tbuckley/cabot-search huggingface dataset:
Prenatal BRCA1 epimutations contribute significantly to triple-negative breast cancer development
Authors: Oleksii Nikolaienko, Hans P. Eikesdal, Elisabet Ognedal, Bjørnar Gilje, Steinar Lundgren, Egil S. Blix, Helge Espelid, Jürgen Geisler, Stephanie Geisler, Emiel A. M. Janssen, Synnøve Yndestad, Laura Minsaas, Beryl Leirvaag, Reidun Lillestøl, Stian Knappskog, Per E. Lønning
Journal: Genome Medicine (2023)

Abstract Background Normal cell BRCA1 epimutations have been associated with increased risk of triple-negative breast cancer (TNBC). However, the fraction of TNBCs that may have BRCA1 epimutations as their underlying cause is unknown. Neither are the time of occurrence and the potential inheritance patterns of BRCA1 epimutations established. Methods To address these questions, we analyzed BRCA1 methylation status in breast cancer tissue and matched white blood cells (WBC) from 408 patients with 411 primary breast cancers, including 66 TNBCs, applying a highly sensitive sequencing assay, allowing allele-resolved methylation assessment. Furthermore, to assess the time of origin and the characteristics of normal cell BRCA1 methylation, we analyzed umbilical cord blood of 1260 newborn girls and 200 newborn boys. Finally, we assessed BRCA1 methylation status among 575 mothers and 531 fathers of girls with ( n = 102) and without ( n = 473) BRCA1 methylation. Results We found concordant tumor and mosaic WBC BRCA1 epimutations in 10 out of 66 patients with TNBC and in four out of six patients with estrogen receptor (ER)-low expression (&lt; 10%) tumors (combined: 14 out of 72; 19.4%; 95% CI 11.1–30.5). In contrast, we found concordant WBC and tumor methylation in only three out of 220 patients with 221 ER ≥ 10% tumors and zero out of 114 patients with 116 HER2-positive tumors. Intraindividually, BRCA1 epimutations affected the same allele in normal and tumor cells. Assessing BRCA1 methylation in umbilical WBCs from girls, we found mosaic, predominantly monoallelic BRCA1 epimutations, with qualitative features similar to those in adults, in 113/1260 (9.0%) of individuals, but no correlation to BRCA1 methylation status either in mothers or fathers. A significantly lower fraction of newborn boys carried BRCA1 methylation (9/200; 4.5%) as compared to girls ( p = 0.038). Similarly, WBC BRCA1 methylation was found less common among fathers (16/531; 3.0%), as compared to mothers (46/575; 8.0%; p = 0.0003). Conclusions Our findings suggest prenatal BRCA1 epimutations might be the underlying cause of around 20% of TNBC and low-ER expression breast cancers. Such constitutional mosaic BRCA1 methylation likely arise through gender-related mechanisms in utero, independent of Mendelian inheritance.
Aspiration of tissues and ascites: the solution to endoscopic ultrasound-related duodenal perforation during pancreatic cancer sampling
Authors: Qin Lu, Zhi-qiang Du, Xiang-rong Zhou, Min Yang, Rui Huang, Wei-hui Liu
Journal: Endoscopy (2023)

Duodenal perforation is one of the most severe complications of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) [1] [2] [3] [4] [5]. Here we report on a patient with a large duodenal perforation during EUS-FNA who was successfully treated under endoscopy with purse-string suture, release of abdominal gas, aspiration of tissues and ascites, and sufficient decompression and drainage ([Video 1]).
A tricky gastric lesion diagnosed by small-bowel capsule endoscopy
Authors: Willian Ferreira Igi, Elen Bruna Teixeira Boulhosa, Magda Priscila Cardoso Afonso, Fernando Lander Mota
Journal: Endoscopy (2023)

Small-bowel capsule endoscopy (SBCE) is the first-line method for investigating overt gastrointestinal bleeding (OGB), ideally within 48 hours after the episode [1]. However, SBCE can also evaluate lesions outside the small bowel, even though that is not its original purpose. This is extremely important when considering the prevalence of lesions outside the small bowel that are missed by conventional esophagogastroduodenoscopy (EGD) or push enteroscopy, a rate that ranges from 3.5% to more than 30% [2].
ALDOB/KAT2A interactions epigenetically modulate TGF-β expression and T cell functions in hepatocellular carcinogenesis
Authors: Chunzhao Yin, Cunzhen Zhang, Yongqiang Wang, Guijun Liu, Ningning Wang, Ningning Liang, Lili Zhang, Qiaochu Tu, Jingwen Lv, Huimin Jiang, Haoran Ma, Chenxi Du, Min Li, Xuxiao He, Shiting Chen, Jiacheng Guo, Shengxian Li, Jun Qin, Nan Li, Yongzhen Tao, Huiyong Yin
Journal: Hepatology (2023)

