tbuckley/cabot-search huggingface dataset:
Ultramicronized N-palmitoylethanolamine associated with analgesics: Effects against persistent pain
Authors: Stefania Nobili, Laura Micheli, Elena Lucarini, Alessandra Toti, Carla Ghelardini, Lorenzo Di Cesare Mannelli
Journal: Pharmacology & Therapeutics (2024)

Current epidemiological data estimate that one in five people suffers from chronic pain with considerable impairment of health-related quality of life. The pharmacological treatment is based on first- and second-line analgesic drugs, including COX-2 selective and nonselective nonsteroidal anti-inflammatory drugs, paracetamol, antidepressants, anti-seizure drugs and opioids, that are characterized by important side effects. N-palmitoylethanolamine (PEA) is a body's own fatty-acid ethanolamide belonging to the family of autacoid local injury antagonist amides. The anti-inflammatory and pain-relieving properties of PEA have been recognized for decades and prompted to depict its role in the endogenous mechanisms of pain control. Together with its relative abundance in food sources, this opened the way to the use of PEA as a pain-relieving nutritional intervention. Naïve PEA is a large particle size lipid molecule with low solubility and bioavailability. Reducing particle size is a useful method to increase surface area, thereby improving dissolution rate and bioavailability accordingly. Micron-size formulations of PEA (e.g., ultramicronized and co-(ultra)micronized) have shown higher oral efficacy compared to naïve PEA. In particular, ultramicronized PEA has been shown to efficiently cross the intestinal wall and, more importantly, the blood-brain and blood-spinal cord barrier. Several preclinical and clinical studies have shown the efficacy, safety and tolerability of ultramicronized PEA. This narrative review summarizes the available pharmacokinetic/pharmacodynamic data on ultramicronized PEA and focuses to its contribution to pain control, in particular as 'add-on' nutritional intervention. Data showing the ability of ultramicronized PEA to limit opioid side effects, including the development of tolerance, have also been reviewed.
When I use a word . . . Medical eggcorns
Authors: Jeffrey K Aronson
Journal: BMJ (2024)

There are many different types of verbal errors that people make from time to time. They include folk etymology, mondegreens, and malapropisms. Eggcorns are verbal errors in which a word is replaced by another that sounds like it and typically shares with it some semantic connotation. Old-timer's disease for Alzheimer's is a good example. In this week's column I list and discuss some medical examples of eggcorns.
Treatment Response Biomarkers: Working Toward Personalized Radiotherapy for Lung Cancer
Authors: Ashley Horne, Ken Harada, Katherine D. Brown, Kevin Lee Min Chua, Fiona McDonald, Gareth Price, Paul Martin Putora, Dominic G. Rothwell, Corinne Faivre-Finn
Journal: Journal of Thoracic Oncology (2024)

Due to major advances in the field of radiation oncology, patients with lung cancer (LC) can now receive technically individualised radiotherapy treatments.However, in the era of precision oncology, radiotherapy-based treatment selection needs to be improved as many patients do not benefit or are not offered optimum therapies.Cost-effective robust biomarkers can address this knowledge gap and lead to individuals being offered more bespoke treatments leading to improved outcome.This narrative review discusses some of the current achievements and challenges in the realisation of personalised radiotherapy delivery in patients with LC.
Hybrid Bioactive Hydrogel Promotes Liver Regeneration through the Activation of Kupffer Cells and ECM Remodeling After Partial Hepatectomy
Authors: Yixiao Pan, Zhigang Zheng, Xueliang Zhang, Shupeng Liu, Shiya Zhuansun, Shiming Gong, Shilun Li, Hongye Wang, Yiwen Chen, Taihua Yang, Huimin Wu, Feng Xue, Qiang Xia, Kang He
Journal: Advanced Healthcare Materials (2024)

