tbuckley/cabot-search huggingface dataset:
A circadian and app-based personalized lighting intervention for the reduction of cancer-related fatigue
Authors: Caleb Mayer, Olivia Walch, Walter Dempsey, Kevin Hannay, Caroline Clingan, Zoe Bowen, Michelle Rozwadowski, Zachery R. Reichert, N. Lynn Henry, Joshi J. Alumkal, Muneesh Tewari, Daniel B. Forger, Sung Won Choi
Journal: Cell Reports Medicine (2025)

Highlights•We develop a lighting intervention based on wearable-measured circadian rhythms•Fatigue T-scores do not significantly differ between intervention and control at week 11•T-scores significantly decrease in intervention, with a significant treatment effect•Daily fatigue, anxiety, sleep, and physical function improve in the interventionSummaryLighting interventions can mitigate fatigue by promoting circadian rhythmicity. We test whether individualized, wearable-based lighting interventions delivered via a mobile app reduce cancer-related fatigue in a randomized controlled trial with 138 breast cancer, prostate cancer, and hematopoietic stem cell transplant patients. Participants are randomized to tailored lighting intervention or control. The primary endpoint is PROMIS fatigue 4a at trial end, with secondary endpoints including change in daily fatigue, sleep, anxiety, depression, physical function, and overall health. Fatigue T-scores at week 11 do not differ between groups but decrease significantly from week 1 to week 11 (3.07 points, p = 0.001) in the intervention group, with a significant final-week treatment effect (p = 0.014). Daily fatigue, anxiety, sleep disturbance, and physical function improve within intervention. Further studies are needed to see if these results generalize in broader cancer care. The trial is registered at ClinicalTrials.gov (trial registration number: NCT04827446).Graphical abstract
Calibration of Toenail Metal Concentrations for Sample Mass Heterogeneity and Between-Batch Variability: The COMET Approach
Authors: Roberto Pastor-Barriuso, Enrique Gutiérrez-González, Elena Varea-Jiménez, José Luis Gómez-Ariza, Gemma Castaño-Vinyals, Nuria Aragonés, Antonio José Molina, Trinidad Dierssen-Sotos, Guillermo Fernández-Tardón, Pilar Amiano, María Ederra-Sanz, Victor Moreno, José Juan Jiménez-Moleón, Ana Molina-Barceló, Rafael Marcos-Gragera, Delphine Casabonne, Juan Alguacil, Jesús Humberto Gómez-Gómez, Tamara García-Barrera, Manolis Kogevinas, Marina Pollán, Beatriz Pérez-Gómez
Journal: Environmental Health Perspectives (2025)

Toenails are promising biomarkers of long-term metal exposure in epidemiologic studies, but their accuracy may be compromised by systematic and random errors associated with heterogeneous toenail sample masses, as well as by substantial variability across laboratory batches. We propose a novel modeling approach to calibrate toenail metal concentrations for the heterogeneity in sample masses and the variability between batches. We developed a heteroscedastic spline mixed model relating sample mass and laboratory batch with measured concentrations, allowing for an average bias in measurements over all batches as a smooth function of sample mass, random variation in mass-related biases across batches, and mass-related heterogeneity in within-batch error variance. The model allowed partitioning the total variance of measured concentrations into the extraneous variances (due to different sample masses and laboratory batches) and the intrinsic variance (resulting from distinct metal exposures). We derived calibrated metal concentrations from the model by removing both sources of extraneous variation and estimating the predicted concentrations had all toenail samples been analyzed in a single batch and of the same mass. We provide the R script COMET (COrrected METals) to fit the proposed model, extract variance components, and calibrate metal concentrations. In a multicase-control study in Spain (MCC-Spain) with toenail determinations for 16 metals in 4,473 incident cases of five common cancers and 3,450 population controls, sample mass and batch accounted for 26-60% of the total variance of measured concentrations for most metals. Compared with calibrated concentrations, odds ratios for measured concentrations were biased by > 10% toward or away from the null in one-quarter of the estimated metal-cancer associations. The proposed model allows correcting toenail metal concentrations for sample mass heterogeneity and between-batch variability, and could be applied to other biological specimens of heterogeneous size, distinct laboratory techniques, and different study designs. https://doi.org/10.1289/EHP14784.
Novel targeted therapies for immunoglobulin light chain amyloidosis: latest updates from the 2024 ASH annual meeting
Authors: Qiling Bu, Hong-Hu Zhu, Wenming Chen
Journal: Journal of Hematology & Oncology (2025)

