Smoking and the Risk of Type 2 Diabetes: A Cross-sectional Analytical Study.

Background: India is undergoing epidemiological transitions with the increase in noncommunicable disease (NCD) burden. Targeting the modifiable risk factors through lifestyle changes in the early years of life remains the most effective strategy for decreasing the prevalence of type 2 diabetes mellitus (T2DM). To determine the association between cigarette smoking and T2DM. Materials and Methods: An analytical cross-sectional study was conducted among the patients attending the outpatient department of a tertiary care teaching hospital in Kolkata, West Bengal, India. Patients aged more than 35 years were enrolled, and details regarding sociodemography, clinical status, and NCD risk factors were collected using pretested semistructured questionnaires after obtaining IEC approval. Data collected were entered in MS Excel and analyzed using SPSS software. Simple logistic regression and multivariable logistic regression analysis were used to calculate the crude and adjusted odds ratio with 95% confidence interval. Results: Out of 434 participants, 37.3% had diabetes mellitus, 51.6% were males, and 28.6% had alcohol consumption. Univariate logistic regression analysis revealed age, BMI, systolic BP, diastolic BP, and cigarette smoking were significantly associated with increased risk of T2DM. Multivariable logistic regression analysis revealed cigarette smoking, systolic BP, age, and female gender were significant risk factors for T2DM. Conclusions: Our study reported cigarette smoking and systolic BP are modifiable risk factors associated with T2DM. Early identification of smoking through screening and appropriate control of hypertension in T2DM patients will decrease the morbidities and mortalities in T2DM cases.

Reporting quality of published reviews of commercial and publicly available mobile health apps (mHealth app reviews): a scoping review protocol.

INTRODUCTION: Reviews of commercial and publicly available smartphone (mobile) health applications (mHealth app reviews) are being undertaken and published. However, there is variation in the conduct and reporting of mHealth app reviews, with no existing reporting guidelines. Building on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we aim to develop the Consensus for APP Review Reporting Items (CAPPRRI) guidance, to support the conduct and reporting of mHealth app reviews. This scoping review of published mHealth app reviews will explore their alignment, deviation, and modification to the PRISMA 2020 items for systematic reviews and identify a list of possible items to include in CAPPRRI. METHOD AND ANALYSIS: We are following the Joanna Briggs Institute approach and Arksey and O'Malley's five-step process. Patient and public contributors, mHealth app review, digital health research and evidence synthesis experts, healthcare professionals and a specialist librarian gave feedback on the methods. We will search SCOPUS, CINAHL Plus, AMED, EMBASE, Medline, APA PsycINFO and the ACM Digital Library for articles reporting mHealth app reviews and use a two-step screening process to identify eligible articles. Information on whether the authors have reported, or how they have modified the PRISMA 2020 items in their reporting, will be extracted. Data extraction will also include the article characteristics, protocol and registration information, review question frameworks used, information about the search and screening process, how apps have been evaluated and evidence of stakeholder engagement. This will be analysed using a content synthesis approach and presented using descriptive statistics and summaries. This protocol is registered on OSF (https://osf.io/5ahjx). ETHICS AND DISSEMINATION: Ethical approval is not required. The findings will be disseminated through peer-reviewed journal publications (shared on our project website and on the EQUATOR Network website where the CAPPRRI guidance has been registered as under development), conference presentations and blog and social media posts in lay language.

Cardiorespiratory dynamics of type 2 diabetes mellitus: An extensive view of breathing and fitness challenges in a diabetes prevalent population.

