tbuckley/cabot-search huggingface dataset:
Exploration of the association of a lipid-related biomarker, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR), and the risk of breast cancer in American women aged 20 years and older
Authors: Xuemei Luo, Jianrui Ye, Ting Xiao, Tao Yi
Journal: International Journal of Surgery (2024)

aDepartment of General Surgery, Mianzhu City People's Hospital, Mianzhu, 618200, China bDepartment of Traditional Chinese Medicine, Longquanyi District Hospital of Traditional Chinese Medicine, Chengdu, 610000, China cDepartment of Rehabilitation Medicine, Mianzhu City People's Hospital, Mianzhu, 618200, China dThe School of Nursing, Chengdu Medical College, Chengdu, 610000, China Xuemei Luo, Jianrui Ye These authors have contributed equally to this work and share co-first authorship. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding Author Address: Chengdu Medical College, CHINA. E-mail address: [email protected] (T. Yi). Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.lww.com/international-journal-of-surgery. Published online ■ ■ This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Integrated safety analysis of filgotinib in patients with moderate-to-severe rheumatoid arthritis over a treatment duration of up to 8.3 years
Authors: Gerd R Burmester, Jacques-Eric Gottenberg, Roberto Caporali, Kevin L Winthrop, Yoshiya Tanaka, Edmund V Ekoka Omoruyi, Vijay Rajendran, Paul Van Hoek, Katrien Van Beneden, Tsutomu Takeuchi, René Westhovens, Daniel Aletaha
Journal: Annals of the Rheumatic Diseases (2024)

To update the long-term safety profile of filgotinib, a Janus kinase-1 preferential inhibitor, in patients with moderate-to-severe rheumatoid arthritis.
Recommendations from the AML molecular MRD expert advisory board
Authors: Stuart Scott, Alison Devonshire, Richard Dillon, Christian Thiede, Nicholas C. P. Cross, Helen E. White, Leandro Lo Cascio, Katya Mokretar, Nicola Potter, Christopher S. Hourigan, Jerald Radich, Adam Corner, Véronique Laloux, Gemma Halliday, Daniel Dilks, Tom Morrison, Katelyn Gilmour, Ashley Cartwright, Liam Whitby
Journal: Leukemia (2024)
How to tackle therapeutic inertia in heart failure with reduced ejection fraction. A scientific statement of the Heart Failure Association of the ESC
Authors: Gianluigi Savarese, Felix Lindberg, Antonio Cannata, Ovidiu Chioncel, Davide Stolfo, Francesca Musella, Daniela Tomasoni, Magdy Abdelhamid, Debasish Banerjee, Antoni Bayes‐Genis, Emmanuelle Berthelot, Frieder Braunschweig, Andrew J.S. Coats, Nicolas Girerd, Ewa A. Jankowska, Loreena Hill, Mitja Lainscak, Yury Lopatin, Lars H. Lund, Aldo P. Maggioni, Brenda Moura, Amina Rakisheva, Robin Ray, Petar M. Seferovic, Hadi Skouri, Cristiana Vitale, Maurizio Volterrani, Marco Metra, Giuseppe M.C. Rosano
Journal: European Journal of Heart Failure (2024)

Abstract Guideline‐directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF) reduces morbidity and mortality, but its implementation is often poor in daily clinical practice. Barriers to implementation include clinical and organizational factors that might contribute to clinical inertia, i.e. avoidance/delay of recommended treatment initiation/optimization. The spectrum of strategies that might be applied to foster GDMT implementation is wide, and involves the organizational set‐up of heart failure care pathways, tailored drug initiation/optimization strategies increasing the chance of successful implementation, digital tools/telehealth interventions, educational activities and strategies targeting patient/physician awareness, and use of quality registries. This scientific statement by the Heart Failure Association of the ESC provides an overview of the current state of GDMT implementation in HFrEF, clinical and organizational barriers to implementation, and aims at suggesting a comprehensive framework on how to overcome clinical inertia and ultimately improve implementation of GDMT in HFrEF based on up‐to‐date evidence.
New insights into immune cells in cancer immunotherapy: from epigenetic modification, metabolic modulation to cell communication
Authors: Sha Qin, Bin Xie, Qingyi Wang, Rui Yang, Jingyue Sun, Chaotao Hu, Shuang Liu, Yongguang Tao, Desheng Xiao
Journal: MedComm (2024)

