Wide-Awake Hand Trauma Surgery: Designing Strategies to Optimise Patient Experience.

INTRODUCTION: The regional hand trauma service in Greater Manchester, United Kingdom, underwent significant reorganisation early in the COVID-19 pandemic, with a shift from predominantly general anaesthesia (GA) procedures to the adoption of a Wide-Awake Local Anaesthetic No Tourniquet (WALANT) technique. We implemented strategies targeted towards optimising patient experience, largely applicable to most healthcare settings. METHODS: Four domains were explored: (i) compliance in timing to nationally agreed treatment guidelines, (ii) the role of patient information leaflets, (iii) the introduction of a post-operative analgesia protocol, and (iv) broadly evaluating the environmental impact following the implementation of a same-day 'see and treat' service. RESULTS: Following reorganisation to a predominantly WALANT service, we observed an increase in compliance with nationally agreed standards for the treatment of common hand injuries. Patient education and peri-operative counselling reduced anxiety, whereas post-operative pain was better managed with the introduction of an analgesic protocol. Using a travel carbon calculator, it can be inferred that there are significant reductions in carbon emissions generated when patients are evaluated and treated on the same day as their clinical presentation. CONCLUSIONS: It is widely acknowledged that WALANT benefits patients and the healthcare system. We contemplated whether further incremental changes in clinical practice could further improve patient experience. Given our findings, we advocate a multi-modal approach with a greater focus on patient outcomes (trials are currently underway, e.g., WAFER) supplemented by universally accepted validated patient-reported outcome measures (PROMs).

Using machine learning to automatically measure kyphotic and lordotic angle measurements on radiographs for children with adolescent idiopathic scoliosis.

Measuring the kyphotic angle (KA) and lordotic angle (LA) on lateral radiographs is important to truly diagnose children with adolescent idiopathic scoliosis. However, it is a time-consuming process to measure the KA because the endplate of the upper thoracic vertebra is normally difficult to identify. To save time and improve measurement accuracy, a machine learning algorithm was developed to automatically extract the KA and LA. The accuracy and reliability of the T1-T12 KA, T5-T12 KA, and L1-L5 LA were reported. A convolutional neural network was trained using 100 radiographs with data augmentation to segment the T1-L5 vertebrae. Sixty radiographs were used to test the method. Accuracy and reliability were reported using the percentage of measurements within clinical acceptance (≤9°), standard error of measurement (SEM), and inter-method intraclass correlation coefficient (ICC2,1). The automatic method detected 95 % (57/60), 100 %, and 100 % for T1-T12 KA, T5-T12 KA, and L1-L5 LA, respectively. The clinical acceptance rate, SEM, and ICC2,1 for T1-T12 KA, T5-T12 KA, and L1-L5 LA were (98 %, 0.80°, 0.91), (75 %, 4.08°, 0.60), and (97 %, 1.38°, 0.88), respectively. The automatic method measured quickly with an average of 4 ± 2 s per radiograph and illustrated how measurements were made on the image, allowing verifications by clinicians.

Does Secondary Mechanical Manipulation of Lipoaspirate Enhance the Vasculogenic Potential of Fat Grafts? A Systematic Review.