BACKGROUND: Diabetes mellitus (DM) is well known for related micro and macrovascular complications. Uncontrolled hyperglycemia in diabetes mellitus leads to endothelial dysfunction, inflammation, microvascular impairment, myocardial dysfunction, and skeletal muscle changes which affect multiple organ systems. This study was designed to take an extensive view of cardiorespiratory dynamics in patients with type 2 DM. METHODS: One hundred healthy controls (HC) and 100 DM patients were enrolled. We measured and compared the breathing patterns (spirometry), VO2 max levels (heart rate ratio method) and self-reported fitness level (international fitness scale) of individuals with and without diabetes. Data was analyzed in SPSS v.22 and GraphPad Prism v8.0. RESULTS: We observed restrictive spirometry patterns (FVC <80%) in 22% of DM as compared to 2% in HC (p = 0.021). There was low mean VO2 max in DM as compared to HC(32.03 ± 5.36 vs 41.91 ± 7.98 ml/kg/min; p value <0.001). When evaluating physical fitness on self-reported IFiS scale, 90% of the HC report average, good, or very good fitness levels. In contrast, only 45% of the DM shared this pattern, with a 53% proportion perceiving their fitness as poor or very poor (p = <0.05). Restrictive respiratory pattern, low VO2 max and fitness level were significantly associated with HbA1c and long-standing DM. CONCLUSION: This study shows decreased pulmonary functions, decreased cardiorespiratory fitness (VO2 max) and IFiS scale variables in diabetic population as compared to healthy controls which are also associated with glycemic levels and long-standing DM. Screening for pulmonary functions can aid optimum management in this population.

Evaluation of the effectiveness of Berberis integerrima Bunge root extract combined with spearmint essential oil in the treatment of acne vulgaris: A randomized controlled clinical trial.

BACKGROUND: Acne vulgaris is one of the most common dermatological disorders. Berberis integerrima Bunge belongs to the Berberidaceae family. Several studies on different Berberis species in addition to B. integerrima have shown antimicrobial, antioxidant, and anti-inflammatory effects. Spearmint essential oil also has antioxidant, antibacterial, and anti-inflammatory activities. This study aimed to evaluate the clinical effectiveness of the topical combination of B. integerrima root extract and spearmint essential oil in the treatment of acne vulgaris. METHODS: Patients with mild to moderate facial acne who met the inclusion criteria were randomly assigned to either drug (B. integerrima extract/spearmint essential oil topical solution) or control (clindamycin 1% topical solution) groups. Each group applied the solution twice a day for 4 weeks. Before and at the end of the intervention, the number of lesions and mGAGS (Modified Global Acne Grading Scale) score were recorded. RESULTS: Thirty patients in each group of drug and control completed the study. Topical B.integerrima root extract/spearmint essential oil significantly reduced the number of lesions (27.33 ± 26.17 vs. 21.58 ± 21.10; p < 0.001) and mGAGS (18.76 ± 8.61 vs. 13.87 ± 8.14; p < 0.001) at the end of the intervention. However, there was no significant difference between the two groups regarding the number of lesions (p = 0.906) and mGAGS (p = 0.882). CONCLUSIONS: B. integerrima root extract combined with spearmint essential oil has significant anti-acne effects, comparable to topical antibiotic clindamycin. It could be considered as a potential treatment for acne vulgaris. However, more studies with larger sample sizes and longer durations are required to confirm this effect.

Users' views on the use of a smartwatch app to collect daily symptom data in individuals with multiple long-term conditions (Multimorbidity): A qualitative study.

Introduction: Long-term conditions are a major burden on health systems. One way to facilitate more research and better clinical care among patients with long-term conditions is to collect accurate data on their daily symptoms (patient-generated health data) using wearable technologies. Whilst evidence is growing for the use of wearable technologies in single conditions, there is less evidence of the utility of frequent symptom tracking in those who have more than one condition. Aims: To explore patient views of the acceptability of collecting daily patient-generated health data for three months using a smartwatch app. Methods: Watch Your Steps was a longitudinal study which recruited 53 patients to track over 20 symptoms per day for a 90-day period using a study app on smartwatches. Semi-structured interviews were conducted with a sub-sample of 20 participants to explore their experience of engaging with the app. Results: In a population of older people with multimorbidity, patients were willing and able to engage with a patient-generated health data app on a smartwatch. It was suggested that to maintain engagement over a longer period, more 'real-time' feedback from the app should be available. Participants did not seem to consider the management of more than one condition to be a factor in either engagement or use of the app, but the presence of severe or chronic pain was at times a barrier. Conclusion: This study has provided preliminary evidence that multimorbidity was not a major barrier to engagement with patient-generated health data via a smartwatch symptom tracking app.