Abstract Partial hepatectomy is an essential surgical technique used to treat advanced liver diseases such as liver tumors, as well as for performing liver transplants from living donors. However, postoperative complications such as bleeding, abdominal adhesions, wound infections, and inadequate liver regeneration pose significant challenges and increase morbidity and mortality rates. A self‐repairing mixed hydrogel (O 5 H 2 /Cu 2+ /SCCK), containing stem cell derived cytokine (SCCK) derived from human umbilical cord mesenchymal stem cells (HUMSCs) treated with the traditional Chinese remedy Tanshinone IIA (TSA), is developed. This SCCK, in conjunction with O 5 H 2 , demonstrates remarkable effects on Kupffer cell activation and extracellular matrix (ECM) remodeling. This leads to the secretion of critical growth factors promoting enhanced proliferation of hepatocytes and endothelial cells, thereby facilitating liver regeneration and repair after partial hepatectomy. Furthermore, the hydrogel, featuring macrophage‐regulating properties, effectively mitigates inflammation and oxidative stress damage in the incision area, creating an optimal environment for postoperative liver regeneration. The injectability and strong adhesion of the hydrogel enables rapid hemostasis at the incision site, while its physical barrier function prevents postoperative abdominal adhesions. Furthermore, the hydrogel's incorporation of Cu 2+ provides comprehensive antibacterial effects, protecting against a wide range of bacteria types and reducing the chances of infections after surgery.
Direct in vivo CAR T cell engineering
Authors: Lauralie Short, Robert A. Holt, Pieter R. Cullis, Laura Evgin
Journal: Trends in Pharmacological Sciences (2024)

T cells modified to express intelligently designed chimeric antigen receptors (CARs) are exceptionally powerful therapeutic agents for relapsed and refractory blood cancers and have the potential to revolutionize therapy for many other diseases. To circumvent the complexity and cost associated with broad-scale implementation of ex vivo manufactured adoptive cell therapy products, alternative strategies to generate CAR T cells in vivo by direct infusion of nanoparticle-formulated nucleic acids or engineered viral vectors under development have received a great deal of attention in the past few years. Here, we outline the ex vivo manufacturing process as a motivating framework for direct in vivo strategies and discuss emerging data from preclinical models to highlight the potency of the in vivo approach, the applicability for new disease indications, and the remaining challenges associated with clinical readiness, including delivery specificity, long term efficacy, and safety.
Reply to Tiruvoipati <i>et al.</i>: VENT-AVOID Trial: Avoiding Acute Hypercapnic Respiratory Failure!
Authors: Abhijit Duggal, Steven A. Conrad, Laurent Brochard, Daniel Brodie, Nicholas S. Hill
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Reply to Tiruvoipati et al.: VENT-AVOID Trial – Avoiding Acute Hypercapnic Respiratory Failure!." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Advances in animal models of prenatal opioid exposure
Authors: Julia R. Ferrante, Julie A. Blendy
Journal: Trends in Neurosciences (2024)

Neonatal opioid withdrawal syndrome (NOWS) is a growing public health concern. The complexity of in utero opioid exposure in clinical studies makes it difficult to investigate underlying mechanisms that could ultimately inform early diagnosis and treatments. Clinical studies are unable to dissociate the influence of maternal polypharmacy or the environment from direct effects of in utero opioid exposure, highlighting the need for effective animal models. Early animal models of prenatal opioid exposure primarily used the prototypical opioid, morphine, and opioid exposure that was often limited to a narrow period during gestation. In recent years, the number of preclinical studies has grown rapidly. Newer models utilize both prescription and nonprescription opioids and vary the onset and duration of opioid exposure. In this review, we summarize novel prenatal opioid exposure models developed in recent years and attempt to reconcile results between studies while critically identifying gaps within the current literature.
Re: Michele Gnech, Lisette ’t Hoen, Alexandra Zachou, et al. Update and Summary of the European Association of Urology/European Society of Paediatric Urology Paediatric Guidelines on Vesicoureteral Reflux in Children. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2023.12.005
Authors: Ping Zhong, Xin Liu, Limin Liao
Journal: European Urology (2024)
The Endeavor to Predict Depression and Anxiety Trajectories in the Context of Chronic Diseases Remains a Formidable Challenge
Authors: Pedro Lucas Santana da Silveira, Guilherme Nobre Nogueira, Marisa Bezerra de Araújo, Fabio Gomes de Matos E Souza, Luísa Weber Bisol
Journal: Psychotherapy and Psychosomatics (2024)
Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study
Authors: Carina A Rodriguez, Eva Natukunda, Renate Strehlau, Esme L Venter, Supattra Rungmaitree, Coleen K Cunningham, Umesh Lalloo, Pope Kosalaraksa, Elizabeth HellstrÖm, Afaaf Liberty, Eric J McGrath, Meenu Kaur, Rory Leisegang, Jason T Hindman, Vinicius A Vieira, Kathryn Kersey, Mark F Cotton, Natella Rakhmanina, Aditya H Gaur
Journal: The Lancet HIV (2024)
[177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial
Authors: Louise Emmett, Shalini Subramaniam, Megan Crumbaker, Andrew Nguyen, Anthony M Joshua, Andrew Weickhardt, Sze-Ting Lee, Siobhan Ng, Roslyn J Francis, Jeffrey C Goh, David A Pattison, Thean Hsiang Tan, Ian D Kirkwood, Craig Gedye, Natalie K Rutherford, Shahneen Sandhu, Aravind Ravi Kumar, David Pook, Shakher Ramdave, David P Nadebaum, Mark Voskoboynik, Andrew D Redfern, William Macdonald, Laurence Krieger, Geoff Schembri, Wei Chua, Peter Lin, Lisa Horvath, Patricia Bastick, Patrick Butler, Alison Yan Zhang, Sonia Yip, Hayley Thomas, Ailsa Langford, Michael S Hofman, Margaret McJannett, Andrew James Martin, Martin R Stockler, Ian D Davis
Journal: The Lancet Oncology (2024)
Fabrication and Characterization of PDMS Waveguides for Flexible Optrodes
Authors: Linda Rudmann, Daniel Scholz, Marie T. Alt, Alexander Dieter, Eva Fiedler, Tobias Moser, Thomas Stieglitz
Journal: Advanced Healthcare Materials (2024)

