bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of blood pressure control level on all-cause mortality and CVD mortality in patients with hypertension and its comorbidities: A prospective cohort study in Southwest China
Authors: Wu Yanli , Li Ling , Zhou Jie , Zhang Ji , Wang Yiying , Yu Lisha , Liu Tao 
Published: June 2024

ABSTRACTBackgroundBlood pressure (BP) control levels may be associated with the risk of all-cause mortality and CVD mortality. The goal of this study was to explore the association of BP control levels with the risk of all-cause mortality and CVD mortality in adults in Guizhou, China.MethodsA 13-year prospective cohort study of 1,905 hypertension patients adults aged 18 years or older was conducted in Guizhou, southwest China from 2010 to 2023. Information of participants death were collected, cause of death was coded according to ICD-10 and codes I00-I99 was categorized as CVD-related deaths. Cox proportional hazard regression was used to examine the associations of BP control levels with all-cause mortality and CVD mortality.Results134 deaths occurred during a median follow-up of 11.72 years. The multivariable cox hazard regression models showed that compared with SBP≥140 mmHg and DBP≥90 mmHg group, participants with SBP <120 mmHg and DBP <80 mmHg, they had the lowest risk of all-cause mortality (HR=0.265, 95%CI:0.111,0.630) and the lower risk of CVD death (HR=0.274, 95%CI:0.092,0.814). Associations between BP control levels with all-cause mortality and CVD mortality were suggested to be even stronger among aged ≥65 years (P<0.05), but ideal BP levels were not significantly associated with CVD mortality in participants with comorbidity (P>0.05).ConclusionOptimal BP control levels(<120/80mmHg) is effective in reducing overall mortality and cardiovascular disease (CVD) mortality, even among older adults. however, for hypertension with comorbidities, mere BP control alone may not suffice, consideration should also be given to the treatment of other coexisting conditions.NOVELTY AND RELEVANCEWhat Is New?To our knowledge, few studies have investigated the relationship between the levels of blood pressure control in hypertensive patients and all-cause mortality in the Chinese population. Furthermore, there exists divergent viewpoints regarding the extent of blood pressure management in geriatric patients diagnosed with hypertension.In this study, we used data from a prospective cohort study in Southwest China to investigate whether the level of blood pressure control of hypertension patients was associated with all-cause mortality and cardiovascular disease (CVD) death and test whether those associations were modified by age or comorbidity factors.What Is Relevant?Using data from a prospective cohort study in Southwest China, we found that maintaining optimal blood pressure control levels (<120/80mmHg) was found to significantly reduce overall mortality and cardiovascular disease (CVD) mortality, even among elderly individuals.Clinical/Pathophysiological Implications?The association between blood pressure and all-cause mortality serves as a guide for the management and control of hypertension in patients.
A New NAEC Level III Epilepsy Center for Adults in Southern San Joaquin Valley of CA – Initial Experience of the Kern Medical Epilepsy Center
Authors: Dao KT , Liu L , Ipe J , Poston C , Zalmay N , Ly B , Nguyen C , Braich S , Chacko C , Greenwood J , Heck CN , Ragoonanan L , Chen JCT , Lee D , Russin J , Lee B , Liu CY , Kunhi-Veedu HP 
Published: June 2024

AbstractEpilepsy care has largely improved across the United States in the past decades, as reflected in Epilepsy Monitoring Units (EMU) bed availability, admissions, neurological procedures, and epileptologists. However, this has not been evident in many underserved areas. The vast majority of National Association of Epilepsy Centers (NAEC) accredited centers are located in major metropolitan areas, and some states lack epilepsy centers entirely. Kern Medical (KM) is the public safety-net hospital in Bakersfield, California (CA) that serves Kern and surrounding counties in the Central Valley. In 2018, an epilepsy center at KM was established with the support of the USC Epilepsy Care Consortium and received NAEC Level III accreditation to serve the over 34,000 patients who suffer from epilepsy in Kern County alone. Here, we review the initial 4-year experience of the KM Epilepsy Center by retrospectively analyzing a prospectively maintained database in light of the general NAEC data from 2012–2019. This experience demonstrates that epilepsy care can be coordinated across complex and competing health systems and socioeconomic barriers separated by large geographic distances through creative, physician-driven strategies of resource sharing and goal alignment across the health care ecosystem. However, considerable challenges remain in providing the requisite care to patients in need, even in highly resourced states like CA. This experience can inform future efforts to integrate epilepsy care across the region and beyond.
The causal role of male pubertal timing for the development of externalizing and internalizing traits: results from Mendelian randomization studies
Authors: Dinkelbach Lars , Peters Triinu , Grasemann Corinna , Hinney Anke , Hirtz Raphael 
Published: June 2024

