tbuckley/cabot-search huggingface dataset:
Antiseptic management of critical wounds: differential bacterial response upon exposure to antiseptics and first insights into antiseptic/phage interactions
Authors: Thaysa Leite Tagliaferri, Sophie Rhode, Priscila Muñoz, Kevin Simon, Alex Krüttgen, Christian Stoppe, Tim Ruhl, Justus P. Beier, Hans-Peter Horz, Bong-Sung Kim
Journal: International Journal of Surgery (2024)

Background: With the antibiotic crisis, the topical antibacterial control including chronic wounds gains increasing importance. However, little is known regarding tolerance development when bacteria face repetitive exposure to the identical antiseptics as commonly found in clinical practice. Materials and Methods: Clinical isolates foremost of chronic wounds were exposed in vitro to dilutions of two antiseptics used for wound therapy: polyhexanide or octenidine. Adaptive response was determined by growth/kill curves, minimal inhibitory concentration (MIC), and whole genome sequencing. Antiseptic/bacteriophage combinations were studied by liquid-infection assays and bacterial plating. Results: Polyhexanide acted stronger against Escherichia coli and Proteus mirabilis while octenidine was more potent against Staphylococcus aureus . Otherwise, the antiseptic efficacy varied across isolates of Klebsiella pneumoniae , Pseudomonas aeruginosa , and Acinetobacter baumannii . Upon repetitive exposure with constant antiseptic concentrations P. aeruginosa and P. mirabilis adaptation was evident by a reduced lag-phase and a twofold increased MIC. Under increasing octenidine concentrations, P. aeruginosa adapted to an eightfold higher dosage with mutations in smvA , opgH , and kinB affecting an efflux pump, alginate and biofilm formation, respectively. S. aureus adapted to a fourfold increase of polyhexanide with a mutation in the multiple peptide resistance factor MprF, also conferring cross-resistance to daptomycin. Antiseptic/bacteriophage combinations enhanced bacterial inhibition and delayed adaptation. Conclusion: Different bacterial species/strains respond unequally to low-level antiseptic concentrations. Bacterial adaptation potential at phenotypic and genotypic levels may indicate the necessity for a more nuanced selection of antiseptics. Bacteriophages represent a promising yet underexplored strategy for supporting antiseptic treatment, which may be particularly beneficial for the management of critical wounds.
The EUropean PErioperative MEdical networking (EUPEMEN) project: recommendations for perioperative care in colorectal surgery. a quality improvement study
Authors: Antonio Pesce, Jose Manuel Ramírez, Nicolò Fabbri, Javier Martínez Ubieto, Ana Pascual Bellosta, Antonio Arroyo, Luis Sánchez-Guillén, Adam Whitley, Petr Kocián, Kristyna Rosetzka, Alejandro Bona Enguita, Orestis Ioannidis, Stefanos Bitsianis, Savvas Symeonidis, Elissavet Anestiadou, Marta Teresa-Fernandéz, Carlo Vittorio Feo
Journal: International Journal of Surgery (2024)

Despite consensus supporting enhanced recovery programs, their full implementation in such a context is difficult due to conventional practices within various groups of professionals. The goal of the EUropean PErioperative MEdical Networking (EUPEMEN) project was to bring together the expertise and experience of national clinical professionals who have previously helped deliver major change programs in their countries and to use them to spread enhanced recovery after surgery protocols (ERAS) in Europe. The specific aim of this study is to present and discuss the key points of the proposed recommendations for colorectal surgery.
Intravenous immunoglobulin as a rescue therapy for severe adult autoimmune hemolytic anemia: Results from a French multicenter observational study
Authors: M. Michel, M. Saïr, E. Rivière, G. Moulis, T. Comont, N. Costedoat‐Chalumeau, C. Pouchelon, D. Boutboul, A. Benyamine, A. Bert, P. ‐Y. Jeandel, S. Hamrouni, N. Belfeki, H. Lobbes, A. Dossier, D. Gobert, M. Mahevas, B. Godeau, Y. Gallien, M. Ebbo
Journal: American Journal of Hematology (2024)
Outcome comparison of meniscal allograft transplantation (MAT) and meniscal scaffold implantation (MSI): A systematic review
Authors: Jize Dong, Moran Huang, Jinrong Lin, Yaying Sun, Xingyu Zhang, Jiwu Chen
Journal: International Journal of Surgery (2024)