With the growth of optogenetic research, the demand for optical probes tailored to specific applications is ever rising. Specifically, for applications like the coiled cochlea of the inner ear, where planar, stiff, and nonconformable probes can hardly be used, transitioning from commonly used stiff glass fibers to flexible probes is required, especially for long-term use. Following this demand, polydimethylsiloxane (PDMS) with its lower Young's modulus compared to glass fibers can serve as material of choice. Hence, the long-term usability of PDMS as a waveguide material with respect to variations in transmission and refractive index over time is investigated. Different manufacturing methods for PDMS-based flexible waveguides are established and compared with the aim to minimize optical losses and thus maximize optical output power. Finally, the waveguides with lowest optical losses (-4.8 dB cm
Associations between change in BMI and the risk of hypertension and dyslipidaemia in people receiving integrase strand-transfer inhibitors, tenofovir alafenamide, or both compared with other contemporary antiretroviral regimens: a multicentre, prospective observational study from the RESPOND consortium cohorts
Authors: Dathan M Byonanebye, Mark N Polizzotto, Fernando Maltez, Andri Rauch, Katharina Grabmeier-Pfistershammer, Ferdinand Wit, Stéphane De Wit, Antonella Castagna, Antonella d'Arminio Monforte, Cristina Mussini, Jan-Christian Wasmuth, Eric Fontas, Irene Abela, Mario Sarcletti, Loveleen Bansi-Matharu, Nadine Jaschinski, Lars Peters, Sean R Hosein, Vani Vannappagari, Cal Cohen, Emiliano Bissio, Amanda Mocroft, Matthew Law, Lene Ryom, Kathy Petoumenos
Journal: The Lancet HIV (2024)
From Blur to Brilliance: The Ascendance of Advanced Microscopy in Neuronal Cell Biology
Authors: Kirby R. Campbell, Liam P. Hallada, Yu-Shan Huang, David J. Solecki
Journal: Annual Review of Neuroscience (2024)

The intricate network of the brain's neurons and synapses poses unparalleled challenges for research, distinct from other biological studies. This is particularly true when dissecting how neurons and their functional units work at a cell biological level. While traditional microscopy has been foundational, it was unable to reveal the deeper complexities of neural interactions. However, an imaging renaissance has transformed our capabilities. Advancements in light and electron microscopy, combined with correlative imaging, now achieve unprecedented resolutions, uncovering the most nuanced neural structures. Maximizing these tools requires more than just technical proficiency. It is crucial to align research aims, allocate resources wisely, and analyze data effectively. At the heart of this evolution is interdisciplinary collaboration, where various experts come together to translate detailed imagery into significant biological insights. This review navigates the latest developments in microscopy, underscoring both the promise of and prerequisites for bending this powerful tool set to understanding neuronal cell biology.
Next-Gen PARP Inhibitor Effective in Breast Cancer
Authors: Mitch Leslie
Journal: Cancer Discovery (2024)

New data from the PETRA clinical trial suggest that the PARP1 inhibitor saruparib induces durable responses in patients with HER-negative breast cancer. Researchers found that the maximum tolerated dose of 90 mg per day produced an overall response rate of 46.7% and median duration of response of 5.6 months. The values for a dose of 60 mg were 48.4% and 7.3 months, leading the researchers to choose this as the optimal dose.
Lipid nanoparticle encapsulated large peritoneal macrophages migrate to the lungs via the systemic circulation in a model of clodronate-mediated lung-resident macrophage depletion
Authors: Dhaval Oza, Fernando Ivich, Joshua Pace, Mikyung Yu, Mark Niedre, Mansoor Amiji
Journal: Theranostics (2024)

