tbuckley/cabot-search huggingface dataset:
Evaluation of gecacitinib vs hydroxyurea in patients with intermediate-2 or high-risk myelofibrosis: final analysis results from a randomized phase 3 study
Authors: Yi Zhang, Hu Zhou, Shanshan Suo, Junling Zhuang, Linhua Yang, Aili He, Qingchi Liu, Xin Du, Sujun Gao, Yarong Li, Yan Li, Yuqing Chen, Wen Wu, Huanling Zhu, Guangsheng He, Mei Hong, Qian Jiang, Zhongxing Jiang, Hongmei Jing, Jishi Wang, Na Xu, Lingling Yue, Cuiping Zheng, Zeping Zhou, Chenghao Jin, Xin Li, Lin Liu, Yajing Xu, Dengshu Wu, Feng Zhang, Jin Zhang, Liqing Wu, Hewen Yin, Binhua Lv, Zhijian Xiao, Jie Jin
Journal: Blood Cancer Journal (2024)

To compare the efficacy and safety of gecacitinib (also known as jaktinib) with hydroxyurea (HU) in treating myelofibrosis (MF) patients. In this multicenter, randomized phase 3 trial (ZGJAK016), intermediate- or high-risk primarily JAK inhibitor naïve MF patients were assigned in a 2:1 ratio to receive either gecacitinib (100 mg twice a day, BID) or HU (500 mg BID). The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) from baseline at week 24. Secondary endpoints included the best spleen response rate, the proportion of patients with a ≥50% reduction in total symptom score (TSS50), anemia improvement, and safety profile. At 24 weeks, the SVR35 was reached by 64.8% of patients on gecacitinib (46/71), compared to 26.5% on HU (9/34), P = 0.0002. The best spleen response rates were also superior for gecacitinib at 81.7%, vs 32.4% for HU, P < 0.0001. The TSS50 rates were 62.0% for gecacitinib- and 50% for HU-treated patients. Among non-transfusion-dependent patients with baseline hemoglobin (HGB) ≤ 100 g/L, 31.0% (13/42) in the gecacitinib group showed a ≥20 g/L increase in HGB, compared to 15.0% (3/20) in HU group. The common grade ≥ 3 treatment-emergent adverse events (TEAEs), including anemia (26.8% vs 44.1%), thrombocytopenia (15.5% vs 32.4%), leukopenia (2.8% vs 20.6%), and neutropenia (1.4% vs 20.6%), were less frequent with gecacitinib than HU. Treatment discontinuation due to TEAEs was lower in gecacitinib (7.0%) compared to HU (11.8%). Gecacitinib demonstrates superior efficacy and a more favorable safety profile compared to HU, making it a promising treatment option for managing MF, particularly in patients with anemia (This trial was registered with ClinicalTrials.gov, (NCT04617028)).
LOX‐1‐Based Assembly Layer on Devices Surface to Promote Endothelial Repair and Reduce Complications for In Situ Interventional Plaque
Authors: Sainan Liu, Jinquan Huang, Jiayan Luo, Xiaowa Gao, Siqi Song, Qihao Bian, Yajun Weng, Junying Chen
Journal: Advanced Healthcare Materials (2024)

Rapid endothelialization and functional recovery are considered as promising methods to extend the long-term effectiveness of cardiovascular implant materials. LOX-1 participates in the initiation and development of atherosclerosis and is highly expressed in a variety of cells involved in atherosclerosis, hence it is feasible to accelerate the recovery of endothelial function and inhibit the development of existing plaques by regulating LOX-1. Herein, the surface is modified with Poly I, a LOX-1 inhibitor, using rich amino dendritic macromolecules (PAMAM) as the linker coating, to against the pathological microenvironment. Poly I modified surface resisted endothelial damage caused by oxidative stress through the LOX-1-NADPH signaling pathway and inhibited endothelial inflammation via the LOX-1-NF-κB signaling pathway. It also promoted endothelial cell migration and inhibited platelet adhesion. Moreover, the Poly I modified surface can inhibit oxLDL-induced macrophage foam cell formation and alleviate inflammation by modulating macrophage phenotypes. Poly I modified surface significantly reduced plaque burden after treatment of atherosclerotic model rats, most importantly, it significantly inhibited post-implantation-induced restenosis and thrombosis. In vivo and in vitro evaluations confirmed its safety and therapeutic efficacy against atherosclerosis. Overall, the multifunctional Poly I with pathological microenvironment regulation exhibits potential application value in the surface engineering of cardiovascular devices.
Controllable Self‐Assembly of V═O Metalloradical Complex with Intramolecular Charge Transfer for Enhanced NIR‐II Fluorescence Imaging‐Guided Photothermal Therapy
Authors: Jianshuai Bao, Zengyin Li, Deliang Wang, Jiefei Wang, Guan Huang, Jianlei Qian, Xiaoyan Yang, Peng‐Cheng Duan, Sheng Zhang, Feng Bai, Yong Zhong
Journal: Advanced Healthcare Materials (2024)