Although numerous studies have reported successful clinical outcomes of meniscal allograft transplantation (MAT) or meniscal scaffold implantation (MSI), the difference between the outcome of MAT and MSI remains unclear.
Continuous renal surface cooling technique (CSCT) in robotic-assisted kidney transplantation: technique and outcomes from a high-volume center: a prospective cohort study
Authors: Haohan Zhang, Jun Zeng, Yu Fan, Ming Ma, Tao Lin, Turun Song
Journal: International Journal of Surgery (2024)

Background: Robot-assisted kidney transplantation (RAKT) surgery is an advanced minimally invasive technique, albeit with extended surgical and kidney ischemia time. To safeguard kidney function, we have devised a continuous surface cooling method (CSCT) for intraoperative kidney cooling. Materials and Methods: Patients receiving RAKT were divided into CSCT group and conventional group. The CSCT is a custom-designed apparatus composed of a single-layer plastic bag, featuring an inflow and an outflow that create a closed circuit for the continuous flow of cooling saline. The conventional group utilized ice slush for kidney graft cooling (Vattikuti Urology Institute-Medanta Technique, VUIMT). Patients who underwent open renal transplantation during the same period were also included in the study. All patients were subject to a minimum 2-month follow-up. And 1:3 propensity score matching was used to minimize selection bias. Results: A total of 144 patients underwent CSCT, 47 underwent VUIMT, and 196 underwent open surgery were included in the study, while after matching, 129, 43, 129 patients were included in the three groups, respectively. The median follow-up time was 19 months. None of the patients experienced delayed graft function, patient mortality, or graft loss. After introducing the kidney into the abdominal cavity for 20 minutes, the surface temperature of the kidney in the CSCT group was notably lower compared to the VUIMT group (15.42±0.88 vs. 21.74±2.53°C, P =0.001). This temperature disparity became more pronounced at 65 minutes (19.74±1.61 vs. 29.82±1.63°C, P &lt;0.001). At both 3 and 7 days post-transplantation, creatinine levels in the VUIMT group were significantly higher than those in the CSCT and open surgery groups (at 3 d, 244.13±45.61 vs. 182.51±55.47 in CSCT group, P &lt;0.001, or vs. 182.77±61.32 in the open surgery group, P &lt;0.001; at 7 d, 162.42±54.86 vs. 143.11±44.32 in the CSCT group, P &lt;0.001, or vs. 135.23±45.27 in the open surgery group, P &lt;0.001). No differences were observed in blood creatinine, estimated glomerular filtration rate, and perioperative complications between the CSCT and open surgery groups. Conclusion: The CSCT presents a significant advantage over the traditional VUIMT method in terms of kidney cooling and early postoperative kidney function preservation. Additional research is required to ascertain whether the CSCT can enhance the long-term prognosis of kidney transplant recipients.
Molecular characteristics of early-onset compared with late-onset colorectal cancer: A case controlled study
Authors: Junwei Tang, Wen Peng, Chuanxing Tian, Yue Zhang, Dongjian Ji, Lu Wang, Kangpeng Jin, Fufeng Wang, Yang Shao, Xiaowei Wang, Yueming Sun
Journal: International Journal of Surgery (2024)

Early-onset colorectal cancer (EOCRC) is associated with a poorer prognosis relative to late-onset colorectal cancer (LOCRC), and its incidence has witnessed a gradual escalation in recent years. This necessitates a comprehensive examination of the underlying pathogenesis and the identification of therapeutic targets specific to EOCRC patients. The present study aimed to delineate the distinct molecular landscape of EOCRC by juxtaposing it with that of LOCRC.
The landscape of NUP98 rearrangements clinical characteristics and treatment response from 1491 acute leukemia patients
Authors: Jie Tian, Yongmei Zhu, Jianfeng Li, Guang Yang, Xiangqin Weng, Ting Huang, Lingling Zhao, Haimin Sun, Zeying Yan, Sujiang Zhang
Journal: Blood Cancer Journal (2024)
SARS-CoV-2 rapid antigen test sensitivity and viral load in newly symptomatic hospital employees in Berlin, Germany, December, 2020 to February, 2022: an observational study
Authors: Leonie Meiners, Johanna Horn, Terry C Jones, Barbara Mühlemann, Marie Luisa Schmidt, Felix Walper, Peter Menzel, Rolf Schwarzer, Ruben Rose, Andi Krumbholz, Victor M Corman, Joachim Seybold, Christian Drosten
Journal: The Lancet Microbe (2024)