AbstractPreexisting epidemiological studies suggest that early pubertal development in males is associated with externalizing (e.g., conduct problems, risky behavior, and aggression) and internalizing (e.g., depression and anxiety) traits and disorders. However, due to problems inherent to observational studies, especially of reverse causation and residual confounding, it remains unclear whether these associations are causal. Mendelian randomization (MR) studies take advantage of the random allocation of genes at conception and can establish causal relationships. In the current study, N=76 independent genetic variants for male puberty timing (MPT) were derived from a large genome-wide association study (GWAS) on 205,354 participants and used as an instrumental variable in MR studies on 17 externalizing and internalizing traits and psychopathologies utilizing outcome GWAS with 16,400 to 1,045,957 participants. In these MR studies, earlier MPT was significantly associated with higher scores for the overarching phenotype of ‘Externalizing Traits’ (beta=-0.03, 95%-CI [-0.06, -0.01]). However, this effect was likely driven by an earlier age at first sex (beta=-0.17, 95%-CI [-0.21, - 0.13]), without evidence for an effect on further externalizing phenotypes. Regarding internalizing phenotypes, earlier MPT was associated with higher levels of the ‘Depressed Affect’ subdomain of neuroticism (beta=-0.04, 95%-CI [-0.07, -0.01]). Late MPT was related to higher scores of internalizing traits in early life (beta=0.04, 95%-CI [0.01, 0.08]). In conclusion, this MR study supports a causal effect of MPT on specific traits and behaviors. However, no evidence for an effect of MPT on long-term clinical outcomes (depression, anxiety disorders, alcohol dependency, cannabis abuse) was found.
Trajectory Modeling and Response Prediction in Transcranial Magnetic Stimulation for Depression
Authors: McInnes Aaron N. , Olsen Sarah T. , Sullivan Christi R.P. , Cooper Dawson C. , Wilson Saydra , Sonmez Ayse Irem , Albott Sophia C. , Olson Stephen C. , Peterson Carol B. , Rittberg Barry R. , Herman Alexander , Bajzer Matej , Nahas Ziad , Widge Alik S. 
Published: June 2024

AbstractRepetitive transcranial magnetic stimulation (rTMS) therapy could be improved by better and earlier prediction of response. Latent class mixture (LCMM) and non-linear mixed effects (NLME) modelling have been applied to model the trajectories of antidepressant response (or non-response) to TMS, but it is not known whether such models can predict clinical outcomes. We compared LCMM and NLME approaches to model the antidepressant response to TMS in a naturalistic sample of 238 patients receiving rTMS for treatment resistant depression (TRD), across multiple coils and protocols. We then compared the predictive power of those models. LCMM trajectories were influenced largely by baseline symptom severity, but baseline symptoms provided little predictive power for later antidepressant response. Rather, the optimal LCMM model was a nonlinear two-class model that accounted for baseline symptoms. This model accurately predicted patient response at 4 weeks of treatment (AUC = 0.70, 95% CI = [0.52-0.87]), but not before. NLME offered slightly improved predictive performance at 4 weeks of treatment (AUC = 0.76, 95% CI = [0.58 – 0.94], but likewise, not before. In showing the predictive validity of these approaches to model response trajectories to rTMS, we provided preliminary evidence that trajectory modeling could be used to guide future treatment decisions.
Nanoliter-scale selection of optimized bioengineered peptide antibiotics that rescue mice with bacterial lung infection
Authors: Böhringer Nils , Wuisan Zerlina G. , Marner Michael , Kresna I Dewa Made , Mettal Ute , Schmitt Steven , Reiter Silke , Liu Yang , Brinkrolf Karina , Rupp Oliver , Schwengers Oliver , Findeisen Julia , Herold Susanne , Matt Ulrich , Schäberle Till F. 
Published: June 2024

