tbuckley/cabot-search huggingface dataset:
Evidence from the large VALIGA cohort validates the subclassification of focal segmental glomerulosclerosis in IgA nephropathy
Authors: Shubha S. Bellur, Stéphan Troyanov, Olga Vorobyeva, Rosanna Coppo, Ian S.D. Roberts, R. Coppo, J. Feehaly, S. Troyanov, D.C. Cattran, H.T. Cook, I. Roberts, John Radcliffe, M.L. Russo, V. Tesar, D. Maixnerova, S. Lundberg, L. Gesualdo, F. Emma, L. Fuiano, G. Beltrame, C. Rollino, A. Amore, R. Camilla, L. Peruzzi, M. Praga, S. Feriozzi, R. Polci, G. Segoloni, L. Colla, A. Pani, D. Piras, A. Angioi, G. Cancarini, S. Ravera, M. Durlik, E. Moggia, J. Ballarin, S. Di Giulio, F. Pugliese, I. Serriello, Y. Caliskan, M. Sever, I. Kilicaslan, F. Locatelli, L. Del Vecchio, J.F.M. Wetzels, H. Peters, U. Berg, F. Carvalho, A.C. da Costa Ferreira, M. Maggio, A. Wiecek, M. Ots-Rosenberg, R. Magistroni, R. Topaloglu, Y. Bilginer, M. D’Amico, K. Papagianni, M. Stangou, F. Giacchino, D. Goumenos, M. Papasotirious, P. Kalliakmani, M. Gerolymos, K. Galesic, L. Toric, C. Geddes, K. Siamopoulos, O. Balafa, M. Galliani, P. Stratta, M. Quaglia, R. Bergia, R. Cravero, M. Salvadori, L. Cirami, B. Fellstrom, H. Kloster Smerud, F. Ferrario, T. Stellato, J. Egido, C. Martin, J. Floege, F. Eitner, A. Lupo, P. Bernich, P. Menè, M. Morosetti, C. van Kooten, T. Rabelink, M.E.J. Reinders, J.M. Boria Grinyo, S. Cusinato, L. Benozzi, S. Savoldi, C. Licata, M. Mizerska-Wasiak, M. Roszkowska-Blaim, M. Durlik, T. Hryszko, M. Klinger, D. Kamińska, M. Krajewska, G. Martina, A. Messuerotti, A. Dal Canton, C. Esposito, C. Migotto, G. Triolo, F. Mariano, C. Pozzi, R. Boero, A. Cambier, S. Bellur, G. Mazzucco, C. Giannakakis, E. Honsova, B. Sundelin, A.M. Di Palma, F. Ferrario, F. Diomedi-Casadei, E. Gutiérrez, A.M. Asunis, J. Barratt, R. Tardanico, A. Perkowska-Ptasinska, J. Arce Terroba, M. Fortunato, A. Pantzaki, Y. Ozluk, E. Steenbergen, M. Soderberg, Z. Riispere, L. Furci, D. Orhan, D. Kipgen, D. Casartelli, D. Galesic Ljubanovic, H. Gakiopoulou, E. Bertoni, P. Cannata Ortiz, H. Karkoszka, H.J. Groene, A. Stoppacciaro, I. Bajema, J. Bruijn, X. Fulladosa Oliveras, J. Maldyk, E. Ioachim, V. Royal
Journal: Kidney International (2024)
Elevation of creatine phosphokinase in moderate-to-severe atopic dermatitis is associated with the use of JAK inhibitors but not dupilumab: A systematic review and meta-analysis
Authors: Daud Manzar, Emmanuel Suntres, Nikhil Nair, Yash Patel, Mohannad Abu-Hilal
Journal: Journal of the American Academy of Dermatology (2024)
Reply to: Comments on “An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis”
Authors: Romée J.A.L.M. Snijders, Anna E.C. Stoelinga, Bart van Hoek, Joost P.H. Drenth
Journal: Journal of Hepatology (2024)
Utility of an in-house real-time PCR in whole blood samples as a minimally invasive method for early and accurate diagnosis of invasive mould infections.
Authors: Mragnayani Pandey, Immaculata Xess, Janya Sachdev, Neha Sharad, Sonakshi Gupta, Gagandeep Singh, Renu Kumari Yadav, Bhaskar Rana, Stephen Raj, M.Nizam Ahmad, Neha Nityadarshini, Upendra Baitha, Manish Soneja, None Shalimar, Bindu Prakash, Kapil Sikka, Purva Mathur, Viveka P. Jyotsna, Rakesh Kumar, Naveet Wig, Sudesh Gourav, Ashutosh Biswas, Alok Thakar
Journal: Journal of Infection (2024)

