tbuckley/cabot-search huggingface dataset:
Race and Ethnicity and Diagnostic Testing for Common Conditions in the Acute Care Setting
Authors: Michael I. Ellenbogen, P. Logan Weygandt, David E. Newman-Toker, Andrew Anderson, Nayoung Rim, Daniel J. Brotman
Journal: JAMA Network Open (2024)

Importance Overuse of diagnostic testing is pervasive, but the extent to which it varies by race and ethnicity in the acute care setting is poorly understood. Objective To use a previously validated diagnostic intensity index to evaluate differences in diagnostic testing rates by race and ethnicity in the acute care setting, which may serve as a surrogate for diagnostic test overuse. Design, Setting, and Participants This was a cross-sectional study of emergency department (ED) discharges, hospital observation stays, and hospital admissions using administrative claims among EDs and acute care hospitals in Kentucky, Maryland, North Carolina, and New Jersey, from 2016 through 2018. The diagnostic intensity index pairs nonspecific principal discharge diagnoses (nausea and vomiting, abdominal pain, chest pain, and syncope) with related diagnostic tests to estimate rates of nondiagnostic testing. Adults with an acute care encounter with a principal discharge diagnosis of interest were included. Data were analyzed from January to February 2024. Exposure Race and ethnicity (Asian, Black, Hispanic, White, other [including American Indian, multiracial, and multiethnic], and missing). Main Outcomes and Measures Receipt of a diagnostic test. Generalized linear models with a hospital-specific indicator variable were estimated to calculate the adjusted odds ratio of receiving a test related to the principal discharge diagnosis by race and ethnicity, controlling for primary payer and zip code income quartile. Results Of 3 683 055 encounters (1 055 575 encounters [28.7%] for Black, 300 333 encounters [8.2%] for Hispanic, and 2 140 335 encounters [58.1%] for White patients; mean [SD] age of patients with encounters, 47.3 [18.8] years; 2 233 024 encounters among females [60.6%]), most (2 969 974 encounters [80.6%]) were ED discharges. Black compared with White patients discharged from the ED with a diagnosis of interest had an adjusted odds ratio of 0.74 (95% CI, 0.72-0.75) of having related diagnostic testing. No other racial or ethnic disparities of a similar magnitude were observed in any acute care settings. Conclusions and Relevance In this study, White patients discharged from the ED with a nonspecific diagnosis of interest were significantly more likely than Black patients to receive related diagnostic testing. The extent to which this represents diagnostic test overuse in White patients vs undertesting and missed diagnoses in Black patients deserves further study.
Growth Restriction in the Offspring of Mothers With Polycystic Ovary Syndrome
Authors: Maren Sophie Aaserud Talmo, Ingvild Skogedal Fløysand, Guro Ørndal Nilsen, Tone S. Løvvik, Rønnaug Ødegård, Petur Benedikt Juliusson, Eszter Vanky, Melanie Rae Simpson
Journal: JAMA Network Open (2024)

Importance Polycystic ovary syndrome (PCOS) is a common endocrine disorder, characterized by subfertility, increased risk of metabolic diseases, and pregnancy complications. Previous studies diverge regarding the association between maternal PCOS and newborn anthropometrics. Objective To explore the association between maternal PCOS and newborn anthropometrics and the modifying effects of maternal body mass index, PCOS phenotype, and gestational diabetes. Design, Setting, and Participants This cohort study followed up women from the first half of pregnancy to birth and combined data from 3 clinical trials of pregnant women with PCOS and a reference population consisting of participants in the Norwegian Mother, Father, and Child Cohort (MoBa) Study, with data from the Medical Birth Registry of Norway. The recruitment period for the clinical trials was between October 1, 2000, and August 31, 2017, and for MoBa, between July 1, 1999, and December 31, 2008. Participants included women with singleton pregnancies and live-born children. Data were analyzed from January 1 to June 15, 2023. Exposure Maternal PCOS status. Main Outcomes and Measures Newborn birth weight, birth length, and head circumference as continuous variables and z scores, and ponderal index (calculated as the birth weight in grams × 100 divided by the birth length in centimeters cubed), placenta weight, and ratio of birth weight to placenta weight (BWPW). Results The cohort included 390 pregnant women with PCOS (mean [SD] age, 29.6 [4.2] years) and 68 708 women in the reference group (mean [SD] age, 30.4 [4.5] years). Offspring in the PCOS group had lower birth weight, birth length, and head circumference than in the reference group offspring. The estimated mean differences in z scores were −0.26 (95% CI, −0.38 to −0.14) for birth weight, −0.19 (95% CI, −0.33 to −0.05) for birth length, and −0.13 (95% CI, −0.26 to −0.01) for head circumference. The PCOS group also had a lower ponderal index (−0.04 [95% CI, −0.07 to −0.004] g × 100/cm 3 ) and placenta weight (−24 [95% CI, −43 to −5)] g), and higher BWPW ratio (0.4 [95% CI, 0.3 to 0.5]). The association between growth restriction and PCOS was more apparent when additionally adjusting for body mass index. Neither PCOS phenotype nor gestational diabetes diagnosis was associated with neonatal anthropometry in women with PCOS. Conclusions and Relevance In this cohort of mother-infant pairs, maternal PCOS status was associated with lower birth weight, shorter birth length, and smaller head circumference in the offspring. This growth restriction was more pronounced when adjusting for BMI, providing insight into the association between PCOS and body mass index. The study contributed to the understanding of how PCOS affects the offspring.
Addressing Polycystic Ovary Syndrome in Pregnancy Care to Improve Outcomes
Authors: Mahnaz Bahri Khomami, Helena J. Teede
Journal: JAMA Network Open (2024)

