tbuckley/cabot-search huggingface dataset:
Cercus electric stimulation enables cockroach with trajectory control and spatial cognition training
Authors: Li Yu, Jieliang Zhao, Yufan Song, Zhiyun Ma, Zhong Liu, Lulu Liang, Mengdi Xu, Wenzhong Wang, Shaoze Yan
Journal: Cyborg and Bionic Systems (2024)

Cyborg insects are highly adaptable for detection and recognition assignments, achieved through the electrical stimulation of multiple organs and nerves to control their locomotion. However, it remains unclear whether these control strategies can promote memory formation in insects, thereby facilitating their training for recognition assignments. In this study, we employed a steering control strategy for cyborg insects in operant learning training of cockroaches in a T-maze. Remarkably, cockroaches developed a preference for specific maze channels after only five consecutive sessions of unilateral cercus electrical stimulation and steering behavior induction, achieving a memory score of 83.5%, outperforming traditional punishing training schemes. The experimental results confirmed the effectiveness of electrical stimulation on the cercus in improving the spatial cognition of cockroaches by inducing them to make specific choices in the maze. Our study revealed that the artificial locomotion control strategy can not only prompt insects to execute predetermined locomotion but also facilitate the formation of preferential memory for specific trajectories. Overall, our study highlights the electrical stimulation of sensory organs as a robust and efficient training protocol for spatial recognition learning in insects.
Association between socioeconomic deprivation, ethnicity and health outcomes in preschool children with recurrent wheeze in England: a retrospective cohort study
Authors: David Lo, Claire Lawson, Clare Gillies, Sharmin Shabnam, Erol A Gaillard, Hilary Pinnock, Jennifer K Quint
Journal: Thorax (2024)

Preschool-aged children have among the highest burden of acute wheeze. We investigated differences in healthcare use, treatment and outcomes for recurrent wheeze/asthma in preschoolers from different ethno-socioeconomic backgrounds.
Olokizumab plus methotrexate: safety and efficacy over 106 weeks of treatment
Authors: Eugen Feist, Roy M Fleischmann, Saeed Fatenejad, Daria Bukhanova, Sergey Grishin, Sofia Kuzkina, Michael Luggen, Evgeniy Nasonov, Mikhail Samsonov, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2024)

Objective To report long-term safety and tolerability of olokizumab (OKZ) in combination with methotrexate (MTX) in subjects with active rheumatoid arthritis (RA), using pooled data from three randomised clinical trials (RCT) followed by open-label extension (OLE) study. Methods Cumulative data from three phase 3 core trials and their OLE were analysed. Safety variables assessed included treatment-emergent adverse events (AEs), serious AEs (SAEs), AEs of special interest and laboratory results. Efficacy assessments included ACR20/50/70 responses, Disease Activity Score 28 (C-reactive protein) &lt;3.2, CDAI remission and low disease activity (LDA), SDAI remission and LDA, HAQ-DI decrease of 0.22 unit and Boolean 2.0 remission. Results A total of 2304 patients received OKZ in combination with MTX either once every 2 weeks or once every 4 weeks. Event rates per 100 patient-years in OKZ every 2 weeks and OKZ every 4 weeks, respectively, were 9.57 and 9.13 for SAEs; 2.95 and 2.34 for serious infections; 0.09 and 0.05 for gastrointestinal perforations; 0.58 and 0.83 for major adverse cardiovascular events; and 0.45 and 0.50 for malignancies. No increase in the rate of any AE was observed over 106 weeks of treatment. The evaluation of laboratory variables demonstrated the expected changes, like neutropenia, elevation of liver enzymes and blood lipids. Clinical response rates remained stable during the OLE. Conclusion The long-term safety and tolerability of OKZ in combination with MTX remained stable. The efficacy of OKZ was maintained through week 106. These findings support OKZ as a treatment option for patients with active RA.
Nephrology Clinical Trials in Learning Health Systems
Authors: Michael G. Collins, Carmel M. Hawley, Stephen P. McDonald
Journal: Journal of the American Society of Nephrology (2024)

1Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, SA, Australia 2Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia 3Australasian Kidney Trials Network, Centre for Health Services Research, University of Queensland, Brisbane, QLD, Australia 4Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, QLD, Australia 5Translational Research Institute, Brisbane, QLD, Australia 6Australia and New Zealand Dialysis and Transplant Registry, South Australia Health and Medical Research Institute, Adelaide, SA, Australia *Correspondence: Dr Michael G Collins, Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000, Australia [email protected]
Inhibiting the NADase CD38 improves cytomegalovirus-specific CD8+ T cell functionality and metabolism
Authors: Nils Mülling, Felix M. Behr, Graham A. Heieis, Kristina Boss, Suzanne van Duikeren, Floortje J. van Haften, Iris N. Pardieck, Esmé T.I. van der Gracht, Ward Vleeshouwers, Tetje C. van der Sluis, J. Fréderique de Graaf, Dominique M.B. Veerkamp, Kees L.M.C. Franken, Xin Lei, Lukas van de Sand, Sjoerd H. van der Burg, Marij J.P. Welters, Sebastiaan Heidt, Wesley Huisman, Simon P. Jochems, Martin Giera, Oliver Witzke, Aiko P.J. de Vries, Andreas Kribben, Bart Everts, Benjamin Wilde, Ramon Arens
Journal: Journal of Clinical Investigation (2024)

Cytomegalovirus (CMV) is one of the most common and relevant opportunistic pathogens in people who are immunocompromised, such as kidney transplant recipients (KTRs). The exact mechanisms underlying the disability of cytotoxic T cells to provide sufficient protection against CMV in people who are immunosuppressed have not been identified yet. Here, we performed in-depth metabolic profiling of CMV-specific CD8+ T cells in patients who are immunocompromised and show the development of metabolic dysregulation at the transcriptional, protein, and functional level of CMV-specific CD8+ T cells in KTRs with noncontrolled CMV infection. These dysregulations comprise impaired glycolysis and increased mitochondrial stress, which is associated with an intensified expression of the nicotinamide adenine dinucleotide nucleotidase (NADase) CD38. Inhibiting NADase activity of CD38 reinvigorated the metabolism and improved cytokine production of CMV-specific CD8+ T cells. These findings were corroborated in a mouse model of CMV infection under conditions of immunosuppression. Thus, dysregulated metabolic states of CD8+ T cells could be targeted by inhibiting CD38 to reverse hyporesponsiveness in individuals who fail to control chronic viral infection.
A Multicenter Real-life Prospective Study of Axicabtagene Ciloleucel versus Tisagenlecleucel Toxicity and Outcomes in Large B-cell Lymphomas
Authors: Federico Stella, Annalisa Chiappella, Beatrice Casadei, Stefania Bramanti, Silva Ljevar, Patrizia Chiusolo, Alice Di Rocco, Maria C. Tisi, Matteo G. Carrabba, Ilaria Cutini, Massimo Martino, Anna Dodero, Francesca Bonifazi, Armando Santoro, Federica Sorà, Barbara Botto, Anna M. Barbui, Domenico Russo, Maurizio Musso, Giovanni Grillo, Mauro Krampera, Jacopo Olivieri, Marco Ladetto, Federica Cavallo, Massimo Massaia, Luca Arcaini, Martina Pennisi, Pier L. Zinzani, Rosalba Miceli, Paolo Corradini
Journal: Blood Cancer Discovery (2024)

This real-world prospective observational study across 21 Italian centers (CART-SIE) compares axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) outcomes in 485 patients with relapsed/refractory large B-cell lymphoma with baseline characteristics matched by stabilized inverse propensity score weighting. Axi-cel versus tisa-cel had higher all-grade cytokine release syndrome (78.6% vs. 89.3%, P = 0.0017) and neurotoxicity (9.9% vs. 32.2%, P < 0.0001) but also superior progression-free survival (PFS) at 1 year (46.5% vs. 34.1%, P = 0.0009). Even among patients who failed bridging therapy, axi-cel PFS was superior to tisa-cel (37.5% vs. 22.7%, P = 0.0059). Differences in overall survival and high-grade immune toxicities were not significant. The CAR-HEMATOTOX score not only predicted hematologic toxicity but also 1-year survival outcomes (51.5% in CAR-HEMATOTOX high vs. 77.2% in CAR-HEMATOTOX low, P < 0.0001). Twenty patients developed second primary malignancies, including two cases of T-cell neoplasms. These findings enable more informed selection of anti-CD19 CAR T-cell therapy, balancing bridging, safety, and efficacy considerations for individual patients. Significance: The findings of this study on 485 patients with relapsed/refractory large B-cell lymphoma treated with commercial axi-cel and tisa-cel indicate axi-cel's superior PFS after propensity score weighting. The predictive utility of CAR-HEMATOTOX in assessing not only toxicity but also outcomes across both CAR T-cell products may guide future risk-stratified management strategies.
Bifunctional Black Phosphorus Quantum Dots Platform: Delivery and Remarkable Immunotherapy Enhancement of STING Agonist
Authors: Yujun Zhang, Shijing Wang, Hyeonji Rha, Chang Xu, Yue Pei, Xiaoyuan Ji, Junmin Zhang, Ruitao Lu, Shaochong Zhang, Zhongjian Xie, Jong Seung Kim
Journal: Biomaterials (2024)
Publisher Correction: Oncolytic adenoviral therapy plus pembrolizumab in BCG-unresponsive non-muscle-invasive bladder cancer: the phase 2 CORE-001 trial
Authors: Roger Li, Paras H Shah, Tyler F Stewart, Jong Kil Nam, Trinity J Bivalacqua, Donald L Lamm, Edward M Uchio, Daniel M Geynisman, Joseph M Jacob, Joshua J Meeks, Rian Dickstein, Shane M Pearce, Seok Ho Kang, Seung Il Jung, Ashish M Kamat, James M Burke, Kirk A Keegan, Gary D Steinberg
Journal: Nature Medicine (2024)
Leveraging altered lipid metabolism in treating B cell malignancies
Authors: Jaewoong Lee, Arya Mani, Min-Jeong Shin, Ronald M. Krauss
Journal: Progress in Lipid Research (2024)

