tbuckley/cabot-search huggingface dataset:
Antimicrobial resistance crisis: could artificial intelligence be the solution?
Authors: Guang-Yu Liu, Dan Yu, Mei-Mei Fan, Xu Zhang, Ze-Yu Jin, Christoph Tang, Xiao-Fen Liu
Journal: Military Medical Research (2024)

Abstract Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed. The discovery and introduction of novel antibiotics are time-consuming and expensive. According to WHO’s report of antibacterial agents in clinical development, only 18 novel antibiotics have been approved since 2014. Therefore, novel antibiotics are critically needed. Artificial intelligence (AI) has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel antibiotics. Here, we first summarized recently marketed novel antibiotics, and antibiotic candidates in clinical development. In addition, we systematically reviewed the involvement of AI in antibacterial drug development and utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well as resistance mechanism prediction, and antibiotic stewardship.
Is a traction device an almighty tool for overcoming the difficulties of endoscopic submucosal dissection?
Authors: Naohisa Yahagi
Journal: Endoscopy (2024)

Endoscopic submucosal dissection (ESD) is the most powerful endoscopic resection technique allowing reliable en bloc resection, regardless of the size and location of a tumor. This technique is however much more difficult and time-consuming than any other endoscopic resection technique, which has resulted in a delay in its widespread use in Western countries. The difficulty comes from the fact that ESD is a single-handed multistep procedure that requires very precise control of the endoscope. In particular, submucosal dissection is something that was not previously done in endoscopic procedures, and it is extremely difficult for beginners to open the submucosa while using a hood on the endoscope and keeping it in a stable position.
The AfrAbia+plus Parkinson's Disease Genomic Consortium
Authors: Wael Mohamed, Mohamed Abdelhalim Eltantawi, Yasser Mecheri, Yared Zenebe Zewde, Walaa A Kamel, Bashayer R Al-Mubarak, Karem H Alzoubi, Najib Kissani, Badrah S Alghamdi, Samia Ben Sassi
Journal: The Lancet Neurology (2024)
A Versatile Intestine‐on‐Chip System for Deciphering the Immunopathogenesis of Inflammatory Bowel Disease
Authors: Oanh T. P. Nguyen, Patrick M. Misun, Andreas Hierlemann, Christian Lohasz
Journal: Advanced Healthcare Materials (2024)

Abstract The multifactorial nature of inflammatory bowel disease (IBD) necessitates reliable and practical experimental models to elucidate its etiology and pathogenesis. To model the intestinal microenvironment at the onset of IBD in vitro, it is important to incorporate relevant cellular and noncellular components before inducing stepwise pathogenic developments. A novel intestine‐on‐chip system for investigating multiple aspects of IBD's immunopathogenesis is presented. The system includes an array of tight and polarized barrier models formed from intestinal epithelial cells on an in‐vivo‐like subepithelial matrix within one week. The dynamic remodeling of the subepithelial matrix by cells or their secretome demonstrates the physiological relevance of the on‐chip barrier models. The system design enables introduction of various immune cell types and inflammatory stimuli at specific locations in the same barrier model, which facilitates investigations of the distinct roles of each cell type in intestinal inflammation development. It is showed that inflammatory behavior manifests in an upregulated expression of inflammatory markers and cytokines (TNF‐α). The neutralizing effect of the anti‐inflammatory antibody Infliximab on levels of TNF‐α and its inducible cytokines could be explicitly shown. Overall, an innovative approach to systematically developing a microphysiological system to comprehend immune‐system‐mediated disorders of IBD and to identify new therapeutic strategies is presented.
Genome-wide DNA methylation and transcriptomic patterns of precancerous gastric cardia lesions
Authors: Xiaoqi Liao, Runhua Lin, Zhihua Zhang, Dongping Tian, Zhaohui Liu, Songqin Chen, Guohua Xu, Min Su
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Intestinal metaplasia (IM) and intraepithelial neoplasia (IEN) are considered precursors of gastric cardia cancer (GCC). Here, we investigated the histopathologic and molecular profiles of precancerous gastric cardia lesions (PGCLs) and biomarkers for risk stratification of gastric cardia IM. Methods We conducted a hospital-based evaluation (n = 4578) for PGCL profiles in high-incidence and non-high-incidence regions for GCC in China. We next performed 850K methylation arrays (n = 42) and RNA-seq (n = 44) in tissues with PGCLs. We then examined the protein expression of candidate biomarker using immunohistochemistry. Results Of the 4578 participants, 791 were diagnosed with PGCLs (600 IM, 62 IM with IEN, and 129 IEN). We found that individuals from high-incidence regions (26.7%) were more likely to develop PGCLs than those from non-high-incidence areas (13.5%). DNA methylation and gene expression alterations, indicated by differentially methylated probes (DMPs) and differentially expressed genes (DEGs), exhibited a progressive increase from type I IM (DMP = 210, DEG = 24), type II IM (DMP = 3402, DEG = 129), to type III IM (DMP = 3735, DEG = 328), peaking in IEN (DMP = 47 373, DEG = 2278). Three DEGs with aberrant promoter methylation were identified, shared exclusively by type III IM and IEN. Of these DEGs, we found that OLFM4 expression appears in IMs and increases remarkably in IENs (P &amp;lt; .001). Conclusions We highlight that type III IM and IEN share similar epigenetic and transcriptional features in gastric cardia and propose biomarkers with potential utility in risk prediction.
A ghost in the machine: is machine learning necessary for prediction of choledocholithiasis?
Authors: Ryan Law, Manuel Perez-Miranda
Journal: Endoscopy (2024)

