Opening the doors of precision medicine: novel tools to assess intestinal barrier in inflammatory bowel disease and colitis-associated neoplasia.

Mounting evidence underscores the pivotal role of the intestinal barrier and its convoluted network with diet and intestinal microbiome in the pathogenesis of inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CRC). Moreover, the bidirectional association of the intestinal barrier with the liver and brain, known as the gut-brain axis, plays a crucial role in developing complications, including extraintestinal manifestations of IBD and CRC metastasis. Consequently, barrier healing represents a crucial therapeutic target in these inflammatory-dependent disorders, with barrier assessment predicting disease outcomes, response to therapy and extraintestinal manifestations.New advanced technologies are revolutionising our understanding of the barrier paradigm, enabling the accurate assessment of the intestinal barrier and aiding in unravelling the complexity of the gut-brain axis. Cutting-edge endoscopic imaging techniques, such as ultra-high magnification endocytoscopy and probe-based confocal laser endomicroscopy, are new technologies allowing real-time exploration of the 'cellular' intestinal barrier. Additionally, novel advanced spatial imaging technology platforms, including multispectral imaging, upconversion nanoparticles, digital spatial profiling, optical spectroscopy and mass cytometry, enable a deep and comprehensive assessment of the 'molecular' and 'ultrastructural' barrier. In this promising landscape, artificial intelligence plays a pivotal role in standardising and integrating these novel tools, thereby contributing to barrier assessment and prediction of outcomes.Looking ahead, this integrated and comprehensive approach holds the promise of uncovering new therapeutic targets, breaking the therapeutic ceiling in IBD. Novel molecules, dietary interventions and microbiome modulation strategies aim to restore, reinforce, or modulate the gut-brain axis. These advancements have the potential for transformative and personalised approaches to managing IBD.

National survey of patient perspectives on cost discussions among recipients of copay assistance.

BACKGROUND: Individuals with cancer and other medical conditions often experience financial concerns from high costs-of-care and may utilize copay assistance programs (CAP). We sought to describe CAP recipients' experiences/preferences for cost discussions with clinicians. METHODS: We conducted a national, cross-sectional electronic-survey from 10/2022 to 11/2022 of CAP recipients with cancer or autoimmune conditions to assess patient perspectives on cost discussions. We used multivariable logistic regression models to explore associations of patient perspectives on cost discussions with patient characteristics and patient-reported outcomes (eg, financial toxicity, depression/anxiety, and health literacy). RESULTS: Among 1,566 participants, 71% had cancer and 29% had autoimmune conditions. Although 62% of respondents desired cost discussions, only 32% reported discussions took place. Additionally, 52% of respondents wanted their doctor to consider out-of-pocket costs when deciding the best treatment, and 61% of respondents felt doctors should ensure patients can afford treatment prescribed. Participants with depression symptoms were more likely to want doctors to consider out-of-pocket costs (OR = 1.54, P = .005) and to believe doctors should ensure patients can afford treatment (OR = 1.60, P = .005). Those with severe financial toxicity were more likely to desire cost discussions (OR = 1.65, P < .001) and want doctors to consider out-of-pocket costs (OR = 1.52, P = .001). Participants with marginal/inadequate health literacy were more likely to desire cost discussions (OR = 1.37, P = .01) and believe doctors should ensure patients can afford treatment (OR = 1.30, P = .036). CONCLUSIONS: In this large sample of CAP recipients with cancer and autoimmune conditions, most reported a desire for cost discussions, but under one-third reported such discussions took place.

Artificial intelligence and machine learning for clinical pharmacology.

Artificial intelligence (AI) will impact many aspects of clinical pharmacology, including drug discovery and development, clinical trials, personalized medicine, pharmacogenomics, pharmacovigilance and clinical toxicology. The rapid progress of AI in healthcare means clinical pharmacologists should have an understanding of AI and its implementation in clinical practice. As with any new therapy or health technology, it is imperative that AI tools are subject to robust and stringent evaluation to ensure that they enhance clinical practice in a safe and equitable manner. This review serves as an introduction to AI for the clinical pharmacologist, highlighting current applications, aspects of model development and issues surrounding evaluation and deployment. The aim of this article is to empower clinical pharmacologists to embrace and lead on the safe and effective use of AI within healthcare.

