tbuckley/cabot-search huggingface dataset:
Reaction Risk to Direct Penicillin Challenges
Authors: Kimberly G. Blumenthal, Liam R. Smith, Jushin Teg S. Mann, Ingrid Salciccioli, John J. O. Accarino, Ruchi J. Shah, Fatima I. Alvi, António Cardoso-Fernandes, Renato Ferreira-da-Silva, Holger J. Schunemann, Bernardo Sousa-Pinto
Journal: JAMA Internal Medicine (2024)

Importance While direct penicillin challenges might support the expansion of penicillin allergy delabeling efforts, the perceived risk of reactions remains a key barrier. Objective To evaluate the frequency of reactions to direct penicillin challenges in individuals with penicillin allergy labels and to identify factors associated with such reactions. Data Sources Three electronic databases were searched (MEDLINE, Web of Science, and Scopus) from inception to July 19, 2023, for primary studies assessing patients undergoing direct penicillin challenges. Articles were included regardless of publication year, language, status, or definition of allergy risk. Study Selection Two reviewers independently selected original studies reporting the frequency of immunologically mediated reactions following a direct penicillin challenge in patients reporting a penicillin allergy. Data Extraction and Synthesis Two reviewers independently extracted data and independently assessed the quality of each primary study using a risk-of-bias tool for prevalence studies. Main Outcomes and Measures The primary outcome was the frequency of reactions to direct penicillin challenges as calculated using random-effects bayesian meta-analysis of proportions. Secondary outcomes included risk factors for reactions and the frequency of severe reactions. Results A total of 56 primary studies involving 9225 participants were included. Among participants, 438 experienced reactions to direct penicillin challenges without prior testing, corresponding to an overall meta-analytic frequency of 3.5% (95% credible interval [CrI], 2.5%-4.6%). Meta-regression analyses revealed that studies performed in North America had lower rates of reaction to direct challenges (odds ratio [OR], 0.36; 95% CrI, 0.20-0.61), while studies performed in children (OR, 3.37; 95% CrI, 1.98-5.98), in outpatients (OR, 2.19; 95% CrI, 1.08-4.75), and with a graded (OR, 3.24; 95% CrI, 1.50-7.06) or prolonged (OR, 5.45; 95% CrI, 2.38-13.28) challenge had higher rates of reaction. Only 5 severe reactions (3 anaphylaxis, 1 fever with rash, and 1 acute kidney injury) were reported, none of which were fatal. Conclusions and Relevance This systematic review and meta-analysis found that reactions to direct penicillin challenges are infrequent, with rates comparable to indirect challenges after allergy testing. These findings suggest that direct challenges are safe for incorporation into penicillin allergy evaluation efforts across age groups and clinical settings.
Heterogeneity in Methods of Estimating Kidney Function for Cancer Clinical Trial Eligibility
Authors: Alexander B. Karol, Rodrigo Paredes, Yu Fujiwara, Anna Argulian, Himanshu Joshi, Matthew Abramson, Matthew D. Galsky
Journal: JAMA Network Open (2024)

This cross-sectional study examined the kidney-function eligibility criteria for patients for enrollment in contemporary cancer clinical trials.
ST-Segment Elevation in a Woman With Out-of-Hospital Cardiac Arrest
Authors: Chang Kai-Chun, Lin Yi-Syuan, Lin Po-Chih
Journal: JAMA Internal Medicine (2024)

This case report describes a patient in their mid 70s who had an out-of-hospital cardiac arrest and was found to have irregular, narrow atrial fibrillation with rapid ventricular rhythm on electrocardiography imaging.
Comprehensive genetic analysis by targeted sequencing identifies risk factors and predicts patient outcome in Mantle Cell Lymphoma: results from the EU-MCL network trials
Authors: Mouhamad Khouja, Linmiao Jiang, Karol Pal, Peter James Stewart, Binaya Regmi, Martin Schwarz, Wolfram Klapper, Stefan K Alig, Nikos Darzentas, Hanneke C Kluin-Nelemans, Olivier Hermine, Martin Dreyling, David Gonzalez de Castro, Eva Hoster, Christiane Pott
Journal: Leukemia (2024)

