tbuckley/cabot-search huggingface dataset:
An Improved Understanding of the Pathophysiology of Pelvic Organ Prolapse: A 3D In Vitro Model under Static and Mechanical Loading Conditions
Authors: Melissa J. J. van Velthoven, Aksel N. Gudde, Marit van der Kruit, Malou P. C. van Loon, Lissy Rasing, Frank A. D. T. G. Wagener, Jan‐Paul Roovers, Zeliha Guler, Paul H. J. Kouwer
Journal: Advanced Healthcare Materials (2024)

Abstract The suboptimal outcomes of pelvic organ prolapse (POP) surgery illustrate the demand for improved therapies. However, their development is hampered by the limited knowledge on the cellular pathophysiology of POP. Current investigations, that are limited to tissues and 2D in vitro models, provide highly inconclusive results on how the extracellular matrix (ECM) metabolism and fibroblasts are affected in POP. This study uses a physiologically relevant 3D in vitro model to investigate the cellular pathophysiology of POP by determining the differences between POP and non‐POP fibroblasts on ECM metabolism, proliferation, and fibroblast‐to‐myofibroblast (FMT) transition. This model, based on the synthetic and biomimetic polyisocyanide hydrogel, enables the incorporation of mechanical loading, which simulates the forces exerted on the pelvic floor. Under static conditions, 3D cultured POP fibroblasts are less proliferative, undergo FMT, and exhibit lower collagen and elastin contents compared to non‐POP fibroblasts. However, under mechanical loading, the differences between POP and non‐POP fibroblasts are less pronounced. This study contributes to the development of more comprehensive models that can accurately mimic the POP pathophysiology, which will aid in an enhanced understanding and may contribute to improved therapies in the future.
Homology‐Activated Ultrasensitive Nanomedicines for Precise NIR‐II FL/MRI Imaging‐Guided “Knock‐On” Dynamic Therapy in Rheumatoid Arthritis
Authors: Rong Dai, Mingxin Zhao, Xiaochun Zheng, Dongsheng Li, Weiwei Kang, Huifang Hao, Xuejiao Chen, Yarong Jin, Juan Li, Qin Liu, Ziliang Zheng, Ruiping Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Stimuli‐responsive nanomedicines represent a pivotal technology for in situ on‐demand drug release and offer multiple advantages over conventional drug delivery systems to combat rheumatoid arthritis(RA). However, the lack of sensitivity to a single‐stimuli source or the inability to synchronize multi‐stimuli responses can easily lead to challenges in achieving precise‐theranostics of RA. Herein, a homology‐activated ultrasensitive nanomedicines MnO 2 ‐CQ4T‐GOx(MCG NMs) is designed for NIR‐II fluorescence(NIR‐II FL)/magnetic resonance imaging(MRI)‐guided effective “knock‐on” dynamic anti‐RA therapy. Building upon the characteristics of the RA‐microenvironment, the MCG innovatively construct a MnO 2 ‐Mn 2+ system, which can normalized activation sites. The ultrasensitive‐responsive degradation is achieved using the multi‐stimuli processes in the RA‐microenvironment, triggering release of functional small molecules. The produced Mn 2+ can exert Fenton‐like activity to generate •OH from H 2 O 2 , thus providing the effective chemodynamic therapy(CDT). Moreover, the up‐regulation of H 2 O 2 by GOx‐catalysis not only sensitizes the MnO 2 ‐Mn 2+ system but also achieves self‐enhancing CDT efficacy. The NIR‐II FL quenching of CQ4T‐BSA in the aggregated state occurs in MCG NMs, which can be rapidly and precisely “turn‐on” via the MnO 2 ‐Mn 2+ system. Meanwhile, the integration of activated Mn 2+ ‐based MRI imaging has successfully developed an activatable dual‐modal imaging. Feedback imaging‐guided precise photodynamic therapy of CQ4T‐BSA can achieve efficient “knock‐on” dynamic therapy for RA.
Affective forecasting and psychopathology: A scoping review
Authors: Jala Rizeq
Journal: Clinical Psychology Review (2024)