Background and Aims: Cross talk between tumor cells and immune cells enables tumor cells to escape immune surveillance and dictate responses to immunotherapy. Previous studies have identified that downregulation of the glycolytic enzyme fructose-1,6-bisphosphate aldolase B (ALDOB) in tumor cells orchestrated metabolic programming to favor HCC. However, it remains elusive whether and how ALDOB expression in tumor cells affects the tumor microenvironment in HCC. Approach and Results: We found that ALDOB downregulation was negatively correlated with CD8 + T cell infiltration in human HCC tumor tissues but in a state of exhaustion. Similar observations were made in mice with liver-specific ALDOB knockout or in subcutaneous tumor models with ALDOB knockdown. Moreover, ALDOB deficiency in tumor cells upregulates TGF-β expression, thereby increasing the number of Treg cells and impairing the activity of CD8 + T cells. Consistently, a combination of low ALDOB and high TGF-β expression exhibited the worst overall survival for patients with HCC. More importantly, the simultaneous blocking of TGF-β and programmed cell death (PD) 1 with antibodies additively inhibited tumorigenesis induced by ALDOB deficiency in mice. Further mechanistic experiments demonstrated that ALDOB enters the nucleus and interacts with lysine acetyltransferase 2A, leading to inhibition of H3K9 acetylation and thereby suppressing TGFB1 transcription. Consistently, inhibition of lysine acetyltransferase 2A activity by small molecule inhibitors suppressed TGF-β and HCC. Conclusions: Our study has revealed a novel mechanism by which a metabolic enzyme in tumor cells epigenetically modulates TGF-β signaling, thereby enabling cancer cells to evade immune surveillance and affect their response to immunotherapy.
Opportunities and challenges of human large language models in surgery: a bibliometric analysis
Authors: Ziyue Luo, Jingwen Wei, Ruihao Zhou
Journal: International Journal of Surgery (2023)

aDepartment of Anaesthesiology, West China Hospital of Sichuan University, Sichuan Province, Chengdu, 610041, China bDepartment of Urology, West China Hospital of Sichuan University, Sichuan Province, Chengdu, 610041, China Ziyue Luo, Jingwen Wei These authors contributed equally to the article and should be considered co-first authors. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Anesthesiology, National Clinical Research Center for Geriatrics, West China Hospital, The Research Units of West China (2018RU012)- Chinese Academy of Medical Sciences, West China Hospital, Sichuan University No. 37 Guoxue Xiang, Wuhou District Chengdu, Sichuan, China. E-mail address: [email protected] (R. Zhou). This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0, which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. http://creativecommons.org/licenses/by-nd/4.0/
RETRACTION: Changes in soft drinks purchased by British households associated with the UK soft drinks industry levy: controlled interrupted time series analysis
Journal: BMJ (2023)

The authors themselves identified the problem and alerted the journal and readers about inaccuracies arising from the way in which the data were prepared for analysis.Correcting the error changed the findings of the paper.The reduction in sugar intake per household was less than previously reported, and an increase in the volume of purchased drinks was found.The journal judged that the policy implications of the paper were affected by these changes and did not think that correction of the paper would be the appropriate course of action.
Adaptive cell wall thickening in Enterococcus faecalis is associated with decreased vancomycin susceptibility
Authors: Theresa Maria Wagner, Anna K. Pöntinen, Mushtaq AL Rubaye, Arnfinn Sundsfjord, Kristin Hegstad
Journal: Clinical Microbiology and Infection (2023)

