tbuckley/cabot-search huggingface dataset:
Piezo1, F-actin Remodeling, and Podocyte Survival and Regeneration
Authors: Maria Elena Melica, Giulia Antonelli, Roberto Semeraro, Gilda La Regina, Tommaso Dafichi, Camilla Fantini, Giulia Carangelo, Giuseppina Comito, Carolina Conte, Laura Maggi, Samuela Landini, Valentina Raglianti, Maria Lucia Angelotti, Alice Molli, Daniela Buonvicino, Letizia De Chiara, Elena Lazzeri, Benedetta Mazzinghi, Anna Julie Peired, Paola Romagnani, Laura Lasagni
Journal: Journal of the American Society of Nephrology (2025)

Podocytes and podocyte progenitors are interdependent components of the kidney's glomerular structure, with podocytes forming the glomerular filtration barrier and progenitors being key players in podocyte regeneration during pathophysiological processes. Both cell types are subjected to constant mechanical forces, whose alterations can initiate podocytopathy and worsen glomerular injury. Despite this, the specific mechanosensors and mechanotransduction pathways involved in their response to mechanical cues remain only partially explored. We used transcriptomics, immunofluorescence, and silencing experiments on human primary podocyte progenitor cell cultures to demonstrate the expression and function of Piezo1 channels. We generated inducible podocyte- and podocyte progenitor-specific Piezo1 knockout mice to evaluate the effects of Piezo1 loss in the context of Adriamycin nephropathy and over 10 months of aging. Silencing of Piezo1 in progenitors triggered F-actin remodelling, induced cell shape modification and nuclear envelope defects with accumulation of DNA damage that led to mitotic catastrophe in differentiated podocytes. Podocyte-specific knockout of Piezo1 induced higher susceptibility to podocyte injury in Adriamycin nephropathy and led to accumulation of DNA damage and mild albuminuria starting from adult age. Podocyte progenitor-specific knockout of Piezo1 in mouse resulted in severe albuminuria during Adriamycin nephropathy, leading to the generation of defective podocytes. These results demonstrated that Piezo1, thanks to its role in F-actin cytoskeleton maintenance, is essential for the survival of podocytes exposed to mechanical stress conditions and for their correct regeneration.
Esketamine Combined With SSRI or SNRI for Treatment-Resistant Depression
Authors: Antonio Del Casale, Sara Spirito, Jan Francesco Arena, Saskia Preissner, Marina Borro, Giovanna Gentile, Martina Nicole Modesti, Robert Preissner, Stefano Ferracuti, Maurizio Simmaco
Journal: JAMA Psychiatry (2025)

Treatment-resistant depression (TRD) remains a critical challenge in psychiatry, with limited effective options. Esketamine, a rapid-acting antidepressant, is usually combined with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), but comparative evidence of these combinations' effectiveness in real-world settings is sparse. To determine whether the combination of esketamine + SNRI shows differences in clinical outcomes compared to esketamine + SSRI in patients with TRD. This retrospective cohort study was conducted in September 2024 using data from the TriNetX global health research network, with a 5-year time window from the first esketamine trial. TriNetX data are drawn from real-world clinical settings and use electronic medical records from more than 90 health care centers across 20 countries. Adults with TRD who were treated with esketamine combined with either an SSRI or an SNRI were eligible for inclusion. Treatment with esketamine combined with an SSRI (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, or vilazodone) or an SNRI (desvenlafaxine, duloxetine, levomilnacipran, milnacipran, or venlafaxine). The primary outcomes were all-cause mortality, hospitalization, depression relapse, and suicide attempts. Kaplan-Meier survival analysis was used to estimate survival probabilities, while risk ratios and odds ratios were calculated for all outcomes. In a population-based sample of 61 882 adult participants with TRD who were treated with esketamine combined with either an SSRI or an SNRI, 55 480 participants were selected after applying propensity score matching for age and sex. These patients were divided into 2 matched cohorts: 27 740 patients treated with esketamine + SSRI (16 007 female participants [57.7%]; mean [SD] age, 46.0 [21.3] years) and 27 740 treated with esketamine + SNRI (16 242 female participants [58.6%]; mean [SD] age, 45.9 [21.9] years). In the entire study population, the incidence of mortality, hospitalizations, depressive relapses, and suicide attempts was low throughout the study period. Patients in the esketamine + SNRI group had significantly lower all-cause mortality (5.3% vs 9.1%; P < .001), hospitalization rates (0.1% vs 0.2%; P < .001), and depression relapses (14.8% vs 21.2%; P < .001) compared to the esketamine + SSRI group, which instead showed a lower incidence of suicidal attempts (0.3% vs 0.5%; P = .04). In this retrospective comparative effectiveness study, among the study sample, incidence of mortality, hospitalizations, depressive relapses, and suicide attempts was low. The esketamine + SNRI group showed lower incidence of mortality, hospitalizations, and depressive relapses, while the esketamine + SSRI group showed a slightly lower incidence of suicidal attempts.
Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation
Authors: Muhammad Tufail, Can-Hua Jiang, Ning Li
Journal: Molecular Cancer (2025)