Quantification of Measurable Residual Disease Detection by Next-Generation Sequencing-Based Clonality Testing in B-Cell and Plasma Cell Neoplasms.

Next-generation sequencing (NGS)-based measurable residual disease (MRD) monitoring in post-treatment settings can be crucial for relapse risk stratification in patients with B-cell and plasma cell neoplasms. Prior studies have focused on validation of various technical aspects of the MRD assays, but more studies are warranted to establish the performance characteristics and enable standardization and broad utilization in routine clinical practice. Here, the authors describe an NGS-based IGH MRD quantification assay, incorporating a spike-in calibrator for monitoring B-cell and plasma cell neoplasms based on their unique IGH rearrangement status. Comparison of MRD status (positive or undetectable) by NGS and flow cytometry (FC) assays showed high concordance (91%, 471/519 cases) and overall good linear correlation in MRD quantitation, particularly for chronic lymphocytic leukemia and B-lymphoblastic leukemia/lymphoma (R = 0.85). Quantitative correlation was lower for plasma cell neoplasms, where underestimation by FC is a known limitation. No significant effects on sequencing efficiency by the spike-in calibrator were observed, with excellent inter- and intra-assay reproducibility within the authors' laboratory, and in comparison to an external laboratory, using the same assay and protocols. Assays performed both at internal and external laboratories showed highly concordant MRD detection (100%) and quantitation (R = 0.97). Overall, this NGS-based MRD assay showed highly reproducible results with quantitation that correlated well with FC MRD assessment, particularly for B-cell neoplasms.

Beliefs About Pain in Pediatric Inflammatory and Noninflammatory Chronic Musculoskeletal Conditions: A Scoping Review.

OBJECTIVE: The Common Sense Self-Regulatory Model posits that beliefs about pain influence coping behaviors and subsequent physical and mental health outcomes in children/young people with chronic musculoskeletal conditions. It was unclear how and what beliefs had been investigated in this population, and whether there were similarities and differences in beliefs held about pain by those experiencing inflammatory versus noninflammatory musculoskeletal conditions. This scoping review addressed this gap. METHODS: A systematic search was conducted using four databases (MEDLINE, PsycINFO, Embase, and CINAHL) in November 2021. Primary studies exploring key stakeholders' (including children, parents, and/or healthcare professionals) beliefs about pain underlying pediatric chronic musculoskeletal conditions were synthesized. RESULTS: Eighteen articles were identified. Cross-sectional designs were predominantly used to explore beliefs (n = 6). The majority used questionnaires to assess beliefs (n = 12). Beliefs common across musculoskeletal conditions were that children/young people felt their pain was not understood by others, and pain affected their physical functioning. Differences included children/young people and parents thinking they had some ability to control pain, and causal beliefs relating to underlying disease activity. These pain beliefs were more likely to be held in relation to inflammatory diagnoses. In contrast, children/young people and parents were more likely to view pain as uncontrollable, with more uncertainty regarding underlying causes, relating to noninflammatory diagnoses. CONCLUSIONS: Methods used to explore pain beliefs were inconsistent. Studies identified similarities and differences which appear to be closely related to the underlying diagnosis. Findings justify further exploration to identify potentially modifiable targets to improve pain outcomes in this population.

Feasibility and acceptability to use a smartphone-based manikin for daily longitudinal self-reporting of chronic pain.