E-cigarette 'tobacco flavor', how do I name thee? Let me count the ways.

INTRODUCTION: In recent years, hundreds of jurisdictions around the world have enacted policies that prohibit sales of flavored e-cigarettes. In most cases, these jurisdictions permit the sale of tobacco flavored e-cigarettes. We sought to understand how tobacco flavor in e-cigarette advertisements were presented. METHODS: Our sample included 2,966 US English language e-cigarette ads compiled by a market research firm, Numerator, that ran from January 2018 to December 2020. We describe the prevalence of different tobacco flavor names in our sample and classified each name into one of the following thematic categories: Traditional Tobacco, Pipe/Cigar Tobacco, Sensory Expectancies, Color, Physical Attribute, Place, and non-characterizing Concept flavor. RESULTS: In our sample, 28% (n=832/2,966) of ads promoted at least one tobacco flavored e-cigarette product (e-cigarette device or liquid). Across the 832 ads, we counted 1,019 tobacco flavored products and identified 51 unique tobacco flavor names. The most common tobacco flavor names were Traditional Tobacco names like 'Tobacco' (n=393), 'Classic tobacco' (n=107) and 'Original' (n=59). Some names were associated with Color (e.g., 'Golden tobacco'; n=153), Sensory Expectancy (e.g., 'Rich tobacco'; n=148), Place where tobacco cultivation takes place (e.g., 'Carolina tobacco'; n=83), Physical Attributes of tobacco (e.g., 'Cut tobacco'; n=17) and non-characterizing Concept flavor (e.g., 'Freedom juice'; n=14). Few tobacco flavors suggested a type of Pipe/Cigar Tobacco (e.g., 'Cavendish'; n=4). CONCLUSION: We identified 51 different tobacco flavor names, highlighting the practice describing the flavor beyond 'tobacco'. Future research can investigate whether these flavor names and descriptors influence consumers' perceptions, including perceived risks, of e-cigarette products. IMPLICATIONS: Flavors are used to market e-cigarettes. Globally, many jurisdictions restrict flavored e-cigarette sales, but few restrict tobacco flavor. This study identified 51 unique ways tobacco flavored e-cigarettes have been named in a sample of US English language ads, suggesting diversified ways to market 'tobacco.' We identified several sub-categories of tobacco flavor names that rely on Color, Sensory Expectancies, and non-characterizing Concept flavor attributes. As e-cigarette flavor restrictions that exempt tobacco flavor are still prevalent, this study highlights the need for continued monitoring of naming conventions of tobacco flavored products and examination of how nuanced flavor names influence perceptions and expectations.

Changes in Compliance with Bans on Tobacco Product Display and Advertising at Traditional and Modern Point-of-Sale Retailers in Depok, Indonesia, 2019-2021.

INTRODUCTION: Banning Point-of-Sale (POS) advertising and product display is an important tobacco control strategy. Depok, Indonesia enacted some regional tobacco control policies regulating the POS environment in 2021. This study examined changes in compliance before and after the implementation of these policies as of 2021. METHODS: Data collectors visited 180 modern retailers (hyper/supermarkets/convenience stores) and 147 traditional retailers (warungs) in 2019. The same retailers were re-visited in 2021. Data collectors assessed compliance with tobacco product display, and advertising regulations at POS, including if products were displayed in spaces to target minors (near candy or at a child's eye-level). Data were analyzed using McNemar and Mann-Whitney U tests. RESULTS: From 2019 to 2021, in modern retailers, tobacco product display (95.6% vs 52.2%) and product advertising (36.1% vs 3.9%) were significantly reduced (p<0.001). In traditional retailers, tobacco product display (94.6% in 2019, 91.2% in 2021, p>0.05) and product advertising (87.1% in 2019, 87.8% in 2021, p>0.05) remained common during both data collection periods. Tobacco products were commonly displayed in spaces to target minors in both modern retailers (43.3% in 2019, 34.4% in 2021, p>0.05) and traditional retailers (90.5% in 2019, 83.0% in 2021, p>0.05). CONCLUSIONS: Compliance with bans on tobacco product advertising and display at modern retailers improved significantly from 2019 to 2021; however, most modern retailers continue to display tobacco products in 2021. Traditional retailers remain largely non-compliant. Tobacco products are commonly displayed in areas that target minors. The enforcement of regional regulations should be strengthened, particularly among traditional retailers. IMPLICATIONS: In Depok, Indonesia, tobacco advertising and product display bans have been implemented; however, more work is needed to support compliance. Enforcement efforts, such as those carried out by civil police, can focus on tobacco product display bans in traditional and modern retailers, and traditional retailers need additional support to remove tobacco product advertising. Retailers may receive money from the tobacco industry for these advertisements. Creative solutions may include supporting retailers in finding alternative advertising revenue.