The Wnt signaling pathway plays a crucial role in development and tissue homeostasis, regulating key cellular processes such as proliferation, differentiation, and apoptosis. However, its abnormal activation is strongly associated with tumorigenesis, metastasis, and resistance to therapy, making it a vital target for cancer treatment. This review provides a comprehensive insight into the role of Wnt signaling in cancer, examining its normal physiological functions, dysregulation in malignancies, and therapeutic potential. We emphasize the importance of predicting Wnt signaling sensitivity and identify key biomarkers across various cancer types. Additionally, we address the challenges and future prospects of Wnt-targeted therapies, including biomarker discovery, advancements in emerging technologies, and their application in clinical practice.
Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways
Authors: Bowei Liu, Zhigang Peng, Hao Zhang, Nan Zhang, Zaoqu Liu, Zhiwei Xia, Shaorong Huang, Peng Luo, Quan Cheng
Journal: Molecular Cancer (2025)

Cellular senescence, a stable state of cell cycle arrest induced by various stressors or genomic damage, is recognized as a hallmark of cancer. It exerts a context-dependent dual role in cancer initiation and progression, functioning as a tumor suppressor and promoter. The complexity of senescence in cancer arises from its mechanistic diversity, potential reversibility, and heterogeneity. A key mediator of these effects is the senescence-associated secretory phenotype (SASP), a repertoire of bioactive molecules that influence tumor microenvironment (TME) remodeling, modulate cancer cell behavior, and contribute to therapeutic resistance. Given its intricate role in cancer biology, senescence presents both challenges and opportunities for therapeutic intervention. Strategies targeting senescence pathways, including senescence-inducing therapies and senolytic approaches, offer promising avenues for cancer treatment. This review provides a comprehensive analysis of the regulatory mechanisms governing cellular senescence in tumors. We also discuss emerging strategies to modulate senescence, highlighting novel therapeutic opportunities. A deeper understanding of these processes is essential for developing precision therapies and improving clinical outcomes.
Accountable Care Organization Participation and Cardiovascular Care Quality
Authors: Erica S. Spatz, D. August Oddleifson, Jehanzeb Kayani, Kensey L. Gosch, Philip G. Jones, Rushabh H. Doshi, Thomas M. Maddox, Nihar R. Desai
Journal: JAMA Cardiology (2025)

The Medicare Shared Savings Program (MSSP) was introduced in 2012 to improve care quality and lower costs to Medicare. Under this program, accountable care organizations (ACOs) assumed responsibility for costs and care quality for a group of Medicare beneficiaries. To compare changes in quality measures for patients at outpatient cardiology practices before and after their participation in a Medicare Shared Savings Program ACO. This pre-post cohort study comparing quality prior to and after ACO participation evaluated the MSSP at 83 ACO outpatient cardiology practices compared with 332 non-ACO-participating cardiology practices, adjusted for secular trends, using 15 performance measures in the National Cardiovascular Data Registry PINNACLE (Practice Innovation and Clinical Excellence) Registry from January 1, 2013, through March 31, 2019. Data analysis was performed from 2022 to 2025. Outpatient cardiology practice participation in the MSSP, which allows ACOs to share in the savings if predetermined cost targets are met, with payments adjusted based on a quality performance score. Primary end points included 15 quality measures for coronary artery disease, heart failure, atrial fibrillation, and hypertension. During the study period, 2 390 244 patients (1 273 615 [53.3%] female; mean [SD] age, 58.5 [17.7] years) were cared for by 83 ACO practices, and 5 415 880 patients (2 810 204 [51.9%] female; mean [SD] age, 61.5 [16.3] years) were cared for by 332 non-ACO practices. Outpatient cardiology practice participation in an MSSP ACO was not associated with differential changes in various performance measures for coronary artery disease, heart failure, atrial fibrillation, and hypertension. There were no differential changes in the odds of β-blocker prescription, blood pressure control, antiplatelet prescription, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) prescription, low-density lipoprotein (LDL) profiles, or smoking cessation for coronary artery disease; left ventricular assessment, β-blocker prescription, ACEI or ARB prescription, or implantable cardioverter defibrillator use for heart failure; anticoagulation for atrial fibrillation; or blood pressure control for hypertension. Exploratory analyses extending follow-up to 24 months revealed an increase in β-blocker use for heart failure (adjusted odds ratio [aOR], 1.23; 95% CI, 1.02-1.49; P = .03) and a decline in LDL profiles less than 100 mg/dL (to convert to millimoles per liter, multiply by 0.0259; aOR, 0.71; 95% CI, 0.51-0.999; P = .049). Among a subset of traditional Medicare patients, there was an increase in implantable cardioverter defibrillator use by 12 months (aOR, 1.66; 95% CI, 1.12-2.45; P = .01) following ACO participation. Participation in an MSSP ACO was not found to be associated with early improvement in quality measures at outpatient cardiology practices.
European guidelines for the management of tuberculosis screening procedures in migrants: A systematic review
Authors: Marina Pinheiro, Carolina Valente, Margarida Cruz, David Nascimento Moreira, Ana Aguiar, Raquel Duarte
Journal: Pulmonology (2025)