Background: As management of chronic pain continues to be suboptimal, there is a need for tools that support frequent, longitudinal pain self-reporting to improve our understanding of pain. This study aimed to assess the feasibility and acceptability of daily pain self-reporting using a smartphone-based pain manikin. Methods: For this prospective feasibility study, we recruited adults with lived experience of painful musculoskeletal condition. They were asked to complete daily pain self-reports via an app for 30 days. We assessed feasibility by calculating pain report completion levels, and investigated differences in completion levels between subgroups. We assessed acceptability via an end-of-study questionnaire, which we analysed descriptively. Results: Of the 104 participants, the majority were female (n = 87; 84%), aged 45-64 (n = 59; 57%), and of white ethnic background (n = 89; 86%). The mean completion levels was 21 (± 7.7) pain self-reports. People who were not working (odds ratio (OR) = 1.84; 95% confidence interval (CI), 1.52-2.23) were more likely, and people living in less deprived areas (OR = 0.77; 95% CI, 0.62-0.97) and of non-white ethnicity (OR = 0.45; 95% CI, 0.36-0.57) were less likely to complete pain self-reports than their employed, more deprived and white counterparts, respectively. Of the 96 participants completing the end-of-study questionnaire, almost all participants agreed that it was easy to complete a pain drawing (n = 89; 93%). Conclusion: It is feasible and acceptable to self-report pain using a smartphone-based manikin over a month. For its wider adoption for pain self-reporting, the feasibility and acceptability should be further explored among people with diverse socio-economic and ethnic backgrounds.

Analysis of deep optic nerve head structures with spectral domain and swept-source optical coherence tomography.

PURPOSE: Histological evidence indicates that the earliest structural changes to the optic nerve head (ONH) in glaucoma occur in the lamina cribrosa (LC) and its interface with the sclera. However, clinical imaging of these structures remains challenging. We compared the visibility of deep ONH structures with newer iterations of spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT). METHODS: Twelve patients with open-angle glaucoma were imaged with SD-OCT with 24 radial B-scans centred on Bruch's membrane opening (BMO) and SS-OCT with a horizontal and vertical raster scan pattern containing five lines each, centred on the ONH. Single best-matched horizontal and vertical scans from the two modalities were selected and exported. Three independent observers masked to modality determined if BMO, posterior choroid surface, anterior scleral canal opening and anterior and posterior LC insertions into the sclera were detectable in the matched B-scan images. We determined the interobserver agreement and concordance in detecting each structure with the two OCT imaging modalities. RESULTS: There was a high interobserver agreement with both SS-OCT and SD-OCT (inter-item correlations: 0.81-0.93 and 0.77-0.82, respectively). There was a consistent tendency for higher overall detection rates with SS-OCT, however, the differences failed to reach statistical significance. With respect to individual structures, only the posterior LC insertion in the nasal quadrant was statistically different, with a detection rate of 13 and 6 (pooled out of a total of 36 across the three observers) with SS-OCT and SD-OCT, respectively (p=0.04). CONCLUSION: Overall, both SS-OCT and SD-OCT showed statistically equivalent visualisation of ONH structures, however, SS-OCT tended to have higher visualisation rates.

Conducting a systematic review and evaluation of commercially available mobile applications (apps) on a health-related topic: the TECH approach and a step-by-step methodological guide.