Tobacco product litter as a form of postconsumption marketing: an observational study in India.

BACKGROUND: Tobacco product litter may be a form of postconsumption marketing if the littered items are branded. We conducted an observational study in India to assess the presence of tobacco product litter and determine the proportion that included branding. METHODS: During November-December 2022, we identified tobacco product litter (cigarette/bidi butts and packaging; smokeless tobacco packaging) in nine Indian cities: Bengaluru, Bhubaneswar, Chennai, Delhi, Guwahati, Hyderabad, Lucknow, Mumbai and Patna. In each city, we conducted observations along 15 different routes, each approximately 250 m in distance, for a total of 135 observational routes. Data collectors classified each piece of tobacco litter (product/packaging) and recorded if the litter had visible branding, such as brand names and/or logos. RESULTS: The study identified 17 261 pieces of tobacco product litter; SLT packaging comprised the largest proportion of the sample (62%), followed by cigarette butts (26%), bidi butts (8%), cigarette packaging (3%) and bidi packaging (1%). Across the sample, 81% (n=13 924) of the litter was branded. A brand was visible on most packaging for cigarettes (98%), bidis (97%) and SLT (86%), and present on 82% of cigarette butts and 26% of bidi butts. CONCLUSION: This study found that the majority of tobacco product litter in India is branded, which could function as a form of postconsumption marketing. Plain and standardised packaging and banning branding features on filters would reduce tobacco litter branding.

Examining mental health and autonomic function as putative mediators of the relationship between sleep and trajectories of cognitive function: findings from the Irish longitudinal study on ageing (TILDA).

OBJECTIVES: This study investigates the mediating roles of autonomic function and mental health in the association between sleep and cognitive decline in adults aged 50 and above. METHOD: A total of 2,697 participants with observations on sleep and mediators at baseline and repeated measures of cognitive function (MMSE) were included. Clusters of individuals with similar cognitive trajectories (high-stable, mid-stable and low-declining) were identified. Multinomial logistic regressions were used to estimate the likelihood of membership to each trajectory group based on sleep duration and disturbance. Finally, mediation analysis tested potential mediating effects of autonomic function and mental health underpinning the sleep-cognition relationship. RESULTS: Short (p = .028), long (p =.019), and disturbed sleep (p =.008) increased the likelihood of a low-declining cognitive trajectory. Mental health measures fully attenuated relationships between cognitive decline and short or disturbed sleep but not long sleep. No autonomic function mediation was observed. CONCLUSION: Older adults with short or disturbed sleep are at risk of cognitive decline due to poor mental health. Individuals with long sleep are also at risk, however, the acting pathways remain to be identified. These outcomes have clinical implications, potentially identifying intervention strategies targeting mental health and sleep as prophylactic measures against dementia.

Is Maintenance or Switching Between Freebase and Nicotine Salt Liquid Associated with Electronic Nicotine Delivery Systems Dependence?

