tbuckley/cabot-search huggingface dataset:
Impact of age, comorbidities and relevant changes on surveillance strategy of intraductal papillary mucinous neoplasms: a competing risk analysis
Authors: Stefano Crippa, Giovanni Marchegiani, Giulio Belfiori, Paola Vittoria Maria Rancoita, Tommaso Pollini, Anna Burelli, Laura Apadula, Maria Giovanna Scarale, Davide Socci, Marco Biancotto, Giuseppe Vanella, Paolo Giorgio Arcidiacono, Gabriele Capurso, Roberto Salvia, Massimo Falconi
Journal: Gut (2024)

Cost-effectiveness of surveillance for branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) is debated. We combined different categories of risks of IPMN progression and of IPMN-unrelated mortality to improve surveillance strategies.
bDMARD can prevent the progression of AA amyloidosis to end-stage renal disease
Authors: Peter Kvacskay, Ute Hegenbart, Hanns-Martin Lorenz, Stefan O Schönland, Norbert Blank
Journal: Annals of the Rheumatic Diseases (2024)

AA amyloidosis (AA) can be the consequence of any chronic inflammatory disease. AA is associated with chronic inflammatory diseases (cid+AA), autoinflammatory syndromes (auto+AA) or AA of unknown origin or idiopathic AA (idio+AA). The major organ manifestation is renal AA that can progress to end-stage renal disease (ESRD) and multiple organ failure.
Disease flares with baricitinib dose reductions and development of flare criteria in patients with CANDLE/PRAAS
Authors: Kader Cetin Gedik, Ana M Ortega-Villa, Grace Materne, Andre Rastegar, Gina A Montealegre Sanchez, Adam Reinhardt, Paul A Brogan, Yackov Berkun, Sara Murias, Maria Robles, Susanne Schalm, Adriana A de Jesus, Raphaela Goldbach-Mansky
Journal: Annals of the Rheumatic Diseases (2024)

Patients with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS) respond to the janus kinase inhibitor 1/2 inhibition with baricitinib at exposures higher than in rheumatoid arthritis. Baricitinib dose reductions to minimise exposure triggered disease flares which we used to develop 'flare criteria'.
Understanding advanced cystic fibrosis liver disease through genetic variation: Where do the pathways lead and how much further must we go?
Authors: A. Jay Freeman, Michael R. Narkewicz
Journal: Hepatology (2024)

1Nationwide Children's Hospital, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA 2Digestive Health Institute, Children's Hospital Colorado and Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA Correspondence A. Jay Freeman, Nationwide Children's Hospital. Email:[email protected]
Engineered Cell Membrane‐Coated Nanoparticles: New Strategies in Glioma Targeted Therapy and Immune Modulation
Authors: Yilei Ma, Jia Yi, Jing Ruan, Jiahui Ma, Qinsi Yang, Kun Zhang, Maolan Zhang, Guoming Zeng, Libo Jin, Xiaobei Huang, Jianshu Li, Haifeng Yang, Wei Wu, Da Sun
Journal: Advanced Healthcare Materials (2024)

Gliomas, the most prevalent primary brain tumors, pose considerable challenges due to their heterogeneity, intricate tumor microenvironment (TME), and blood-brain barrier (BBB), which restrict the effectiveness of traditional treatments like surgery and chemotherapy. This review provides an overview of engineered cell membrane technologies in glioma therapy, with a specific emphasis on targeted drug delivery and modulation of the immune microenvironment. This study investigates the progress in engineered cell membranes, encompassing physical, chemical, and genetic alterations, to improve drug delivery across the BBB and effectively target gliomas. The examination focuses on the interaction of engineered cell membrane-coated nanoparticles (ECM-NPs) with the TME in gliomas, emphasizing their potential to modulate glioma cell behavior and TME to enhance therapeutic efficacy. The review further explores the involvement of ECM-NPs in immunomodulation techniques, highlighting their impact on immune reactions. While facing obstacles related to membrane stability and manufacturing scalability, the review outlines forthcoming research directions focused on enhancing membrane performance. This review underscores the promise of ECM-NPs in surpassing conventional therapeutic constraints, proposing novel approaches for efficacious glioma treatment.
Spatiotemporal Landscape of Kidney Tubular Responses to Glomerular Proteinuria
Authors: Anna Faivre, Milica Bugarski, Anna Rinaldi, Imene B. Sakhi, Thomas Verissimo, David Legouis, Sara Correia, Monika Kaminska, Delal Dalga, Daniele Malpetti, Pietro E. Cippa, Sophie de Seigneux, Andrew M. Hall
Journal: Journal of the American Society of Nephrology (2024)