BACKGROUND: Fat grafting is a highly versatile option in the reconstructive armamentarium but with unpredictable retention rates and outcomes. The primary outcome of this systematic review was to assess whether secondary mechanically processed lipoaspirate favorably enhances the vasculogenic potential of fat grafts when compared to unprocessed lipoaspirate or fat grafts prepared using centrifugation alone. The secondary outcome was to assess the evidence around graft retention and improved outcomes when comparing the aforementioned groups. METHODS: A search on MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted up to February 2022. All human and animal research, which provided a cross-comparison between unprocessed, centrifuged, secondary mechanically fragmented (SMF) or secondary mechanically disrupted (SMD) fat grafts, was included. RESULTS: Thirty-one full texts were included. Vasculogenic potential was assessed by quantification of angiogenic growth factors and cellular composition. Cellular composition of mesenchymal stem cells, perivascular stem cells, and endothelial progenitor cells was quantified by fluorescence activated cell sorting (FACS) analysis. Fat graft volume retention rates and fat grafting to aid wound healing were assessed. Although the presence of industry-funded studies and inadequate reporting of methodological data in some studies were sources of bias, data showed SMF grafts contain an enriched pericyte population with increased vascular endothelial growth factor (VEGF) secretion. Animal studies indicate that SMD grafts may increase rates of fat graft retention and wound closure compared to centrifuged grafts; however, clinical studies are yet to show similar results. CONCLUSIONS: In this systematic review, we were able to conclude that the existing literature suggests mechanically processing fat, whether it be through fragmentation or disruption, improves vasculogenic potential by enhancing angiogenic growth factor and relevant vascular progenitor cell levels. Whilst in vivo animal studies are scarce, the review findings suggest that secondary mechanically processed fat enhances fat graft retention and can aid with wound healing. Further clinical studies are required to assess potential differences in human studies.

ERCC2 mutations alter the genomic distribution pattern of somatic mutations and are independently prognostic in bladder cancer.

Excision repair cross-complementation group 2 (ERCC2) encodes the DNA helicase xeroderma pigmentosum group D, which functions in transcription and nucleotide excision repair. Point mutations in ERCC2 are putative drivers in around 10% of bladder cancers (BLCAs) and a potential positive biomarker for cisplatin therapy response. Nevertheless, the prognostic significance directly attributed to ERCC2 mutations and its pathogenic role in genome instability remain poorly understood. We first demonstrated that mutant ERCC2 is an independent predictor of prognosis in BLCA. We then examined its impact on the somatic mutational landscape using a cohort of ERCC2 wild-type (n = 343) and mutant (n = 39) BLCA whole genomes. The genome-wide distribution of somatic mutations is significantly altered in ERCC2 mutants, including T[C>T]N enrichment, altered replication time correlations, and CTCF-cohesin binding site mutation hotspots. We leverage these alterations to develop a machine learning model for predicting pathogenic ERCC2 mutations, which may be useful to inform treatment of patients with BLCA.

Expanded PAH analysis of household air pollution in a rural region of China with high lung cancer incidence.

The domestic combustion of locally sourced smoky (bituminous) coal in Xuanwei and Fuyuan counties, China, is responsible for some of the highest lung cancer rates in the world. Recent research has pointed to methylated PAHs (mPAHs), particularly 5-methylchrysene (5MC), within coal combustion products as a driving factor. Here we describe measurements of mPAHs in Xuanwei and Fuyuan derived from controlled burnings (i.e., water boiling tests, WBT, n = 27) representing exposures during stove use, and an exposure assessment (EA) study (n=116) representing 24 h weighted exposures. Using smoky coal leads to significantly higher concentrations of known and likely human carcinogens than using smokeless coal, including 5MC (3.7 ng/m3 vs. 1.0 ng/m3 for EA samples and 100.8 ng/m3 vs. 2.2 ng/m3 for WBT samples), benzo[a]pyrene (38.0 ng/m3 vs. 7.9 ng/m3 for EA samples and 455.3 ng/m3 vs. 12.0 ng/m3 for WBT samples), and 7,12-dimethylbenz[a]anthracene (1.9 ng/m3 vs. 0.2 ng/m3 for EA samples and 47.7 ng/m3 vs. 0.6 ng/m3 for WBT samples). Mixed effect models for both EA samples and WBT samples revealed clear variation in mPAHs concentrations depending on smoky coal source while stove ventilation was consistently found to reduce measured concentrations (by up to nine fold and 65 fold for EA and WBT samples respectively when using smoky coal). Fuel type had a larger influence on mPAHs concentrations than stove type. These findings indicate that users of smoky coal experience exposure to many PAHs, including known and suspected human carcinogens (especially during cooking activities), many of which are not routinely tested for. Collectively, this provides insights into the potential etiologies of lung cancer in the region and further highlights the importance of clean fuel transitions and stove refinements as the final goal for reducing household air pollution and its associated health risks.