Near-infrared second region (NIR-II) fluorescence imaging provides enhanced tissue penetration, achieving efficient NIR-II fluorescence and photoacoustic imaging (PA)-guided photothermal therapy (PTT) all in one material remains a challenging yet promising approach in cancer treatment. Herein, open-shell V═O metalloradical complex (VONc) is self-assembled into VONc nanospheres (VONc NPs). VONc NPs exhibit light absorption from 300 to 1400 nm, fluorescence spectra ranging from 900 to 1400 nm, and a distinct fluorescence signal even at 1550 nm. Moreover, VONc NPs exhibit outstanding photostability and a higher photothermal conversion efficiency of 46.6% than that of closed-shell zinc naphthalocyanine nanorods (ZnNc NRs). V═O centered metalloradical serves as transient electron-withdrawing groups to facilitate charge transfer (CT), introducing additional nonradiative energy dissipation pathways and enhancing efficient heat generation. In vitro experiments of VONc NPs indicate that a highly effective photothermal action causes harm to both mitochondria and lysosomes, resulting in the death of tumor cells, closed-shell ZnNc NPs exhibit almost no cell killing as contrast. In vivo anti-tumor therapy results of VONc NPs demonstrate excellent NIR-II fluorescence imaging-guided PTT against tumors with a favorable biosafety profile. "Centered metalloradical boosting CT" toward open-shell metal complexes provides significant insight for developing single-material integrated nanosystems for diagnostic and therapeutic applications.
How human–AI feedback loops alter human perceptual, emotional and social judgements
Authors: Moshe Glickman, Tali Sharot
Journal: Nature Human Behaviour (2024)

Abstract Artificial intelligence (AI) technologies are rapidly advancing, enhancing human capabilities across various fields spanning from finance to medicine. Despite their numerous advantages, AI systems can exhibit biased judgements in domains ranging from perception to emotion. Here, in a series of experiments ( n = 1,401 participants), we reveal a feedback loop where human–AI interactions alter processes underlying human perceptual, emotional and social judgements, subsequently amplifying biases in humans. This amplification is significantly greater than that observed in interactions between humans, due to both the tendency of AI systems to amplify biases and the way humans perceive AI systems. Participants are often unaware of the extent of the AI’s influence, rendering them more susceptible to it. These findings uncover a mechanism wherein AI systems amplify biases, which are further internalized by humans, triggering a snowball effect where small errors in judgement escalate into much larger ones.
A single-cell mass cytometry-based atlas of the developing mouse brain
Authors: Amy L. Van Deusen, Sushanth Kumar, O. Yipkin Calhan, Sarah M. Goggin, Jiachen Shi, Corey M. Williams, Austin B. Keeler, Kristen I. Fread, Irene C. Gadani, Christopher D. Deppmann, Eli R. Zunder
Journal: Nature Neuroscience (2024)
Blastic Plasmocytoid Dendritic Cell Neoplasm With Pseudo‐Lymphoid Morphology Mimicking Lymphoid Malignancy
Authors: Romain Ravel‐Chapuis, Gérard Buchonnet, Catherine Boutet, Francine Garnache Ottou, Anne Roggy, Florian Renosi, Olivier Matray, Victor Bobée
Journal: American Journal of Hematology (2024)

