tbuckley/cabot-search huggingface dataset:
Characterising the SARS-CoV-2 nucleocapsid (N) protein antibody response
Authors: CCA Noble, E McDonald, S Nicholson, S Biering-Sørensen, LF Pittet, AL Byrne, J Croda, M Dalcolmo, MVG Lacerda, M Lucas, DJ Lynn, C Prat Aymerich, PC Richmond, A Warris, N Curtis, NL Messina
Journal: Journal of Infection (2025)

<h2>Abstract</h2><h3>Objectives</h3> SARS-CoV-2 nucleocapsid (N) protein antibodies can be used to detect the serological response to natural infection in those previously receiving a COVID-19 spike-based vaccine. Anti-N antibody responses can also be detected in those receiving inactivated whole SARS-CoV-2 virus vaccines, such as <i>CoronaVac</i>. We aimed to characterise antibody responses to the N protein following COVID-19 and following vaccination with <i>CoronaVac</i>. <h3>Methods</h3> Using participants from an international randomised controlled trial, we investigated the evolution of anti-N antibody responses over time in two separate groups: following COVID-19, or following vaccination with <i>CoronaVac</i>. <h3>Results</h3> In 212 participants who had COVID-19, the anti-N seroconversion rate was 96.9% in those infected following an incomplete course of COVID-19 (spike-based) vaccinations and 88.2% in those fully vaccinated. Anti-N antibody indices were highly variable between participants, and higher in participants who had more severe COVID-19 symptoms, were aged ≥60 years, were unvaccinated, had comorbidities and those resident in Brazil. Most participants remained seropositive after 12 months. In 317 separate participants, the anti-N seroconversion rate was 63.5% following <i>CoronaVac</i> vaccination, with variable antibody indices. <h3>Conclusions</h3> Anti-N responses to COVID-19 and <i>CoronaVac</i> are highly variable but persistent. A prior complete COVID-19 spike-based vaccination course reduced both anti-N seroconversion and antibody indices following COVID-19.
Identifying strategies for disseminating research to patients with chronic kidney disease and caregivers: a workshop report
Authors: Anastasia Hughes, Nicole Scholes-Robertson, Dale Coghlan, Rebecca Wu, Noa Amir, Hayley Candler, Brydee Cashmore, Yeoungjee Cho, Jonathan C Craig, Rosanna Cazzolli, Feruza Kholmurodova, Chandana Guha, Carmel M Hawley, Amandi Hiyare, Martin Howell, Shilpanjali Jesudason, David W Johnson, Dominic Keuskamp, Karine Manera, Jasmin Mazis, Stephen McDonald, Shyamsundar Muthuramalingam, Javier Recabarren Silva, Amanda Sluiter, Armando Teixeira-Pinto, David J Tunnicliffe, Anita van Zwieten, Pushparaj Velayudham, Andrea K Viecelli, Germaine Wong, Allison Jaure
Journal: Kidney International (2025)
Pathological Findings of Immunotherapy-Induced Nephrotoxicity in a Humanized Immune System Mouse Model
Authors: Sarah Asby, Lauren E Thompson, Michael Goedken, Scott M Lucia, Adrian T Dominguez, Adwitiya Kar, Todd M Pitts, Katja Kiseljak-Vassiliades, Julie Lang, Lauren M Aleksunes, Melanie S Joy
Journal: Kidney International (2025)
Supracortical Microstimulation: Advances in Microelectrode Design and In Vivo Validation
Authors: Cecilia Schmitz, J. Evan Smith, Iakov Rachinskiy, Bijan Pesaran, Flavia Vitale, Marc Sommer, Jonathan Viventi
Journal: Annual Review of Biomedical Engineering (2025)

Electrical stimulation of the brain is being developed as a treatment for an increasing number of neurological disorders. Technologies for delivering electrical stimulation are advancing rapidly and vary in specificity, coverage, and invasiveness. Supracortical microstimulation (SCMS), characterized by microelectrode contacts placed on the epidural or subdural cortical surface, achieves a balance between the advantages and limitations of other electrical stimulation technologies by delivering spatially precise activation without disrupting the integrity of the cortex. However, in vivo experiments involving SCMS have not been comprehensively summarized. Here, we review the field of SCMS, focusing on recent advances, to guide the development of clinically translatable supracortical microelectrodes. We also highlight the gaps in our understanding of the biophysical effects of this technology. Future work investigating the unique electrochemical properties of supracortical microelectrodes and validating SCMS in nonhuman primate preclinical studies can enable rapid clinical translation of innovative treatments for humans with neurological disorders.
Lessons Learned and Challenges Ahead in the Translation of Implantable Microscale Sensors and Actuators
Authors: Jae Young Park, Nikolas Barrera, Tianyu Bai, Ellis Meng, Hui Fang, Hyowon Lee
Journal: Annual Review of Biomedical Engineering (2025)