Validity and accuracy of automatic cobb angle measurement on 3D spinal ultrasonographs for children with adolescent idiopathic scoliosis: SOSORT 2024 award winner.

PURPOSE: Ultrasonography for scoliosis is a novel imaging method that does not expose children with adolescent idiopathic scoliosis (AIS) to radiation. A single ultrasound scan provides 3D spinal views directly. However, measuring ultrasonograph parameters is challenging, time-consuming, and requires considerable training. This study aimed to validate a machine learning method to measure the coronal curve angle on ultrasonographs automatically. METHODS: A total of 144 3D spinal ultrasonographs were extracted to train and validate a machine learning model. Among the 144 images, 70 were used for training, and 74 consisted of 144 curves for testing. Automatic coronal curve angle measurements were validated by comparing them with manual measurements performed by an experienced rater. The inter-method intraclass correlation coefficient (ICC2,1), standard error of measurement (SEM), and percentage of measurements within clinical acceptance (≤ 5°) were analyzed. RESULTS: The automatic method detected 125/144 manually measured curves. The averages of the 125 manual and automatic coronal curve angle measurements were 22.4 ± 8.0° and 22.9 ± 8.7°, respectively. Good reliability was achieved with ICC2,1 = 0.81 and SEM = 1.4°. A total of 75% (94/125) of the measurements were within clinical acceptance. The average measurement time per ultrasonograph was 36 ± 7 s. Additionally, the algorithm displayed the predicted centers of laminae to illustrate the measurement. CONCLUSION: The automatic algorithm measured the coronal curve angle with moderate accuracy but good reliability. The algorithm's quick measurement time and interpretability can make ultrasound a more accessible imaging method for children with AIS. However, further improvements are needed to bring the method to clinical use.

Nonspecific Signs and/or Symptoms of Cancer: A Retrospective, Observational Analysis from a Secondary Care, US Community Oncology Dataset.

To help determine the unmet need for improved diagnostic tools to evaluate patients with nonspecific signs and/or symptoms (NSSS) and suspicion of cancer, we examined patient characteristics, diagnostic journey, and cancer incidence of patients with NSSS within The US Oncology Network (The Network), a secondary care community oncology setting. This retrospective, observational cohort study included patients aged ≥40 years with ≥1 NSSS in their problem list at their first visit within The Network (the index date) between 1 January 2016 and 31 December 2020. Patients were followed longitudinally with electronic health record data for initial cancer diagnosis, new noncancer diagnosis, death, end of study observation period, or 12 months, whichever occurred first. Of 103,984 patients eligible for inclusion, 96,722 presented with only 1 NSSS at index date; 6537/103,984 (6.3%) were diagnosed with 1 primary cancer within 12 months after the index date; 3825/6537 (58.5%) with hematologic malignancy, and 2712/6537 (41.5%) with solid tumor. Among patients diagnosed with cancer (n = 6774), the median time to cancer diagnosis after their first visit within The Network was 5.13 weeks. This study provides a real-world perspective on cancer incidence in patients with NSSS referred to a secondary care setting and highlights the unmet need for improved diagnostic tools to improve cancer outcomes.

R-loop resolution by ARIP4 helicase promotes androgen-mediated transcription induction.