Immunoglobulin light chain (AL) amyloidosis is an incurable disease caused by the accumulation and sedimentation of unstable free light chains produced by monoclonal plasma cells. The key to treatment is to achieve a deep hematologic remission in order to improve organ function or reverse organ dysfunction. Conventional treatment has not been able to fully meet the treatment needs of patients with AL, while therapies targeting malignant plasma cells or amyloid have potentially improved treatment outcomes. This study provides an overview of the latest reports on targeted therapies for AL amyloidosis from the 2024 ASH Annual Meeting.
Cancer-associated fibroblasts serve as decoys to suppress NK cell anti-cancer cytotoxicity in breast cancer
Authors: Aviad Ben-Shmuel, Yael Gruper, Coral Halperin, Oshrat Levi-Galibov, Hallel Rosenberg-Fogler, Debra Barki, Giulia Carradori, Yaniv Stein, Gal Yagel, Mariia Naumova, Shimrit Mayer, Maya Dadiani, Dana Morzaev-Sulzbach, Ofra Golani, Reinat Nevo, Ziv Porat, Einav Nili Gal-Yam, Ruth Scherz-Shouval
Journal: Cancer Discovery (2025)

Cancer-associated fibroblasts (CAFs) are abundant components of the breast tumor microenvironment and major contributors to immune-modulation. CAFs regulate the activity of many immune cells including T-cells, macrophages and dendritic cells, however little is known about their interaction with natural killer (NK) cells, which constitute an important arm of anti-tumor immunity. Using mouse models of breast cancer and ex-vivo co-cultures, we find that CAFs inhibit NK cell cytotoxicity towards cancer cells. We unravel the mechanism by which suppression occurs, through ligand-receptor engagement between NK cells and CAFs, leading to CAF cytolysis and downregulation of activating receptor expression on NK cells, promoting cancer cell escape from NK cell surveillance. In triple negative breast cancer patients, we find enrichment of NK cells in CAF-rich regions, and upregulation of NK binding ligands on CAFs which correlates with poor disease outcome. These results reveal a CAF-mediated immunosuppressive decoy mechanism with implications for treatment of carcinomas.
Misspecification Strikes: ASTRAL can Mislead in the Presence of Hybridization, even for Non-Anomalous Scenarios
Authors: Vu Dinh, Hector Baños
Journal: Molecular Biology and Evolution (2025)

ASTRAL is a powerful and widely used tool for species tree inference, known for its computational speed and robustness under incomplete lineage sorting. The method has often been used as an initial step in species network inference to provide a backbone tree structure upon which hybridization events are later added to such a tree via other methods. However, we show empirically and theoretically, that this methodology can yield flawed results. Specifically, we demonstrate that under the Network Multispecies Coalescent model - including non-anomalous scenarios - ASTRAL can produce a tree that does not correspond to any topology displayed by the true underlying network. This finding highlights the need for caution when using ASTRAL-based inferences in suspected hybridization cases.
Identification of a conserved subset of cold tumors responsive to immune checkpoint blockade
Authors: Jade Moore, Jim Gkantalis, Ines Guix, William Chou, Kobe Yuen, Ann A Lazar, Matthew Spitzer, Alexis Combes, Mary Helen Barcellos-Hoff
Journal: Journal for ImmunoTherapy of Cancer (2025)

