tbuckley/cabot-search huggingface dataset:
School performance in Danish children exposed to maternal type 1 diabetes in utero: A nationwide retrospective cohort study
Authors: Anne Lærke Spangmose, Niels Skipper, Sine Knorr, Tina Wullum Gundersen, Rikke Beck Jensen, Peter Damm, Erik Lykke Mortensen, Anja Pinborg, Jannet Svensson, Tine Clausen
Journal: PLoS Medicine (2022)

Background Conflicting results have been reported concerning possible adverse effects on the cognitive function of offspring of mothers with type 1 diabetes (O-mT1D). Previous studies have included offspring of parents from the background population (O-BP), but not offspring of fathers with type 1 diabetes (O-fT1D) as the unexposed reference group. Methods and findings This is a population-based retrospective cohort study from 2010 to 2016. Nationally standardized school test scores (range, 1 to 100) were obtained for public school grades 2, 3, 4, 6, and 8 in O-mT1D and compared with those in O-fT1D and O-BP. Of the 622,073 included children, 2,144 were O-mT1D, and 3,474 were O-fT1D. Multiple linear regression models were used to compare outcomes, including the covariates offspring with type 1 diabetes, parity, number of siblings, offspring sex, smoking during pregnancy, parental age, and socioeconomic factors. Mean test scores were 54.2 (standard deviation, SD 24.8) in O-mT1D, 54.4 (SD 24.8) in O-fT1D, and 56.4 (SD 24.7) in O-BP. In adjusted analyses, the mean differences in test scores were −1.59 (95% CI −2.48 to −0.71, p &lt; 0.001) between O-mT1D and O-BP and −0.78 (95% CI −1.48 to −0.08, p = 0.03) between O-fT1D and O-BP. No significant difference in the adjusted mean test scores was found between O-mT1D and O-fT1D ( p = 0.16). The study’s limitation was no access to measures of glycemic control during pregnancy. Conclusions O-mT1D achieved lower test scores than O-BP but similar test scores compared with O-fT1D. Glycemic control during pregnancy is essential to prevent various adverse pregnancy outcomes in women with type 1 diabetes. However, the present study reduces previous concerns regarding adverse effects of in utero hyperglycemia on offspring cognitive function.
Improving Outcomes for Hospitalized Children—Include the Voice of the Patient and Caregiver When Prioritizing for Implementation
Authors: Rajendu Srivastava, Karen Wilson
Journal: JAMA Network Open (2022)

Peter J. Gill, MD, DPhil; Ann Bayliss, MD; Aubrey Sozer, RN; Francine Buchanan, PhD; Karen Breen-Reid, RN; Kim De Castris-Garcia; Mairead Green; Michelle Quinlan, BA; Noel Wong, RN; Shelley Frappier, BA; Katherine Cowan, MA; Carol Chan, BSc; Dana Arafeh, BSc; Mohammed Rashid Anwar, MSc; Colin Macarthur, PhD; Patricia C. Parkin, MD; Eyal Cohen, MD, MSc; Sanjay Mahant, MD, MSc; Canadian Pediatric Inpatient Research Network (PIRN); Olivier Drouin; Catherine Pound; Gita Wahi; Gemma Vomiero; Kim Zhou; Mahmoud Sakran; Anupam Sehgal; Thuy Mai Luuy; Karen Forbes; Tom McLaughlin; Krista Baerg; Geert t Jong; Sepi Taheri; Patricia Li; Evelyn Constantin; Joanna Holland; Leigh-Ann Newhook; Sean Murray
Melanoma with peripheral globules: Clinical and dermatoscopic features
Authors: Ana F.A. Moraes, Tatiana C.M.P. Blumetti, Clovis Pinto, Eduardo Bertolli, Gisele Rezze, Ashfaq A. Marghoob, Juliana C.T. Braga
Journal: Journal of the American Academy of Dermatology (2022)
The phenotype of HLA-binding B cells from sensitized kidney transplant recipients correlates with clinically prognostic patterns of interferon-γ production against purified HLA proteins
Authors: Hannah Burton, Laura McLaughlin, Kin Yee Shiu, Olivia Shaw, Nizam Mamode, Jo Spencer, Anthony Dorling
Journal: Kidney International (2022)