A mature tissue resident macrophage (TRM) population residing in the peritoneal cavity has been known for its unique ability to migrate to peritoneally located injured tissues and impart wound healing properties. Here, we sought to expand on this unique ability of large peritoneal macrophages (LPMs) by investigating whether these GATA6+ LPMs could also intravasate into systemic circulation and migrate to extra-peritoneally located lungs upon ablating lung-resident alveolar macrophages (AMs) by intranasally administered clodronate liposomes in mice.
Harnessing gastrointestinal organoids for cancer therapy
Authors: Gunter Maubach, Michael Naumann
Journal: Trends in Molecular Medicine (2024)

Gastrointestinal organoids have emerged as a model system that authentically recapitulates the in vivo situation. Despite biomedical and technical challenges, self-assembled 3D structures derived from pluripotent stem cells or healthy and diseased tissues have proved to be invaluable tools for cancer drug discovery, disease modeling, and studying infection with carcinogenic pathogens.
Triplet‐Triplet Annihilation Upconversion‐Based Photolysis: Applications in Photopharmacology
Authors: Maxime Klimezak, Juliane Chaud, Anaïs Brion, Frédéric Bolze, Benoit Frisch, Béatrice Heurtault, Antoine Kichler, Alexandre Specht
Journal: Advanced Healthcare Materials (2024)

The emerging field of photopharmacology is a promising chemobiological methodology for optical control of drug activities that could ultimately solve the off-target toxicity outside the disease location of many drugs for the treatment of a given pathology. The use of photolytic reactions looks very attractive for a light-activated drug release but requires to develop photolytic reactions sensitive to red or near-infrared light excitation for better tissue penetration. This review will present the concepts of triplet-triplet annihilation upconversion-based photolysis and their recent in vivo applications for light-induced drug delivery using photoactivatable nanoparticles.
High‐risk multiple myeloma: Redefining genetic, clinical, and functional high‐risk disease in the era of molecular medicine and immunotherapy
Authors: Matthew J. Rees, Shaji Kumar
Journal: American Journal of Hematology (2024)

Abstract Multiple myeloma (MM) exhibits significant heterogeneity in its presentation, genetics, and treatment response. Despite therapeutic advances, some patients continue to relapse early (ER, &lt;18‐months) and rapidly cycle through therapies. Myriad prognostic factors have been identified and incorporated into risk stratification models; however, these produce discordant, often three‐tiered outputs that fail to identify many patients destined for ER. Treatment strategies are increasingly focused on disease biology and trials enriched for high‐risk (HR)MM, but consensus on the minimum required testing and a succinct, specific, and clinically meaningful definition for HRMM remains elusive. We review the risk‐factors, definitions, and future directions for HRMM.
Galectin‐8 inhibition and functions in immune response and tumor biology
Authors: Edvin Purić, Ulf J. Nilsson, Marko Anderluh
Journal: Medicinal Research Reviews (2024)

Abstract Galectins are among organisms' most abundantly expressed lectins (carbohydrate‐binding proteins) that specifically bind β‐galactosides. They act not only outside the cell, where they bind to extracellular matrix glycans, but also inside the cell, where they have a significant impact on signaling pathways. Galectin‐8 is a galectin family protein encoded by the LGALS8 gene. Its role is evident in both T‐ and B‐cell immunity and in the innate immune response, where it acts directly on dendritic cells and induces some pro‐inflammatory cytokines. Galectin‐8 also plays an important role in the defense against bacterial and viral infections. It is known to promote antibacterial autophagy by recognizing and binding glycans present on the vacuolar membrane, thus acting as a danger receptor. The most important role of galectin‐8 is the regulation of cancer growth, metastasis, tumor progression, and tumor cell survival. Importantly, the expression of galectins is typically higher in tumor tissues than in noncancerous tissues. In this review article, we focus on galectin‐8 and its function in immune response, microbial infections, and cancer. Given all of these functions of galectin‐8, we emphasize the importance of developing new and selective galectin‐8 inhibitors and report the current status of their development.
Deep learning evaluation of echocardiograms to identify occult atrial fibrillation
Authors: Neal Yuan, Nathan R. Stein, Grant Duffy, Roopinder K. Sandhu, Sumeet S. Chugh, Peng-Sheng Chen, Carine Rosenberg, Christine M. Albert, Susan Cheng, Robert J. Siegel, David Ouyang
Journal: npj Digital Medicine (2024)

