tbuckley/cabot-search huggingface dataset:
How Healthy Are the Diets of Cancer Survivors? Characteristics of Those Most at Risk and Opportunities for Improvement
Authors: Harleen Kaur, Maria Pisu, Dori W. Pekmezi, Laura Q. Rogers, Michelle Y. Martin, Kevin R. Fontaine, Kaitlyn J. Waugaman, Wendy Demark-Wahnefried
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: Diet quality and adherence to dietary guidelines are strong predictors of positive cancer outcomes among survivors. Methods: A cross-sectional analysis was conducted using 2-day dietary recalls from a nationwide sample of 818 survivors of 9 obesity-related cancers with ≥70% 5-year survival who expressed interest in a web-based diet and exercise trial. Total diet quality scores and component subscores were generated using the Health Eating Index-2020 (HEI-2020). Subgroup analyses examined differences by cancer diagnosis and treatment, body weight status, and sociodemographic factors. Results: The mean [SD] HEI-2020 score among survivors was 51.6 [12.05] out of 100—approximately 10 points below norms for comparably aged Americans in the general population. Clinically meaningful deficits were observed for intakes of fruits, vegetables, dairy products, and protein (especially from plant and seafood sources). Survivors’ intakes also included excessive amounts of refined grains. Compared with the general population, however, survivors’ intakes more closely aligned with guidelines in terms of higher whole grain intake and lower consumption of sodium, saturated fat, and sugar (including sugar-sweetened beverages). Overall diet quality and/or component scores were significantly lower among younger survivors (age &lt;65 years) and those within 5 years of diagnosis, with obesity (body mass index ≥30 kg/m 2 ), of lower education (high school diploma or less), and residing in areas of higher socioeconomic deprivation (Area Deprivation Index ≥50th percentile) (all P &lt;.05). No significant subgroup differences were detected by cancer type or treatment. Conclusions: Diet quality among survivors of obesity-related cancers is notably suboptimal. Clinicians should leverage survivors’ interest in diet and exercise interventions to provide support and referrals targeting identified areas of need, particularly for those at highest risk, such as individuals with obesity, within 5 years of diagnosis, aged &lt;65 years, with a high school diploma or less, and residing in areas of higher socioeconomic deprivation.
Bridging the evidence gap: expert consensus on management of SARS-CoV-2 acute infection and post-COVID-19 condition in immunocompromised patients
Authors: Lorenzo M Canziani, Antonella d'Arminio Monforte, Maddalena Giannella, Jesús Rodríguez-Baño, Evelina Tacconelli
Journal: Clinical Microbiology and Infection (2025)
Clinical and Biological Remission With Tezepelumab: The Real‐World Response in Severe Uncontrolled Asthma
Authors: Jessica Gates, Faizan Haris, Francesca Cefaloni, Paniz Khooshemehri, Linda Green, Mariana Fernandes, Louise Thomson, Cris Roxas, Jodie Lam, Grainne d'Ancona, Alexandra M. Nanzer, Jaideep Dhariwal, David J. Jackson
Journal: Allergy (2025)

ABSTRACT Introduction Tezepelumab is an anti‐TSLP monoclonal antibody approved for the treatment of severe asthma. It has broad downstream anti‐T2 effects, offering the prospect of biological remission. Real‐world data on clinical remission rates with tezepelumab is lacking, and the relationship between clinical and biological remission is unclear. Finally, the effectiveness of tezepelumab in patients who have failed to respond to existing biologic therapies is unknown. Methods Clinical and biomarker data from adults with severe asthma treated with tezepelumab in a real‐world setting was analyzed. Clinical outcome measures including clinical remission were recorded along with rates of biological remission (defined as blood eosinophil count &lt; 300 cells/mcL and FeNO &lt; 25 ppb). Results One hundred seventy‐five patients were included. 98/175 (56%) had switched from another biologic. Following tezepelumab initiation, the exacerbation rate decreased from 3.1 (2.5) to 0.8 (1.4), with 59% of patients remaining exacerbation‐free at 1 year. 54% achieved an ACQ score &lt; 1.5. Clinical remission at 1 year was observed in 36%, with a rate of 55% in T2‐high patients versus 19% in T2 low patients. The clinical response in biologic‐naïve and biologic switch patients was similar. FeNO declined from 41 ppb (24–76) to 24 ppb (16–38) and BEC fell from 300 cells/μL (60–610) to 180 cells/μL (105–320) (both p &lt; 0.001). 38% achieved biological remission. 15% attained both clinical and biological remission. Conclusion Tezepelumab led to substantial clinical improvements and clinical remission in up to 55% of T2‐high patients with severe asthma. A disconnect between clinical and biological remission was observed. The long‐term significance of residual T2 inflammation on tezepelumab is unknown.