BACKGROUND: Electronic nicotine delivery systems (ENDS) use one of two formulations of nicotine-freebase or nicotine salt. This study examines whether maintenance or switching between nicotine formulations is associated with ENDS dependence using longitudinal survey data. METHODS: 543 U.S. adults (21+) using ENDS frequently (5+ days/week) self-reported and uploaded photos of their most used ENDS liquids in wave 3-5 online surveys from September 2021 to April 2023. Nicotine formulation from photo data was used if available; otherwise, self-reported data were used. ENDS dependence was measured in each wave by a 4-item E-cigarette Dependence Scale (EDS: range 0-4, 4 being most dependent). Data were analyzed using ANCOVA. RESULTS: Participants using nicotine salt liquids in three waves reported the highest EDS in wave 5 (49.3%, EDS = 2.59), followed by participants switching from salt to freebase (3.2%, EDS = 2.58), participants switching from freebase to salt (10.1%, EDS = 2.52), participants using freebase in three waves (34.9%, EDS = 2.18), and participants changing back and forth (2.4%, EDS = 2.11). After controlling for smoking status, participants stably using nicotine salt and participants switching from freebase to salt reported significantly higher EDS than those stably using freebase (p < 0.01). CONCLUSIONS: Over an 18-month period, people consistently using nicotine salt liquids and participants switching from freebase to nicotine salt were more likely to have a higher ENDS dependence than those consistently using freebase liquids. Understanding how switching between nicotine formulations relates to ENDS dependence can inform nicotine formulation and concentration regulations that may impact addiction.

Social Care Education and Training Among US Pediatric Emergency Medicine Fellowship Programs.

OBJECTIVE: The aim of the study is to assess the association of social determinants of health (SDOH) education and social needs training on pediatric emergency medicine (PEM) physician perception and practices of social care. METHODS: Data were derived from the 2021 National Social Care Practices Survey of PEM program directors (PDs) and fellows. Ordinal and binary logistic regression modeling were completed for educational/training factors and social care perspective and practice outcomes. RESULTS: A national sample of 44 PDs (49% response rate) and 109 fellows (28%) participated. A minority of fellows received SDOH education and social needs training during fellowship. Fellows and PDs with SDOH education had a 3.1 odds (95% confidence interval CI, 1.4-6.9) of screening for social needs, with 4.4 odds among fellows (95% CI, 1.2-20.7). Those with social needs training were more comfortable assessing social risk, with 2.4 odds overall (95% CI, 1.2-4.7) and 3.1 odds among fellows (95% CI, 1.4-6.7). They also had 2.4 odds overall (95% CI, 1.1-4.9) of screening for social needs, with a 2.9 odds among fellows (95% CI, 1.3-6.8). CONCLUSIONS: Social care education and training appear to be associated with comfort assessing social risk and social needs screening tendency among both PEM PDs and fellows. Key areas for educational interventions are identified among PEM fellows, who are uniquely positioned as clinical leaders and patient advocates.

The Emerging Role and Clinical Applications of Morphomics in Diagnostic Imaging.

Analytic morphomics refers to the accurate measurement of specific biological markers of human body composition in diagnostic medical imaging. The increasing prevalence of disease processes that alter body composition including obesity, cachexia, and sarcopenia has generated interest in specific targeted measurement of these metrics to possibly prevent or reduce negative health outcomes. Typical morphomic measurements include the area and density of muscle, bone, vascular calcification, visceral fat, and subcutaneous fat on a specific validated axial level in the patient's cross-sectional diagnostic imaging. A distinct advantage of these measurements is that they can be made retrospectively and opportunistically with pre-existing datasets. We provide a narrative review of the current state of art in morphomics, but also consider some potential future directions for this exciting field. Imaging based quantitative assessment of body composition has enormous potential across the breadth and scope of modern clinical practice. From risk stratification to treatment planning, and outcome assessment, all can be enhanced with the use of analytic morphomics. Moreover, it is likely that many new opportunities for personalized medicine will emerge as the field evolves. As radiologists, embracing analytic morphomics will enable us to contribute added value in the care of every patient.