Evolving SARS-CoV-2 variants and changing levels of pre-existing immunity require re-evaluation of antigen-detecting rapid diagnostic test (Ag-RDT) performance. We investigated possible associations between Ag-RDT sensitivity and various potential influencing factors, such as immunisation status and viral variant, in symptomatic hospital employees.
Perivascular NOTCH3+ Stem Cells Drive Meningioma Tumorigenesis and Resistance to Radiotherapy
Authors: Abrar Choudhury, Martha A. Cady, Calixto-Hope G. Lucas, Hinda Najem, Joanna J. Phillips, Brisa Palikuqi, Naomi Zakimi, Tara Joseph, Janeth O. Birrueta, William C. Chen, Nancy A. Oberheim Bush, Shawn L. Hervey-Jumper, Ophir D. Klein, Christine M. Toedebusch, Craig M. Horbinski, Stephen T. Magill, Aparna Bhaduri, Arie Perry, Peter J. Dickinson, Amy B. Heimberger, Alan Ashworth, Elizabeth E. Crouch, David R. Raleigh
Journal: Cancer Discovery (2024)

Abstract Meningiomas are the most common primary intracranial tumors. Treatments for patients with meningiomas are limited to surgery and radiotherapy, and systemic therapies remain ineffective or experimental. Resistance to radiotherapy is common in high-grade meningiomas and the cell types and signaling mechanisms that drive meningioma tumorigenesis and resistance to radiotherapy are incompletely understood. Here, we report that NOTCH3 drives meningioma tumorigenesis and resistance to radiotherapy and find that perivascular NOTCH3+ stem cells are conserved across meningiomas from humans, dogs, and mice. Integrating single-cell transcriptomics with lineage tracing and imaging approaches in genetically engineered mouse models and xenografts, we show NOTCH3 drives tumor-initiating capacity, cell proliferation, angiogenesis, and resistance to radiotherapy to increase meningioma growth and reduce survival. To translate these findings to patients, we show that an antibody stabilizing the extracellular negative regulatory region of NOTCH3 blocks meningioma tumorigenesis and sensitizes meningiomas to radiotherapy, reducing tumor growth and improving survival. Significance: There are no effective systemic therapies to treat meningiomas, and meningioma stem cells are poorly understood. Here, we report perivascular NOTCH3+ stem cells to drive meningioma tumorigenesis and resistance to radiotherapy. Our results identify a conserved mechanism and a therapeutic vulnerability to treat meningiomas that are resistant to standard interventions.
Stimuli‐Responsive Aptamer‐Drug Conjugates for Targeted Drug Delivery and Controlled Drug Release
Authors: Shanshan Zhu, Huan Gao, Wenyuan Li, Xiaocong He, Panpan Jiang, Feng Xu, Guorui Jin, Hui Guo
Journal: Advanced Healthcare Materials (2024)

Chemotherapy is widely used for cancer therapy but with unsatisfied efficacy, mainly due to the inefficient delivery of anticancer agents. Among the critical "five steps" drug delivery process, internalization into tumor cells and intracellular drug release are two important steps for the overall therapeutic efficiency. Strategy based on active targeting or TME-responsive is developed individually to improve therapeutic efficiency, but with limited improvement. However, the combination of these two strategies could potentially augment the drug delivery efficiency and therapeutic efficiency, consequently. Therefore, this work constructs a library of stimuli-responsive aptamer-drug conjugates (srApDCs), as "dual-targeted" strategy for cancer treatment that enables targeted drug delivery and controlled drug release. Specifically, this work uses different stimuli-responsive linkers to conjugate a tumor-targeting aptamer (i.e., AS1411) with drugs, forming the library of srApDCs for targeted cancer treatment. This design hypothesis is validated by the experimental data, which indicated that the aptamer could selectively enhance uptake of the srApDCs and the linkers could be cleaved by pathological cues in the TME to release the drug payload, leading to a significant enhancement of therapeutic efficacy. These results underscore the potential of the approach, providing a promising methodology for cancer therapy.
Harnessing the potential of monocytes/macrophages to regenerate tissue engineered vascular grafts
Authors: Arundhati Das, Randall J Smith, Stelios T Andreadis
Journal: Cardiovascular Research (2024)