Efficacy and safety of tildrakizumab in patients with early- vs late-onset psoriasis
Authors: April W Armstrong, Andrew Blauvelt, Mark Lebwohl, Akihiko Asahina, Ranga Gogineni, Christopher E M Griffiths
Journal: British Journal of Dermatology (2025)

Abstract Background Age of psoriasis onset is bimodally distributed with distinct peaks at &amp;lt;40 (early onset) and ≥40 years (late onset). Although age of psoriasis onset is associated with distinct disease profiles, few well-controlled studies report efficacy of biologics in patients with early- vs late-onset disease. Efficacy and safety of tildrakizumab, an interleukin-23 p19 inhibitor, for the treatment of moderate-to-severe plaque psoriasis were investigated in the Phase 3 trials reSURFACE 1 and reSURFACE 2. Objectives To determine efficacy and safety of tildrakizumab in patients with early- vs late-onset psoriasis through 28 weeks of treatment. Methods This was a post hoc subgroup analysis of patients from reSURFACE 1 and reSURFACE 2. Patients ≥50 years of age were grouped by age of psoriasis onset at &amp;lt;40 vs ≥40 years. Efficacy endpoints included absolute Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), and proportions of patients who achieved a ≥75%/≥90%/100% improvement from baseline in PASI (PASI 75/90/100), Physician Global Assessment score of 0 or 1 (PGA 0/1), and DLQI of 0 or 1 (DLQI 0/1), adjusted for potential confounders. Safety was assessed from treatment-emergent adverse events (TEAEs). Results Higher percentages and adjusted responder rate estimates of patients with late- (n = 130) vs early-onset psoriasis (n = 111) achieved absolute PASI &amp;lt;1 (36.2% vs 27.9%; estimate, 32.2% vs 25.0%), PASI 90 (50.8% vs 39.6%; estimate, 49.4% vs 40.2%), and PASI 100 (21.5% vs 8.1%; estimate, 13.7% vs 7.9%) at Week 28 (all P &amp;lt;0.05). Age of onset did not significantly affect change from baseline in absolute PASI or DLQI, or achievement of PASI &amp;lt;5, PASI &amp;lt;3, PASI 75, DLQI 0/1, or PGA 0/1 (all P &amp;gt; 0.05). Efficacy findings were supported in a subset of patients matched by disease duration. Among patients with early- vs late-onset psoriasis, TEAEs and serious TEAEs occurred in 65.8% vs 66.2% and 3.6% vs 6.9%, respectively. Conclusions Treatment with tildrakizumab was effective with no safety signals in both patient subgroups. Patients with late-onset psoriasis were more likely to achieve complete or near-complete clearance than were patients with early-onset psoriasis. Clinical trial registration NCT01722331 and NCT01729754
Cinacalcet-Induced Hypocalcemia in Refractory Darier Disease
Authors: Luis Alonso-Mtz de Salinas, Jorge Naharro-Rodriguez, Raquel Dominguez-Lopez, Blanca Santos-Latasa, Alba Lecumberri-Indart, Montserrat Fernandez-Guarino, Bibiana Perez-Garcia
Journal: British Journal of Dermatology (2025)

Darier disease (DD) is a rare genetic disease characterized by abnormal keratinocytes adhesion due to disrupted calcium regulation. This article presents a case of a patient with DD, refractory to multiple treatments who developed hypocalcemia due to systemic absorption of topical cinacalcet.