Affective forecasting - estimations of future emotional reactions - is an important aspect of future thinking that informs judgement and decision making. Biases in affective forecasting have been noted generally and with people with emotional disturbances specifically. Still, the role of affective forecasting within models of psychopathology has received little attention. Given the state of the literature, a scoping review method was adopted to summarize and synthesize the methodological approaches used in measuring affective forecasting within the context of psychopathology and the scope of the evidence on this association. Three databases were searched for research published on or before November 13th, 2023. Original quantitative research that examined affective forecasting and its association with psychopathology was reviewed. Data were charted using a form designed for this study. Overall, the review highlights the heterogeneity in operationalization of affective forecasting. The majority of the evidence supports an association between severity of psychopathology and intensity of affective forecasts, with notable exceptions, which are discussed within the scope of methodology and operationalization of affective forecasting. This remains an important process to investigate in information processing models of psychopathology to elucidate its role in the development and maintenance of psychopathology and potential as a target for intervention.
Treatment-associated imaging changes in newly diagnosed <i>MGMT</i> promoter-methylated glioblastoma undergoing chemoradiation with or without cilengitide
Authors: Christina Maria Flies, Michel Friedrich, Philipp Lohmann, Karin Alida van Garderen, Marion Smits, Joerg-Christian Tonn, Michael Weller, Norbert Galldiks, Tom Jan Snijders
Journal: Neuro-Oncology (2024)

Abstract Background Radiological progression may originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. We assessed radiological progression in O6-methylguanine-DNA methyltransferase (MGMT) promoter-methylated glioblastoma treated with standard-of-care chemoradiotherapy with or without the integrin inhibitor cilengitide according to the modified response assessment in neuro-oncology (RANO) criteria of 2017. Methods Patients with ≥ 3 follow-up MRIs were included. Preliminary PD was defined as a ≥ 25% increase of the sum of products of perpendicular diameters (SPD) of a new or increasing lesion compared to baseline. PD required a second ≥25% increase of the SPD. Treatment-associated changes require stable or regressing disease after preliminary PD. Results Of the 424 evaluable patients, 221 patients (52%) were randomized into the cilengitide and 203 patients (48%) into the control arm. After chemoradiation with or without cilengitide, preliminary PD occurred in 274 patients (65%) during available follow-up, and 88 of these patients (32%) had treatment-associated changes, whereas 67 patients (25%) had PD. The remaining 119 patients (43%) had no further follow-up after preliminary PD. Treatment-associated changes were more common in the cilengitide arm than in the standard-of-care arm (24% vs. 17%; relative risk, 1.3; 95% CI, 1.004–1.795; P = .047). Treatment-associated changes occurred mainly during the first 6 months after RT (54% after 3 months vs. 13% after 6 months). Conclusions With the modified RANO criteria, the rate of treatment-associated changes was low compared to previous studies in MGMT promoter-methylated glioblastoma. This rate was higher after cilengitide compared to standard-of-care treatment. Confirmatory scans, as recommended in the modified RANO criteria, were not always available reflecting current clinical practice.
Pump‐Less, Recirculating Organ‐on‐Chip (rOoC) Platform to Model the Metabolic Crosstalk between Islets and Liver
Authors: Aleksandra Aizenshtadt, Chencheng Wang, Shadab Abadpour, Pedro Duarte Menezes, Ingrid Wilhelmsen, Andrea Dalmao‐Fernandez, Justyna Stokowiec, Alexey Golovin, Mads Johnsen, Thomas M. D. Combriat, Hanne Røberg‐Larsen, Nikolaj Gadegaard, Hanne Scholz, Mathias Busek, Stefan J. K. Krauss
Journal: Advanced Healthcare Materials (2024)

