Impact of systemic disease on CNS disease control after stereotactic radiosurgery to breast cancer brain metastases (The SYBRA Study).

The objective of the study is to assess impact of systemic disease (SD) status on overall survival and brain metastasis (BM) control, adopting a novel landmark approach to categorize SD among breast cancer (BC) patients. This single institution retrospective study included BCBM patients who have received stereotactic radiosurgery (SRS) to brain. Separate endpoints [CNS failure-free survival (cFFS), overall survival (OS)] were analyzed from each Landmark (LM): LM1 (3-months), LM2 (6-months). Patients were categorized into early and non-early progression (EP, NEP) groups depending on SD status before LMs. Median survivals from LM were assessed with Kaplan Meier plots, compared with Log-Rank test. EP was associated with worse median cFFS and OS vs NEP in both LM analyses (cFFS- LM1: 3.6 vs. 9.7 months, p = 0.0016; LM2: 2.3 vs. 12.5 months, p < 0.0001; OS- LM1: 3.6 vs. 24.3 months, p < 0.0001; LM2: 5.3 vs. 30.2 months, p < 0.0001). In multivariate analyses, EP was associated with shorter cFFS [LM1: Hazard Ratio (HR) with 95% confidence interval (CI) 3.16, 1.46-6.83, p = 0.0034; LM2: 5.32, 2.33-12.15, p = <0.0001] and shorter OS (LM1: HR with 95% CI 4.28, 1.98-9.12, p = 0.0002; LM2: 7.40, 3.10-17.63, p = <0.0001) vs NEP. Early systemic disease progressions after 1st SRS to brain is associated with worse cFFS and OS in patients with BCBM.

Simplification of Mobility Tests and Data Processing to Increase Applicability of Wearable Sensors as Diagnostic Tools for Parkinson's Disease.

Quantitative mobility analysis using wearable sensors, while promising as a diagnostic tool for Parkinson's disease (PD), is not commonly applied in clinical settings. Major obstacles include uncertainty regarding the best protocol for instrumented mobility testing and subsequent data processing, as well as the added workload and complexity of this multi-step process. To simplify sensor-based mobility testing in diagnosing PD, we analyzed data from 262 PD participants and 50 controls performing several motor tasks wearing a sensor on their lower back containing a triaxial accelerometer and a triaxial gyroscope. Using ensembles of heterogeneous machine learning models incorporating a range of classifiers trained on a set of sensor features, we show that our models effectively differentiate between participants with PD and controls, both for mixed-stage PD (92.6% accuracy) and a group selected for mild PD only (89.4% accuracy). Omitting algorithmic segmentation of complex mobility tasks decreased the diagnostic accuracy of our models, as did the inclusion of kinesiological features. Feature importance analysis revealed that Timed Up and Go (TUG) tasks to contribute the highest-yield predictive features, with only minor decreases in accuracy for models based on cognitive TUG as a single mobility task. Our machine learning approach facilitates major simplification of instrumented mobility testing without compromising predictive performance.

Evaluating trends in cigarette and HTP use in Japan and measurement issues in the National Health and Nutrition Survey.

INTRODUTION: Studies have reported that the rapid rise in heated tobacco product (HTP) sales in Japan accompanied an accelerated decline in cigarette sales. However, these studies do not distinguish whether those who previously smoked cigarettes became dual users with HTPs (smoking fewer cigarettes) or instead switched completely to HTPs. If HTPs present lower health risks than cigarettes, replacing cigarettes with HTPs is more likely to improve public health than cigarette users continuing as dual users. METHODS: To evaluate the role of HTP introduction relative to smoking prevalence, we examine trends in cigarette prevalence as related to trends in HTP use using Japan's National Health and Nutrition Survey (NHNS) from 2011 to 2019. We develop measures of relative changes in smoking prevalence use by age and gender in the pre-HTP and post-HTP periods. We then analyse prevalence data by year using joinpoint regression to statistically distinguish changes in trend. RESULTS: Compared with the pre-HTP 2011-2014 period, cigarette prevalence decreased more rapidly during the post-HTP 2014-2017 period, particularly among younger age groups. However, the changing format of NHNS questions limits our ability to determine the impact on smoking prevalence, particularly after 2017. CONCLUSIONS: While suggesting that HTPs helped some people who smoke to quit smoking, this study also shows the difficulties in eliciting accurate survey responses about product use and distinguishing the impact of a potentially harm-reducing product in an environment subject to rapidly evolving patterns of use.