B cell malignancies, comprising over 80 heterogeneous blood cancers, pose significant prognostic challenges due to intricate oncogenic signaling. Emerging evidence emphasizes the pivotal role of disrupted lipid metabolism in the development of these malignancies. Variations in lipid species, such as phospholipids, cholesterol, sphingolipids, and fatty acids, are widespread across B cell malignancies, contributing to uncontrolled cell proliferation and survival. Phospholipids play a crucial role in initial signaling cascades leading to B cell activation and malignant transformation through constitutive B cell receptor (BCR) signaling. Dysregulated cholesterol and sphingolipid homeostasis support lipid raft integrity, crucial for propagating oncogenic signals. Sphingolipids impact malignant B cell stemness, proliferation, and survival, while glycosphingolipids in lipid rafts modulate BCR activation. Additionally, cancer cells enhance fatty acid-related processes to meet heightened metabolic demands. In obese individuals, the obesity-derived lipids and adipokines surrounding adipocytes rewire lipid metabolism in malignant B cells, evading cytotoxic therapies. Genetic drivers such as MYC translocations also intrinsically alter lipid metabolism in malignant B cells. In summary, intrinsic and extrinsic factors converge to reprogram lipid metabolism, fostering aggressive phenotypes in B cell malignancies. Therefore, targeting altered lipid metabolism has translational potential for improving risk stratification and clinical management of diverse B cell malignancy subtypes.
Potentiation of BKCa channels by cystic fibrosis transmembrane conductance regulator (CFTR) correctors VX-445 and VX-121
Authors: Aaron Kolski-Andreaco, Stefanie Taiclet, Michael M. Myerburg, John Sembrat, Robert J. Bridges, Adam C. Straub, Zachary P. Wills, Michael B. Butterworth, Daniel C. Devor
Journal: Journal of Clinical Investigation (2024)

Cystic fibrosis (CF) results from mutations in the CFTR anion channel, ultimately leading to diminished transepithelial anion secretion and mucociliary clearance. CFTR correctors are therapeutics that restore the folding/trafficking of mutated CFTR to the plasma membrane. The BKCa potassium channel is also critical for maintaining lung ASL volume. Here, we show the CFTR corrector, VX-445 (Elexacaftor), a component of Trikafta, induces K+ secretion across WT and F508del CFTR primary human bronchial epithelial cells (HBEs), which was entirely inhibited by the BKCa antagonist paxilline. Similar results were observed with VX-121 – a corrector under clinical evaluation. Whole-cell patch-clamp recordings confirmed potentiated channel activity from CFTR correctors on the BKCa α-subunit, and excised patch-clamp recordings demonstrated a significant increase in open probability. In mesenteric artery, VX-445 induced a paxilline-sensitive vasorelaxation of preconstricted arteries. VX-445 also reduced action potential firing frequency in primary hippocampal and cortical neurons. VX-445 effects were observed at low micomolar concentrations (1-10 µM) – within the range reported in plasma and tissues from CF patients. We raise the possibilities that CFTR correctors gain additional clinical benefit by activation of BKCa in the lung, yet may lead to adverse events through BKCa activation, elsewhere.
Inflammation primes the murine kidney for recovery by activating AZIN1 adenosine-to-inosine editing
Authors: Segewkal Hawaze Heruye, Jered Myslinski, Chao Zeng, Amy Zollman, Shinichi Makino, Azuma Nanamatsu, Quoseena Mir, Sarath Chandra Janga, Emma H. Doud, Michael T. Eadon, Bernhard Maier, Michiaki Hamada, Tuan M. Tran, Pierre C. Dagher, Takashi Hato
Journal: Journal of Clinical Investigation (2024)