Pausing of RNA polymerase II (Pol II) at transcription start sites (TSSs) primes target genes for productive elongation. Coincidentally, DNA double-strand breaks (DSBs) enrich at highly transcribed and Pol II-paused genes, although their interplay remains undefined. Using androgen receptor (AR) signaling as a model, we have uncovered AR-interacting protein 4 (ARIP4) helicase as a driver of androgen-dependent transcription induction. Chromatin immunoprecipitation sequencing analysis revealed that ARIP4 preferentially co-occupies TSSs with paused Pol II. Moreover, we found that ARIP4 complexes with topoisomerase II beta and mediates transient DSB formation upon hormone stimulation. Accordingly, ARIP4 deficiency compromised release of paused Pol II and resulted in R-loop accumulation at a panel of highly transcribed AR target genes. Last, we showed that ARIP4 binds and unwinds R-loops in vitro and that its expression positively correlates with prostate cancer progression. We propose that androgen stimulation triggers ARIP4-mediated unwinding of R-loops at TSSs, enforcing Pol II pause release to effectively drive an androgen-dependent expression program.

Epigenetic developmental mechanisms underlying sex differences in cancer.

Cancer risk is modulated by hereditary and somatic mutations, exposures, age, sex, and gender. The mechanisms by which sex and gender work alone and in combination with other cancer risk factors remain underexplored. In general, cancers that occur in both the male and female sexes occur more commonly in XY compared with XX individuals, regardless of genetic ancestry, geographic location, and age. Moreover, XY individuals are less frequently cured of their cancers, highlighting the need for a greater understanding of sex and gender effects in oncology. This will be necessary for optimal laboratory and clinical cancer investigations. To that end, we review the epigenetics of sexual differentiation and its effect on cancer hallmark pathways throughout life. Specifically, we will touch on how sex differences in metabolism, immunity, pluripotency, and tumor suppressor functions are patterned through the epigenetic effects of imprinting, sex chromosome complement, X inactivation, genes escaping X inactivation, sex hormones, and life history.

Automated Detection of In-Home Activities with Ultra-Wideband Sensors.

As Canada's population of older adults rises, the need for aging-in-place solutions is growing due to the declining quality of long-term-care homes and long wait times. While the current standards include questionnaire-based assessments for monitoring activities of daily living (ADLs), there is an urgent need for advanced indoor localization technologies that ensure privacy. This study explores the use of Ultra-Wideband (UWB) technology for activity recognition in a mock condo in the Glenrose Rehabilitation Hospital. UWB systems with built-in Inertial Measurement Unit (IMU) sensors were tested, using anchors set up across the condo and a tag worn by patients. We tested various UWB setups, changed the number of anchors, and varied the tag placement (on the wrist or chest). Wrist-worn tags consistently outperformed chest-worn tags, and the nine-anchor configuration yielded the highest accuracy. Machine learning models were developed to classify activities based on UWB and IMU data. Models that included positional data significantly outperformed those that did not. The Random Forest model with a 4 s data window achieved an accuracy of 94%, compared to 79.2% when positional data were excluded. These findings demonstrate that incorporating positional data with IMU sensors is a promising method for effective remote patient monitoring.

Regional differences in heart failure risk in the United Kingdom are partially explained by biological aging.

Background: Heart failure (HF) risk is greater in rural versus urban regions in the United States (US), potentially due to differences in healthcare coverage and access. Whether this excess risk applies to countries with universal healthcare is unclear and the underlying biological mechanisms are unknown. In the prospective United Kingdom (UK) Biobank, we investigated urban-rural regional differences in HF risk and the mechanistic role of biological aging. Methods: Multivariable Cox regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HF in relation to residential urban-rural region and a Biological Health Score (BHS) that reflects biological aging from environmental, social, or dietary stressors. We estimated the proportion of the total effect of urban-rural region on HF mediated through BHS. Results: Among 417,441 European participants, 10,332 incident HF cases were diagnosed during the follow-up. Compared to participants in large urban regions of Scotland, those in England/Wales had significantly increased HF risk (smaller urban: HR = 1.83, 95%CI: 1.64-2.03; suburban: HR = 1.77, 95%CI: 1.56-2.01; very rural: HR = 1.61, 95%CI: 1.39-1.85). Additionally, we found a dose-response relationship between increased biological aging and HF risk (HRper 1 SD increase = 1.14 (95%CI: 1.12-1.17). Increased biological aging mediated a notable 6.6% (p < 0.001) of the total effect of urban-rural region on HF. Conclusion: Despite universal healthcare in the UK, disparities in HF risk by region were observed and may be partly explained by environmental, social, or dietary factors related to biological aging. Our study contributes to precision public health by informing potential biological targets for intervention.