Endoscopic retrograde cholangiopancreatography (ERCP) remains the standard of care for management of biliary lithiasis; however, ERCP carries a substantial risk of post-procedure pancreatitis, warranting its judicious use. Several manuscripts over the years have attempted to create predictive models for the presence of choledocholithiasis, all of which had certain limitations. With the continued push for technological advancement, more recent attempts have utilized advanced modeling or artificial intelligence, though these have also been unable to gain a substantial clinical foothold. At present, guidelines from American Society for Gastrointestinal Endoscopy (ASGE) and European Society of Gastrointestinal Endoscopy (ESGE) remain widely utilized to guide management for patients with suspected common bile duct (CBD) stones.
The construct validity, responsiveness, reliability and interpretability of the Recap of atopic eczema questionnaire (RECAP) in children
Authors: Aviël Ragamin, Junfen Zhang, Suzanne G M A Pasmans, Renske Schappin, Geertruida L E Romeijn, Maroos A van Reusel, Jart A F Oosterhaven, Marie L A Schuttelaar
Journal: British Journal of Dermatology (2024)

Abstract Background The Recap of atopic eczema questionnaire (RECAP) was developed to measure eczema control in patients with atopic dermatitis (AD). The measurement properties of RECAP have not yet been validated in caregivers of children with AD. Objectives To assess the construct validity, responsiveness, reliability and interpretability of the Dutch proxy version of RECAP. Methods A prospective validation study was conducted in children (aged &amp;lt; 12 years) with AD and their caregivers (in a Dutch tertiary hospital). At three timepoints (T0 = baseline; T1 = after 1–7 days; T2 = after 4–8 weeks) RECAP and multiple reference instruments were completed by caregivers of child patients. Single- and change-score validity (responsiveness) were tested with a priori hypotheses on correlations with reference instruments. Intraclass correlation coefficients (ICCagreement) and standard error of agreement (SEMagreement) were reported. Bands for perceived eczema control were proposed. The smallest detectable change (SDC) and minimally important change (MIC) were determined. Two anchor-based methods based on receiver operating characteristic curve (ROC) and predictive modelling were used to determine the MIC. Results A total of 231 children with AD and their caregivers participated. Of our a priori hypotheses for single-score and change-score validity, 77% and 80% were confirmed, respectively. A stronger correlation than hypothesized was found for all rejected hypotheses. Excellent reliability was found (ICCagreement = 0.94, 95% confidence interval 0.90–0.96). The SEMagreement was 1.9 points. The final banding was 0–1 (completely controlled), 2–7 (mostly controlled), 8–12 (moderately controlled), 13–18 (a little controlled) and 19–28 (not at all controlled). A cutoff point of ≥ 8 was selected to identify children whose AD is not under control. The SDC was 5.3 and the MIC values were 1.5 and 3.6 for the ROC and predictive modelling approaches, respectively. No floor or ceiling effects were observed. Conclusions The proxy version of RECAP is a valid, reliable and responsive measurement instrument for measuring eczema control in children with AD. An improvement of ≥ 6 points can be regarded as a real and important change in children with AD.
Multiscale Modeling of Magnetoelectric Nanoparticles for the Analysis of Spatially Selective Neural Stimulation
Authors: Prachi Kumari, Hannah Wunderlich, Aleksandra Milojkovic, Jorge Estudillo López, Arianna Fossati, Ali Jahanshahi, Kristen Kozielski
Journal: Advanced Healthcare Materials (2024)

