serostatus with ambient and personal ultraviolet radiation (UVR) and vitamin D exposure., Methods: Using data from a multicenter case-control study, we included 1026 controls subjects in 2014-2017 in Hong Kong, China. Odds ratios (ORs) and 95% confidence intervals (CIs) of the association between UVR exposure and EBV VCA-IgA (seropositivity vs seronegativity) were calculated using unconditional logistic regression models adjusted for potential confounders., Results: We observed a large increase in seropositivity of EBV VCA-IgA in association with duration of sunlight exposures at both 10 years before recruitment and age 19-30 years (adjusted OR = 3.59, 95% CI = 1.46-8.77; and adjusted OR = 2.44, 95% CI = 1.04-5.73 for ≥8 vs <2 hours/day; P for trend = .005 and .048, respectively). However, no association of EBV VCA-IgA serostatus with other indicators of UVR exposure was found. In addition, both circulating 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD were not associated with EBV VCA-IgA serostatus., Conclusions: Our results suggest that personal UVR exposure may be associated with higher risk of EBV reactivation, but we did not find clear evidence of vitamin D exposure (observational or genetic), a molecular mediator of UVR exposure. Further prospective studies in other populations are needed to confirm this finding and to explore the underlying biological mechanisms. Information on photosensitizing agents, and serological markers of EBV, and biomarkers related to systemic immunity and inflammation should be collected and are also highly relevant in future studies., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature 1 . Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses 3-15 , enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated-but distinct-DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.

Radiation exposure with repeated radiography required at follow-up poses serious health concerns for scoliosis patients. Although spinous process angle (SPA) measurement of spinal curvatures with ultrasound has been reported with promising results, an evidence-based account on its accuracy for translational application remains undefined. This prospective study involved 952 idiopathic scoliosis patients (75.7% female, mean age 16.7 ± 3.0 y, Cobb 28.7 ± 11.6°). Among 1432 curves (88.1%) detected by ultrasound, there was good correlation between radiologic Cobb angles measured manually on EOS (E&#95;Cobb) whole-spine radiographs and automatic ultrasound SPA measurement for upper spinal curves (USCs) (r = 0.873, apices T7-T12/L1 intervertebral disc) and lower spinal curves (LSCs) (r = 0.740, apices L1 or below) (p < 0.001). Taller stature was associated with stronger correlation. For E&#95;Cobb <30°, 66.6% USCs and 62.4% LSCs had absolute differences between E&#95;Cobb and predicted Cobb angle calculated from SPA ≤5°. Ultrasound could be a viable option in lieu of radiography for measuring coronal curves with apices at T7 or lower and Cobb angle <30°., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The much higher incidence of nasopharyngeal carcinoma (NPC) in men suggests sex hormones as a risk factor, and dairy products contain measurable amounts of steroid hormones. Milk consumption has greatly increased in endemic regions of NPC. We investigated the association between NPC and milk consumption across life periods in Hong Kong. Methods: A multicentre case-control study included 815 histologically confirmed NPC incident cases and 1,502 controls who were frequency-matched on age and sex at five major hospitals in Hong Kong in 2014-2017. Odds ratios (ORs) of NPC (cases vs. controls) for milk consumption at different life periods were estimated by unconditional logistic regression, adjusting for sex, age, socioeconomic status score, smoking and alcohol drinking status, exposure to occupational hazards, family history of cancer, IgA against Epstein-Barr virus viral capsid antigen, and total energy intake. Results: Compared with abstainers, lower risks of NPC were consistently observed in regular users (consuming ≥5 glasses of milk [fresh and powdered combined] per month) across four life periods of age 6-12 (adjusted OR 0.74, 95% CI 0.54-0.86), 13-18 (0.68, 0.55-0.84), 19-30 (0.68, 0.55-0.84), and 10 years before recruitment (0.72, 0.59-0.87). Long-term average milk consumption of ≤2.5, >2.5, and ≤12.5, >12.5 glasses per month yielded adjusted OR (95% CI) of 1.00 (0.80-1.26), 0.98 (0.81-1.18), 0.95 (0.76-1.18), and 0.55 (0.43-0.70), respectively (all P -values for trend < 0.05). Conclusion: Consumption of milk across life periods was associated with lower risks of NPC. If confirmed to be causal, this has important implications for dairy product consumption and prevention of NPC.