Maren Sophie Aaserud Talmo, MD; Ingvild Skogedal Fløysand, MD; Guro Ørndal Nilsen, MD; Tone S. Løvvik, MD, PhD; Rønnaug Ødegård, MD, PhD; Petur Benedikt Juliusson, MD, PhD; Eszter Vanky, MD, PhD; Melanie Rae Simpson, MD, PhD
Heart failure risk assessment in patients with hypertrophic cardiomyopathy based on the <scp>H<sub>2</sub>FPEF</scp> score
Authors: Dorien Laenens, Thomas Zegkos, Vasileios Kamperidis, Raymond C.C. Wong, Tony Yi‐Wei Li, Ching‐Hui Sia, William K.F. Kong, Georgios Efthimiadis, Kian Keong Poh, Antonios Ziakas, Jeroen J. Bax, Nina Ajmone Marsan
Journal: European Journal of Heart Failure (2024)

Abstract Aims The aim of this study was to investigate whether the H 2 FPEF score, which was developed to improve the diagnosis of heart failure (HF) with preserved ejection fraction, is associated with HF outcomes in patients with hypertrophic cardiomyopathy (HCM). Methods and results Patients with HCM and preserved left ventricular ejection fraction (LVEF ≥50%) were included from a multicentre registry and the H 2 FPEF score was calculated. Patients were divided into three groups: low (0–1), intermediate (2–5) and high (6–9) H 2 FPEF score. The primary combined endpoint was a composite of all‐cause death and HF admissions, while the secondary endpoints were all‐cause death and HF admissions separately. A total of 955 patients were included (age 51 ± 17 years, 310 [32.5%] female). Patients with a high H 2 FPEF score ( n = 105) were more often female, and presented with more symptoms and comorbidities. On echocardiography, patients with a high H 2 FPEF score had lower LVEF, more impaired diastolic function and more frequently left ventricular outflow tract obstruction. During follow‐up (median 90 months [interquartile range 49–176]), 103 (11%) patients died and 57 (6%) patients had a first HF hospitalization. Event‐free survival rate for the primary combined and secondary endpoints was lower for patients with an intermediate and high H 2 FPEF score. On multivariate Cox regression analysis, female sex (hazard ratio [HR] 1.670, 95% confidence interval [CI] 1.157–2.410; p = 0.006), Asian ethnicity (HR 6.711, 95% CI 4.076–11.048; p &lt; 0.001), ischaemic heart disease (HR 1.732, 95% CI 1.133–2.650; p = 0.011), left atrial diameter (HR 1.028, 95% CI 1.005–1.051; p = 0.016) and intermediate (HR 2.757, 95% CI 1.612–4.713; p &lt; 0.001) or high H 2 FPEF score (HR 3.689, 95% CI 1.908–7.134; p &lt; 0.001) were independently associated with the primary combined endpoint. Conclusion The H 2 FPEF score is independently associated with HF outcome in patients with HCM and may be considered for risk stratification.
Clinical sequelae of gut microbiome development and disruption in hospitalized preterm infants
Authors: Robert Thänert, Drew J Schwartz, Eric C Keen, Carla Hall-Moore, Bin Wang, Nurmohammad Shaikh, Jie Ning, L Colleen Rouggly-Nickless, Anna Thänert, Aura Ferreiro, Skye R S Fishbein, Janice E Sullivan, Paula Radmacher, Marilyn Escobedo, Barbara B Warner, Phillip I Tarr, Gautam Dantas
Journal: Cell Host & Microbe (2024)