IntroductionInvasive mould infections (IMIs) are a leading cause of death in patients with compromised immune systems. Proven invasive mould infection requires detection of a fungus by histopathological analysis of a biopsied specimen, sterile culture, or fungal DNA amplification by PCR in tissue. However, the clinical performance of a PCR assay on blood samples taken from patients suspected of invasive mould disease has not been fully evaluated, particularly for the differential diagnosis of invasive aspergillosis (IA) and invasive Mucormycosis (IM).ObjectivesTo assess the diagnostic utility of our previously validated in-house real-time PCR in blood samples for diagnosis of invasive aspergillosis and mucormycosis in patients with suspected invasive mould infection.MethodsAll patients with suspected invasive mould infection were prospectively enrolled from May 2021 to July 2021. Conventional fungal diagnosis was performed using tissue and respiratory samples. In-house PCR was performed on blood samples and its diagnostic performance evaluated.ResultsA total of 158 cases of suspected invasive mould infection were enrolled in the study. The sensitivity and specificity of in-house PCR performed on blood samples was found to be 92.5% and 81.4% respectively for diagnosis of probable IA, and 65% and 84.62% respectively for diagnosis of proven and probable IM. It was also able to detect 3 out of 5 cases of possible IM where no other microbiological evidence of IM was obtained.ConclusionsThis assay could be helpful in minimally invasive diagnosis of IMIs for patients in whom invasive sampling is not feasible, especially as a preliminary or screening test. It can help in early diagnosis, anticipating conventional laboratory confirmation by days or weeks. Possible correlation between fungal load and mortality can help in initiating aggressive treatment for patients with high initial fungal load.
Impact of Endoscopic Treatment in Severe Duodenal Polyposis: A National Study in Familial Adenomatous Polyposis Patients
Authors: Pierrine Le Bras, Estelle Cauchin, Glenn De Lange, Driffa Moussata, Géraldine-Anne Garcia, Lucille Quénéhervé, Jean-Christophe Saurin, Emmanuel Coron
Journal: Clinical Gastroenterology and Hepatology (2024)
The clinical antiprotozoal drug nitazoxanide and its metabolite tizoxanide extend Caenorhabditis elegans lifespan and healthspan
Authors: Wenfeng Li, Shuming Chen, Jing Lang, Jing Luo, Jiahui Chen, Liping Zhang, Zhijie Sun, Deli Dong
Journal: Acta Pharmaceutica Sinica B (2024)

The drugs extending healthspan in clinic have always been searched. Nitazoxanide is an FDA-approved clinical antiprotozoal drug. Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo. Our previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK, oral nitazoxanide protects against experimental hyperlipidemia, hepatic steatosis, and atherosclerosis. Here, we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of C. elegans through Akt/AMPK/sir 2.1/daf16 pathway. Additionally, both nitazoxanide and tizoxanide improve high glucose-induced shortening of C. elegans lifespan. Nitazoxanide has been a clinical drug with a good safety profile, we suggest that it is a novel anti-aging drug.
Gastrointestinal signals in supplemented media reveal a role in adherence for the <i>Shigella flexneri sap</i> autotransporter gene
Authors: Yrvin León, Raphael Honigsberg, David A. Rasko, Christina S. Faherty
Journal: Gut Microbes (2024)

Shigella flexneri causes severe diarrheal disease worldwide. While many aspects of pathogenesis have been elucidated, significant knowledge gaps remain regarding the role of putative chromosomally-encoded virulence genes. The uncharacterized sap gene encoded on the chromosome has significant nucleotide sequence identity to the fluffy (flu) antigen 43 autotransporter gene in pathogenic Escherichia coli. Here, we constructed a Δsap mutant in S. flexneri strain 2457T and examined the effects of this mutation on bacterial cell aggregation, biofilm formation, and adherence to colonic epithelial cells. Analyses included the use of growth media supplemented with glucose and bile salts to replicate small intestinal signals encountered by S. flexneri. Deletion of the sap gene in 2457T affected epithelial cell adherence, resulted in quicker bacterial cell aggregation, but did not affect biofilm formation. This work highlights a functional role for the sap gene in S. flexneri pathogenesis and further demonstrates the importance of using relevant and appropriate gastrointestinal signals to characterize virulence genes of enteropathogenic bacteria.
Targeting the nuclear long noncoding transcript LSP1P5 abrogates extracellular matrix deposition by trans-upregulating CEBPA in keloids
Authors: Shuchen Gu, Xin Huang, Shenying Luo, Yunhan Liu, Yimin Khoong, Hsin Liang, Liying Tu, Ruoqing Xu, En Yang, Yixuan Zhao, Min Yao, Tao Zan
Journal: Molecular Therapy (2024)