Understanding somatic mutations and structural variations in domestic pigs (Sus scrofa domestica) is critical due to their increasing importance as model organisms in biomedical research. In this study, we conducted a comprehensive analysis through whole-genome sequencing of skin, organs, and blood samples. By examining two pig pedigrees, we investigated the inheritance and sharedness of structural variants among fathers, mothers, and offsprings. Utilizing single-cell clonal expansion techniques, we observed significant variations in the number of somatic mutations across different tissues. An in-house developed pipeline enabled precise filtering and analysis of these mutations, resulting in the construction of individual phylogenetic trees for two pigs. These trees explored the developmental relationships between different tissues, revealing insights into clonal expansions from various anatomical locations. This study enhances the understanding of pig genomes, affirming their increasing value in clinical and genomic research, and provides a foundation for future studies in other animals, paralleling previous studies in mice and humans. This approach not only deepens our understanding of mammalian genomic variations but also strengthens the role of pigs as a crucial model in human health and disease research., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We evaluated the reliability of early life nasopharyngeal carcinoma (NPC) aetiology factors in the questionnaire of an NPC case-control study in Hong Kong during 2014-2017. 140 subjects aged 18+ completed the same computer-assisted questionnaire twice, separated by at least 2 weeks. The questionnaire included most known NPC aetiology factors and the present analysis focused on early life exposure. Test-retest reliability of all the 285 questionnaire items was assessed in all subjects and in 5 subgroups defined by cases/controls, sex, time between 1 st and 2 nd questionnaire (2-29/≥30 weeks), education (secondary or less/postsecondary), and age (25-44/45-59/60+ years) at the first questionnaire. The reliability of items on dietary habits, body figure, skin tone and sun exposure in early life periods (age 6-12 and 13-18) was moderate-to-almost perfect, and most other items had fair-to-substantial reliability in all life periods (age 6-12, 13-18 and 19-30, and 10 years ago). Differences in reliability by strata of the 5 subgroups were only observed in a few items. This study is the first to report the reliability of an NPC questionnaire, and make the questionnaire available online. Overall, our questionnaire had acceptable reliability, suggesting that previous NPC study results on the same risk factors would have similar reliability.

As a major class of mechanically interlocked molecules, not only are catenanes topologically intriguing targets that challenge the chemical synthesis to the efficient formation of mechanical bonds, but also the mechanical properties arising from the topology offer unique and attractive features for the development of novel functional molecular materials. Despite advancements in templated methods for different types of interlocked architectures, [ n]catenane possessing multiple numbers of interlocked macrocycles still remains a difficult synthetic target with very few reported examples. If the unique mechanical properties of catenanes are to be fully exploited, reliable, controllable, and efficient strategies for accessing [ n]catenanes will be necessary. In this Viewpoint, challenges, considerations, and strategies to [ n]catenanes are discussed.

Objective: To investigate the diagnostic performance of ultrasound-guided synovial biopsy., Methods: Clinical notes, pathology and microbiology reports, ultrasound and other imaging studies of 100 patients who underwent 111 ultrasound-guided synovial biopsies were reviewed. Biopsies were compared with the final clinical diagnosis established after synovectomy (n = 43) or clinical/imaging follow-up (n = 57) (mean 30 months)., Results: Other than a single vasovagal episode, no complication of synovial biopsy was encountered. One hundred and seven (96 %) of the 111 biopsies yielded synovium histologically. Pathology ± microbiology findings for these 107 conclusive biopsies comprised synovial tumour (n = 30, 28 %), synovial infection (n = 18, 17 %), synovial inflammation (n = 45, 42 %), including gouty arthritis (n = 3), and no abnormality (n = 14, 13 %). The accuracy, sensitivity, and specificity of synovial biopsy was 99 %, 97 %, and 100 % for synovial tumour; 100 %, 100 %, and 100 % for native joint infection; and 78 %, 45 %, and 100 % for prosthetic joint infection. False-negative synovial biopsy did not seem to be related to antibiotic therapy., Conclusion: Ultrasound-guided Tru-cut synovial biopsy is a safe and reliable technique with a high diagnostic yield for diagnosing synovial tumour and also, most likely, for joint infection. Regarding joint infection, synovial biopsy of native joints seems to have a higher diagnostic yield than that for infected prosthetic joints., Key Points: • Ultrasound-guided Tru-cut synovial biopsy has high accuracy (99 %) for diagnosing synovial tumour. • It has good accuracy, sensitivity, and high specificity for diagnosis of joint infection. • Synovial biopsy of native joints works better than biopsy of prosthetic joints. • A negative synovial biopsy culture from a native joint largely excludes septic arthritis. • Ultrasound-guided Tru-cut synovial biopsy is a safe and well-tolerated procedure.

