tbuckley/cabot-search huggingface dataset:
Sustained Effectiveness of an Advanced Hybrid Closed-Loop System in a Cohort of Children and Adolescents With Type 1 Diabetes: A 1-Year Real-World Study
Authors: Stefano Passanisi, Giuseppina Salzano, Bruno Bombaci, Nicola Minuto, Marta Bassi, Riccardo Bonfanti, Francesco Scialabba, Enza Mozzillo, Francesca Di Candia, Sara Monti, Vanna Graziani, Claudio Maffeis, Claudia Anita Piona, Claudia Arnaldi, Davide Tosini, Barbara Felappi, Rosalia Roppolo, Angela Zanfardino, Maurizio Delvecchio, Donatella Lo Presti, Elena Calzi, Carlo Ripoli, Roberto Franceschi, Petra Reinstadler, Ivana Rabbone, Giulio Maltoni, Angela Alibrandi, Stefano Zucchini, Marco Marigliano, Fortunato Lombardo, Caterina Grosso, Valentino Cherubini, Valentina Tiberi, Elvira Piccinno, Clara Zecchino, Elena Prandi, Maria Rossella Ricciardi, Filomena Stamati, Giuseppe Costanza, Giulia Pezzino, De Marco Rosaria, Anna Bratta, Giordano Spacco, Andrea Rigamonti, Giulio Frontino, Barbara Predieri, Dario Iafusco, Francesco Rosanio, Erica Pozzi, Francesca Cardella, Sara Dal Bo, Chiara Riso
Journal: Diabetes Care (2024)

OBJECTIVE To investigate glucose metrics and identify potential predictors of the achievement of glycemic outcomes in children and adolescents during their first 12 months of MiniMed 780G use. RESEARCH DESIGN AND METHODS This multicenter, longitudinal, real-world study recruited 368 children and adolescents with type 1 diabetes (T1D) starting SmartGuard technology between June 2020 and June 2022. Ambulatory glucose profile data were collected during a 15-day run-in period (baseline), 2 weeks after automatic mode activation, and every 3 months. The influence of covariates on glycemic outcomes after 1 year of MiniMed 780G use was assessed. RESULTS After 15 days of automatic mode use, all glucose metrics improved compared with baseline (P &amp;lt; 0.001), except for time below range (P = 0.113) and coefficient of variation (P = 0.330). After 1 year, time in range (TIR) remained significantly higher than at baseline (75.3% vs. 62.8%, P &amp;lt; 0.001). The mean glycated hemoglobin (HbA1c) over the study duration was lower than the previous year (6.9 ± 0.6% vs. 7.4 ± 0.9%, P &amp;lt; 0.001). Time spent in tight range (70–140 mg/dL) was 51.1%, and the glycemia risk index was 27.6. Higher TIR levels were associated with a reduced number of automatic correction boluses (P &amp;lt; 0.001), fewer SmartGuard exits (P = 0.021), and longer time in automatic mode (P = 0.030). Individuals with baseline HbA1c &amp;gt;8% showed more relevant improvement in TIR levels (from 54.3% to 72.3%). CONCLUSIONS Our study highlights the sustained effectiveness of MiniMed 780G among youth with T1D. Findings suggest that even children and adolescents with low therapeutic engagement may benefit from SmartGuard technology.
Effects of <i>Prevotella copri</i> on insulin, gut microbiota and bile acids
Authors: Jiatai Gong, Qianjin Zhang, Ruizhi Hu, Xizi Yang, Chengkun Fang, Liping Yao, Jing Lv, Long Wang, Mingkun Shi, Wentao Zhang, Siqi Ma, Hongkun Xiang, Hongfu Zhang, De-Xing Hou, Yulong Yin, Jianhua He, Lijun Peng, Shusong Wu
Journal: Gut Microbes (2024)