OBJECTIVES: To provide an overview of the methodological considerations for conducting commercial smartphone health app reviews (mHealth reviews), with the aim of systematising the process and supporting high-quality evaluations of mHealth apps. DESIGN: Synthesis of our research team's experiences of conducting and publishing various reviews of mHealth apps available on app stores and hand-searching the top medical informatics journals (eg, The Lancet Digital Health, npj Digital Medicine, Journal of Biomedical Informatics and the Journal of the American Medical Informatics Association) over the last five years (2018-2022) to identify other app reviews to contribute to the discussion of this method and supporting framework for developing a research (review) question and determining the eligibility criteria. RESULTS: We present seven steps to support rigour in conducting reviews of health apps available on the app market: (1) writing a research question or aims, (2) conducting scoping searches and developing the protocol, (3) determining the eligibility criteria using the TECH framework, (4) conducting the final search and screening of health apps, (5) data extraction, (6) quality, functionality and other assessments and (7) analysis and synthesis of findings. We introduce the novel TECH approach to developing review questions and the eligibility criteria, which considers the Target user, Evaluation focus, Connectedness and the Health domain. Patient and public involvement and engagement opportunities are acknowledged, including co-developing the protocol and undertaking quality or usability assessments. CONCLUSION: Commercial mHealth app reviews can provide important insights into the health app market, including the availability of apps and their quality and functionality. We have outlined seven key steps for conducting rigorous health app reviews in addition to the TECH acronym, which can support researchers in writing research questions and determining the eligibility criteria. Future work will include a collaborative effort to develop reporting guidelines and a quality appraisal tool to ensure transparency and quality in systematic app reviews.

Inhibiting Angiogenesis by Anti-Cancer Saponins: From Phytochemistry to Cellular Signaling Pathways.

Saponins are one of the broadest classes of high-molecular-weight natural compounds, consisting mainly of a non-polar moiety with 27 to 30 carbons and a polar moiety containing sugars attached to the sapogenin structure. Saponins are found in more than 100 plant families as well as found in marine organisms. Saponins have several therapeutic effects, including their administration in the treatment of various cancers. These compounds also reveal noteworthy anti-angiogenesis effects as one of the critical strategies for inhibiting cancer growth and metastasis. In this study, a comprehensive review is performed on electronic databases, including PubMed, Scopus, ScienceDirect, and ProQuest. Accordingly, the structural characteristics of triterpenoid/steroid saponins and their anti-cancer effects were highlighted, focusing on their anti-angiogenic effects and related mechanisms. Consequently, the anti-angiogenic effects of saponins, inhibiting the expression of genes related to vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-α (HIF-1α) are two main anti-angiogenic mechanisms of triterpenoid and steroidal saponins. The inhibition of inflammatory signaling pathways that stimulate angiogenesis, such as pro-inflammatory cytokines, mitogen-activated protein kinase (MAPKs), and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt), are other anti-angiogenic mechanisms of saponins. Furthermore, the anti-angiogenic and anti-cancer activity of saponins was closely related to the binding site of the sugar moiety, the type and number of their monosaccharide units, as well as the presence of some functional groups in their aglycone structure. Therefore, saponins are suitable candidates for cancer treatment by inhibiting angiogenesis, for which extensive pre-clinical and comprehensive clinical trial studies are recommended.

Clonal Characterization and Somatic Hypermutation Assessment by Next-Generation Sequencing in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Detailed Description of the Technical Performance, Clinical Utility, and Platform Comparison.

Somatic hypermutation status of the IGHV gene is essential for treating patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. Unlike the conventional low-throughput method, assessment of somatic hypermutation by next-generation sequencing (NGS) has potential for uniformity and scalability. However, it lacks standardization or guidelines for routine clinical use. We critically assessed the performance of an amplicon-based NGS assay across 458 samples. Using a validation cohort (35 samples), the comparison of two platforms (Ion Torrent versus Illumina) and two primer sets [leader versus framework region 1 (FR1)] in their ability to identify clonotypic IGHV rearrangement(s) revealed 97% concordance. The mutation rates were identical by both platforms when using the same primer set (FR1), whereas a slight overestimation bias (+0.326%) was found when comparing FR1 with leader primers. However, for nearly all patients this did not affect the stratification into mutated or unmutated categories, suggesting that use of FR1 may provide comparable results if leader sequencing is not available and allowing for a simpler NGS laboratory workflow. In routine clinical practice (423 samples), the productive rearrangement was successfully detected by either primer set (leader, 97.7%; FR1, 94.7%), and a combination of both in problematic cases reduced the failure rate to 1.2%. Higher sensitivity of the NGS-based analysis also detected a higher frequency of double IGHV rearrangements (19.1%) compared with traditional approaches.