Objective: To compare the effect of traction during non-arthrographic and arthrographic MR examination of the wrist with regard to joint space width, joint fluid dispersion and cartilage surface visibility., Methods: Prospective 3-T MRI study of 100 wrists in 96 patients. The first 50 wrists underwent MR arthrography first without traction and then with traction. The following 50 wrists underwent standard MR first without traction and then with traction. On these examinations, two radiologists independently measured (i) joint space width, semi-quantitatively graded (ii) joint fluid dispersion between opposing cartilage surfaces and (iii) articular cartilage surface visibility. The three parameters were compared between the two groups., Results: Traction led to an increase in joint space width at nearly all joints in all patients (p < 0.05), although more so in the arthrography (∆ = 0.08-0.79 mm, all p < 0.05) than in the non-arthrography (∆ = 0.001-0.61 mm, all p < 0.05) group. Joint fluid dispersion and cartilage surface visibility improved after traction in nearly all joints (p < 0.05) in all patients and more so in the arthographic than in the non-arthrography group., Conclusion: Traction did significantly improve cartilage surface visibility for standard MRI of the wrist although the effect was not as great as that seen with MR arthography or MR arthrography with traction. Advances in knowledge: This is the first study to show the beneficial effect of traction during standard non-arthrography MRI of the wrist and compare the effect of traction between non-arthrographic and arthrographic MRI of the wrist.

Purpose: To compare axial and oblique axial planes on MR arthrography (MRA) and multidetector CT arthrography (CTA) to evaluate dorsal and volar parts of scapholunate (SLIL) and lunotriquetral interosseous (LTIL) ligaments., Methods: Nine cadaveric wrists of five male subjects were studied. The visibility of dorsal and volar parts of the SLIL and LTIL was graded semi-quantitatively (good, intermediate, poor) on MRA and CTA. The presence of a ligament tear was determined on arthrosocopy and sensitivity, specificity and accuracy of tear detection were calculated., Results: Oblique axial imaging was particularly useful for delineating dorsal and volar parts of the LTIL on MRA with overall 'good' visibility increased from 11 % to 78 %. The accuracy of MRA and CTA in revealing SLIL and LTIL tear was higher using the oblique axial plane. The overall accuracy for detecting SLIL tear on CTA improved from 94 % to 100 % and from 89 % to 94 % on MRA; the overall accuracy of detecting LTIL tear on CTA improved from 89 % to 100 % and from 72 % to 89 % on MRA CONCLUSION: Oblique axial imaging during CT and MR arthrography improves detection of tears in the dorsal and volar parts of both SLIL and LTIL., Key Points: • Oblique axial imaging improves SLIL and LTIL visibility and tear detection. • This improvement is greater for the LTIL than for the SLIL ligament. • Overall, CT arthrography performed better than MR arthrography.