Obesity is becoming a major global health problem in children that can cause diseases such as type 2 diabetes and metabolic disorders, which are closely related to the gut microbiota. However, the underlying mechanism remains unclear. In this study, a significant positive correlation was observed between Prevotella copri (P. copri) and obesity in children (p = 0.003). Next, the effect of P. copri on obesity was explored by using fecal microbiota transplantation (FMT) experiment. Transplantation of P. copri. increased serum levels of fasting blood glucose (p < 0.01), insulin (p < 0.01) and interleukin-1β (IL-1β) (p < 0.05) in high-fat diet (HFD)-induced obese mice, but not in normal mice. Characterization of the gut microbiota indicated that P. copri reduced the relative abundance of the Akkermansia genus in mice (p < 0.01). Further analysis on bile acids (BAs) revealed that P. copri increased the primary BAs and ursodeoxycholic acid (UDCA) in HFD-induced mice (p < 0.05). This study demonstrated for the first time that P. copri has a significant positive correlation with obesity in children, and can increase fasting blood glucose and insulin levels in HFD-fed obese mice, which are related to the abundance of Akkermansia genus and bile acids.
Modulating gut microbiome in cancer immunotherapy: Harnessing microbes to enhance treatment efficacy
Authors: Xing Kang, Harry Cheuk-Hay Lau, Jun Yu
Journal: Cell Reports Medicine (2024)

Immunotherapy has emerged as a robust approach against cancer, yet its efficacy has varied among individuals, accompanied by the occurrence of immune-related adverse events. As a result, the efficacy of immunotherapy is far from satisfactory, and enormous efforts have been invested to develop strategies to improve patient outcomes. The gut microbiome is now well acknowledged for its critical role in immunotherapy, with better understanding on host-microbes interaction in the context of cancer treatment. Also, an increasing number of trials have been conducted to evaluate the potential and feasibility of microbiome-targeting approaches to enhance efficacy of cancer treatment in patients. Here, the role of the gut microbiome and metabolites (e.g., short-chain fatty acids, tryptophan metabolites) in immunotherapy and the underlying mechanisms are explored. The application of microbiome-targeting approaches that aim to improve immunotherapy efficacy (e.g., fecal microbiota transplantation, probiotics, dietary intervention) is also elaborated, with further discussion on current challenges and suggestions for future research.
Context matters: Tumor microenvironments impact cellular therapy success
Authors: Eli P. Darnell, Marcela V. Maus
Journal: Cell Reports Medicine (2024)

In a recent publication, Locke et al. present data from pretreatment tumor biopsies taken on the ZUMA-7 trial. Their results identify tumor microenvironment (TME) contexts and level of CD19 expression as prognostic indicators for responses to axicabtagene ciloleucel (axi-cel).
Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York
Authors: Hai-Wei Liang, Hannu Koistinen, Emily S. Barrett, Xiaoshuang Xun, Qing Yin, Kurunthachalam Kannan, Nora K. Moog, Carla Ng, Thomas G. O’Connor, Rich Miller, Jennifer J. Adibi
Journal: Environmental Health Perspectives (2024)

Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity.
Microbiome and cancer immunotherapies
Authors: Haoyan Chen, Laurence Zitvogel, Zhi Peng, Xiaochen Yin, Florencia McAllister
Journal: Cell Reports Medicine (2024)

Here, we present 3 different perspectives on how the microbiome has impacted cancer patients, treatment, and clinical studies. We hear about the challenges of implementing microbiome analyses into the clinics, the impact these analyses might have on patients' care, and treatment in the future, specifically for gastric cancer treatment. These are a few of the many voices that are highlighting the role of the microbiome in cancer development, treatment, and clinical outcomes.
Take CT, get PET free: AI-powered breakthrough in lung cancer diagnosis and prognosis
Authors: Tonghe Wang, Xiaofeng Yang
Journal: Cell Reports Medicine (2024)

PET scans provide additional clinical value but are costly and not universally accessible. Salehjahromi et al.<sup>1</sup> developed an AI-based pipeline to synthesize PET images from diagnostic CT scans, demonstrating its potential clinical utility across various clinical tasks for lung cancer.
Jennifer A. Wargo, Nadim J. Ajami, and Carrie R. Daniel-MacDougall
Authors: Jennifer A. Wargo, Nadim J. Ajami, Carrie R. Daniel-MacDougall
Journal: Cell Reports Medicine (2024)