Feasibility, Safety, and Efficacy of Aggressive Multimodal Management of Elderly Patients with Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: We aimed to evaluate the safety and efficacy of NAT followed by surgical resection in patients with PDAC aged ≥75 years. SUMMARY BACKGROUND DATA: Whether administration of neoadjuvant therapy (NAT) followed by surgical resection in elderly patients with pancreatic ductal adenocarcinoma (PDAC) is safe and effective is unknown. METHODS: The present study is a three-part comparison of older (≥ 75 years) versus younger (< 75 years) patients in different settings throughout the continuum of PDAC care. The first analysis was a comparison of older versus younger consecutive patients with non-metastatic PDAC who were initiated on FOLFIRINOX. The second was a comparison of older vs. younger patients who underwent NAT followed by surgical resection, and the third and final analysis was a comparison of older patients who underwent either NAT followed by surgical resection vs. upfront surgical resection. Postoperative complications, overall survival (OS), and time to recurrence (TTR), were compared. Propensity-score matching (PSM) analysis was performed to adjust for potential confounders. RESULTS: In the first analysis, a lower proportion of older patients (n=40) were able to complete the intended neoadjuvant FOLFIRINOX (8) cycles compared to younger patients (n=214) (65.0% vs. 81.4%, P=0.021). However, older patients were just as likely to undergo surgical exploration as younger patients (77.5% vs 78.5%, P=0.89) as well as surgical resection (57.5% vs 55.6%, P=0.70). In the second analysis, PSM was conducted to compare older (n=54) vs. younger patients (n=54) who underwent NAT followed by surgical resection. There were no significant differences in postoperative complications between the matched groups. While there was a significant difference in overall survival (OS) between older and younger patients (median OS: 16.43 months vs. 30.83 months, P=0.002), importantly, there was no significant difference in time to recurrence (TTR, median: 7.65 months vs. 11.83 months, P=0.215). In the third analysis, older patients who underwent NAT followed by surgical resection (n=48) were compared with similar older patients who underwent upfront surgical resection (n=48). After PSM, there was a significant difference in OS (median OS: 15.78 months vs. 11.51 months, P=0.037) as well as TTR (median TTR: 8.81 months vs. 7.10 months, P=0.046) representing an association with improved outcomes that favored the neoadjuvant approach among older patients alone. CONCLUSIONS: This comprehensive three-part study showed that administration of NAT followed by surgical resection appears to be safe and effective among patients ≥ 75 years of age. An aggressive approach should be offered to older adults undergoing multimodal treatment of PDAC.

Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Versus the Standard of Care Imaging in the Diagnosis of Peritoneal Carcinomatosis.

OBJECTIVE: To compare positron emission tomography (PET)/magnetic resonance imaging (MRI) to the standard of care imaging (SCI) for the diagnosis of peritoneal carcinomatosis (PC) in primary abdominopelvic malignancies. SUMMARY BACKGROUND DATA: Identifying PC impacts prognosis and management of multiple cancer types. METHODS: Adult subjects were prospectively and consecutively enrolled from April 2019 to January 2021. Inclusion criteria were: 1) acquisition of whole-body contrast-enhanced (CE) 18F-fluorodeoxyglucose PET/MRI, 2) pathologically confirmed primary abdominopelvic malignancies. Exclusion criteria were: 1) greater than 4 weeks interval between SCI and PET/MRI, 2) unavailable follow-up. SCI consisted of whole-body CE PET/computed tomography (CT) with diagnostic quality CT, and/or CE-CT of the abdomen and pelvis, and/or CE-MRI of the abdomen±pelvis. If available, pathology or surgical findings served as the reference standard, otherwise, imaging followup was used. When SCI and PET/MRI results disagreed, medical records were checked for management changes. Follow-up data were collected until August 2021. RESULTS: One hundred sixty-four subjects were included, 85 (52%) were female, and the median age was 60 years (interquartile range 50-69). At a subject level, PET/MRI had higher sensitivity (0.97, 95% CI 0.86-1.00) than SCI (0.54, 95% CI 0.37-0.71), P < 0.001, without a difference in specificity, of 0.95 (95% CI 0.90-0.98) for PET/MRI and 0.98 (95% CI 0.93-1.00) for SCI, P » 0.250. PET/MRI and SCI results disagreed in 19 cases. In 5/19 (26%) of the discordant cases, PET/MRI findings consistent with PC missed on SCI led to management changes. CONCLUSION: PET/MRI improves detection of PC compared with SCI which frequently changes management.