Aberrant preterm infant gut microbiota assembly predisposes to early-life disorders and persistent health problems. Here, we characterize gut microbiome dynamics over the first 3 months of life in 236 preterm infants hospitalized in three neonatal intensive care units using shotgun metagenomics of 2,512 stools and metatranscriptomics of 1,381 stools. Strain tracking, taxonomic and functional profiling, and comprehensive clinical metadata identify Enterobacteriaceae, enterococci, and staphylococci as primarily exploiting available niches to populate the gut microbiome. Clostridioides difficile lineages persist between individuals in single centers, and Staphylococcus epidermidis lineages persist within and, unexpectedly, between centers. Collectively, antibiotic and non-antibiotic medications influence gut microbiome composition to greater extents than maternal or baseline variables. Finally, we identify a persistent low-diversity gut microbiome in neonates who develop necrotizing enterocolitis after day of life 40. Overall, we comprehensively describe gut microbiome dynamics in response to medical interventions in preterm, hospitalized neonates.
Association of ventricular–arterial coupling with biomarkers involved in heart failure pathophysiology – the <scp>STANISLAS</scp> cohort
Authors: Hannes Holm, Martin Magnusson, Amra Jujić, Jérémy Lagrange, Erwan Bozec, Zohra Lamiral, Emmanuel Bresso, Olivier Huttin, Guillaume Baudry, Luca Monzo, Patrick Rossignol, Faiez Zannad, Nicolas Girerd
Journal: European Journal of Heart Failure (2024)

Aims Impaired left ventricular–arterial coupling (VAC) has been shown to correlate with worse prognosis in cardiac diseases and heart failure (HF). The extent of the relationship between VAC and circulating biomarkers associated with HF has been scarcely documented. We aimed to explore associations of VAC with proteins involved in HF pathophysiology within a large population‐based cohort of middle‐aged individuals. Methods and results In the forth visit of the STANISLAS family cohort, involving 1309 participants (mean age 48 ± 14 years; 48% male) from parent and children generations, we analysed the association of 32 HF‐related proteins with non‐invasively assessed VAC using pulse wave velocity (PWV)/global longitudinal strain (GLS) and arterial elastance (E a )/ventricular end‐systolic elastance (E es ). Among the 32 tested proteins, fatty acid‐binding protein adipocyte 4, interleukin‐6, growth differentiation factor 15, matrix metalloproteinase (MMP)‐1, and MMP‐9 and adrenomedullin were positively associated with PWV/GLS whereas transforming growth factor beta receptor type 3, MMP‐2 and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) were negatively associated. In multivariable models, only MMP‐2 and NT‐proBNP were significantly and inversely associated with PWV/GLS in the whole population and in the parent generation. Higher levels of NT‐proBNP were also negatively associated with E a /E es in the whole cohort but this association did not persist in the parent subgroup. Conclusion Elevated MMP‐2 and NT‐proBNP levels correlate with better VAC (lower PWV/GLS), possibly indicating a compensatory cardiovascular response to regulate left ventricular pressure amidst cardiac remodelling and overload.
Metabolite-based inter-kingdom communication controls intestinal tissue recovery following chemotherapeutic injury
Authors: Christopher J Anderson, Laura Boeckaerts, Priscilla Chin, Javier Burgoa Cardas, Wei Xie, Amanda Gonçalves, Gillian Blancke, Sam Benson, Sebastian Rogatti, Mariska S Simpson, Anna Davey, Sze Men Choi, Sandrien Desmet, Summer D Bushman, Geert Goeminne, Peter Vandenabeele, Mahesh S Desai, Lars Vereecke, Kodi S Ravichandran
Journal: Cell Host & Microbe (2024)
Engineered probiotic ameliorates ulcerative colitis by restoring gut microbiota and redox homeostasis
Authors: Peilin Guo, Wenjing Wang, Qian Xiang, Chao Pan, Yefeng Qiu, Tingting Li, Dongfang Wang, Jian Ouyang, Rongrong Jia, Min Shi, Yugang Wang, Junxia Li, Jiale Zou, Yuan Zhong, Jiawei Zhao, Diwei Zheng, Yimin Cui, Guanghui Ma, Wei Wei
Journal: Cell Host & Microbe (2024)
Genetic Risk, Health-Associated Lifestyle, and Risk of Early-onset Total Cancer and Breast Cancer
Authors: Yin Zhang, Sara Lindström, Peter Kraft, Yuxi Liu
Journal: JNCI Journal of the National Cancer Institute (2024)