Valve type and post-dilation impact on transprosthetic gradients in patients undergoing transcatheter aortic valve-in-valve procedure
Authors: Manuela Muratori, Laura Fusini, Gloria Tamborini, Paola Gripari, Sarah Ghulam Ali, Valentina Mantegazza, Anna Garlaschè, Francesco Doni, Andrea Baggiano, Francesco Cannata, Alberico Del Torto, Fabio Fazzari, Antonio Frappampina, Daniele Junod, Riccardo Maragna, Saima Mushtaq, Luigi Tassetti, Alessandra Volpe, Stefano Galli, Franco Fabbiocchi, Marco Gennari, Marco Agrifoglio, Antonio L Bartorelli, Federico De Marco, Mauro Pepi, Gianluca Pontone
Journal:  (2025)

Abstract Aims Valve-in-Valve transcatheter aortic valve replacement (ViV-TAVR) is an appealing treatment option for patients with degenerated aortic bioprosthetic valves. However, higher post-procedural transprosthetic gradients are more common after ViV-TAVR than after TAVR for native aortic valve stenosis. We sought to evaluate the impact of type of implanted valve and balloon post-dilation on echocardiographic results and mortality in ViV-TAVR patients. Methods and results One hundred and eleven consecutive patients were enrolled. A balloon-expandable valve, a self-expandable valve without balloon post-dilation, and a self-expandable valve with balloon post-dilation were performed in 35 (Group 1), 39 (Group 2), and 37 (Group 3) patients, respectively. All patients underwent comprehensive transthoracic echocardiography at baseline, discharge, and 6–12 months follow-up. Successful ViV-TAVR was performed in 110 patients (99%). Baseline transprosthetic gradients, left ventricular volumes, ejection fraction, and pulmonary artery systolic pressure were similar among groups. All groups experienced a significant reduction in post-procedural gradients at discharge and during the 6–12 months follow-up compared with baseline. At discharge, the lowest mean gradient was observed in Group 3 (12 ± 7 mmHg) compared with both Group 1 (20 ± 9 mmHg) and Group 2 (17 ± 8 mmHg, P = 0.001). This result was confirmed at 6–12 months follow-up (P = 0.012). Similar 5-year all-cause mortality was observed among groups (34%, 36%, 14%, respectively, P = 0.056). Conclusion In patients with failed surgical aortic prosthesis, ViV-TAVR is an effective treatment option associated with sustained improved haemodynamics regardless of transcatheter valve type and use of balloon post-dilation. However, self-expandable valves with balloon post-dilation showed lower transprosthetic gradients.
Cascade Regulation of Blood Clot Stabilization‐Cell Migration‐Osteogenic Differentiation by Hollow Hydrogels for Periodontal Bone Regeneration and Repair
Authors: Lubin Liu, Zhiguo Wang, Yan Sun, Ye Liu, Tingting Li, Qiyun Zheng, Jingshu Yang, Haoyue Dong, Hongzhao Qi, Quanchen Xu
Journal: Advanced Healthcare Materials (2025)

Abstract Periodontal bone destruction caused by periodontitis presents a significant clinical challenge. Optimal regeneration of periodontal bone shall progress through three distinct physiological stages: 1) formation of a blood clot; 2) recruitment of stem cells to the clot; and 3) osteogenic differentiation of the stem cells. In this context, the present study proposes a hollow carboxymethyl chitosan (CMCS)/sodium alginate (SA)/CaCO 3 microparticles (CACC) hydrogel. Its formation utilizes temporal differences in cross‐linking between the outer and inner regions. The results indicate that the hollow structure of the CACC hydrogel enhances blood clot formation and stability. Additionally, the hydrogel facilitates the migration of human‐derived periodontal ligament stem cells (PDLSCs) and MC3T3‐E1 cells through the release of calcium ions (Ca 2+ ). Furthermore, it supports osteogenic differentiation of both PDLSCs and MC3T3‐E1 cells by upregulating osteogenesis‐related proteins. In conclusion, by leveraging the cross‐linking and entanglement properties of polymers, a hollow hydrogel that sequentially regulates the three critical stages of periodontal bone regeneration is developed. Notably, this hydrogel effectively preserves blood clots, an often‐overlooked aspect of bone repair, within its hollow structure. This innovation encourages the advancement of biomaterials that more closely mimic the natural repair process.