B cells play crucial roles in cell-mediated alloimmune responses. In vitro, B cells can support or regulate indirect T-cell alloreactivity in response to donor antigens on ELISpot and these patterns associate with clinical outcome. Previous reports of associations between B-cell phenotype and function have examined global phenotypes and responses to polyclonal stimuli. We hypothesized that studying antigen-specific B cells, using samples from sensitized patients, would inform further study to identify novel targets for intervention. Using biotinylated HLA proteins, which bind HLA-specific B cells via the B-cell receptor in a dose-dependent fashion, we report the specific phenotype of HLA-binding B cells and define how they associated with patterns of anti-HLA response in interferon-γ ELISpot. HLA-binding class-switched and IgM+CD27+ memory cells associated strongly with B-dependent interferon-γ production and appeared not suppressible by endogenous Tregs. When the predominant HLA-binding phenotype was naïve B cells, the associated functional ELISpot phenotype was determined by other cells present. High numbers of non-HLA-binding transitional cells associated with B-suppressed interferon-γ production, especially if Tregs were present. However, high frequencies of HLA-binding marginal-zone precursors associated with B-dependent interferon-γ production that appeared suppressible by Tregs. Finally, non-HLA-binding marginal zone precursors may also suppress interferon-γ production, though this association only emerged when Tregs were absent from the ELISpot. Thus, our novel data provide a foundation on which to further define the complexities of interactions between HLA-specific T and B cells and identify new targets for intervention in new therapies for chronic rejection.
A Potential Path to Universal Coverage With Medicare Advantage for All—Reply
Authors: Greg J. Zahner, Peter W. Croughan, Daniel M. Blumenthal
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
<i>TRAF3</i> alterations are frequent in del‐3′<scp>IGH</scp> chronic lymphocytic leukemia patients and define a specific subgroup with adverse clinical features
Authors: Claudia Pérez‐Carretero, María Hernández‐Sánchez, Teresa González, Miguel Quijada‐Álamo, Marta Martín‐Izquierdo, Sandra Santos‐Mínguez, Cristina Miguel‐García, María‐Jesús Vidal, Alfonso García‐De‐Coca, Josefina Galende, Emilia Pardal, Carlos Aguilar, Manuel Vargas‐Pabón, Julio Dávila, Isabel Gascón‐Y‐Marín, José‐Ángel Hernández‐Rivas, Rocío Benito, Jesús‐María Hernández‐Rivas, Ana‐Eugenia Rodríguez‐Vicente
Journal: American Journal of Hematology (2022)

Abstract Interstitial 14q32 deletions involving IGH gene are infrequent events in chronic lymphocytic leukemia (CLL), affecting less than 5% of patients. To date, little is known about their clinical impact and molecular underpinnings, and its mutational landscape is currently unknown. In this work, a total of 871 CLLs were tested for the IGH break‐apart probe, and 54 (6.2%) had a 300 kb deletion of 3′IGH (del‐3′IGH CLLs), which contributed to a shorter time to first treatment (TFT). The mutational analysis by next‐generation sequencing of 317 untreated CLLs (54 del‐3′IGH and 263 as the control group) showed high mutational frequencies of NOTCH1 (30%), ATM (20%), genes involved in the RAS signaling pathway ( BRAF , KRAS , NRAS , and MAP2K1 ) (15%), and TRAF3 (13%) within del‐3′IGH CLLs. Notably, the incidence of TRAF3 mutations was significantly higher in del‐3′IGH CLLs than in the control group ( p &lt; .001). Copy number analysis also revealed that TRAF3 loss was highly enriched in CLLs with 14q deletion ( p &lt; .001), indicating a complete biallelic inactivation of this gene through deletion and mutation. Interestingly, the presence of mutations in the aforementioned genes negatively refined the prognosis of del‐3′IGH CLLs in terms of overall survival ( NOTCH1 , ATM , and RAS signaling pathway genes) and TFT ( TRAF3 ). Furthermore, TRAF3 biallelic inactivation constituted an independent risk factor for TFT in the entire CLL cohort. Altogether, our work demonstrates the distinct genetic landscape of del‐3′IGH CLL with multiple molecular pathways affected, characterized by a TRAF3 biallelic inactivation that contributes to a marked poor outcome in this subgroup of patients.
Scalable fabrication, compartmentalization and applications of living microtissues
Authors: Maik Schot, Nuno Araújo-Gomes, Bas van Loo, Tom Kamperman, Jeroen Leijten
Journal: Bioactive Materials (2022)