The efficacy of immune checkpoint blockade (ICB) depends on restoring immune recognition of cancer cells that have evaded immune surveillance. Transforming growth factor-beta (TGFβ) is associated with immune-poor, so-called cold tumors whereas loss of its signaling promotes DNA misrepair that could stimulate immune response. We analyzed transcriptomic data from IMvigor210, The Cancer Genome Atlas, and Tumor Immune Syngeneic MOuse data sets to evaluate the predictive value of high βAlt, a score representing low expression of a signature consisting of TGFβ targets and high expression of genes involved in error-prone DNA repair. The immune context of βAlt was assessed by evaluating tumor-educated immune signatures. An ICB-resistant, high βAlt preclinical tumor model was treated with a TGFβ inhibitor, radiation, and/or ICB and assessed for immune composition and tumor control. We found that a high βAlt score predicts ICB response yet is paradoxically associated with an immune-poor tumor microenvironmentcancer in both human and mouse tumors. We postulated that high βAlt cancers consist of cancer cells in which loss of TGFβ signaling generates a TGFβ rich, immunosuppressive tumor microenvironment. Accordingly, preclinical modeling showed that TGFβ inhibition followed by radiotherapy could convert an immune-poor, high βAlt tumor to an immune-rich, ICB-responsive tumor. Mechanistically, TGFβ inhibition increased activated natural killer (NK) cells, which were required to recruit lymphocytes to respond to ICB in irradiated tumors. NK cell activation signatures were also increased in high βAlt, cold mouse and human tumors that responded to ICB. These studies indicate that loss of TGFβ signaling competency and gain of error-prone DNA repair identifies a subset of cold tumors that are responsive to ICB. Our mechanistic studies show that inhibiting TGFβ activity can convert a high βAlt, cold tumor into ICB-responsive tumors via NK cells. A biomarker consisting of combined TGFβ, DNA repair, and immune context signatures is a means to prospectively identify patients whose cancers may be converted from cold to hot with appropriate therapy.
Efficacy of cognitive functional therapy for pain intensity and disability in patients with non-specific chronic low back pain: a randomised sham-controlled trial
Authors: Mariana Romano de Lira, Ney Meziat-Filho, Gabriela Zuelli Martins Silva, Julia Castro, Jessica Fernandez, Rinaldo Roberto de Jesus Guirro, Roger Berg, Thais Cristina Chaves
Journal: British Journal of Sports Medicine (2025)

This study investigated the efficacy of cognitive functional therapy (CFT) versus a sham procedure for pain intensity and disability for patients with non-specific chronic low back pain (CLBP). This is a randomised sham-controlled trial conducted in a primary care public health service. A total of 152 participants were randomly assigned to the CFT group (n=76) and the sham group (n=76). The CFT group received six 1 hour individualised sessions; the sham procedure group received six individual sessions of neutral talking+detuned photobiomodulation (low-level laser therapy) equipment. Both groups received an education booklet with information on strategies for CLBP self-management. Primary outcomes were pain intensity and disability at 6 weeks. Participants were assessed preintervention, postintervention (at 6 weeks), and 3 and 6 months after randomisation. We obtained primary outcome data from 97.4% (n=74) of participants in the CFT group and 98.7% (n=75) from the sham group. The CFT group showed greater effects in pain intensity (mean difference (MD)=-1.8; 95% CI -2.5 to -1.1) and disability (MD=-9.9; 95% CI -13.2 to -6.5) postintervention compared with the sham group. The effect remained at the 3-month and 6-month follow-ups. CFT showed sustained clinical efficacy compared with a sham procedure for treating pain intensity and disability in patients with CLBP. This trial was registered in ClinicalTrials.gov, NCT04518891 and was previously published https://pubmed.ncbi.nlm.nih.gov/35788240/.
Early clinical remission and its role in lung function decline and exacerbation in adult Korean patients with asthma
Authors: Eunhye Bae, Hyun-Jun Park, Heemoon Park, Jung-Kyu Lee, Eun Young Heo, Chang Hoon Lee, Deog Kyeom Kim, Hyun Woo Lee
Journal: Thorax (2025)