AbstractIncreasing numbers of multi-drug resistant pathogens call for new chemical scaffolds, addressing novel targets, that can serve as lead structures for the development of life-saving drugs. For antibiotics, natural product-inspired molecules represent a most promising resource. Natural products evolved to high chemical complexity and occupy a chemical space different than synthetic libraries. However, clinical translation of promising natural products is often impeded by their relative inaccessibility to medicinal chemistry optimization,e.g.iterative synthesis of large series of derivatives. Here, this limitation is addressed with a randomized library of bicyclic heptapeptides based on the natural product darobactin that hits the clinically not addressed target BamA. Variants of the ribosomally synthesized and post-translationally modified peptides were generated using heterologous mutasynthesis. A parallelized screening assay is adapted in nanoliter-scale beads to test the darobactin derivatives against our sensor strain. Loss of fluorescence sorting prioritized 563 events out of the analyzed ∼500k beads. Re-testing confirmed 48 hit events, of which 40 proved to produce distinct darobactin-type molecules. Most promising structures were isolated and the growth inhibitory effects against Gram-negative pathogens validated. One of our current frontrunner compounds (i.e., darobactin B) was reinforced by the randomized screen. While microbiological investigations of the new derivatives is ongoing, darobactin B was profiled in later tier assays and compared to another promising, rationally-designed analog (i.e., darobactin B9, “D22”). Early ADMET profiling and efficacy tests in a mouse pneumonia model were performed. Darobactin B reduced bacterial load ofPseudomonas aeruginosaandKlebsiella pneumoniaeby intraperitoneal, as well as intratracheal administration. Our study showcases the potential of mutasynthetic libraries for high-throughput screening and identification of functional peptides for drug lead discovery.
Transfer of IgG from Long COVID patients induces symptomology in mice
Authors: Chen Hung-Jen , Appelman Brent , Willemen Hanneke , Bos Amelie , Prado Judith , Geyer Chiara. E. , Santos Ribeiro Patrícia Silva , Versteeg Sabine , Larsen Mads , Schüchner Eline , Bomers Marije K. , Lavell Ayesha H.A. ,   Amsterdam UMC COVID-19 biobank, Charlton Braeden , Wüst Rob , Wiersinga W. Joost , van Vugt Michèle , Vidarsson Gestur , Eijkelkamp Niels , den Dunnen Jeroen 
Published: June 2024

AbstractSARS-CoV-2 infections worldwide led to a surge in cases of Long COVID, a post-infectious syndrome. It has been hypothesized that autoantibodies play a crucial role in the development of Long COVID and other syndromes, such as fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, we tested this hypothesis by passively transferring total IgG from Long COVID patients to mice. Using Glial Fibrillary Acidic Protein (GFAP) and type-I interferon expression, we stratified patients into three Long COVID subgroups, each with unique plasma proteome signatures. Remarkably, IgG transfer from the two subgroups, which are characterized by higher plasma levels of neuronal proteins and leukocyte activation markers, induced pronounced and persistent sensory hypersensitivity with distinct kinetics. Conversely, IgG transfer from the third subgroup, which are characterized by enriched skeletal and cardiac muscle proteome profiles, reduced locomotor activity in mice without affecting their motor coordination. These findings demonstrate that transfer of IgG from Long COVID patients to mice replicates disease symptoms, underscoring IgG’s causative role in Long COVID pathogenesis. This work proposes a murine model that mirrors Long COVID’s pathophysiological mechanisms, which may be used as a tool for screening and developing targeted therapeutics.
Transcriptome-wide mapping of small-molecule RNA-binding sites in live cells
Authors: Tong Yuquan , Zanon Patrick R. A. , Yang Xueyi , Su Xiaoxuan , Childs-Disney Jessica L. , Disney Matthew D. 
Published: June 2024

AbstractSmall molecules targeting RNA can be valuable chemical probes and potential therapeutics. The interactions between small molecules, particularly fragments, and RNA, however, can be difficult to detect due to their modest affinities and short residence times. Here, we describe the procedures for mapping the molecular fingerprints of small molecules in vitro and throughout the human transcriptome in live cells, identifying both the targets bound by the small molecule and the sites of binding therein. For complete details on the use and execution of this protocol, please refer to1.
Advancing the genetic engineering toolbox by combiningAsCas12aknock-in mice with ultra-compact screening
Authors: Jin Wei , Deng Yexuan , La Marca John E. , Lelliott Emily J. , Diepstraten Sarah T. , Snetkova Valentina , Dorighi Kristel M. , Hoberecht Luke , Whelan Lauren , Liao Yang , Tai Lin , Healey Geraldine , Shi Wei , Kueh Andrew J. , Haley Benjamin , Fortin Jean-Philippe , Herold Marco J. 
Published: June 2024

