tbuckley/cabot-search huggingface dataset:
LRP11 promotes stem-like T cells via MAPK13-mediated TCF1 phosphorylation, enhancing anti-PD1 immunotherapy
Authors: Lingjuan Sun, Zhibo Ma, Xiangli Zhao, Xiaosheng Tan, Yuhao Tu, Jingzeng Wang, Li Chen, Zhishui Chen, Gang Chen, Peixiang Lan
Journal: Journal for ImmunoTherapy of Cancer (2024)

Tumor-infiltrating T cells enter an exhausted or dysfunctional state, which limits antitumor immunity. Among exhausted T cells, a subset of cells with features of progenitor or stem-like cells has been identified as TCF1
Multimodal profiling of chordoma immunity reveals distinct immune contextures
Authors: Siddh van Oost, Debora M Meijer, Marieke E Ijsselsteijn, Jessica P Roelands, Brendy E M W van den Akker, Ruud van der Breggen, Inge H Briaire-de Bruijn, Manon van der Ploeg, Pauline M Wijers-Koster, Samuel B Polak, Wilco C Peul, Robert J P van der Wal, Noel F C C de Miranda, Judith V M G Bovee
Journal: Journal for ImmunoTherapy of Cancer (2024)

Chordomas are rare cancers from the axial skeleton which present a challenging clinical management with limited treatment options due to their anatomical location. In recent years, a few clinical trials demonstrated that chordomas can respond to immunotherapy. However, an in-depth portrayal of chordoma immunity and its association with clinical parameters is still lacking.
<scp>Myositis‐Associated</scp> Autoantibodies in Patients With Juvenile Myositis Are Associated With Refractory Disease and Mortality
Authors: Matthew A. Sherman, Payam Noroozi Farhadi, Katherine Pak, Edward P. Trieu, Kakali Sarkar, Ira N. Targoff, Megan L. Neely, Andrew L. Mammen, Lisa G. Rider
Journal: Arthritis & Rheumatology (2024)

Objective Myositis‐associated autoantibodies (MAAs) have been associated with overlap myositis, certain disease manifestations such as interstitial lung disease (ILD), and worse prognosis in the idiopathic inflammatory myopathies. MAAs overall remain largely uncharacterized in patients with juvenile‐onset myositis. Moreover, it is unknown whether the number of MAAs is associated with disease severity. Methods Patients with juvenile myositis in cross‐sectional natural history studies who underwent testing for myositis autoantibodies were included. Demographics, myositis autoantibodies, clinical characteristics, medications received, and outcomes of those with and without MAAs were compared. Multivariable logistic regression was performed to determine whether the number of MAAs detected was associated with severe disease features. Results Among 551 patients, 36% had an MAA and 13% had more than one MAA. Among those who were MAA positive, there was a higher frequency of overlap myositis (18% vs 5.9%, P &lt; 0.001). MAA positivity was associated with certain clinical features, including Raynaud phenomenon (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.41–4.28) and ILD (OR 3.43, 95% CI 1.75–6.96), as well as a chronic disease course (OR 1.72, 95% CI 1.10–2.72) and mortality (OR 3.76, 95% CI 1.72–8.43). The number of MAAs was also associated with mortality (OR 1.83, 95% CI 1.16–2.86). Conclusion MAAs were prevalent in a large cohort of patients with juvenile myositis. ILD, refractory disease, and mortality were associated with MAA positivity. Prospective studies are needed to determine whether early detection of MAAs may lead to improved outcomes for patients with juvenile myositis.
Vitamin D and Marine n‐3 Fatty Acids for Autoimmune Disease Prevention: Outcomes Two Years After Completion of a <scp>Double‐Blind</scp>, <scp>Placebo‐Controlled</scp> Trial
Authors: Karen H. Costenbader, Nancy R. Cook, I‐Min Lee, Jill Hahn, Joseph Walter, Vadim Bubes, Gregory Kotler, Nicole Yang, Sonia Friedman, Erik K. Alexander, JoAnn E. Manson
Journal: Arthritis & Rheumatology (2024)