Abstract Cancer is one of the leading causes of death worldwide, and more effective ways of attacking cancer are being sought. Cancer immunotherapy is a new and effective therapeutic method after surgery, radiotherapy, chemotherapy, and targeted therapy. Cancer immunotherapy aims to kill tumor cells by stimulating or rebuilding the body's immune system, with specific efficiency and high safety. However, only few tumor patients respond to immunotherapy and due to the complex and variable characters of cancer immune escape, the behavior and regulatory mechanisms of immune cells need to be deeply explored from more dimensions. Epigenetic modifications, metabolic modulation, and cell‐to‐cell communication are key factors in immune cell adaptation and response to the complex tumor microenvironment. They collectively determine the state and function of immune cells through modulating gene expression, changing in energy and nutrient demands. In addition, immune cells engage in complex communication networks with other immune components, which are mediated by exosomes, cytokines, and chemokines, and are pivotal in shaping the tumor progression and therapeutic response. Understanding the interactions and combined effects of such multidimensions mechanisms in immune cell modulation is important for revealing the mechanisms of immunotherapy failure and developing new therapeutic targets and strategies.
Lung function trajectories in South African children with pulmonary tuberculosis compared to those with non-TB lower respiratory tract infection: a prospective study
Authors: Diane M. Gray, Leah Githinji, Kirsty Brittain, Zoe Franckling-Smith, Lindy Bateman, Margaretha Prins, Cynthia B. Baard, David McFarlane, Mark P. Nicol, Lesley Workman, Heather J. Zar
Journal: European Respiratory Journal (2024)

Paediatric pulmonary tuberculosis (PTB) contributes substantially to child illness globally [1]. Advances in diagnosis and treatment have improved survival, [2] but the long-term impact is a concern [3, 4]. Childhood PTB has been associated with chronic radiological changes, respiratory symptoms and reduced lung function, with impaired lung volumes common after TB treatment completion [5–7]. However, whether such impairment is similar with PTB compared to those with non-TB lower respiratory tract infection (LRTI) from the time of LRTI diagnosis until three months is unknown. We aimed to investigate the impact on lung health, by longitudinally measuring lung function in children with PTB compared to those with non-TB LRTI from the time of TB diagnosis until three months in all and extended follow up in children with PTB until six months after treatment completion. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflicts of Interest: This work was supported by the Regional Prospective Observational Research in Tuberculosis (RePORT TB) Consortium which is co-funded by the Medical Research Council of South Africa and the Division of AIDS Research of the National Institutes of Health, USA. Additional funding was received from the European and Developing Countries Clinical Trials Partnership (EDCTP), the South African Medical Research Council for the Tuberculosis Collaborating Centre for Child Health and the SA-MRC Unit on Child and Adolescent Health, and the National Institutes of Health, USA (RO1HD058971). HJZ is supported by the SA-MRC. LG is supported by EDCTP2 program supported by European Union (Grant number TMA2020CDF-3200). The authors have identified no competing interests.
Bronchiectasis management in adults: state of the art and future directions
Authors: Hayoung Choi, Pamela J. McShane, Stefano Aliberti, James D. Chalmers
Journal: European Respiratory Journal (2024)

