tbuckley/cabot-search huggingface dataset:
Impact of the UK soft drinks industry levy on health and health inequalities in children and adolescents in England: An interrupted time series analysis and population health modelling study
Authors: Linda J. Cobiac, Nina T. Rogers, Jean Adams, Steven Cummins, Richard Smith, Oliver Mytton, Martin White, Peter Scarborough
Journal: PLoS Medicine (2024)

Background The soft drinks industry levy (SDIL) in the United Kingdom has led to a significant reduction in household purchasing of sugar in drinks. In this study, we examined the potential medium- and long-term implications for health and health inequalities among children and adolescents in England. Methods and findings We conducted a controlled interrupted time series analysis to measure the effects of the SDIL on the amount of sugar per household per week from soft drinks purchased, 19 months post implementation and by index of multiple deprivation (IMD) quintile in England. We modelled the effect of observed sugar reduction on body mass index (BMI), dental caries, and quality-adjusted life years (QALYs) in children and adolescents (0 to 17 years) by IMD quintile over the first 10 years following announcement (March 2016) and implementation (April 2018) of the SDIL. Using a lifetable model, we simulated the potential long-term impact of these changes on life expectancy for the current birth cohort and, using regression models with results from the IMD-specific lifetable models, we calculated the impact of the SDIL on the slope index of inequality (SII) in life expectancy. The SDIL was found to have reduced sugar from purchased drinks in England by 15 g/household/week (95% confidence interval: −10.3 to −19.7). The model predicts these reductions in sugar will lead to 3,600 (95% uncertainty interval: 946 to 6,330) fewer dental caries and 64,100 (54,400 to 73,400) fewer children and adolescents classified as overweight or obese, in the first 10 years after implementation. The changes in sugar purchasing and predicted impacts on health are largest for children and adolescents in the most deprived areas (Q1: 11,000 QALYs [8,370 to 14,100] and Q2: 7,760 QALYs [5,730 to 9,970]), while children and adolescents in less deprived areas will likely experience much smaller simulated effects (Q3: −1,830 QALYs [−3,260 to −501], Q4: 652 QALYs [−336 to 1,680], Q5: 1,860 QALYs [929 to 2,890]). If the simulated effects of the SDIL are sustained over the life course, it is predicted there will be a small but significant reduction in slope index of inequality: 0.76% (95% uncertainty interval: −0.9 to −0.62) for females and 0.94% (−1.1 to −0.76) for males. Conclusions We predict that the SDIL will lead to medium-term reductions in dental caries and overweight/obesity, and long-term improvements in life expectancy, with the greatest benefits projected for children and adolescents from more deprived areas. This study provides evidence that the SDIL could narrow health inequalities for children and adolescents in England.
Gut Microbiota and Blood Metabolites Related to Fiber Intake and Type 2 Diabetes
Authors: Zheng Wang, Brandilyn A. Peters, Bing Yu, Megan L. Grove, Tao Wang, Xiaonan Xue, Bharat Thyagarajan, Martha L. Daviglus, Eric Boerwinkle, Gang Hu, Yasmin Mossavar-Rahmani, Carmen R. Isasi, Rob Knight, Robert D. Burk, Robert C. Kaplan, Qibin Qi
Journal: Circulation Research (2024)

BACKGROUND: Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D). METHODS: This study included up to 11 394 participants from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Diet was assessed with two 24-hour dietary recalls at baseline. We examined associations of dietary fiber intake with gut microbiome measured by shotgun metagenomics (350 species/85 genera and 1958 enzymes; n=2992 at visit 2), serum metabolome measured by untargeted metabolomics (624 metabolites; n=6198 at baseline), and associations between fiber-related gut bacteria and metabolites (n=804 at visit 2). We examined prospective associations of serum microbial-associated metabolites (n=3579 at baseline) with incident T2D over 6 years. RESULTS: We identified multiple bacterial genera, species, and related enzymes associated with fiber intake. Several bacteria (eg, Butyrivibrio , Faecalibacterium ) and enzymes involved in fiber degradation (eg, xylanase EC3.2.1.156) were positively associated with fiber intake, inversely associated with prevalent T2D, and favorably associated with T2D-related metabolic traits. We identified 159 metabolites associated with fiber intake, 47 of which were associated with incident T2D. We identified 18 of these 47 metabolites associated with the identified fiber-related bacteria, including several microbial metabolites (eg, indolepropionate and 3-phenylpropionate) inversely associated with the risk of T2D. Both Butyrivibrio and Faecalibacterium were associated with these favorable metabolites. The associations of fiber-related bacteria, especially Faecalibacterium and Butyrivibrio , with T2D were attenuated after further adjustment for these microbial metabolites. CONCLUSIONS: Among United States Hispanics/Latinos, dietary fiber intake was associated with favorable profiles of gut microbiota and circulating metabolites for T2D. These findings advance our understanding of the role of gut microbiota and microbial metabolites in the relationship between diet and T2D.
Meet the First Authors
Authors: Zheng Wang
Journal: Circulation Research (2024)