Abstract The growing field of nanoscale neural stimulators offers a potential alternative to larger scale electrodes for brain stimulation. Nanoelectrodes made of magnetoelectric nanoparticles (MENPs) can provide an alternative to invasive electrodes for brain stimulation via magnetic‐to‐electric signal transduction. However, the magnetoelectric effect is a complex phenomenon and challenging to probe experimentally. Consequently, quantifying the stimulation voltage provided by MENPs is difficult, hindering precise regulation and control of neural stimulation and limiting their practical implementation as wireless nanoelectrodes. The work herein develops an approach to determine the stimulation voltage for MENPs in a finite element analysis (FEA) model. This model is informed by atomistic material properties from ab initio Density Functional Theory (DFT) calculations and supplemented by experimentally obtainable nanoscale parameters. This process overcomes the need for experimentally inaccessible characteristics for magnetoelectricity, and offers insights into the effect of the more manageable variables, such as the driving magnetic field. The model's voltage to in vivo experimental data is compared to assess its validity. With this, a predictable and controllable stimulation is simulated by MENPs, computationally substantiating their spatial selectivity. This work proposes a generalizable and accessible method for evaluating the stimulation capability of magnetoelectric nanostructures, facilitating their realization as wireless neural stimulators in the future.
Evaluating the efficacy and safety of pozelimab in patients with CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy disease: an open-label phase 2 and 3 study
Authors: Ahmet Ozen, Voranush Chongsrisawat, Asena Pinar Sefer, Burcu Kolukisa, Jessica J Jalbert, Karoline A Meagher, Taylor Brackin, Hagit Baris Feldman, Safa Baris, Elif Karakoc-Aydiner, Rabia Ergelen, Ivan J Fuss, Heather Moorman, Narissara Suratannon, Kanya Suphapeetiporn, Lorah Perlee, Olivier A Harari, George D Yancopoulos, Michael J Lenardo, Jutta L. Miller, Orly Eshach Adiv, Sevgi Bilgic Eltan, Melek Yorgun Altunbas, Mary Magliocco, Helen Matthews, Beatriz E. Marciano, Pantipa Chatchatee, Caryn F. Trbovic, Michael E. Burczynski, Umesh Chaudhari, Yusuf Usta, Cansu Altuntaş, Sibel Yavuz, Ahmet Baştürk, Fatma Demirbaş Ar, Erdem Topal, Ayhan Gazi Kalaycı, Wanlapa Weerapakorn, Ana Andrea Calabi Martínez, Adriana Bottero
Journal: The Lancet (2024)
Antimicrobial resistance and the great divide: inequity in priorities and agendas between the Global North and the Global South threatens global mitigation of antimicrobial resistance
Authors: Marc Mendelson, Ramanan Laxminarayan, Direk Limmathurotsakul, Samuel Kariuki, Martha Gyansa-Lutterodt, Esmita Charani, Sanjeev Singh, Kamini Walia, Ana C Gales, Mirfin Mpundu
Journal: The Lancet Global Health (2024)

To limit the catastrophic effects of the increasing bacterial resistance to antimicrobials on health, food, environmental, and geopolitical security, and ensure that no country or region is left behind, a coordinated global approach is required. In this Viewpoint, we argue that the diverging resource availabilities, needs, and priorities of the Global North and the Global South in terms of the actions required to mitigate the antimicrobial resistance pandemic are a direct threat to success. We argue that evidence suggests a need to prioritise and support infection prevention interventions (ie, clean water and safe sanitation, increased vaccine coverage, and enhanced infection prevention measures for food production in the Global South contrary to the focus on research and development of new antibiotics in the Global North) and to recalibrate global funding resources to address this need. We call on global leaders to redress the current response, which threatens mitigation of the antimicrobial resistance pandemic.
Smart Bactericidal Capsules Based on Cationic Luminescent Nanoclusters for Controllable Treatment of Drug‐Resistant Bacterial Infection
Authors: Yixiao Li, Tianyi Wang, Jiaxin Zhang, Gleb B. Sukhorukov, Lianbing Zhang, Yumeng Xue, Li Shang
Journal: Advanced Healthcare Materials (2024)