Abstract Type 2 diabetes mellitus (T2DM), obesity, and metabolic dysfunction‐associated steatotic liver disease (MASLD) are epidemiologically correlated disorders with a worldwide growing prevalence. While the mechanisms leading to the onset and development of these conditions are not fully understood, predictive tissue representations for studying the coordinated interactions between central organs that regulate energy metabolism, particularly the liver and pancreatic islets, are needed. Here, a dual pump‐less recirculating organ‐on‐chip platform that combines human pluripotent stem cell (sc)‐derived sc‐liver and sc‐islet organoids is presented. The platform reproduces key aspects of the metabolic cross‐talk between both organs, including glucose levels and selected hormones, and supports the viability and functionality of both sc‐islet and sc‐liver organoids while preserving a reduced release of pro‐inflammatory cytokines. In a model of metabolic disruption in response to treatment with high lipids and fructose, sc‐liver organoids exhibit hallmarks of steatosis and insulin resistance, while sc‐islets produce pro‐inflammatory cytokines on‐chip. Finally, the platform reproduces known effects of anti‐diabetic drugs on‐chip. Taken together, the platform provides a basis for functional studies of obesity, T2DM, and MASLD on‐chip, as well as for testing potential therapeutic interventions.
Time independent factors that predict relapse in adults with acute myeloid leukemia
Authors: John J. Lim, Megan Othus, Carole M. Shaw, Kathryn Russell, Anna B. Halpern, Jacob S. Appelbaum, Paul Hendrie, Roland B. Walter, Elihu H. Estey, Mary-Elizabeth M. Percival
Journal: Blood Cancer Journal (2024)
Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial
Authors: Knut Jørgen Labori, Svein Olav Bratlie, Bodil Andersson, Jon-Helge Angelsen, Christina Biörserud, Bergthor Björnsson, Erling Audun Bringeland, Nils Elander, Herish Garresori, Jon Erik Grønbech, Johan Haux, Oskar Hemmingsson, Maria Gustafsson Liljefors, Tor Åge Myklebust, Linn Såve Nymo, Katriina Peltola, Per Pfeiffer, Ville Sallinen, Per Sandström, Ernesto Sparrelid, Helge Stenvold, Kjetil Søreide, Bobby Tingstedt, Caroline Verbeke, Daniel Öhlund, Leif Klint, Svein Dueland, Kristoffer Lassen, Eirik Kjus Aahlin, Charlotte Bratthäll, Asif Halimi, Ingunn Hatlevoll, Margareta Heby, Arto Kokkola, Maximilian Kordes, Stina Lindblad, Linda Lundgren, Michael Bau Mortensen, Kim Erlend Mortensen, Jan Persson, Elena Rangelova, Elin Rønne, Oddvar Mathias Sandvik, Jon Arne Søreide, Caroline Vilhav, Kim Waardal, Johanna Wennerblom, Caroline Williamsson, Sheraz Yaqub
Journal: The Lancet. Gastroenterology & hepatology (2024)
Correction to Lancet Healthy Longev 2024; 5: e66–75
Journal: The Lancet Healthy Longevity (2024)

In this Article, the second sentence of the Results section should have read "…1863 participants were found to have audiometry-measured hearing loss and complete data at the time of NHANES participation…".The subsequent sentence has also been amended to "…among the 2026 original participants who had audiometry-measured hearing loss, 163 (8•0%) had missing data".These corrections have been made as of Jan 15, 2024.
Arbovirus research in the Asia-Pacific needs more women in leadership
Authors: Francesca D Frentiu, Ann Florence V Belvis, Myrielle Dupont-Rouzeyrol, Frances E Edillo, Jeevanie Harishchandra, Joanne Mariasua, Thuy T T Nguyen, Olivia O'Connor, Marsha Sinditia Santoso, Ninh T H Tran, Frilasita Aisyah Yudhaputri
Journal: The Lancet Infectious Diseases (2024)
Gabapentinoids and Risk for Severe Exacerbation in Chronic Obstructive Pulmonary Disease
Authors: Alvi A. Rahman, Sophie Dell’Aniello, Erica E.M. Moodie, Madeleine Durand, Janie Coulombe, Jean-François Boivin, Samy Suissa, Pierre Ernst, Christel Renoux
Journal: Annals of Internal Medicine (2024)

North American and European health agencies recently warned of severe breathing problems associated with gabapentinoids, including in patients with chronic obstructive pulmonary disease (COPD), although supporting evidence is limited.
Effectiveness of Existing Insomnia Therapies for Patients Undergoing Hemodialysis
Authors: Rajnish Mehrotra, Daniel Cukor, Susan M. McCurry, Tessa Rue, Maria-Eleni Roumelioti, Patrick J. Heagerty, Mark Unruh
Journal: Annals of Internal Medicine (2024)

