tbuckley/cabot-search huggingface dataset:
Tumor‐associated exosomes in cancer progression and therapeutic targets
Authors: Xiaomin Liu, Fan Wu, Wei Pan, Guangchao Liu, Hui Zhang, Dawei Yan, Saijing Zheng, Zhongliang Ma, Xiaojun Ren
Journal: MedComm (2024)

Exosomes are small membrane vesicles that are released by cells into the extracellular environment. Tumor-associated exosomes (TAEs) are extracellular vesicles that play a significant role in cancer progression by mediating intercellular communication and contributing to various hallmarks of cancer. These vesicles carry a cargo of proteins, lipids, nucleic acids, and other biomolecules that can be transferred to recipient cells, modifying their behavior and promoting tumor growth, angiogenesis, immune modulation, and drug resistance. Several potential therapeutic targets within the TAEs cargo have been identified, including oncogenic proteins, miRNAs, tumor-associated antigens, immune checkpoint proteins, drug resistance proteins, and tissue factor. In this review, we will systematically summarize the biogenesis, composition, and function of TAEs in cancer progression and highlight potential therapeutic targets. Considering the complexity of exosome-mediated signaling and the pleiotropic effects of exosome cargoes has challenge in developing effective therapeutic strategies. Further research is needed to fully understand the role of TAEs in cancer and to develop effective therapies that target them. In particular, the development of strategies to block TAEs release, target TAEs cargo, inhibit TAEs uptake, and modulate TAEs content could provide novel approaches to cancer treatment.
Which trial do we need? Shorter antifungal treatment for candidemia – challenging the 14-day dogma
Authors: Nico Bekaan, Oliver A Cornely, Tim Friede, Jürgen Prattes, Rosanne Sprute, Martin Hellmich, Philipp Koehler, Jon Salmanton-García, Jannik Stemler, Ilana Reinhold
Journal: Clinical Microbiology and Infection (2024)
Myopic Shift Over Five Years Following Pediatric Lensectomy with Primary Intraocular Lens Implantation
Authors: Alejandra G de Alba Campomanes, Michael X Repka, Sarah R Hatt, Desirae R Sutherland, David A Leske, David G Morrison, Nicole Fallaha, B Michele Melia, Raymond T Kraker, Susan A Cotter, Jonathan M Holmes
Journal: Ophthalmology (2024)
Angiotensin receptor blocker attacks armored and cold tumors and boosts immune checkpoint blockade
Authors: Jie Mei, Jiahui Chu, Kai Yang, Zhiwen Luo, Jiayue Yang, Junying Xu, Qing Li, Yan Zhang, Qinglin Zhang, Mengyun Wan, Ningyi Xue, Junli Ding, Yichao Zhu, Yun Cai, Yongmei Yin
Journal: Journal for ImmunoTherapy of Cancer (2024)

Immune checkpoint blockade (ICB) has made remarkable achievements, but newly identified armored and cold tumors cannot respond to ICB therapy. The high prevalence of concomitant medications has huge impact on immunotherapeutic responses, but the clinical effects on the therapeutic outcome of armored and cold tumors are still unclear.
Autologous CD7 CAR T cells generated without T-cell pre-selection in pediatric patients with relapsed/refractory T-ALL: a phase I trial
Authors: Liping Zhao, Chuo Li, Shiyu Zuo, Yajing Han, Biping Deng, Zhuojun Ling, Yanlei Zhang, Shuixiu Peng, Jinlong Xu, Jiajia Duan, Zelin Wang, Xinjian Yu, Qinlong Zheng, Xiuwen Xu, Ying Yuan, Zhenglong Tian, Kaiting Tang, Yibing Zhang, Qing Niu, Jiecheng Zhang, Alex H Chang, Yuechen Luo, Xiaoming Feng, Jing Pan
Journal: Molecular Therapy (2024)
MHC class I and II-deficient humanized mice are suitable tools to test the long-term antitumor efficacy of immune checkpoint inhibitors and T-cell engagers
Authors: Iñaki Eguren-Santamaria, Eva Fernández de Piérola, Gracián Camps, Paula Martín-Muñoz, María Campos, Doina Cuculescu, Inmaculada Aguilera-Buenosvinos, Inmaculada Rodríguez López, Rafael Salido-Vallejo, Raluca Alexandru, Carlos E De Andrea, Laura Álvarez-Gigli, Pedro Berraondo, Ignacio Melero, Miguel F Sanmamed
Journal: Journal for ImmunoTherapy of Cancer (2024)