Associations between mosaic loss of sex chromosomes and incident hospitalization for atrial fibrillation in the United Kingdom.

Background: Mosaic loss of chromosome Y (mLOY) in leukocytes of men reflects genomic instability from aging, smoking, and environmental exposures. A similar mosaic loss of chromosome X (mLOX) occurs among women. However, the associations between mLOY, mLOX, and risk of incident heart diseases are unclear. Methods: We estimated associations between mLOY, mLOX, and risk of incident heart diseases requiring hospitalization, including atrial fibrillation, myocardial infarction, ischemic heart disease, cardiomyopathy, and heart failure. We analyzed 190,613 men and 224,853 women with genotyping data from the UK Biobank. Among these participants, we analyzed 37,037 men with mLOY and 13,978 women with mLOX detected using Mosaic Chromosomal Alterations caller. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of each incident heart disease in relation to mLOY in men and mLOX in women. Additionally, Mendelian randomization (MR) was conducted to estimate causal associations. Results: Among men, detectable mLOY was associated with elevated risk of atrial fibrillation (HR=1.06, 95%CI:1.03-1.11). The associations were apparent in both never-smokers (HR=1.07, 95%:1.01-1.14) and ever-smokers (HR=1.05, 95%CI:1.01-1.11) as well as men > and ≤60 years of age. MR analyses supported causal associations between mLOY and atrial fibrillation (HRMR-PRESSO=1.15, 95%CI:1.13-1.18). Among post-menopausal women, we found a suggestive inverse association between detectable mLOX and atrial fibrillation risk (HR=0.90, 95%CI:0.83-0.98). However, associations with mLOY and mLOX were not found for other heart diseases. Conclusions: Our findings suggest that mLOY and mLOX reflect sex-specific biological processes or exposure profiles related to incident atrial fibrillation requiring hospitalization.

Longitudinal evolution of the HIV effective reproduction number following sequential expansion of treatment as prevention and pre-exposure prophylaxis in British Columbia, Canada: a population-level programme evaluation.

BACKGROUND: Treatment as prevention and pre-exposure prophylaxis (PrEP) are key strategies in the control of HIV/AIDS. We aimed to characterise the longitudinal effects of antiretroviral therapy (ART), followed by treatment as prevention and the addition of PrEP, on the HIV effective reproduction number (Re) in British Columbia, Canada. METHODS: This population-level programme evaluation used data from the Drug Treatment Program of the British Columbia Centre for Excellence in HIV/AIDS (Vancouver, British Columbia, Canada). We also used estimates of HIV incidence and prevalence from the Public Health Agency of Canada, data on the number of new HIV diagnoses per year from the British Columbia Centre for Disease Control, and mortality data from the British Columbia Vital Statistics Agency. Data were obtained from 1985 until 2022, depending on the database source. Outcomes were the annual HIV prevalence, HIV incidence, number of new HIV diagnoses, number of people living with HIV on ART, HIV/AIDS-related and all-cause mortality rates, the HIV incidence-to-all-cause-mortality ratio, and Re. We calculated the modified effective reproduction number (Rme) using two thresholds of viral suppression and compared these values with Re. FINDINGS: We found a 95% decline in HIV/AIDS-related mortality and a 91% decrease in HIV incidence over the study period. The Re progressively declined from 1996 to 2022; however, from 1996 to 2017, Rme remained stable (>1) when calculated for people living with HIV with unsuppressed viraemia, suggesting that treatment as prevention reduces HIV incidence by decreasing the pool of individuals who are potentially able to transmit the virus. From 2018 to 2022, a decline in the estimated Re and Rme (<1) was observed regardless of whether we considered all people living with HIV or only those who were virologically unsuppressed. This finding suggests that PrEP decreases HIV incidence by reducing the number of susceptible individuals in the community, independently of viral suppression. INTERPRETATION: Our results show the synergy between generalised treatment as prevention and targeted PrEP in terms of decreasing HIV incidence. These findings support the incorporation of longitudinal monitoring of Re at a programmatic level to identify opportunities for the optimisation of treatment-as-prevention and PrEP programmes. FUNDING: British Columbia Ministry of Health, Health Canada, Public Health Agency of Canada, Vancouver Coastal Health, Vancouver General Hospital Foundation, Genome British Columbia, and the Canadian Institutes of Health Research.

