tbuckley/cabot-search huggingface dataset:
Carcinogenicity of cobalt, antimony compounds, and weapons-grade tungsten alloy
Authors: Margaret R Karagas, Amy Wang, David C Dorman, Amy L Hall, Jingbo Pi, Consolato M Sergi, Elaine Symanski, Elizabeth M Ward, Victoria H Arrandale, Kenichi Azuma, Eduardo Brambila, Gloria M Calaf, Jason M Fritz, Shoji Fukushima, Joanna M Gaitens, Tom K Grimsrud, Lei Guo, Elsebeth Lynge, Amélia P Marinho-Reis, Melissa A McDiarmid, Daniel R S Middleton, Thomas P Ong, David A Polya, Betzabet Quintanilla-Vega, Georgia K Roberts, Tiina Santonen, Riitta Sauni, Maria J Silva, Pascal Wild, Changwen W Zhang, Qunwei Zhang, Yann Grosse, Lamia Benbrahim-Tallaa, Aline de Conti, Nathan L DeBono, Fatiha El Ghissassi, Federica Madia, Bradley Reisfeld, Leslie T Stayner, Eero Suonio, Susana Viegas, Roland Wedekind, Shukrullah Ahmadi, Heidi Mattock, William M Gwinn, Mary K Schubauer-Berigan
Journal: The Lancet Oncology (2022)
Mitochondria and the future of RASopathies: the emergence of bioenergetics
Authors: Maria I. Kontaridis, Saravanakkumar Chennappan
Journal: Journal of Clinical Investigation (2022)

RASopathies are a family of rare autosomal dominant disorders that affect the canonical Ras/MAPK signaling pathway and manifest as neurodevelopmental systemic syndromes, including Costello syndrome (CS). In this issue of the JCI, Dard et al. describe the molecular determinants of CS using a myriad of genetically modified models, including mice expressing HRAS p.G12S, patient-derived skin fibroblasts, hiPSC-derived human cardiomyocytes, an HRAS p.G12V zebrafish model, and human lentivirally induced fibroblasts overexpressing HRAS p.G12S or HRAS p.G12A. Mitochondrial proteostasis and oxidative phosphorylation were altered in CS, and inhibition of the AMPK signaling pathway mediated bioenergetic changes. Importantly, the pharmacological induction of this pathway restored cardiac function and reduced the developmental defects associated with CS. These findings identify a role for altered bioenergetics and provide insights into more effective treatment strategies for patients with RASopathies.
Diagnostic Imaging and Medical Management of Acute Left-Sided Colonic Diverticulitis
Authors: Ethan M. Balk, Gaelen P. Adam, Monika Reddy Bhuma, Kristin J. Konnyu, Ian J. Saldanha, Michael D. Beland, Nishit Shah
Journal: Annals of Internal Medicine (2021)