Immunodeficient mice engrafted with peripheral blood mononuclear cells (PBMCs) are models to study new cancer immunotherapy agents. However, this approach is associated with xenograft-versus-host disease (xGVHD), which starts early after PBMC transfer and limits the duration and interpretation of experiments. Here, we explore different approaches to overcome xGVHD and better support the development of cancer immunotherapies.
Intratumoral CXCL13<sup>+</sup>CD160<sup>+</sup>CD8<sup>+</sup>T cells promote the formation of tertiary lymphoid structures to enhance the efficacy of immunotherapy in advanced gastric cancer
Authors: Jiawei Wang, Yuan Liang, Ao Xue, Jian Xiao, Xinyu Zhao, Shuqing Cao, Pengyu Li, Jiacheng Dong, Yuan Li, Zekuan Xu, Li Yang
Journal: Journal for ImmunoTherapy of Cancer (2024)

Stage IV gastric cancer is a highly heterogeneous and lethal tumor with few therapeutic strategies. The combination of programmed cell death protein 1 inhibitors and chemotherapy is currently the standard frontline treatment regimen for advanced gastric cancer. Nevertheless, it remains a great challenge to screen the beneficiaries of immunochemotherapy and expand indications for this treatment regimen.
Redesigned Chondroitinase ABC degrades inhibitory chondroitin sulfate proteoglycans in vitro and in vivo in the stroke-injured rat brain
Authors: Nitzan Letko Khait, Sabrina Zuccaro, Dhana Abdo, Hong Cui, Ricky Siu, Eric Ho, Cindi M Morshead, Molly S Shoichet
Journal: Biomaterials (2024)
Prevention of Prostate Cancer Metastasis by a CRISPR-delivering Nanoplatform for Interleukin-30 Genome Editing
Authors: Cristiano Fieni, Stefania Livia Ciummo, Carlo Sorrentino, Simona Marchetti, Simone Vespa, Paola Lanuti, Lavinia Vittoria Lotti, Emma Di Carlo
Journal: Molecular Therapy (2024)
The human accelerated region HAR202 controls <i>NPAS3</i> expression in the developing forebrain displaying differential enhancer activity between modern and archaic human sequences
Authors: Alfredo Leandro Caporale, Alejandro Raúl Cinalli, Marcelo Rubinstein, Lucía F Franchini
Journal: Molecular Biology and Evolution (2024)

Abstract It has been proposed that the phenotypic differences in cognitive abilities between humans and our closest living relatives, the chimpanzees, are largely due to changes in the regulation of neurodevelopmental genes. We have previously found that the neurodevelopmental transcription factor gene NPAS3 accumulates the largest number of human accelerated regions (HARs), suggesting it may play some role in the phenotypic evolution of the human nervous system. In this work, we performed a comparative functional analysis of NPAS3-HAR202 using enhancer reporter assays in transgenic zebrafish and mice. We found that the Homo sapiens HAR202 ortholog failed to drive reporter expression to the zebrafish nervous system, in high contrast to the strong expression displayed by the rest of vertebrate ortholog sequences tested. Remarkably, the HAR202 ortholog from archaic humans (Neanderthals/Denisovans) also displayed a pan-vertebrate expression pattern, despite the fact that archaic and modern humans have only one nucleotide substitution. Moreover, similar results were found when comparing enhancer activity in transgenic mice, where we observed loss of activity of the modern human version in the mouse developing brain. To investigate the functional importance of HAR202 we generated mice lacking HAR202 and found a remarkable decrease of Npas3 expression in the forebrain during development. Our results place HAR202 as one of the very few examples of a neurodevelopmental transcriptional enhancer displaying functional evolution in the brain as a result of a fast molecular evolutionary process that specifically occurred in the human lineage.
Prospective single-arm trial on feasibility and safety of endoscopic robotic system for colonic endoscopic submucosal dissection
Authors: Philip Wai Yan Chiu, Hon Chi Yip, Simon Chu, Shannon M Chan, Ho Shing Louis Lau, Raymond SY Tang, Soo Jay Phee, Khek Yu Ho, Simon Siu Man Ng
Journal: Endoscopy (2024)