Keloids are characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix (ECM) and are a major global health care burden among cutaneous diseases. However, the function of long noncoding RNA (lncRNA)-mediated ECM remodeling during the pathogenesis of keloids is still unclear. Herein, we identified a long noncoding transcript, namely, lymphocyte-specific protein 1 pseudogene 5 (LSP1P5), that modulates ECM component deposition in keloids. First, high-throughput transcriptome analysis showed that LSP1P5 was selectively upregulated in keloids and correlated with more severe disease in a clinical keloid cohort. Therapeutically, the attenuation of LSP1P5 significantly decreased the expression of ECM markers (COL1, COL3, and FN1) both in vitro and in vivo. Intriguingly, an antifibrotic gene, CCAAT enhancer binding protein alpha (CEBPA), is a functional downstream candidate of LSP1P5. Mechanistically, LSP1P5 represses CEBPA expression by hijacking Suppressor of Zeste 12 to the promoter of CEBPA, thereby enhancing the polycomb repressive complex 2-mediated H3K27me3 and changing the chromosomal opening status of CEBPA. Taken together, these findings indicate that targeting LSP1P5 abrogates fibrosis in keloids through epigenetic regulation of CEBPA, revealing a novel antifibrotic therapeutic strategy that bridges our current understanding of lncRNA regulation, histone modification and ECM remodeling in keloids.
Oncogenic extrachromosomal DNA identification using whole-genome sequencing from formalin-fixed glioblastomas
Authors: I Noorani, J Luebeck, A Rowan, E Grönroos, V Barbe, M Fabian, J A R Nicoll, D Boche, V Bafna, P S Mischel, C Swanton
Journal: Annals of Oncology (2024)
Efficacy and safety of tildrakizumab for the treatment of moderate-to-severe plaque psoriasis of the scalp: A multicenter, randomized, double-blind, placebo-controlled, Phase 3b study
Authors: Kurt Gebauer, Lynda Spelman, Paul S. Yamauchi, Jerry Bagel, Tushar Nishandar, Michael Crane, Iris Kopeloff, Mudgal Kothekar, Siu-Long Yao, Howard L. Sofen
Journal: Journal of the American Academy of Dermatology (2024)

Background Scalp psoriasis is common and difficult to treat. Objective To evaluate efficacy and safety of tildrakizumab for the treatment of scalp psoriasis. Methods In this Phase 3b, randomized, double-blind, placebo-controlled study (NCT03897088), patients with moderate-to-severe plaque psoriasis affecting the scalp (Investigator Global Assessment modified [IGA mod] 2011 [scalp] ≥3, Psoriasis Scalp Severity Index [PSSI] ≥12, ≥30% scalp surface area affected) received tildrakizumab 100 mg or placebo at W0 and W4. The primary endpoint was IGA mod 2011 (scalp) score of "clear" or "almost clear" with ≥2-point reduction from baseline at W16 (IGA mod 2011 [scalp] response). Key secondary endpoints were PSSI 90 response at W12 and W16 and IGA mod 2011 (scalp) response at W12. Safety was assessed from adverse events. Results Of patients treated with tildrakizumab (n = 89) vs placebo (n = 82), 49.4% vs 7.3% achieved IGA mod 2011 (scalp) response at W16 (primary endpoint) and 46.1% vs 4.9% at W12; 60.7% vs 4.9% achieved PSSI 90 response at W16 and 48.3% vs 2.4% at W12 (all P <0.00001). No serious treatment-related adverse events occurred. Limitations Only short-term data are presented. Conclusion Tildrakizumab was efficacious for the treatment of scalp psoriasis with no new safety signals.
Multi-domain stain normalization for digital pathology: A cycle-consistent adversarial network for whole slide images
Authors: Martin J. Hetz, Tabea-Clara Bucher, Titus J. Brinker
Journal: Medical Image Analysis (2024)