This systematic review assesses the current available evidence across the WHO European region on the effectiveness and cost-effectiveness of the different approaches used for TB screening and also explores the facilitators and barriers that migrants face during screening programmes. We conducted an extensive, comprehensive, and systematic literature search across multiple databases, including MEDLINE, Cochrane, Scopus, and ISI Web of Knowledge, without any restrictions on publication date or language. In addition, we reviewed grey literature and reports. The data were meticulously analysed with a focus on screening of TB active disease and infection effectiveness indicators, and cost-effectiveness economic analyses as a primary objective and the comprehension of barriers and facilitators of screening as a secondary objective. Our review included 43 studies covering over 8 million migrants from 11 countries. The findings demonstrate that while screening uptake was high, coverage varied, and completion rates for preventive treatments were low. Economic analyses supported the high cost-effectiveness of the screening programmes, particularly when integrating both active TB and TBI screening strategies. This review underscores the cost-effectiveness and public health importance of TB screening in migrant populations within Europe. However, the disparities in screening practices highlight the urgent need for standardisation at the European level.
Assessment of Cutaneous and Mucosal Direct Immunofluorescence Testing Practices in the US
Authors: Julia S. Lehman, Anthony P. Fernandez, Kristin M. Leiferman, Nooshin K. Brinster, Donna A. Culton, Randie H. Kim, Jeffrey P. North, Benjamin K. Stoff, Michael J. Camilleri, Margaret M. Cocks, Rosalie Elenitsas, Maxwell A. Fung, Raminder K. Grover, Jaroslaw J. Jedrych, Melanie K. Kuechle, Jennifer M. McNiff, Ata S. Moshiri, Kiran Motaparthi, Michael J. Murphy, Carlos H. Nousari, Sara C. Shalin, John J. Zone, Alina G. Bridges
Journal: JAMA Dermatology (2025)