Charting a Course for Smartphones and Wearables to Transform Population Health Research.

The use of data from smartphones and wearable devices has huge potential for population health research, given the high level of device ownership; the range of novel health-relevant data types available from consumer devices; and the frequency and duration with which data are, or could be, collected. Yet, the uptake and success of large-scale mobile health research in the last decade have not met this intensely promoted opportunity. We make the argument that digital person-generated health data are required and necessary to answer many top priority research questions, using illustrative examples taken from the James Lind Alliance Priority Setting Partnerships. We then summarize the findings from 2 UK initiatives that considered the challenges and possible solutions for what needs to be done and how such solutions can be implemented to realize the future opportunities of digital person-generated health data for clinically important population health research. Examples of important areas that must be addressed to advance the field include digital inequality and possible selection bias; easy access for researchers to the appropriate data collection tools, including how best to harmonize data items; analysis methodologies for time series data; patient and public involvement and engagement methods for optimizing recruitment, retention, and public trust; and methods for providing research participants with greater control over their data. There is also a major opportunity, provided through the linkage of digital person-generated health data to routinely collected data, to support novel population health research, bringing together clinician-reported and patient-reported measures. We recognize that well-conducted studies need a wide range of diverse challenges to be skillfully addressed in unison (eg, challenges regarding epidemiology, data science and biostatistics, psychometrics, behavioral and social science, software engineering, user interface design, information governance, data management, and patient and public involvement and engagement). Consequently, progress would be accelerated by the establishment of a new interdisciplinary community where all relevant and necessary skills are brought together to allow for excellence throughout the life cycle of a research study. This will require a partnership of diverse people, methods, and technologies. If done right, the synergy of such a partnership has the potential to transform many millions of people's lives for the better.

Exploring the Cross-cultural Acceptability of Digital Tools for Pain Self-reporting: Qualitative Study.

BACKGROUND: Culture and ethnicity influence how people communicate about their pain. This makes it challenging to develop pain self-report tools that are acceptable across ethnic groups. OBJECTIVE: We aimed to inform the development of cross-culturally acceptable digital pain self-report tools by better understanding the similarities and differences between ethnic groups in pain experiences and self-reporting needs. METHODS: Three web-based workshops consisting of a focus group and a user requirement exercise with people who self-identified as being of Black African (n=6), South Asian (n=10), or White British (n=7) ethnicity were conducted. RESULTS: Across ethnic groups, participants shared similar lived experiences and challenges in communicating their pain to health care professionals. However, there were differences in beliefs about the causes of pain, attitudes toward pain medication, and experiences of how stigma and gender norms influenced pain-reporting behavior. Despite these differences, they agreed on important aspects for pain self-report, but participants from non-White backgrounds had additional language requirements such as culturally appropriate pain terminologies to reduce self-reporting barriers. CONCLUSIONS: To improve the cross-cultural acceptability and equity of digital pain self-report tools, future developments should address the differences among ethnic groups on pain perceptions and beliefs, factors influencing pain reporting behavior, and language requirements.

Examining the variability of multiple daily symptoms over time among individuals with multiple long-term conditions (MLTC-M/multimorbidity): An exploratory analysis of a longitudinal smartwatch feasibility study.

Introduction: People living with multiple long-term conditions (MLTC-M) (multimorbidity) experience a range of inter-related symptoms. These symptoms can be tracked longitudinally using consumer technology, such as smartphones and wearable devices, and then summarised to provide useful clinical insight. Aim: We aimed to perform an exploratory analysis to summarise the extent and trajectory of multiple symptom ratings tracked via a smartwatch, and to investigate the relationship between these symptom ratings and demographic factors in people living with MLTC-M in a feasibility study. Methods: 'Watch Your Steps' was a prospective observational feasibility study, administering multiple questions per day over a 90 day period. Adults with more than one clinician-diagnosed long-term condition rated seven core symptoms each day, plus up to eight additional symptoms personalised to their LTCs per day. Symptom ratings were summarised over the study period at the individual and group level. Symptom ratings were also plotted to describe day-to-day symptom trajectories for individuals. Results: Fifty two participants submitted symptom ratings. Half were male and the majority had LTCs affecting three or more disease areas (N = 33, 64%). The symptom rated as most problematic was fatigue. Patients with increased comorbidity or female sex seemed to be associated with worse experiences of fatigue. Fatigue ratings were strongly correlated with pain and level of dysfunction. Conclusion: In this study we have shown that it is possible to collect and descriptively analyse self reported symptom data in people living with MLTC-M, collected multiple times per day on a smartwatch, to gain insights that might support future clinical care and research.