Associations between immune checkpoint inhibitor response, immune-related adverse events, and steroid use in RADIOHEAD: a prospective pan-tumor cohort study
Authors: Zoe Quandt, Anastasia Lucas, Samantha I Liang, EnJun Yang, Samantha Stone, Muhammad Zaki Hidayatullah Fadlullah, Nicholas L Bayless, Sara Siebel Marr, Marshall A Thompson, Lacey J Padron, Samantha Bucktrout, Lisa H Butterfield, Aik Choon Tan, Kevan C Herold, Jeffrey A Bluestone, Mark S Anderson, Christine N Spencer, Arabella Young, John E Connolly
Journal: Journal for ImmunoTherapy of Cancer (2025)

Immune checkpoint inhibitors (ICIs) have led to enduring responses in subsets of patients with cancer. However, these responses carry the risk of immune-related adverse events (irAEs), which can diminish the overall benefit of ICI treatment. While associations between irAE development and overall survival have been increasingly documented, there is a need for further understanding of these connections in large prospective real-world cohorts. The Resistance Drivers for Immuno-Oncology Patients Interrogated by Harmonized Molecular Datasets (RADIOHEAD) study, a pan-tumor, prospective cohort of 1,070 individuals undergoing standard of care first-line ICI treatment, aims to identify factors driving irAEs and clinical response. Clinical data and longitudinal blood samples were collected prospectively at multiple time points from 49 community-based oncology clinics across the USA. Structured, harmonized clinical data underwent unbiased statistical analysis to uncover predictors of real-world overall survival (rwOS) and risk factors for irAEs. Across 1,070 participants' treatment courses, RADIOHEAD accumulated over 4,500 clinical data points. Patients experiencing any irAE (25.4%, n=272) exhibited significantly improved rwOS in the pan-tumor cohort (n=1,028, HR=0.41, 95% CI=(0.31, 0.55)). This association persisted when adjusting for age and metastatic disease in multivariate time-dependent Cox proportional hazard analysis, and was consistent across major tumor subtypes, including lung cancer and melanoma. Skin and endocrine irAEs of any grade were strongly associated with improved rwOS (Cox proportional hazard analysis, skin, p=2.03e-05; endocrine, p=0.0006). In this real-world cohort, the irAE rate appeared lower than those reported in clinical trials. Patients receiving corticosteroids prior to initiation of ICI treatment had significantly worse survival outcomes than non-users (HR 1.37, p=0.0054), with a stronger association with systemic steroid use (HR 1.75, p=0.0022). The risk of irAE was increased by exposure to combination immunotherapy relative to monotherapy (OR 4.17, p=2.8e-7), zoster vaccine (OR 2.4, p=5.2e-05), and decreased by prior chemotherapy (OR 1.69, p=0.0005). The RADIOHEAD cohort is a well-powered, real-world cohort that clearly demonstrates the association between irAE development with improved response and baseline steroid use with worse response to ICI treatment after adjustment for survival bias.