Objective In the 5.3‐year randomized, 2 × 2 factorial, double‐blind, placebo‐controlled Vitamin D and Omega‐3 Trial (VITAL), vitamin D supplementation reduced autoimmune disease (AD) incidence (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.61–0.99). Omega‐3 (n‐3) fatty acid supplementation showed a statistically nonsignificant reduction (HR 0.85, 95% CI 0.67–1.08). We aimed to confirm further AD cases arising during and after randomization and assess sustained effects with two years of postintervention observation. Methods Of the 12,786 men aged ≥50 and 13,085 women aged ≥55 initially randomized, we observed surviving and willing participants for two more years. We continued to confirm annual participant‐reported new AD by medical record review. Cox models calculated HRs for all confirmed incident AD, (and secondary endpoints, including probable cases, and individual ADs), during the observational and randomized periods. Results A total of 21,592 participants (83.5%) were observed for two more years; 514 participants developed incident confirmed AD (236 since prior report), of whom 255 had been randomized to vitamin D versus 259 to vitamin D placebo (HR 0.98 [95% CI 0.83–1.17] at 7 years). AD was confirmed in 234 participants initially randomized to n‐3 fatty acids versus 280 randomized to its placebo (HR 0.83 [95% CI 0.70–0.99] at 7 years). Of newly confirmed cases, 65 had onset during randomization; their inclusion changed randomized results as follows: HR 0.85 (95% CI 0.70–1.04) for vitamin D and HR 0.87 (95% CI 0.71–1.06) for n‐3 fatty acids. Conclusion Two years after trial termination, the protective effects of 2000 IU/day of vitamin D dissipated, but 1,000 mg/day of n‐3 fatty acids had a sustained effect in reducing AD incidence.
Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis–Associated Lymphoproliferative Disorders
Authors: Yoshihiko Hoshida, Atsuko Tsujii, Shiro Ohshima, Yukihiko Saeki, Masato Yagita, Tomoya Miyamura, Masao Katayama, Tomonori Kawasaki, Yasushi Hiramatsu, Hisaji Oshima, Toshihiko Murayama, Shinji Higa, Kazuya Kuraoka, Fuminori Hirano, Kenji Ichikawa, Mitsutoshi Kurosawa, Hiroaki Suzuki, Noriyuki Chiba, Takao Sugiyama, Yuko Minami, Hitoshi Niino, Atsushi Ihata, Ikuo Saito, Akiko Mitsuo, Toshitaka Maejima, Atsuhiro Kawashima, Hiroshi Tsutani, Koichiro Takahi, Takahiko Kasai, Yoko Shinno, Yoshiro Tachiyama, Norihiro Teramoto, Kenichi Taguchi, Shinji Naito, Shigeru Yoshizawa, Masahiro Ito, Yasuo Suenaga, Shunsuke Mori, Shoichi Nagakura, Norie Yoshikawa, Mitsuharu Nomoto, Atsuhisa Ueda, Shouhei Nagaoka, Yukio Tsuura, Keigo Setoguchi, Shoji Sugii, Asami Abe, Toshiaki Sugaya, Hiroyuki Sugahara, Shigeki Fujita, Yasuo Kunugiza, Norishige Iizuka, Ryosuke Yoshihara, Hiroki Yabe, Tomoaki Fujisaki, Eiichi Morii, Morishige Takeshita, Masakazu Sato, Kazuyoshi Saito, Kiyoshi Matsui, Yasuhiko Tomita, Hiroshi Furukawa, Shigeto Tohma
Journal: Arthritis & Rheumatology (2024)

Objective In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). Methods In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann‐Whitney U ‐test, the log‐rank test, logistic regression analysis, and Cox proportional hazards models. Results Overall, 752 patients with RA‐associated LPD (RA‐LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA‐LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD‐associated immunosuppressive conditions. Furthermore, patients with RA‐LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX‐only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein‐Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)–only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. Conclusion Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA‐LPD, with patterns changing over time. Furthermore, TCZ‐only regimens are recommended after LPD onset. image
Photo‐induced Oriented Crystallization of Intracellular Nanocrystals Based on Phase Separation for Diagnostic Bioimaging and Analysis
Authors: Hao Liu, Zhiming Liu, Jiang Xiao, Xiaohui Liu, Hui Jiang, Xuemei Wang
Journal: Advanced Healthcare Materials (2024)