Clinicians need to better understand the value of computed tomography (CT) imaging and nonsurgical treatment options to manage acute left-sided colonic diverticulitis. To evaluate CT imaging, outpatient treatment of uncomplicated diverticulitis, antibiotic treatment, and interventional radiology for patients with complicated diverticulitis. MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, CINAHL, and ClinicalTrials.gov from 1 January 1990 through 16 November 2020. Existing systematic reviews of CT imaging accuracy, as well as randomized trials and adjusted nonrandomized comparative studies reporting clinical or patient-centered outcomes. 6 researchers extracted study data and risk of bias, which were verified by an independent researcher. The team assessed strength of evidence across studies. Based on moderate-strength evidence, CT imaging is highly accurate for diagnosing acute diverticulitis. For patients with uncomplicated acute diverticulitis, 6 studies provide low-strength evidence that initial outpatient and inpatient management have similar risks for recurrence or elective surgery, but they provide insufficient evidence regarding other outcomes. Also, for patients with uncomplicated acute diverticulitis, 5 studies comparing antibiotics versus no antibiotics provide low-strength evidence that does not support differences in risks for treatment failure, elective surgery, recurrence, posttreatment complications, and other outcomes. Evidence is insufficient to determine choice of antibiotic regimen (7 studies) or effect of percutaneous drainage (2 studies). The evidence base is mostly of low strength. Studies did not adequately assess heterogeneity of treatment effect. Computed tomography imaging is accurate for diagnosing acute diverticulitis. For patients with uncomplicated diverticulitis, no differences in outcomes were found between outpatient and inpatient care. Avoidance of antibiotics for uncomplicated acute diverticulitis may be safe for most patients. The evidence is too sparse for other evaluated questions. Agency for Healthcare Research and Quality and American College of Physicians. (PROSPERO: CRD42020151246).
Expansion of CD4dimCD8+ T cells characterizes macrophage activation syndrome and other secondary HLH
Authors: Arianna De Matteis, Manuela Colucci, Marianna N. Rossi, Ivan Caiello, Pietro Merli, Nicola Tumino, Valentina Bertaina, Manuela Pardeo, Claudia Bracaglia, Franco Locatelli, Fabrizio De Benedetti, Giusi Prencipe
Journal: Blood (2022)
Diminished Immune Surveillance during Histologic Progression of Intraductal Papillary Mucinous Neoplasms Offers a Therapeutic Opportunity for Cancer Interception
Authors: Sharia Hernandez, Edwin Roger Parra, Naohiro Uraoka, Ximing Tang, Yu Shen, Wei Qiao, Mei Jiang, Shanyu Zhang, Barbara Mino, Wei Lu, Renganayaki Pandurengan, Cara Haymaker, Kajsa Affolter, Courtney L. Scaife, Michele Yip-Schneider, C. Max Schmidt, Matthew A. Firpo, Sean J. Mulvihill, Eugene J. Koay, Huamin Wang, Ignacio I. Wistuba, Anirban Maitra, Luisa M. Solis, Subrata Sen
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Intraductal papillary mucinous neoplasms (IPMN) are bona fide precursors to pancreatic ductal adenocarcinoma (PDAC). While genomic alterations during multistep IPMN progression have been well cataloged, the accompanying changes within the tumor immune microenvironment (TIME) have not been comprehensively studied. Herein, we investigated TIME-related alterations during IPMN progression, using multiplex immunofluorescence (mIF) coupled with high-resolution image analyses. Experimental Design: Two sets of formalin-fixed, paraffin-embedded tissue samples from surgically resected IPMNs were analyzed. The training set of 30 samples consisted of 11 low-grade IPMN (LG-IPMN), 17 high-grade IPMN (HG-IPMN), and 2 IPMN with PDAC, while a validation set of 93 samples comprised of 55 LG-IPMN and 38 HG-IPMN. The training set was analyzed with two panels of immuno-oncology–related biomarkers, while the validation set was analyzed with a subset of markers found significantly altered in the training set. Results: Cell types indicative of enhanced immune surveillance, including cytotoxic and memory T cells, and antigen-experienced T cells and B cells, were all found at higher densities within isolated LG-IPMNs compared with HG-IPMNs. Notably, the TIME of LG-IPMNs that had progressed at the time of surgical resection (progressor LGD) resembled that of the synchronous HG-IPMNs, underscoring that attenuated immune surveillance occurs even in LG-IPMNs destined for progression. Conclusions: Our findings provide a basis for interception of cystic neoplasia to PDAC, through maintenance of sustained immune surveillance using vaccines and other prevention approaches.
Implications of the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Chest Pain Guideline for Cardiovascular Imaging
Authors: Ron Blankstein, Leslee J. Shaw, Martha Gulati, Michael K. Atalay, Jeroen Bax, Dennis A. Calnon, Christopher K. Dyke, Maros Ferencik, Jonathan F. Heitner, Timothy D. Henry, Judy Hung, Juhani Knuuti, Jonathan R. Lindner, Lawrence M. Phillips, Subha V. Raman, Sunil V. Rao, Frank J. Rybicki, Antti Saraste, Raymond F. Stainback, Randall C. Thompson, Eric Williamson, Koen Nieman, Jennifer A. Tremmel, Pamela K. Woodard, Marcelo F. Di Carli, Y.S. Chandrashekhar
Journal: JACC. Cardiovascular imaging (2022)
How do psychologically based interventions for chronic musculoskeletal pain work? A systematic review and meta-analysis of specific moderators and mediators of treatment
Authors: Carlos Murillo, Tat-Thang Vo, Stijn Vansteelandt, Lauren E. Harrison, Barbara Cagnie, Iris Coppieters, Marjolein Chys, Inge Timmers, Mira Meeus
Journal: Clinical Psychology Review (2022)
Prediction of End-Stage Kidney Disease Using Estimated Glomerular Filtration Rate With and Without Race
Authors: Joshua D. Bundy, Katherine T. Mills, Amanda H. Anderson, Wei Yang, Jing Chen, Jiang He
Journal: Annals of Internal Medicine (2022)