Direct immunofluorescence (DIF) testing has been an important ancillary tool for the diagnosis of various inflammatory mucocutaneous conditions for more than 50 years. Current DIF test panels are based on historical clinical descriptions; few studies have rigorously addressed preanalytical, analytical, and/or postanalytical aspects, and even fewer have been replicated or validated. Recent unresolved key issues include whether DIF testing and test panels should be triaged or truncated based on clinical indication or histopathologic findings. To assess levels of consensus regarding practical aspects of DIF testing among immunodermatology testing specialists in the US. Using modified Delphi methods with a priori characterized criteria, a survey containing 54 statements pertaining to DIF testing was created and distributed to assess consensus. Statements not initially reaching consensus were discussed in 2 live virtual sessions, which were supplemented by relevant literature review and free-text survey comments. These statements were then reassessed in a second survey. Immunodermatology testing specialists in US academic institution-based and independent laboratories were invited based on serving as immunodermatology laboratory medical directors, authoring pertinent literature, or delivering relevant talks at major conferences or by referral. The first survey was conducted from January to February 2024, and the second survey was conducted from March to April 2024. The primary measured outcome was degree of consensus for various DIF testing practice, including DIF testing triage by histopathology/dermatopathology findings and DIF testing panel tailored truncations by clinical indication. A total of 23 respondents to the survey invitation had a mean (SD) of 18.5 (11.1) years and median (range) of 20.0 (1.5-46.0) years in immunodermatology laboratory practice. Consensus was achieved for 46 of 54 statements (85.2%) in the initial survey and for an additional 4 statements in the second survey (50 of 54 [92.6%]). Strong consensus was found against tailored truncation of DIF panel based on the clinical indication in the first survey round. The general acceptability of triaging specimens for DIF testing based on histopathology findings remained without consensus after both surveys. Overall, participating US specialists in immunodermatology laboratory testing agreed on many practical aspects of DIF testing, including matters not queried previously. The findings also revealed areas of continued controversy and identified issues for prioritized future study.
Quality of life associated with breathlessness in the multinational Burden of Obstructive Lung Disease (BOLD) study: A cross-sectional analysis
Authors: Alexander Müller, Emiel F M Wouters, Peter Burney, James Potts, Joao Cardoso, Mohammed Al Ghobain, Michael Studnicka, Daniel Obaseki, Asma Elsony, Kevin Mortimer, David Mannino, Rain Jõgi, Rana Ahmed, Asaad Nafees, Maria Fatima Rodrigues, Cristina Bárbara, Rune Nielsen, Thorarinn Gíslason, Hamid Hacene Cherkaski, Karima El Rhazi, Christer Janson, Mahesh Padukudru Anand, Sanjay Juvekar, Herminia Brites Dias, Frits M E Franssen, Dhiraj Agarwal, Sylvia Hartl, Terence Seemungal, Stefanni Nonna Paraguas, Imed Harrabi, Meriam Denguezli, Abdul Rashid, Gregory Erhabor, Mohammed El Biaze, Parvaiz Koul, Daisy J A Janssen, André F S Amaral
Journal: Pulmonology (2025)

Evidence of an association between breathlessness and quality of life from population-based studies is limited. We aimed to investigate the association of both physical and mental quality of life with breathlessness across several low-, middle- and high-income countries. We analysed data from 19 714 adults (31 sites, 25 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We measured both mental and physical quality of life components using the SF-12 questionnaire, and defined breathlessness as grade ≥2 on the modified Medical Research Council scale. We used multivariable linear regression to assess the association of each quality-of-life component with breathlessness. We pooled site-specific estimates using random-effects meta-analysis. Both physical and mental component scores were lower in participants with breathlessness compared to those without. This association was stronger for the physical component (coefficient = -7.59; 95%CI -8.60, -6.58; I2 = 78.5%) than for the mental component (coefficient = -3.50; 95%CI -4.36, -2.63; I2 = 71.4%). The association between physical component and breathlessness was stronger in high-income countries (coefficient = -8.82; 95%CI -10.15, -7.50). Heterogeneity across sites was partly explained by sex and tobacco smoking. Quality of life is worse in people with breathlessness, but this association varies widely across the world.
Psychometric Validation and Interpretation Thresholds of the Hidradenitis Suppurativa Quality of Life (HiSQOL©) Questionnaire Using Pooled Data from the Phase 3 BE HEARD I &amp; II Trials of Bimekizumab in Hidradenitis Suppurativa
Authors: Joslyn S Kirby, Linnea Thorlacius, Jérémy Lambert, Valerie Ciaravino, Robert Rolleri, Ingrid Pansar, Edward Muller, Christopher G Pelligra, John R Ingram
Journal: British Journal of Dermatology (2025)

The Hidradenitis Suppurativa Quality of Life questionnaire (HiSQOL©) was developed to assess HS-specific changes in health-related quality of life. Here, the psychometric properties of HiSQOL total and domain scores are evaluated and interpretation thresholds to guide score interpretation are determined. In these analyses, the HiSQOL subscale and total scores demonstrated robust psychometric properties, supporting its use and that it is fit for purpose in patients with HS.
Cardiac implantable electronic and other monitoring devices in continuous‐flow left ventricular assist device patients. A clinical consensus statement of the Heart Failure Association and the European Heart Rhythm Association of the <scp>ESC</scp>
Authors: Offer Amir, Stamatis Adamopoulos, Haran Burri, Antoni Bayes‐Genis, Christophe Leclercq, Maja Cikes, Anastasia Egorova, Petr Peichl, Marat Fudim, Archana Rao, Finn Gustafsson, Sergio Richter, Matteo Pagnesi, Giuseppe Rosano, Frank Ruschitzka, Jens Cosedis Nielsen
Journal: European Journal of Heart Failure (2025)
Association of Obesity and Innate Immune Markers With Resistance to Biologic Therapy in Psoriasis
Authors: Hee Joo Kim, Eun-Hui Lee, YunJae Jung
Journal: JAMA Dermatology (2025)

