tbuckley/cabot-search huggingface dataset:
Global Antimicrobial Susceptibility Patterns of <i>Staphylococcus aureus</i> in Atopic Dermatitis
Authors: Itzel Guadalupe Elizalde-Jiménez, Fernando Gerardo Ruiz-Hernández, Silvia Angélica Carmona-Cruz, Elena Pastrana-Arellano, Alejandra Aquino-Andrade, Carolina Romo-González, Eduardo Arias-de la Garza, Neri Alejandro Álvarez-Villalobos, Maria Teresa García-Romero
Journal: JAMA Dermatology (2024)

Importance Individuals with atopic dermatitis are frequently colonized and infected with Staphylococcus aureus . Empirical antibiotic therapy for individuals with atopic dermatitis is common, but data about the antimicrobial susceptibility profiles of S aureus strains isolated from these individuals are scarce for those living in particular geographic areas. Objective To determine the antimicrobial susceptibility of S aureus from individuals with atopic dermatitis and analyze differences according to the income level of the country of origin and the data collection period. Data Sources A meta-analysis of the literature was performed from the inception of the included databases (MEDLINE, Embase, Web of Science, Scopus, and Cochrane) to June 20, 2023, using predetermined Medical Subject Headings. Study Selection Studies were included if they reported antibiotic susceptibility profiles of 1 or more S aureus cutaneous isolates from individuals with atopic dermatitis. Articles written in English, Spanish, French, or German were included. Data Extraction and Synthesis Working in pairs, 6 of the authors conducted the data extraction. The guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) were followed. Main Outcomes and Measures The outcome of interest was antimicrobial susceptibility. Results A total of 61 studies reported 4091 S aureus isolates from individuals with atopic dermatitis. For 4 of the 11 commonly used antibiotics (36.4%), antimicrobial susceptibility was 85% or less, including for methicillin (binomial proportion, 0.85 [95% CI, 0.76-0.91]), erythromycin (binomial proportion, 0.73 [95% CI, 0.61-0.83]), fusidic acid (binomial proportion, 0.80 [95% CI, 0.62-0.91]), and clindamycin (binomial proportion, 0.79 [95% CI, 0.65-0.89]). Most studies (46; 75.4%) were conducted in high-income countries. Antimicrobial susceptibility to erythromycin, methicillin, and trimethoprim and sulfamethoxazole was significantly lower in lower middle–income countries and upper middle–income countries. Regarding the temporal trends, 33 studies (54.1%) reported data collected from 1998 to 2010. Antimicrobial susceptibility patterns have not changed over time. Conclusions and Relevance In this systematic review and meta-analysis, antimicrobial susceptibility of S aureus to β-lactams, erythromycin, clindamycin, and fusidic acid may be suboptimal for empirical use in individuals with atopic dermatitis. Significant differences in antimicrobial susceptibility patterns were found in high-income countries and in lower middle–income countries and upper middle–income countries for some antibiotics.
Urinary Concentrations of Organophosphate Flame-Retardant Metabolites in the US Population
Authors: Yu-Song Huang, Hui-Zhong Shi, Xi Huang, Yi-Ming Pan, Yu-Chen Wang, Zi-Jun Gao, Pei-Yao Jiang, Wen-Yi Yang
Journal: JAMA Network Open (2024)