The progression of kidney disease varies among individuals, but a general methodology to quantify disease timelines is lacking. Particularly challenging is the task of determining the potential for recovery from acute kidney injury following various insults. Here, we report that quantitation of post-transcriptional adenosine-to-inosine (A-to-I) RNA editing offers a distinct genome-wide signature, enabling the delineation of disease trajectories in the kidney. A well-defined murine model of endotoxemia permitted the identification of the origin and extent of A-to-I editing, along with temporally discrete signatures of double-stranded RNA stress and adenosine deaminase isoform switching. We found that A-to-I editing of antizyme inhibitor 1 (AZIN1), a positive regulator of polyamine biosynthesis, serves as a particularly useful temporal landmark during endotoxemia. Our data indicate that AZIN1 A-to-I editing, triggered by preceding inflammation, primes the kidney and activates endogenous recovery mechanisms. By comparing genetically modified human cell lines and mice locked in either A-to-I-edited or uneditable states, we uncovered that AZIN1 A-to-I editing not only enhances polyamine biosynthesis but also engages glycolysis and nicotinamide biosynthesis to drive the recovery phenotype. Our findings implicate that quantifying AZIN1 A-to-I editing could potentially identify individuals who have transitioned to an endogenous recovery phase. This phase would reflect their past inflammation and indicate their potential for future recovery.
Author Correction: Meta-reinforcement learning via orbitofrontal cortex
Authors: Ryoma Hattori, Nathan G. Hedrick, Anant Jain, Shuqi Chen, Hanjia You, Mariko Hattori, Jun-Hyeok Choi, Byung Kook Lim, Ryohei Yasuda, Takaki Komiyama
Journal: Nature Neuroscience (2024)

for ORC imaging and recording, "~2.45 mm lateral and ~2.6 mm anterior from bregma", which has now been amended to read "~1.45 mm lateral and ~2.6 mm anterior from bregma" in the HTML and PDF versions of the article.
Race and Ethnicity, Socioeconomic Factors, and Epigenetic Age Acceleration in Survivors of Childhood Cancer
Authors: Cheng Chen, Noel-Marie Plonski, Qian Dong, Nan Song, Xijun Zhang, Hemang M. Parikh, Emily R. Finch, John Easton, Heather L. Mulder, Emily Walker, Geoffrey Neale, Yue Pan, Qian Li, Jinghui Zhang, Kevin Krull, Leslie L. Robison, Gregory T. Armstrong, Yutaka Yasui, Kirsten K. Ness, Melissa M. Hudson, Hui Wang, I-Chan Huang, Zhaoming Wang
Journal: JAMA Network Open (2024)

Current research in epigenetic age acceleration (EAA) is limited to non-Hispanic White individuals. It is imperative to improve inclusivity by considering racial and ethnic minorities in EAA research.
Dulaglutide and Glomerular Hyperfiltration, Proteinuria, and Albuminuria in Youth With Type 2 Diabetes: Post Hoc Analysis of the AWARD-PEDS Study
Authors: Petter Bjornstad, Silva A. Arslanian, Tamara S. Hannon, Philip S. Zeitler, Jennie L. Francis, Alexandra M. Curtis, Ibrahim Turfanda, David A. Cox
Journal: Diabetes Care (2024)

To examine changes in glomerular hyperfiltration and other measures of kidney function in youth with type 2 diabetes treated with dulaglutide or placebo.
In-Hospital Delirium and Disability and Cognitive Impairment After COVID-19 Hospitalization
Authors: Ramya Kaushik, Gail J. McAvay, Terrence E. Murphy, Denise Acampora, Katy Araujo, Peter Charpentier, Sumon Chattopadhyay, Mary Geda, Thomas M. Gill, Tamar A. Kaminski, Seohyuk Lee, Judy Li, Andrew B. Cohen, Alexandra M. Hajduk, Lauren E. Ferrante
Journal: JAMA Network Open (2024)

