tbuckley/cabot-search huggingface dataset:
A phase 2 clinical trial of axitinib and avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (ACC).
Authors: Renata Ferrarotto, Diana Bell, Lei Feng, Kaiyi Li, Frank Mott, George R. Blumenschein, Luana Guimaraes de Sousa, Mehmet Altan, Mario L. Marques-Piubelli, Eduardo Andreazza Dal Lago, Diana Kaya, Myrna Godoy, Michael Elliot Kupferman, Bonnie S. Glisson, Adel K. El-Naggar, Yasir Y Elamin
Journal: Journal of Clinical Oncology (2022)

6019 Background: ACC is a heterogeneous neoplasm and there is no standard treatment for patients (pts) with recurrent/metastatic (R/M) disease. Vascular endothelial growth factor receptor inhibitors (VEGFRi) are frequently used to treat R/M ACC rendering mostly disease stabilization. ACC is resistant to PD-1/PD-L1 inhibitors (PD-L1i), consistent with its low mutational burden and uninflamed immune microenvironment. We hypothesized that the immunomodulatory role of VEGFRi (axitinib) would enhance PD-L1i (Avelumab) activity and be a more effective therapy for R/M ACC. Methods: Eligible pts had R/M ACC with radiological or clinical progression within 6 months (mos) of enrollment. Treatment consisted of axitinib 5 mg PO bid and avelumab 10 mg/Kg IV every 2 weeks. Primary endpoint was objective response rate (ORR) per RECIST 1.1; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. Simon 2-stage design was applied to test the null hypothesis of ORR ≤ 5% versus the alternative ORR ≥ 20%; ≥ 4 responses out of 29 pts was required to reject the null hypothesis. Results: 41 pts enrolled from 07/24/19 to 06/29/21; 28 were evaluable for the primary endpoint (7 screen failures, 6 evaluable for safety only due to loss of insurance/logistics issues related to COVID-19 pandemic); 16 pts were treated in first-line. Mutation data was available for 23 of 28 evaluable pts; 7 had NOTCH1 activating mutations. The ORR was 17.9% (5/28, 95%CI: 6.1-36.9%). One response was unconfirmed (pt progressed in non-target lesions 2 mos after achieving a PR), for a confirmed ORR of 14.3% (95%CI: 4-32.7%). The median follow-up time for the 15 alive pts was 11.6 mos (min-max: 7.7-29.2 mos). Median PFS was 7.2 mos (95%CI: 3.7-11.7 mos) with a 6-mos PFS rate of 57% (95%CI: 41-79%). Median OS was 17.4 mos (95%CI: 13-NA). 5 pts remain on therapy, 2/5 with a PR. The median DOR for the 5 responders was 5.2 mos (95% CI: 3.7–NA mos). The most common treatment-related adverse events (TRAEs) were fatigue (62%), hypertension (32%), diarrhea (29%), and stomatitis (29%). Serious TRAEs occurred in 8 (24%) pts, all grade 3 and manageable. 4 (15%) pts discontinued avelumab and 9 (32%) underwent axitinib dose reduction due to toxicity. Conclusions: The study reached its primary endpoint with ≥ 4 responses out of 28 evaluable pts (ORR of 17.8%; confirmed ORR of 14.3%). The ORR and 6-mos PFS rate of 57% with axitinib and avelumab compares favorably with single agent axitinib and warrants further study of the combination. Clinical trial information: NCT03990571.
Effectiveness of adjuvant chemoradiotherapy for oral cavity squamous cell carcinoma with minor and major extranodal extension: A multi-institutional consortium study.
Authors: Mirko Manojlovic Kolarski, Jie Su, Ilan Weinreb, Bayardo Perez-Ordonez, Snehal G. Patel, Cristina Valero, Bin Xu, Nora Katabi, Jonathan Clark, Tsu-Hui (Hubert) Low, Ruta Gupta, Evan Michael Graboyes, Joel C Davies, Mary Richardson, David Paul Goldstein, Shao Hui Huang, Brian O'Sullivan, Wei Xu, Aaron Richard Hansen, John R de Almeida
Journal: Journal of Clinical Oncology (2022)

