Comparative transcriptome analysis of doramectin-producing Streptomyces avermitilis N72 and its mutant strains.

Doramectin, an essential animal anthelmintic, is synthesized through the fermentation process of Streptomyces avermitilis. This study delves into the transcriptomic profiles of two strains, namely the doramectin-producing wild-type S. avermitilis N72 and its highly doramectin-producing mutant counterpart, S. avermitilis XY-62. Comparative analysis revealed 860 up-regulated genes and 762 down-regulated genes in the mutant strain, notably impacting the expression of key genes pivotal in doramectin biosynthesis, including aveA1, aveA2, aveA3, aveA4, aveE, and aveBI. These findings shed light on the molecular mechanisms underpinning the heightened doramectin production in S. avermitilis XY-62, presenting promising avenues for optimizing doramectin production processes.

Cardiac sympathetic overdrive, M2 macrophage activation and fibroblast heterogeneity are associated with cardiac remodeling in a chronic pressure overload rat model of HFpEF.

Heart failure with preserved ejection fraction (HFpEF) is a multifaceted pathogenesis disease and the exact mechanisms driving HFpEF have not been completely elucidated. Pressure overload hypertrophy (POH) related fibroblasts and M2 macrophages in HFpEF myocardium have been recently identified and are now of great interest. Sympathetic overdrive has also been implicated in HFpEF. This study is designed to dynamically observe the potential roles of aforementioned mechanisms in pathological remodeling and cardiac dysfunction in chronic PO rats. Surgical constriction of the abdominal aorta was used for induction of HFpEF. Echocardiography, electrocardiogram, hemodynamic measurement, hematoxylin and eosin staining, Masson staining, immunohistochemistry and immunofluorescence were performed to assess the changes in heart dysfunction, cardiac remodeling and driving mechanisms at different time points (2, 18, 24 weeks). The PO induced HFpEF model was well established, which was confirmed by the persistent increase in carotid artery systolic and diastolic blood pressure, and left ventricle hypertrophy at the corresponding postoperative stage. Meanwhile, PO hypertrophy gradually developed into HFpEF, associated with QT and QTc intervals prolongation, normal systolic (EF was maintained at >50%) but impaired diastolic function (increasing LVEDP and LV -dP/dtmin, abnormal E/A ratio), increased myocytes size, and observed relatively slight inflammatory infiltration but robust reactive fibrosis. IHC staining further confirmed that macrophages (CD68) but not neutrophils (MPO) or T cells (CD3) accounted for a predominant proportion of infiltrating cells. Mechanistically, we found that the infiltrating macrophages in the heart expressed high levels of CD206 which was simultaneously adjacent to POH fibroblasts appeared to overexpression of α-SMA in PO rats at late stages. Interestingly, we distinguished two different POHF sub-populations during PO induced HFpEF development, according to non overlapping signals of α-SMA and PDGFRα/ß proteins. Additionally, PO led to a pronounced exaggeration in sympathetic fibers at all time points. These findings suggest that the establishing model here begins with cardiac sympathetic overdrive, subsequently along with immune cells especially M2 macrophage accumulation and fibroblast heterogeneity at later stages is associated with the development of cardiac maladaptive remodeling and diastolic dysfunction thus further progression to HFpEF.

A hybrid deep learning scheme for MRI-based preliminary multiclassification diagnosis of primary brain tumors.

Objectives: The diagnosis and treatment of brain tumors have greatly benefited from extensive research in traditional radiomics, leading to improved efficiency for clinicians. With the rapid development of cutting-edge technologies, especially deep learning, further improvements in accuracy and automation are expected. In this study, we explored a hybrid deep learning scheme that integrates several advanced techniques to achieve reliable diagnosis of primary brain tumors with enhanced classification performance and interpretability. Methods: This study retrospectively included 230 patients with primary brain tumors, including 97 meningiomas, 66 gliomas and 67 pituitary tumors, from the First Affiliated Hospital of Yangtze University. The effectiveness of the proposed scheme was validated by the included data and a commonly used data. Based on super-resolution reconstruction and dynamic learning rate annealing strategies, we compared the classification results of several deep learning models. The multi-classification performance was further improved by combining feature transfer and machine learning. Classification performance metrics included accuracy (ACC), area under the curve (AUC), sensitivity (SEN), and specificity (SPE). Results: In the deep learning tests conducted on two datasets, the DenseNet121 model achieved the highest classification performance, with five-test accuracies of 0.989 ± 0.006 and 0.967 ± 0.013, and AUCs of 0.999 ± 0.001 and 0.994 ± 0.005, respectively. In the hybrid deep learning tests, LightGBM, a promising classifier, achieved accuracies of 0.989 and 0.984, which were improved from the original deep learning scheme of 0.987 and 0.965. Sensitivities for both datasets were 0.985, specificities were 0.988 and 0.984, respectively, and relatively desirable receiver operating characteristic (ROC) curves were obtained. In addition, model visualization studies further verified the reliability and interpretability of the results. Conclusions: These results illustrated that deep learning models combining several advanced technologies can reliably improve the performance, automation, and interpretability of primary brain tumor diagnosis, which is crucial for further brain tumor diagnostic research and individualized treatment.

