tbuckley/cabot-search huggingface dataset:
Experimental demonstration and pan-structurome prediction of climate-associated riboSNitches in Arabidopsis
Authors: Ángel Ferrero-Serrano, Megan M. Sylvia, Peter C. Forstmeier, Andrew J. Olson, Doreen Ware, Philip C. Bevilacqua, Sarah M. Assmann
Journal: Genome biology (2022)

Abstract Background Genome-wide association studies (GWAS) aim to correlate phenotypic changes with genotypic variation. Upon transcription, single nucleotide variants (SNVs) may alter mRNA structure, with potential impacts on transcript stability, macromolecular interactions, and translation. However, plant genomes have not been assessed for the presence of these structure-altering polymorphisms or “riboSNitches.” Results We experimentally demonstrate the presence of riboSNitches in transcripts of two Arabidopsis genes, ZINC RIBBON 3 ( ZR3 ) and COTTON GOLGI-RELATED 3 ( CGR3 ), which are associated with continentality and temperature variation in the natural environment. These riboSNitches are also associated with differences in the abundance of their respective transcripts, implying a role in regulating the gene's expression in adaptation to local climate conditions. We then computationally predict riboSNitches transcriptome-wide in mRNAs of 879 naturally inbred Arabidopsis accessions. We characterize correlations between SNPs/riboSNitches in these accessions and 434 climate descriptors of their local environments, suggesting a role of these variants in local adaptation. We integrate this information in CLIMtools V2.0 and provide a new web resource, T-CLIM, that reveals associations between transcript abundance variation and local environmental variation. Conclusion We functionally validate two plant riboSNitches and, for the first time, demonstrate riboSNitch conditionality dependent on temperature, coining the term “conditional riboSNitch.” We provide the first pan-genome-wide prediction of riboSNitches in plants. We expand our previous CLIMtools web resource with riboSNitch information and with 1868 additional Arabidopsis genomes and 269 additional climate conditions, which will greatly facilitate in silico studies of natural genetic variation, its phenotypic consequences, and its role in local adaptation.
COVID-19 Vaccination and Estimated Public Health Impact in California
Authors: Sophia T. Tan, Hailey J. Park, Isabel Rodríguez-Barraquer, George W. Rutherford, Kirsten Bibbins-Domingo, Robert Schechter, Nathan C. Lo
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Despite widespread vaccination against COVID-19 in the United States, there are limited empirical data quantifying their public health impact in the population. <h3>Objective</h3> To estimate the number of COVID-19 cases, hospitalizations, and deaths directly averted because of COVID-19 vaccination in California. <h3>Design, Setting, and Participants</h3> This modeling study used person-level data provided by the California Department of Public Health (CDPH) on COVID-19 cases, hospitalizations, and deaths as well as COVID-19 vaccine administration from January 1, 2020, to October 16, 2021. A statistical model was used to estimate the number of COVID-19 cases that would have occurred in the vaccine era (November 29, 2020, to October 16, 2021) in the absence of vaccination based on the ratio of the number of cases among the unvaccinated (aged &lt;12 years) and vaccine-eligible groups (aged ≥12 years) before vaccine introduction. Vaccine-averted COVID-19 cases were estimated by finding the difference between the projected and observed number of COVID-19 cases. Averted COVID-19 hospitalizations and deaths were assessed by applying estimated hospitalization and case fatality risks to estimates of vaccine-averted COVID-19 cases. As a sensitivity analysis, a second independent model was developed to estimate the number of vaccine-averted COVID-19 outcomes by applying published data on vaccine effectiveness to data on COVID-19 vaccine administration and estimated risk of COVID-19 over time. <h3>Exposure</h3> COVID-19 vaccination. <h3>Main Outcomes and Measures</h3> Number of COVID-19 cases, hospitalizations, and deaths estimated to have been averted because of COVID-19 vaccination. <h3>Results</h3> There were 4 585 248 confirmed COVID-19 cases, 240 718 hospitalizations, and 70 406 deaths in California from January 1, 2020, to October 16, 2021, during which 27 164 680 vaccine-eligible individuals aged 12 years and older were reported to have received at least 1 dose of a COVID-19 vaccine in the vaccine era (79.5% of the eligible population). The primary model estimated that COVID-19 vaccination averted 1 523 500 (95% prediction interval [PI], 976 800-2 230 800) COVID-19 cases in California, corresponding to a 72% (95% PI, 53%-91%) relative reduction in cases because of vaccination. COVID-19 vaccination was estimated to have averted 72 930 (95% PI, 53 250-99 160) hospitalizations and 19 430 (95% PI, 14 840-26 230) deaths during the study period. The alternative model identified comparable findings. <h3>Conclusions and Relevance</h3> This study provides evidence of the public health benefit of COVID-19 vaccination in the United States and further supports the urgency for continued vaccination.