Key Points Glomerular proteinuria induces large-scale changes in gene expression along the nephron. Increased protein uptake in the proximal tubule results in axial remodeling and injury. Increased protein delivery to the distal tubule causes dedifferentiation of the epithelium. Background Large increases in glomerular protein filtration induce major changes in body homeostasis and are associated with a higher risk of kidney functional decline and cardiovascular disease. We investigated how elevated protein exposure modifies the landscape of tubular function along the entire nephron, to understand the cellular changes that mediate these important clinical phenomena. Methods We conducted single-nucleus RNA sequencing, functional intravital imaging, and antibody staining to spatially map transport processes along the mouse kidney tubule. We then delineated how these were altered in a transgenic mouse model of inducible glomerular proteinuria (POD-ATTAC) at 7 and 28 days. Results Glomerular proteinuria activated large-scale and pleiotropic changes in gene expression in all major nephron sections. Extension of protein uptake from early (S1) to later (S2) parts of the proximal tubule initially triggered dramatic expansion of a hybrid S1/2 population, followed by injury and failed repair, with the cumulative effect of loss of canonical S2 functions. Proteinuria also induced acute injury in S3. Meanwhile, overflow of luminal proteins to the distal tubule caused transcriptional convergence between specialized regions and generalized dedifferentiation. Conclusions Proteinuria modulated cell signaling in tubular epithelia and caused distinct patterns of remodeling and injury in a segment-specific manner.
FLT3 Agonists and Secondary Hematopoietic Malignancies: A Potential Class Effect
Authors: Henry W. Raeder, Michael W. Drazer
Journal: Clinical Cancer Research (2024)

Summary Expansion of conventional dendritic cells via FMS-like tyrosine kinase 3 agonism has promising therapeutic potential in the treatment of advanced solid tumors. In this study, we discuss the results of a clinical trial using GS-3583, an FMS-like tyrosine kinase 3 agonist, that was stopped after a patient in the study developed acute myeloid leukemia. See related article by Tolcher et al., p. 2954
Classifying Glioma via Liquid Biopsy: Progress toward an Unmet Clinical Need
Authors: Kalil G. Abdullah
Journal: Clinical Cancer Research (2024)

The diagnosis and classification of glioma by liquid biopsy represent a critical unmet need in neuro-oncology. A recent study demonstrates targeted next-generation sequencing of cell-free DNA from cerebrospinal fluid as an evolving option for liquid biopsy in patients with glioma. See related article by Iser et al., p. 2974.
Time-to-Event Genome-Wide Association Study for Incident Cardiovascular Disease in People With Type 2 Diabetes
Authors: Soo Heon Kwak, Ryan B. Hernandez-Cancela, Daniel A. DiCorpo, David E. Condon, Jordi Merino, Peitao Wu, Jennifer A. Brody, Jie Yao, Xiuqing Guo, Fariba Ahmadizar, Mariah Meyer, Murat Sincan, Josep M. Mercader, Sujin Lee, Jeffrey Haessler, Ha My T. Vy, Zhaotong Lin, Nicole D. Armstrong, Shaopeng Gu, Noah L. Tsao, Leslie A. Lange, Ningyuan Wang, Kerri L. Wiggins, Stella Trompet, Simin Liu, Ruth J.F. Loos, Renae Judy, Philip H. Schroeder, Natalie R. Hasbani, Maxime M. Bos, Alanna C. Morrison, Rebecca D. Jackson, Alexander P. Reiner, JoAnn E. Manson, Ninad S. Chaudhary, Lynn K. Carmichael, Yii-Der Ida Chen, Kent D. Taylor, Mohsen Ghanbari, Joyce van Meurs, Achilleas N. Pitsillides, Bruce M. Psaty, Raymond Noordam, Ron Do, Kyong Soo Park, J. Wouter Jukema, Maryam Kavousi, Adolfo Correa, Stephen S. Rich, Scott M. Damrauer, Catherine Hajek, Nam H. Cho, Marguerite R. Irvin, James S. Pankow, Girish N. Nadkarni, Robert Sladek, Mark O. Goodarzi, Jose C. Florez, Daniel I. Chasman, Susan R. Heckbert, Charles Kooperberg, Josée Dupuis, Rajeev Malhotra, Paul S. de Vries, Ching-Ti Liu, Jerome I. Rotter, James B. Meigs
Journal: Diabetes Care (2024)