6010 Background: Extranodal extension (ENE) in oral cavity squamous cell carcinoma (OSCC) is a poor prognostic feature and an indication for adjuvant chemoradiotherapy. Recent pathology reporting guidelines recommend stratifying ENE into minor (≤2mm) or major (&gt;2mm) extent. Prior studies have suggested that the addition of chemotherapy to adjuvant radiation may not improve oncologic outcomes in minor ENE. We evaluated this through a large multi-institutional cohort study. Methods: Surgically resected primary T1-4,N1-N3,M0 OSCC with pathologic nodal disease treated between 2005-2018 from four institutions in three countries were included. Extent of ENE was re-classified by pathologists on archived tissue. Adjuvant radiotherapy or chemoradiotherapy was recommended as per standard guidelines, unless contraindicated. Uni- (UVA) and Multivariable analysis (MVA) assessed the effect of chemotherapy on survival and disease control in minor and major ENE subgroups. Outcomes were also assessed in propensity score matched cohorts for each subgroup. Results: A total of 764 patients were included, of whom 126 (16%) had minor ENE and 242 (32%) had major ENE. Adjuvant chemoradiotherapy was given in 51 (40.5%) with minor ENE and 115 (47.5%) with major ENE. On MVA, chemotherapy was not associated with improved overall survival (OS) (HR 0.97, 95% CI 0.55-1.73, p=0.92) for patients with minor ENE, however, there was significant OS benefit for patients with major ENE (HR 0.61, 95% CI 0.38-0.98, p=0.041) after adjusting for age, T-category, N-category, margin status, adjuvant radiation, LN ratio, LVI, PNI, and ECOG status. Patients with major ENE receiving adjuvant chemoradiotherapy had improved locoregional control (LRC) (HR 0.67, 95% CI 0.42-1.09, p=0.1) although this did not reach statistical significance. Propensity score matched analysis found that patients with minor ENE who did and did not receive chemotherapy had no difference in OS (52% vs. 52%, p=0.85), but those with major ENE did (44% vs 13%, p=0.008). Conclusions: In OSCC, the addition of chemotherapy to adjuvant treatment is beneficial in major ENE, but our group failed to demonstrate a benefit for minor ENE. The benefit of chemotherapy in major ENE may result from improved LRC. Minor ENE is a clinically relevant subgroup in OSCC that warrants distinctive adjuvant treatment considerations.
soibean: High-resolution Taxonomic Identification of Ancient Environmental DNA Using Mitochondrial Pangenome Graphs
Authors: Nicola Alexandra Vogel, Joshua Daniel Rubin, Anders Gorm Pedersen, Peter Wad Sackett, Mikkel Winther Pedersen, Gabriel Renaud
Journal: Molecular Biology and Evolution (2024)