Aim: To report the authors' experience of focal nodular haematopoietic marrow hyperplasia (FNHMH) and diffuse haematopoietic marrow hyperplasia (DHMH) clinically masquerading as skip, distant, or disseminated metastasis in seven patients with underlying malignant neoplasms., Materials and Methods: Five patients with FNHMH and two with DHMH mistaken radiologically as skip and disseminated metastasis, respectively, were compared and contrasted with four patients with osteosarcomas and two with chondrosarcomas harbouring skip metastasis, noting the temporal relationship with their haematological profile., Results: FNHMH and DHMH were undetectable by plain radiography and computed tomography (CT) except one showing subtle sclerosis on CT. They showed either isointense or hyperintense, but not hypointense, attenuation at T1-weighted imaging, and all showed hyperintense attenuation at T2-weighted MRI relative to skeletal muscle. Of the five patients who underwent bone scintigraphy, one showed mildly increased uptake, and one out of two showed markedly increased 2-[ 18 F]-fluoro-2-deoxy-d-glucose (FDG)-positron-emission tomography (PET) uptake. The rates for sarcoma skip metastasis by plain radiography, CT, MRI, and bone scintigraphy were 40%, 66.7%, 100%, and 66.7%, respectively. At MRI, 60% showed hypointense and 40% isointense attenuation at T1-weighted, 80% hyperintense and 20% hypointense attenuation at T2-weighted imaging. Combined FDG-PET and CT, which was performed in only one patient, failed to show the skip metastasis. Not every patient with FNHMH or DHMH received granulocyte colony-stimulating factor (GCSF), but all had low or falling haemoglobin levels, which may thus be the prime cause for HMH., Conclusions: Due to overlapping radiological features, FNHMH and DHMH are great radiological mimics of malignancy. In some cases, needle biopsy is required for their definitive differentiation., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Melbourne Health is celebrating the 13th year of a wound care champion program that has transformed 85 ward nurses into a unique group of Wound Resource Nurses (WReNs) to meet the challenges and demands of implementing evidence based wound care practices.

Background: Most women with advanced breast cancer (ABC) show little distress, but about one in ten show persistent distress over time. It remains unclear if meanings ascribed by patients to ABC differentiate these distress trajectories., Study Aims: This qualitative study (a) compared illness meanings of ABC between women with persistent psychological distress and those with low/transient distress, and (b) examined how illness meanings might influence coping strategies., Methods: The sample was drawn from a prior quantitative study exploring psychological distress trajectories following ABC diagnosis. Overall, 42 Cantonese- or Mandarin-speaking Chinese women diagnosed with locally advanced or metastatic ABC were recruited based on their distress trajectory status (low-stable, transient, or persistent distress). Interviews were recorded, transcribed, and analyzed following grounded theory approach using simultaneous analysis., Results: Women with persistent distress viewed their diagnosis as another blow in life, the illness was global, permeating every aspect of their life. Maladaptive rumination and thought suppression were common responses to illness demands. These women had poor social support. A sense of demoralization stood out in their narratives. In contrast, women with transient/low-stable distress encapsulated the illness, with minimum impacts of their life. They did not evidence dysfunctional repetitive thoughts. Living in a supportive environment, they were able to accept and/or live in the present-moment., Conclusions: Rumination, thought suppression, social constraints, and pre-existing exposure to life stress may be potential risks for chronic distress in response to advanced breast cancer. Persistent and transient distress responses to cancer may have different underpinnings. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objective: To assess the effect of axial traction during MR arthrography (MRA) of the elbow joint on joint space widening, contrast dispersion between opposing cartilage surfaces and cartilage surface visibility., Methods: 11 patients with elbow MRA with and without axial traction were prospectively studied. Two radiologists independently measured the elbow joint space width and semi-quantitatively graded contrast material dispersion between the opposing cartilage surfaces as well as the articular cartilage surface visibility before and after traction. The detection and visibility of articular cartilage defects were also compared before and after traction. Patients were instructed to report on pain or any other symptoms during elbow traction., Results: No patient reported discomfort, pain or any other symptoms related to traction on immediate and intermediate-term follow-up. Joint space width increased, more at the radiocapitellar joint space (Δ = 0.63 mm, p = 0.005) than at the ulnotrochlear joint space (Δ = 0.17 mm, p = 0.012), with contrast dispersion into the radiocapitellar joint and cartilage visibility of the radiocapitellar joint space significantly improving after traction (all p < 0.05). All of these parameters also improved at the ulnotrochlear joint, although this did not reach statistical significance. Traction improved the visibility of cartilage defects., Conclusion: This is the first study to evaluate the effect of traction on MRA of the elbow joint. This technique is safe and technically feasible. Traction MRA improves the cartilage surface visibility and cartilage defect visibility., Advances in Knowledge: This technique is safe and technically feasible. Traction MRA improves cartilage surface visibility and cartilage defect visibility.