Precisely Tailored Annulated Porphyrin with Intense NIR Absorption for Highly Efficient Photothermal Therapy and Photoacoustic Imaging
Authors: Chulin Qu, Chengyan Zhao, Yingzhe Hu, Shaohai Liu, Haodong Xu, Xidan Wen, Pengfei Li, Xinhua Zhu, Fan Wu, Zhen Shen
Journal: Advanced Healthcare Materials (2025)

Abstract Constructing near‐infrared (NIR) phototherapy agents with good biosafety is highly desirable for cancer therapy. Herein, the combined “β‐meso‐core” engineering of porphyrin produces excellent photothermal/photoacoustic agents that exhibit locally excited NIR bands with high molar extinction coefficients reaching 10 5 scale. The β‐anthracene fusion of porphyrins via retro‐Diels‐Alder reactions extends the π‐systems, generating red‐shifted and intensified Q bands with narrow half‐widths. The change of meso‐substituents leads to distorted, non‐aggregated molecules with improved solubility and fine‐tunes the photophysical characteristics. The core coordination of copper ions promotes non‐radioactive decay in the energy‐releasing process and enhances photobleaching resistance. The biocompatible nanoparticles encapsulating the designed porphyrin exhibit a high photothermal conversion efficiency of 68% and promising photoacoustic responses, enabling effective photoacoustic imaging‐guided photothermal therapy in vivo at a safe laser intensity (808 nm, 0.3 W cm − 2 ). This study provides a novel strategy in the molecular engineering of porphyrin for designing highly efficient photothermal agents.
Dynamic Mechanical Stimulation of Thermoresponsive Nanofibers for Activation of Fibroblasts in Skin Repair
Authors: Xuran Guo, Ying Gao, Jiajia Yu, Sha Qiu, Xiaoli Wang, Shasha Wang, Chunling Zhang, Bingcheng Yi, Yinghua Gao
Journal: Advanced Healthcare Materials (2025)

Abstract Substrate stiffness regulates fibroblast phenotype through focal adhesion‐mediated mechanotransduction pathways to facilitate tissue repair and regeneration. To analyze the effects of dynamic mechanical stimulation of substrates on cell behavior and skin wound healing, collagen‐like hydrogel nanofibers are fabricated using coaxial electrospinning of gelatin methacryloyl (GelMA) and poly‐L‐lactic acid (PLLA). These nanofibers are then grafted with thermoresponsive poly(N‐vinylcaprolactam) (PNVCL) via dehydration condensation reaction, providing temperature‐dependent mechanical signals. The incorporation of PLLA significantly enhanced the mechanical properties of the GelMA hydrogel nanofibers, while the subsequent grafting of PNVCL effectively reduced the swelling ratio and porosity. Upon exposure to temperatures above the lowest critical solution temperature (LCST), PNVCL molecules underwent a phase transition and self‐contraction, improving mechanical properties by forming robust hydrogen bonds with GelMA and expelling water molecules from the polymer matrix. This dynamic mechanical stimulation further promoted cytoskeletal remodeling of mouse skin fibroblasts (MSFs) without significantly affecting cell proliferation and migration. Additionally, it stimulated the differentiation of fibroblasts into myofibroblasts, thereby enhancing extracellular matrix secretion and skin regeneration in vivo. Overall, the engineering of thermoresponsive hydrogel nanofibers with dynamic mechanical stimulation introduces a novel design paradigm in functional tissue engineering, enabling precise regulation of cellular behaviors for effective skin wound healing.