Living microtissues are used in a multitude of applications as they more closely resemble native tissue physiology, as compared to 2D cultures. Microtissues are typically composed of a combination of cells and materials in varying combinations, which are dictated by the applications' design requirements. Their applications range wide, from fundamental biological research such as differentiation studies to industrial applications such as cruelty-free meat production. However, their translation to industrial and clinical settings has been hindered due to the lack of scalability of microtissue production techniques. Continuous microfluidic processes provide an opportunity to overcome this limitation as they offer higher throughput production rates as compared to traditional batch techniques, while maintaining reproducible control over microtissue composition and size. In this review, we provide a comprehensive overview of the current approaches to engineer microtissues with a focus on the advantages of, and need for, the use of continuous processes to produce microtissues in large quantities. Finally, an outlook is provided that outlines the required developments to enable large-scale microtissue fabrication using continuous processes.
Making decisions about radiological imaging in pregnancy
Authors: Rebecca Wiles, Beth Hankinson, Emily Benbow, Andrew Sharp
Journal: BMJ (2022)

<h3>Introduction</h3> Patient records are often fragmented across organisations and departments in UK health and care services, often due to substandard information technology. However, although government policy in the UK and internationally is strongly pushing 'digital transformation', the evidence for the positive impact of electronic information systems on cost, quality and safety of healthcare is far from clear. In particular, the mechanisms by which information availability is translated into better decision-making are not well understood. We do not know when a full interorganisational record is more useful than a key information summary or an institutional record. In this paper, we describe our scoping review of how interorganisational electronic health records affect decision-making by hospital physicians and pharmacists. <h3>Methods and analysis</h3> This scoping review will follow the Arksey and O'Malley (2005) methodology. The review has adopted sociotechnical systems thinking and the notion of distributed cognition as its guiding conceptual models. The UK National Institute for Health and Care Excellence Healthcare Databases Advanced Search will be used, as it incorporates key sources including PubMed, Medline, Embase, HMIC and Health Business Elite. A hand search will be conducted using the reference lists of included studies to identify additional relevant articles. A two-part study selection process will be used: (1) a title and abstract review and (2) full text review. During the first step, two researchers separately will review the citations yielded from the search to determine eligibility based on the defined inclusion and exclusion criteria. Related articles will be included if they are empirical studies that address how interorganisational records affect decision-making by hospital physicians and pharmacists. <h3>Ethics and dissemination</h3> The results will be disseminated through stakeholder meetings, conference presentations and peer-reviewed publication. The data used are from publicly available secondary sources, so this study does not require ethical review.
Inotuzumab ozogamicin as single agent in pediatric patients with relapsed and refractory acute lymphoblastic leukemia: results from a phase II trial
Authors: Edoardo Pennesi, Naomi Michels, Erica Brivio, Vincent H. J. van der Velden, Yilin Jiang, Adriana Thano, Anneke J. C. Ammerlaan, Judith M. Boer, H. Berna Beverloo, Barbara Sleight, Ying Chen, Britta Vormoor-Bürger, Susana Rives, Bella Bielorai, Claudia Rössig, Arnaud Petit, Carmelo Rizzari, Gernot Engstler, Jan Starý, Francisco J. Bautista Sirvent, Christiane Chen-Santel, Benedicte Bruno, Yves Bertrand, Fanny Rialland, Geneviève Plat, Dirk Reinhardt, Luciana Vinti, Arend Von Stackelberg, Franco Locatelli, Christian M. Zwaan
Journal: Leukemia (2022)

Inotuzumab Ozogamicin is a CD22-directed antibody conjugated to calicheamicin, approved in adults with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (BCP-ALL). Patients aged 1-18 years, with R/R CD22 + BCP-ALL were treated at the RP2D of 1.8 mg/m2. Using a single-stage design, with an overall response rate (ORR) ≤ 30% defined as not promissing and ORR > 55% as expected, 25 patients needed to be recruited to achieve 80% power at 0.05 significance level. Thirty-two patients were enrolled, 28 were treated, 27 were evaluable for response. The estimated ORR was 81.5% (95%CI: 61.9-93.7%), and 81.8% (18/22) of the responding subjects were minimal residual disease (MRD) negative. The study met its primary endpoint. Median follow up of survivors was 16 months (IQR: 14.49-20.07). One year Event Free Survival was 36.7% (95% CI: 22.2-60.4%), and Overall Survival was 55.1% (95% CI: 39.1-77.7%). Eighteen patients received consolidation (with HSCT and/or CAR T-cells therapy). Sinusoidal obstructive syndrome (SOS) occurred in seven patients. MRD negativity seemed correlated to calicheamicin sensitivity in vitro, but not to CD22 surface expression, saturation, or internalization. InO was effective in this population. The most relevant risk was the occurrence of SOS, particularly when InO treatment was followed by HSCT.
Bridging the AI Chasm: Can EBM Address Representation and Fairness in Clinical Machine Learning?
Authors: Nicole Martinez-Martin, Mildred K. Cho
Journal: The American Journal of Bioethics (2022)