A 60-year-old male presented with spontaneous hematomas and cervical adenopathy. Laboratory workup revealed hemoglobin 12.3 g/dL, platelet 56 × 109/L, and leukocyte 14.7 × 109/L. The automated cell counter (Sysmex XN) reported 9% neutrophils (1.32 × 109/L) and 86% lymphocytes (12.6 × 109/L), suggestive of a lymphoproliferative disorder. Blood smear showed atypical lymphoid cells with normal size, mature chromatin, and scant cytoplasm Figure 1 (Panel A), while numerous lysed cells were also observed (Panel B). About 10% of these cells displayed cytoplasmic vacuoles, occasionally coalescing, and 10% appeared larger with grayish cytoplasm (Panel C and D). Due to the apparent lymphocytosis, flow cytometry immunophenotyping was performed (Navios EX, Beckman-Coulter). Surprisingly, 62% of the leukocytes consisted of a CD45+low blastic population. These cells were negative for common lymphoid (CD19/CD20/CD22/CD24/cCD79a/CD3/CD5/CD8/CD10) and myeloid antigens (CD34/CD38/CD13/CD14/CD42b/CD61/CD64/CD65/CD117/cMPO), but were positive for CD4(weak)/CD56/CD123(strong)/HLA-DR(strong)/CD33 (Panel E and F). A cutaneous lesion was found on the patient's back, and bone marrow aspiration confirmed 82% of the same population with additional phenotypic markers indicative of pDC lineage (CD303+weak/CD304+/cTCL1+/BadLamp+), supporting the diagnosis of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). The neurological examination was normal, and cerebrospinal involvement was inconclusive due to hemorrhagic cerebrospinal fluid samples. Furthermore, the mutational profile performed on bone marrow aspirate was consistent with BPDCN, revealing mutations in TET2, ASXL1, and NF1, as well as a subclonal NRAS mutation and deletions in the IKZF1 and ETV6 loci. BPDCN is a rare hematologic malignancy, with diverse morphological presentations. While the classic blastic morphology, often exhibiting "pearl necklace" cytoplasmic appearances and "hand-mirror-like" projections, is the most common presentation, this case displayed an unusual morphology dominated by pseudo-lymphoid cells. Although a subset of pseudo-lymphoid cells is commonly observed in BPDCN, this case was remarkable in that nearly all cells exhibited this distinctive morphology. Such atypical presentation can be deceptive, initially mimicking lymphoid malignancies. Here, the immunophenotypic profile was crucial in establishing the accurate diagnosis. R.R.-C.: analyzed date and wrote the paper. O.B., G.B., C.B., F.G.O., A.R., and F.R.: analyzed data. V.B.: coordinated the study, wrote the paper and supervised analysis. All data has been anonymized to ensure confidentiality and privacy. The authors declare no conflicts of interest.
Association between body mass index and clinical outcomes in patients with acute myocardial infarction and reduced systolic function: Analysis of <scp>PARADISE</scp>‐<scp>MI</scp> trial data
Authors: Offer Amir, Gabby Elbaz‐Greener, Shemy Carasso, Brian Claggett, Olga Barbarash, Azfar Zaman, Christina Christersson, Songsak Kiatchoosakun, John Anonuevo, Grzegorz Opolski, Mody F. Vaghaiwalla, Peter van der Meer, Yinong Zhou, Douglas L. Mann, Lars Kober, Gabriel Steg, Karola Jering, Ian Kulac, Carmine G. De Pasquale, John J.V. McMurray, Marc A. Pfeffer
Journal: European Journal of Heart Failure (2024)

The relationship between body mass index (BMI) and clinical outcomes in patients with cardiovascular disease, including acute heart failure (AHF) and acute myocardial infarction (AMI), remains debated. This study investigates the association between BMI and clinical outcomes within the PARADISE-MI cohort, while also evaluating the impact of angiotensin receptor-neprilysin inhibitor (ARNI) versus angiotensin-converting enzyme inhibitor (ACE-I) treatment on this relationship.
Follistatin From hiPSC-Cardiomyocytes Promotes Myocyte Proliferation in Pigs With Postinfarction LV Remodeling
Authors: Yuhua Wei, Gregory Walcott, Thanh Nguyen, Xiaoxiao Geng, Bijay Guragain, Hanyu Zhang, Akazha Green, Manuel Rosa-Garrido, Jack M. Rogers, Daniel J. Garry, Lei Ye, Jianyi Zhang
Journal: Circulation Research (2024)