Background: Disease management programs (DMPs) have proliferated recently as a means of improving the quality and efficiency of care for patients with chronic illness. These programs include education about disease, optimization of evidence-based medications, information and support from case managers, and institution of self-management principles. Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in Singapore and worldwide. DMP aims to reduce mortality, hospitalizations, and average length of stay in such patients. This study assesses the outcomes of the DMP, comparing the propensity score matched DMP patients with controls., Methods: DMP patients were compared with the controls, who were COPD patients fulfilling the DMP's inclusion criteria but not included in the program. Control patients were identified from Operations Data Store (ODS) database. The outcomes of interest were average length of stay, number of days admitted to hospital per 100 person days, readmission, and mortality rates per person year. The risk of death and readmission was estimated using Cox, and competing risk regression respectively. Propensity score was estimated to identify the predictors of DMP enrolment. DMP patients and controls were matched on their propensity score., Results: There were 170 matched DMP patients and control patients having 287 and 207 hospitalizations respectively. Program patient had lower mortality than the controls (0.12 vs. 0.27 per person year); cumulative 1-year survival was 91% among program patient and 76% among the control patients. Readmission, and hospital days per 100 person-days was higher for the program patients (0.36 vs. 0.17 per person year), and (2.19 vs. 1.88 per person year) respectively., Conclusions: Participation in "DMP" was associated with lower all-cause mortality when compared to the controls. This survival gain in the program patients was paradoxically associated with an increase in readmission rate and total hospital days.

In Drosophila, Dicer-1 binds Loquacious-PB (Loqs-PB) as its major co-factor. Previous analyses indicated that loqs mutants only partially impede miRNA processing, but the activity of minor isoforms or maternally deposited Loqs was not eliminated in these studies. We addressed this by generating a cell line from loqs-null embryos and found that only ∼40% of miRNAs showed clear Loqs dependence. Genome-wide comparison of the hairpin structure and Loqs dependence suggested that Loqs substrates are influenced by base-pairing status at the dicing site. Artificial alteration of base-pairing stability at this position in model miRNA hairpins resulted in predicted changes in Loqs dependence, providing evidence for this hypothesis. Finally, we found that evolutionarily young miRNA genes tended to be Loqs dependent. We propose that Loqs may have roles in assisting the de novo emergence of miRNA genes by facilitating dicing of suboptimal hairpin substrates., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: American College of Chest Physicians (ACCP) provides guidelines to manage pulmonary nodules. Pulmonary nodules however can be malignant or benign. Similar incidence of tuberculosis (TB) and lung cancer in Asian countries raises concern over the relevance of suggested guidelines in Asian population. There is little data on the pattern of clinical practice in the management of pulmonary nodules in Asian country (Singapore). Our study describes the current pattern of clinical practice in this area highlighting the variation in practice and discussing the potential reasons., Methods: Retrospective review of the medical records of patients diagnosed with lung cancer in 2010., Results: Sixty nodules were identified in 32 patients. Nodules were detected incidentally on routine imaging in 7 (21.9%) patients. TB contact tracing and pre-employment screening were common ways by which nodules were detected incidentally. Over one third (37.5%) were non-smokers. Majority of nodules were located in the upper lobes of right and left lung followed by right lower lobe (RLL). Only few patients 8 (25%) had positron emission tomography (PET) scan for staging purposes. There were no difference in survival between patients who presented with single, 747 (range, 25-1,840) days vs. multiple nodules 928 (range, 30-2,572) days, P=0.26. In a retrospective analysis of malignancy risk with the probability calculator, 62.5% patients were at low-moderate risk whilst 32.5% were at high risk., Conclusions: The clinical practice of managing pulmonary nodules in Asian population differs from ACCP guidelines. None of the patient had pre-test probability calculated, and few had PET scan. This is because upper lobe predominance of lung cancer is identical to TB, non-smoking history does not have any weight in discounting malignancy risk where many of the Asian lung cancer patients are non-smokers, and the local endemicity of TB and its confounding effect on radiological findings of CT scan and PET scan.