Abstract Cell-free tissue-engineered vascular grafts provide a promising alternative to treat cardiovascular disease, but timely endothelialization is essential for ensuring patency and proper functioning post-implantation. Recent studies from our lab showed that blood cells like monocytes (MCs) and macrophages (Mϕ) may contribute directly to cellularization and regeneration of bioengineered arteries in small and large animal models. While MCs and Mϕ are leucocytes that are part of the innate immune response, they share common developmental origins with endothelial cells (ECs) and are known to play crucial roles during vessel formation (angiogenesis) and vessel repair after inflammation/injury. They are highly plastic cells that polarize into pro-inflammatory and anti-inflammatory phenotypes upon exposure to cytokines and differentiate into other cell types, including EC-like cells, in the presence of appropriate chemical and mechanical stimuli. This review focuses on the developmental origins of MCs and ECs; the role of MCs and Mϕ in vessel repair/regeneration during inflammation/injury; and the role of chemical signalling and mechanical forces in Mϕ inflammation that mediates vascular graft regeneration. We postulate that comprehensive understanding of these mechanisms will better inform the development of strategies to coax MCs/Mϕ into endothelializing the lumen and regenerate the smooth muscle layers of cell-free bioengineered arteries and veins that are designed to treat cardiovascular diseases and perhaps the native vasculature as well.
Shortcut learning in medical AI hinders generalization: method for estimating AI model generalization without external data
Authors: Cathy Ong Ly, Balagopal Unnikrishnan, Tony Tadic, Tirth Patel, Joe Duhamel, Sonja Kandel, Yasbanoo Moayedi, Michael Brudno, Andrew Hope, Heather Ross, Chris McIntosh
Journal: npj Digital Medicine (2024)

Healthcare datasets are becoming larger and more complex, necessitating the development of accurate and generalizable AI models for medical applications. Unstructured datasets, including medical imaging, electrocardiograms, and natural language data, are gaining attention with advancements in deep convolutional neural networks and large language models. However, estimating the generalizability of these models to new healthcare settings without extensive validation on external data remains challenging. In experiments across 13 datasets including X-rays, CTs, ECGs, clinical discharge summaries, and lung auscultation data, our results demonstrate that model performance is frequently overestimated by up to 20% on average due to shortcut learning of hidden data acquisition biases (DAB). Shortcut learning refers to a phenomenon in which an AI model learns to solve a task based on spurious correlations present in the data as opposed to features directly related to the task itself. We propose an open source, bias-corrected external accuracy estimate, P
Activated factor X stimulates atrial endothelial cells and tissues to promote remodelling responses through AT1R/NADPH oxidases/SGLT1/2
Authors: Walaa Fakih, Ali Mroueh, Dal-Seong Gong, Shinnosuke Kikuchi, Michael Paul Pieper, Michel Kindo, Jean-Philippe Mazzucottelli, Arnaud Mommerot, Mohamad Kanso, Patrick Ohlmann, Olivier Morel, Valérie Schini-Kerth, Laurence Jesel
Journal: Cardiovascular Research (2024)