Importance Older adults who are hospitalized for COVID-19 are at risk of delirium. Little is known about the association of in-hospital delirium with functional and cognitive outcomes among older adults who have survived a COVID-19 hospitalization. Objective To evaluate the association of delirium with functional disability and cognitive impairment over the 6 months after discharge among older adults hospitalized with COVID-19. Design, Setting, and Participants This prospective cohort study involved patients aged 60 years or older who were hospitalized with COVID-19 between June 18, 2020, and June 30, 2021, at 5 hospitals in a major tertiary care system in the US. Follow-up occurred through January 11, 2022. Data analysis was performed from December 2022 to February 2024. Exposure Delirium during the COVID-19 hospitalization was assessed using the Chart-based Delirium Identification Instrument (CHART-DEL) and CHART-DEL-ICU. Main Outcomes and Measures Primary outcomes were disability in 15 functional activities and the presence of cognitive impairment (defined as Montreal Cognitive Assessment score &amp;amp;lt;22) at 1, 3, and 6 months after hospital discharge. The associations of in-hospital delirium with functional disability and cognitive impairment were evaluated using zero-inflated negative binominal and logistic regression models, respectively, with adjustment for age, month of follow-up, and baseline (before COVID-19) measures of the respective outcome. Results The cohort included 311 older adults (mean [SD] age, 71.3 [8.5] years; 163 female [52.4%]) who survived COVID-19 hospitalization. In the functional disability sample of 311 participants, 49 participants (15.8%) experienced in-hospital delirium. In the cognition sample of 271 participants, 31 (11.4%) experienced in-hospital delirium. In-hospital delirium was associated with both increased functional disability (rate ratio, 1.32; 95% CI, 1.05-1.66) and increased cognitive impairment (odds ratio, 2.48; 95% CI, 1.38-4.82) over the 6 months after discharge from the COVID-19 hospitalization. Conclusions and Relevance In this cohort study of 311 hospitalized older adults with COVID-19, in-hospital delirium was associated with increased functional disability and cognitive impairment over the 6 months following discharge. Older survivors of a COVID-19 hospitalization who experience in-hospital delirium should be assessed for disability and cognitive impairment during postdischarge follow-up.
Short-latency preference for faces in primate superior colliculus depends on visual cortex
Authors: Gongchen Yu, Leor N. Katz, Christian Quaia, Adam Messinger, Richard J. Krauzlis
Journal: Neuron (2024)

Face processing is fundamental to primates and has been extensively studied in higher-order visual cortex. Here, we report that visual neurons in the midbrain superior colliculus (SC) of macaque monkeys display a preference for images of faces. This preference emerges within 40 ms of stimulus onset—well before "face patches" in visual cortex—and, at the population level, can be used to distinguish faces from other visual objects with accuracies of ∼80%. This short-latency face preference in SC depends on signals routed through early visual cortex because inactivating the lateral geniculate nucleus, the key relay from retina to cortex, virtually eliminates visual responses in SC, including face-related activity. These results reveal an unexpected circuit in the primate visual system for rapidly detecting faces in the periphery, complementing the higher-order areas needed for recognizing individual faces.
Protection from environmental enteric dysfunction and growth improvement in malnourished newborns by amplification of secretory IgA
Authors: Lisa Perruzza, Tanja Rezzonico Jost, Matteo Raneri, Giorgio Gargari, Martina Palatella, Benedetta De Ponte Conti, Frauke Seehusen, Julia Heckmann, Dorothee Viemann, Simone Guglielmetti, Fabio Grassi
Journal: Cell Reports Medicine (2024)

Environmental enteric dysfunction (EED) is a condition associated with malnutrition that can progress to malabsorption and villous atrophy. Severe EED results in linear growth stunting, slowed neurocognitive development, and unresponsiveness to oral vaccines. Prenatal exposure to malnutrition and breast feeding by malnourished mothers replicates EED. Pups are characterized by deprivation of secretory IgA (SIgA) and altered development of the gut immune system and microbiota. Extracellular ATP (eATP) released by microbiota limits T follicular helper (Tfh) cell activity and SIgA generation in Peyer's patches (PPs). Administration of a live biotherapeutic releasing the ATP-degrading enzyme apyrase to malnourished pups restores SIgA levels and ameliorates stunted growth. SIgA is instrumental in improving the growth and intestinal immune competence of mice while they are continuously fed a malnourished diet. The analysis of microbiota composition suggests that amplification of endogenous SIgA may exert a dominant function in correcting malnourishment dysbiosis and its consequences on host organisms, irrespective of the actual microbial ecology.