Objective: The purpose of this study was to assess the effects of traction during MR arthrography of the wrist on joint space widening, cartilage visibility, and detection of tears of the triangular fibrocartilage complex (TFCC) and intrinsic ligaments., Subjects and Methods: A prospective study included 40 wrists in 39 patients (25 men, 14 women; mean age, 35 years). MR arthrography was performed with a 3-T MRI system with and without axial traction. Two radiologists independently measured wrist and carpal joint space widths and semiquantitatively graded articular cartilage visibility. Using conventional arthrography as the reference standard and working in consensus, they assessed for the presence of tears of the TFCC, lunotriquetral ligament (LTL), and scapholunate ligament (SLL). Visibility of a tear before traction was compared with visibility after traction., Results: With traction, all joint spaces in the wrist and carpus were significantly widened (change, 0.15-1.01 mm; all p < 0.006). Subjective cartilage visibility of all joint spaces improved after traction (all p ≤ 0.048) except for that of the radioscaphoid space, which was well visualized even before traction. Conventional arthrography depicted 24 TFCC tears, seven LTL tears, and three SLL tears. The accuracy of tear detection improved after traction for the TFCC (98% after traction vs 83% before traction), the LTL (100% vs 88%), and the SLL (100% vs 95%). Tear visibility improved after traction for 54% of TFCC tears, 71% of LTL tears, and 66% of SLL tears., Conclusion: Wrist MR arthrography with axial traction significantly improved the visibility of articular cartilage and the detection and visibility of tears of the TFCC and intrinsic ligaments. The results favor more widespread use of traction during MR arthrography of the wrist.

Objective: A diagnosis of advanced breast cancer (ABC) challenges a woman's ambitions. This longitudinal study explored (1) if goal adjustment disposition influenced psychological adjustment patterns among women with ABC and (2) if dispositional hope and optimism moderate effects of goal adjustment on psychological adjustment., Methods: One hundred ninety three out of 225 women with ABC were assessed while they were awaiting/receiving initial chemotherapy, then again at 6 weeks, 3 months, 6 months, and 12 months post-baseline. Goal disengagement, goal reengagement, optimism, hope, and psychological adjustment (anxiety, depression, and positive affect) were assessed at baseline; psychological adjustment was reassessed at each follow-up. Latent growth curve modeling was used to examine the change of psychological adjustment and test the study objectives., Results: High goal disengagement, low reengagement, and high optimism were associated with lower initial anxiety, while high goal disengagement and optimism predicted a slower rate of change in anxiety. High goal disengagement, reengagement, and optimism were associated with lower initial depression. High goal reengagement, optimism, and hope were associated with initial positive affect scores, while optimism predicted its rate of change. Optimism moderated the effect of goal disengagement on anxiety and depression, whereas hope moderated the effect of goal reengagement on positive affect., Conclusion: Goal disengagement and reengagement are two relatively independent processes influencing psychological well-being. These findings will help clinicians to tailor specific interventions to help women coping with the diagnosis of ABC., (Copyright © 2015 John Wiley & Sons, Ltd.)

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.)

Ultrasound (US) is increasingly being used as the first-line imaging modality for investigating the chest wall for soft tissue and bony lesions. This article describes the technique used for the US examination, the relevant chest-wall anatomy, and the appearances on US scanning of pathologic entities either unique to or common in the region of the chest wall., (© 2015 Wiley Periodicals, Inc.)