Support for banning sale of smoked tobacco products among adults who smoke: findings from the International Tobacco Control Four Country Smoking and Vaping Surveys (2018-2022).

BACKGROUND: Many people continue to smoke despite strong policies to deter use, thus stronger regulatory measures may be required. In four high-income countries, we examined whether people who smoke would support a total ban on smoked tobacco products under two differing policy scenarios. METHODS: Data were from 14 363 adults (≥18) who smoked cigarettes (≥monthly) and participated in at least one of the 2018, 2020 or 2022 International Tobacco Control Four Country Smoking and Vaping Surveys in Australia, Canada, England and the USA. In 2018, respondents were asked whether they would support a law that totally bans smoked tobacco if the government provides smoking cessation assistance (Cessation Assistance scenario). In 2020 and 2022, respondents were asked a slightly different question as to whether they would support a law that totally bans smoked tobacco if the government encourages people who smoke to use alternative nicotine products like vaping products and nicotine replacement products instead (substitution scenario). Responses (support vs oppose/don't know) were estimated on weighted data. RESULTS: Support was greater for the cessation assistance scenario (2018, 36.6%) than the nicotine substitution scenario (2020, 26.9%; 2022, 26.3%, both p<0.0001). In the longitudinal analysis, there was a significant scenario by country interaction effect with lower support in Canada, the USA and Australia under the substitution scenario than in the cessation scenario, but equivalent levels in England under both scenarios. The strongest correlates of support under both scenarios were planning to quit smoking within 6 months, wanting to quit smoking 'a lot' and recent use of nicotine replacement therapy. CONCLUSIONS: Opposition to banning smoked tobacco predominates among people who smoke, but less with a cessation assistance scenario than one encouraging nicotine substitution. Wanting to quit a lot was the strongest indicator of support.

Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with type 2 diabetes mellitus: A single-blind cross-over trial.

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1c): 61.1 ± 14.1 mmol mol-1; aged 64.2 ± 9.4 years; four female] completed a single-blind, randomised, sham-controlled, cross-over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2 [ F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ] = 0.155; ∼2500 m simulated altitude) or normoxic conditions ( F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$  = 0.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor-1α]; [interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2 h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon-like peptide-1]); and gut microbiota diversity and abundance [16S rRNA amplicon sequencing]. During intervention periods, accelerometers measured physical activity, sleep duration and efficiency, whereas continuous glucose monitors were used to assess estimated HbA1c and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P > 0.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P = 0.10; P = 0.08 respectively) for a medium beneficial effect (d = 0.49; d = 0.59 respectively). Ten nights of overnight moderate hypoxic exposure did not significantly affect glycaemic control, gut microbiome, appetite, or inflammation in adults with T2DM. However, the intervention was well tolerated and a medium effect-size for improved insulin sensitivity and reduced alpha diversity warrants further investigation. KEY POINTS: Living at altitude lowers the incidence of type 2 diabetes mellitus (T2DM). Animal studies suggest that exposure to hypoxia may lead to weight loss and suppressed appetite. In a single-blind, randomised sham-controlled, cross-over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O2 ∼0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]) and hypoxic stress ([hypoxia inducible factor 1α]; heat shock protein 70]) in 13 adults with T2DM. Appetite and inflammatory markers were unchanged following hypoxic exposure, but an increased insulin sensitivity and reduced gut microbiota alpha diversity were associated with a medium effect-size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial. Hypoxic exposure may represent a viable therapeutic intervention in people with T2DM and particularly those unable or unwilling to exercise because barriers to uptake and adherence may be lower than for other lifestyle interventions (e.g. diet and exercise).