OBJECTIVE To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS We conducted a multiancestry time-to-event genome-wide association study for incident CVD among people with T2D. We also tested 204 known coronary artery disease (CAD) variants for association with incident CVD. RESULTS Among 49,230 participants with T2D, 8,956 had incident CVD events (event rate 18.2%). We identified three novel genetic loci for incident CVD: rs147138607 (near CACNA1E/ZNF648, hazard ratio [HR] 1.23, P = 3.6 × 10−9), rs77142250 (near HS3ST1, HR 1.89, P = 9.9 × 10−9), and rs335407 (near TFB1M/NOX3, HR 1.25, P = 1.5 × 10−8). Among 204 known CAD loci, 5 were associated with incident CVD in T2D (multiple comparison–adjusted P &amp;lt; 0.00024, 0.05/204). A standardized polygenic score of these 204 variants was associated with incident CVD with HR 1.14 (P = 1.0 × 10−16). CONCLUSIONS The data point to novel and known genomic regions associated with incident CVD among individuals with T2D.
Correction: Sex Differences in Age-Related Loss of Kidney Function
Authors: Toralf Melsom, Norvik. Jon Viljar, Inger Therese. Enoksen, Vidar Stefansson, Ulla Dorte. Mathisen, Ole Martin. Fuskevåg, Trond G. Jenssen, Marit D. Solbu, Bjørn O. Eriksen
Journal: Journal of the American Society of Nephrology (2024)

Melsom, Toralf; Viljar, Norvik. Jon; Enoksen, Inger Therese.; Stefansson, Vidar; Mathisen, Ulla Dorte.; Fuskevåg, Ole Martin.; Jenssen, Trond G.; Solbu, Marit D.; Eriksen, Bjørn O. Author Information
Acute Kidney Injury Receiving Dialysis and Dialysis Care after Hospital Discharge
Authors: Seda Babroudi, Daniel E. Weiner, Javier A. Neyra, David A. Drew
Journal: Journal of the American Society of Nephrology (2024)

The number of patients with AKI receiving outpatient hemodialysis (AKI-D) is increasing. At present, on the basis of limited data, approximately one third of patients with AKI-D who receive outpatient dialysis after hospital discharge survive and regain sufficient kidney function to discontinue dialysis. Data to inform dialysis management strategies that promote kidney function recovery and processes of care among patients with AKI-D receiving outpatient dialysis are lacking. In this article, we detail current trends in the incidence, risk factors, clinical outcomes, proposed management, and health policy landscape for patients with AKI-D receiving outpatient dialysis and identify areas for further research.
A genome-wide association study identified PTPN2 as a population-specific susceptibility gene locus for primary biliary cholangitis
Authors: Yuki Hitomi, Kazuko Ueno, Yoshihiro Aiba, Nao Nishida, Michihiro Kono, Mitsuki Sugihara, Yosuke Kawai, Minae Kawashima, Seik-Soon Khor, Kazuhiro Sugi, Hirotaka Kouno, Hiroshi Kouno, Atsushi Naganuma, Satoru Iwamoto, Shinji Katsushima, Kiyoshi Furuta, Toshiki Nikami, Tomohiko Mannami, Tsutomu Yamashita, Keisuke Ario, Tatsuji Komatsu, Fujio Makita, Masaaki Shimada, Noboru Hirashima, Shiro Yokohama, Hideo Nishimura, Rie Sugimoto, Takuya Komura, Hajime Ota, Motoyuki Kojima, Makoto Nakamuta, Naoyuki Fujimori, Kaname Yoshizawa, Yutaka Mano, Hironao Takahashi, Kana Hirooka, Satoru Tsuruta, Takeaki Sato, Kazumi Yamasaki, Yuki Kugiyama, Yasuhide Motoyoshi, Tomoyuki Suehiro, Akira Saeki, Kosuke Matsumoto, Shinya Nagaoka, Seigo Abiru, Hiroshi Yatsuhashi, Masahiro Ito, Kazuhito Kawata, Akinobu Takaki, Kuniaki Arai, Teruko Arinaga, Masanori Abe, Masaru Harada, Makiko Taniai, Mikio Zeniya, Hiromasa Ohira, Shinji Shimoda, Atsumasa Komori, Atsushi Tanaka, Kazuyoshi Ishigaki, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura
Journal: Hepatology (2024)

Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-nonspecific) and nonshared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC.
β-Cell Function, Incretin Effect, and Glucose Kinetics in Response to a Mixed Meal in Patients With Type 2 Diabetes Treated With Dapagliflozin Plus Saxagliptin
Authors: Giuseppe Daniele, Andrea Tura, Alex Brocchi, Alessandro Saba, Beatrice Campi, Veronica Sancho-Bornez, Angela Dardano, Stefano Del Prato
Journal: Diabetes Care (2024)

To explore the complementary effects of a combination of dipeptidyl peptidase 4 and sodium-glucose cotransporter 2 inhibitors added to metformin on hormonal and metabolic responses to meal ingestion.
Autologous neutralizing antibody responses after antiretroviral therapy in acute and early HIV-1
Authors: Gregory D. Whitehill, Jaimy Joy, Francesco E. Marino, Ryan Krause, Suvadip Mallick, Hunter Courtney, Kyewon Park, John Carey, Rebecca Hoh, Heather Hartig, Vivian Pae, Sannidhi Sarvadhavabhatla, Sophia Donaire, Steven G. Deeks, Rebecca M. Lynch, Sulggi A. Lee, Katharine J. Bar
Journal: Journal of Clinical Investigation (2024)

BACKGROUNDEarly antiretroviral therapy initiation (ARTi) in HIV-1 restricts reservoir size and diversity while preserving immune function, potentially improving opportunities for immunotherapeutic cure strategies. For antibody-based cure approaches, the development of autologous neutralizing antibodies (anAbs) after acute/early ARTi is relevant but is poorly understood.METHODSWe characterized antibody responses in a cohort of 23 participants following ARTi in acute HIV (<60 days after acquisition) and early HIV (60-128 days after acquisition).RESULTSPlasma virus sequences at the time of ARTi revealed evidence of escape from anAbs after early, but not acute, ARTi. HIV-1 envelopes representing the transmitted/founder virus(es) (acute ARTi) or escape variants (early ARTi) were tested for sensitivity to longitudinal plasma IgG. After acute ARTi, no anAb responses developed over months to years of suppressive ART. In 2 of the 3 acute ARTi participants who experienced viremia after ARTi, however, anAbs arose shortly thereafter. After early ARTi, anAbs targeting those early variants developed between 12 and 42 weeks of ART and continued to increase in breadth and potency thereafter.CONCLUSIONResults indicate a threshold of virus replication (~60 days) required to induce anAbs, after which they continue to expand on suppressive ART to better target the range of reservoir variants.TRIAL REGISTRATIONClinicalTrials.gov NCT02656511.FUNDINGNIH grants U01AI169767, R01AI162646, UM1AI164570, UM1AI164560, U19AI096109, K23GM112526, T32AI118684, P30AI045008, P30AI027763, R24AI067039; Gilead Sciences grant INUS2361354; Viiv Healthcare grant A126326.
Diagnostic accuracy of artificial intelligence assisted clinical imaging in the detection of oral potentially malignant disorders and oral cancer: A systematic review and meta-analysis
Authors: JingWen Li, Wai Ying Kot, Colman Patrick McGrath, Bik Wan Amy Chan, Joshua Wing Kei Ho, Li Wu Zheng
Journal: International Journal of Surgery (2024)