Dr. Jennifer A. Wargo, Dr. Nadim J. Ajami, and Dr. Carrie R. Daniel-MacDougall describe their academic and clinical work on the role of the microbiome to determine response to immunotherapies and discuss current challenges and potential needs to integrate their findings into clinical practice.
Hypertension, Cardiovascular Risk Factors, and Uterine Fibroid Diagnosis in Midlife
Authors: Susanna D. Mitro, Lauren A. Wise, L. Elaine Waetjen, Catherine Lee, Eve Zaritsky, Siobán D. Harlow, Daniel H. Solomon, Rebecca C. Thurston, Samar R. El Khoudary, Nanette Santoro, Monique M. Hedderson
Journal: JAMA Network Open (2024)

Importance Fibroids are benign neoplasms associated with severe gynecologic morbidity. There are no strategies to prevent fibroid development. Objective To examine associations of hypertension, antihypertensive treatment, anthropometry, and blood biomarkers with incidence of reported fibroid diagnosis in midlife. Design, Setting, and Participants The Study of Women’s Health Across the Nation is a prospective, multisite cohort study in the US. Participants were followed-up from enrollment (1996-1997) through 13 semiannual visits (1998-2013). Participants had a menstrual period in the last 3 months, were not pregnant or lactating, were aged 42 to 52 years, were not using hormones, and had a uterus and at least 1 ovary. Participants with prior fibroid diagnoses were excluded. Data analysis was performed from November 2022 to February 2024. Exposures Blood pressure, anthropometry, biomarkers (cholesterol, triglycerides, and C-reactive protein), and self-reported antihypertensive treatment at baseline and follow-up visits were measured. Hypertension status (new-onset, preexisting, or never [reference]) and hypertension treatment (untreated, treated, or no hypertension [reference]) were categorized. Main Outcomes and Measures Participants reported fibroid diagnosis at each visit. Discrete-time survival models estimated hazard ratios (HRs) and 95% CIs for associations of time-varying hypertension status, antihypertensive treatment, anthropometry, and biomarkers with incident reported fibroid diagnoses. Results Among 2570 participants without a history of diagnosed fibroids (median [IQR] age at screening, 45 [43-48] years; 1079 [42.1%] college educated), 526 (20%) reported a new fibroid diagnosis during follow-up. Risk varied by category of hypertension treatment: compared with those with no hypertension, participants with untreated hypertension had a 19% greater risk of newly diagnosed fibroids (HR, 1.19; 95% CI, 0.91-1.57), whereas those with treated hypertension had a 20% lower risk (HR, 0.80; 95% CI, 0.56-1.15). Among eligible participants with hypertension, those taking antihypertensive treatment had a 37% lower risk of newly diagnosed fibroids (HR, 0.63; 95% CI, 0.38-1.05). Risk also varied by hypertension status: compared with never-hypertensive participants, participants with new-onset hypertension had 45% greater risk of newly diagnosed fibroids (HR, 1.45; 95% CI, 0.96-2.20). Anthropometric factors and blood biomarkers were not associated with fibroid risk. Conclusions and Relevance Participants with untreated and new-onset hypertension had increased risk of newly diagnosed fibroids, whereas those taking antihypertensive treatment had lower risk, suggesting that blood pressure control may provide new strategies for fibroid prevention.
Anti–Tumor Necrosis Factor Therapy and Risk of Kidney Function Decline and Mortality in Inflammatory Bowel Disease
Authors: Keiichi Sumida, Prabin Shrestha, Yamini Mallisetty, Fridtjof Thomas, Geeta Gyamlani, Elani Streja, Kamyar Kalantar-Zadeh, Csaba P. Kovesdy
Journal: JAMA Network Open (2024)