Biomineral crystals form complex nonequilibrium structures based on the multistep nucleation theory, via transient amorphous precursors. However, the intricate nature of the biological system results in the inconsistent frequency of nucleation and crystallization, which making it problematic to obtain homogeneous nanocrystals, limits their application in biomedicine. Here, it is reported that homogeneous nanocrystals of photoinduced oriented crystallization with protein coronas are based on intracellular liquid-liquid phase separation for in situ analysis and mapping of surface-enhanced Raman spectroscopy (SERS). Near-infrared light promotes the formation of intracellular dense phases, accelerates the nucleation of gold atoms at secondary structure sites of proteins, and promotes the growth of crystals. Homogeneous gold nanocrystals with stable SERS signals can be used to analysis different cell cycles and acquire in situ molecular information of metastatic tumor cells. Of note are tag molecule is embedded in protein coronas of gold nanocrystals to enable the mapping of patient tumor tissue samples and the portable recognition of tumor cells. Thus, this study proposes a new strategy for biomineralization of intracellular homogeneous gold nanocrystals and its potential application.
Clinical Images: Erosive tophaceous gout and uric acid nephrolithiasis: microscopic and three‐dimensional high‐resolution peripheral quantitative computed tomography findings
Authors: Giovanni Adami, Francesca Ruzzon, Angelo Fassio, Davide Gatti, Matteo Gatti, Maurizio Rossini
Journal: Arthritis & Rheumatology (2024)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Hydroxychloroquine in Lupus Pregnancy and Risk of Preeclampsia
Authors: Amadeia Rector, Ivana Marić, Yashaar Chaichian, Eliza Chakravarty, Miranda Cantu, Michael H. Weisman, Gary M. Shaw, Maurice L. Druzin, Julia F. Simard
Journal: Arthritis & Rheumatology (2024)

Systemic lupus erythematosus (SLE) disproportionately affects women during childbearing years, and hydroxychloroquine (HCQ) is the standard first-line treatment. Preeclampsia complicates up to one-third of pregnancies in lupus patients, although reports vary by parity and multifetal gestation. We investigated whether taking HCQ early in pregnancy may reduce the risk of preeclampsia.
Extracellular vesicles released by transforming growth factor-beta 1-preconditional mesenchymal stem cells promote recovery in mice with spinal cord injury
Authors: Guoliang Chen, Kuileung Tong, Shiming Li, Zerong Huang, Shuangjiang Liu, Haoran Zhu, Yanheng Zhong, Zhisen Zhou, Genlong Jiao, Fuxin Wei, Ningning Chen
Journal: Bioactive Materials (2024)

Spinal cord injury (SCI) causes neuroinflammation, neuronal death, and severe axonal connections. Alleviating neuroinflammation, protecting residual cells and promoting neuronal regeneration via endogenous neural stem cells (eNSCs) represent potential strategies for SCI treatment. Extracellular vesicles (EVs) released by mesenchymal stem cells have emerged as pathological mediators and alternatives to cell-based therapies following SCI. In the present study, EVs isolated from untreated (control, C-EVs) and TGF-β1-treated (T-EVs) mesenchymal stem cells were injected into SCI mice to compare the therapeutic effects and explore the underlying mechanisms. Our study demonstrated for the first time that the application of T-EVs markedly enhanced the proliferation and antiapoptotic ability of NSCs in vitro. The infusion of T-EVs into SCI mice increased the shift from the M1 to M2 polarization of reactive microglia, alleviated neuroinflammation, and enhanced the neuroprotection of residual cells during the acute phase. Moreover, T-EVs increased the number of eNSCs around the epicenter. Consequently, T-EVs further promoted neurite outgrowth, increased axonal regrowth and remyelination, and facilitated locomotor recovery in the chronic stage. Furthermore, the use of T-EVs in Rictor−/− SCI mice (conditional knockout of Rictor in NSCs) showed that T-EVs failed to increase the activation of eNSCs and improve neurogenesis sufficiently, which suggested that T-EVs might induce the activation of eNSCs by targeting the mTORC2/Rictor pathway. Taken together, our findings indicate the prominent role of T-EVs in the treatment of SCI, and the therapeutic efficacy of T-EVs for SCI treatment might be optimized by enhancing the activation of eNSCs via the mTORC2/Rictor signaling pathway.
Perspectives and awareness of endoscopy healthcare professionals on sustainable practices in gastrointestinal endoscopy: results of the LEAFGREEN survey
Authors: João A. Cunha Neves, Enrique Rodriguez de Santiago, Heiko Pohl, Vicente Lorenzo-Zúñiga, Miguel F. Cunha, Andrei M. Voiosu, Christoph Römmele, Douglas G. Penman, Eduardo Albéniz, Keith Siau, Leigh Donnelly, Luca Elli, Mathieu Pioche, Ulrike Beilenhoff, Marianna Arvanitakis, Bas L.A.M. Weusten, Raf Bisschops, Cesare Hassan, Helmut Messmann, Ian M. Gralnek, Mário Dinis-Ribeiro
Journal: Endoscopy (2024)