Exploring the links between indoor air pollutants and health outcomes in South Asian countries: a systematic review.

Indoor air pollution (IAP) has adverse effects on the health of people, globally. The objective of this systematic review was to present the range of health problems studied in association with indoor air pollutants in South Asian countries. We searched five databases, including PubMed, Web of Science, Scopus, Google Scholar, and CAB Direct for articles published between the years 2000 and 2020. We retrieved 5,810 articles, out of which we included 90 articles in our review. Among South Asian countries, only five countries have published results related to relationship between indoor air pollutants and adverse health conditions. All studies have shown adversity of indoor air pollutants on human's health. We found indoor solid fuel burning as a key source of indoor air pollution in the included studies, while women and children were most affected by their exposure to solid fuel burning. More than half of the studies accounted particulate matter responsible for indoor air pollution bearing negative health effects. In the included studies, eyes and lungs were the most commonly affected body organs, exhibiting common symptoms like cough, breathing difficulty and wheezing. This might have developed into common conditions like respiratory tract infection, chronic obstructive pulmonary diseases and eye cataract. In addition to promote research in South Asian countries, future research should focus on novel digital ways of capturing effects of indoor air pollutants among vulnerable segments of the population. As a result of this new knowledge, public health agencies should develop and test interventions to reduce people's exposure levels and prevent them to develop adverse health outcomes.

Immune-checkpoint inhibitor therapy response evaluation using oncophysics-based mathematical models.

The field of oncology has transformed with the advent of immunotherapies. The standard of care for multiple cancers now includes novel drugs that target key checkpoints that function to modulate immune responses, enabling the patient's immune system to elicit an effective anti-tumor response. While these immune-based approaches can have dramatic effects in terms of significantly reducing tumor burden and prolonging survival for patients, the therapeutic approach remains active only in a minority of patients and is often not durable. Multiple biological investigations have identified key markers that predict response to the most common form of immunotherapy-immune checkpoint inhibitors (ICI). These biomarkers help enrich patients for ICI but are not 100% predictive. Understanding the complex interactions of these biomarkers with other pathways and factors that lead to ICI resistance remains a major goal. Principles of oncophysics-the idea that cancer can be described as a multiscale physical aberration-have shown promise in recent years in terms of capturing the essence of the complexities of ICI interactions. Here, we review the biological knowledge of mechanisms of ICI action and how these are incorporated into modern oncophysics-based mathematical models. Building on the success of oncophysics-based mathematical models may help to discover new, rational methods to engineer immunotherapy for patients in the future. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Charting a course for smartphones and wearables to transform population health research.