Background: New estimated glomerular filtration rate (eGFR) equations removed race adjustment, but the impact of its removal on prediction of end-stage kidney disease (ESKD) is unknown. Objective: To compare the ESKD prediction performance of different eGFR equations. Design: Observational, prospective cohort study. Setting: 7 U.S. clinical centers. Participants: 3873 participants with chronic kidney disease (CKD) from the CRIC (Chronic Renal Insufficiency Cohort) Study contributing 13 902 two-year risk periods. Measurements: ESKD was defined as initiation of dialysis or transplantation. eGFR was calculated using 5 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on serum creatinine and/or cystatin C, with or without race adjustment. The predicted 2-year risk for ESKD was calculated using the 4-variable Kidney Failure Risk Equation (KFRE). We evaluated the prediction performance of eGFR equations and the KFRE score using discrimination and calibration analyses. Results: During a maximum 16 years of follow-up, 856 participants developed ESKD. Across all eGFR equations, the KFRE score was superior for predicting 2-year incidence of ESKD compared with eGFR alone (area under the curve ranges, 0.945 to 0.954 vs. 0.900 to 0.927). Prediction performance of KFRE scores using different eGFR equations was similar, but the creatinine equation without race adjustment improved calibration among Black participants. Among all participants, compared with an eGFR less than 20 mL/min/1.73 m2, a KFRE score greater than 20% had similar specificity for predicting 2-year ESKD risk (ranges, 0.94 to 0.97 vs. 0.95 to 0.98) but higher sensitivity (ranges, 0.68 to 0.78 vs. 0.42 to 0.66). Limitation: Data are solely from the United States. Conclusion: The KFRE score better predicts 2-year risk for ESKD compared with eGFR alone, regardless of race adjustment. The creatinine equation with age and sex may improve calibration among Black patients. A KFRE score greater than 20% showed high specificity and sensitivity for predicting 2-year risk for ESKD. Primary Funding Source: National Institutes of Health.
Static Socio-Ecological COVID-19 Vulnerability Index and Vaccine Hesitancy Index for England
Authors: Claire E. Welsh, David R. Sinclair, Fiona E. Matthews
Journal: The Lancet Regional Health - Europe (2021)