BACKGROUND: When human induced pluripotent stem cells (hiPSCs) that CCND2-OE (overexpressed cyclin-D2) were differentiated into cardiomyocytes ( CCND2-OE hiPSC-CMs) and administered to the infarcted hearts of immunodeficient mice, the cells proliferated after administration and repopulated &gt;50% of the scar. Here, we knocked out human leukocyte antigen class I and class II expression in CCND2-OE hiPSC-CMs ( KO/OE hiPSC-CMs) to reduce the cells’ immunogenicity and then assessed the therapeutic efficacy of KO/OE hiPSC-CMs for the treatment of myocardial infarction. METHODS: KO/OE hiPSC-CM and wild-type hiPSC-CM ( WT hiPSC-CM) spheroids were differentiated in shaking flasks, purified, characterized, and intramyocardially injected into pigs after ischemia/reperfusion injury; control animals were injected with basal medium. Cardiac function was evaluated via cardiac magnetic resonance imaging, and cardiomyocyte proliferation was assessed via immunostaining and single-nucleus RNA sequencing. RESULTS: Measurements of cardiac function and scar size were significantly better in pigs treated with KO/OE hiPSC-CM spheroids than in animals treated with medium or WT hiPSC-CM spheroids. KO/OE hiPSC-CMs were detected for just 1 week after administration, but assessments of cell cycle activity and proliferation were significantly higher in the endogenous pig cardiomyocytes of the hearts from the KO/OE hiPSC-CM spheroid group than in those from the other 2 groups. Single-nucleus RNA-sequencing analysis identified a cluster of proliferating cardiomyocytes that was significantly more prevalent in the KO/OE hiPSC-CM spheroid–treated hearts (3.65%) than in the hearts from the medium (0.89%) or WT hiPSC-CM spheroid (1.33%) groups at week 1. YAP (Yes-associated protein) protein levels and nuclear localization were also significantly upregulated in pig cardiomyocytes after treatment with KO/OE hiPSC-CM spheroids. Follistatin, which interacts with the HIPPO/YAP pathway, was significantly more abundant in the medium from KO/OE hiPSC-CM spheroids than WT hiPSC-CM spheroids (30.29±2.39 versus 16.62±0.83 ng/mL, P =0.0056). Treatment with follistatin increased WT hiPSC-CM cell counts by 28.3% over 16 days in culture and promoted cardiomyocyte proliferation in the infarcted hearts of adult mice. CONCLUSIONS: KO/OE hiPSC-CM spheroids significantly improved cardiac function and reduced infarct size in pig hearts after ischemia/reperfusion injury by secreting follistatin, which upregulated HIPPO/YAP signaling and proliferation in endogenous pig cardiomyocytes.
ACKR1 <sup>hi</sup> ECs Promote Aortic Dissection Through Adjusting Macrophage Behavior
Authors: Yayu Wang, Xiong Jia, Yifei Zhang, Bin Zhang, Yazhe Zhou, Xiaoru Li, Xiaoying Zhu, Jinquan Xia, Jun Ren, Chang Zou, Qijun Zheng
Journal: Circulation Research (2024)