Enterococcus faecalis can adopt both a commensal and a nosocomial lifestyle, resisting numerous antibiotics. In this study, we aim to investigate the relationship between the cell wall (CW) thickness and decreased susceptibility to vancomycin (VD) in van-gene negative clinical isolates of E. faecalis (n
Alcoholic Foamy Degeneration, an Entity Resembling Alcohol-Associated Hepatitis: Diagnosis, Prognosis, and Molecular Profiling
Authors: Jordi Gratacós-Ginès, Emma Avitabile, Carla Montironi, Alex Guillamon-Thiery, Helena Hernández-Évole, María José Moreta, Delia Blaya, Silvia Ariño, Ana Belén Rubio, Martina Pérez-Guasch, Marta Cervera, Marta Carol, Núria Fabrellas, Anna Soria, Adrià Juanola, Isabel Graupera, Pau Sancho-Bru, Alba Díaz, Mar Coll, Ramón Bataller, Pere Ginès, Elisa Pose
Journal: Clinical Gastroenterology and Hepatology (2023)

Background Alcoholic Foamy Degeneration (AFD) is a condition with similar clinical presentation to alcohol-associated hepatitis (AH) but with a specific histological pattern. Information regarding prevalence and prognosis of AFD is scarce and there are no tools for non-invasive diagnosis. Methods a cohort of patients admitted to Hospital Clinic of Barcelona for clinical suspicion of AH that underwent liver biopsy was included. Patients were classified in AFD, AH or other findings, according to histology. Clinical features, histology and genetic expression of liver biopsies were analyzed. Accuracy of NIAAA criteria and laboratory parameters for differential diagnosis were investigated. Results Out of 230 patients with suspicion of AH, 18 (8%) met histological criteria for AFD, 184 (80%) had definite AH and 28 (12%) had other findings. In patients with AFD, massive steatosis was more frequent and fibrosis stage was lower. AFD was characterized by down-regulation of genes of liver fibrosis and inflammation and up-regulation of genes of lipid-metabolism and mitochondrial function. Patients with AFD had markedly better long-term survival (100% vs 57% in AFD vs AH, P=.002) despite not receiving corticosteroid treatment, even in a MELD-matched sensitivity analysis. Serum triglycerides had an AUROC of 0.886 (0.807-0.964) for the diagnosis of AFD, while NIAAA criteria performed poorly. A one-step algorithm using triglyceride levels of 225mg/dL (sensitivity 0.77, specificity 0.90, Youden 0.67) is proposed for differential diagnosis. Conclusions AFD in the setting of suspicion of AH is not uncommon. Differential diagnosis is important because prognosis and treatment differ largely. Triglyceride levels successfully identify most patients with AFD and may be helpful in decision-making.
<i>Bifidobacterium</i> mechanisms of immune modulation and tolerance
Authors: Samuel J Gavzy, Allison Kensiski, Zachariah L Lee, Emmanuel F Mongodin, Bing Ma, Jonathan S Bromberg
Journal: Gut Microbes (2023)

Bifidobacterium is a widely distributed commensal bacterial genus that displays beneficial pro-homeostatic and anti-inflammatory immunomodulatory properties. Depletion or absence of Bifidobacterium in humans and model organisms is associated with autoimmune responses and impaired immune homeostasis. At the cellular level, Bifidobacterium upregulates suppressive regulatory T cells, maintains intestinal barrier function, modulates dendritic cell and macrophage activity, and dampens intestinal Th2 and Th17 programs. While there has been a large volume of literature characterizing the probiotic properties of various Bifidobacterial species, the likely multifactorial mechanisms underlying these effects remain elusive, in particular, its immune tolerogenic effect. However, recent work has shed light on Bifidobacterium surface structural polysaccharide and protein elements, as well as its metabolic products, as commensal mediators of immune homeostasis. This review aims to discuss several mechanisms Bifidobacterium utilizes for immune modulation as well as their indirect impact on the regulation of gut microbiome structure and function, from structural molecules to produced metabolites. These mechanisms are pertinent to an increasingly networked understanding of immune tolerance and homeostasis in health and disease.
A global analysis of the determinants of maternal health and transitions in maternal mortality
Authors: João Paulo Souza, Louise Tina Day, Ana Clara Rezende-Gomes, Jun Zhang, Rintaro Mori, Adama Baguiya, Kapila Jayaratne, Alfred Osoti, Joshua P Vogel, Oona Campbell, Kidza Y Mugerwa, Pisake Lumbiganon, Özge Tunçalp, Jenny Cresswell, Lale Say, Allisyn Carol Moran, Olufemi T Oladapo
Journal: The Lancet Global Health (2023)