Population characteristics can be used to infer vulnerability of communities to COVID-19, or to the likelihood of high levels of vaccine hesitancy. Communities harder hit by the virus, or at risk of being so, stand to benefit from greater resource allocation than their population size alone would suggest. This study reports a simple but efficacious method of ranking small areas of England by relative characteristics that are linked with COVID-19 vulnerability and vaccine hesitancy.Publicly available data on a range of characteristics previously linked with either poor COVID-19 outcomes or vaccine hesitancy were collated for all Middle Super Output Areas of England (MSOA, n=6790, excluding Isles of Scilly), scaled and combined into two numeric indices. Multivariable linear regression was used to build a parsimonious model of vulnerability (static socio-ecological vulnerability index, SEVI) in 60% of MSOAs, and retained variables were used to construct two simple indices. Assuming a monotonic relationship between indices and outcomes, Spearman correlation coefficients were calculated between the SEVI and cumulative COVID-19 case rates at MSOA level in the remaining 40% of MSOAs over periods both during and out with national lockdowns. Similarly, a novel vaccine hesitancy index (VHI) was constructed using population characteristics aligned with factors identified by an Office for National Statistics (ONS) survey analysis. The relationship between the VHI and vaccine coverage in people aged 12+years (as of 2021-06-24) was determined using Spearman correlation. The indices were split into quintiles, and MSOAs within the highest vulnerability and vaccine hesitancy quintiles were mapped.The SEVI showed a moderate to strong relationship with case rates in the validation dataset across the whole study period, and for every intervening period studied except early in the pandemic when testing was highly selective. The SEVI was more strongly correlated with case rates than any of its domains (rs 0·59 95% CI 0.57-0.62) and outperformed an existing MSOA-level vulnerability index. The VHI was significantly negatively correlated with COVID-19 vaccine coverage in the validation data at the time of writing (rs -0·43 95% CI -0·46 to -0·41). London had the largest number and proportion of MSOAs in quintile 5 (most vulnerable/hesitant) of SEVI and VHI concurrently.The indices presented offer an efficacious way of identifying geographical disparities in COVID-19 risk, thus helping focus resources according to need.Funder: Integrated Covid Hub North East.n/a.Fiona Matthews.
Venous Tone and Stressed Blood Volume in Heart Failure
Authors: Marat Fudim, David M. Kaye, Barry A. Borlaug, Sanjiv J. Shah, Stuart Rich, Navin K. Kapur, Maria Rosa Costanzo, Michael I. Brener, Kenji Sunagawa, Daniel Burkhoff
Journal: Journal of the American College of Cardiology (2022)
Maladaptive myelination promotes generalized epilepsy progression
Authors: Juliet K. Knowles, Haojun Xu, Caroline Soane, Ankita Batra, Tristan Saucedo, Eleanor Frost, Lydia T. Tam, Danielle Fraga, Lijun Ni, Katlin Villar, Sydney Talmi, John R. Huguenard, Michelle Monje
Journal: Nature Neuroscience (2022)

Activity-dependent myelination can fine-tune neural network dynamics. Conversely, aberrant neuronal activity, as occurs in disorders of recurrent seizures (epilepsy), could promote maladaptive myelination, contributing to pathogenesis. In this study, we tested the hypothesis that activity-dependent myelination resulting from absence seizures, which manifest as frequent behavioral arrests with generalized electroencephalography (EEG) spike-wave discharges, promote thalamocortical network hypersynchrony and contribute to epilepsy progression. We found increased oligodendrogenesis and myelination specifically within the seizure network in two models of generalized epilepsy with absence seizures (Wag/Rij rats and Scn8a
Naturally Selected CD7 CAR-T Therapy without Genetic Manipulations for T-ALL/LBL: First-in-human Phase I Clinical Trial
Authors: Peihua Lu, Ying Liu, Junfang Yang, Xian Zhang, Xiao Yang, Hui Wang, Lin Wang, Qinglong Wang, David Jin, Jianqiang Li, Xiaojun Huang
Journal: Blood (2022)