The use of data from smartphones and wearable devices has huge potential for population health research given high device ownership, the range of novel health-relevant data types available from consumer devices, and the frequency and duration over which data are, or could be, collected. Yet the uptake and success of large-scale mobile health research in the last decade has not matched the hyped opportunity. We make the argument that digital person-generated health data is required and necessary to answer many top priority research questions through illustrative examples taken from the James Lind Alliance Priority Setting Partnership. We then summarise the findings from two UK initiatives that considered the challenges and possible solutions for what needs to be done, and in what way, to realise the future opportunities of digital person-generated health data for clinically important population health research. Examples of important areas to be addressed to advance the field include digital inequality and addressing possible selection bias, easy access for researchers to the appropriate data collection tools including how best to harmonise data items, analysis methodology for time series data, methods for patient and public involvement and engagement to optimise recruitment, retention and public trust, and providing greater control of their data to research participants. There is also a major opportunity through the linkage of digital persongenerated health data to routinely-collected data to support novel population health research, bringing together clinician-reported and patient-reported measures. We recognise that well conducted studies need a wide range of diverse challenges to be skilfully addressed in unison: for example, epidemiology, data science and biostatistics, psychometrics, behavioural and social science, software engineering, user interface design, information governance, data management and patient and public involvement and engagement. Consequently, progress would be accelerated by the establishment of a new interdisciplinary community where all relevant and necessary skills are brought together to allow excellence throughout the lifecycle of a research study. This will require a partnership of diverse people, of methods and of technology. Get this right and the synergy has the potential to transform many millions of people's lives for the better.

FAP-Specific Signalling Is an Independent Diagnostic Approach in ACC and Not a Surrogate Marker of MRI Sequences.

BACKGROUND: Fibroblast Activation Protein (FAP) is a new target for positron emission tomography and computed tomography (PET/CT) imaging of epithelial tumours embedded in a fibrous stroma. Adenoid cystic carcinomas (ACCs) have shown elevated tracer uptake in 68Gallium (68Ga)-labelled FAPIs in previous studies. The current gold standard for ACC imaging is contrast-enhanced (ce) MRI, where intertumoural heterogeneity leads to variable appearance on T1-weighted (T1w) and T2-weighted (T2w) images. In this retrospective analysis, we correlated 68Ga-FAPI PET signalling at three time points with ceT1w and T2w MRI signals to further characterise the significance of 68Ga-FAPI uptake in ACCs. METHODS: Clinical PET/CT scans of 12 ACC patients were performed at 10, 60 and 180 min post i.v. administration of 68Ga-labelled-FAPI tracer molecules. 68Ga-PET- and corresponding MRI-scans were co-registered, and 3D volumetric segmentations were performed on ceT1w and T2w lesions of co-registered MRI slides. Signal intensity values of 68Ga-FAPI PET signalling and ceT1w/T2w MRI scans were analysed for their pixelwise correlation in each patient. Pooled estimates of the correlation coefficients were calculated using the Fisher z-transformation. RESULTS: 68Ga-FAPI PET signals showed a very weak positive correlation with ceT1w values (pooled correlation 0.114, 0.147 and 0.162 at 10, 60 and 180 min) and a weak negative correlation with T2w values (pooled correlation -0.148, -0.121 and -0.225 at 10, 60 and 180 min). Individual r-values at 60 min ranged from -0.130 to 0.434 in ceT1w and from -0.466 to 0.637 in T2w MRI scans. CONCLUSION: There are only slight correlations between the intensity of 68Ga-FAPI PET signals and tumour appearance in ceT1w or T2w MRI scans, which underlines that 68Ga-FAPI PET signalling is not a surrogate marker of MRI sequences but an independent signal.

Adoption of Digital Pain Manikins for Research Data Collection: A Systematic Review.

Chronic pain is common and disabling. Researchers need robust methods to collect pain data in large populations to enhance knowledge on pain prevalence, causes and treatment. Digital pain manikins address this by enabling self-reporting of location-specific pain. However, it is unknown to what extent pain studies adopted digital manikins for data collection. Therefore, we systematically searched the literature. We included 17 studies. Most were published after 2017, collected pain data cross-sectionally in ≥50 participants, and reported pain distribution and pain extent as manikin-derived summary metrics. Across the studies, 13 unique manikins were used, of which four had been evaluated. Our review shows that adoption of digital pain manikins in research settings has been slow. Harnessing the digital nature of manikins, enabling use of personal devices, and assessing and improving the reliability, validity and responsiveness of digital manikins will expedite their adoption as digital data collection tools for pain research.