Currently available biologics specifically target dermal adaptive immune molecules, such as interleukin (IL)-17 and IL-23, which are crucial in the pathogenesis of psoriasis. Despite their remarkably enhanced therapeutic effects compared with those of traditional anti-inflammatory systemic medications, 25% to 50% of patients are still resistant to biologic therapy. To delineate the inflammatory microenvironmental factors that affect sustained treatment response in patients with severe psoriasis. A cross-sectional study was carried out including patients aged 18 years or older who visited the Gachon University Gil Medical Center dermatology clinic between January 2012 and December 2022 with plaque-type severe psoriasis with a Psoriasis Area and Severity Index score greater than 10 and body surface area larger than 10 despite conventional treatment with cyclosporine, methotrexate, acitretin, and phototherapy for longer than 3 months, and treatment with biologics for at least 24 months. Analysis was carried out from December 2023 to September 2024. Clinical and inflammatory factors associated with sustained response to biologics therapy. Among the 87 patients (mean [SD] age, 42.2 [12.5] years; 24 female patients and 63 male patients) included in the study, 16 (18.4%) had to switch to other biologics because of an early loss of therapeutic efficacy. Having overweight (body mass index, >25) was the only clinically relevant factor (odds ratio, 17.3; 95% CI, 3.2-434.6; P = .009). Other factors, including initial disease severity before biologics or disease duration until the first use of biologics, were not different between patients with treatment-resistant disease and those with a sustained treatment response. Spatial transcriptomics pathway analyses revealed enriched innate immune signaling and T-helper 17 cells (Th17)/IL-17 signaling pathways, with upregulated expression of innate immune- or neutrophil-related genes, such as TNFSF10, CXCL8, LCN2, S100A8, and S100A9, mainly in the epidermis. Enriched ligand-receptor interactions were observed in the IL-36 family of cytokines, antimicrobial peptides, and tumor necrosis factor (TNF) signaling. Immunofluorescence analysis showed enhanced protein expression of lipocalin 2, S100A8/A9, IL-36α, IL-36γ, IL-1RA, and TNF-related apoptosis-inducing ligand (TRAIL) in the epidermis. This cross-sectional study found that dysregulated innate immune responses in the epidermis and heightened neutrophil activity may be responsible for decreased sustainability of therapeutic responses to biologics. Given that current biologics mainly target dermal adaptive immune-related mediators, the development of novel therapeutic strategies to target the epidermal innate immune response, including neutrophils, is warranted.
Hydrogel Adhesive Integrated‐Microstructured Electrodes for Cuff‐Free, Less‐Invasive, and Stable Interface for Vagus Nerve Stimulation
Authors: Jae Young Park, Jongcheon Lim, Carl R. Russell, Pei‐Lun Chen, Deniz Eksioglu, Seokkyoon Hong, Juan C. Mesa, Matthew P. Ward, Chi Hwan Lee, Hyowon Lee
Journal: Advanced Healthcare Materials (2025)

Vagus nerve stimulation (VNS) is a recognized treatment for neurological disorders, yet the surgical procedure carries significant risks. During the process of isolating or cuffing the vagus nerve, there is a danger of damaging the nerve itself or the adjacent carotid artery or jugular vein. To minimize this risk, here we introduce a novel hydrogel adhesive-integrated and stretchable microdevice that provides a less invasive, cuff-free option for interfacing with the vagus nerve. The device features a novel hydrogel adhesive formulation that enables crosslinking on biological tissue. The inclusion of kirigami structures within the thin-film microdevice creates space for uniform hydrogel-to-epineurium contact while accommodating the stiffness changes of the hydrogel upon hydration. Using a rodent model, we demonstrate a robust device adhesion on a partially exposed vagus nerve in physiological fluid even without the vagus nerve isolation and cuffing process. Our device elicted stable and clear evoked compound action potential (~1500 µV peak-to-peak) in C-fibers with a current amplitude of 0.4 mA. We believe this innovative platform provides a novel, less-risky approach to interface with fragile nerve and vascular structures during VNS implantation.