Objective: Critically ill patients are at high risk of developing pressure ulcers (PU), with the sacrum and heels being highly susceptible to pressure injuries. The objective of our study was to evaluate the clinical effectiveness of a new multi-layer, self-adhesive soft silicone foam heel dressing to prevent PU development in trauma and critically ill patients in the intensive care unit (ICU)., Method: A cohort of critically ill patients were enrolled at the Royal Melbourne Hospital. Each patient had the multi-layer soft silicone foam dressing applied to each heel on admission to the emergency department. The dressings were retained with a tubular bandage for the duration of the patients' stay in the ICU. The skin under the dressings was examined daily and the dressings were replaced every three days. The comparator for our cohort study was the control group from the recently completed Border Trial., Results: Of the 191 patients in the initial cohort, excluding deaths, loss to follow-up and transfers to another ward, 150 patients were included in the final analysis. There was no difference in key demographic or physiological variables between the cohorts, apart from a longer ICU length of stay for our current cohort. No PUs developed in any of our intervention cohort patients compared with 14 patients in the control cohort (n=152; p<0.001) who developed a total of 19 heel PUs., Conclusion: We conclude, based on our results, that the multi-layer soft silicone foam dressing under investigation was clinically effective in reducing ICU-acquired heel PUs. The findings also support previous research on the clinical effectiveness of multi-layer soft silicone foam dressings for PU prevention in the ICU.

The prevention of hospital acquired pressure ulcers in critically ill patients remains a significant clinical challenge. The aim of this trial was to investigate the effectiveness of multi-layered soft silicone foam dressings in preventing intensive care unit (ICU) pressure ulcers when applied in the emergency department to 440 trauma and critically ill patients. Intervention group patients (n = 219) had Mepilex(®) Border Sacrum and Mepilex(®) Heel dressings applied in the emergency department and maintained throughout their ICU stay. Results revealed that there were significantly fewer patients with pressure ulcers in the intervention group compared to the control group (5 versus 20, P = 0·001). This represented a 10% difference in incidence between the groups (3·1% versus 13·1%) and a number needed to treat of ten patients to prevent one pressure ulcer. Overall there were fewer sacral (2 versus 8, P = 0·05) and heel pressure ulcers (5 versus 19, P = 0·002) and pressure injuries overall (7 versus 27, P = 0·002) in interventions than in controls. The time to injury survival analysis indicated that intervention group patients had a hazard ratio of 0·19 (P = 0·002) compared to control group patients. We conclude that multi-layered soft silicone foam dressings are effective in preventing pressure ulcers in critically ill patients when applied in the emergency department prior to ICU transfer., (© 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Little is known about the cost-benefit of soft silicone foam dressings in pressure ulcer (PU) prevention among critically ill patients in the emergency department (ED) and intensive care unit (ICU). A randomised controlled trial to assess the efficacy of soft silicone foam dressings in preventing sacral and heel PUs was undertaken among 440 critically ill patients in an acute care hospital. Participants were randomly allocated either to an intervention group with prophylactic dressings applied to the sacrum and heels in the ED and changed every 3 days in the ICU or to a control group with standard PU prevention care provided during their ED and ICU stay. The results showed a significant reduction of PU incidence rates in the intervention group (P = 0·001). The intervention cost was estimated to be AU$36·61 per person based on an intention-to-treat analysis, but this was offset by lower downstream costs associated with PU treatment (AU$1103·52). Therefore, the average net cost of the intervention was lower than that of the control (AU$70·82 versus AU$144·56). We conclude that the use of soft silicone multilayered foam dressings to prevent sacral and heel PUs among critically ill patients results in cost savings in the acute care hospital., (© 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Study Design: Cohort study., Objective: To investigate the diagnostic capability of low-field magnetic resonance imaging (MRI) compared with high-field MRI for degenerative disease of the lumbar spine., Summary of Background Data: Low-field MRI has several advantages over high-field magnetic resonance systems (easier installation, lower purchase, and maintenance cost). The diagnostic capability of low-field MRI for degenerative disease of the lumbar spine has not been compared with that of high-field MRI., Methods: Hundred patients (mean age: 56.3 yr, range: 32-80; F:M = 59:41) with neurogenic claudication or sciatica were studied. All patients underwent MRI of the lumbar spine on both low-field (0.25T) and high-field (1.5T or 3.0T) magnetic resonance systems. Intervertebral disc herniation, central canal, lateral recess, and exit foraminal stenosis as well as nerve root compression at L3-L4, L4-L5, and L5-S1 were evaluated by 2 radiologists for both low- and high-field systems using established reliable grading systems., Results: There was excellent agreement between low- and high- field MRI with regard to grading the presence and severity of disc herniation (r = 0.92-0.94; P < 0.05), central canal stenosis (r = 0.89-0.91; P < 0.05), lateral recess stenosis (r = 0.81-0.87; P < 0.05), and exit foramen stenosis (r = 0.81-0.89; P < 0.05). Descending or exiting nerve root compression occurred in 52% of patients at L3-L4, L4-L5, or L5-S1 levels, with good agreement between low-field and high-field MRI (r = 0.71-0.76; P < 0.05) for nerve root compression., Conclusion: Excellent reliability between low- and high- field MRI was found for most features of lumbar disc degeneration, with good agreement for nerve root compression. 0.25T MRI was more susceptible to motion artifact, probably due to longer scanning time., Level of Evidence: 3.