Despite advancements in asthma management, many patients continue to experience poor disease control, lung function decline, and frequent exacerbations. Clinical remission (CR) has been proposed as a novel treatment target and surrogate marker for long-term outcomes. This study evaluates whether early CR at 1 year after inhaled corticosteroid (ICS) initiation influences lung function decline and exacerbation risk in asthma. This retrospective cohort study evaluated 492 asthma patients treated with ICS at two teaching hospitals. Patients were classified into early CR and non-early CR groups. Early CR was defined based on a composite set of criteria, including sustained absence of exacerbations, no systemic corticosteroid use, symptom control and stable or improved lung function in the first year following ICS initiation. Study outcomes were the annual forced expiratory volume in one second (FEV1) decline and the moderate-to-severe exacerbations. Early CR was significantly associated with slower annual FEV1 decline (4-component CR, adjusted β=31.6 mL/year, p=0.001; 3-component CR, adjusted β=15.7 mL/year, p=0.043). The benefits of early 4-component CR on attenuating annual FEV1 decline were more pronounced in specific phenotypes, including type-2 high asthma, persistent airflow limitation, severe asthma and patients requiring add-on long-acting muscarinic antagonists. Early 4-component CR had a reduced risk of moderate-to-severe (adjusted HR (aHR)=0.591, p=0.011) and severe exacerbations (aHR=0.508, p=0.025). Achieving CR within 1 year of ICS initiation was associated with improved lung function preservation and reduced exacerbation risk. These findings suggest the importance of achieving early CR as a clinical target in asthma management.
Effectiveness of exercise for improving cognition, memory and executive function: a systematic umbrella review and meta-meta-analysis
Authors: Ben Singh, Hunter Bennett, Aaron Miatke, Dorothea Dumuid, Rachel Curtis, Ty Ferguson, Jacinta Brinsley, Kimberley Szeto, Jasmine M Petersen, Claire Gough, Emily Eglitis, Catherine Em Simpson, Christina L Ekegren, Ashleigh E Smith, Kirk I Erickson, Carol Maher
Journal: British Journal of Sports Medicine (2025)

To evaluate systematic reviews of randomised controlled trials (RCTs) on the effects of exercise on general cognition, memory and executive function across all populations and ages. Systematic reviews and meta-analyses of RCTs evaluating the effects of exercise on general cognition, memory and executive function were eligible. Data extraction and risk of bias scoring were conducted in duplicate. The A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) was used to assess the risk of bias. Effect sizes were pooled using random effects models and reported as standardised mean differences (SMD). Subgroup analyses were conducted for participant and intervention characteristics.General cognition, memory and executive function. CINAHL, The Cochrane Library, Embase, MEDLINE via OVID, Emcare, ProQuest Central, ProQuest Nursing and Allied Health Source, PsycINFO, Scopus, Sport Discus and Web of Science. 133 systematic reviews (2,724 RCTs and 258 279 participants) were included. Exercise significantly improved general cognition (SMD=0.42), memory (SMD=0.26) and executive function (SMD=0.24). Memory and executive function improvements from exercise were greater for children and adolescents than for adults and older adults. Those with attention-deficit/hyperactivity disorder exhibited greater improvement in executive function than other populations. Effects were generally larger for low- and moderate-intensity interventions. Shorter interventions (1-3 months) and exergames (video games that require physical movement) had the largest effects on general cognition and memory. Findings remained statistically significant after excluding reviews rated as low and critically low quality. These findings provide strong evidence that exercise, even light intensity, benefits general cognition, memory and executive function across all populations, reinforcing exercise as an essential, inclusive recommendation for optimising cognitive health. PROSPERO ID: CRD42023468991.
Immunosuppressive microenvironment of liver restrains chemotherapeutic efficacy in triple-negative breast cancer
Authors: Mingduo Liu, Mengjia Qian, Wen Sun, Xiaowei Sun, Yue Sun, Muxin Yu, Xinyu Tang, Xinrui Mao, Chang Sun, Qi Qi, Weiya Zhang, Peiwen Ling, Zheng Pang, Wei Li, Hong Pan, Shui Wang, Wenbin Zhou
Journal: Journal for ImmunoTherapy of Cancer (2025)