Formerly regarded as a rare disease, bronchiectasis is increasingly recognised. A renewed interest in this disease has led to significant progress in bronchiectasis research. Randomised clinical trials (RCTs) have demonstrated the benefits of airway clearance techniques, inhaled antibiotics and long-term macrolide therapy in bronchiectasis patients. However, the heterogeneity of bronchiectasis remains one of the most challenging aspects of management. Phenotypes and endotypes of bronchiectasis have been identified to help find “treatable traits” and partially overcome disease complexity. The goals of therapy for bronchiectasis are to reduce the symptom burden, improve quality of life, reduce exacerbations and prevent disease progression. We review the pharmacological and non-pharmacological treatments that can improve mucociliary clearance, reduce airway inflammation and tackle airway infection, the key pathophysiological features of bronchiectasis. There are also promising treatments in development for the management of bronchiectasis, including novel anti-inflammatory therapies. This review provides a critical update on the management of bronchiectasis focusing on treatable traits and recent RCTs.
Short oral treatment regimens for rifampicin-resistant tuberculosis are safe and effective for young children: results from a field-based non-randomized clinical trial, Kandahar Afghanistan
Authors: Anita Mesic, Ine Decuyper, Sadiqqullah Ishaq, Taiba Azizi, Fazal Hadi Ziamal, Shirbaz Amiri, Kees Keus, Moe Thandar Pyae, Khan Mohammed Mangal, Hashim Khan Amirzada, Assadullah Rasooli, Mohammad Reza Aloudal, Mohammad Zaher Daldar, Tom Decroo
Journal: European Respiratory Journal (2024)

Clinical trials, evaluating 9-month/7-drug and 6-month/4-drug all-oral rifampicin-resistant tuberculosis (RR-TB) treatment regimens showed that these are at least as effective and safer than previously used longer and injectable-containing regimens [1–4]. Findings directly informed World Health Organization (WHO) guidelines for the treatment of adults with RR-TB, including pre-extensively drug-resistant TB (pre-XDR-TB; RR-TB with resistance to fluoroquinolones, FQ) [5]. However, children were not included in these trials. Especially for children with pre-XDR-TB, severe TB disease, or extrapulmonary TB (other than peripheral lymphadenitis) this has dire consequences. They are still treated with individualized 18-month regimens, which are not only longer, but also more toxic, less effective and with a higher pill burden than regimens for adults with a similar condition [5, 6]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of Interest: All authors have nothing to disclose.
A requirement for the use of supplementary oxygen to guide medical treatment decisions may introduce bias against non-white individuals
Authors: Colin J. Crooks, Joe West, Joanne R. Morling, Mark Simmonds, Irene Juurlink, Steve Briggs, Simon Cruickshank, Susan Hammond-Pears, Dominick Shaw, Timothy R. Card, Andrew W. Fogarty
Journal: European Respiratory Journal (2024)

In England and Wales there was excess mortality from Covid-19 infection in individuals whose forebears originated outside the UK, often in Africa or South East Asia [1]. The reasons for this are still unclear. We suggest that the use of oxygen saturations derived from pulse oximetry to guide treatment may have been a contributory factor. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of Interest: All authors have nothing to disclose.
Immunotherapy in the neoadjuvant treatment of gastrointestinal tumors: is the time ripe?
Authors: Lorenzo Gervaso, Davide Ciardiello, Rivadavio Antunes Oliveira, Michele Borghesani, Lorenzo Guidi, Lavinia Benini, Laura Algeri, Francesca Spada, Maria Giulia Zampino, Chiara Alessandra Cella, Nicola Fazio
Journal: Journal for ImmunoTherapy of Cancer (2024)