Dengue fever, a viral disease epidemic in some parts of the world, is of considerable international concern, with a growing incidence owing to developing urbanization, tourism, and trade. Ocular manifestations of dengue fever are uncommon, but of great significance. Proposed mechanisms include direct viral infection as well as immunologic phenomena. Common manifestations include subconjunctival, vitreous, and retinal hemorrhages; posterior uveitis; optic neuritis; and maculopathies such as foveolitis, hemorrhage, and edema. Main symptoms include blurring of vision, scotomata, metamorphopsia, and floaters. Diagnostic and monitoring investigations described included optical coherence tomography, fundus fluorescein and indocyanine green angiography, visual field analysis, and electrophysiologic tests. Management is based on clinical presentation and includes active surveillance as well as various anti-inflammatory and immunosuppressive therapies. There have been no prospective, randomized therapeutic trials, and it is unclear if the disease is self-limiting or if treatment is actually beneficial. Prognosis varies, ranging from full resolution to permanent vision loss despite intervention., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Idiopathic spontaneous intraperitoneal haemorrhage (ISIH), historically known as abdominal apoplexy, is spontaneous haemorrhage due to rupture of an intra-abdominal visceral vessel in the absence of trauma or underlying pathology. It is an exceptionally rare condition, with mostly scattered case reports available. The aim of this study was to describe this rare condition, possible associated risk factors, and usefulness of multislice-CT (MS-CT) angiogram in its diagnosis prior to intervention., Methods: A retrospective review of patients diagnosed with ISIH. Radiological records of haemoperitoneum from a single tertiary hospital in 2006-2013 were analysed, and the cases of ISIH were identified. Demographics (including pre-morbid hypertension status), abdominal aortic calcification as a measure of atherosclerotic changes, MS-CT angiogram +/- conventional digital subtraction angiograph images, surgical records and outcomes were reviewed., Results: 425 cases of haemoperitoneum were retrieved from hospital radiology database from 2006 to 2013, and 5 patients (1.1%) diagnosed with ISIH were identified (4 males, 1 female, mean age of 64 years). 4 out of 5 patients (80%) had a history of hypertension (mean 150/90 mmHg) and 3 patients had moderate abdominal aortic atherosclerosis. MS-CT angiogram was able to diagnose the bleeding source in 4 out of 5 patients, while the bleeding source remained occult in the last patient even with both MS-CT and traditional DSA angiography. Patients who underwent either embolization or surgery had no further re-bleeding in clinical follow up, ranging from 5 to 8 years., Conclusions: Hypertension and abdominal aortic atherosclerosis appear to be associated risk factors for ISIH, and MS-CT angiogram has a high sensitivity in detecting the site of haemorrhage. An integrated angiographic and surgical approach is important in managing patients with ISIH.

Epidermoid cysts are benign slow growing extra-axial tumours that insinuate between brain structures, while their occurrences in intra-axial or intradiploic locations are exceptionally rare. We present the clinical, imaging, and pathological findings in two patients with atypical epidermoid cysts. CT and MRI findings for the first case revealed an intraparenchymal epidermoid cyst that demonstrated no restricted diffusion. The second case demonstrated an aggressive epidermoid cyst that invaded into the intradiploic spaces, transverse sinus, and the calvarium. The timing of ectodermal tissue sequestration during fetal development may account for the occurrence of atypical epidermoid cysts.

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]