Decentralized Distributed Multi-institutional PET Image Segmentation Using a Federated Deep Learning Framework
Authors: Isaac Shiri, Alireza Vafaei Sadr, Mehdi Amini, Yazdan Salimi, Amirhossein Sanaat, Azadeh Akhavanallaf, Behrooz Razeghi, Sohrab Ferdowsi, Abdollah Saberi, Hossein Arabi, Minerva Becker, Slava Voloshynovskiy, Deniz Gündüz, Arman Rahmim, Habib Zaidi
Journal: Clinical Nuclear Medicine (2022)

Purpose The generalizability and trustworthiness of deep learning (DL)–based algorithms depend on the size and heterogeneity of training datasets. However, because of patient privacy concerns and ethical and legal issues, sharing medical images between different centers is restricted. Our objective is to build a federated DL-based framework for PET image segmentation utilizing a multicentric dataset and to compare its performance with the centralized DL approach. Methods PET images from 405 head and neck cancer patients from 9 different centers formed the basis of this study. All tumors were segmented manually. PET images converted to SUV maps were resampled to isotropic voxels (3 × 3 × 3 mm 3 ) and then normalized. PET image subvolumes (12 × 12 × 12 cm 3 ) consisting of whole tumors and background were analyzed. Data from each center were divided into train/validation (80% of patients) and test sets (20% of patients). The modified R2U-Net was used as core DL model. A parallel federated DL model was developed and compared with the centralized approach where the data sets are pooled to one server. Segmentation metrics, including Dice similarity and Jaccard coefficients, percent relative errors (RE%) of SUV peak , SUV mean , SUV median , SUV max , metabolic tumor volume, and total lesion glycolysis were computed and compared with manual delineations. Results The performance of the centralized versus federated DL methods was nearly identical for segmentation metrics: Dice (0.84 ± 0.06 vs 0.84 ± 0.05) and Jaccard (0.73 ± 0.08 vs 0.73 ± 0.07). For quantitative PET parameters, we obtained comparable RE% for SUV mean (6.43% ± 4.72% vs 6.61% ± 5.42%), metabolic tumor volume (12.2% ± 16.2% vs 12.1% ± 15.89%), and total lesion glycolysis (6.93% ± 9.6% vs 7.07% ± 9.85%) and negligible RE% for SUV max and SUV peak . No significant differences in performance ( P &gt; 0.05) between the 2 frameworks (centralized vs federated) were observed. Conclusion The developed federated DL model achieved comparable quantitative performance with respect to the centralized DL model. Federated DL models could provide robust and generalizable segmentation, while addressing patient privacy and legal and ethical issues in clinical data sharing.
