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In-air handwriting is a contemporary human computer interaction (HCI) technique which enables users to write and communicate in free space in a simple and intuitive manner. Air-written characters exhibit wide variations depending upon different writing styles of users and their speed of articulation, which presents a great challenge towards effective recognition of linguistic characters. So, in this paper we have proposed an ensemble model for in-air handwriting recognition which is based on convolutional neural network (CNN) and a long short-term memory neural network (LSTM-NN). The method collaborates overall character trajectory appearance modeling and temporal trajectory feature modeling for efficient recognition of varied types of air-written characters. In contrast to two-dimensional handwriting, in-air handwriting generally involves writing of characters interlinked by a continuous stroke, which makes segregation of intended writing activity from insignificant connecting motions an intricate task. So, a two-stage statistical framework is incorporated in the system for automatic detection and extraction of relevant writing segments from air-written characters. Identification of writing events from a continuous stream of air-written data is accomplished by formulating a Markov Random Field (MRF) model, while the segmentation of writing events into meaningful handwriting segments and redundant parts is performed by implementation of a Mahalanobis distance (MD) classifier. The proposed approach is assessed on an air-written character dataset comprising of Assamese vowels, consonants and numerals. The experimental results connote that our hybrid network can assimilate more information from the air-writing patterns and hence offer better recognition performance than the state-of-the-art approaches.

Localized prostate cancer shows great clinical, genetic and environmental heterogeneity; however, prostate cancer treatment is currently guided solely by clinical staging, serum PSA levels and histology. Increasingly, the roles of differential genomics, multifocality and spatial distribution in tumorigenesis are being considered to further personalize treatment. The human prostate is divided into three zones based on its histological features: the peripheral zone (PZ), the transition zone (TZ) and the central zone (CZ). Each zone has variable prostate cancer incidence, prognosis and outcomes, with TZ prostate tumours having better clinical outcomes than PZ and CZ tumours. Molecular and cell biological studies can improve understanding of the unique molecular, genomic and zonal cell type features that underlie the differences in tumour progression and aggression between the zones. The unique biology of each zonal tumour type could help to guide individualized treatment and patient risk stratification.The prostate is divided into the peripheral, transition and central zones, which have different prostate cancer incidences and prognoses. Differences between the zones suggest their potential roles in tumour aggressiveness, but treatment of prostate cancer remains zonal agnostic. Improved understanding of the zones and their roles in tumorigenesis could improve prostate cancer management.

Two radiotherapy fractionation schedules are used to treat locally advanced bladder cancer: 64 Gy in 32 fractions over 6·5 weeks and a hypofractionated schedule of 55 Gy in 20 fractions over 4 weeks. Long-term outcomes of these schedules in several cohort studies and case series suggest that response, survival, and toxicity are similar, but no direct comparison has been published. The present study aimed to assess the non-inferiority of 55 Gy in 20 fractions to 64 Gy in 32 fractions in terms of invasive locoregional control and late toxicity in patients with locally advanced bladder cancer. We did a meta-analysis of individual patient data from patients (age ≥18 years) with locally advanced bladder cancer (T1G3 [high-grade non-muscle invasive] or T2–T4, N0M0) enrolled in two multicentre, randomised, controlled, phase 3 trials done in the UK: BC2001 (NCT00024349; assessing addition of chemotherapy to radiotherapy) and BCON (NCT00033436; assessing hypoxia-modifying therapy combined with radiotherapy). In each trial, the fractionation schedule was chosen according to local standard practice. Co-primary endpoints were invasive locoregional control (non-inferiority margin hazard ratio [HR]=1·25); and late bladder or rectum toxicity, assessed with the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic tool (non-inferiority margin for absolute risk difference [RD]=10%). If non-inferiority was met for invasive locoregional control, superiority could be considered if the 95% CI for the treatment effect excluded the null effect (HR=1). One-stage individual patient data meta-analysis models for the time-to-event and binary outcomes were used, accounting for trial differences, within-centre correlation, randomised treatment received, baseline variable imbalances, and potential confounding from relevant prognostic factors. 782 patients with known fractionation schedules (456 from the BC2001 trial and 326 from the BCON trial; 376 (48%) received 64 Gy in 32 fractions and 406 (52%) received 55 Gy in 20 fractions) were included in our meta-analysis. Median follow-up was 120 months (IQR 99–159). Patients who received 55 Gy in 20 fractions had a lower risk of invasive locoregional recurrence than those who received 64 Gy in 32 fractions (adjusted HR 0·71 [95% CI 0·52–0·96]). Both schedules had similar toxicity profiles (adjusted RD −3·37% [95% CI −11·85 to 5·10]). A hypofractionated schedule of 55 Gy in 20 fractions is non-inferior to 64 Gy in 32 fractions with regard to both invasive locoregional control and toxicity, and is superior with regard to invasive locoregional control. 55 Gy in 20 fractions should be adopted as a standard of care for bladder preservation in patients with locally advanced bladder cancer. Cancer Research UK.