Ancient environmental DNA (aeDNA) is becoming a powerful tool to gain insights about past ecosystems, overcoming the limitations of conventional fossil records. However, several methodological challenges remain, particularly for classifying the DNA to species level and conducting phylogenetic analysis. Current methods, primarily tailored for modern datasets, fail to capture several idiosyncrasies of aeDNA, including species mixtures from closely related species and ancestral divergence. We introduce soibean, a novel tool that utilises mitochondrial pangenomic graphs for identifying species from aeDNA reads. It outperforms existing methods in accurately identifying species from multiple closely related sources within a sample, enhancing phylogenetic analysis for aeDNA. soibean employs a damage-aware likelihood model for precise identification at low coverage with a high damage rate. Additionally, we reconstructed ancestral sequences for soibean's database to handle aeDNA that is highly diverged from modern references. soibean demonstrates effectiveness through simulated data tests and empirical validation. Notably, our method uncovered new empirical results in published datasets, including using porpoise whales as food in a Mesolithic community in Sweden, demonstrating its potential to reveal previously unrecognised findings in aeDNA studies.
Deciphering resistance mechanisms in cancer: final report of MATCH-R study with a focus on molecular drivers and PDX development
Authors: Damien Vasseur, Ludovic Bigot, Kristi Beshiri, Juan Flórez-Arango, Francesco Facchinetti, Antoine Hollebecque, Lambros Tselikas, Mihaela Aldea, Felix Blanc-Durand, Anas Gazzah, David Planchard, Ludovic Lacroix, Noémie Pata-Merci, Catline Nobre, Alice Da Silva, Claudio Nicotra, Maud Ngo-Camus, Floriane Braye, Sergey I Nikolaev, Stefan Michiels, Gérôme Jules-Clement, Ken André Olaussen, Fabrice André, Jean-Yves Scoazec, Fabrice Barlesi, Santiago Ponce, Jean-Charles Soria, Benjamin Besse, Yohann Loriot, Luc Friboulet
Journal: Molecular Cancer (2024)
A Response to the Letter to the Editor: “Comment on Stereotactic Body Radiotherapy for Centrally Located Inoperable Early Stage NSCLC: EORTC 22113-08113 LungTech Phase II Trial Results”
Authors: Antonin Levy, Sonja Adebahr, Coen Hurkmans, Catherine Fortpied, Cécile Le Pechoux, Corinne Faivre-Finn, Ursula Nestle
Journal: Journal of Thoracic Oncology (2024)
Age, anticoagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis
Authors: Natalie J M Chaddock, Charlotte J Harden, Louise Sorensen, Hannah R Mathieson, Michal Zulcinski, Catherine A Lawson, Eoin O'Sullivan, Susan P Mollan, Javier Martin, Sarah L Mackie, Mark M Iles, Ann W Morgan
Journal: Annals of the Rheumatic Diseases (2024)

This project aimed to determine whether cranial ischaemic complications at the presentation of giant cell arteritis (GCA) were associated with pre-existing cardiovascular (CV) risk factors, CV disease or genetic risk of CV-related traits. 1946 GCA patients with clinicodemographic data at GCA presentation were included. Associations between pre-existing CV-related traits (including Polygenic Risk Scores (PRS) for CV traits) and cranial ischaemic complications were tested. A model for cranial ischaemic complications was optimised using an elastic net approach. Positional gene mapping of associated PRS was performed to improve biological understanding. In a sample of 1946 GCA patients (median age=71, 68.7% female), 17% had cranial ischaemic complications at presentation. In univariable analyses, 10 variables were associated with complications (likelihood-ratio test p≤0.05). In multivariable analysis, the two variables with the strongest effects, with or without PRS in the model, were anticoagulant therapy (adjusted OR (95% CI)=0.21 (0.05 to 0.62), p=4.95×10-3) and age (adjusted OR (95% CI)=1.60 (0.73 to 3.66), p=2.52×10-3, for ≥80 years versus <60 years). In sensitivity analyses omitting anticoagulant therapy from multivariable analysis, age and hypertension were associated with cranial ischaemic complications at presentation (hypertension: adjusted OR (95% CI)=1.35 (1.03 to 1.75), p=0.03). Positional gene mapping of an associated transient ischaemic attack PRS identified TEK, CD96 and MROH9 loci. Age and hypertension were risk factors for cranial ischaemic complications at GCA presentation, but in this dataset, anticoagulation appeared protective. Positional gene mapping suggested a role for immune and coagulation-related pathways in the pathogenesis of complications. Further studies are needed before implementation in clinical practice.
Comparison of definitions of early knee osteoarthritis for likelihood of progression at 2-year and 5-year follow-up: the Multicenter Osteoarthritis Study
Authors: Jean W Liew, Eva Petrow, Sarah Tilley, Michael P LaValley, Frank W Roemer, Ali Guermazi, Cora E Lewis, James Torner, Michael C Nevitt, John A Lynch, David Felson
Journal: Annals of the Rheumatic Diseases (2024)