Bempegaldesleukin plus nivolumab in first-line renal cell carcinoma: results from the PIVOT-02 study
Authors: Nizar M Tannir, Daniel C Cho, Adi Diab, Mario Sznol, Mehmet A Bilen, Arjun V Balar, Giovanni Grignani, Erika Puente, Lily Tang, David Chien, Ute Hoch, Arkopal Choudhury, Danni Yu, Sue L Currie, Mary A Tagliaferri, Jonathan Zalevsky, Arlene O Siefker-Radtke, Michael E Hurwitz
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Immune checkpoint inhibitor-based combinations have expanded the treatment options for patients with renal cell carcinoma (RCC); however, tolerability remains challenging. The aim of this study was to evaluate the safety and efficacy of the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) as first-line therapy in patients with advanced clear-cell RCC. Methods This was an open-label multicohort, multicenter, single-arm phase 1/2 study; here, we report results from the phase 1/2 first-line RCC cohort (N=49). Patients received BEMPEG 0.006 mg/kg plus NIVO 360 mg intravenously every 3 weeks. The primary objectives were safety and objective response rate (ORR; patients with measurable disease at baseline and at least one postbaseline tumor response assessment). Secondary objectives included overall survival (OS) and progression-free survival (PFS). Exploratory biomarker analyses: association between baseline biomarkers and ORR. Results At a median follow-up of 32.7 months, the ORR was 34.7% (17/49 patients); 3/49 patients (6.1%) had a complete response. Of the 17 patients with response, 14 remained in response for &gt;6 months, and 6 remained in response for &gt;24 months. Median PFS was 7.7 months (95% CI 3.8 to 13.9), and median OS was not reached (95% CI 37.3 to not reached). Ninety-eight per cent (48/49) of patients experienced ≥1 treatment-related adverse event (TRAE) and 38.8% (19/49) had grade 3/4 TRAEs, most commonly syncope (8.2%; 4/49) and increased lipase (6.1%; 3/49). No association between exploratory biomarkers and ORR was observed. Limitations include the small sample size and single-arm design. Conclusions BEMPEG plus NIVO showed preliminary antitumor activity as first-line therapy in patients with advanced clear-cell RCC and was well tolerated. These findings warrant further investigation.
Monoclonal gammopathy of renal significance (MGRS): Real‐world data on outcomes and prognostic factors
Authors: Alessandro Gozzetti, Andrea Guarnieri, Elena Zamagni, Elena Zakharova, Daniel Coriu, Max Bittrich, Tomáš Pika, Natalia Tovar, Natalia Schutz, Sara Ciofini, Camila Peña, Serena Rocchi, Michael Rassner, Irit Avivi, Anna Waszczuk‐Gajda, Saurabh Chhabra, Lidia Usnarska‐Zubkiewicz, Verónica González‐Calle, Maria‐Victoria Mateos, Monica Bocchia, Flavia Bigi, Hannah Füllgraf, Bhavna Bhasin‐Chhabra, Massimo Gentile, Julio Davila, David H. Vesole, Michele Cavo, Bicky Thapa, Edvan Crusoe, Hermann Einsele, Wojciech Legiec, Grzegorz Charliński, Artur Jurczyszyn
Journal: American Journal of Hematology (2022)

Abstract Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis‐related to MGRS (MGRS‐A) was present in 180 patients; nonamyloidosis MGRS (MGRS‐NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0–121.0). Patients with MGRS‐A had a shorter overall survival than patients with MGRS‐NA (HR = 0.41, 95%CI: 0.25–0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04–115.96; p &lt; 0.0001), one‐fourth of patients with ≥VGPR were renal nonresponders. In MGRS‐A, factors associated with poor prognosis included elevated levels of creatinine, beta‐2‐microglobulin, and hemodialysis at diagnosis. In MGRS‐NA, only age &gt;65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS.
Evaluation of Racial Disparities in Quality of Care for Patients With Gastrointestinal Tract Cancer Treated With Surgery
Authors: Baylee F. Bakkila, Daniel Kerekes, Marcella Nunez-Smith, Kevin G. Billingsley, Nita Ahuja, Karen Wang, Carol Oladele, Caroline H. Johnson, Sajid A. Khan
Journal: JAMA Network Open (2022)