Hypoxia is common in non-small cell lung cancer (NSCLC) and an attractive therapeutic target. As hypoxia-targeting treatments are effective in patients with the most hypoxic tumours, we aimed to develop a lung adenocarcinoma (LUAD) hypoxia-related gene expression signature. RNAseq was used to identify genes significantly differentially expressed under hypoxia (1% O 2 ) in four LUAD cell lines. Identified genes were used for unsupervised clustering of a TCGA-LUAD training dataset (n = 252) and in a machine learning approach to build a hypoxia-related signature. Thirty-five genes were upregulated in common in three of the four lines and reduced in the training cohort to a 28-gene signature. The signature was prognostic in the TCGA training (HR 2.12, 95% CI 1.34–3.37, p = 0.0011) and test (n = 250; HR 2.13, 95% CI 1.32–3.45, p = 0.0016) datasets. The signature was prognostic for overall survival in a meta-analysis of nine other datasets (n = 1257; HR 2.08, 95% CI 1.60–2.70, p < 0.0001). The 28-gene LUAD hypoxia related signature can be taken forward for further validation using a suitable gene expression platform.

Introduction Recent data has demonstrated that hypoxia drives an immunosuppressive tumour microenvironment (TME) via various mechanisms including hypoxia inducible factor (HIF)-dependent upregulation of programmed death ligand 1 (PD-L1). Both hypoxia and an immunosuppressive TME are targetable independent negative prognostic factors for bladder cancer. Therefore we sought to investigate whether hypoxia is associated with upregulation of PD-L1 in the disease. Materials and methods Three human muscle-invasive bladder cancer cell lines (T24, J82, UMUC3) were cultured in normoxia (20% oxygen) or hypoxia (1 and 0.1% oxygen) for 24 h. Differences in PD-L1 expression were measured using Western blotting, quantitative polymerase chain reaction (qPCR) and flow cytometry (≥3 independent experiments). Statistical tests performed were unpaired t tests and ANOVA. For in silico work an hypoxia signature was used to apply hypoxia scores to muscle-invasive bladder cancers from a clinical trial (BCON; n  = 142) and TCGA ( n  = 404). Analyses were carried out using R and RStudio and statistical tests performed were linear models and one-way ANOVA. Results When T24 cells were seeded at < 70% confluence, there was decreased PD-L1 protein ( p  = 0.009) and mRNA ( p  < 0.001) expression after culture in 0.1% oxygen. PD-L1 protein expression decreased in both 0.1% oxygen and 1% oxygen in a panel of muscle-invasive bladder cancer cells: T24 ( p  = 0.009 and 0.001), J82 ( p  = 0.008 and 0.013) and UMUC3 ( p  = 0.003 and 0.289). Increasing seeding density decreased PD-L1 protein ( p  < 0.001) and mRNA ( p  = 0.001) expression in T24 cells grown in both 20 and 1% oxygen. Only when cells were 100% confluent, were PD-L1 protein and mRNA levels higher in 1% versus 20% oxygen ( p  = 0.056 and p  = 0.037). In silico analyses showed a positive correlation between hypoxia signature scores and PD-L1 expression in both BCON ( p  = 0.003) and TCGA ( p  < 0.001) cohorts, and between hypoxia and IFNγ signature scores ( p  < 0.001 for both). Conclusion Tumour hypoxia correlates with increased PD-L1 expression in patient derived bladder cancer tumours. In vitro PD-L1 expression was affected by cell density and decreased PD-L1 expression was observed after culture in hypoxia in muscle-invasive bladder cancer cell lines. As cell density has such an important effect on PD-L1 expression, it should be considered when investigating PD-L1 expression in vitro.