Chronic insomnia is common in patients undergoing in-center hemodialysis, yet there is limited evidence on effective treatments for this population.
The Test of Time (Or, The Insolence of Dementia)
Authors: Bonnie Salomon
Journal: Annals of Internal Medicine (2024)

Ad LibitumJanuary 2024The Test of Time (Or, The Insolence of Dementia)Bonnie Salomon, MDBonnie Salomon, MDNorthwestern Medicine Lake Forest Hospital, Lake Forest, IllinoisSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M23-1748 Audio Reading - “The Test of Time (Or, The Insolence of Dementia)” Supplement. Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “The Test of Time (Or, The Insolence of Dementia)” by Bonnie Salomon Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In timeThe forgetting is all they will remember:The worry of lost wallets hid beneath pillows,Never found, since never lost.Bundled in winter clothes, mid-July,Ready for work, retired twenty years.Lips quiver, words stumbling out,Weak voices once a lusty baritone.Diminished without grandeur, cracks in pavement:Whereupon a timePolished boots shone in victory parades,Banners dancing in the breeze. Author, Article, and Disclosure InformationAuthors: Bonnie Salomon, MDAffiliations: Northwestern Medicine Lake Forest Hospital, Lake Forest, IllinoisCorresponding Author: Bonnie Salomon, MD; e-mail, BonSalomon@aol.com. PreviousarticleNextarticle Advertisement Audio Reading - “The Test of Time (Or, The Insolence of Dementia)” Supplement. Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “The Test of Time (Or, The Insolence of Dementia)” by Bonnie Salomon Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Current Issue January 2024Volume 177, Issue 1 Page: 100 ePublished: 16 January 2024 Issue Published: January 2024 Copyright & PermissionsCopyright © 2024 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Annals Consult Guys - Postoperative Euglycemic Diabetic Ketoacidosis
Authors: Howard H. Weitz, Geno J. Merli
Journal: Annals of Internal Medicine (2024)

Web ExclusivesJanuary 2024Annals Consult Guys - Postoperative Euglycemic Diabetic KetoacidosisFREEHoward H. Weitz, MD, and Geno J. Merli, MDHoward H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Search for more papers by this author, and Geno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W23-0012 CME/MOC SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Annals Consult Guys provide a viewer consultation of a patient who developed ketoacidosis after a Whipple procedure.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Howard H. Weitz, MD; Geno J. Merli, MDAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Disclosures: Drs. Merli and Weitz report that they have no financial relationships or interests to disclose. All relevant financial relationships have been mitigated. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=W23-0012.Editors' Disclosures: The editors have no relevant financial relationships to disclose. Individual forms may be viewed at www.annals.org/editorsdisclosures. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Current Issue January 2024Volume 177, Issue 1 ePublished: 16 January 2024 Issue Published: January 2024 Copyright & PermissionsCopyright © 2024 by American College of Physicians. All Rights Reserved.Loading ...
Gravy
Authors: Dean Gianakos
Journal: Annals of Internal Medicine (2024)

On Being a DoctorJanuary 2024GravyDean Gianakos, MDDean Gianakos, MDCentra Health, Lynchburg, VirginiaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M23-2711 Audio Reading - “Gravy” Supplement. Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Gravy” by Dean Gianakos, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail John arrives late to the burial service for his patient and colleague Nick. He stands under a large oak tree a few yards away from the other mourners. Spring wildflowers adorn hundreds of tombstones on the grassy hills of the cemetery. The sky is blazing in South Carolina and so are emotions. John puts on his sunglasses. A small group of friends and family surrounds the black casket lying near a deep, rectangular hole. He listens to the Greek Orthodox priest chant a traditional funeral hymn: “mem- orr- ryy eter- er- er- nal.”May his memory be eternal.Not all ... Author, Article, and Disclosure InformationAuthors: Dean Gianakos, MDAffiliations: Centra Health, Lynchburg, VirginiaCorresponding Author: Dean Gianakos, MD, Centra Health, 1901 Thomson Drive, Lynchburg, VA 24501; e-mail, deangianakos@yahoo.com. PreviousarticleNextarticle Advertisement Audio Reading - “Gravy” Supplement. Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Gravy” by Dean Gianakos, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Current Issue January 2024Volume 177, Issue 1 Page: 99-100 ePublished: 16 January 2024 Issue Published: January 2024 Copyright & PermissionsCopyright © 2024 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Adeno‐Associated Virus‐Encapsulated Alginate Microspheres Loaded in Collagen Gel Carriers for Localized Gene Transfer
Authors: Yuta Kurashina, Sho Kurihara, Takeshi Kubota, Shuhei Takatsuka, Motoki Hirabayashi, Hajime Shimmura, Hideo Miyahara, Aiki Hioki, Yutaka Matsushita, Jumpei Muramatsu, Yuki Ogawa, Masato Fujioka, Hirotaka J. Okano, Hiroaki Onoe
Journal: Advanced Healthcare Materials (2024)