Immune checkpoint inhibitors (ICIs) revolutionized the management of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal (GI) cancers. Based on notable results observed in the metastatic setting, several clinical trials investigated ICIs as neoadjuvant treatment (NAT) for localized dMMR/MSI-H GI cancers, achieving striking results in terms of clinical and pathological responses and creating the opportunity to spare patients from neoadjuvant chemotherapy and/or radiotherapy and even surgical resection. Nevertheless, these impressive findings are mainly derived from small proof of concept phase II studies and there are still several open questions to address. Moreover, dMMR/MSI-H represents a limited subgroup accounting for less than 10% of GI cancers. Consequently, many efforts have been produced to investigate neoadjuvant ICIs also in mismatch repair-proficient/microsatellite stable (MSS) cancers, considering the potential synergistic effect in combining immune-targeted agents with standard therapies such as chemo and/or radiotherapy. However, results for combining ICIs to the standard of care in the unselected population are still unsatisfactory, without improvements in event-free survival in esophago-gastric adenocarcinoma for the addition of pembrolizumab to chemotherapy, and sometimes limited benefit in patients with locally advanced rectal cancer. Therefore, a major challenge will be to identify among the heterogenous spectrum of this disease, those patients that could take advantage of neoadjuvant immunotherapy and deliver the most effective treatment. In this review we discuss the rationale of NAT in GI malignancies, summarize the available evidence regarding the completed trials that evaluated this treatment strategy in both MSI-H and MSS tumors. Finally, we discuss ongoing studies and future perspectives to render neoadjuvant immunotherapy another arrow in the quiver for the treatment of locally advanced GI tumors.
Abstract 16198: Evaluation of Multiple Biomarkers of Cardiomyocyte Stress or Injury to Predict Cardiovascular Death or CHF in STEMI: Findings from CLARITY-TIMI 28
Authors: Nihar R Desai, David A Morrow, Sabina A Murphy, Robert E Gerszten, Christopher P Cannon, Marc S Sabatine
Journal: Circulation (2011)

Background: Markers of cardiomyocyte stress including atrial naturetic peptide (ANP), adrenomedullin (ADM), and copeptin help predict mortality in heart failure (HF). Little is known about the util...
Rigorous Donor Selection for Fecal Microbiota Transplantation in Active Ulcerative Colitis: Key Lessons From a Randomized Controlled Trial Halted for Futility
Authors: Clara Caenepeel, Sara Deleu, Jorge Francisco Vazquez Castellanos, Kaline Arnauts, Sara Braekeleire, Kathleen Machiels, Filip Baert, Fazia Mana, Lieven Pouillon, Pieter Hindryckx, Triana Lobaton, Edouard Louis, Denis Franchimont, Bram Verstockt, Marc Ferrante, João Sabino, Sara Vieira-Silva, Gwen Falony, Jeroen Raes, Séverine Vermeire
Journal: Clinical Gastroenterology and Hepatology (2024)

Rigorous donor preselection on microbiota level, strict anaerobic processing, and repeated fecal microbiota transplantation (FMT) administration were hypothesized to improve FMT induction of remission in ulcerative colitis (UC). The RESTORE-UC trial was a multi-centric, double-blind, sham-controlled, randomized trial. Patients with moderate to severe UC (defined by total Mayo 4-10) were randomly allocated to receive 4 anaerobic-prepared allogenic or autologous donor FMTs. Allogenic donor material was selected after a rigorous screening based on microbial cell count, enterotype, and the abundance of specific genera. The primary endpoint was steroid-free clinical remission (total Mayo ≤2, no sub-score >1) at week 8. A pre-planned futility analysis was performed after 66% (n = 72) of intended inclusions (n = 108). Quantitative microbiome profiling (n = 44) was performed at weeks 0 and 8. In total, 72 patients were included, of which 66 received at least 1 FMT (allogenic FMT, n = 30 and autologous FMT, n = 36). At week 8, respectively, 3 and 5 patients reached the primary endpoint of steroid-free clinical remission (P = .72), indicating no treatment difference of at least 5% in favor of allogenic FMT. Hence, the study was stopped due to futility. Microbiome analysis showed numerically more enterotype transitions upon allogenic FMT compared with autologous FMT, and more transitions were observed when patients were treated with a different enterotype than their own at baseline (P = .01). Primary response was associated with lower total Mayo scores, lower bacterial cell counts, and higher Bacteroides 2 prevalence at baseline. The RESTORE-UC trial did not meet its primary endpoint of increased steroid-free clinical remission at week 8. Further research should additionally consider patient selection, sterilized sham-control, increased frequency, density, and viability of FMT prior to administration. gov, Number: NCT03110289.
(Single-stranded DNA) gaps in understanding BRCAness
Authors: Anne Schreuder, Tiemen J. Wendel, Carlo G.V. Dorresteijn, Sylvie M. Noordermeer
Journal: Trends in Genetics (2024)