Effective treatment of drug-resistant bacteria infected wound has been a longstanding challenge for healthcare systems. In particular, the development of novel strategies for controllable delivery and smart release of antimicrobial agents is greatly demanded. Herein, the design of biodegradable microcapsules carrying bactericidal gold nanoclusters (AuNCs) as an attractive platform for the effective treatment of drug-resistant bacteria infective wounds is reported. AuNC capsules are fabricated via the well-controlled layer-by-layer strategy, which possess intrinsic near-infrared fluorescence and good biocompatibility. Importantly, these AuNC capsules exhibit strong, specific antibacterial activity toward both S. aureus and methicillin-resistant S. aureus (MRSA). Further mechanistic studies by fluorescence confocal imaging and inductively coupled plasma mass spectrometry reveal that these AuNC capsules will be degraded in the S. aureus environment rather than E. coli, which then controllably release the loaded cationic AuNCs to exert antibacterial effect. Consequently, these AuNC capsules show remarkable therapeutic effect for the MRSA infected wound on a mouse model, and intrinsic fluorescence property of AuNC capsules enables in situ visualization of wound dressings. This study suggests the great potential of microcapsule-based platform as smart carriers of bactericidal agents for the effective treatment of drug-resistant bacterial infection as well as other therapeutic purposes.
Helen Salisbury: Primary care networks in a tangle
Authors: Helen Salisbury
Journal: BMJ (2024)

When primary care networks (PCNs) were first set up in 2019 they were envisaged as groups of general practices joining together to provide and develop services for a local population.Each PCN is allocated a budget that it can spend on additional staff-pharmacists, paramedics, physiotherapists, and others (but not doctors or nurses)-and the size of that budget depends on the number of patients in the PCN.In some cases the additional staff work across the PCN providing services for patients of all the practices; in others, each surgery hires its own.There's no stipulation that the practices should be adjacent, only that they should serve a population of 30 000 to 50 000 patients.This could be one "super practice" but is more commonly three to six practices (our PCN currently has five, but two are merging very soon).This has led to some slightly unlikely geographical groupings in our county, and the situation has been made more complicated by a number of recent mergers.
Mononuclear myeloid cells can shape neutrophils in brain tumors
Authors: Sven Brandau
Journal: Trends in Immunology (2024)

In most human solid cancer types, a high frequency of intratumoral neutrophils is associated with poor prognosis. In a recent study, Maas et al. identified an intratumoral niche in which mononuclear myeloid cells drive proinflammatory neutrophil activation in brain tumors. This study sheds new light on the intratumoral modulation of neutrophils.
Plant Foods Intake and Risk of Premature Aging in Adult Survivors of Childhood Cancer in the St Jude Lifetime Cohort (SJLIFE)
Authors: Mei Wang, Tuo Lan, AnnaLynn M. Williams, Matthew J. Ehrhardt, Jennifer Q. Lanctot, Shu Jiang, Kevin R. Krull, Gregory T. Armstrong, Melissa M. Hudson, Graham A. Colditz, Leslie L. Robison, Kirsten K. Ness, Yikyung Park
Journal: Journal of Clinical Oncology (2024)

To identify dietary factors that are related to premature aging in adult survivors of childhood cancer, we examined the associations between plant food intakes and age-related deficit accumulation.
Heterogeneity of Benefit from Earlier Time-to-Antibiotics for Sepsis
Authors: Rachel K. Hechtman, Patricia Kipnis, Jennifer Cano, Sarah Seelye, Vincent X. Liu, Hallie C. Prescott
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Shorter time-to-antibiotics improves survival from sepsis, particularly among patients in shock. There may be other subgroups for whom faster antibiotics are particularly beneficial.
Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3
Authors: Petros Grivas, Damien Pouessel, Chandler H. Park, Philippe Barthelemy, Manojkumar Bupathi, Daniel P. Petrylak, Neeraj Agarwal, Sumati Gupta, Aude Fléchon, Chethan Ramamurthy, Nancy B. Davis, Alejandro Recio-Boiles, Cora N. Sternberg, Astha Bhatia, Cabilia Pichardo, Mitch Sierecki, Julia Tonelli, Huafeng Zhou, Scott T. Tagawa, Yohann Loriot
Journal: Journal of Clinical Oncology (2024)