Identifying Pertinent Digital Health Topics to Incorporate into Self-Care Pharmacy Education.

The ever-evolving landscape of digital health technology has dramatically enhanced patients' ability to manage their health through self-care effectively. These advancements have created various categories of self-care products, including medication management, health tracking, and wellness. There is no published research regarding integrating digital health into pharmacy self-care courses. This study aims to identify pertinent digital health devices and applications to incorporate into self-care course education. Digital health limitations, challenges incorporating digital health in self-care pharmacy education, and potential solutions are also reviewed. In conducting this research, many resources, including PubMed, APhA, ASHP, fda.gov, and digital.health, were reviewed in March 2024 to gather information on digital health devices and applications. To supplement this, targeted keyword searches were conducted on topics such as "digital health", "devices", "applications", "technology", and "self-care" across various online platforms. We identified digital health devices and applications suitable for self-care education across eight topics, as follows: screening, insomnia, reproductive disorders, eye disorders, home medical equipment, GI disorders, pediatrics, and respiratory disorders. Among these topics, wellness screening had the most digital health products available. For all other topics, at least three or more products were identified as relevant to self-care curriculum. By equipping students with digital health knowledge, they can effectively apply it in patient care throughout their rotations and future practice. Many digital health products, including telemedicine, electronic health records, mobile health applications, and wearable devices, are ideal for inclusion in pharmacy curriculum as future educational material. Future research is needed to develop the best strategies for incorporating relevant digital health into self-care education and defining the best student-learning strategies.

Epigenome-wide association study of lung cancer among never smokers in two prospective cohorts in Shanghai, China.

BACKGROUND: The aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted. METHODS: We conducted a nested case-control study of 80 never-smoking incident lung cancer cases and 83 never-smoking controls within the Shanghai Women's Health Study and Shanghai Men's Health Study. DNAm was measured in prediagnostic oral rinse samples using Illumina MethylationEPIC array. Initially, we conducted an EWAS to identify differentially methylated positions (DMPs) associated with lung cancer in the discovery sample of 101 subjects. The top 50 DMPs were further evaluated in a replication sample of 62 subjects, and results were pooled using fixed-effect meta-analysis. RESULTS: Our study identified three DMPs significantly associated with lung cancer at the epigenome-wide significance level of p<8.22×10-8. These DMPs were identified as cg09198866 (MYH9; TXN2), cg01411366 (SLC9A10) and cg12787323. Furthermore, examination of the top 1000 DMPs indicated significant enrichment in epithelial regulatory regions and their involvement in small GTPase-mediated signal transduction pathways. Additionally, GrimAge acceleration was identified as a risk factor for lung cancer (OR=1.19 per year; 95% CI 1.06 to 1.34). CONCLUSIONS: While replication in a larger sample size is necessary, our findings suggest that DNAm patterns in prediagnostic oral rinse samples could provide novel insights into the underlying mechanisms of lung cancer in never smokers.

Impact of the COVID-19 Pandemic on Hepatitis C Treatment Initiation in British Columbia, Canada: An Interrupted Time Series Study.