Activation of RAS/MEK/ERK signalling drives biliary differentiation in primary liver cancer
Authors: Thomas Rösner, Carina Rupp, Christian Lechler, Ulrike Bauer, Saumya Sukumary Manmadhan, Sophia Bernatik, Fabian Delugré, Franziska Ihli, Tanja Derowski, Simone Jörs, Birgit Kohnke-Ertel, Henrik Einwächter, Nicole Pfarr, Katja Steiger, Carolin Mogler, Maximilian Reichert, Dieter Saur, Diana Becker, Jens U Marquardt, Rupert Öllinger, Thomas Engleitner, Roland Rad, Roland M Schmid, Ursula Ehmer
Journal: Gut (2025)

RAS mutations are frequently observed in human cholangiocarcinoma (CCA), while they are relatively rare in hepatocellular carcinoma (HCC). The role of RAS-dependent signalling pathways in CCA development is currently not well understood. The objective of this study was to investigate RAS-dependent signalling pathways in CCA and their role in tumour development and differentiation. We used genetically engineered mouse models with liver-specific deletion of tumour suppressors Rb and p53 together with activation of oncogenic Kras to investigate the cell of origin in intrahepatic CCA and to elucidate the role of RAS-dependent signalling pathways in CCA development. In mice, Kras-mutant intrahepatic CCA develops primarily from hepatocytes and shows activation of PI3K/AKT and MEK/ERK signalling downstream of KRAS. Targeted genetic inactivation of each of these pathways leads to delayed tumour growth and profound alterations in tumour differentiation. Specifically, reduced PI3K/AKT signalling promotes more well-differentiated tumours, whereas the inactivation of MEK/ERK signalling induces a differentiation switch towards a more hepatocyte-like phenotype. This switch is accompanied by activation of WNT/β-catenin signalling, a pathway commonly activated in human HCC. These findings provide insights into the role of RAS-dependent pathways in liver cancer differentiation and offer a compelling explanation for the high prevalence of RAS mutations in human CCA compared with HCC.
Long-term mortality outcomes among immunotherapy recipients treated with dupilumab for the management of cutaneous immune-related adverse events
Authors: Sara Khattab, Guihong Wan, Suzanne Xu, Cameron Moseley, Matthew Tran, Emma Beagles, Chuck Lin, Bonnie W Leung, Marjan Azin, Ninghui Hao, Kerry L Reynolds, Shadmehr Demehri, Nicole R LeBoeuf, Yevgeniy R Semenov
Journal: Journal for ImmunoTherapy of Cancer (2025)

Dupilumab has been added to National Cancer Comprehensive Network guidelines as a therapeutic strategy for managing certain cutaneous immune-related adverse events (cirAEs) from immune checkpoint blockade (ICB). However, little is known about the implications of dupilumab for cancer outcomes in this population. In this multi-institutional study, we evaluate the impact of dupilumab treatment on survival among ICB recipients. We conducted a multi-institutional retrospective cohort study of ICB recipients from the Mass General Brigham Healthcare System and Dana-Farber Cancer Institute. The dupilumab group was compared with two control groups who did not receive dupilumab: with and without cirAEs (control groups 1 and 2, respectively) that were 1:2 matched on sex, race, age at ICB initiation, Charlson Comorbidity Score, year of ICB initiation, and ICB type. Manual chart review was performed to obtain cirAE characteristics, systemic glucocorticoid use, dupilumab treatment, vital status, and last contact date. Time-varying multivariable Cox proportional hazards regressions were used to evaluate the impact of dupilumab on overall survival, adjusted for sex, race, age at ICB initiation, ICB type, Charlson Comorbidity Index score, cancer type, cancer stage at ICB initiation, and systemic glucocorticoid use. A total of 53 cirAE patients treated with dupilumab were compared with two control groups of 106 patients each. Most patients receiving dupilumab demonstrated either complete or partial resolution of their cirAE (88.7%). In multivariable modeling, the overall survival of the dupilumab group was not significantly different from control group 1 (HR=0.74, 95% CI: 0.35 to 1.60, p=0.5) or control group 2 (HR=0.70, 95% CI: 0.32 to 1.51, p=0.4). However, the use of systemic glucocorticoids within 2 years after ICB initiation was associated with poorer overall survival when comparing the dupilumab group to control group 1 (HR=2.03, 95% CI: 1.04 to 3.96, p=0.039) and control group 2 (HR=2.21, 95% CI: 1.25 to 3.91, p=0.006). This study suggests that dupilumab is an effective therapy for recalcitrant cirAEs and does not adversely impact mortality. Due to the observed detrimental effects of systemic glucocorticoid therapy, this study suggests the need to shift away from systemic glucocorticoid immunosuppression and toward targeted immune modulators for irAE management, though prospective randomized trials are necessary to investigate this.