Racial disparities have been demonstrated in many facets of health care, but a comprehensive understanding of who is most at risk for substandard surgical care of gastrointestinal tract cancers is lacking.To examine racial disparities in quality of care of patients with gastrointestinal tract cancers.This retrospective cohort study of patients with gastrointestinal tract cancer included the US population as captured in the National Cancer Database with a diagnosis from January 1, 2004, to December 31, 2017. Participants included 565 124 adults who underwent surgical resection of gastrointestinal tract cancers. Data were analyzed from June 21 to December 23, 2021.Race and site of cancer.Oncologic standard of care, as defined by negative resection margin, adequate lymphadenectomy, and receipt of indicated adjuvant chemotherapy and/or radiotherapy.Among 565 124 adult patients who underwent surgical resection of a gastrointestinal tract cancer, 10.9% were Black patients, 83.5% were White patients, 54.7% were men, and 50.7% had Medicare coverage. The most common age range at diagnosis was 60 to 69 years (28.5%). Longer median survival was associated with negative resection margins (87.3 [IQR, 28.5-161.9] months vs 22.9 [IQR, 8.8-69.2] months; P < .001) and adequate lymphadenectomies (80.7 [IQR, 25.6 to not reached] months vs 57.6 [IQR, 17.7-153.8] months; P < .001). After adjustment for covariates, Black patients were less likely than White patients to have negative surgical margins overall (odds ratio [OR], 0.96 [95% CI, 0.93-0.98]) and after esophagectomy (OR, 0.71 [95% CI, 0.58-0.87]), proctectomy (OR, 0.71 [95% CI, 0.66-0.76]), and biliary resection (OR, 0.75 [95% CI, 0.61-0.91]). Black patients were also less likely to have adequate lymphadenectomy overall (OR, 0.89 [95% CI, 0.87-0.91]) and after colectomy (OR, 0.89 [95% CI, 0.87-0.92]), esophagectomy (OR, 0.72 [95% CI, 0.63-0.83]), pancreatectomy (OR, 0.90 [95% CI, 0.85-0.96]), proctectomy (OR, 0.93 [95% CI, 0.88-0.98]), proctocolectomy (OR, 0.90 [95% CI, 0.81-1.00]), and enterectomy (OR, 0.71 [95% CI, 0.65-0.79]). Black patients were more likely than White patients not to be recommended for chemotherapy (OR, 1.15 [95% CI, 1.10-1.21]) and radiotherapy (OR, 1.49 [95% CI, 1.35-1.64]) because of comorbidities and more likely not to receive recommended chemotherapy (OR, 1.68 [95% CI, 1.55-1.82]) and radiotherapy (OR, 2.18 [95% CI, 1.97-2.41]) for unknown reasons.These findings suggest that there are significant racial disparities in surgical care of gastrointestinal tract cancers. Black patients are less likely than White patients to receive standard of care with respect to negative surgical margins, adequate lymphadenectomies, and use of adjuvant therapies. Both system- and physician-level reforms are needed to eradicate these disparities in health care.
Targeting TGF-β signal transduction for fibrosis and cancer therapy
Authors: Dandan Peng, Minyang Fu, Manni Wang, Yuquan Wei, Xiawei Wei
Journal: Molecular Cancer (2022)

Transforming growth factor β (TGF-β) has long been identified with its intensive involvement in early embryonic development and organogenesis, immune supervision, tissue repair, and adult homeostasis. The role of TGF-β in fibrosis and cancer is complex and sometimes even contradictory, exhibiting either inhibitory or promoting effects depending on the stage of the disease. Under pathological conditions, overexpressed TGF-β causes epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, cancer-associated fibroblast (CAF) formation, which leads to fibrotic disease, and cancer. Given the critical role of TGF-β and its downstream molecules in the progression of fibrosis and cancers, therapeutics targeting TGF-β signaling appears to be a promising strategy. However, due to potential systemic cytotoxicity, the development of TGF-β therapeutics has lagged. In this review, we summarized the biological process of TGF-β, with its dual role in fibrosis and tumorigenesis, and the clinical application of TGF-β-targeting therapies.