Preventing worsening osteoarthritis (OA) in persons with early OA is a major treatment goal. We evaluated if different early OA definitions yielded enough cases of worsening OA within 2-5 years to make trial testing treatments feasible. We assessed different definitions of early OA using data from Multicenter Osteoarthritis (MOST) Study participants who were followed up longitudinally. We defined early OA as having at least minimal knee pain (WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain ≥3/20) with different levels of pre-radiographic OA. For MRI, we required knee pain and used MRI definitions with combinations of cartilage damage, osteophytes, bone marrow lesions and meniscus damage. The primary outcome, worsening OA at 2 or 5 years, combined structural (Kellgren and Lawrence grade ≥2 with joint space narrowing ≥1) and symptom (WOMAC pain ≥6 with increase ≥2 from baseline) outcomes. We also examined structural and symptom outcomes separately. For worsening OA at 2 years, we included 750 participants (mean age 65 years, 60% female, 90% white, mean body mass index 29.2 kg/m2). Fewer than 10% of early OA knees had the combined outcome at 2 or 5 years. At 2 years, for several early OA definitions, roughly 20% of knees had either structural or symptom worsening outcomes. Two-year trials of either, but not both, outcomes would need to recruit over 1200 patients. Most knees with early OA are stable and do not progress. Some painful knees experience worse pain but not structural progression and vice versa. Trial testing treatments to prevent OA illness or disease will be challenging.
Decline of Mpox Antibody Responses After Modified Vaccinia Ankara–Bavarian Nordic Vaccination
Authors: Ai-ris Y. Collier, Katherine McMahan, Catherine Jacob-Dolan, Jinyan Liu, Erica N. Borducchi, Bernard Moss, Dan H. Barouch
Journal: JAMA (2024)

This study assesses mpox-specific immune responses for 12 months after MVA-BN vaccination.
Transcription factor KROX20 marks epithelial stem cells for hair follicle formation
Authors: Elnaz Ghotbi, Edem Tchegnon, Zhiguo Chen, Stephen Li, Tracey Shipman, Yong Wang, Jenny Raman, Yumeng Zhang, Renee M McKay, Chung-Ping Liao, Lu Q Le
Journal: Journal of Clinical Investigation (2024)

Epidermal stem cells control homeostasis and regeneration of skin and hair. In the hair follicle (HF) bulge of mammals, populations of slow-cycling stem cells regenerate the HF during cyclical rounds of anagen (growth), telogen (quiescence), and catagen (regression). Multipotent epidermal cells are also present in the HF above the bulge area, contributing to the formation and maintenance of sebaceous gland and upper and middle portions of the HF. Here, we report that the transcription factor Krox20 is enriched in an epidermal stem cell population located in the upper/ middle HF. Expression analyses and lineage tracing using inducible Krox20-CreERT showed that Krox20-lineage cells migrate out of this HF region and contribute to the formation of bulge in the HF, serving as ancestors of bulge stem cells. In vivo depletion of these cells arrests HF morphogenesis. This study identifies a novel marker for an epidermal stem cell population that is indispensable for hair homeostasis.
Obesity-induced Neuronal Senescence: Unraveling the Pathophysiological Links
Authors: Puja Ghosh, Rosaria Anna Fontanella, Lucia Scisciola, Fatemeh Taktaz, Ada Pesapane, Manuela Giovanna Basilicata, Giovanni Tortorella, Giulia Mattacchione, Annalisa Capuano, Maria Teresa Vietri, Francesco Selvaggi, Giuseppe Paolisso, Michelangela Barbieri
Journal: Ageing Research Reviews (2024)
Oral Antibiotic Use in Adulthood and Risk of Early-Onset Colorectal Cancer: A Case-Control Study
Authors: Kevin J Kane, Christopher D Jensen, Jingrong Yang, Huyun Dong, Sophie A Merchant, Pradeep Koripella, Xiaoran Li, Jeffrey M Hendel, Douglas A Corley, Jeffrey K Lee
Journal: Clinical Gastroenterology and Hepatology (2024)
Pathogenic variants in<i>CFAP46</i>,<i>CFAP54</i>,<i>CFAP74</i>, and<i>CFAP221</i>cause Primary Ciliary Dyskinesia with a defective C1d projection of the central apparatus
Authors: Kai Wohlgemuth, Niklas Hoersting, Julia Koenig, Niki Tomas Loges, Johanna Raidt, Sebastian George, Sandra Cindrić, Andre Schramm, Luisa Biebach, Simon Lay, Gerard W Dougherty, Heike Olbrich, Petra Pennekamp, Bernd Dworniczak, Heymut Omran
Journal: European Respiratory Journal (2024)

Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by insufficient mucociliary clearance leading to chronic airway infections. The diagnostic guideline of the European Respiratory Society (ERS) primarily recommends the evaluation of the clinical history (e. g. by the PICADAR prediction tool), nasal nitric oxide (nNO) production rate measurements, high-speed videomicroscopy analysis (HSVMA) of ciliary beating, and the assessment of ciliary axonemes
Residential exposure to<i>Aspergillus spp.</i>is associated with exacerbations in COPD
Authors: Pei Yee Tiew, Janice M Leung, Micheál Mac Aogáin, Parteek Johal, Tavleen Kaur Jaggi, Agnes Che Yan Yuen, Fransiskus Xaverius Ivan, Julia Yang, Tina Afshar, Augustine Tee, Mariko Siyue Koh, Yee Hui Lim, Anthony Wong, Lakshmi Chandrasekaran, Justine G Dacanay, Daniela I Drautz-Moses, Thun How Ong, John A Abisheganaden, Fook Tim Chew, Stephan C Schuster, Christopher Carlsten, Sanjay H Chotirmall
Journal: European Respiratory Journal (2024)

Sensitisation to
Anti-slit diaphragm antibodies on kidney biopsy identify pediatric patients with steroid-resistant nephrotic syndrome responsive to second-line immunosuppressants.
Authors: Valentina Raglianti, Maria Lucia Angelotti, Luigi Cirillo, Fiammetta Ravaglia, Samuela Landini, Viviana Palazzo, Maria Elena Melica, Giulia Antonelli, Carolina Conte, Elisa Buti, Carmela Errichiello, Letizia De Chiara, Anna Julie Peired, Laura Lasagni, Anna Maria Buccoliero, Marco Allinovi, Anna Manonelles Montero, Josep Maria Cruzado, Maurizio Bruschi, Gian Marco Ghiggeri, Andrea Angeletti, Hans-Joachim Anders, Elena Lazzeri, Benedetta Mazzinghi, Francesca Becherucci, Paola Romagnani
Journal: Kidney International (2024)
Fracture Risk Prediction Using the Fracture Risk Assessment Tool in Individuals With Cancer
Authors: Carrie Ye, William D. Leslie, Saeed Al-Azazi, Lin Yan, Lisa M. Lix, Piotr Czaykowski, Eugene V. McCloskey, Helena Johansson, Nicholas C. Harvey, John A. Kanis, Harminder Singh
Journal: JAMA Oncology (2024)