Importance Organophosphate flame retardants (OPFRs) are an important group of pollutants associated with endocrine disorders, cancer, and nephrotoxicity. However, temporal trends in OPFR metabolite concentrations remain understudied. Objectives To examine changes in urinary concentrations of OPFR metabolites among US children, youths, and adults from 2011 to 2020, and to evaluate whether sociodemographic factors were associated with variations in temporal trends. Design, Setting, and Participants This population-based cross-sectional study used data from 4 US National Health and Nutrition Examination Survey (NHANES) cycles (2011-2012, 2013-2014, 2015-2016, and 2017-2020 [to March 2020 before the COVID-19 pandemic]). The study included children and youths (aged 6-19 years) and adults (aged ≥20 years) with valid urinary concentrations of the following OPFR metabolites: bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), diphenyl phosphate (DPhP), and dibutyl phosphate (DBuP). Data analysis was performed between February and May 2024. Exposures Calendar year and key sociodemographic subgroups (age, race and ethnicity, sex, educational attainment, and poverty-to-income ratio). Main Outcomes and Measures The main outcome was urinary concentrations of OPFR metabolites among children, youths, and adults. Survey-weighted linear regression models were applied to estimate trends. Results The study population of 10 549 NHANES participants included 3154 children and youths (mean [SE] age, 12.5 [0.1] years; 51.2% were male) and 7395 adults (mean [SE] age, 47.8 [0.4] years; 52.0% were women). Among children and youths, mean (95% CI) BCEtP concentrations decreased from 0.68 (0.60-0.77) μg/L in 2011-2012 to 0.41 (0.37-0.45) μg/L in 2017-2020 ( P for trend &amp;amp;lt; .001). Among adults, mean (95% CI) BCEtP concentrations decreased from 0.43 (0.37-0.50) μg/L in 2011-2012 to 0.29 (0.27-0.33) μg/L in 2017-2020 ( P for trend &amp;amp;lt; .001), and mean BCPP concentrations decreased from 0.15 (0.14-0.17) μg/L to 0.13 (0.12-0.14) μg/L ( P for trend = .002). Parent level of educational attainment was associated with concentrations of BCPP and BCEtP among children and youths; however, no significant differences among adults were observed. Conclusions and Relevance This study identified variations in temporal trends in urinary concentrations of OPFR metabolites among the US population from 2011 to 2020. In addition, substantial disparities in exposure levels persisted among children with different levels of parent educational attainment. These findings suggest that policy makers should consider socioeconomic factors to further reduce OPFR exposure and promote equity, ensuring a safe living environment for all individuals.
Hospital Heart Failure Medical Therapy Score and Associated Clinical Outcomes and Costs
Authors: Vincenzo B. Polsinelli, Jie-Lena Sun, Stephen J. Greene, Karen Chiswell, Gary K. Grunwald, Larry A. Allen, Pamela Peterson, Ambarish Pandey, Gregg C. Fonarow, Paul Heidenreich, P. Michael Ho, Paul L. Hess
Journal: JAMA Cardiology (2024)

A composite score for guideline-directed medical therapy (GDMT) for patients with heart failure (HF) is associated with increased survival. Whether hospital performance according to a GDMT score is associated with a broader array of clinical outcomes at lower costs is unknown.
Additional Lesion Sets in Ablation of Outflow Tract Premature Ventricular Contractions
Authors: Kexin Wang, Fu Yi, Fangyi Xiao, Cao Zou, Yuzhen Zhang, Yuegang Wang, Linsheng Shi, Chengzong Li, Long Chen, Shuanglun Xie, Wenzhi Shen, Ning Zhang, Qiang Wu, Qiang Xu, Yuan Ji, Cheng Wang, Zhiyu Lin, Youquan Wei, Zhongbao Ruan, Yumin Sun, Weizhu Ju, Minglong Chen, Caiyi Jin, Jie Li, Shengjie Wu, Jing Zhou, Hairuo Lin, Xiaoli Chen, Xiaoqing Hu, Yaowu Lin, Yuyang Chen, Tong Pan, Xie Yun, Jianshu Chen, Liuyang Wu, Jingcheng Chen, Qingsong Xiong, Jichun Liu, Xiangwei Ding, Bin Cao
Journal: JAMA Cardiology (2024)

Importance Recurrence remains a challenge after ablation of outflow tract premature ventricular contractions (OT-PVCs). Although adding additional lesions next to the index effective ablation site is sometimes performed to reinforce the ablation, it remains uncertain whether this approach is effective. Objective To test the hypothesis that additional ablation lesions would reduce the recurrence rate compared with single-point ablation at the index effective site for the ablation of OT-PVCs. Design, Setting, and Participants This study was a multicenter, prospective, randomized clinical trial. Patients receiving their first catheter ablation for OT-PVCs were enrolled from 18 hospitals in China between October 2021 and February 2023. Scheduled follow-up duration was 3 months after the procedure. Intervention After identifying the target point and eliminating the PVC by a single-point ablation, patients were randomized 1:1 into an additional ablation group or a control group. Main Outcomes and Measures The primary end point of the study was freedom from PVC recurrence (≥80% reduction of PVC burden, which is the number of PVCs in 24 hours/total heartbeats in 24 hours × 100%) from baseline to 3 months postprocedure. Results Of 308 patients enrolled in the study, 286 (mean [SD] age, 49.2 [14.6] years; 173 female [60.5%]) were randomized to the additional ablation or the control group. The additional ablation group had a mean (SD) of 6.3 (1.1) radiofrequency applications, whereas the control group (single-point ablation group) had a mean (SD) of 1 (0) radiofrequency application. After a median (IQR) follow-up of 3.2 (0) months, the rate of freedom from PVCs was significantly higher in the additional ablation group (139 of 142 [97.9%]) compared with the control group (115 of 139 [82.7%]; P &amp;amp;lt; .001). Patients in the additional ablation group also had a more substantial reduction in PVC burden than the control group (mean [SD] reduction, 23.0% [10.5%] vs 19.0% [10.4%]; P = .002). There were no severe periprocedural complications in either group. Conclusions and Relevance This randomized clinical trial showed a benefit of additional ablation in reducing the recurrence of OT-PVCs compared with the single-point ablation strategy, without increased complication risk. Additional ablations surrounding the index effective ablation point should be considered in OT-PVC ablation. Trial Registration Chinese Clinical Trials Registry Identifier: ChiCTR2200055340
Suicidal Ideation and Suicide Attempts After Direct or Indirect Psychotherapy
Authors: Wouter van Ballegooijen, Josine Rawee, Christina Palantza, Clara Miguel, Mathias Harrer, Ioana Cristea, Remco de Winter, Renske Gilissen, Merijn Eikelenboom, Aartjan Beekman, Pim Cuijpers
Journal: JAMA Psychiatry (2024)