Abstract Background Gastrointestinal (GI) endoscopy is one of healthcare’s main contributors to climate change. We aimed to assess healthcare professionals’ attitudes and the perceived barriers to implementation of sustainable GI endoscopy. Methods The LEAFGREEN web-based survey was a cross-sectional study conducted by the European Society of Gastrointestinal Endoscopy (ESGE) Green Endoscopy Working Group. The questionnaire comprised 39 questions divided into five sections (respondent demographics; climate change and sustainability beliefs; waste and resource management; single-use endoscopes and accessories; education and research). The survey was available via email to all active members of the ESGE and the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) in March 2023. Results 407 respondents participated in the survey (11% response rate). Most participants (86%) agreed climate change is real and anthropogenic, but one-third did not consider GI endoscopy to be a significant contributor to climate change. Improvement in the appropriateness of endoscopic procedures (41%) and reduction in single-use accessories (34%) were considered the most important strategies to reduce the environmental impact of GI endoscopy. Respondents deemed lack of institutional support and knowledge from staff to be the main barriers to sustainable endoscopy. Strategies to reduce unnecessary GI endoscopic procedures and comparative studies of single-use versus reusable accessories were identified as research priorities. Conclusions In this survey, ESGE and ESGENA members acknowledge climate change as a major threat to humanity. Further improvement in sustainability beliefs and professional attitudes, reduction in inappropriate GI endoscopy, and rational use of single-use accessories and endoscopes are critically required.
Self‐Supplied Reactive Oxygen Species‐Responsive Mitoxantrone Polyprodrug for Chemosensitization‐Enhanced Chemotherapy under Moderate Hyperthermia
Authors: Hongjie Zhang, Jing Wang, Ruiying Wu, Benyan Zheng, Yanxiang Sang, Bibo Wang, Lei Song, Yuan Hu, Xiaopeng Ma
Journal: Advanced Healthcare Materials (2024)

Abstract Currently, the secondary development and modification of clinical drugs has become one of the research priorities. Researchers have developed a variety of TME‐responsive nanomedicine carriers to solve certain clinical problems. Unfortunately, endogenous stimuli such as reactive oxygen species (ROS), as an important prerequisite for effective therapeutic efficacy, are not enough to achieve the expected drug release process, therefore, it is difficult to achieve a continuous and efficient treatment process. Herein, a self‐supply ROS‐responsive cascade polyprodrug (PMTO) is designed. The encapsulation of the chemotherapy drug mitoxantrone (MTO) in a polymer backbone could effectively reduce systemic toxicity when transported in vivo. After PMTO is degraded by endogenous ROS of the TME, another part of the polyprodrug backbone becomes cinnamaldehyde (CA), which can further enhance intracellular ROS, thereby achieving a sustained drug release process. Meanwhile, due to the disruption of the intracellular redox environment, the efficacy of chemotherapy drugs is enhanced. Finally, the anticancer treatment efficacy is further enhanced due to the mild hyperthermia effect of PMTO. In conclusion, the designed PMTO demonstrates remarkable antitumor efficacy, effectively addressing the limitations associated with MTO.
Vascularized 3D Human Skin Models in the Forefront of Dermatological Research
Authors: Rahul Rimal, Saradaprasan Muduli, Prachi Desai, Andrea Bonnin Marquez, Martin Möller, Ilia Platzman, Joachim Spatz, Smriti Singh
Journal: Advanced Healthcare Materials (2024)

In vitro engineered skin models are emerging as an alternative platform to reduce and replace animal testing in dermatological research. Despite the progress made in recent years, considerable challenges still exist for the inclusion of diverse cell types within skin models. Blood vessels, in particular, are essential in maintaining tissue homeostasis and are one of many primary contributors to skin disease inception and progression. Substantial efforts in the past have allowed the successful fabrication of vascularized skin models that are currently utilized for disease modeling and drugs/cosmetics testing. This review first discusses the need for vascularization within tissue-engineered skin models, highlighting their role in skin grafting and disease pathophysiology. Second, the review spotlights the milestones and recent progress in the fabrication and utilization of vascularized skin models. Additionally, advances including the use of bioreactors, organ-on-a-chip devices, and organoid systems are briefly explored. Finally, the challenges and future outlook for vascularized skin models are addressed.
Designing Difference-in-Difference Studies with Staggered Treatment Adoption: Key Concepts and Practical Guidelines
Authors: Coady Wing, Madeline Yozwiak, Alex Hollingsworth, Seth Freedman, Kosali Simon
Journal: Annual Review of Public Health (2024)