Introduction The development of EndoMaster EASE system aims to enhance safety and efficacy of colonic ESD through two flexible robotic arms for tissue retraction and dissection. This is the first clinical trial to evaluate the performance of colorectal ESD using EndoMaster. Method Patients with early mucosal colorectal neoplasia not feasible for en-bloc resection with snare-based techniques were recruited. The EndoMaster EASE robotic system consisted of an independently designed flexible robotic platform with 2 robotic arms. The primary outcome was complete resection rate using EndoMaster. Secondary outcomes included operating time, hospital stay, procedure-related complications and oncological outcomes. Results From May 2020 to Jan 2022, 43 patients received robotic ESD with median age of 66 years (40-83). The mean robotic dissection time was 62.0 ± 45.1 minutes. All procedures except six were completed using EndoMaster with technical success rate of 86.1% (37/43). The en-bloc resection rate among cases with technical success was 94.6% (35/37) while the complete resection rate was 83.8% (31/37). The median size of specimen was 35mm (15-90mm). The mean hospital stay was 2.6 ± 1.2 days and there was one delayed bleeding 4 days after ESD which was controlled by endoscopy. One patient sustained perforation during procedure which was completely closed using clips without sequelae. 2 patients required salvage surgery due to deep margin involvement by adenocarcinoma in histopathology. Conclusion This first clinical trial confirmed the safety and efficacy of performing colorectal ESD using EndoMaster EASE robotic system (Clinicaltrial.gov: NCT04196062).
Correction: Rescue endoscopic treatment with completion by radical surgery following misplacement of a partially covered metal stent in an anastomotic fistula post-Lewis Santy esophagectomy
Authors: Pierre Mayer, Lucile Héroin, François Habersetzer, Pierre-Yves Christmann, Jérôme Huppertz, Leonardo Sosa-Valencia, Abdenor Badaoui
Journal: Endoscopy (2024)
Cardiometabolic Aspects of Congenital Adrenal Hyperplasia
Authors: Robert Krysiak, Hedi L Claahsen-van der Grinten, Nicole Reisch, Philippe Touraine, Henrik Falhammar
Journal: Endocrine Reviews (2024)

Abstract Treatment of classic congenital adrenal hyperplasia (CAH) is directed at replacing deficient hormones and reducing androgen excess. However, even in the era of early diagnosis and lifelong hormonal substitution, the presence of CAH is still associated with numerous complications and also with increased mortality. The aim of this article was to create an authoritative and balanced review concerning cardiometabolic risk in patients with CAH. The authors searched all major databases and scanned reference lists of all potentially eligible articles to find relevant articles. The risk was compared with that in other forms of adrenal insufficiency. The reviewed articles, most of which were published recently, provided conflicting results, which can be partially explained by differences in the inclusion criteria and treatment, small sample sizes, and gene–environment interactions. However, many studies showed that the presence of CAH is associated with an increased risk of weight gain, worsening of insulin sensitivity, high blood pressure, endothelial dysfunction, early atherosclerotic changes in the vascular wall, and left ventricular diastolic dysfunction. These complications were more consistently reported in patients with classic than nonclassic CAH and were in part related to hormonal and functional abnormalities associated with this disorder and/or to the impact of overtreatment and undertreatment. An analysis of available studies suggests that individuals with classic CAH are at increased cardiometabolic risk. Excess cardiovascular and metabolic morbidity is likely multifactorial, related to glucocorticoid overtreatment, imperfect adrenal hormone replacement therapy, androgen excess, and adrenomedullary failure. Cardiometabolic effects of new therapeutic approaches require future targeted studies.
Intention-to-treat outcomes of patients with hepatocellular carcinoma receiving immunotherapy before liver transplant: the multicenter VITALITY study
Authors: Parissa Tabrizian, Matthew Holzner, Veeral Ajmera, Amy K Kim, Kali Zhou, Gabriel T Schnickel, Kelly Torosian, Maarouf Hoteit, Rebecca Marino, Michael Li, Francis Yao, Sander S Florman, Myron E Schwartz, Neil Mehta
Journal: Journal of Hepatology (2024)
Inflammation promotes stomach epithelial defense by stimulating the secretion of antimicrobial peptides in the mucus
Authors: Megi Vllahu, Antonia Voli, Valerio Licursi, Claudia Zagami, Antonella D’Amore, Jan Traulsen, Sara Woelffling, Monika Schmid, Robbie Crickley, Richard Lisle, Alexander Link, Alessandra Tosco, Thomas F. Meyer, Francesco Boccellato
Journal: Gut Microbes (2024)