Importance Suicidal ideation and suicide attempts are debilitating mental health problems that are often treated with indirect psychotherapy (ie, psychotherapy that focuses on other mental health problems, such as depression or personality disorders). The effects of direct and indirect psychotherapy on suicidal ideation have not yet been examined in a meta-analysis, and several trials have been published since a previous meta-analysis examined the effect size of direct and indirect psychotherapy on suicide attempts. Objective To investigate the effect sizes of direct and indirect psychotherapy on suicidal ideation and the incidence of suicide attempts. Data Sources PubMed, Embase, PsycInfo, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials were searched for articles published up until April 1, 2023. Study Selection Randomized clinical trials of psychotherapy for any mental health problem, delivered in any setting, compared with any control group, and reporting suicidal ideation or suicide attempts were included. Studies measuring suicidal ideation with 1 item were excluded. Data Extraction and Synthesis PRISMA guidelines were followed. Summary data were extracted by 2 independent researchers and pooled using 3-level meta-analyses. Main Outcomes and Measures Hedges g was pooled for suicidal ideation and relative risk (RR) was pooled for suicide attempts. Results Of 15 006 studies identified, 147 comprising 193 comparisons and 11 001 participants were included. Direct and indirect psychotherapy conditions were associated with reduced suicidal ideation (direct: g , −0.39; 95% CI, −0.53 to −0.24; I 2 , 83.2; indirect: g , −0.30; 95% CI, −0.42 to −0.18; I 2 , 52.2). Direct and indirect psychotherapy conditions were also associated with reduced suicide attempts (direct: RR, 0.72; 95% CI, 0.62 to 0.84; I 2 , 40.5; indirect: RR, 0.68; 95% CI, 0.48 to 0.95; I 2 , 0). Sensitivity analyses largely confirmed these results. Conclusions and Relevance Direct and indirect interventions had similar effect sizes for reducing suicidal ideation and suicide attempts. Suicide prevention strategies could make greater use of indirect treatments to provide effective interventions for people who would not likely seek treatment for suicidal ideation or self-harm.
Re: Niklas Klümper, Viktor Grünwald, Arndt Hartmann, et al. The Role of Microsatellite Instability/DNA Mismatch Repair Deficiency and Tumor Mutational Burden as Biomarkers in Predicting Response to Immunotherapy in Castration-resistant Prostate Cancer. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.04.026
Authors: Feng Qi
Journal: European Urology (2024)
A Meta-Analysis and Meta-Regression of the Efficacy, Toxicity, and Quality of Life Outcomes Following Prostate-Specific Membrane Antigen Radioligand Therapy Utilising Lutetium-177 and Actinium-225 in Metastatic Prostate Cancer
Authors: Yang-Hong Dai, Po-Huang Chen, Ding-Jie Lee, Gerard Andrade, Katherine A Vallis
Journal: European Urology (2024)

Management of metastatic prostate cancer (mPCa) presents significant challenges. In this systematic review, meta-analysis, and meta-regression, the efficacy, safety, and quality of life (QoL) outcomes of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT) utilising lutetium-177 ([
A microenvironment responsive polyetheretherketone implant with antibacterial and osteoimmunomodulatory properties facilitates osseointegration
Authors: Miao Chen, Yusen Qiao, Lei Yu, Wei Wang, Wentao Wang, Haifu Sun, Yaozeng Xu, Jiaxiang Bai, Jun Zhou, Dechun Geng
Journal: Bioactive Materials (2024)
Reduction of prolonged excitatory neuron swelling after spinal cord injury improves locomotor recovery in mice
Authors: Qiang Li, Alfredo Sandoval, John Moth, Junkui Shang, Jia Yi Liew, Tiffany Dunn, Zhiyun Yang, Junfeng Su, Melissa Henwood, Philip Williams, Bo Chen
Journal: Science Translational Medicine (2024)