BACKGROUND: Type A aortic dissection (TAAD) is a life-threatening condition characterized by complex pathophysiology, in which macrophages play a critical but not yet fully understood role. This study focused on the role of endothelial cells with elevated expression of ACKR1 (atypical chemokine receptor 1) and their interaction with proinflammatory macrophages in TAAD development. METHODS AND RESULTS: Single-cell transcriptomic analysis of human aortic tissues revealed increased populations of endothelial cells exhibiting high ACKR1 expression and proinflammatory macrophages in TAAD samples. Both clinical and animal studies revealed that ACKR1 expression levels were strongly linked to TAAD severity. Gain- and loss-of-function studies demonstrated that ACKR1 promotes TAAD progression. Specific knockdown of ACKR1 in endothelial cells suppressed the NF-κB (nuclear factor-κB) signaling pathway and SPP1 (secreted phosphoprotein 1) expression, leading to reduced macrophage migration and proinflammatory polarization, which subsequently inhibited TAAD development. Conversely, ACKR1 overexpression accelerated TAAD progression. Notably, molecular docking and comprehensive evaluation identified amikacin as a potential novel modulator of ACKR1. Extensive in vitro and in vivo studies demonstrated that amikacin can regulate macrophage behavior through the ACKR1/NF-κB/SPP1 signaling pathway, thereby attenuating TAAD progression and improving survival rates in TAAD mice. CONCLUSIONS: This study reveals how endothelial cells exhibiting high ACKR1 expression modulate macrophage migration and proinflammatory polarization through the ACKR1/NF-κB/SPP1 signaling pathway, a crucial mechanism in TAAD progression. Targeting ACKR1 through both functional and pharmacological approaches effectively suppressed TAAD progression and extended survival in TAAD mice, offering promising new intervention strategies for clinical evaluation.
Breast implant silicone exposure induces immunogenic response and autoimmune markers in human periprosthetic tissue
Authors: Isabelle Pluvy, Eve Randrianaridera, Ismail Tahmaz, Martine Melin, Florelle Gindraux, Céline Keime, Arnaud Ponche, Tatiana Petithory, Laurent Pieuchot, Karine Anselme, Isabelle Brigaud
Journal: Biomaterials (2024)
Short-term effects of home-based pulmonary rehabilitation during outpatient-managed exacerbations of COPD: a randomised controlled trial
Authors: Ana Machado, Cíntia Dias, Cátia Paixão, António Pedro Gonçalves, Chris Burtin, Alda Marques
Journal: Thorax (2024)

Uncertainty exists about the beneficial effects of delivering pulmonary rehabilitation (PR) during exacerbations of chronic obstructive pulmonary disease (ECOPD). This study explored the short-term effects and self-reported impact of a home-based PR programme for people with outpatient-managed ECOPD.
Obstructive sleep apnoea syndrome and future risk of dementia among individuals managed in UK general practice
Authors: Jingya Wang, Anuradhaa Subramanian, Neil Cockburn, Jingyi Xiao, Krishnarajah Nirantharakumar, Shamil Haroon
Journal: Thorax (2024)

Background Obstructive sleep apnoea syndrome (OSAS) has been recognised as a potential risk factor for cognitive decline, yet its precise relationship with dementia remains uncertain. This study aimed to determine the risk of dementia among individuals with and without OSAS. Methods Data derived from 2.3 million adults (aged ≥18 years) were extracted from the Clinical Practice Research Datalink (2000–2022), a nationally representative primary care electronic health records database in the UK. 193 600 individuals with OSAS were propensity score-matched to 536 701 individuals without OSAS. Cox proportional hazard regression models were applied to quantify the risk of developing all-cause dementia, vascular dementia and Alzheimer’s disease between individuals with and without OSAS. Results With a median follow-up of 4.0 (IQR 1.8–7.5) years, 2802 and 6211 individuals developed all-cause dementia in those with and without OSAS, corresponding to crude incidence rates of 2.47 and 2.34 per 1000 person-years, respectively. The presence of OSAS was associated with higher risks of all-cause dementia (adjusted HR (aHR) 1.12, 95% CI 1.07 to 1.17), vascular dementia (1.29, 95% CI 1.19 to 1.41) and unchanged risk of Alzheimer’s disease (1.07, 95% CI 0.99 to 1.16). Individuals with OSAS who had received continuous positive airway pressure (CPAP) treatment exhibited a similar risk of all-cause dementia as their matched counterparts (0.99, 95% CI 0.74 to 1.32). Conclusion OSAS is associated with higher risks of all-cause dementia and some of its subtypes. Further investigation is needed to investigate the clinical benefits of screening for cognitive impairment in people with OSAS and to further evaluate the impact of CPAP on cognitive decline and dementia risk.
Hospitalised older adults with community-acquired pneumonia and sepsis have dysregulated neutrophil function but preserved glycolysis
Authors: Frances Grudzinska, Aduragbemi A Faniyi, Kylie B R Belchamber, Celine Chen, Robert Stockley, Alice Jasper, Dhruv Parekh, Elizabeth Sapey, Aaron Scott, David R Thickett
Journal: Thorax (2024)