Abstract Aims Atrial fibrillation (AF), the most common cardiac arrhythmia favouring ischemic stroke and heart failure involves left atrial remodelling, fibrosis and a complex interplay between cardiovascular risk factors. This study examined whether activated factor X (FXa) induces pro-remodelling and pro-fibrotic responses in atrial endothelial cells (AECs) and human atrial tissues and determined the underlying mechanisms. Methods and results AECs collected from porcine hearts and human right atrial appendages (RAA) from patients undergoing heart surgery. Protein expression levels were assessed by Western blot and immunofluorescence staining, mRNA levels by RT-qPCR, formation of reactive oxygen species (ROS) and NO using fluorescent probes, thrombin and angiotensin II generation by specific assays, fibrosis by Sirius red staining and senescence by senescence-associated beta-galactosidase (SA-β-gal) activity. In AECs, FXa increased ROS formation, senescence (SA-β-gal activity, p53, p21), angiotensin II generation and the expression of pro-inflammatory (VCAM-1, MCP-1), pro-thrombotic (tissue factor), pro-fibrotic (TGF-β and collagen-1/3a) and pro-remodelling (MMP-2/9) markers whereas eNOS levels and NO formation were reduced. These effects were prevented by inhibitors of FXa but not thrombin, protease-activated receptors antagonists (PAR-1/2) and inhibitors of NADPH oxidases, ACE, AT1R, SGLT1/SGLT2. FXa also increased expression levels of ACE1, AT1R, SGLT1/2 proteins which were prevented by SGLT1/2 inhibitors. Human RAA showed tissue factor mRNA levels that correlated with markers of endothelial activation, pro-remodelling and pro-fibrotic responses and SGLT1/2 mRNA levels. They also showed protein expression levels of ACE1, AT1R, p22phox, SGLT1/2, and immunofluorescence signals of nitrotyrosine and SGLT1/2 colocalized with those of CD31. FXa increased oxidative stress levels which were prevented by inhibitors of the AT1R/NADPH oxidases/SGLT1/2 pathway. Conclusion FXa promotes oxidative stress triggering premature endothelial senescence and dysfunction associated with pro-thrombotic, pro-remodelling and pro-fibrotic responses in AECs and human RAA involving the AT1R/NADPH oxidases/SGLT1/2 pro-oxidant pathway. Targeting this pathway may be of interest to prevent atrial remodelling and the progression of atrial fibrillation substrate.
Prevalence of comorbidities in individuals with neurodevelopmental disorders from the aggregated phenomics data of 51,227 pediatric individuals
Authors: Alexander J. M. Dingemans, Sandra Jansen, Jeroen van Reeuwijk, Nicole de Leeuw, Rolph Pfundt, Janneke Schuurs-Hoeijmakers, Bregje W. van Bon, Carlo Marcelis, Charlotte W. Ockeloen, Marjolein Willemsen, Pleuntje J. van der Sluijs, Gijs W. E. Santen, R. Frank Kooy, Anneke T. Vulto-van Silfhout, Tjitske Kleefstra, David A. Koolen, Lisenka E. L. M. Vissers, Bert B. A. de Vries
Journal: Nature Medicine (2024)
Dynamics of cognitive variability with age and its genetic underpinning in NIHR BioResource Genes and Cognition cohort participants
Authors: Md Shafiqur Rahman, Emma Harrison, Heather Biggs, Chloe Seikus, Paul Elliott, Gerome Breen, Nathalie Kingston, John R Bradley, Steven M Hill, Brian D M Tom, Patrick F Chinnery
Journal: Nature Medicine (2024)

Abstract A leading explanation for translational failure in neurodegenerative disease is that new drugs are evaluated late in the disease course when clinical features have become irreversible. Here, to address this gap, we cognitively profiled 21,051 people aged 17–85 years as part of the Genes and Cognition cohort within the National Institute for Health and Care Research BioResource across England. We describe the cohort, present cognitive trajectories and show the potential utility. Surprisingly, when studied at scale, the APOE genotype had negligible impact on cognitive performance. Different cognitive domains had distinct genetic architectures, with one indicating brain region-specific activation of microglia and another with glycogen metabolism. Thus, the molecular and cellular mechanisms underpinning cognition are distinct from dementia risk loci, presenting different targets to slow down age-related cognitive decline. Participants can now be recalled stratified by genotype and cognitive phenotype for natural history and interventional studies of neurodegenerative and other disorders.
Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial
Authors: Kohei Shitara, Yung-Jue Bang, Satoru Iwasa, Naotoshi Sugimoto, Min-Hee Ryu, Daisuke Sakai, Hyun Cheol Chung, Hisato Kawakami, Hiroshi Yabusaki, Yasuhiro Sakamoto, Tomohiro Nishina, Koichiro Inaki, Yusuke Kuwahara, Naoya Wada, Fumitaka Suto, Takeo Arita, Masahiro Sugihara, Zenta Tsuchihashi, Kaku Saito, Akihito Kojima, Kensei Yamaguchi
Journal: Nature Medicine (2024)

Trastuzumab deruxtecan (T-DXd) showed statistically significant clinical improvement in patients with human epidermal growth factor receptor 2-positive (HER2