Importance The Fracture Risk Assessment Tool (FRAX) is a fracture risk prediction tool for 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Whether FRAX is useful in individuals with cancer is uncertain. Objective To determine the performance of FRAX for predicting incident fractures in individuals with cancer. Design, Setting, and Participants This retrospective population-based cohort study included residents of Manitoba, Canada, with and without cancer diagnoses from 1987 to 2014. Diagnoses were identified through the Manitoba Cancer Registry. Incident fractures to March 31, 2021, were identified in population-based health care data. Data analysis occurred between January and March 2023. Main Outcomes and Measures FRAX scores were computed for those with bone mineral density (BMD) results that were recorded in the Manitoba BMD Registry. Results This study included 9877 individuals with cancer (mean [SD] age, 67.1 [11.2] years; 8693 [88.0%] female) and 45 877 individuals in the noncancer cohort (mean [SD] age, 66.2 [10.2] years; 41 656 [90.8%] female). Compared to individuals without cancer, those with cancer had higher rates of incident MOF (14.5 vs 12.9 per 1000 person-years; P &amp;amp;lt; .001) and hip fracture (4.2 vs 3.5 per 1000 person-years; P = .002). In the cancer cohort, FRAX with BMD results were associated with incident MOF (HR per SD increase, 1.84 [95% CI, 1.74-1.95]) and hip fracture (HR per SD increase, 3.61 [95% CI, 3.13-4.15]). In the cancer cohort, calibration slopes for FRAX with BMD were 1.03 for MOFs and 0.97 for hip fractures. Conclusions and Relevance In this retrospective cohort study, FRAX with BMD showed good stratification and calibration for predicting incident fractures in patients with cancer. These results suggest that FRAX with BMD can be a reliable tool for predicting incident fractures in individuals with cancer.
Time to COVID-19 Vaccination by Language and Country of Origin
Authors: Margaret B. Nolan, Ella Chrenka, Malini B. DeSilva
Journal: JAMA Network Open (2024)

Importance Disparities in COVID-19 vaccination rates by race and ethnicity are well documented. Less is known about primary language and COVID-19 vaccine uptake. Objective To describe the time to COVID-19 primary series vaccination and booster doses by primary language and country of origin. Design, Setting, and Participants This retrospective cohort study included patients aged 6 months or older with at least 1 health encounter from July 1, 2019, to June 30, 2023, at a single health care system serving patients across Minnesota and western Wisconsin. Exposure Primary language and country of origin documented in the electronic health record. Main Outcomes and Measures Three COVID-19 vaccine coverage outcomes were evaluated: (1) primary series (1 Ad26.COV.S vaccine or 2 mRNA COVID-19 vaccines), (2) first-generation booster (primary series Ad26.COV.S vaccine plus 1 Ad26.COV.S or mRNA COVID-19 vaccine at least 2 months after the second dose or primary series mRNA vaccine plus 1 mRNA vaccine at least 5 months after the second dose), and (3) bivalent booster. Vaccine coverage was described by patient characteristics. Associations of primary language, race and ethnicity, and other patient characteristics with COVID-19 vaccine uptake were evaluated using time-to-event analysis in multivariable Cox proportional hazards regression models, and adjusted hazard ratios (AHRs) with 95% CIs were reported. Results There were 1 001 235 patients included (53.7% female). Most patients reported English as a primary language (94.1%) and were born in the US (91.8%). Primary series coverage was 63.7%; first-generation booster coverage, 64.4%; and bivalent booster coverage, 39.5%. Coverage for all outcomes was lower among those with a non-English primary language compared with English as the primary language (56.9% vs 64.1% for primary series; 47.5% vs 65.3% for first-generation booster; 26.2% vs 40.3% for bivalent booster). Those with a non-English primary language had lower COVID-19 vaccine uptake for the primary series (AHR, 0.85; 95% CI, 0.84-0.86), first-generation booster (AHR, 0.74; 95% CI, 0.73-0.75), and bivalent booster (AHR, 0.65; 95% CI, 0.64-0.67) compared with patients with English as their primary language. Non–US-born patients had higher primary series uptake compared with US-born patients (AHR, 1.19; 95% CI, 1.18-1.20) but similar first-generation booster (AHR, 1.01; 95% CI, 0.99-1.02) and bivalent booster (AHR, 1.00; 95% CI, 0.98-1.02) uptake. Conclusions and Relevance In this retrospective cohort study, patients with a non-English primary language had both lower coverage and delays in receiving COVID-19 vaccines compared with those with English as their primary language. Reporting on language may identify health disparities that can be addressed with language-specific interventions.