Microscale sensors and actuators have been widely explored by the scientific community to augment the functionality of conventional medical implants. However, despite the many innovative concepts proposed, a negligible fraction has successfully made the leap from concept to clinical translation. This shortfall is primarily due to the considerable disparity between academic research prototypes and market-ready products. As such, it is critically important to examine the lessons learned in successful commercialization efforts to inform early-stage translational research efforts. Here, we review the regulatory prerequisites for market approval and provide a comprehensive analysis of commercially available microimplants from a device design perspective. Our objective is to illuminate both the technological advances underlying successfully commercialized devices and the key takeaways from the commercialization process, thereby facilitating a smoother pathway from academic research to clinical impact.
Analysis of Intensive Longitudinal Data: Putting Psychological Processes in Perspective
Authors: E.L. Hamaker
Journal: Annual Review of Clinical Psychology (2025)

Research based on intensive longitudinal data (ILD)—consisting of many repeated measures from one or multiple individuals—is rapidly gaining popularity in psychological science. To appreciate the unique potential of ILD research for clinical psychology, this review begins by examining how our three traditional research approaches fall short when the goal is to investigate processes. It then explores how the analysis of ILD can be used to study a process as it unfolds within a specific person over time but also to study average process features or individual differences therein. By emphasizing the alignment between research questions, data collection, and analytical strategies, the potential of ILD research is further highlighted. It is argued that for future progress it is essential to integrate machine learning and causal inference methods with statistical techniques for ILD and to become more explicit about timescales, time frames, and dynamics in psychological theories.
Post sleeve gastrectomy-enriched gut commensal Clostridia promotes secondary bile acid increase and weight loss
Authors: Shaoqian Zhao, Huibin Lin, Wen Li, Xiaoqiang Xu, Qihan Wu, Zhifeng Wang, Juan Shi, Yufei Chen, Lingxia Ye, Liuqing Xi, Lijia Chen, Mingyang Yuan, Junlei Su, Aibo Gao, Jiabin Jin, Xiayang Ying, Xiaolin Wang, Yaorui Ye, Yingkai Sun, Yifei Zhang, Xiaxing Deng, Baiyong Shen, Weiqiong Gu, Guang Ning, Weiqing Wang, Jie Hong, Jiqiu Wang, Ruixin Liu
Journal: Gut Microbes (2025)