Importance Inflammatory bowel disease (IBD) is associated with adverse clinical outcomes, including chronic kidney disease and mortality, due in part to chronic inflammation. Little is known about the effects of anti–tumor necrosis factor (TNF) therapy on kidney disease progression and mortality among patients with new-onset IBD. Objective To examine the association of incident use of TNF inhibitors with subsequent decline in kidney function and risk of all-cause mortality. Design, Setting, and Participants This retrospective cohort study used data from the US Department of Veterans Affairs health care system. Participants were US veterans with new-onset IBD enrolled from October 1, 2004, through September 30, 2019. Data were analyzed from December 2022 to February 2024. Exposures Incident use of TNF inhibitors. Main Outcomes and Measures The main outcomes were at least 30% decline in estimated glomerular filtration rate (eGFR) and all-cause mortality. Results Among 10 689 patients (mean [SD] age, 67.4 [12.3] years; 9999 [93.5%] male) with incident IBD, 3353 (31.4%) had diabetes, the mean (SD) baseline eGFR was 77.2 (19.2) mL/min/1.73 m 2 , and 1515 (14.2%) were newly initiated on anti-TNF therapy. During a median (IQR) follow-up of 4.1 (1.9-7.0) years, 3367 patients experienced at least 30% decline in eGFR, and over a median (IQR) follow-up of 5.0 (2.5-8.0) years, 2502 patients died. After multivariable adjustments, incident use (vs nonuse) of TNF inhibitors was significantly associated with higher risk of decline in eGFR (adjusted hazard ratio [HR], 1.34 [95% CI, 1.18-1.52]) but was not associated with risk of all-cause mortality (adjusted HR, 1.02 [95% CI, 0.86-1.21]). Similar results were observed in sensitivity analyses. Conclusions and Relevance In this cohort study of US veterans with incident IBD, incident use (vs nonuse) of TNF inhibitors was independently associated with higher risk of progressive eGFR decline but was not associated with risk of all-cause mortality. Further studies are needed to elucidate potentially distinct pathophysiologic contributions of TNF inhibitor use to kidney and nonkidney outcomes in patients with IBD.
Unlocking ferroptosis in prostate cancer — the road to novel therapies and imaging markers
Authors: Pham Hong Anh Cao, Abishai Dominic, Fabiola Ester Lujan, Sanjanaa Senthilkumar, Pratip K. Bhattacharya, Daniel E. Frigo, Elavarasan Subramani
Journal: Nature Reviews Urology (2024)
The secreted micropeptide C4orf48 enhances renal fibrosis via an RNA-binding mechanism
Authors: Jiayi Yang, Hongjie Zhuang, Jinhua Li, Ana B. Nunez-Nescolarde, Ning Luo, Huiting Chen, Andy Li, Xinli Qu, Qing Wang, Jinjin Fan, Xiaoyan Bai, Zhiming Ye, Bing Gu, Yue Meng, Xingyuan Zhang, Di Wu, Youyang Sia, Xiaoyun Jiang, Wei Chen, Alexander N. Combes, David J. Nikolic-Paterson, Xueqing Yu
Journal: Journal of Clinical Investigation (2024)

Renal interstitial fibrosis is an important mechanism in the progression of chronic kidney disease (CKD) to end-stage kidney disease. However, we lack specific treatments to slow or halt renal fibrosis. Ribosome profiling identified upregulation of a secreted micropeptide, C4orf48 (Cf48), in mouse diabetic nephropathy. Cf48 RNA and protein levels were upregulated in tubular epithelial cells in human and experimental CKD. Serum Cf48 levels were increased in human CKD and correlated with loss of kidney function, increasing CKD stage, and the degree of active interstitial fibrosis. Cf48 overexpression in mice accelerated renal fibrosis, while Cf48 gene deletion or knockdown by antisense oligonucleotides significantly reduced renal fibrosis in CKD models. In vitro, recombinant Cf48 (rCf48) enhanced TGF-β1-induced fibrotic responses in renal fibroblasts and epithelial cells independent of Smad3 phosphorylation. Cellular uptake of Cf48 and its pro-fibrotic response in fibroblasts operated via the transferrin receptor. RNA immunoprecipitation-sequencing identified Cf48 binding to mRNA of genes involved in the fibrotic response, including Serpine1, Acta2, Ccn2, and Col4a1. rCf48 binds to the 3′-untranslated region of Serpine1 and increases mRNA half-life. We identify the secreted Cf48 micropeptide as a potential enhancer of renal fibrosis which operates as an RNA-binding peptide to promote the production of extracellular matrix.
British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults
Authors: Abid Suddle, Helen Reeves, Richard Hubner, Aileen Marshall, Ian Rowe, Dina Tiniakos, Stefan Hubscher, Mark Callaway, Dinesh Sharma, Teik Choon See, Maria Hawkins, Suzanne Ford-Dunn, Sarah Selemani, Tim Meyer
Journal: Gut (2024)

Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.
Viable mutations of mouse midnolin suppress B cell malignancies
Authors: Xue Zhong, Nagesh Peddada, James J. Moresco, Jianhui Wang, Yiao Jiang, Jonathan J. Rios, Eva Marie Y. Moresco, Jin Huk Choi, Bruce Beutler
Journal: The Journal of Experimental Medicine (2024)

In a genetic screen, we identified two viable missense alleles of the essential gene Midnolin (Midn) that were associated with reductions in peripheral B cells. Causation was confirmed in mice with targeted deletion of four of six MIDN protein isoforms. MIDN was expressed predominantly in lymphocytes where it augmented proteasome activity. We showed that purified MIDN directly stimulated 26S proteasome activity in vitro in a manner dependent on the ubiquitin-like domain and a C-terminal region. MIDN-deficient B cells displayed aberrant activation of the IRE-1/XBP-1 pathway of the unfolded protein response. Partial or complete MIDN deficiency strongly suppressed Eμ-Myc–driven B cell leukemia and the antiapoptotic effects of Eμ-BCL2 on B cells in vivo and induced death of Sp2/0 hybridoma cells in vitro, but only partially impaired normal lymphocyte development. Thus, MIDN is required for proteasome activity in support of normal lymphopoiesis and is essential for malignant B cell proliferation over a broad range of differentiation states.
Evolution of the clinical-stage hyperactive TcBuster transposase as a platform for robust non-viral production of adoptive cellular therapies
Authors: Joseph G. Skeate, Emily J. Pomeroy, Nicholas J. Slipek, Bryan J. Jones, Bryce J. Wick, Jae-Woong Chang, Walker S. Lahr, Erin M. Stelljes, Xiaobai Patrinostro, Blake Barnes, Trevor Zarecki, Joshua B. Krueger, Jacob E. Bridge, Gabrielle M. Robbins, Madeline D. McCormick, John R. Leerar, Kari T. Wenzel, Kathlyn M. Hornberger, Kirsti Walker, Dalton Smedley, David A. Largaespada, Neil Otto, Beau R. Webber, Branden S. Moriarity
Journal: Molecular Therapy (2024)