Derivation of CD7-targeted chimeric antigen receptor (7CAR) T cells often requires genetic manipulations to ablate the CD7 gene or block CD7 cell surface expression. Our novel approach deriving naturally selected 7CAR-T cells (NS7CAR) from bulk T cells were able to overcome major fratricide by minimizing accessible CD7 epitopes. The CD7 molecules of NS7CAR-T cells were masked or sequestered by the CD7-targeting CAR. Compared to sorted CD7-negative 7CAR-T cells and CD7 knocked-out 7CAR-T cells, NS7CAR exhibited similar or superior therapeutic properties including a greater percentage of CAR+ cells and a higher proportion of CD8+ central memory T cells. In our first-in-human phase 1 trial (NCT04572308), 20 patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL, n=14) and lymphoblastic lymphoma (T-LBL, n=6) were treated with NS7CAR. Nineteen patients achieved minimal residual disease negative complete remission (CR) in the bone marrow by Day 28 and 5 of 9 patients achieved extramedullary CR. With a median follow-up of 142.5 (32-311) days post infusion, 14 patients subsequently received allogeneic hematopoietic stem cell transplant (10 consolidative, 4 salvage) following NS7CAR infusion with no relapses to date. Of the six patients who did not receive a transplant, four remained in CR at a median time of 54 (32-180) days. Eighteen patients experienced mild cytokine release syndrome (CRS, Grade ≤2), one developed Grade 3 CRS, and two had Grade 1 neurotoxicity. These results indicate that NS7CAR-T therapy is a safe and highly effective treatment for T-ALL/T-LBL. More patients and longer follow-up are needed for validation. Clinical Trial can be found at NCT04572308, https://clinicaltrials.gov/
The characteristics of seronegative and seropositive non-hepatitis-associated cryoglobulinemic glomerulonephritis
Authors: Vincent Javaugue, Anthony M Valeri, Insara Jaffer Sathick, Samar M Said, Sibel Erdogan Damgard, David L Murray, Tyler Klobucher, Nicole K Andeen, Sanjeev Sethi, Fernando C Fervenza, Nelson Leung, Samih H Nasr
Journal: Kidney International (2022)
The Charcot–Leyden crystal protein galectin‐10 is not a major determinant of human regulatory T‐cell function
Authors: Rebeca Arroyo‐Hornero, Helena Aegerter, Ibrahim Hamad, Beatriz Corte‐Real, Katrien Staes, Bas van der Woning, Kenneth Verstraete, Savvas N. Savvides, Bart N. Lambrecht, Markus Kleinewietfeld
Journal: Allergy (2022)

Bart Lambrecht has received consultancy fees from Astra-Zeneca, Sanofi, GSK, Novartis, Oncoarendi and argenx BV. Bas van der Woning is a full-time employee of argenx BV. These disclosures do not affect content of this article. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Colorectal Cancer Genomics by Genetic Ancestry
Authors: Cathy Eng, Andreana N. Holowatyj
Journal: Cancer Discovery (2022)

Understanding molecular features of colorectal cancer across diverse populations is an indispensable step toward reducing the pronounced disparities in this disease burden. Based on the findings that individuals of African ancestry have an observed increase in the frequency of KRAS, AOC, and PIK3CA mutations, Myer and colleagues suggest that patients of African ancestry should consider treatment and clinical trials specific to these mutations. See related article by Myer et al., p. 1282 (2).
SARS-CoV-2 Omicron sublineage BA.2 replaces BA.1.1: Genomic surveillance in Japan from September 2021 to March 2022
Authors: Yosuke Hirotsu, Makoto Maejima, Masahiro Shibusawa, Yume Natori, Yuki Nagakubo, Kazuhiro Hosaka, Hitomi Sueki, Hitoshi Mochizuki, Toshiharu Tsutsui, Yumiko Kakizaki, Yoshihiro Miyashita, Masao Omata
Journal: Journal of Infection (2022)
Calcium-Based Phosphate Binders and Plasma Oxalate Concentration in Dialysis Patients
Authors: Yoshinari Oka, Masashi Miyazaki, Shigeko Takatsu, Hiroaki Matsuda
Journal: Journal of the American Society of Nephrology (2022)

Pfau et al. [1][1] demonstrated that high serum oxalate levels are a new risk factor for sudden cardiac death in patients receiving hemodialysis. Cardiovascular death in patients receiving hemodialysis has been a major problem for a long time. Various studies on CKD–mineral and bone disorders have
Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions
Authors: Simon C. Dyall, Laurence Balas, Nicolas G. Bazan, J. Thomas Brenna, Nan Chiang, Felipe da Costa Souza, Jesmond Dalli, Thierry Durand, Jean-Marie Galano, Pamela J. Lein, Charles N. Serhan, Ameer Y. Taha
Journal: Progress in Lipid Research (2022)

Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids, and influence cellular function via effects on membrane properties, and also by acting as a precursor pool for lipid mediators. These lipid mediators are formed via activation of pathways involving at least one step of dioxygen-dependent oxidation, and are consequently called oxylipins. Their biosynthesis can be either enzymatically-dependent, utilising the promiscuous cyclooxygenase, lipoxygenase, or cytochrome P450 mixed function oxidase pathways, or nonenzymatic via free radical-catalyzed pathways. The oxylipins include the classical eicosanoids, comprising prostaglandins, thromboxanes, and leukotrienes, and also more recently identified lipid mediators. With the advent of new technologies there is growing interest in identifying these different lipid mediators and characterising their roles in health and disease. This review brings together contributions from some of those at the forefront of research into lipid mediators, who provide brief introductions and summaries of current understanding of the structure and functions of the main classes of nonclassical oxylipins. The topics covered include omega-3 and omega-6 PUFA biosynthesis pathways, focusing on the roles of the different fatty acid desaturase enzymes, oxidized linoleic acid metabolites, omega-3 PUFA-derived specialized pro-resolving mediators, elovanoids, nonenzymatically oxidized PUFAs, and fatty acid esters of hydroxy fatty acids.
Pregnancy Outcomes in Women With a Prior Cervical Intraepithelial Neoplasia Grade 3 Diagnosis
Authors: Wei He, Pär Sparén, Fang Fang, Verena Sengpiel, Björn Strander, Kamila Czene
Journal: Annals of Internal Medicine (2022)

Background: Treatment of cervical intraepithelial neoplasia grade 3 (CIN 3) removes or destroys part of the cervix and might subsequently influence pregnancy outcomes. Objective: To investigate pregnancy outcomes in women diagnosed with CIN 3. Design: Population- and sibling-matched cohort study. Setting: Sweden, 1973 to 2018. Participants: The general population comparison included 78 450 singletons born to women diagnosed with CIN 3 and 784 500 matched singletons born to women in the general population who had no CIN 3 diagnosis; the sibling comparison included 23 199 singletons born to women diagnosed with CIN 3 and 28 135 singletons born to their sisters without a CIN 3 diagnosis. Measurements: Preterm birth, including spontaneous or iatrogenic preterm birth; infection-related outcomes, including chorioamnionitis and infant sepsis; and early neonatal death, defined as death during the first week after birth. Results: Compared with the matched general population, women previously diagnosed with CIN 3 were more likely to have a preterm birth, especially extremely preterm (22 to 28 weeks; odds ratio [OR], 3.00 [95% CI, 2.69 to 3.34]) or spontaneous preterm (OR, 2.12 [CI, 2.05 to 2.20]); infection-related outcomes, including chorioamnionitis (OR, 3.23 [CI, 2.89 to 3.62]) and infant sepsis (OR, 1.72 [CI, 1.60 to 1.86]); or early neonatal death (OR, 1.83 [CI, 1.61 to 2.09]). Sibling comparison analyses rendered largely similar results. Over time, the risk difference attenuated for all outcomes and disappeared for early neonatal death. Limitation: Lack of data on CIN 3 treatment and spontaneous abortion. Conclusion: History of CIN 3 is associated with adverse pregnancy outcomes even after accounting for familial factors. Decreasing risk estimates over time suggest that adverse pregnancy outcomes among women diagnosed with CIN 3 may be minimized by improving treatment methods. Primary Funding Source: The Swedish Research Council, the Swedish Cancer Society, and the Swedish Research Council for Health, Working Life and Welfare.
Assessing Toripalimab in NSCLC
Journal: Cancer Discovery (2022)

According to CHOICE-01, a phase III trial in China, the PD-1 inhibitor toripalimab plus chemotherapy improves progression-free survival in patients with untreated non-small cell lung cancer lacking actionable mutations. The findings boost combination chemo-immunotherapy, rather than chemotherapy alone, as the new standard for this population.
The Natural History of Asymptomatic Gallstones: A Longitudinal Study and Prediction Model
Authors: Gareth Morris-Stiff, Shashank Sarvepalli, Bo Hu, Niyati Gupta, Pooja Lal, Carol A. Burke, Ari Garber, John McMichael, Maged K. Rizk, John J. Vargo, Mounir Ibrahim, Michael B. Rothberg
Journal: Clinical Gastroenterology and Hepatology (2022)