The mucus serves as a protective barrier in the gastrointestinal tract against microbial attacks. While its role extends beyond merely being a physical barrier, the extent of its active bactericidal properties remains unclear, and the mechanisms regulating these properties are not yet understood. We propose that inflammation induces epithelial cells to secrete antimicrobial peptides, transforming mucus into an active bactericidal agent. To investigate the properties of mucus, we previously developed mucosoid culture models that mimic the healthy human stomach epithelium. Similar to organoids, mucosoids are stem cell-driven cultures; however, the cells are cultivated on transwells at air-liquid interface. The epithelial cells of mucosoids form a polarized monolayer, allowing differentiation into all stomach lineages, including mucus-secreting cells. This setup facilitates the secretion and accumulation of mucus on the apical side of the mucosoids, enabling analysis of its bactericidal effects and protein composition, including antimicrobial peptides. Our findings show that TNFα, IL1β, and IFNγ induce the secretion of antimicrobials such as lactotransferrin, lipocalin2, complement component 3, and CXCL9 into the mucus. This antimicrobial-enriched mucus can partially eliminate
Melanoma Incidence and Mortality Trends in Sweden
Authors: Hildur Helgadottir, Rasmus Mikiver, Karina Schultz, Kari Nielsen, Francesca Portelli, Jan Lapins, Susana Puig, Karolin Isaksson
Journal: JAMA Dermatology (2024)