His research has focused on human microbiome, especially the diet-microbiota-host interactions in specific populations, and integrative multi-omics (e.g., metagenomics and metabolomics) of chronic diseases such as obesity and cardiovascular diseases.He is also interested in exploring the mechanisms and functional genomic basis of specific microbial taxa that contributed to the development of cardiovascular diseases.
Author Correction: International Guideline for Idiopathic Inflammatory Myopathy-Associated Cancer Screening: an International Myositis Assessment and Clinical Studies Group (IMACS) initiative
Authors: Alexander G. S. Oldroyd, Jeffrey P. Callen, Hector Chinoy, Lorinda Chung, David Fiorentino, Patrick Gordon, Pedro M. Machado, Neil McHugh, Albert Selva-O’Callaghan, Jens Schmidt, Sarah L. Tansley, Ruth Ann Vleugels, Victoria P. Werth, Anthony A. Amato, Helena Andersson, Lilia Andrade-Ortega, Dana Ascherman, Olivier Benveniste, Lorenzo Cavagna, Christina Charles-Shoeman, Benjamin F. Chong, Lisa Christopher-Stine, Jennie T. Clarke, Emma J. Crosbie, Philip A. J. Crosbie, Sonye Danoff, Maryam Dastmalchi, Marianne De Visser, Paul F. Dellaripa, Louise Pyndt Diederichsen, Mazen M. Dimachkie, Erik Ensrud, Floranne Ernste, D. Gareth R. Evans, Manabu Fujimoto, Ignacio Garcia-De La Torre, Abraham Garcia-Kutzbach, Zoltan Griger, Latika Gupta, Marie Hudson, Florenzo Iannone, David Isenberg, Joseph Jorizzo, Helen Kurtz, Masataka Kuwana, Vidya Limaye, Ingrid E. Lundberg, Andrew L. Mammen, Herman Mann, Frank Mastaglia, Lorna McWilliams, Christopher A. Mecoli, Federica Meloni, Frederick W. Miller, Siamak Moghadam-Kia, Sergey Moiseev, Yoshinao Muro, Melinda Nagy-Vincze, Clive Nayler, Merrilee Needham, Ichizo Nishino, Chester V. Oddis, Julie J. Paik, Joost Raaphorst, Lisa G. Rider, Jorge Rojas-Serrano, Lesley Ann Saketkoo, Adam Schiffenbauer, Samuel Katsuyuki Shinjo, Vineeta Shobha, Yeong-Wook Song, Tania Tillett, Yves Troyanov, Anneke J. van der Kooi, Mónica Vázquez-Del Mercado, Jiri Vencovsky, Qian Wang, Steven Ytterberg, Rohit Aggarwal
Journal: Nature Reviews Rheumatology (2024)
The roles of protective factors in facing gender-related interpersonal stigma among Chinese transgender and gender diverse individuals: A mixed-method study
Authors: Zoe Jiwen Zhang, Fei Zhang, Herman Hay Ming Lo
Journal: International Journal of Transgender Health (2024)

Background Transgender and gender diverse (TGD) individuals report high rates of mistreatment in the form of interpersonal stigma. These experiences can negatively impact their mental health. However, few studies have explored this relationship within a Chinese context. This study aims to investigate the connection between various forms of interpersonal stigma and mental health among Chinese TGD individuals. It also seeks to understand the role of collective and personal protective factors in mitigating the effects of interpersonal stigma.
Polysomnographic airflow shapes and site of collapse during drug-induced sleep endoscopy
Authors: Sara Op de Beeck, Daniel Vena, Dwayne Mann, Ali Azarbarzin, Phillip Huyett, Eli Van de Perck, Laura K. Gell, Raichel M. Alex, Marijke Dieltjens, Marc Willemen, Johan Verbraecken, Andrew Wellman, Olivier M. Vanderveken, Scott A. Sands
Journal: European Respiratory Journal (2024)