Cellular therapies for the treatment of human diseases, such as chimeric antigen receptor (CAR) T and natural killer (NK) cells have shown remarkable clinical efficacy in treating hematological malignancies; however, current methods mainly utilize viral vectors that are limited by their cargo size capacities, high cost, and long timelines for production of clinical reagent. Delivery of genetic cargo via DNA transposon engineering is a more timely and cost-effective approach, yet has been held back by less efficient integration rates. Here, we report the development of a novel hyperactive TcBuster (TcB-M) transposase engineered through structure-guided and in vitro evolution approaches that achieves high-efficiency integration of large, multicistronic CAR-expression cassettes in primary human cells. Our proof-of-principle TcB-M engineering of CAR-NK and CAR-T cells shows low integrated vector copy number, a safe insertion site profile, robust in vitro function, and improves survival in a Burkitt lymphoma xenograft model in vivo. Overall, TcB-M is a versatile, safe, efficient and open-source option for the rapid manufacture and preclinical testing of primary human immune cell therapies through delivery of multicistronic large cargo via transposition.Graphical abstract
A spatiotemporal atlas of mouse liver homeostasis and regeneration
Authors: Jiangshan Xu, Pengcheng Guo, Shijie Hao, Shuncheng Shangguan, Quan Shi, Giacomo Volpe, Keke Huang, Jing Zuo, Juan An, Yue Yuan, Mengnan Cheng, Qiuting Deng, Xiao Zhang, Guangyao Lai, Haitao Nan, Baihua Wu, Xinyi Shentu, Liang Wu, Xiaoyu Wei, Yujia Jiang, Xin Huang, Fengyu Pan, Yumo Song, Ronghai Li, Zhifeng Wang, Chuanyu Liu, Shiping Liu, Yuxiang Li, Tao Yang, Zhicheng Xu, Wensi Du, Ling Li, Tanveer Ahmed, Kai You, Zhen Dai, Li Li, Baoming Qin, Yinxiong Li, Liangxue Lai, Dajiang Qin, Junling Chen, Rong Fan, Yongyin Li, Jinlin Hou, Michael Ott, Amar Deep Sharma, Tobias Cantz, Axel Schambach, Karsten Kristiansen, Andrew P. Hutchins, Berthold Göttgens, Patrick H. Maxwell, Lijian Hui, Xun Xu, Longqi Liu, Ao Chen, Yiwei Lai, Miguel A. Esteban
Journal: Nature Genetics (2024)
Reporting quality of heart failure randomized controlled trials 2000–2020: Temporal trends in adherence to CONSORT criteria
Authors: Mohamed B. Jalloh, Veronica A. Bot, Cristiana Z. Borjaille, Lehana Thabane, Guowei Li, Javed Butler, Faiez Zannad, Christopher B. Granger, Harriette G.C. Van Spall
Journal: European Journal of Heart Failure (2024)

ABSTRACT Aim Heart failure (HF) is a major cause of morbidity and mortality in older adults. Randomized controlled trials (RCTs) inform HF policy and practice, but the accurate interpretation of results is contingent on clear and transparent reporting. The CONsolidated Standards Of Reporting Trials (CONSORT) statement serves as a guide to RCT reporting. We evaluated the quality of reporting in HF RCTs in high‐impact journals by assessing their adherence to CONSORT. Methods and results We searched MEDLINE, EMBASE and CINAHL for HF RCTs published in high‐impact journals 2000–2020. We assessed the proportion of CONSORT criteria that individual HF RCTs adhered to, and used the Jonckheere–Terpstra test to examine temporal trends in adherence. Multivariable linear regression explored the association between trial characteristics and adherence to CONSORT. Primary analysis assessed adherence to CONSORT 2010 update. A sensitivity analysis assessed adherence to the original (1996) CONSORT criteria. Among 221 RCTs analysed, the mean (standard deviation [SD]) adherence was suboptimal overall (mean [SD] adherence 69.7 [11.5]%) (5513/7913 criteria), with a temporal increase in adherence over the 20‐year period ( p &lt; 0.001). Factors associated with adherence included publication after versus during/before 2010 ( β = 10.17, 95% confidence interval [CI] 7.64–12.70; p &lt; 0.001); two‐group parallel individual‐level randomization versus other (including multi‐group or cluster randomization) ( β = 5.81, 95% CI 2.88–8.73; p &lt; 0.001); and multicentre versus single‐centre trials ( β = 7.26, 95% CI 3.25–11.27; p &lt; 0.001). There was no difference in trial adherence to the updated CONSORT (2010) versus the original (1996) CONSORT criteria, and temporal trends in adherence to both sets of criteria were similar, likely due to overlap between the two sets of criteria. Trials with greater adherence to CONSORT were published in higher impact factor journals, with a positive correlation ( r = 0.312; p &lt; 0.001). Conclusion The quality of reporting in HF RCTs, as measured by CONSORT adherence, has improved over time but remains suboptimal.