AbstractCas12a is a gene-editing tool that simplifies multiplexed gene targeting through its RNase activity, enabling maturation of individual crRNAs from a pre-crRNA-encoding RNA. Here, we present a mouse model that constitutively expresses enhancedAcidaminococcus sp. Cas12a(enAsCas12a) linked to an mCherry fluorescent reporter. We demonstrate efficient single and multiplexed gene-editing in cells fromenAsCas12aKImice. To testin vivoactivity, we transduced haematopoietic stem cells fromEμ-MycT/+;enAsCas12aKI/+animals withTrp53-targeting pre-crRNAs followed by transplantation into irradiated recipient animals. Tumour development was accelerated and TRP53 protein lost. We generated compact, genome-wide Cas12a knockout libraries targeting each gene with four guide RNAs encoded on two (Menuetto) or one (Scherzo) vector. Introducing these libraries intoEμ-MycT/+;enAsCas12aKI/+lymphoma cells followed by treatment with an MCL-1 inhibitor (S63845) or TRP53-inducer (nutlin-3a) identified known and novel drug resistance genes. Finally, we demonstrate simultaneous gene knockouts (Trp53 or combined Bax/Bak) and activation (Cd19) in primary T cells and mouse dermal fibroblasts from crosses of ourenAsCas12aand CRISPR activation models (dCas9a-SAM). OurenAsCas12amouse model and accompanying libraries enhance genome engineering capabilities and complements current CRISPR technologies.
Improved gene targeting in vivo using EoHR, a small molecule inhibitor of 53BP1
Authors: Spencer Sarah J. , O’donoghue Finn , Ristovski Angelina , Glaser Astrid , Maniam Subashani , Mohsenipour Mitra , Soch Alita , Deans Andrew J. , Headey Stephen 
Published: June 2024

AbstractPrecise genome editing by programmable nucleases such as Cas9 has revolutionised medical research by enabling the creation of gene-edited or knock-in mouse models of disease. However, a major limitation of the approach is the inefficient process of homology driven recombination (HDR) from an exogenous DNA repair template. This is because error-prone, 53BP1-dependent non-homologous end joining (NHEJ) predominates at Cas9-induced double strand breaks (DSBs). Here we report the validation of a cell-permeable and non-toxic inhibitor of 53BP1 called EoHR. In vitro, EoHR prevents 53BP1 binding to dimethylated lysine 20 on histone H4, a marker of DSBs. In cells, EoHR prevents localisation of 53BP1 at nuclease mediated DSBs and promotes HDR at a Cas9-induced break. When tested in vivo during mouse Cas9-mediated gene editing, inclusion of EoHR at the time of microinjection more than doubled the recovery of correctly edited mice and halved the time to project success. Our work shows that inhibition of 53BP by EoHR is a simple and robust way to increase HDR at Cas9 breaks that can also dramatically increase the success rates of animal model generation.
Diagnostic Accuracy of Vision-Language Models on Japanese Diagnostic Radiology, Nuclear Medicine, and Interventional Radiology Specialty Board Examinations
Authors: Oura Tatsushi , Tatekawa Hiroyuki , Horiuchi Daisuke , Matsushita Shu , Takita Hirotaka , Atsukawa Natsuko , Mitsuyama Yasuhito , Yoshida Atsushi , Murai Kazuki , Tanaka Rikako , Shimono Taro , Yamamoto Akira , Miki Yukio , Ueda Daiju 
Published: June 2024

AbstractPurposeThe performance of vision-language models (VLMs) with image interpretation capabilities, such as GPT-4 omni (GPT-4o), GPT-4 vision (GPT-4V), and Claude-3, has not been compared and remains unexplored in specialized radiological fields, including nuclear medicine and interventional radiology. This study aimed to evaluate and compare the diagnostic accuracy of various VLMs, including GPT-4 + GPT-4V, GPT-4o, Claude-3 Sonnet, and Claude-3 Opus, using Japanese diagnostic radiology, nuclear medicine, and interventional radiology (JDR, JNM, and JIR, respectively) board certification tests.MethodsIn total, 383 questions from the JDR test (358 images), 300 from the JNM test (92 images), and 322 from the JIR test (96 images) from 2019 to 2023 were consecutively collected. The accuracy rates of the GPT-4 + GPT-4V, GPT-4o, Claude-3 Sonnet, and Claude-3 Opus were calculated for all questions or questions with images. The accuracy rates of the VLMs were compared using McNemar’s test.ResultsGPT-4o demonstrated the highest accuracy rates across all evaluations with the JDR (all questions, 49%; questions with images, 48%), JNM (all questions, 64%; questions with images, 59%), and JIR tests (all questions, 43%; questions with images, 34%), followed by Claude-3 Opus with the JDR (all questions, 40%; questions with images, 38%), JNM (all questions, 51%; questions with images, 43%), and JIR tests (all questions, 40%; questions with images, 30%). For all questions, McNemar’s test showed that GPT-4o significantly outperformed the other VLMs (allP< 0.007), except for Claude-3 Opus in the JIR test. For questions with images, GPT-4o outperformed the other VLMs in the JDR and JNM tests (allP< 0.001), except Claude-3 Opus in the JNM test.ConclusionThe GPT-4o had the highest success rates for questions with images and all questions from the JDR, JNM, and JIR board certification tests.Secondary abstractThis study compared the diagnostic accuracy of vision-language models, including the GPT-4V, GPT-4o, and Claude-3, in Japanese radiological certification tests. GPT-4o demonstrated superior performance across diagnostic radiology, nuclear medicine, and interventional radiology tests, including image-based questions, highlighting its potential for medical image interpretation.
Prediction of oncogene mutation status in non-small cell lung cancer: A systematic review and meta-analysis with a special focus on artificial-intelligence-based methods
Authors: Fuster-Matanzo Almudena , Picó Peris Alfonso , Bellvís Bataller Fuensanta , Jimenez-Pastor Ana , Weiss Glen J. , Martí-Bonmatí Luis , Sánchez Antonio Lázaro , Banna Giuseppe L. , Addeo Alfredo , Alberich-Bayarri Ángel 
Published: June 2024