The tumour-suppressive roles of BRCA1 and 2 have been attributed to three seemingly distinct functions - homologous recombination, replication fork protection, and single-stranded (ss)DNA gap suppression - and their relative importance is under debate. In this review, we examine the origin and resolution of ssDNA gaps and discuss the recent advances in understanding the role of BRCA1/2 in gap suppression. There are ample data showing that gap accumulation in BRCA1/2-deficient cells is linked to genomic instability and chemosensitivity. However, it remains unclear whether there is a causative role and the function of BRCA1/2 in gap suppression cannot unambiguously be dissected from their other functions. We therefore conclude that the three functions of BRCA1 and 2 are closely intertwined and not mutually exclusive.
β-catenin mRNA encapsulated in SM-102 lipid nanoparticles enhances bone formation in a murine tibia fracture repair model
Authors: Anna Laura Nelson, Chiara Mancino, Xueqin Gao, Joshua A. Choe, Laura Chubb, Katherine Williams, Molly Czachor, Ralph Marcucio, Francesca Taraballi, John P. Cooke, Johnny Huard, Chelsea Bahney, Nicole Ehrhart
Journal: Bioactive Materials (2024)

Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture healing. In this study, we aimed to develop an osteoanabolic therapy which activates the Wnt/β-catenin pathway, a molecular driver of endochondral ossification. We hypothesize that using an mRNA-based therapeutic encoding β-catenin could promote cartilage to bone transformation formation by activating the canonical Wnt signaling pathway in chondrocytes. To optimize a delivery platform built on recent advancements in liposomal technologies, two FDA-approved ionizable phospholipids, DLin-MC3-DMA (MC3) and SM-102, were used to fabricate unique ionizable lipid nanoparticle (LNP) formulations and then tested for transfection efficacy both in vitro and in a murine tibia fracture model. Using firefly luciferase mRNA as a reporter gene to track and quantify transfection, SM-102 LNPs showed enhanced transfection efficacy in vitro and prolonged transfection, minimal fracture interference and no localized inflammatory response in vivo over MC3 LNPs. The generated β-cateninGOF mRNA encapsulated in SM-102 LNPs (SM-102-β-cateninGOF mRNA) showed bioactivity in vitro through upregulation of downstream canonical Wnt genes, axin2 and runx2. When testing SM-102-β-cateninGOF mRNA therapeutic in a murine tibia fracture model, histomorphometric analysis showed increased bone and decreased cartilage composition with the 45 μg concentration at 2 weeks post-fracture. μCT testing confirmed that SM-102-β-cateninGOF mRNA promoted bone formation in vivo, revealing significantly more bone volume over total volume in the 45 μg group. Thus, we generated a novel mRNA-based therapeutic encoding a β-catenin mRNA and optimized an SM-102-based LNP to maximize transfection efficacy with a localized delivery.
Phosphodiesterase-mediated modulation of subcellular cAMP levels to reduce heart failure
Authors: Maurizio Forte, Giacomo Frati, Sebastiano Sciarretta
Journal: Cardiovascular Research (2024)

Journal Article Accepted manuscript Phosphodiesterase-mediated modulation of subcellular cAMP levels to reduce heart failure Get access Maurizio Forte, Maurizio Forte IRCCS Neuromed, Pozzilli, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Giacomo Frati, Giacomo Frati IRCCS Neuromed, Pozzilli, ItalyDepartment of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy https://orcid.org/0000-0003-2703-3761 Search for other works by this author on: Oxford Academic PubMed Google Scholar Sebastiano Sciarretta Sebastiano Sciarretta IRCCS Neuromed, Pozzilli, ItalyDepartment of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy Corresponding author Sebastiano Sciarretta, MD, PhD, Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. Mail: sebastiano.sciarretta@uniroma1.it Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, cvae108, https://doi.org/10.1093/cvr/cvae108 Published: 24 May 2024 Article history Received: 07 March 2024 Accepted: 15 March 2024 Published: 24 May 2024