Positive-unlabeled learning identifies vaccine candidate antigens in the malaria parasite Plasmodium falciparum.

Malaria vaccine development is hampered by extensive antigenic variation and complex life stages of Plasmodium species. Vaccine development has focused on a small number of antigens, many of which were identified without utilizing systematic genome-level approaches. In this study, we implement a machine learning-based reverse vaccinology approach to predict potential new malaria vaccine candidate antigens. We assemble and analyze P. falciparum proteomic, structural, functional, immunological, genomic, and transcriptomic data, and use positive-unlabeled learning to predict potential antigens based on the properties of known antigens and remaining proteins. We prioritize candidate antigens based on model performance on reference antigens with different genetic diversity and quantify the protein properties that contribute most to identifying top candidates. Candidate antigens are characterized by gene essentiality, gene ontology, and gene expression in different life stages to inform future vaccine development. This approach provides a framework for identifying and prioritizing candidate vaccine antigens for a broad range of pathogens.

Adaptive Radiotherapy: Next-Generation Radiotherapy.

Radiotherapy, a crucial technique in cancer therapy, has traditionally relied on the premise of largely unchanging patient anatomy during the treatment course and encompassing uncertainties by target margins. This review introduces adaptive radiotherapy (ART), a notable innovation that addresses anatomy changes and optimizes the therapeutic ratio. ART utilizes advanced imaging techniques such as CT, MRI, and PET to modify the treatment plan based on observed anatomical changes and even biological changes during the course of treatment. The narrative review provides a comprehensive guide on ART for healthcare professionals and trainees in radiation oncology and anyone else interested in the topic. The incorporation of artificial intelligence in ART has played a crucial role in improving effectiveness, particularly in contour segmentation, treatment planning, and quality assurance. This has expedited the process to render online ART feasible, lowered the burden for radiation oncology practitioners, and enhanced the precision of dynamically personalized treatment. Current technical and clinical progress on ART is discussed in this review, highlighting the ongoing development of imaging technologies and AI and emphasizing their contribution to enhancing the applicability and effectiveness of ART.

Evaluación de las políticas contra el tabaquismo en países latinoamericanos en la era del Convenio Marco para el Control del Tabaco / Evaluating tobacco control policy in Latin American countries during the era of the Framework Convention on Tobacco Control

OBJETIVO: El Convenio Marco para el Control del Tabaco (CMCT) pretende coordinar las políticas mundiales que reducen el consumo de tabaco. Con toda probabilidad, estas medidas tendrán efectos en países de ingresos medianos y bajos; no obstante, se requieren estudios de evaluación para determinar sus consecuencias y las posibles sinergias entre las directrices. MATERIAL Y MÉTODOS: El Proyecto Internacional de Evaluación de Políticas para el Control del Tabaco (ITC) es una colaboración internacional para evaluar el efecto psicosocial y conductual que causan las políticas promovidas por el CMCT en adultos fumadores de nueve países. El marco de evaluación ITC utiliza diversos controles de país, con un diseño longitudinal y un modelo conceptual basado en teorías para probar las hipótesis sobre los efectos anticipados de determinadas políticas. RESULTADOS: Los resultados del análisis de datos confirman por lo general los hallazgos anteriores de investigaciones basadas en las recomendaciones del CMCT, y se refieren a las siguientes políticas: promover etiquetas de advertencia con imágenes gráficas, prohibir el uso de las descripciones "ligero" y "suave", establecer ambientes libres de humo de tabaco, incrementar los impuestos, prohibir la publicidad del cigarro e implementar nuevos métodos para evaluar los componentes del cigarro. CONCLUSIONES: Los hallazgos iniciales sugieren que los países latinoamericanos podrían aplicar métodos similares para vigilar y evaluar sus propias directrices, así como fortalecer el cuerpo de conocimiento sobre políticas en otros países.