The reduction of maternal mortality and the promotion of maternal health and wellbeing are complex tasks. This Series paper analyses the distal and proximal determinants of maternal health, as well as the exposures, risk factors, and micro-correlates related to maternal mortality. This paper also examines the relationship between these determinants and the gradual shift over time from a pattern of high maternal mortality to a pattern of low maternal mortality (a phenomenon described as the maternal mortality transition). We conducted two systematic reviews of the literature and we analysed publicly available data on indicators related to the Sustainable Development Goals, specifically, estimates prepared by international organisations, including the UN and the World Bank. We considered 23 frameworks depicting maternal health and wellbeing as a multifactorial process, with superdeterminants that broadly affect women's health and wellbeing before, during, and after pregnancy. We explore the role of social determinants of maternal health, individual characteristics, and health-system features in the production of maternal health and wellbeing. This paper argues that the preventable deaths of millions of women each decade are not solely due to biomedical complications of pregnancy, childbirth, and the postnatal period, but are also tangible manifestations of the prevailing determinants of maternal health and persistent inequities in global health and socioeconomic development. This paper underscores the need for broader, multipronged actions to improve maternal health and wellbeing and accelerate sustainable reductions in maternal mortality. For women who have pregnancy, childbirth, or postpartum complications, the health system provides a crucial opportunity to interrupt the chain of events that can potentially end in maternal death. Ultimately, expanding the health sector ecosystem to mitigate maternal health determinants and tailoring the configuration of health systems to counter the detrimental effects of eco-social forces, including though increased access to quality-assured commodities and services, are essential to improve maternal health and wellbeing and reduce maternal mortality.
Neglected medium-term and long-term consequences of labour and childbirth: a systematic analysis of the burden, recommended practices, and a way forward
Authors: Joshua P Vogel, Jenny Jung, Tina Lavin, Grace Simpson, Dvora Kluwgant, Edgardo Abalos, Virginia Diaz, Soo Downe, Veronique Filippi, Ioannis Gallos, Hadiza Galadanci, Geetanjali Katageri, Caroline S E Homer, G Justus Hofmeyr, Tippawan Liabsuetrakul, Imran O Morhason-Bello, Alfred Osoti, João Paulo Souza, Ranee Thakar, Shakila Thangaratinam, Olufemi T Oladapo
Journal: The Lancet Global Health (2023)

Over the past three decades, substantial progress has been made in reducing maternal mortality worldwide. However, the historical focus on mortality reduction has been accompanied by comparative neglect of labour and birth complications that can emerge or persist months or years postnatally. This paper addresses these overlooked conditions, arguing that their absence from the global health agenda and national action plans has led to the misconception that they are uncommon or unimportant. The historical limitation of postnatal care services to the 6 weeks after birth is also a contributing factor. We reviewed epidemiological data on medium-term and long-term complications arising from labour and childbirth beyond 6 weeks, along with high-quality clinical guidelines for their prevention, identification, and treatment. We explore the complex interplay of human evolution, maternal physiology, and inherent predispositions that contribute to these complications. We offer actionable recommendations to change the current trajectories of these neglected conditions and help achieve the targets of Sustainable Development Goal 3. This paper is the third in a Series of four papers about maternal health in the perinatal period and beyond.
Implementation of a liver health check in people with type 2 diabetes
Authors: Kushala W M Abeysekera, Luca Valenti, Zobair Younossi, John F Dillon, Alina M Allen, Mazen Noureddin, Mary E Rinella, Frank Tacke, Sven Francque, Pere Ginès, Maja Thiele, Philip N Newsome, Indra Neil Guha, Mohammed Eslam, Jörn M Schattenberg, Saleh A Alqahtani, Marco Arrese, Annalisa Berzigotti, Adriaan G Holleboom, Cyrielle Caussy, Kenneth Cusi, Michael Roden, Hannes Hagström, Vincent Wai-Sun Wong, Vincent Mallet, Laurent Castera, Jeffrey V Lazarus, Emmanuel A Tsochatzis
Journal: The Lancet. Gastroenterology & hepatology (2023)
SARS-CoV-2 mucosal neutralising immunity after vaccination
Authors: Edward J Carr, Guilia Dowgier, David Greenwood, Lou S Herman, Agnieszka Hobbs, Martina Ragno, Phoebe Stevenson-Leggett, Joshua Gahir, Hermaleigh Townsley, Ruth Harvey, Chris Bailey, Ashley S Fowler, Murad Miah, Callie Smith, Mauro Miranda, Philip Bawumia, Harriet V Mears, Lorin Adams, Emine Hatipoglu, Nicola O'Reilly, Scott Warchal, Chelsea Sawyer, Karen Ambrose, Amy Strange, Gavin Kelly, Rupert Beale, Padmasayee Papineni, Tumena Corrah, Richard Gilson, Steve Gamblin, George Kassiotis, Vincenzo Libri, Bryan Williams, Charles Swanton, Sonia Gandhi, David L V Bauer, Emma Wall, Mary Y Wu
Journal: The Lancet Infectious Diseases (2023)
European validation of an image-derived AI-based short-term risk model for individualized breast cancer screening—a nested case-control study
Authors: Mikael Eriksson, Marta Román, Axel Gräwingholt, Xavier Castells, Andrea Nitrosi, Pierpaolo Pattacini, Sylvia Heywang-Köbrunner, Paolo G. Rossi
Journal: The Lancet Regional Health - Europe (2023)