ABSTRACTBackgroundIn non-small cell lung cancer (NSCLC), alternative strategies to determine patient oncogene mutation status are essential to overcome some of the drawbacks associated with current methods. We aimed to review the use of radiomics alone or in combination with clinical data and to evaluate the performance of artificial intelligence (AI)-based models on the prediction of oncogene mutation status.MethodsA PRISMA-compliant literature review was conducted. The Medline (via Pubmed), Embase, and Cochrane Library databases were searched for studies published through June 30, 2023 predicting oncogene mutation status in patients with NSCLC using radiomics. Independent meta-analyses evaluating the performance of AI-based models developed with radiomics features or with a combination of radiomics features plus clinical data for the prediction of different oncogenic driver mutations were performed. A meta-regression to analyze the influence of methodological/clinical factors was also conducted.ResultsOut of the 615 studies identified, 89 evaluating models for the prediction of epidermal growth factor-1 (EGFR), anaplastic lymphoma kinase (ALK), and Kirsten rat sarcoma virus (KRAS) mutations were included in the systematic review. A total of 38 met the inclusion criteria for the meta-analyses. The AI algorithms’ sensitivity/false positive rate (FPR) in predicting EGFR, ALK, and KRAS mutations using radiomics-based models was 0.753 (95% CI 0.721–0.783)/0.346 (95% CI 0.305–0.390), 0.754 (95% CI 0.639–0.841)/ 0.225 (95% CI 0.163–0.302), and 0.744 (95% CI 0.605–0.846)/0.376 (95% CI 0.274–0.491), respectively. A meta-analysis of combined models was only possible for EGFR mutation, revealing a sensitivity/FPR of 0.800 (95% CI 0.767–0.830)/0.335 (95% CI 0.279–0.396). No statistically significant results were obtained in the meta-regression.ConclusionsRadiomics-based models may represent valuable non-invasive tools for the determination of oncogene mutation status in NSCLC. Further investigation is required to analyze whether clinical data might boost their performance.
Biochemical analyses can complement sequencing-based ARG load monitoring: a case study in Indian hospital sewage networks
Authors: Bhanushali S. , Pärnänen K. , Mongad D. , Dhotre D. , Lahti L. 
Published: June 2024

AbstractAntibiotic resistance is an emerging global crisis which has been estimated to cause increasing numbers of deaths. Low and middle-income countries (LMICs) are challenged with a larger burden of antibiotic resistance, as antibiotic resistance is more common in LMICs, and access to antibiotics and health care is often limited compared to high-income countries. Further exacerbating the issue is the possible lack of efficient treatment of hospital sewage which can have high concentrations of clinically relevant antibiotic-resistant pathogens. Monitoring of antibiotic resistance genes (ARGs) in sewage along the sewage networks (from hospitals to community sewers and sewage treatment plant effluents) would provide crucial tools for identifying hotspots of ARG pollution. However, the methods that are currently used to quantify ARGs rely on expensive shotgun sequencing or qPCR. Therefore, we investigated whether ARG load monitoring could be complemented with inexpensive standard biochemical analyses. Our results show that across four different sewage networks and three seasons, biological oxygen demand (BOD) and total organic carbon (TOC) can provide robust indicators of total ARG load. This lays grounds for finding cost-efficient techniques for sewage ARG pollution monitoring in low-resource settings.