Difference-in-difference (DID) estimators are a valuable method for identifying causal effects in the public health researcher's toolkit. A growing methods literature points out potential problems with DID estimators when treatment is staggered in adoption and varies with time. Despite this, no practical guide exists for addressing these new critiques in public health research. We illustrate these new DID concepts with step-by-step examples, code, and a checklist. We draw insights by comparing the simple 2 × 2 DID design (single treatment group, single control group, two time periods) with more complex cases: additional treated groups, additional time periods of treatment, and treatment effects possibly varying over time. We outline newly uncovered threats to causal interpretation of DID estimates and the solutions the literature has proposed, relying on a decomposition that shows how the more complex DIDs are an average of simpler 2 × 2 DID subexperiments.
Neural alterations underlying executive dysfunction in Parkinson’s Disease: a systematic review and coordinate-based meta-analysis of functional neuroimaging studies.
Authors: Eleonora Arrigoni, Paola Antoniotti, Virginia Bellocchio, Laura Veronelli, Massimo Corbo, Alberto Pisoni
Journal: Ageing Research Reviews (2024)

Parkinson’s Disease’s (PD) neuropsychological profile is often characterized by altered performance in executive functions (EF) tasks, with a remarkable impact on patients’ quality of life. To date, the available neuroimaging literature lacks conclusive evidence about neural patterns underlying EF deficits in PD. Here, we aimed to synthesize the results of PET/fMRI studies examining the differences in brain activation between PD patients and controls during EF tasks, focussing on the three main EF sub-components: cognitive flexibility, working memory, and response inhibition. We conducted a coordinate-based meta-analysis to assess the converging alterations in brain activity in PD patients compared to controls. We assessed the association between aberrant patterns of activity and the EF sub-domains. We found a significant association between hypoactivation patterns in PD converging at the level of the right inferior frontal gyrus in response inhibition tasks, whereas hypoactivation in the left inferior frontal gyrus was found in association with the cognitive flexibility domain. Our results confirm the existence of neural alterations in PD patients in relation to specific EF sub-domains.
Azacitidine, Venetoclax, and Gilteritinib in Newly Diagnosed and Relapsed or Refractory <i>FLT3</i>-Mutated AML
Authors: Nicholas J. Short, Naval Daver, Courtney D. Dinardo, Tapan Kadia, Lewis F. Nasr, Walid Macaron, Musa Yilmaz, Gautam Borthakur, Guillermo Montalban-Bravo, Guillermo Garcia-Manero, Ghayas C. Issa, Kelly S. Chien, Elias Jabbour, Cedric Nasnas, Xuelin Huang, Wei Qiao, Jairo Matthews, Christopher J. Stojanik, Keyur P. Patel, Regina Abramova, Jennifer Thankachan, Marina Konopleva, Hagop Kantarjian, Farhad Ravandi
Journal: Journal of Clinical Oncology (2024)

PURPOSE Azacitidine plus venetoclax is a standard of care for patients with newly diagnosed AML who are unfit for intensive chemotherapy. However, FLT3 mutations are a common mechanism of resistance to this regimen. The addition of gilteritinib, an oral FLT3 inhibitor, to azacitidine and venetoclax may improve outcomes in patients with FLT3-mutated AML. METHODS This phase I/II study evaluated azacitidine, venetoclax, and gilteritinib in two cohorts: patients with (1) newly diagnosed FLT3-mutated AML who were unfit for intensive chemotherapy or (2) relapsed/refractory FLT3-mutated AML (ClinicalTrials.gov identifier: NCT04140487 ). The primary end points were the maximum tolerated dose of gilteritinib (phase I) and the combined complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate (phase II). RESULTS Fifty-two patients were enrolled (frontline [n = 30]; relapsed/refractory [n = 22]). The recommended phase II dose was gilteritinib 80 mg once daily in combination with azacitidine and venetoclax. In the frontline cohort, the median age was 71 years and 73% of patients had an FLT3-internal tandem duplication (ITD) mutation. The CR/CRi rate was 96% (CR, 90%; CRi, 6%). Sixty-five percent of evaluable patients achieved FLT3-ITD measurable residual disease &lt;5 × 10 –5 within four cycles. With a median follow-up of 19.3 months, the median relapse-free survival (RFS) and overall survival (OS) have not been reached and the 18-month RFS and OS rates are 71% and 72%, respectively. In the relapsed/refractory cohort, the CR/CRi rate was 27%; nine additional patients (41%) achieved a morphologic leukemia–free state. The most common grade 3 or higher nonhematologic adverse events were infection (62%) and febrile neutropenia (38%), which were more frequent in the relapsed/refractory cohort. CONCLUSION The combination of azacitidine, venetoclax, and gilteritinib resulted in high rates of CR/CRi, deep FLT3 molecular responses, and encouraging survival in newly diagnosed FLT3-mutated AML. Myelosuppression was manageable with mitigative dosing strategies.