Cancer affects one in two people in the UK and the incidence is set to increase. The UK National Health Service is facing major workforce deficits and cancer services have struggled to recover after the COVID-19 pandemic, with waiting times for cancer care becoming the worst on record. There are severe and widening disparities across the country and survival rates remain unacceptably poor for many cancers. This is at a time when cancer care has become increasingly complex, specialised, and expensive. The current crisis has deep historic roots, and to be reversed, the scale of the challenge must be acknowledged and a fundamental reset is required. The loss of a dedicated National Cancer Control Plan in England and Wales, poor operationalisation of plans elsewhere in the UK, and the closure of the National Cancer Research Institute have all added to a sense of strategic misdirection. The UK finds itself at a crossroads, where the political decisions of governments, the cancer community, and research funders will determine whether we can, together, achieve equitable, affordable, and high-quality cancer care for patients that is commensurate with our wealth, and position our outcomes among the best in the world. In this Policy Review, we describe the challenges and opportunities that are needed to develop radical, yet sustainable plans, which are comprehensive, evidence-based, integrated, patient-outcome focused, and deliver value for money.

Adolescence, derived from the Latin word \"adolescere\" meaning \"to grow up\" is a critical developmental period. During adolescence, major biological as well as psychological developments take place. Development of sexuality is an important bio-psycho-social development, which takes an adult shape during this period. During adolescence, an individual′s thought, perception as well as response gets colored sexually. Puberty is an important landmark of sexuality development that occurs in the adolescence. The myriad of changes that occurs in adolescents puts them under enormous stress, which may have adverse physical, as well as psychological consequences. Understanding adolescent sexuality has important clinical, legal, social, cultural, as well as educational implications.

The aim of this work was to review the literature on the mechanisms by which lifestyle interventions attenuate radiation therapy-induced side effects. A scoping review based on the Joanna Briggs Institute methodological framework was undertaken. MEDLINE, CINAHL and CENTRAL were searched up until 13 March 2024. Studies assessing the potential mechanistic effects of lifestyle interventions on outcomes in adult (>18 years of age) cancer patients undergoing radiotherapy, including any cancer type or intervention timing (before, during, after radiotherapy), were included. Data were extracted regarding study design, intervention characteristics and included outcome measures. Nine studies were included in the review. Study populations included patients with a range of cancers, including head and neck, prostate, breast, lung, lower gastrointestinal, rectal, pelvic and leukaemia. Lifestyle interventions consisted primarily of nutritional supplements, diets or traditional Chinese medicinal ingredients. Exercise programmes were also included. Those that were available involved either resistance training alone or in combination with aerobic exercise. The most common side effects included site-specific toxicity, with some interventions noting improvements to symptoms, alongside alterations to inflammatory cytokine and lymphocyte concentrations. Radiation-induced weight loss and frailty were noted, which may be prevented with interventions that target skeletal muscle metabolism. With more research to fully elucidate the potential mechanisms and consistent evidence of efficacy, lifestyle interventions may present promising non-pharmacological therapeutic options to alleviate some of the side effects of radiotherapy.

Background miRNAs are promising biomarkers in oncology as their small size makes them less susceptible to degradation than mRNA in FFPE tissue. We aimed to derive a hypoxia-associated miRNA signature for bladder cancer. Methods Taqman miRNA array cards identified miRNA seed genes induced under hypoxia in bladder cancer cell lines. A signature was derived using feature selection methods in a TCGA BLCA training data set. miRNA expression data were generated for 190 tumours from the BCON Phase 3 trial and used for independent validation. Results A 14-miRNA hypoxia signature was derived, which was prognostic for poorer overall survival in the TCGA BLCA cohort ( n  = 403, p  = 0.001). Univariable analysis showed that the miRNA signature predicted an overall survival benefit from having carbogen–nicotinamide with radiotherapy (HR = 0.30, 95% CI 0.094–0.95, p  = 0.030) and performed similarly to a 24-gene mRNA signature (HR = 0.47, 95% CI 0.24–0.92, p  = 0.025). Combining the signatures improved performance (HR = 0.26, 95% CI 0.08–0.82, p  = 0.014) with borderline significance for an interaction test ( p  = 0.065). The interaction test was significant for local relapse-free survival LRFS ( p  = 0.033). Conclusion A 14-miRNA hypoxia signature can be used with an mRNA hypoxia signature to identify bladder cancer patients benefitting most from having carbogen and nicotinamide with radiotherapy.