The variation in histologic staining between different medical centers is one of the most profound challenges in the field of computer-aided diagnosis. The appearance disparity of pathological whole slide images causes algorithms to become less reliable, which in turn impedes the wide-spread applicability of downstream tasks like cancer diagnosis. Furthermore, different stainings lead to biases in the training which in case of domain shifts negatively affect the test performance. Therefore, in this paper we propose MultiStain-CycleGAN, a multi-domain approach to stain normalization based on CycleGAN. Our modifications to CycleGAN allow us to normalize images of different origins without retraining or using different models. We perform an extensive evaluation of our method using various metrics and compare it to commonly used methods that are multi-domain capable. First, we evaluate how well our method fools a domain classifier that tries to assign a medical center to an image. Then, we test our normalization on the tumor classification performance of a downstream classifier. Furthermore, we evaluate the image quality of the normalized images using the Structural similarity index and the ability to reduce the domain shift using the Fréchet inception distance. We show that our method proves to be multi-domain capable, provides a very high image quality among the compared methods, and can most reliably fool the domain classifier while keeping the tumor classifier performance high. By reducing the domain influence, biases in the data can be removed on the one hand and the origin of the whole slide image can be disguised on the other, thus enhancing patient data privacy.
Prevascularized spongy-like hydrogels maintain their angiogenic potential after prolonged hypothermic storage
Authors: Sara Freitas-Ribeiro, Helena Moreira, Lucília P. da Silva, Jennifer Noro, Belém Sampaio-Marques, Paula Ludovico, Mariana Jarnalo, Ricardo Horta, Alexandra P. Marques, Rui L. Reis, Rogério P. Pirraco
Journal: Bioactive Materials (2024)

The chronic shortage of organs and tissues for transplantation represents a dramatic burden on healthcare systems worldwide. Tissue engineering offers a potential solution to address these shortages, but several challenges remain, with prevascularization being a critical factor for in vivo survival and integration of tissue engineering products. Concurrently, a different challenge hindering the clinical implementation of such products, regards their efficient preservation from the fabrication site to the bedside. Hypothermia has emerged as a potential solution for this issue due to its milder effects on biologic systems in comparison with other cold preservation methodologies. Its impact on prevascularization, however, has not been well studied. In this work, 3D prevascularized constructs were fabricated using adipose-derived stromal vascular fraction cells and preserved at 4 °C using Hypothermosol or basal culture media (α-MEM). Hypothermosol efficiently preserved the structural and cellular integrity of prevascular networks as compared to constructs before preservation. In contrast, the use of α-MEM led to a clear reduction in prevascular structures, with concurrent induction of high levels of apoptosis and autophagy at the cellular level. In vivo evaluation using a chorioallantoic membrane model demonstrated that, in opposition to α-MEM, Hypothermosol preservation retained the angiogenic potential of constructs before preservation by recruiting a similar number of blood vessels from the host and presenting similar integration with host tissue. These results emphasize the need of studying the impact of preservation techniques on key properties of tissue engineering constructs such as prevascularization, in order to validate and streamline their clinical application.
Schema therapy for older adults?
Authors: Erkki Isometsä
Journal: The Lancet Healthy Longevity (2024)

In an ageing world, studies addressing mental health disorders that have been uninvestigated in older adults are valuable. One such topic is treatment of older adults with personality disorders. Personality disorders are around as common in older adults as they are in younger adults1. However, treatment is often sought because of concurrent depression or anxiety. Because underlying personality disorders can remain unrecognised, they could be more common than perceived.
Bridging modifiable risk factors and cognitive decline: the mediating role of brain age
Authors: Marcella Montagnese, Timothy Rittman
Journal: The Lancet Healthy Longevity (2024)

The increased incidence of dementia has driven research towards early detection of individuals at the greatest risk of cognitive decline. The potential of early intervention to address both dementia and age-related cognitive decline without dementia underlines the urgency of this research. An innovative and expanding field within neuroscience examines brain age through advanced neuroimaging techniques, especially using MRI. The concept of brain age is to measure the cumulative effect of biological ageing and degeneration separately from chronological age.
Supporting social connections across the life course
Authors: None The Lancet Healthy Longevity
Journal: The Lancet Healthy Longevity (2024)