Use of a Bougie vs Endotracheal Tube With Stylet and Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation—Reply
Authors: Brian E. Driver, Matthew E. Prekker, Jonathan D. Casey
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Venetoclax combinations delay the time to deterioration of HRQoL in unfit patients with acute myeloid leukemia
Authors: Keith W. Pratz, Panayiotis Panayiotidis, Christian Recher, Xudong Wei, Brian A. Jonas, Pau Montesinos, Vladimir Ivanov, Andre C. Schuh, Courtney D. DiNardo, Jan Novak, Vlatko Pejsa, Don Stevens, Su-Peng Yeh, Inho Kim, Mehmet Turgut, Nicola Fracchiolla, Kazuhito Yamamoto, Yishai Ofran, Andrew H. Wei, Cat N. Bui, Katy Benjamin, Rajesh Kamalakar, Jalaja Potluri, Wellington Mendes, Jacob Devine, Walter Fiedler
Journal: Blood Cancer Journal (2022)

Abstract Phase 3 trials Viale-A and Viale-C evaluated health-related quality of life (HRQoL) in patients with AML unfit for intensive chemotherapy who received venetoclax (VEN) + (AZA) (Viale-A) or low-dose cytarabine (LDAC) (Viale-C) or placebo (PBO) + AZA or LDAC. Patient-reported outcomes included: EORTC QLQ-C30 global health status (GHS/QoL) and physical functioning (PF), PROMIS Cancer Fatigue Short Form 7a (Fatigue), and EQ-5D-5L health status visual analog scale (HS-VAS). Time to deterioration (TTD), defined as worsening from baseline in meaningful change thresholds (MCT) of ≥10, 5, or 7 points for GHS/QoL or PF, fatigue, and HS-VAS, respectively, was assessed; differences between groups were analyzed using Kaplan-Meier and unadjusted log-rank analyses. VEN + AZA vs PBO + AZA patients had longer TTD in GHS/QoL ( P = 0.066) and fatigue ( P = 0.189), and significantly longer TTD in PF ( P = 0.028) and HS-VAS ( P &lt; 0.001). VEN + LDAC vs PBO + LDAC patients had significantly longer TTD in GHS/QoL ( P = 0.011), P F ( P = 0.020), and fatigue ( P = 0.004), and a trend in HS-VAS ( P = 0.057). Approximately 43%, 35%, 32%, and 18% of patients treated with VEN + AZA, AZA + PBO, VEN + LDAC, or LDAC + PBO, respectively, saw improvements &gt;MCT in GHS/QoL. Overall, VEN may positively impact HRQoL in patients with AML ineligible for intensive chemotherapy, leading to longer preservation of functioning and overall health status.
Assessment of cell cycle regulators in human peripheral blood cells as markers of cellular senescence
Authors: Lihuan Guan, Karen C. Crasta, Andrea B. Maier
Journal: Ageing Research Reviews (2022)

Cellular senescence has gained increasing interest during recent years, particularly due to causal involvement in the aging process corroborated by multiple experimental findings. Indeed, cellular senescence considered to be one of the hallmarks of aging, is defined as a stable growth arrest predominantly mediated by cell cycle regulators p53, p21 and p16. Senescent cells have frequently been studied in the peripheral blood of humans due to its accessibility. This review summarizes ex vivo studies describing cell cycle regulators as markers of senescence in human peripheral blood cells, along with detection methodologies and associative studies examining demographic and clinical characteristics. The utility of techniques such as the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), microarray, RNA sequencing and nCounter technologies for detection at the transcriptional level, along with Western blotting, enzyme-linked immunosorbent assay and flow cytometry at the translational level, will be brought up at salient points throughout this review. Notably, housekeeping genes or proteins serving as controls such as GAPDH and β-Actin, were found not to be stably expressed in some contexts. As such, optimization and validation of such genes during experimental design were recommended. In addition, the expression of cell cycle regulators was found to vary not only between different types of blood cells such as T cells and B cells but also between stages of cellular differentiation such as naïve T cells and highly differentiated T cells. On the other hand, the associations of the presence of cell cycle regulators with demographics (age, gender, ethnicity, and socioeconomic status), clinical characteristics (body mass index, specific diseases, disease-related parameters) and lifestyle vary in groups of participants. One envisions that increased understanding and insights into the assessment of cell cycle regulators as markers of senescence in human peripheral blood cells will help inform prognostication and clinical intervention in elderly individuals.
Prostate-Specific Membrane Antigen–Avid Bone Metastases From Urothelial Carcinoma of the Bladder
Authors: Bo Zhao, Aisheng Dong, Changjing Zuo
Journal: Clinical Nuclear Medicine (2022)

Prostate-specific membrane antigen (PSMA) PET findings of urothelial carcinoma were rarely reported. We describe 18 F-FDG PET/CT and 68 Ga-PSMA-11 PET/MRI findings in a case of urothelial carcinoma of the bladder with bone metastases in the sternum, ribs, spine, pelvis, and femurs. The bone metastases showed isodensity to hyperdensity and mild to intense FDG uptake on FDG PET/CT and moderate to intense PSMA uptake on PSMA PET/MRI. PSMA PET/MRI more clearly delineated the bone metastases compared with FDG PET/CT.