Early-onset cancer (diagnosed under age 50) generally manifests as an aggressive disease phenotype. The association between healthy lifestyle and early-onset cancer and whether it varies by common genetic variants remains unclear.
Community-Based Participatory Research and System Dynamics Modeling for Improving Retention in Hypertension Care
Authors: Jiancheng Ye, Ikechukwu A. Orji, Michelle A. Birkett, Lisa R. Hirschhorn, Theresa L. Walunas, Justin D. Smith, Namratha R. Kandula, Gabriel L. Shedul, Mark D. Huffman, Dike B. Ojji
Journal: JAMA Network Open (2024)

Importance The high prevalence of hypertension calls for broad, multisector responses that foster prevention and care services, with the goal of leveraging high-quality treatment as a means of reducing hypertension incidence. Health care system improvements require stakeholder input from across the care continuum to identify gaps and inform interventions that improve hypertension care service, delivery, and retention; system dynamics modeling offers a participatory research approach through which stakeholders learn about system complexity and ways to model sustainable system-level improvements. Objective To assess the association of simulated interventions with hypertension care retention rates in the Nigerian primary health care system using system dynamics modeling. Design, Setting, and Participants This decision analytical model used a participatory research approach involving stakeholder workshops conducted in July and October 2022 to gather insights and inform the development of a system dynamics model designed to simulate the association of various interventions with retention in hypertension care. The study focused on the primary health care system in Nigeria, engaging stakeholders from various sectors involved in hypertension care, including patients, community health extension workers, nurses, pharmacists, researchers, administrators, policymakers, and physicians. Exposure Simulated intervention packages. Main Outcomes and Measures Retention rate in hypertension care at 12, 24, and 36 months, modeled to estimate the effectiveness of the interventions. Results A total of 16 stakeholders participated in the workshops (mean [SD] age, 46.5 [8.6] years; 9 [56.3%] male). Training of health care workers was estimated to be the most effective single implementation strategy for improving retention in hypertension care in Nigeria, with estimated retention rates of 29.7% (95% CI, 27.8%-31.2%) at 12 months and 27.1% (95% CI, 26.0%-28.3%) at 24 months. Integrated intervention packages were associated with the greatest improvements in hypertension care retention overall, with modeled retention rates of 72.4% (95% CI, 68.4%-76.4%), 68.1% (95% CI, 64.5%-71.7%), and 67.1% (95% CI, 64.5%-71.1%) at 12, 24, and 36 months, respectively. Conclusions and Relevance This decision analytical model study showed that community-based participatory research could be used to estimate the potential effectiveness of interventions for improving retention in hypertension care. Integrated intervention packages may be the most promising strategies.
Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis
Authors: Glenda Trujillo, Alicia Regueiro-Ren, Chunjian Liu, Buqu Hu, Ying Sun, Farida Ahangari, Vitoria Fiorini, Genta Ishikawa, Karam Al Jumaily, Johad Khoury, John McGovern, Chris J Lee, Xue Yan Peng, Taylor Pivarnik, Huanxing Sun, Anjali Walia, Samuel Woo, Sheeline Yu, Danielle E. Antin-Ozerkis, Maor Sauler, Naftali Kaminski, Erica L. Herzog, Changwan Ryu
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease for which current treatment options only slow clinical progression. Previously, we identified a subset of patients with IPF with an accelerated disease course associated with fibroblast expression of Toll-Like Receptor 9 (TLR9) mediated by interactions with its ligand mitochondrial DNA (mtDNA).
Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic risk to childhood-onset asthma
Authors: Sarah Djeddi, Daniela Fernandez-Salinas, George X Huang, Vitor R C Aguiar, Chitrasen Mohanty, Christina Kendziorski, Steven Gazal, Joshua A Boyce, Carole Ober, James E Gern, Nora A Barrett, Maria Gutierrez-Arcelus
Journal: Cell Genomics (2024)