Abstract Recent studies highlighted genetic aberrations associated with prognosis in Mantle Cell lymphoma (MCL), yet comprehensive testing is not implemented in clinical routine. We conducted a comprehensive genomic characterization of 180 patients from the European MCL network trials by targeted sequencing of peripheral blood DNA using the EuroClonality(EC)-NDC assay. The IGH::CCND1 fusion was identified in 94% of patients, clonal IGH-V-(D)-J rearrangements in all, and 79% had ≥1 somatic gene mutation. The top mutated genes were ATM , TP53 , KMT2D , SAMHD1 , BIRC3 and NFKBIE . Copy number variations (CNVs) were detected in 83% of patients with RB1 , ATM , CDKN2A/B and TP53 being the most frequently deleted and KLF2 , CXCR4 , CCND1 , MAP2K1 and MYC the top amplified genes. CNVs and mutations were more frequently observed in older patients with adverse impact on prognosis. TP53 mut , NOTCH1 mut , FAT1 mut TRAF2 del , CDKN2A/B del and MAP2K1 amp were linked to inferior failure-free (FFS) and overall survival (OS), while TRAF2 mut , EGR2 del and BCL2 amp related to inferior OS only. Genetic complexity (≥3 CNVs) observed in 51% of analysed patients was significantly associated with impaired FFS and OS. We demonstrate that targeted sequencing from peripheral blood and bone marrow reliably detects diagnostically and prognostically important genetic factors in MCL patients, facilitating genetic characterization in clinical routine.
Trifecta Outcomes After Use of 3-Dimensional Digital Models for Planning of Robotic Prostatectomy
Authors: Joseph D. Shirk, Robert E. Reiter, Eric M. Wallen, Raymond W. Pak, Thomas Ahlering, Ketan K. Badani, James R. Porter
Journal: JAMA Network Open (2024)

Planning complex operations such as robotic-assisted laparoscopic radical prostatectomy (RALP) requires surgeons to review 2-dimensional magnetic resonance imaging (MRI) scans to understand 3-dimensional (3D) patient anatomy. Three-dimensional digital models for planning RALP may allow better understanding of patient anatomy and may lead to better patient outcomes, although data are currently limited.
Sexual Dysfunction Following Retinoids: A Systematic Review
Authors: Heidi Oi-Yee Li, Elena Pastukhova, Olivier Brandts-Longtin, Adrian Bailey, Marcus G Tan, Mark G Kirchhof
Journal: British Journal of Dermatology (2024)

Despite product monograph warnings of post-retinoid sexual dysfunction (PRSD) for isotretinoin and recent policy decisions regarding the safety of isotretinoin, this study demonstrates that there remains conflicting and low-quality evidence on this topic and it is not possible to ascertain causation between retinoids and PRSD. Dermatologists and patients should be aware of the conflicting data regarding sexual dysfunction associated with systemic retinoid therapy. Routine screening for sexual side-effects during systemic retinoid treatment may be reasonable, as patients are less likely to self-disclose sexual health concerns.
ESCHR: a hyperparameter-randomized ensemble approach for robust clustering across diverse datasets
Authors: Sarah M Goggin, Eli R Zunder
Journal: Genome biology (2024)