The gut microbiome is altered after bariatric surgery and is associated with weight loss. However, the commensal bacteria involved and the underlying mechanism remain to be determined. We performed shotgun metagenomic sequencing in obese subjects before and longitudinally after sleeve gastrectomy (SG), and found a significant enrichment in microbial species in Clostridia and bile acid metabolizing genes after SG treatment. Bile acid profiling further revealed decreased primary bile acids (PBAs) and increased conjugated secondary bile acids (C-SBAs) after SG. Specifically, glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) were increased at different follow-ups after SG, and were associated with the increased abundance of Clostridia and body weight reduction. Fecal microbiome transplantation with post-SG feces increased SBA levels, and alleviated body weight gain in the recipient mice. Furthermore, both Clostridia-enriched spore-forming bacteria and GDCA supplementation increased the expression of genes responsible for lipolysis and fatty acid oxidation in adipose tissue and reduced adiposity via Takeda G-protein-coupled receptor 5 (TGR5) signaling. Our findings reveal post-SG gut microbiome and C-SBAs as contributory to SG-induced weight loss, in part via TGR5 signaling, and suggest SBA-producing gut microbes as a potential therapeutic target for obesity intervention.
Pembrolizumab hybrid dosing is non-inferior to flat dosing in advanced non-small cell lung cancer: a real-world, retrospective bicenter cohort study
Authors: Michiel M Smeenk, Vincent van der Noort, Jeroen M A Hendrikx, Hanieh Abedian Kalkhoran, Egbert F Smit, Willemijn S M E Theelen
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but come with high costs. Alternative ICI dosing strategies could reduce costs without losing efficacy. However, clinical efficacy data are lacking. Methods In this retrospective cohort trial, consecutive patients with advanced non-small cell lung cancer (NSCLC) who received ≥1 cycle pembrolizumab±chemotherapy at two tertiary institutions were included. Hybrid dosed patients received either 100, 150 or 200 mg pembrolizumab every 3 weeks or double every 6 weeks depending on their weight: &lt;65 kg, 65–90 kg or &gt;90 kg, respectively. Standard-of-care flat dosed patients received 200 mg every 3 weeks or 400 mg every 6 weeks. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier estimation, compared by log-rank test and HRs were calculated with the Cox proportional hazards model in both unweighted and inverse probability of treatment weighted (IPTW) cohorts. Non-inferiority margin was set at an HR of 1.15. Results In total, 375 patients and 391 patients were included and median follow-up was 43.1 and 61.0 months in the hybrid and flat dose cohort, respectively. OS was non-inferior in the hybrid dose cohort compared with the flat dose cohort: median 17.7 months (95% CI 14.9 to 20.9) vs 11.8 months (95% CI 9.3 to 13.8, HR 0.76, 95% CI 0.65 to 0.90, p&lt;0.0001 for non-inferiority). After correcting for confounders by IPTW, OS remained non-inferior (HR 0.76, 95% CI 0.63 to 0.91, p&lt;0.0001 for non-inferiority). PFS in the hybrid cohort was also non-inferior to the flat dose cohort with a median of 6.4 months (95% CI 5.7 to 7.7) vs 4.6 months (95% CI 3.9 to 5.5, HR 0.82, 95% CI 0.70 to 0.96, p&lt;0.0001 for non-inferiority). In total, 26.2% (or 52.5 mg per cycle, p&lt;0.0001) pembrolizumab was saved in the hybrid dose cohort accounting to US$36 331.36 per patient. Conclusions In this retrospective analysis of a large cohort of advanced NSCLC patients treated with pembrolizumab±chemotherapy, OS of hybrid dosed patients was non-inferior to flat dosed patients. OS remained non-inferior after correcting for possible confounding factors. This hybrid regimen resulted in significant savings of pembrolizumab and costs.
Phase I study of efineptakin alfa (NT-I7) for the treatment of Kaposi sarcoma
Authors: Ramya Ramaswami, Angela Shaulov Kask, Leonard D’Amico, Manoj P Menon, Kathryn Lurain, Robert Yarchoan, Irene Ekwede, Paul Couey, Eli Burnham, Allysson Angeldekao, Byung Ha Lee, Judith C Kaiser, Martin Cheever, Thomas S Uldrick, Li-Lian Kwok, Anna Wright, Steven P Fling, Chia-Ching Jackie Wang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background CD4 + T-cell lymphocytopenia and immune dysfunction are factors that drive the onset and persistence of Kaposi sarcoma (KS) in people with (PWH) and without HIV. Standard chemotherapy agents for KS can contribute to increasing CD4 + T cell lymphocytopenia. IL-7 is a cytokine that is essential in T-cell development, proliferation and homeostasis. In PWH, IL-7 administration leads to increased numbers of circulating central memory and naïve T-cell phenotypes. Methods In this multicenter phase I study with a 3+3 dose escalation design, participants with KS with or without HIV received up to four intramuscular injections of IL-7 (NT-I7) every 9 weeks. The primary endpoint of the study was to evaluate safety over three escalating dose levels (DL) of NT-I7 (DL1:480 µg/kg, DL2: 960 µg/kg and DL3: 1200 µg/kg) and identify a maximum tolerated dose. Secondary endpoints included evaluation of antitumor activity per the modified AIDS Clinical Trials Group Criteria and assessment of the effect of NT-I7 on the kinetics of CD4 + and CD8 + T-cells. Results Eight cisgender male participants (five with HIV infection) were enrolled. Six participants were treated at DL1, and two were treated at DL2. The study was closed to accrual after enrolment of the second participant on DL2 due to termination of study funding. Four of the eight participants (three in DL1 and one in DL2) completed all four doses of the NT-I7. With regard to treatment-emergent adverse events (AEs), all participants had &lt;grade 2 AEs, which included injection site reaction and alanine aminotransferase increase. Injection site reaction was a dose-limiting toxicity in one participant at DL1. The overall KS objective response rate to NT-I7 was 42.9% (95% CI 9.9%, 81.6%) and all three responders were PWH. Absolute lymphocyte counts, CD4 + and CD8 + T-cell counts increased among all participants following administration of NT-I7. Participants who experienced a response had HIV and lower CD4/CD8 ratio at baseline and throughout the study as compared with those who did not have KS response to NT-I7. Conclusions Preliminary data demonstrate safety and activity of IL-7 in patients with KS and activity specifically among individuals HIV-associated KS. Trial registration number NCT04893018 .
Complete metabolic response as early predictor of long-term efficacy after adoptive T cell therapy using tumor-infiltrating lymphocytes
Authors: Troels Holz Borch, Rikke Andersen, Helle Westergren Hendel, Kasper Madsen, Eva Ellebaek, Inge Marie Svane
Journal: Journal for ImmunoTherapy of Cancer (2025)