Importance Over the past decades, many global regions have experienced a steady increase in the incidence of cutaneous melanoma. However, more recently, a downward trend has been observed in the younger age groups in Australia and the US. Yet, in Europe, none of the countries have reported any significant decline in melanoma incidence for any age group. Objective To assess melanoma incidence and mortality trends in Sweden, with a focus on individuals younger than the average age of melanoma onset. Design, Setting, and Participants This cohort study used data on the national population from the Swedish Melanoma Registry and the Swedish Cancer Registry, which cover more than 99% of all primary invasive cutaneous melanomas diagnosed in the country. All patients diagnosed from 1990 to 2022 were included. Main Outcomes and Measures Incidence and mortality rates per 100 000 inhabitants were calculated for each year and shown as average annual rates for every 5-year period from 1990 to 2022. Joinpoint regression models were used to evaluate statistical significance of temporal trends and points of change. Results There were 34 800 primary invasive cutaneous melanomas (19 582 [56.3%] in females and 15 218 [43.7%] in males) reported in 33 324 individuals younger than 60 years (median [IQR] age, 48 [36-58] years) from 1990 to 2022. A consistent rise in melanoma incidence was observed among those 50 to 59 years old. The age groups from 20 to 29 years, 30 to 39 years, and 40 to 49 years showed an incidence peak in 2013 to 2015 followed by stable or significantly declining rates until 2022. In patients younger than 20 years, melanoma incidence remained low with no significant trends. There was also a significant decline in melanoma mortality among 30- to 59-year-old individuals, but not in those 60 years and older. Conclusions and Relevance The findings of this cohort study showed a significant recent downward trend in both melanoma incidence and melanoma mortality in the age group 30 to 49 years in Sweden. The reasons for these declines are unclear but may include UV protection, public health campaigns, changing population demographics, and the introduction of effective melanoma treatment. None of these possibilities were evaluated; further study is needed.
OSTEOCHONDRAL REGENERATION WITH A TRI-LAYERED BIOMIMETIC RESORBABLE SCAFFOLD: IN VIVO STUDY IN A SHEEP MODEL UP TO 12 MONTHS OF FOLLOW-UP
Authors: Alessandro Di Martino, Manuela Salerno, Elisabetta Galassi, Laura Grillini, Alessandro Dotti, Claudio De Luca, Giuseppe Filardo
Journal: Biomaterials (2024)
Tissue levels of <i>Alternaria</i> allergen <scp>Alt a 1</scp> reflect recurrence of refractory airway diseases
Authors: Yui Miyabe, Tomoe Abe, Toshiki Yamada, Tentaro Endo, Yohei Kawasaki, Shinsuke Suzuki, Misaki Arima, Shigeharu Ueki, Takechiyo Yamada
Journal: Allergy (2024)
Association of cytotoxic effector memory <scp>CD8</scp><sup>+</sup> T cells with sustained unresponsiveness after peanut oral immunotherapy
Authors: Hana Seastedt, Xiaorui Han, Andrea Fernandes, Stephen J. Galli, Scott D. Boyd, Kari C. Nadeau, Monali Manohar, Sharon Chinthrajah
Journal: Allergy (2024)
Risk of hepatic events associated with use of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists, and thiazolidinediones among patients with metabolic dysfunction-associated steatotic liver disease
Authors: Sungho Bea, Hwa Yeon Ko, Jae Hyun Bae, Young Min Cho, Yoosoo Chang, Seungho Ryu, Christopher D Byrne, Ju-Young Shin
Journal: Gut (2024)

To examine the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) through a head-to-head comparison with glucagon-like peptide-1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).
Rational design of a poly-L-glutamic acid-based combination conjugate for hormone-responsive breast cancer treatment
Authors: Paz Boix-Montesinos, María Medel, Alessio Malfanti, Snežana Đorđević, Esther Masiá, David Charbonnier, Paula Carrascosa-Marco, Ana Armiñán, María J Vicent
Journal: Journal of Controlled Release (2024)
Health outcomes 3 months and 6 months after molnupiravir treatment for COVID-19 for people at higher risk in the community (PANORAMIC): a randomised controlled trial
Authors: Victoria Harris, Jane Holmes, Oghenekome Gbinigie-Thompson, Najib M Rahman, Duncan B Richards, Gail Hayward, Jienchi Dorward, David M Lowe, Joseph F Standing, Judith Breuer, Saye Khoo, Stavros Petrou, Kerenza Hood, Haroon Ahmed, Andrew Carson-Stevens, Jonathan S Nguyen-Van-Tam, Mahendra G Patel, Benjamin R Saville, Nick Francis, Nicholas P B Thomas, Philip Evans, Melissa Dobson, May Ee Png, Mark Lown, Oliver van Hecke, Bhautesh D Jani, Nigel D Hart, Daniel Butler, Lucy Cureton, Meena Patil, Monique Andersson, Maria Coates, Clare Bateman, Jennifer C Davies, Ivy Raymundo-Wood, Andrew Ustianowski, Ly-Mee Yu, F D Richard Hobbs, Paul Little, Christopher C Butler
Journal: The Lancet Infectious Diseases (2024)
Efficacy and safety of fedratinib in patients with myelofibrosis previously treated with ruxolitinib (FREEDOM2): results from a multicentre, open-label, randomised, controlled, phase 3 trial
Authors: Claire N Harrison, Ruben Mesa, Moshe Talpaz, Haifa Kathrin Al-Ali, Blanca Xicoy, Francesco Passamonti, Francesca Palandri, Giulia Benevolo, Alessandro Maria Vannucchi, Clemence Mediavilla, Alessandra Iurlo, InHo Kim, Shelonitda Rose, Patrick Brown, Christopher Hernandez, Jia Wang, Jean-Jacques Kiladjian
Journal: The Lancet Haematology (2024)
Closing the gap between open source and commercial large language models for medical evidence summarization
Authors: Gongbo Zhang, Qiao Jin, Yiliang Zhou, Song Wang, Betina Idnay, Yiming Luo, Elizabeth Park, Jordan G Nestor, Matthew E Spotnitz, Ali Soroush, Thomas R Campion, Zhiyong Lu, Chunhua Weng, Yifan Peng
Journal: npj Digital Medicine (2024)
Evaluating metagenomics and targeted approaches for diagnosis and surveillance of viruses
Authors: Sarah Buddle, Leysa Forrest, Naomi Akinsuyi, Luz Marina Martin Bernal, Tony Brooks, Cristina Venturini, Charles Miller, Julianne R Brown, Nathaniel Storey, Laura Atkinson, Timothy Best, Sunando Roy, Sian Goldsworthy, Sergi Castellano, Peter Simmonds, Heli Harvala, Tanya Golubchik, Rachel Williams, Judith Breuer, Sofia Morfopoulou, Oscar Enrique Torres Montaguth
Journal: Genome Medicine (2024)
Knee Osteoarthritis
Authors: Allan C. Gelber
Journal: Annals of Internal Medicine (2024)