Patients with liver metastases of triple-negative breast cancer (TNBC) show poor prognosis compared with other metastases. Chemotherapy is the primary treatment for advanced TNBC. Tumor cell diversity and the tumor microenvironment could affect therapeutic effect. However, whether liver metastases of TNBC exhibit differential chemotherapy efficacy compared with the primary tumors remains inadequately understood. The specific mechanisms that modulate chemotherapy efficacy in liver metastases need further investigation. Single-cell RNA sequencing data from public databases were leveraged to contrast the immune profiles of liver metastases and primary tumors in TNBC. Murine models bearing liver tumors or primary tumors of TNBC were used to evaluate chemotherapy efficacy. Techniques such as immunohistochemistry, wound healing assays, and colony formation assays were employed to account for tumor heterogeneity. Intratumoral T lymphocytes and macrophages were quantified and characterized using RNA sequencing, immunohistochemistry, and flow cytometry. Antibody-mediated depletion of CD8+T cells or macrophages in mice substantiated their impact on chemotherapy responses. Single-cell RNA sequencing data showed the immune microenvironments of liver metastases and primary tumors exhibited significant differences, which may critically influence chemotherapy outcomes. Mouse models confirmed that chemotherapy was less effective against liver tumors compared with subcutaneous tumors. After excluding the influence of tumor cell heterogeneity, the weaker responsiveness in liver tumors was mediated by the impeded infiltration of CD8+T cells, attributed to the decreased activation of macrophages. Augmenting macrophage activation can improve the chemotherapeutic efficacy in liver tumors. Moreover, chemotherapy drove the immune microenvironment towards increased suppression through distinct mechanisms, with neutrophil extracellular traps (NETs) accumulating in liver tumors and impaired functionality of macrophages at the primary site. The combination of NET inhibitors or macrophage activators with chemotherapy enhanced treatment effectiveness. These findings disclose the compromised chemotherapeutic efficacy in liver tumors of TNBC and elucidate the underlying immune-related mechanisms within the tumor microenvironment. Targeting the specific underpinnings of immune suppression at different tumor sites with selective drugs could optimize chemotherapeutic efficacy.
Prognostic and predictive values of a multimodal nomogram incorporating tumor and peritumor morphology with immune status in resectable lung adenocarcinoma
Authors: Huan Lin, Junjie Hua, Yumeng Wang, Mingwei Chen, Yanting Liang, LiXu Yan, Wei Zhao, Shiwei Luo, Deqing Hong, Xin Chen, Xipeng Pan, Jun Liu, Zaiyi Liu
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Current prognostic and predictive biomarkers for lung adenocarcinoma (LUAD) predominantly rely on unimodal approaches, limiting their characterization ability. There is an urgent need for a comprehensive and accurate biomarker to guide individualized adjuvant therapy decisions. Methods In this retrospective study, data from patients with resectable LUAD (stage I–III) were collected from two hospitals and a publicly available dataset, forming a training dataset (n=223), a validation dataset (n=95), a testing dataset (n=449), and the non-small cell lung cancer (NSCLC) Radiogenomics dataset (n=59). Tumor and peritumor scores were constructed from preoperative CT radiomics features (shape/intensity/texture). An immune score was derived from the density of tumor-infiltrating lymphocytes (TILs) within the cancer epithelium and stroma on hematoxylin and eosin-stained whole-slide images. A clinical score was constructed based on clinicopathological risk factors. A Cox regression model was employed to integrate these scores, thereby constructing a multimodal nomogram to predict disease-free survival (DFS). The adjuvant chemotherapy benefit rate was subsequently calculated based on this nomogram. Results The multimodal nomogram outperformed each of the unimodal scores in predicting DFS, with a C-index of 0.769 (vs 0.634–0.731) in the training dataset, 0.730 (vs 0.548–0.713) in the validation dataset, and 0.751 (vs 0.660–0.692) in the testing dataset. It was independently associated with DFS after adjusting for other clinicopathological risk factors (training dataset: HR=3.02, p&lt;0.001; validation dataset: HR=2.33, p&lt;0.001; testing dataset: HR=2.03, p=0.001). The adjuvant chemotherapy benefit rate effectively distinguished between patients benefiting from adjuvant chemotherapy and those from observation alone (interaction p&lt;0.001). Furthermore, the high-/low-risk groups defined by the multimodal nomogram provided refined stratification of candidates for adjuvant chemotherapy identified by current guidelines (p&lt;0.001). Gene set enrichment analyses using the NSCLC Radiogenomics dataset revealed associations between tumor/peritumor scores and pathways involved in epithelial-mesenchymal transition, angiogenesis, IL6-JAK-STAT3 signaling, and reactive oxidative species. Conclusion The multimodal nomogram, which incorporates tumor and peritumor morphology with anti-tumor immune response, provides superior prognostic accuracy compared with unimodal scores. Its defined adjuvant chemotherapy benefit rates can inform individualized adjuvant therapy decisions.