Clustering is widely used for single-cell analysis, but current methods are limited in accuracy, robustness, ease of use, and interpretability. To address these limitations, we developed an ensemble clustering method that outperforms other methods at hard clustering without the need for hyperparameter tuning. It also performs soft clustering to characterize continuum-like regions and quantify clustering uncertainty, demonstrated here by mapping the connectivity and intermediate transitions between MNIST handwritten digits and between hypothalamic tanycyte subpopulations. This hyperparameter-randomized ensemble approach improves the accuracy, robustness, ease of use, and interpretability of single-cell clustering, and may prove useful in other fields as well.
Vagus nerve stimulation recruits the central cholinergic system to enhance perceptual learning
Authors: Kathleen A Martin, Eleni S Papadoyannis, Jennifer K Schiavo, Saba Shokat Fadaei, Habon A Issa, Soomin C Song, Sofia Orrey Valencia, Nesibe Z Temiz, Matthew J McGinley, David A McCormick, Robert C Froemke
Journal: Nature Neuroscience (2024)
White blood cell count levels are associated with inflammatory response and constitute independent outcome predictors in adult patients with acute myeloid leukemia aged &lt;60 years
Authors: Michael Ozga, Deedra Nicolet, Krzysztof Mrózek, Christopher J. Walker, James S. Blachly, Jessica Kohlschmidt, Shelley Orwick, Andrew J. Carroll, Richard A. Larson, Jonathan E. Kolitz, Bayard L. Powell, Richard M. Stone, John C. Byrd, Ann‐Kathrin Eisfeld, Alice S. Mims
Journal: American Journal of Hematology (2024)
Zolbetuximab in Gastric or Gastroesophageal Junction Adenocarcinoma
Authors: Kohei Shitara, Manish A. Shah, Florian Lordick, Eric Van Cutsem, David H. Ilson, Samuel J. Klempner, Yoon-Koo Kang, Sara Lonardi, Yi-Ping Hung, Kensei Yamaguchi, Peter Enzinger, Tomoko Nakajima, Maria Matsangou, Ying Cao, Ran Li, Diarmuid Moran, Rupesh Pophale, Mok Oh, Radhika Ranganath, Jaffer A. Ajani, Rui-Hua Xu
Journal: New England Journal of Medicine (2024)
Response from Harmon et al to Letter Regarding Article, “Sudden Cardiac Death in National Collegiate Athletic Association Athletes”
Authors: Kimberly G. Harmon, Timothy W. Churchill, Nathaniel Moulson, Stephanie A. Kliethermes, Aaron L. Baggish, Jonathan A. Drezner, Manesh R. Patel, Michael J. Ackerman, David M. Siebert, Lauren Salerno, Monica Zigman Suchsland, Irfan M. Asif, Joseph J. Maleszewski, Bradley J. Petek
Journal: Circulation (2024)
Pancreatic Cancer-Associated Fibroblasts: Where do we go from here?
Authors: Eileen S. Carpenter, Debora Barbosa Vendramini-Costa, Marie C. Hasselluhn, Anirban Maitra, Kenneth P. Olive, Edna Cukierman, Marina Pasca di Magliano, Mara H. Sherman
Journal: Cancer Research (2024)

Abstract Pancreatic ductal adenocarcinoma is a deadly disease and is projected to become the second leading cause of cancer-related death by 2030. A major hallmark is the exuberant host response comprising the tumor microenvironment, of which, cancer-associated fibroblasts (CAF) are a prevalent component. Despite the gains in understanding of their heterogeneity and functionality from CAF studies in recent years, there are many unanswered questions surrounding this diverse population of cells. Here, we summarize the views of several experts in the field, focusing on the current understanding of CAFs and challenges to address.
Racial and Ethnic Representation in Food Allergen Immunotherapy Trial Participants
Authors: Hannah Suffian, Aarti Pandya, Lauren Davidson, Vincent Staggs, Bridgette L. Jones
Journal: JAMA Network Open (2024)

The lack of inclusion of diverse population samples in food allergy immunotherapy clinical trials not only leads to decreased applicability to the general population in terms of results and treatments but can also be seen as a broader social injustice contributing to inequity within the health care system.
The interplay between gut microbiota, short-chain fatty acids, and implications for host health and disease
Authors: Kallie E. Hays, Jacob M. Pfaffinger, Rebecca Ryznar
Journal: Gut Microbes (2024)