Differences in the pharyngeal site of collapse influence efficacy of non-continuous positive airway pressure therapies for obstructive sleep apnoea (OSA). Notably, complete concentric collapse at the level of the palate (CCCp) during drug-induced sleep endoscopy (DISE) is associated with reduced efficacy of hypoglossal nerve stimulation, but CCCp is currently not recognisable using polysomnography. Here we develop a means to estimate DISE-based site of collapse using overnight polysomnography.
Whole-genome mapping of APOBEC mutagenesis in metastatic urothelial carcinoma identifies driver hotspot mutations and a novel mutational signature
Authors: J. Alberto Nakauma-González, Maud Rijnders, Minouk T.W. Noordsij, John W.M. Martens, Astrid A.M. van der Veldt, Martijn P.J. Lolkema, Joost L. Boormans, Harmen J.G. van de Werken
Journal: Cell Genomics (2024)

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) enzymes mutate specific DNA sequences and hairpin-loop structures, challenging the distinction between passenger and driver hotspot mutations. Here, we characterized 115 whole genomes of metastatic urothelial carcinoma (mUC) to identify APOBEC mutagenic hotspot drivers. APOBEC-associated mutations were detected in 92% of mUCs and were equally distributed across the genome, while APOBEC hotspot mutations (ApoHMs) were enriched in open chromatin. Hairpin loops were frequent targets of didymi (twins in Greek), two hotspot mutations characterized by the APOBEC SBS2 signature, in conjunction with an uncharacterized mutational context (Ap[C>T]). Next, we developed a statistical framework that identified ApoHMs as drivers in coding and non-coding genomic regions of mUCs. Our results and statistical framework were validated in independent cohorts of 23 non-metastatic UCs and 3,744 samples of 17 metastatic cancers, identifying cancer-type-specific drivers. Our study highlights the role of APOBEC in cancer development and may contribute to developing novel targeted therapy options for APOBEC-driven cancers.
Integrative analysis identifies molecular features of fibroblast and the significance of fibrosis on neoadjuvant chemotherapy response in breast cancer
Authors: Xiaomin Wang, Bo Chen, Hanghao Zhang, Lushan Peng, Xiangyan Liu, Qian Zhang, Xiaoxiao Wang, Shuai Peng, Kuangsong Wang, Liqiu Liao
Journal: International Journal of Surgery (2024)

Background: The molecular features of fibroblasts and the role of fibrosis in neoadjuvant chemotherapy (NAC) response and breast cancer (BRCA) prognosis remain unclear. Therefore, this study aimed to investigate the impact of interstitial fibrosis on the response and prognosis of patients with BRCA undergoing NAC treatment. Materials and Methods: The molecular characteristics of pathologic complete response (pCR) and non-pCR (npCR) in patients with BRCA were analyzed using multi-omics analysis. A clinical cohort was collected to investigate the predictive value of fibrosis in patients with BRCA. Results: Fibrosis-related signaling pathways were significantly upregulated in patients with npCR. npCR may be associated with distinct and highly active fibroblast subtypes. Patients with high fibrosis had lower pCR rates. The fibrosis-dependent nomogram for pCR showed efficient predictive ability (training set: area under the curve [AUC]=0.871, validation set: AUC=0.792). Patients with low fibrosis had a significantly better prognosis than those with high fibrosis, and those with a high fibrotic focus index had significantly shorter overall and recurrence-free survival. Therefore, fibrosis can be used to predict pCR. Our findings provide a basis for decision-making in the treatment of BRCA. Conclusions: npCR is associated with a distinct and highly active fibroblast subtype. Furthermore, patients with high fibrosis have lower pCR rates and shorter long-term survival. Therefore, fibrosis can predict pCR. A nomogram that includes fibrosis can provide a basis for decision-making in the treatment of BRCA.
A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast
Authors: Austin D. Reed, Sara Pensa, Adi Steif, Jack Stenning, Daniel J. Kunz, Linsey J. Porter, Kui Hua, Peng He, Alecia-Jane Twigger, Abigail J. Q. Siu, Katarzyna Kania, Rachel Barrow-McGee, Iain Goulding, Jennifer J. Gomm, Valerie Speirs, J Louise Jones, John C. Marioni, Walid T. Khaled
Journal: Nature Genetics (2024)