Asthma is a complex disease caused by genetic and environmental factors. Studies show that wheezing during rhinovirus infection correlates with childhood asthma development. Over 150 non-coding risk variants for asthma have been identified, many affecting gene regulation in T cells, but the effects of most risk variants remain unknown. We hypothesized that airway epithelial cells could also mediate genetic susceptibility to asthma given they are the first line of defense against respiratory viruses and allergens. We integrated genetic data with transcriptomics of airway epithelial cells subject to different stimuli. We demonstrate that rhinovirus infection significantly upregulates childhood-onset asthma-associated genes, particularly in non-ciliated cells. This enrichment is also observed with influenza infection but not with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or cytokine activation. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.
Horizontal gene transfer of a key translation factor and its role in polyproline proteome evolution
Authors: Tess E Brewer, Andreas Wagner
Journal: Molecular Biology and Evolution (2024)

Abstract Prolines cause ribosomes to stall during translation due to their rigid structure. This phenomenon occurs in all domains of life and is exacerbated at polyproline motifs. Such stalling can be eased by the elongation factor P (EF-P) in bacteria. We discovered a potential connection between the loss of ancestral EF-P, the appearance of horizontally transferred EF-P variants, and genomic signs of EF-P dysfunction. Horizontal transfer of the efp gene has occurred several times among bacteria and is associated with the loss of highly conserved polyproline motifs. In this study, we pinpoint cases of horizontal EF-P transfer among a diverse set of bacteria and examine genomic features associated with these events in the phyla Thermotogota and Planctomycetes. In these phyla, horizontal EF-P transfer is also associated with the loss of entire polyproline motif-containing proteins, whose expression is likely dependent on EF-P. In particular, three proteases (Lon, ClpC, and FtsH) and three tRNA synthetases (ValS, IleS1, and IleS2) appear highly sensitive to EF-P transfer. The conserved polyproline motifs within these proteins all reside within close proximity to ATP-binding-regions, some of which are crucial for their function. Our work shows that an ancient EF-P dysfunction has left genomic traces that persist to this day, although it remains unclear whether this dysfunction was strictly due to loss of ancestral EF-P or was related to the appearance of an exogenous variant. The latter possibility would imply that the process of “domesticating” a horizontally transferred efp gene can perturb the overall function of EF-P.
Long‐term immune changes in patients with relapsed/refractory chronic lymphocytic leukemia following treatment with venetoclax plus rituximab
Authors: Arnon P. Kater, Barbara F. Eichhorst, Carolyn J. Owen, Ulrich Jaeger, Brenda Chyla, Marcus Lefebure, Rosemary Millen, Yanwen Jiang, Maria Thadani‐Mulero, Michelle Boyer, John F. Seymour
Journal: HemaSphere (2024)

Abstract Immune dysregulation is a hallmark of chronic lymphocytic leukemia (CLL). Anti‐CD20 antibodies (e.g., rituximab [R]) can be combined with venetoclax (Ven) to treat CLL. However, anti‐CD20 antibodies can increase hypogammaglobulinemia risk, while the effects of Ven on immune dysregulation are still uncertain. We report long‐term immune changes in VenR‐ and bendamustine‐R (BR)‐treated patients with relapsed/refractory CLL in the MURANO trial (NCT02005471). Patients were randomized to fixed‐duration VenR (2 years Ven; VenR for the first 6 months) or BR (6 months). Immune cell levels were evaluated at the end of combination treatment (EOCT), end of treatment (EOT; VenR arm only), and 12 and 24 months post‐EOCT. Overall, 130/194 VenR‐ and 134/195 BR‐treated patients completed treatment without progressive disease. In patients who completed VenR combination therapy, median immunoglobulin (Ig)G and IgM levels decreased from baseline to EOT ( p ≤ 0.01 and p ≤ 0.0001, respectively); by 24 months, post‐EOT IgG had returned to baseline level and IgM had increased from baseline ( p ≤ 0.001). Median IgA levels increased from baseline to 12 ( p ≤ 0.0001) and 24 months post‐EOT ( p ≤ 0.0001). In BR‐treated patients, changes in IgG, IgA, and IgM levels across the assessed time points were not significant, and by 24 months, post‐EOCT IgG, IgA, and IgM were above baseline levels. Grade ≥3 infection rates on treatment were low. Overall, immune recovery was observed with VenR and BR, with stabilization of Ig levels after treatment. Post‐treatment infection rates were generally low, making these very tolerable therapies for CLL.
Elexacaftor/Tezacaftor/Ivacaftor Markedly Reduces <i>Aspergillus fumigatus</i> in Cystic Fibrosis
Authors: Sarah J Morgan, David P. Nichols, Wendy Ni, Gina Hong, Stephen J. Salipante, George M Solomon, Steven M. Rowe, John P Clancy, Robert A Cramer, Pradeep K Singh
Journal: American Journal of Respiratory and Critical Care Medicine (2024)