Short-chain fatty acids (SCFAs) - acetate, propionate, and butyrate - are important bacterial fermentation metabolites regulating many important aspects of human physiology. Decreases in the concentrations of any or multiple SCFAs are associated with various detrimental effects to the host. Previous research has broadly focused on gut microbiome produced SCFAs as a group, with minimal distinction between acetate, propionate, and butyrate independently, each with significantly different host effects. In this review, we comprehensively delineate the roles of these SCFAs with emphasis on receptor affinity, signaling pathway involvement, and net host physiologic effects. Butyrate is highlighted due to its unique role in gastrointestinal-associated functions, especially maintaining gut barrier integrity. Butyrate functions by promoting epithelial tight junctions, serving as fuel for colonocyte ATP production, and modulating the immune system. Interaction with the immune system occurs locally in the gastrointestinal tract and systemically in the brain. Investigation into research conducted on butyrate production pathways and specific bacterial players involved highlights a unique risk associated with use of gram-positive targeted antibiotics. We review and discuss evidence showing the relationship between the butyrate-producing gram-positive genus,
Observational and genetic evidence disagree on the association between loneliness and risk of multiple diseases
Authors: Yannis Yan Liang, Mingqing Zhou, Yu He, Weijie Zhang, Qiqi Wu, Tong Luo, Jun Zhang, Fujun Jia, Lu Qi, Sizhi Ai, Jihui Zhang
Journal: Nature Human Behaviour (2024)

Loneliness-the subjective experience of social disconnection-is now widely regarded as a health risk factor. However, whether the associations between loneliness and multiple diseases are consistent with causal effects remains largely unexplored. Here we combined behavioural, genetic and hospitalization data from the UK Biobank to examine the associations of loneliness with a wide range of non-overlapping diseases. During a median 12.2-year follow-up, loneliness was associated with greater risks in 13 of 14 disease categories and 30 of 56 individual diseases considered. Of the 30 diseases significantly associated with loneliness, 26 had genetic data available for Mendelian randomization (MR) analyses. After Benjamini‒Hochberg correction and multiple sensitivity analyses within the MR framework, non-causal associations were identified between genetic liability to loneliness and 20 out of the 26 specific diseases, including cardiovascular diseases, type 2 diabetes mellitus, obesity, chronic liver diseases, chronic kidney disease, most neurological diseases and the other common diseases. Genetic liability to loneliness was only potentially causally associated with the remaining six diseases. Socioeconomic factors, health behaviours, baseline depressive symptoms and comorbidities largely explained the associations between loneliness and diseases. Overall, our study revealed a dissociation between observational and genetic evidence regarding the associations of loneliness with multiple diseases. These findings suggest that loneliness may serve as a potential surrogate marker rather than a causal risk factor for most diseases tested here.
Mycophenolate Mofetil and New-Onset Systemic Lupus Erythematosus
Authors: Yijun You, Zhuochao Zhou, Fan Wang, Jian Li, Honglei Liu, Xiaobing Cheng, Yutong Su, Xiaowei Chen, Hui Zheng, Yue Sun, Hui Shi, Qiongyi Hu, Jing Xu, Jialin Teng, Chengde Yang, Junna Ye
Journal: JAMA Network Open (2024)