Spinal cord injury (SCI) results in acute damage and triggers secondary injury responses with sustained neuronal loss and dysfunction. However, the underlying mechanisms for these delayed neuronal pathologies are not entirely understood. SCI results in the swelling of spinal neurons, but the contribution of cell swelling to neuronal loss and functional deficits after SCI has not been systematically characterized. In this study, we devised a three-dimensional image analysis pipeline to evaluate spinal neurons, examining their types, quantities, volumes, and spatial distribution in a double-lateral hemisection SCI mouse model. We found that both excitatory and inhibitory neurons swell and are lost, albeit with distinct temporal patterns. Inhibitory neurons demonstrated marked swelling and decline in number on day 2 after SCI, which resolved by day 14. In contrast, excitatory neurons maintained persistent swelling and continued cell loss for at least 35 days after SCI in mice. Excitatory neurons exhibited sustained expression of the Na + -K + -Cl − cotransporter 1 (NKCC1), whereas inhibitory neurons down-regulated the protein by day 14 after SCI. Treatment with a Food and Drug Administration–approved NKCC1 inhibitor, bumetanide, mitigated swelling of excitatory neurons and reduced their loss in the secondary injury phase after SCI. The administration of bumetanide after SCI in mouse improved locomotor recovery, with functional benefits persisting for at least 4 weeks after treatment cessation. This study advances our understanding of SCI-related pathology and introduces bumetanide as a potential treatment to mitigate sustained neuronal swelling and enhance recovery after SCI.
Spermidine metabolism regulates leukemia stem and progenitor cell function through KAT7 expression in patient-derived mouse models
Authors: Vincent Rondeau, Jacob M. Berman, Tianyi Ling, Cristiana O’Brien, Rachel Culp-Hill, Julie A. Reisz, Mark Wunderlich, Yun Chueh, Karina E. Jiménez-Camacho, Christina Sexton, Katharine M. Carter, Cody Stillwell, Jonathan St-Germain, Duhan Yendi, Aarushi Gupta, Mary Shi, Aleksandra Bourdine, Vikram R. Paralkar, Soheil Jahangiri, Kristin J. Hope, Anastasia N. Tikhonova, Andrea Arruda, Mark D. Minden, Brian Raught, Angelo D’Alessandro, Courtney L. Jones
Journal: Science Translational Medicine (2024)

Acute myeloid leukemia (AML) is a devastating disease initiated and maintained by a rare subset of cells called leukemia stem cells (LSCs). LSCs are responsible for driving disease relapse, making the development of new therapeutic strategies to target LSCs urgently needed. The use of mass spectrometry–based metabolomics profiling has enabled the discovery of unique and targetable metabolic properties in LSCs. However, we do not have a comprehensive understanding of metabolite differences between LSCs and their normal counterparts, hematopoietic stem and progenitor cells (HSPCs). In this study, we used an unbiased mass spectrometry–based metabolomics analysis to define differences in metabolites between primary human LSCs and HSPCs, which revealed that LSCs have a distinct metabolome. Spermidine was the most enriched metabolite in LSCs compared with HSPCs. Pharmacological reduction of spermidine concentrations decreased LSC function but spared normal HSPCs. Polyamine depletion also decreased leukemic burden in patient-derived xenografts. Mechanistically, spermidine depletion induced LSC myeloid differentiation by decreasing eIF5A-dependent protein synthesis, resulting in reduced expression of a select subset of proteins. KAT7, a histone acetyltransferase, was one of the top candidates identified to be down-regulated by spermidine depletion. Overexpression of KAT7 partially rescued polyamine depletion–induced decreased colony-forming ability, demonstrating that loss of KAT7 is an essential part of the mechanism by which spermidine depletion targets AML clonogenic potential. Together, we identified and mechanistically dissected a metabolic vulnerability of LSCs that has the potential to be rapidly translated into clinical trials to improve outcomes for patients with AML.
Inhibition of heme-thiolate monooxygenase CYP1B1 prevents hepatic stellate cell activation and liver fibrosis by accumulating trehalose
Authors: Hung-Chun Tung, Jong-Won Kim, Junjie Zhu, Sihan Li, Jiong Yan, Qing Liu, Imhoi Koo, Sergei A. Koshkin, Fuhua Hao, Guo Zhong, Meishu Xu, Zehua Wang, Jingyuan Wang, Yixian Huang, Yue Xi, Xinran Cai, Pengfei Xu, Songrong Ren, Takanobu Higashiyama, Frank J. Gonzalez, Song Li, Nina Isoherranen, Da Yang, Xiaochao Ma, Andrew D. Patterson, Wen Xie
Journal: Science Translational Medicine (2024)