Knee osteoarthritis (OA) typically presents with joint pain that is exacerbated by use and alleviated with rest. There is relatively brief, self-limited morning stiffness and absence of constitutional symptoms. Overweight and obesity are the most important modifiable risk factors. Although pharmacologic and nonpharmacologic interventions are generally effective at alleviating pain and improving physical function, they do not fundamentally reverse the pathologic and radiographic process of knee OA. As the severity of disease increases, the magnitude of pain and functional impairment intensifies. Surgical intervention should be pursued to relieve pain and restore functionality only when nonpharmacologic approaches and pharmacologic agents fail to control pain.
Hormonal Treatments and Vaginal Moisturizers for Genitourinary Syndrome of Menopause
Authors: Elisheva R. Danan, Catherine Sowerby, Kristen E. Ullman, Kristine Ensrud, Mary L. Forte, Nicholas Zerzan, Maylen Anthony, Caleb Kalinowski, Hamdi I. Abdi, Jessica K. Friedman, Adrienne Landsteiner, Nancy Greer, Rahel Nardos, Cynthia Fok, Philipp Dahm, Mary Butler, Timothy J. Wilt, Susan Diem
Journal: Annals of Internal Medicine (2024)

Postmenopausal women commonly experience vulvovaginal, urinary, and sexual symptoms associated with genitourinary syndrome of menopause (GSM).
Complementary and Alternative Therapies for Genitourinary Syndrome of Menopause
Authors: Kristen E. Ullman, Susan Diem, Mary L. Forte, Kristine Ensrud, Catherine Sowerby, Nicholas Zerzan, Maylen Anthony, Adrienne Landsteiner, Nancy Greer, Mary Butler, Timothy J. Wilt, Elisheva R. Danan
Journal: Annals of Internal Medicine (2024)

Women seeking nonhormonal interventions for vulvovaginal, urinary, and sexual symptoms associated with genitourinary syndrome of menopause (GSM) may seek out complementary and alternative medicine or therapies (CAMs).
Association Between Hospital Type and Resilience During COVID-19 Caseload Stress
Authors: Maniraj Neupane, Sarah Warner, Alex Mancera, Junfeng Sun, Christina Yek, Sadia H. Sarzynski, Roxana Amirahmadi, Mary Richert, Emad Chishti, Morgan Walker, Bruce J. Swihart, Steven H. Mitchell, John Hick, Bram Rochwerg, Eddy Fan, Cumhur Y. Demirkale, Sameer S. Kadri
Journal: Annals of Internal Medicine (2024)

Imbalances between hospital caseload and care resources that strained U.S. hospitals during the pandemic have persisted after the pandemic amid ongoing staff shortages. Understanding which hospital types were more resilient to pandemic overcrowding-related excess deaths may prioritize patient safety during future crises.