Importance Anti–double-stranded DNA (dsDNA) antibody has been reported to have a close relationship with systemic lupus erythematosus (SLE) flares and participates in the pathogenesis of lupus nephritis (LN) as well as causing damage to other organs. However, whether early use of mycophenolate mofetil (MMF) could prevent SLE flares is not clear. Objective To assess the efficacy and safety of MMF plus prednisone and hydroxychloroquine sulfate compared with prednisone and hydroxychloroquine sulfate alone in patients with SLE. Design, Setting, and Participants This investigator-initiated, multicenter, observer-blinded randomized clinical trial enrolled 130 participants aged 18 to 65 years and was conducted in 3 hospitals across China. Treatment-naive patients with newly diagnosed SLE, a high titer of anti-dsDNA antibody, and no major organ involvement were included. The study was started September 1, 2018, and the follow-up was completed September 30, 2021. Data were analyzed from December 1, 2021, to March 31, 2022. Interventions Patients were randomized 1:1 to receive oral prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) (control group) or prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) plus MMF (500 mg twice daily) (MMF group) for 96 weeks. Main Outcomes and Measures The primary outcome was the proportion of patients presenting with flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare Index. The secondary outcomes included the proportion with lupus low disease activity state at week 96, 36-Item Short Form Health Survey scores before and after treatment, proportion of adverse events (AEs), and changes in SLEDAI-2000 scores and prednisone doses. Results Among 130 randomized patients (mean [SD] age, 34.5 [12.5] years; 112 [86.2%] women), 119 (91.5%) completed the follow-up. The risk of severe flare was significantly lower in the MMF group (7 of 65 [10.8%]) vs the control group (18 of 65 [27.7%]) (relative risk [RR], 0.39 [95% CI, 0.17-0.87]; P = .01). Additionally, 1 of 65 patients in the MMF group (1.5%) and 9 of 65 in the control group (13.8%) manifested LN (RR, 0.11 [95% CI, 0.01-0.85]; P = .008). Most common serious study drug–related AEs were infections (20 of 65 [30.8%] in the control group and 22 of 65 [33.8%] in the MMF group). Conclusions and Relevance The findings of this randomized clinical trial suggest that MMF may reduce the rate of severe flare and lower the incidence of LN in patients with new-onset SLE and a high titer of anti-dsDNA antibody without major organ involvement. Trial Registration Chinese Clinical Trial Registry: ChiCTR1800017540
Correction: Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants
Authors: Heidi Greulich, Tzu-Hsiu Chen, Whei Feng, Pasi A. Jänne, James V. Alvarez, Mauro Zappaterra, Sara E. Bulmer, David A. Frank, William C. Hahn, William R. Sellers, Matthew Meyerson
Journal: PLoS Medicine (2024)

[This corrects the article DOI: 10.1371/journal.pmed.0020313.].
Antagonism between H3K27me3 and genome–lamina association drives atypical spatial genome organization in the totipotent embryo
Authors: Isabel Guerreiro, Franka J Rang, Yumiko K Kawamura, Carla Kroon-Veenboer, Jeroen Korving, Femke C Groenveld, Ramada E van Beek, Silke J A Lochs, Ellen Boele, Antoine H M F Peters, Jop Kind
Journal: Nature Genetics (2024)

In mammals, early embryonic development exhibits highly unusual spatial positioning of genomic regions at the nuclear lamina, but the mechanisms underpinning this atypical genome organization remain elusive. Here, we generated single-cell profiles of lamina-associated domains (LADs) coupled with transcriptomics, which revealed a striking overlap between preimplantation-specific LAD dissociation and noncanonical broad domains of H3K27me3. Loss of H3K27me3 resulted in a restoration of canonical LAD profiles, suggesting an antagonistic relationship between lamina association and H3K27me3. Tethering of H3K27me3 to the nuclear periphery showed that the resultant relocalization is partially dependent on the underlying DNA sequence. Collectively, our results suggest that the atypical organization of LADs in early developmental stages is the result of a tug-of-war between intrinsic affinity for the nuclear lamina and H3K27me3, constrained by the available space at the nuclear periphery. This study provides detailed insight into the molecular mechanisms regulating nuclear organization during early mammalian development.
Community-Acquired Pneumonia
Authors: Valerie M. Vaughn, Robert P. Dickson, Jennifer K. Horowitz, Scott A. Flanders
Journal: JAMA (2024)