Abstract Atrial fibrillation (AF) often escapes detection, given its frequent paroxysmal and asymptomatic presentation. Deep learning of transthoracic echocardiograms (TTEs), which have structural information, could help identify occult AF. We created a two-stage deep learning algorithm using a video-based convolutional neural network model that (1) distinguished whether TTEs were in sinus rhythm or AF and then (2) predicted which of the TTEs in sinus rhythm were in patients who had experienced AF within 90 days. Our model, trained on 111,319 TTE videos, distinguished TTEs in AF from those in sinus rhythm with high accuracy in a held-out test cohort (AUC 0.96 (0.95–0.96), AUPRC 0.91 (0.90–0.92)). Among TTEs in sinus rhythm, the model predicted the presence of concurrent paroxysmal AF (AUC 0.74 (0.71–0.77), AUPRC 0.19 (0.16–0.23)). Model discrimination remained similar in an external cohort of 10,203 TTEs (AUC of 0.69 (0.67–0.70), AUPRC 0.34 (0.31–0.36)). Performance held across patients who were women (AUC 0.76 (0.72–0.81)), older than 65 years (0.73 (0.69–0.76)), or had a CHA 2 DS 2 VASc ≥2 (0.73 (0.79–0.77)). The model performed better than using clinical risk factors (AUC 0.64 (0.62–0.67)), TTE measurements (0.64 (0.62–0.67)), left atrial size (0.63 (0.62–0.64)), or CHA 2 DS 2 VASc (0.61 (0.60–0.62)). An ensemble model in a cohort subset combining the TTE model with an electrocardiogram (ECGs) deep learning model performed better than using the ECG model alone (AUC 0.81 vs. 0.79, p = 0.01). Deep learning using TTEs can predict patients with active or occult AF and could be used for opportunistic AF screening that could lead to earlier treatment.
Hemotympanum with a Basilar Skull Fracture
Authors: Carlos Carazo Casas, Marimar Medina Gonzalez
Journal: New England Journal of Medicine (2024)

A 15-year-old boy presented with a 1-hour history of hearing loss and pain in the left ear after he had tripped and fallen on the street. An otoscopic examination of the left ear showed blood behind the tympanic membrane.
Combination therapies with ponatinib and asciminib in a preclinical model of chronic myeloid leukemia blast crisis with compound mutations
Authors: Nikola Curik, Adam Laznicka, Vaclava Polivkova, Jitka Krizkova, Eva Pokorna, Pavel Semerak, Pavla Suchankova, Pavel Burda, Andreas Hochhaus, Katerina Machova Polakova
Journal: Leukemia (2024)
Long‐term follow‐up of neutrophil activation after severe‐to‐critical <scp>SARS‐CoV</scp>‐2 infection: A longitudinal study
Authors: Simon Valentin, Veronique Regnault, Jean‐Louis Gueant, Bruno Ribeiro Baptista, Thery Abel, Patrick Lacolley, Frederic Schlemmer, Ari Chaouat, François Chabot, Rosa‐Maria Gueant‐Rodriguez
Journal: Allergy (2024)

The data that support the findings of this study are available from the corresponding author upon reasonable request. Appendix S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Towards a common European ethical and legal framework for conducting clinical research: the GATEKEEPER experience
Authors: Alessia Maccaro, Vasiliki Tsiompanidou, Davide Piaggio, Alba M. Gallego Montejo, Gloria Cea Sánchez, Jordi de Batlle, Adrian Quesada Rodriguez, Giuseppe Fico, Leandro Pecchia
Journal: npj Digital Medicine (2024)

Abstract This paper examines the ethical and legal challenges encountered during the GATEKEEPER Project and how these challenges informed the development of a comprehensive framework for future Large-Scale Pilot (LSP) projects. GATEKEEPER is a LSP Project with 48 partners conducting 30 implementation studies across Europe with 50,000 target participants grouped into 9 Reference Use Cases. The project underscored the complexity of obtaining ethical approval across various jurisdictions with divergent regulations and procedures. Through a detailed analysis of the issues faced and the strategies employed to navigate these challenges, this study proposes an ethical and legal framework. This framework, derived from a comparative analysis of ethical application forms and regulations, aims to streamline the ethical approval process for future LSP research projects. By addressing the hurdles encountered in GATEKEEPER, the proposed framework offers a roadmap for more efficient and effective project management, ensuring smoother implementation of similar projects in the future.