This article is referred to by:Promoting Ethical Deployment of Artificial Intelligence and Machine Learning in HealthcareResponse to Open Peer Commentaries: On Social Harms, Big Tech, and Institutional Accountability
Analysis of Race and Sex Bias in the Autism Diagnostic Observation Schedule (ADOS-2)
Authors: Luther G. Kalb, Vini Singh, Ji Su Hong, Calliope Holingue, Natasha N. Ludwig, Danika Pfeiffer, Rachel Reetzke, Alden L. Gross, Rebecca Landa
Journal: JAMA Network Open (2022)

<h3>Importance</h3> There are long-standing disparities in the prevalence of autism spectrum disorder (ASD) across race and sex. Surprisingly, few studies have examined whether these disparities arise partially out of systematic biases in the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), the reference standard measure of ASD. <h3>Objective</h3> To examine differential item functioning (DIF) of ADOS-2 items across sex and race. <h3>Design, Setting, and Participants</h3> This is a cross-sectional study of children who were evaluated for ASD between 2014 and 2020 at a specialty outpatient clinic located in the Mid-Atlantic region of the US. Data were analyzed from July 2021 to February 2022. <h3>Exposures</h3> Child race (Black/African American vs White) and sex (female vs male). <h3>Main Outcomes and Measures</h3> Item-level biases across ADOS-2 harmonized algorithm items, including social affect (SA; 10 items) and repetitive/restricted behaviors (RRBs; 4 items), were evaluated across 3 modules. Measurement bias was identified by examining DIF and differential test functioning (DTF), within a graded response, item response theory framework. Statistical significance was determined by a likelihood ratio χ<sup>2</sup>test, and a series of metrics was used to examine the magnitude of DIF and DTF. <h3>Results</h3> A total of 6269 children (mean [SD] age, 6.77 [3.27] years; 1619 Black/African American [25.9%], 3151 White [50.3%], and 4970 male [79.4%]), were included in this study. Overall, 16 of 140 ADOS-2 diagnostic items (11%) had a significant DIF. For race, 8 items had a significant DIF, 6 of which involved SA. No single item showed DIF consistently across all modules. Most items with DIF had greater difficulty and poorer discrimination in Black/African American children compared with White children. For sex, 5 items showed significant DIF. DIF was split across SA and RRB. However, hand mannerisms evidenced DIF across all 5 algorithms, with generally greater difficulty. The magnitude of DIF was only moderate to large for 2 items: hand mannerisms (among female children) and repetitive interests (among Black/African American children). The overall estimated effect of DIF on total DTF was not large. <h3>Conclusions and Relevance</h3> These findings suggest that the ADOS-2 does not have widespread systematic measurement bias across race or sex. However, the findings raise some concerns around underdetection that warrant further research.
An engineered ACE2 decoy neutralizes the SARS-CoV-2 Omicron variant and confers protection against infection in vivo
Authors: Nariko Ikemura, Shunta Taminishi, Tohru Inaba, Takao Arimori, Daisuke Motooka, Kazutaka Katoh, Yuhei Kirita, Yusuke Higuchi, Songling Li, Tatsuya Suzuki, Yumi Itoh, Yuki Ozaki, Shota Nakamura, Satoaki Matoba, Daron M. Standley, Toru Okamoto, Junichi Takagi, Atsushi Hoshino
Journal: Science Translational Medicine (2022)