Introduction: Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has proved to be an effective treatment for metastatic melanoma, even in patients failing anti-PD-1 blockade. Nevertheless, progression is observed in a substantial subgroup of patients following an initial objective response to treatment with TILs. These patients might benefit from additional consolidating treatment before clinical progression, but thus far, it is not possible to identify this subgroup of patients prone to progress. In this study the predictive value of early metabolic response after TIL therapy is explored. Materials and methods: 60 patients treated with TIL therapy in 4 different clinical trials and with available [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography-CT (FDG-PET/CT) scans at baseline and at least one follow-up scan 6–8 weeks and/or 12–16 weeks post-TIL infusion were included. Results: Obtaining complete metabolic response (CMR) was associated with significantly superior median overall survival (mOS) compared with not obtaining CMR (p&lt;0.0001). Of particular interest, metabolic response divided RECIST partial responders (22 patients) into two groups with significantly different clinical outcomes. Neither mOS (range 32.2–149.8+) nor median progression-free survival (mPFS; range 20.7–123.4+) were reached for patients with partial response (PR)/CMR (10 patients), whereas patients with PR/non-CMR (12 patients) had a mOS of 28.7 months (p=0.0016) and a mPFS of 7.8 months (p&lt;0.0001). Overall, not achieving a CMR was associated with a short mPFS of 3.2 months, and 97.9% (47/48) of all patients in this group progressed within 12 months. Conclusion: In conclusion, early CMR is a strong predictor of long-term survival after TIL therapy in metastatic melanoma patients. Furthermore, FDG-PET/CT scans appear superior to CT scans for providing early prognostic information after TIL therapy in melanoma and can be used to tailor patient-specific management and follow-up strategies.
Targeting IL-33 in patients with cancer under immune checkpoint inhibitors for a better antitumor response and prevent thromboembolism?
Authors: Gianluca Azzellino, Lia Ginaldi, Massimo De Martinis
Journal: Journal for ImmunoTherapy of Cancer (2025)

We read with great interest the article by Nan et al on the possibility of targeting interleukin (IL)-33 to obtain an improved antitumor response to anti-programmed death-ligand 1 (PD-L1) immunotherapy, recently published in the Journal. The authors demonstrate how by blocking both IL-33 and PD-L1
Refining α-synuclein seed amplification assays to distinguish Parkinson’s disease from multiple system atrophy
Authors: James A. Wiseman, Clinton P. Turner, Richard L. M. Faull, Glenda M. Halliday, Birger Victor Dieriks
Journal: Translational Neurodegeneration (2025)

Abstract Background Parkinson’s disease (PD) and multiple system atrophy (MSA) are two distinct α-synucleinopathies traditionally differentiated through clinical symptoms. Early diagnosis of MSA is problematic, and seed amplification assays (SAAs), such as real-time quaking-induced conversion (RT-QuIC), offer the potential to distinguish these diseases through their underlying α-synuclein (α-Syn) pathology and proteoforms. Currently, SAAs provide a binary result, signifying either the presence or absence of α-Syn seeds. To enhance the diagnostic potential and biological relevance of these assays, there is a pressing need to incorporate quantification and stratification of α-Syn proteoform-specific aggregation kinetics into current SAA pipelines. Methods Optimal RT-QuIC assay conditions for α-Syn seeds extracted from PD and MSA patient brains were determined, and assay kinetics were assessed for α-Syn seeds from different pathologically relevant brain regions (medulla, substantia nigra, hippocampus, middle temporal gyrus, and cerebellum). The conformational profiles of disease- and region-specific α-Syn proteoforms were determined by subjecting the amplified reaction products to concentration-dependent proteolytic digestion with proteinase K. Results Using our protocol, PD and MSA could be accurately delineated using proteoform-specific aggregation kinetics, including α-Syn aggregation rate, maximum relative fluorescence, the gradient of amplification, and core protofilament size. MSA cases yielded significantly higher values than PD cases across all four kinetic parameters in brain tissues, with the MSA-cerebellar phenotype having higher maximum relative fluorescence than the MSA-Parkinsonian phenotype. Statistical significance was maintained when the data were analysed regionally and when all regions were grouped. Conclusions Our RT-QuIC protocol and analysis pipeline can distinguish between PD and MSA, and between MSA phenotypes. MSA α-Syn seeds induce faster propagation and exhibit higher aggregation kinetics than PD α-Syn, mirroring the biological differences observed in brain tissue. With further validation of these quantitative parameters, we propose that SAAs could advance from a yes/no diagnostic to a theranostic biomarker that could be utilised in developing therapeutics.
GULP1 as a Novel Diagnostic and Predictive Biomarker in Hepatocellular Carcinoma
Authors: Hyung Seok Kim, Jung Hwan Yoon, Ji Yi Choi, Moon Gyeong Yoon, Geum Ok Baek, Minji Kang, Se Ha Jang, Won Park, Yunjin Go, Jestlin Tianthing Ng, Suk Woo Nam, Jee-Yeong Jeong, Ji Eun Han, Hyo Jung Cho, Su Bin Lim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
Journal: Clinical and Molecular Hepatology (2025)