Image-derived artificial intelligence (AI)-based risk models for breast cancer have shown high discriminatory performances compared with clinical risk models based on family history and lifestyle factors. However, little is known about their generalizability across European screening settings. We therefore investigated the discriminatory performances of an AI-based risk model in European screening settings. Using four European screening populations in three countries (Italy, Spain, Germany) screened between 2009 and 2020 for women aged 45–69, we performed a nested case-control study to assess the predictive performance of an AI-based risk model. In total, 739 women with incident breast cancers were included together with 7812 controls matched on year of study-entry. Mammographic features (density, microcalcifications, masses, left-right breast asymmetries of these features) were extracted using AI from negative digital mammograms at study-entry. Two-year absolute risks of breast cancer were predicted and assessed after two years of follow-up. Adjusted risk stratification performance metrics were reported per clinical guidelines. The overall adjusted Area Under the receiver operating characteristic Curve (aAUC) of the AI risk model was 0.72 (95% CI 0.70–0.75) for breast cancers developed in four screening populations. In the 6.2% [529/8551] of women at high risk using the National Institute of Health and Care Excellence (NICE) guidelines thresholds, cancers were more likely diagnosed after 2 years follow-up, risk-ratio (RR) 6.7 (95% CI 5.6–8.0), compared with the 69% [5907/8551] of women classified at general risk by the model. Similar risk-ratios were observed across levels of mammographic density. The AI risk model showed generalizable discriminatory performances across European populations and, predicted ∼30% of clinically relevant stage 2 and higher breast cancers in ∼6% of high-risk women who were sent home with a negative mammogram. Similar results were seen in women with fatty and dense breasts. Swedish Research Council.
Combination Therapy and Appropriate Dosing to Target KRAS in Colorectal Cancer
Authors: Rona Yaeger
Journal: New England Journal of Medicine (2023)

In this issue of the Journal, Fakih et al.1 report the results from CodeBreaK 300, a phase 3 trial of the selective Kirsten rat sarcoma viral oncogene homologue (KRAS) glycine-to-cysteine mutation at codon 12 (KRAS G12C) inhibitor sotorasib in combination with the epidermal growth factor receptor (EGFR) inhibitor panitumumab in patients with metastatic colorectal cancer with KRAS G12C mutation. In this trial, two investigational groups — one that received full-dose sotorasib (960 mg once daily) in combination with panitumumab and one that received lower-dose sotorasib (240 mg once daily) in combination with panitumumab — were compared with a group that . . .
Tominersen in Adults with Manifest Huntington’s Disease
Authors: Peter McColgan, Alpa Thobhani, Lauren Boak, Scott A Schobel, Alessia Nicotra, Giuseppe Palermo, Dylan Trundell, Julian Zhou, Valerie Schlegel, Patricia Sanwald Ducray, David J Hawellek, Jonas Dorn, Cedric Simillion, Michael Lindemann, Vicki Wheelock, Alexandra Durr, Karen E Anderson, Jeffrey D Long, Edward J Wild, G Bernhard Landwehrmeyer, Blair R Leavitt, Sarah J Tabrizi, Rachelle Doody
Journal: New England Journal of Medicine (2023)