Pembrolizumab is standard therapy for patients with metastatic urothelial cancer (mUC) who progress after first-line platinum-based chemotherapy; however, only approximately 21% of patients respond. Sacituzumab govitecan (SG) is a trophoblast cell surface antigen-2-directed antibody-drug conjugate with US Food and Drug Administration-accelerated approval to treat patients with locally advanced or mUC who previously received platinum-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report the primary analysis of TROPHY-U-01 cohort 3.
Hypusine Signaling Promotes Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension
Authors: Sarah-Eve Lemay, Yann Grobs, Charlotte Romanet, Sandra Martineau, Mabrouka Salem, Tsukasa Shimauchi, Sandra Breuils-Bonnet, Alice Bourgeois, Charlie Théberge, Andréanne Pelletier, François Potus, Steeve Provencher, Sébastien Bonnet, Olivier Boucherat
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

The ubiquitous polyamine spermidine is essential for cell survival and proliferation. One important function of spermidine is to serve as a substrate for hypusination, a posttranslational modification process that occurs exclusively on eukaryotic translation factor 5A (eIF5A) and ensures efficient translation of various gene products. Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive obliteration of the small pulmonary arteries (PAs) caused by excessive proliferation of PA smooth muscle cells (PASMCs) and suppressed apoptosis.
VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of CKD in Patients with Metabolic Acidosis
Authors: Navdeep Tangri, Vandana S. Mathur, David A. Bushinsky, Gerrit Klaerner, Elizabeth Li, Dawn Parsell, Yuri Stasiv, Michael Walker, Donald E. Wesson, David C. Wheeler, Vlado Perkovic, Lesley A. Inker
Journal: Journal of the American Society of Nephrology (2024)

Significance Statement Metabolic acidosis is a common complication of CKD and is associated with more rapid decline of kidney function, but well-powered controlled randomized trials testing the effect of treating metabolic acidosis on slowing CKD progression have not been conducted. The VALOR-CKD study randomized 1480 individuals with CKD and metabolic acidosis, across 320 sites to placebo or veverimer (a novel hydrochloric acid binder). The findings did not demonstrate the efficacy of veverimer in slowing CKD progression, but the difference in serum bicarbonate between placebo and drug arms was only approximately 1 mEq/L. Veverimer was safe and well tolerated. Background Metabolic acidosis is common in CKD, but whether its treatment slows CKD progression is unknown. Veverimer, a novel hydrochloric acid binder that removes acid from the gastrointestinal tract, leads to an increase in serum bicarbonate. Methods In a phase 3, double-blind, placebo-controlled trial, patients with CKD (eGFR of 20–40 ml/min per 1.73 m 2 ) and metabolic acidosis (serum bicarbonate of 12–20 mEq/L) from 35 countries were randomized to veverimer or placebo. The primary outcome was the composite end point of CKD progression, defined as the development of ESKD (kidney transplantation or maintenance dialysis), a sustained decline in eGFR of ≥40% from baseline, or death due to kidney failure. Results The mean (±SD) baseline eGFR was 29.2±6.3 ml/min per 1.73 m 2 , and serum bicarbonate was 17.5±1.4 mEq/L; this increased to 23.4±2.0 mEq/L after the active treatment run-in. After randomized withdrawal, the mean serum bicarbonate was 22.0±3.0 mEq/L and 20.9±3.3 mEq/L in the veverimer and placebo groups at month 3, and this approximately 1 mEq/L difference remained stable for the first 24 months. A primary end point event occurred in 149/741 and 148/739 patients in the veverimer and placebo groups, respectively (hazard ratio, 0.99; 95% confidence interval, 0.8 to 1.2; P = 0.90). Serious and overall adverse event incidence did not differ between the groups. Conclusions Among patients with CKD and metabolic acidosis, treatment with veverimer did not slow CKD progression. The lower than expected bicarbonate separation may have hindered the ability to test the hypothesis. Clinical Trial registry name and registration number VALOR-CKD, NCT03710291.