Objective Community-acquired pneumonia (CAP) is a leading cause of hospitalisation in older adults and is associated with a high likelihood of adverse outcomes. Given the ageing population and lack of therapeutic advances in CAP, new strategies to manage the burden of this disease are needed. Neutrophil dysfunction has been widely demonstrated in CAP and is associated with poor outcomes. We hypothesised that impaired glycolytic metabolism was driving neutrophil dysfunction in older adults with CAP. Methods To investigate the mechanism underlying neutrophil dysfunction in CAP, we recruited older adults with CAP and sepsis, age-matched controls and healthy young adults to assess neutrophil function and glycolytic metabolism in peripheral blood neutrophils. Results We demonstrate that neutrophils from older donors with CAP display a broad range of functional defects, including inaccurate migration to interleukin 8, impaired respiratory burst in response to phorbol 12-myristate 13-acetate and increased spontaneous degranulation compared with age-matched controls. Glycolysis (assessed by extracellular flux and RNA-sequencing) was not significantly altered between age-matched groups; however, basal rates of neutrophil glycolysis were significantly higher in patients with CAP and older adult controls compared with healthy young adults, and stimulated glycolysis was significantly higher in young adults compared with older adults with and without CAP. Conclusions Our findings suggest that neutrophil dysfunction in older adults with CAP may be implicated in poor outcomes, irrespective of glycolytic metabolism.
Diameter thresholds for pure ground-glass pulmonary nodules at low-dose CT screening: Chinese experience
Authors: Wenjun Ye, Wenhai Fu, Caichen Li, Jianfu Li, Shan Xiong, Bo Cheng, Bin Xu, Qixia Wang, Yi Feng, Peiling Chen, Jianxing He, Wenhua Liang
Journal: Thorax (2024)

Limited research exists on screening thresholds for low-dose CT in detecting malignant pure ground-glass lung nodules (pGGNs) in the Chinese population. A retrospective analysis of the Guangzhou Lung-Care programme was conducted, retrieving average transverse diameter, location, histopathology, frequency and follow-up intervals. Diagnostic performances for 'lung cancers' were evaluated using areas under the curve (AUCs), decision curve analysis (DCA), sensitivities and specificities, with thresholds ranging from 5 mm to 10 mm. We divide malignant pGGNs into three groups: (1) minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA), (2) atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) and MIA and IA and (3) IA-only. In 'MIA+IA', increasing the threshold from 5 mm to 8 mm improved specificity (60.97% to 88.85%, p<0.001) and positive predictive values (PPVs; 5.87% to 14.88%, p<0.001), but decreased sensitivity (94.44% to 75.56%, p<0.001). Further raising threshold from 8 mm reduced sensitivity (75.56% to 60.00%, p<0.001), while slightly increasing specificity (88.85% to 93.47%, p<0.001) and PPVs (14.88% to 19.15%, p<0.001). Increasing threshold from 5 mm to 7 mm enhanced the AUC for 'MIA+IA' (from 0.711 to 0.829), 'AAH+AIS+MIA+IA' (from 0.748 to 0.804) and 'IA-only' (from 0.783 to 0.833). At 8 mm, the AUCs for these categories were similar. However, increasing the threshold from 7 mm to 10 mm resulted in reduced AUCs for 'MIA+IA' (0.829 to 0.767), 'AAH+AIS+MIA+IA' (0.804 to 0.744) and 'IA-only' (0.833 to 0.800). DCA reveals that the 8 mm predictive model demonstrates greater clinical utility compared with models with other thresholds. Increasing the diameter threshold for positive results for pGGNs, up to 8 mm could enhance diagnostic performance. NCT04938804.