The Omicron (B.1.1.529) SARS-CoV-2 variant contains an unusually high number of mutations in the spike protein, raising concerns of escape from vaccines, convalescent serum, and therapeutic drugs. Here, we analyzed the degree to which Omicron pseudo-virus evades neutralization by serum or therapeutic antibodies. Serum samples obtained 3 months after two doses of BNT162b2 vaccination exhibited 18-fold lower neutralization titers against Omicron than parental virus. Convalescent serum samples from individuals infected with the Alpha and Delta variants allowed similar frequencies of Omicron breakthrough infections. Domain-wise analysis using chimeric spike proteins revealed that this efficient evasion was primarily achieved by mutations clustered in the receptor binding domain but that multiple mutations in the N-terminal domain contributed as well. Omicron escaped a therapeutic cocktail of imdevimab and casirivimab, whereas sotrovimab, which targets a conserved region to avoid viral mutation, remains effective. Angiotensin-converting enzyme 2 (ACE2) decoys are another virus-neutralizing drug modality that are free, at least in theory, from complete escape. Deep mutational analysis demonstrated that an engineered ACE2 molecule prevented escape for each single-residue mutation in the receptor binding domain, similar to immunized serum. Engineered ACE2 neutralized Omicron comparably to the Wuhan strain and also showed a therapeutic effect against Omicron infection in hamsters and human ACE2 transgenic mice. Similar to previous SARS-CoV-2 variants, some sarbecoviruses showed high sensitivity against engineered ACE2, confirming the therapeutic value against diverse variants, including those that are yet to emerge.
Identification of BRAF V600E mutation in odontogenic tumors by high-performance MALDI-TOF analysis
Authors: Lucrezia Togni, Antonio Zizzi, Roberta Mazzucchelli, Andrea Santarelli, Corrado Rubini, Marco Mascitti
Journal: International Journal of Oral Science (2022)

Odontogenic tumors are rare lesions with unknown etiopathogenesis. Most of them are benign, but local aggressiveness, infiltrative potential, and high recurrence rate characterize some entities. The MAP-kinase pathway activation can represent a primary critical event in odontogenic tumorigenesis. Especially, the BRAF V600E mutation has been involved in 80-90% of ameloblastic lesions, offering a biological rationale for developing new targeted therapies. The study aims to evaluate the BRAF V600E mutation in odontogenic lesions, comparing three different detection methods and focusing on the Sequenom MassARRAY System. 81 surgical samples of odontogenic lesions were subjected to immunohistochemical analysis, Sanger Sequencing, and Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometry (Sequenom). The BRAF V600E mutation was revealed only in ameloblastoma samples. Moreover, the presence of BRAF V600E was significantly associated with the mandibular site (ρ = 0.627; P value <0.001) and the unicystic histotype (ρ = 0.299, P value <0.001). However, any significant difference of 10-years disease-free survival time was not revealed. Finally, Sequenom showed to be a 100% sensitive and 98.1% specific, suggesting its high-performance diagnostic accuracy. These results suggest the MAP-kinase pathway could contribute to ameloblastic tumorigenesis. Moreover, they could indicate the anatomical specificity of the driving mutations of mandibular ameloblastomas, providing a biological rational for developing new targeted therapies. Finally, the high diagnostic accuracy of Sequenom was confirmed.
Systematic literature review of observational cohorts and clinical trials into the success rate of glucocorticoid discontinuation after their use as bridging therapy in patients with rheumatoid arthritis
Authors: Lotte van Ouwerkerk, Andriko Palmowski, Isabell S Nevins, Frank Buttgereit, Patrick Verschueren, Josef S Smolen, Robert BM Landewé, Johannes JW Bijlsma, Andreas Kerschbaumer, René Westhovens, Tom WJ Huizinga, Cornelia F Allaart, Sytske Anne Bergstra
Journal: Annals of the Rheumatic Diseases (2022)

To investigate the success rate of glucocorticoid (GC) discontinuation during follow-up in observational cohorts and clinical trials using temporary GC as part of initial therapy ('bridging') in newly diagnosed patients with rheumatoid arthritis (RA).Systematic literature searches were conducted to identify observational cohorts and clinical trials including patients with RA treated with initial GC bridging therapy, defined as discontinuation of GC within 1 year. Patient percentages still using GC were considered the reverse of successful discontinuation. Random effects meta-analyses were performed stratified by time point.The scoping literature search for observational cohort studies could not identify studies answering the research question. The literature search for clinical trials identified 7160 abstracts, resulting in 10 included studies, with varying type and dose of GC and varying tapering schedules, of which 4 reported sufficient data on GC discontinuation or use after the bridging phase. The pooled proportion of patients who were still or again using GC was 22% (95% CI 8% to 37%, based on four trials) at 12 months and 10% at 24 months (95% CI -1 to 22, based on two trials). Heterogeneity was substantial (I²≥65%).The success rate of GC discontinuation after bridging as part of initial treatment of RA has been described in a limited number of studies. Reports on observational cohorts did not answer the research question. In clinical trials, protocolised discontinuation was mostly successful, although 22% of the patients who started GC bridging therapy still or again used GC at 12 months, and 10% at 24 months.