Dehydropolymerization of Amine-Boranes using Bis(imino)pyridine Rhodium Pre-Catalysis: σ-Amine-Borane Complexes, Nanoparticles, and Low Residual-Metal BN-Polymers that can be Chemically Repurposed.

The sigma amine-borane complexes [Rh(L1)(η2 :η2 -H3 B⋅NRH2 )][OTf] (L1=2,6-bis-[1-(2,6-diisopropylphenylimino)ethyl]pyridine, R=Me, Et, n Pr) are described, alongside [Rh(L1)(NMeH2 )][OTf]. Using R=Me as a pre-catalyst (1 mol %) the dehydropolymerization of H3 B ⋅ NMeH2 gives [H2 BNMeH]n selectively. Added NMeH2 , or the direct use of [Rh(L1)(NMeH2 )][OTf], is required for initiation of catalysis, which is suggested to operate through the formation of a neutral hydride complex, Rh(L1)H. The formation of small (1-5 nm) nanoparticles is observed at the end of catalysis, but studies are ambiguous as to whether the catalysis is solely nanoparticle promoted or if there is a molecular homogeneous component. [Rh(L1)(NMeH2 )][OTf] is shown to operate at 0.025 mol % loadings on a 2 g scale of H3 B ⋅ NMeH2 to give polyaminoborane [H2 BNMeH]n [Mn =30,900 g/mol, Ð=1.8] that can be purified to a low residual [Rh] (6 µg/g). Addition of Na[N(SiMe3 )2 ] to [H2 BNMeH]n results in selective depolymerization to form the eee-isomer of N,N,N-trimethylcyclotriborazane [H2 BNMeH]3 : the chemical repurposing of a main-group polymer.

cytoNet: Spatiotemporal network analysis of cell communities.

We introduce cytoNet, a cloud-based tool to characterize cell populations from microscopy images. cytoNet quantifies spatial topology and functional relationships in cell communities using principles of network science. Capturing multicellular dynamics through graph features, cytoNet also evaluates the effect of cell-cell interactions on individual cell phenotypes. We demonstrate cytoNet's capabilities in four case studies: 1) characterizing the temporal dynamics of neural progenitor cell communities during neural differentiation, 2) identifying communities of pain-sensing neurons in vivo, 3) capturing the effect of cell community on endothelial cell morphology, and 4) investigating the effect of laminin α4 on perivascular niches in adipose tissue. The analytical framework introduced here can be used to study the dynamics of complex cell communities in a quantitative manner, leading to a deeper understanding of environmental effects on cellular behavior. The versatile, cloud-based format of cytoNet makes the image analysis framework accessible to researchers across domains.

Nicotine-related content in English language ENDS advertisements in the US: 2018-2020.

There is no standard way to communicate to consumers how much nicotine is present in electronic nicotine delivery systems (ENDS). This study assessed the inclusion of nicotine-related content, including nicotine strength, in a sample of English language ENDS advertisements that appeared in consumer and business-to-business outlets in the US during 2018-2020. The sample, provided by a media surveillance company, included ads from television, radio, newspapers, magazines (consumer and business-to-business), online platforms, outdoor/billboards, and direct-to-consumer emails. We coded for the presence of nicotine-related content (excluding FDA-required warnings) including nicotine strength presentation, such as mg, mg/ml and percent. The sample included 2966 unique ads, of which 33% (n = 979) featured nicotine-related content. The proportion of ads in the entire sample with nicotine-related content differed by manufacturer/retailer. Ads for Logic e-cigarettes had the highest proportion of nicotine content (62%, n = 258), while ads for JUUL and Vapor4Life had the lowest proportion (13.0% (n = 95) and 19.8% (n = 65), respectively). The proportion of ads with nicotine-related content also differed by media outlet: B2B magazines: 64.8% (n = 68); emails: 41% (n = 529); consumer magazines: 30.4% (n = 41); online: 25.3% (n = 227); television: 20% (n = 6); radio: 19.1% (n = 89); and outdoor (0%, n = 0). Across the sample of ads, 15% reported nicotine strength in mg or mg/ml (n = 444), and 9% reported nicotine strength in percent (n = 260). Most ENDS ads do not include nicotine-related content. There is substantial variation in presentation of nicotine strength, which may present challenges for consumer understanding of absolute and relative nicotine-related content.