Activation of extracellular matrix–producing hepatic stellate cells (HSCs) is a key event in liver fibrogenesis. We showed that the expression of the heme-thiolate monooxygenase cytochrome P450 1B1 (CYP1B1) was elevated in human and mouse fibrotic livers and activated HSCs. Systemic or HSC-specific ablation and pharmacological inhibition of CYP1B1 attenuated HSC activation and protected male but not female mice from thioacetamide (TAA)–, carbon tetrachloride (CCl 4 )–, or bile duct ligation (BDL)–induced liver fibrosis. Metabolomic analysis revealed an increase in the disaccharide trehalose in CYP1B1-deficient HSCs resulting from intestinal suppression of the trehalose-metabolizing enzyme trehalase, whose gene we found to be a target of RARα. Trehalose or its hydrolysis-resistant derivative lactotrehalose exhibited potent antifibrotic activity in vitro and in vivo by functioning as an HSC-specific autophagy inhibitor, which may account for the antifibrotic effect of CYP1B1 inhibition. Our study thus reveals an endobiotic function of CYP1B1 in liver fibrosis in males, mediated by liver-intestine cross-talk and trehalose. At the translational level, pharmacological inhibition of CYP1B1 or the use of trehalose/lactotrehalose may represent therapeutic strategies for liver fibrosis.
B cells drive neuropathic pain–related behaviors in mice through IgG–Fc gamma receptor signaling
Authors: Michael J. Lacagnina, Kendal F. Willcox, Nabila Boukelmoune, Alexis Bavencoffe, Ishwarya Sankaranarayanan, Daniel T. Barratt, Younus A. Zuberi, Dorsa Dayani, Melissa V. Chavez, Jonathan T. Lu, Alex Bersellini Farinotti, Stephanie Shiers, Allison M. Barry, Juliet M. Mwirigi, Diana Tavares-Ferreira, Geoffrey A. Funk, Anna M. Cervantes, Camilla I. Svensson, Edgar T. Walters, Mark R. Hutchinson, Cobi J. Heijnen, Theodore J. Price, Nathan T. Fiore, Peter M. Grace
Journal: Science Translational Medicine (2024)

Neuroimmune interactions are essential for the development of neuropathic pain, yet the contributions of distinct immune cell populations have not been fully unraveled. Here, we demonstrate the critical role of B cells in promoting mechanical hypersensitivity (allodynia) after peripheral nerve injury in male and female mice. Depletion of B cells with a single injection of anti-CD20 monoclonal antibody at the time of injury prevented the development of allodynia. B cell–deficient (muMT) mice were similarly spared from allodynia. Nerve injury was associated with increased immunoglobulin G (IgG) accumulation in ipsilateral lumbar dorsal root ganglia (DRGs) and dorsal spinal cords. IgG was colocalized with sensory neurons and macrophages in DRGs and microglia in spinal cords. IgG also accumulated in DRG samples from human donors with chronic pain, colocalizing with a marker for macrophages and satellite glia. RNA sequencing revealed a B cell population in naive mouse and human DRGs. A B cell transcriptional signature was enriched in DRGs from human donors with neuropathic pain. Passive transfer of IgG from injured mice induced allodynia in injured muMT recipient mice. The pronociceptive effects of IgG are likely mediated through immune complexes interacting with Fc gamma receptors (FcγRs) expressed by sensory neurons, microglia, and macrophages, given that both mechanical allodynia and hyperexcitability of dissociated DRG neurons were abolished in nerve-injured FcγR-deficient mice. Consistently, the pronociceptive effects of IgG passive transfer were lost in FcγR-deficient mice. These data reveal that a B cell–IgG–FcγR axis is required for the development of neuropathic pain in mice.
Clinical, mechanistic, and therapeutic landscape of cutaneous fibrosis
Authors: Dayan J. Li, Charlotte E. Berry, Derrick C. Wan, Michael T. Longaker
Journal: Science Translational Medicine (2024)

When dysregulated, skin fibrosis can lead to a multitude of pathologies. We provide a framework for understanding the wide clinical spectrum, mechanisms, and management of cutaneous fibrosis encompassing a variety of matrix disorders, fibrohistiocytic neoplasms, injury-induced scarring, and autoimmune scleroses. Underlying such entities are common mechanistic pathways that leverage morphogenic signaling, immune activation, and mechanotransduction to modulate fibroblast function. In light of the limited array of available treatments for cutaneous fibrosis, scientific insights have opened new therapeutic and investigative avenues for conditions that still lack effective interventions.