The objective of this study is to examine the application of artificial intelligence (AI) algorithms in detecting oral potentially malignant disorders (OPMD) and oral cancerous lesions, and to evaluate the accuracy variations among different imaging tools employed in these diagnostic processes.
NR2E3 loss disrupts photoreceptor cell maturation and fate in human organoid models of retinal development
Authors: Nathaniel K. Mullin, Laura R. Bohrer, Andrew P. Voigt, Lola P. Lozano, Allison T. Wright, Vera L. Bonilha, Robert F. Mullins, Edwin M. Stone, Budd A. Tucker
Journal: Journal of Clinical Investigation (2024)

While dysfunction and death of light-detecting photoreceptor cells underlie most inherited retinal dystrophies, knowledge of the species-specific details of human rod and cone photoreceptor cell development remains limited. Here, we generate retinal organoids carrying retinal disease-causing variants in NR2E3, as well as isogenic and unrelated controls. Organoids were sampled using single-cell RNA sequencing across the developmental window encompassing photoreceptor specification, emergence, and maturation. Using scRNAseq data, we reconstruct the rod photoreceptor developmental lineage and identify a branchpoint unique to the disease state. We show that the rod-specific transcription factor NR2E3 is required for the proper expression of genes involved in phototransduction, including rhodopsin, which is absent in divergent rods. NR2E3-null rods additionally misexpress several cone-specific phototransduction genes. Using joint multimodal single-cell sequencing, we further identify putative regulatory sites where rod-specific factors act to steer photoreceptor cell development. Finally, we show that rod-committed photoreceptor cells form and persist throughout life in a patient with NR2E3-associated disease. Importantly, these findings are strikingly different than those observed in Nr2e3 rodent models. Together, these data provide a roadmap of human photoreceptor development and leverage patient iPSCs to define the specific roles of rod transcription factors in photoreceptor cell emergence and maturation in health and disease.
Human NLRC4 expression promotes cancer survival and associates with type I interferon signaling and immune infiltration
Authors: Charlotte Domblides, Steven Crampton, Hong Liu, Juliet M. Bartleson, Annie Nguyen, Claudia Champagne, Emily E. Landy, Lindsey Spiker, Christopher Proffitt, Sunil Bhattarai, Anissa P. Grawe, Matias Fuentealba Valenzuela, Lydia Lartigue, Isabelle Mahouche, Jeremy Dupaul-Chicoine, Kazuho Nishimura, Félix Lefort, Marie Decraecker, Valérie Velasco, Sonia Netzer, Vincent Pitard, Christian Roy, Isabelle Soubeyran, Victor Racine, Patrick Blanco, Julie Déchanet-Merville, Maya Saleh, Scott W. Canna, David Furman, Benjamin Faustin
Journal: Journal of Clinical Investigation (2024)

The immune system can control cancer progression. However, even though some innate immune sensors of cellular stress are expressed intrinsically in epithelial cells, their potential role in cancer aggressiveness and subsequent overall survival in humans is mainly unknown. Here, we show that nucleotide-binding oligomerization domain-like receptor (NLR) family CARD domain-containing 4 (NLRC4) is downregulated in epithelial tumor cells of patients with colorectal cancer (CRC) by using spatial tissue imaging. Strikingly, only the loss of tumor NLRC4, but not stromal NLRC4, was associated with poor immune infiltration (mainly DCs and CD4+ and CD8+ T cells) and accurately predicted progression to metastatic stage IV and decrease in overall survival. By combining multiomics approaches, we show that restoring NLRC4 expression in human CRC cells triggered a broad inflammasome-independent immune reprogramming consisting of type I interferon (IFN) signaling genes and the release of chemokines and myeloid growth factors involved in the tumor infiltration and activation of DCs and T cells. Consistently, such reprogramming in cancer cells was sufficient to directly induce maturation of human DCs toward a Th1 antitumor immune response through IL-12 production in vitro. In multiple human carcinomas (colorectal, lung, and skin), we confirmed that NLRC4 expression in patient tumors was strongly associated with type I IFN genes, immune infiltrates, and high microsatellite instability. Thus, we shed light on the epithelial innate immune sensor NLRC4 as a therapeutic target to promote an efficient antitumor immune response against the aggressiveness of various carcinomas.
Oncogene-induced matrix reorganization controls CD8+ T cell function in the soft-tissue sarcoma microenvironment
Authors: Ashley M. Fuller, Hawley C. Pruitt, Ying Liu, Valerie M. Irizarry-Negron, Hehai Pan, Hoogeun Song, Ann DeVine, Rohan S. Katti, Samir Devalaraja, Gabrielle E. Ciotti, Michael V. Gonzalez, Erik F. Williams, Ileana Murazzi, Dimitris Ntekoumes, Nicolas Skuli, Hakon Hakonarson, Daniel J. Zabransky, Jose G. Trevino, Ashani Weeraratna, Kristy Weber, Malay Haldar, Joseph A. Fraietta, Sharon Gerecht, T.S. Karin Eisinger-Mathason
Journal: Journal of Clinical Investigation (2024)