Hepatocellular carcinoma (HCC) is characterized by high recurrence and mortality, necessitating the identification of reliable biomarkers. In this study, we aimed to identify the predictive gene signatures for HCC recurrence and evaluate the efficiency of GULP PTB domain-containing engulfment adaptor 1 (GULP1) as a predictive and diagnostic marker and therapeutic target for HCC. We analyzed genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases via least absolute shrinkage and selection operator Cox regression and 10-fold cross-validation, leading to the development of a 15-gene risk score model, which was validated using three independent datasets. Serum GULP1 and α-fetoprotein levels were assessed to determine the diagnostic accuracy of the model. Using clinical cohorts and patient sera, GULP1 roles were examined, and functional assays in vitro and in vivo were used to evaluate its effects on cell growth, epithelial-mesenchymal transition (EMT), ADP-ribosylation factor 6 activation, and β-catenin signaling. Our newly developed risk-score model accurately predicted recurrent HCC in all datasets. Among the 15 genes in the risk score model, GULP1 was overexpressed in patients with HCC and independently predicted HCC recurrence. Its expression modulation influenced cell growth and EMT, with observed effects on ADP-ribosylation factor 6 activation and β-catenin signaling pathways. GULP1 is a crucial biomarker for HCC, serving as a non-invasive diagnostic and predictive tool. It also plays key roles in HCC progression. Our findings highlight the potential use of GULP1 in treatment strategies targeting EMT and HCC recurrence to improve the personalized care and patient outcomes.
Fructose-induced progression of steatohepatitis involves disrupting aldolase B-AMPK signaling in methionine adenosyltransferase 1A deficient mice
Authors: Lucía Barbier-Torres, María Luque-Urbano, Jyoti Chhimwal, Aaron E. Robinson, David Fernández-Ramos, Fernando Lopitz-Otsoa, Jennifer E. Van Eyk, Oscar Millet, José M. Mato, Shelly C. Lu
Journal: Metabolism (2025)
Beyond Doomsday Fears: Why We Need to Consider the Potential Harms of AI Psychotherapy
Authors: Şerife Tekin, Megan Delehanty
Journal: The American Journal of Bioethics (2025)

There is increased enthusiasm about the use of Artificial Intelligence (AI) technologies in psychotherapy. Notably, AI psychotherapy chatbots are increasing in popularity, especially since the US Food and Drug Administration (FDA) gave one of these apps breakthrough device designation. This article raises concerns about the lack of consideration of potential harms of this technology for clinical trial participants, and current and future users. We outline what these harms might be, by turning to the Belmont Report and the existing literature on harms of (typical) psychotherapy and conclude with two recommendations. Note that our goal is not to articulate doomsday fears regarding the use of AI in psychotherapy contexts; rather we offer a constructive proposal in thinking about the potential harms of these tools and invite clinicians, patients, developers, researchers, policymakers and funding agencies to work together to augment the benefits of these tools and minimize their potential harms.
Abortion and Embodiment
Authors: Laura Hermer
Journal: The American Journal of Bioethics (2025)

Each of us is embodied. Our relationships are reinforced and swayed by physiological processes. States that impose unwanted childbirth on women also force them into unwanted bonds of care. While most people who have given birth understand this because they experienced it, this formative experience is alien to cisgender men. Yet the physiological changes that birthing people undergo are points that few commentators on abortion raise. There are several possible reasons for this, including concerns about reifying biological processes that have been used to assert alleged truths about the "natural" role of women in society and culture. I discuss the physiological underpinnings of maternal/neonate bonds, the importance of this issue in the abortion debate, and the role it ought to play, while keeping in mind the valid critiques of historical and current appeals to biology as a means of subjugating women socially and culturally.