Abstract Here we use single-cell RNA sequencing to compile a human breast cell atlas assembled from 55 donors that had undergone reduction mammoplasties or risk reduction mastectomies. From more than 800,000 cells we identified 41 cell subclusters across the epithelial, immune and stromal compartments. The contribution of these different clusters varied according to the natural history of the tissue. Age, parity and germline mutations, known to modulate the risk of developing breast cancer, affected the homeostatic cellular state of the breast in different ways. We found that immune cells from BRCA1 or BRCA2 carriers had a distinct gene expression signature indicative of potential immune exhaustion, which was validated by immunohistochemistry. This suggests that immune-escape mechanisms could manifest in non-cancerous tissues very early during tumor initiation. This atlas is a rich resource that can be used to inform novel approaches for early detection and prevention of breast cancer.
Real-time glioblastoma tumor microenvironment assessment by SpiderMass for improved patient management
Authors: Yanis Zirem, Léa Ledoux, Lucas Roussel, Claude Alain Maurage, Pierre Tirilly, Émilie Le Rhun, Bertrand Meresse, Gargey Yagnik, Mark J. Lim, Kenneth J. Rothschild, Marie Duhamel, Michel Salzet, Isabelle Fournier
Journal: Cell Reports Medicine (2024)

Glioblastoma is a highly heterogeneous and infiltrative form of brain cancer associated with a poor outcome and limited therapeutic effectiveness. The extent of the surgery is related to survival. Reaching an accurate diagnosis and prognosis assessment by the time of the initial surgery is therefore paramount in the management of glioblastoma. To this end, we are studying the performance of SpiderMass, an ambient ionization mass spectrometry technology that can be used in vivo without invasiveness, coupled to our recently established artificial intelligence pipeline. We demonstrate that we can both stratify isocitrate dehydrogenase (IDH)-wild-type glioblastoma patients into molecular sub-groups and achieve an accurate diagnosis with over 90% accuracy after cross-validation. Interestingly, the developed method offers the same accuracy for prognosis. In addition, we are testing the potential of an immunoscoring strategy based on SpiderMass fingerprints, showing the association between prognosis and immune cell infiltration, to predict patient outcome.
State of the art review | Advances in COPD imaging using CT and MRI: Linkage with lung physiology and clinical outcomes
Authors: Amany F. Elbehairy, Helen Marshall, Josephine H. Naish, Jim M. Wild, Grace Parraga, Alexander Horsley, Jørgen Vestbo
Journal: European Respiratory Journal (2024)

Recent years have witnessed major advances in lung imaging in patients with COPD. These include significant refinements in images obtained by computed tomography (CT) scans together with the introduction of new techniques and software that aim for obtaining the best image whilst using the lowest possible radiation dose. Magnetic resonance imaging (MRI) has also emerged as a useful radiation-free tool in assessing structural and more importantly functional derangements in patients with well-established COPD and smokers without COPD, even before the existence of overt changes in resting physiological lung function tests. Together, CT and MRI now allow objective quantification and assessment of structural changes within the airways, lung parenchyma and pulmonary vessels. Furthermore, CT and MRI can now provide objective assessments of regional lung ventilation and perfusion, and multinuclear MRI provides further insight into gas exchange; this can help in structured decisions regarding treatment plans. These advances in chest imaging techniques have brought new insights into our understanding of disease pathophysiology and characterising different disease phenotypes. The present review discusses, in detail, the advances in lung imaging in patients with COPD and how structural and functional imaging are linked with common resting physiological tests and important clinical outcomes.
Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes
Authors: Mikhail N. Kosiborod, Mark C. Petrie, Barry A. Borlaug, Javed Butler, Melanie J. Davies, G. Kees Hovingh, Dalane W. Kitzman, Daniél V. Møller, Marianne B. Treppendahl, Subodh Verma, Thomas J. Jensen, Karoline Liisberg, Marie L. Lindegaard, Walter Abhayaratna, Fozia Z. Ahmed, Tuvia Ben-Gal, Vijay Chopra, Justin A. Ezekowitz, Michael Fu, Hiroshi Ito, Małgorzata Lelonek, Vojtěch Melenovský, Bela Merkely, Julio Núñez, Eduardo Perna, Morten Schou, Michele Senni, Kavita Sharma, Peter van der Meer, Dirk Von Lewinski, Dennis Wolf, Sanjiv J. Shah
Journal: New England Journal of Medicine (2024)