Abstract This work reports localized in vivo gene transfer by biodegradation of the adeno‐associated virus‐encapsulating alginate microspheres (AAV‐AMs) loaded in collagen gel carriers. AAV‐AMs are centrifugally synthesized by ejecting a mixed pre‐gel solution of alginate and AAV to CaCl 2 solution to form an ionically cross‐linked hydrogel microsphere immediately. The AAV‐AMs are able to preserve the AAV without diffusing out even after spreading them on the cells, and the AAV is released and transfected by the degradation of the alginate microsphere. In addition, AAV‐AMs can be stored by cryopreservation until use. By implanting this highly convenient AAV‐encapsulated hydrogel, AAV‐AMs can be loaded into collagen gel carriers to fix the position of the implanted AAV‐AMs and achieve localized gene transfer in vivo. In vivo experiments show that the AAV‐AMs loaded in collagen gel carriers are demonstrated to release the encapsulated AAV for gene transfer in the buttocks muscles of mice. While conventional injections caused gene transfer to the entire surrounding tissue, the biodegradation of AAV‐AMs shows that gene transfer is achieved locally to the muscles. This means that the proposed AAV‐loaded system is shown to be a superior method for selective gene transfer.
Driver mutation zygosity is a critical factor in predicting clonal hematopoiesis transformation risk
Authors: Ashwin Kishtagari, M. A. Wasay Khan, Yajing Li, Caitlyn Vlasschaert, Naimisha Marneni, Alexander J. Silver, Kelly von Beck, Travis Spaulding, Shannon Stockton, Christina Snider, Andrew Sochacki, Dixon Dorand, Taralynn M. Mack, P. Brent Ferrell, Yaomin Xu, Cosmin A. Bejan, Michael R. Savona, Alexander G. Bick
Journal: Blood Cancer Journal (2024)

Abstract Clonal hematopoiesis (CH) can be caused by either single gene mutations (eg point mutations in JAK2 causing CHIP) or mosaic chromosomal alterations (e.g., loss of heterozygosity at chromosome 9p). CH is associated with a significantly increased risk of hematologic malignancies. However, the absolute rate of transformation on an annualized basis is low. Improved prognostication of transformation risk is urgently needed for routine clinical practice. We hypothesized that the co-occurrence of CHIP and mCAs at the same locus (e.g., transforming a heterozygous JAK2 CHIP mutation into a homozygous mutation through concomitant loss of heterozygosity at chromosome 9) might have important prognostic implications for malignancy transformation risk. We tested this hypothesis using our discovery cohort, the UK Biobank ( n = 451,180), and subsequently validated it in the BioVU cohort ( n = 91,335). We find that individuals with a concurrent somatic mutation and mCA were at significantly increased risk of hematologic malignancy (for example, In BioVU cohort incidence of hematologic malignancies is higher in individuals with co-occurring JAK2 V617F and 9p CN-LOH; HR = 54.76, 95% CI = 33.92–88.41, P &lt; 0.001 vs. JAK2 V617F alone; HR = 44.05, 95% CI = 35.06–55.35, P &lt; 0.001). Currently, the ‘zygosity’ of the CHIP mutation is not routinely reported in clinical assays or considered in prognosticating CHIP transformation risk. Based on these observations, we propose that clinical reports should include ‘zygosity’ status of CHIP mutations and that future prognostication systems should take mutation ‘zygosity’ into account.