On April 1, 2024, Japan is set to enact the Act on Promotion of Policy for Loneliness and Isolation aimed at tackling social isolation and loneliness in the country. The legislation follows a 2022 government survey that revealed that 40% of respondents in the country aged 16 years and older felt lonely. Although not all countries are drawing up legislation, social connection is being increasingly prioritised in the health-care agenda. In November, 2023, WHO announced the launch of its commission on social connection which aims to "analyse the central role social connection plays in improving health for people of all ages and outline solutions to build social connections at scale".
Group schema therapy combined with psychomotor therapy for older adults with a personality disorder: an open-label, multicentre, randomised controlled trial
Authors: Martine S Veenstra-Spruit, Renske Bouman, Silvia DM van Dijk, Antoinette DI van Asselt, Sebastiaan PJ van Alphen, Dorothee H Veenstra, Marije de Ruiter, Saskia E Troost, Monique W Lammers, Frank Vulker, Maureen MJ Smeets-Janssen, Rob HS van den Brink, Richard C Oude Voshaar
Journal: The Lancet Healthy Longevity (2024)

BackgroundAlthough several types of psychotherapy effectively reduce psychological distress associated with personality disorders, randomised controlled trials (RCT) have systematically excluded older patients. We aimed to examine the effectiveness of group schema therapy combined with psychomotor therapy (GST + PMT) in later life compared with treatment as usual (TAU).MethodsWe did an open-label, multicentre, RCT in eight outpatient clinics for geriatric psychiatry in the Netherlands. Adults aged 60 years or older with a full or subthreshold cluster B or C personality disorder according to DSM criteria were included and randomly assigned 1:1 to GST + PMT or TAU by an independent researcher applying a computer-generated sequence per study site when 8 to 16 patients had given informed consent; investigators and interviewers were kept blinded until end of follow-up. Included individuals received 20 weekly sessions of GST + PMT or TAU with 1 year of follow-up. The primary outcome was psychological distress, measured with the 53-item Brief Symptom Inventory. The trial was registered with International Clinical Trials Registry Platform, NTR6621.FindingsOf the 145 study participants recruited between Feb 21, 2018, and Jan 21, 2020, 102 patients (median age of 69 years [IQR 63–71], 62 [61%] female) who concluded therapy before the COVID-19 pandemic (cutoff March 20, 2020) were included in the intention-to-treat analysis (51 in each study group), because COVID-19 measures substantially disrupted delivery of group therapy. GST + PMT significantly improved psychological distress compared with TAU over the 6-month treatment period (Cohen's d 0·42, 95% CI 0·16 to 0·68; p=0·0016). The pre-post effect of GST + PMT remained stable during follow-up, whereas patients receiving TAU further improved, resulting in a non-significant difference between groups at 1 year (Cohen's d 0·21, 95% CI –0·07 to 0·48; p=0·14). No patients reported adverse events.InterpretationPsychotherapy focused on personality disorders is effective in later life, resulting in a faster improvement in psychopathology than TAU. Future studies should focus on increasing effectiveness by intensifying or prolonging treatment.FundingNetherlands Organization for Health Research and Development.TranslationFor the Dutch translation of the abstract see Supplementary Materials section.
Eradicating gross tumor disease: a prerequisite for efficient radioimmunotherapy?
Authors: Eric Deutsch, Antonin Levy
Journal: JNCI Journal of the National Cancer Institute (2024)

Radiation therapy may induce off-target antitumor "abscopal" immunostimulatory and immunosuppressive effects. Several preclinical and early clinical studies revealed promising results when combining radiation therapy with immunostimulatory agents. Most radioimmunotherapy randomized trials showed disappointing results in patients with advanced tumors. In contrast, outcomes were encouraging when immunotherapy was delivered on top of gross disease elimination with curative-intent radiation therapy. In this review, we highlight available results from randomized trials and discuss the potential impact of overall tumor burden on the observed efficacy of radioimmunotherapy.
Response of bilateral Wilms tumor to chemotherapy suggests histologic subtype and guides treatment
Authors: Colton Duncan, Suraj Sarvode Mothi, Teresa C Santiago, Jordan A Coggins, Dylan E Graetz, Michael W Bishop, Elizabeth A Mullen, Andrew J Murphy, Daniel M Green, Matthew J Krasin, Andrew M Davidoff
Journal: JNCI Journal of the National Cancer Institute (2024)

Patients with bilateral Wilms tumor initially receive neoadjuvant chemotherapy to shrink the tumors and increase the likelihood of successful nephron-sparing surgery. Biopsy of poorly responding tumors is often done to better understand therapy resistance. The purpose of this retrospective, single-institution study was to determine whether initial chemotherapy response is associated with tumor histology, potentially obviating the need for biopsy or change in chemotherapy.