Obesity and type 2 diabetes are prevalent in patients with heart failure with preserved ejection fraction and are characterized by a high symptom burden. No approved therapies specifically target obesity-related heart failure with preserved ejection fraction in persons with type 2 diabetes.
Tumor Intrinsic Subtypes and Gene Expression Signatures in Early-Stage <i>ERBB2/HER2</i>-Positive Breast Cancer
Authors: Aranzazu Fernandez-Martinez, Mattia Rediti, Gong Tang, Tomás Pascual, Katherine A. Hoadley, David Venet, Naim U. Rashid, Patricia A. Spears, Md N. Islam, Sarra El-Abed, Judith Bliss, Matteo Lambertini, Serena Di Cosimo, Jens Huobe, David Goerlitz, Rong Hu, Peter C. Lucas, Sandra M. Swain, Christos Sotiriou, Charles M. Perou, Lisa A. Carey
Journal: JAMA Oncology (2024)

Importance Biologic features may affect pathologic complete response (pCR) and event-free survival (EFS) after neoadjuvant chemotherapy plus ERBB2/HER2 blockade in ERBB2/HER2 -positive early breast cancer (EBC). Objective To define the quantitative association between pCR and EFS by intrinsic subtype and by other gene expression signatures in a pooled analysis of 3 phase 3 trials: CALGB 40601, NeoALTTO, and NSABP B-41. Design, Setting, and Participants In this retrospective pooled analysis, 1289 patients with EBC received chemotherapy plus either trastuzumab, lapatinib, or the combination, with a combined median follow-up of 5.5 years. Gene expression profiling by RNA sequencing was obtained from 758 samples, and intrinsic subtypes and 618 gene expression signatures were calculated. Data analyses were performed from June 1, 2020, to January 1, 2023. Main Outcomes and Measures The association of clinical variables and gene expression biomarkers with pCR and EFS were studied by logistic regression and Cox analyses. Results In the pooled analysis, of 758 women, median age was 49 years, 12% were Asian, 6% Black, and 75% were White. Overall, pCR results were associated with EFS in the ERBB2-enriched (hazard ratio [HR], 0.45; 95% CI, 0.29-0.70; P &amp;amp;lt; .001) and basal-like (HR, 0.19; 95% CI, 0.04-0.86; P = . 03) subtypes but not in luminal A or B tumors. Dual trastuzumab plus lapatinib blockade over trastuzumab alone had a trend toward EFS benefit in the intention-to-treat population; however, in the ERBB2-enriched subtype there was a significant and independent EFS benefit of trastuzumab plus lapatinib vs trastuzumab alone (HR, 0.47; 95% CI, 0.27-0.83; P = .009). Overall, 275 of 618 gene expression signatures (44.5%) were significantly associated with pCR and 9 of 618 (1.5%) with EFS. The ERBB2/HER2 amplicon and multiple immune signatures were significantly associated with pCR. Luminal-related signatures were associated with lower pCR rates but better EFS, especially among patients with residual disease and independent of hormone receptor status. There was significant adjusted HR for pCR ranging from 0.45 to 0.81 (higher pCR) and 1.21-1.94 (lower pCR rate); significant adjusted HR for EFS ranged from 0.71 to 0.94. Conclusions and relevance In patients with ERBB2/HER2 -positive EBC, the association between pCR and EFS differed by tumor intrinsic subtype, and the benefit of dual ERBB2/HER2 blockade was limited to ERBB2-enriched tumors. Immune-activated signatures were concordantly associated with higher pCR rates and better EFS, whereas luminal signatures were associated with lower pCR rates.
Optimizing Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Older Adults
Authors: Safi U. Khan, Neal S. Kleiman
Journal: JAMA Network Open (2024)

Dae Yong Park, MD; Jiun-Ruey Hu, MD, MPH; Yasser Jamil, MD; Michelle D. Kelsey, MD; W. Schuyler Jones, MD; Jennifer Frampton, DO, MPH; Ajar Kochar, MD, MHS; Wilbert S. Aronow, MD; Abdulla A. Damluji, MD, PhD; Michael G. Nanna, MD, MHS