How Media Stories in Low- and Middle-Income Countries Discussed the U.S. Food and Drug Administration's Modified Risk Tobacco Product Order for IQOS.

INTRODUCTION: In 2020, the U.S. Food and Drug Administration authorized the marketing of IQOS as a modified risk tobacco product (MRTP) with reduced exposure information (reduces exposure to harmful chemicals compared to cigarettes) but prohibited Philip Morris International from making reduced risk claims (reduces risk of disease compared to cigarettes). We aimed to assess how news media in low- and middle-income countries (LMICs) discussed this authorization and whether articles discussed IQOS as a reduced exposure versus reduced risk product. AIMS AND METHODS: News articles published between July 7, 2020 and January 7, 2021 were obtained by searching Tobacco Watcher (www.tobaccowatcher.org), a surveillance platform for tobacco-related news. Articles were eligible if they were published in an LMIC and mentioned the IQOS MRTP order. Non-English language articles were professionally translated. Articles were double coded to identify country of origin, reduced risk and reduced exposure language, discussions of potential impacts of the authorization on regulations in LMICs, and quotes from tobacco industry and public health stakeholders. RESULTS: We identified 50 eligible articles published in 20 LMICs. Twenty-six (52%) and 40 (80%) included reduced risk and reduced exposure language, respectively. Twenty-two (44%) discussed potential impacts of the MRTP order on regulations in LMICs. Thirty (60%) included quotes from tobacco industry representatives, 6 (12%) included quotes from public health or medical professionals, and 2 (4%) included both. CONCLUSIONS: News articles in LMICs frequently misreported the MRTP order by using reduced risk language. The authorization is potentially being used to shape perspectives on tobacco regulations in LMICs. Tobacco control experts need to more frequently share their perspectives with the news media. IMPLICATIONS: News articles from LMICs frequently misrepresented the IQOS MRTP order by using reduced risk language (reduces harm compared to cigarettes) rather than only using reduced exposure language (reduces exposure to harmful chemicals compared to cigarettes). Many articles referred to IQOS as a "better alternative" to cigarettes without specifically referencing reduced risk. Few articles included perspectives from public health or medical professionals, while most included tobacco industry quotes, suggesting that tobacco control experts need to more frequently engage with the news media. These findings also highlight how the U.S. FDA's actions can potentially shape perspectives on tobacco product regulations in LMICs.

Establishment of mouse expanded potential stem cells.

Mouse embryonic stem cells derived from the epiblast contribute to the somatic lineages and the germline but are excluded from the extra-embryonic tissues that are derived from the trophectoderm and the primitive endoderm upon reintroduction to the blastocyst. Here we report that cultures of expanded potential stem cells can be established from individual eight-cell blastomeres, and by direct conversion of mouse embryonic stem cells and induced pluripotent stem cells. Remarkably, a single expanded potential stem cell can contribute both to the embryo proper and to the trophectoderm lineages in a chimaera assay. Bona fide trophoblast stem cell lines and extra-embryonic endoderm stem cells can be directly derived from expanded potential stem cells in vitro. Molecular analyses of the epigenome and single-cell transcriptome reveal enrichment for blastomere-specific signature and a dynamic DNA methylome in expanded potential stem cells. The generation of mouse expanded potential stem cells highlights the feasibility of establishing expanded potential stem cells for other mammalian species.

Perceived effectiveness of four different cigarette health warning label themes among a sample of urban smokers and non-smokers in China.