We investigated the impacts of the COVID-19 pandemic on hepatitis C (HCV) treatment initiation, including by birth cohort and injection drug use status, in British Columbia (BC), Canada. Using population data from the BC COVID-19 Cohort, we conducted interrupted time series analyses, estimating changes in HCV treatment initiation following the introduction of pandemic-related policies in March 2020. The study included a pre-policy period (April 2018 to March 2020) and three follow-up periods (April to December 2020, January to December 2021, and January to December 2022). The level of HCV treatment initiation decreased by 26% in April 2020 (rate ratio 0.74, 95% confidence interval [CI] 0.60 to 0.91). Overall, no statistically significant difference in HCV treatment initiation occurred over the 2020 and 2021 post-policy periods, and an increase of 34.4% (95% CI 0.6 to 75.8) occurred in 2022 (equating to 321 additional people initiating treatment), relative to expectation. Decreases in HCV treatment initiation occurred in 2020 for people born between 1965 and 1974 (25.5%) and people who inject drugs (24.5%), relative to expectation. In summary, the pandemic was associated with short-term disruptions in HCV treatment initiation in BC, which were greater for people born 1965 to 1974 and people who inject drugs.

Vaccine Hesitancy among Immigrants: A Narrative Review of Challenges, Opportunities, and Lessons Learned.

(1) Background: Vaccination reluctance is a major worldwide public health concern as it poses threats of disease outbreaks and strains on healthcare systems. While some studies have examined vaccine uptake within specific countries, few provide an overview of the barriers and trends among migrant groups. To fill this knowledge gap, this narrative review analyzes immunization patterns and vaccine hesitancy among immigrant populations. (2) Methods: Four researchers independently evaluated the quality and bias risk of the 18 identified articles using validated critical appraisal tools. (3) Results: Most studies focused on vaccine hesitancy among migrants in the United States and Canada, with a higher COVID-19 vaccine reluctance than native-born residents. Contributing factors to this hesitancy include demographics, cultural views, obstacles to healthcare access, financial hardship, and distrust in health policies. Additionally, immigrants in North America and Europe face unfair vaccine challenges due to misinformation, safety concerns, personal perspectives, language barriers, immigration status, and restricted healthcare access. (4) Conclusions: Tailored vaccine education programs and outreach campaigns sensitive to immigrants' diversity should be developed to address this issue. It is also important to investigate community-specific obstacles and assess the long-term sustainability of current efforts to promote vaccination among marginalized migrant groups. Further research into global immunization disparities among immigrant populations is crucial.

A nested case-control study of untargeted plasma metabolomics and lung cancer among never-smoking women within the prospective Shanghai Women's Health Study.

The etiology of lung cancer in never-smokers remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Here, we aimed to enhance our understanding of lung cancer pathogenesis among never-smokers using untargeted metabolomics. This nested case-control study included 395 never-smoking women who developed lung cancer and 395 matched never-smoking cancer-free women from the prospective Shanghai Women's Health Study with 15,353 metabolic features quantified in pre-diagnostic plasma using liquid chromatography high-resolution mass spectrometry. Recognizing that metabolites often correlate and seldom act independently in biological processes, we utilized a weighted correlation network analysis to agnostically construct 28 network modules of correlated metabolites. Using conditional logistic regression models, we assessed the associations for both metabolic network modules and individual metabolic features with lung cancer, accounting for multiple testing using a false discovery rate (FDR) < 0.20. We identified a network module of 121 features inversely associated with all lung cancer (p = .001, FDR = 0.028) and lung adenocarcinoma (p = .002, FDR = 0.056), where lyso-glycerophospholipids played a key role driving these associations. Another module of 440 features was inversely associated with lung adenocarcinoma (p = .014, FDR = 0.196). Individual metabolites within these network modules were enriched in biological pathways linked to oxidative stress, and energy metabolism. These pathways have been implicated in previous metabolomics studies involving populations exposed to known lung cancer risk factors such as traffic-related air pollution and polycyclic aromatic hydrocarbons. Our results suggest that untargeted plasma metabolomics could provide novel insights into the etiology and risk factors of lung cancer among never-smokers.