CD8+ T cell dysfunction impedes antitumor immunity in solid cancers, but the underlying mechanisms are diverse and poorly understood. Extracellular matrix (ECM) composition has been linked to impaired T cell migration and enhanced tumor progression; however, impacts of individual ECM molecules on T cell function in the tumor microenvironment (TME) are only beginning to be elucidated. Upstream regulators of aberrant ECM deposition and organization in solid tumors are equally ill-defined. Therefore, we investigated how ECM composition modulates CD8+ T cell function in undifferentiated pleomorphic sarcoma (UPS), an immunologically active desmoplastic tumor. Using an autochthonous murine model of UPS and data from multiple human patient cohorts, we discovered a multifaceted mechanism wherein the transcriptional coactivator YAP1 promotes collagen VI (COLVI) deposition in the UPS TME. In turn, COLVI induces CD8+ T cell dysfunction and immune evasion by remodeling fibrillar collagen and inhibiting T cell autophagic flux. Unexpectedly, collagen I (COLI) opposed COLVI in this setting, promoting CD8+ T cell function and acting as a tumor suppressor. Thus, CD8+ T cell responses in sarcoma depend on oncogene-mediated ECM composition and remodeling.
Distinct proteomes and allergen profiles appear across the life-cycle stages of Alternaria alternata
Authors: Michael Brad Strader, Aishwarya L. Saha, Chantal Fernandes, Kavita Sharma, Christian Hadiwinarta, Daniela Calheiros, Gonçalo Conde-de-Oliveira, Teresa Gonçalves, Jay E. Slater
Journal: Journal of Allergy and Clinical Immunology (2024)
A simple and quick solution for Buried Bumper Syndrome – a case series using the balloon assisted extraction method
Authors: M. Zimmerli, A. Feiden, S. Kahl, F. Rybinski, L. Degen, H. Heinrich
Journal: Endoscopy (2024)

Aims Percutaneous endoscopic gastrostomy (PEG) is a simple, safe and widely used method for feeding seriously and/or chronically ill people with swallowing problems. Long-term use of PEG with a hard internal holding disc and too tight fixation can lead to buried bumper syndrome (BBS) in approximately 0.3-2.4% of cases. Several methods to treat BBS some with dedicated, expensive tools have been published [1] The ballon- assisted technique to treat BBS first described by Strocke and Weber 2005 is a simple, safe and fast method with low cost tools available in every endoscopy unit. The aim was to evaluate success in the treatment of BBS in a series of cases.
Modified endoscopic vacuum therapy: the 4S’s procedure – Simple, Successful, Suitable and economically Sustainable
Authors: J. P. Pereira, F. Baldaque-Silva, M. Nunes, L. Freire, T. Rama, P. Costa Moreira, P. Antunes
Journal: Endoscopy (2024)

Aims Anastomotic upper gastrointestinal leaks are the most dreaded complications in esophagogastric surgery and are associated with high morbidity and mortality. The optimal management of such leaks remains challenging.