OBJECTIVE: This study, conducted in China, evaluated the effectiveness of four different themes of health warning labels (HWLs) that used both text and pictures: (1) self-harm from using cigarettes, (2) harming family or children with secondhand smoke, (3) reinforcing compliance with existing smoke-free policies and (4) anticigarette gift giving practices. METHODS: A cross-sectional randomised experimental survey was conducted among 3247 adult (aged 18+ years) participants in Beijing, Shanghai and Shenzhen in 2017, using quotas for age group, gender and smoking status. Participants were randomly assigned to one of the four HWL themes. Each participant viewed eight HWLs and rated how effective these themed-labels were in terms of credibility, raising awareness of health harms of smoking on family and children, improving compliance with public smoking bans, stopping the practice of gifting cigarettes, thinking about quitting and preventing smoking using a 10-point scale, with 10 being most effective. Analysis of variance and independent t-tests were used to analyse these data. FINDINGS: All four HWL themes performed well for each outcome with average ratings >6.5. Harming family or children with secondhand smoke was the theme that received the highest ratings for each outcome, with credibility (8.0, 95% CI 7.86 to 8.09) and prevention of smoking (8.8, 95% CI 8.63 to 8.91) outcomes being significantly higher (p<0.05). Overall, analysis of ratings by gender, income and education did not impact outcomes. CONCLUSION: All four HWL themes tested could be effective in China; the theme of secondhand smoke harming family or children may be a particularly credible/effective theme.

Nicotine pouches: a summary of regulatory approaches across 67 countries.

INTRODUCTION: Nicotine pouches are small, permeable pouches containing nicotine. The nicotine may either be derived from tobacco plants or synthetically produced. Nicotine pouches are available worldwide, but little is known as to how various countries regulate these products. This study summarises nicotine pouch regulatory policies across 67 countries. METHODS: This research summarises insights obtained through active policy surveillance work in which we requested information on the availability of nicotine pouches and applicable policies and analysed responses from representatives of 67 countries (representatives included subject matter experts in government or civil society organisations). These countries span all WHO regions. RESULTS: We found significant variation in how countries classify nicotine pouches, with many countries' current regulatory approach failing to regulate nicotine pouches that used synthetic nicotine. We found 34 countries regulate nicotine pouches with 23 of these countries' policies encompassing synthetic nicotine. Countries regulating both synthetic and tobacco-derived nicotine pouches generally (1) rely on existing policies for tobacco products and/or medicines or (2) have developed new policies or regulatory classifications that specify nicotine as the substance at issue rather than linking policies solely to tobacco. CONCLUSION: Our work offers novel insight into nicotine pouch markets and national regulatory approaches. Policy approaches vary from not regulating nicotine pouches at all to banning both forms of nicotine pouches. Policies used by countries regulating both tobacco-derived and synthetic nicotine pouches offer a roadmap for how other jurisdictions can add effective guardrails to the use of these and other non-medicinal nicotine products.

Analytic Morphomics in Myositis-Related Interstitial Lung Disease.

PURPOSE: Interstitial lung disease (ILD) is the most common non-musculoskeletal manifestation of idiopathic inflammatory myopathies (IIM). Identification of body composition change may enable early intervention to improve prognosis. We investigated muscle quantity and quality derived from cross-sectional imaging in IIM, and its relationship to ILD severity. METHODS: A retrospective cohort study assessing IIM of ILD patients (n = 31) was conducted. Two datasets separated in time were collected, containing demographics, biochemical data, pulmonary function testing and thoracic CT data. Morphomic analysis of muscle quantity (cross-sectional area) and quality (density in Hounsfield Units) on thoracic CT were analysed utilising a web-based tool allowing segmentation of muscle and fat. Bilateral erector spinae and pectoralis muscle (ESM&PM) were measured at defined vertebral levels. RESULTS: FVC and DLCO decreased but within acceptable limits of treatment response (FVC: 83.7-78.7%, p < 0.05, DLCO 63.4-60.6%, p < 0.05). The cross-sectional area of the PM and ESM increased (PM: 39.8 to 40.7 cm2, p = 0.491; ESM: 35.2 to 39.5 cm2, p = 0.098). Density significantly fell for both the PM and ESM (PM: 35.3-31 HU, p < 0.05; ESM: 38-33.7, p < 0.05). Subcutaneous fat area increased from 103.9 to 136.1 cm2 (p < 0.05), while the visceral fat area increased but not reaching statistical significance. The change in PM density between time points demonstrated an inverse correlation with DLCO (p < 0.05, R = - 0.49). CONCLUSION: Patients with IIM ILD demonstrated significant body composition changes on CT imaging unlikely to be detected by traditional measurement tools. An increase in muscle area with an inverse decrease in density suggests poor muscle quality.