Importance Community-acquired pneumonia (CAP) results in approximately 1.4 million emergency department visits, 740 000 hospitalizations, and 41 000 deaths in the US annually. Observations Community-acquired pneumonia can be diagnosed in a patient with 2 or more signs (eg, temperature &amp;amp;gt;38 °C or ≤36 °C; leukocyte count &amp;amp;lt;4000/μL or &amp;amp;gt;10 000/μL) or symptoms (eg, new or increased cough or dyspnea) of pneumonia in conjunction with consistent radiographic findings (eg, air space density) without an alternative explanation. Up to 10% of patients with CAP are hospitalized; of those, up to 1 in 5 require intensive care. Older adults (≥65 years) and those with underlying lung disease, smoking, or immune suppression are at highest risk for CAP and complications of CAP, including sepsis, acute respiratory distress syndrome, and death. Only 38% of patients hospitalized with CAP have a pathogen identified. Of those patients, up to 40% have viruses identified as the likely cause of CAP, with Streptococcus pneumoniae identified in approximately 15% of patients with an identified etiology of the pneumonia. All patients with CAP should be tested for COVID-19 and influenza when these viruses are common in the community because their diagnosis may affect treatment (eg, antiviral therapy) and infection prevention strategies. If test results for influenza and COVID-19 are negative or when the pathogens are not likely etiologies, patients can be treated empirically to cover the most likely bacterial pathogens. When selecting empirical antibacterial therapy, clinicians should consider disease severity and evaluate the likelihood of a bacterial infection—or resistant infection—and risk of harm from overuse of antibacterial drugs. Hospitalized patients without risk factors for resistant bacteria can be treated with β-lactam/macrolide combination therapy, such as ceftriaxone combined with azithromycin, for a minimum of 3 days. Systemic corticosteroid administration within 24 hours of development of severe CAP may reduce 28-day mortality. Conclusions Community-acquired pneumonia is common and may result in sepsis, acute respiratory distress syndrome, or death. First-line therapy varies by disease severity and etiology. Hospitalized patients with suspected bacterial CAP and without risk factors for resistant bacteria can be treated with β-lactam/macrolide combination therapy, such as ceftriaxone combined with azithromycin, for a minimum of 3 days.
Microplastics in the Olfactory Bulb of the Human Brain
Authors: Luís Fernando Amato-Lourenço, Katia Cristina Dantas, Gabriel Ribeiro Júnior, Vitor Ribeiro Paes, Rômulo Augusto Ando, Raul de Oliveira Freitas, Ohanna Maria Menezes M. da Costa, Renata S. Rabelo, Kelly Cristina Soares Bispo, Regiani Carvalho-Oliveira, Thais Mauad
Journal: JAMA Network Open (2024)

Microplastic (MP) pollution is an emerging environmental and health concern. While MPs have been detected in various human tissues, their presence in the human brain has not been documented, raising important questions about potential neurotoxic effects and the mechanisms by which MPs might reach brain tissues.
<i>LMNA</i> Q353R Mutation Causes Dilated Cardiomyopathy Through Impaired Vitamin D Signaling
Authors: Masamichi Ito, Manami Katoh, Tatsuro Sassa, Toshiyuki Ko, Kanna Fujita, Shintaro Yamada, Koichiro Miura, Masashi Toyoda, Shuji Takada, Takashige Tobita, Mikako Katagiri, Masayuki Kubota, Takanobu Yamada, Satoshi Hatsuse, Hiroyuki Morita, Masashi Ikeuchi, Katsuhisa Matsuura, Akihiro Umezawa, Seitaro Nomura, Hiroyuki Aburatani, Issei Komuro
Journal: Circulation (2024)
Publisher Correction: Efferocytosis drives a tryptophan metabolism pathway in macrophages to promote tissue resolution
Authors: Santosh R Sukka, Patrick B Ampomah, Lancia N F Darville, David Ngai, Xiaobo Wang, George Kuriakose, Yuling Xiao, Jinjun Shi, John M Koomen, Robert H McCusker, Ira Tabas
Journal: Nature Metabolism (2024)