Cannabidiol is a behavioral modulator in BTBR mouse model of idiopathic autism.

Introduction: The prevalence of Autism Spectrum Disorder (ASD) has drastically risen over the last two decades and is currently estimated to affect 1 in 36 children in the U.S., according to the center for disease control (CDC). This heterogenous neurodevelopmental disorder is characterized by impaired social interactions, communication deficits, and repetitive behaviors plus restricted interest. Autistic individuals also commonly present with a myriad of comorbidities, such as attention deficit hyperactivity disorder, anxiety, and seizures. To date, a pharmacological intervention for the treatment of core autistic symptoms has not been identified. Cannabidiol (CBD), the major nonpsychoactive constituent of Cannabis sativa, is suggested to have multiple therapeutic applications, but its effect(s) on idiopathic autism is unknown. We hypothesized that CBD will effectively attenuate the autism-like behaviors and autism-associated comorbid behaviors in BTBR T+Itpr3tf/J (BTBR) mice, an established mouse model of idiopathic ASD. Methods: Male BTBR mice were injected intraperitoneally with either vehicle, 20 mg/kg CBD or 50 mg/kg CBD daily for two weeks beginning at postnatal day 21 ± 3. On the final treatment day, a battery of behavioral assays were used to evaluate the effects of CBD on the BTBR mice, as compared to age-matched, vehicle-treated C57BL/6 J mice. Results: High dose (50 mg/kg) CBD treatment attenuated the elevated repetitive self-grooming behavior and hyperlocomotion in BTBR mice. The social deficits exhibited by the control BTBR mice were rescued by the 20 mg/kg CBD treatment. Discussion: Our data indicate that different doses for CBD are needed for treating specific ASD-like behaviors. Together, our results suggest that CBD may be an effective drug to ameliorate repetitive/restricted behaviors, social deficits, and autism-associated hyperactivity.

Characteristics of urban network and city functions in the Yangtze River Delta Region: A multi-scale perspective.

The development of cities and regions emerges from the complex associations at various spatial levels, highlighting the importance of a multi-scale approach to analyzing regional urban networks. This study attempts to establish a new analysis framework encompassing national, regional, and local dimensions by employing a population flow network in the Yangtze River Delta in China. It explores the inter-city connections and spatial structures of regional urban networks as well as the correlations and differentiations of urban functions under multi-scale interaction. The results indicate that: (1) Regional network demonstrates notable multi-scale interactions with an explicit hierarchical structure; (2) The roles and positions of different cities vary significantly across scales due to economic, administrative, locational, and transportation differences; (3) Different city types can drive their evolution by navigating through rescaling in a diverse multi-scale environment; (4) A positive correlation is observed when comparing the functional behaviors of cities across various scales. This study provides insights for cities to identify their strategic roles and adapt development strategies within the wider network framework, offering theoretical and practical contributions to multi-scale urban networks analysis.

Manipulation of magnetic beads for actively capturing Vibrio parahaemolyticus and nucleic acid based on microfluidic system.

Rapid biological detection of pathogen micro-organisms has attracted much attention for practical biomedical applications. Despite the development in this field, it is still challenging to achieve simple and rapid biological detection using the microfluidic method. Herein, we propose a novel strategy of biological detection that combines precise detection control of the capillary microfluidic chip and versatile manipulation of magnetic beads. The microfluidic chip was fabricated via laser cutting, which utilized capillary pressure to realize rapid passive injection of liquid samples. Under an external magnetic field, the aptamer-modified magnetic beads were actuated to mix with Vibrio parahaemolyticus (V. parahaemolyticus) and its nucleic acid in the capillary microfluidic chip for rapid selective capture and detection, which could be achieved within 40 min. The experimental results demonstrated that V. parahaemolyticus could be captured using on-chip immunomagnetic beads with a high efficiency and significantly enhanced detection value. Due to these superior performances, the capillary microfluidic system, based on the manipulation of magnetic beads, demonstrated great potential for automatic biological detection.

A synthetic position decoding technology for rotary transformers based rotor position measurement system.

This article proposes a rotary transformer position decoding scheme for motor drive control. In this scheme, a simple analog circuit is used to design the excitation circuit and signal conditioning circuit. Demodulate the modulated sine/cosine signal through software and decode it through a phase locked loop (PLL) to obtain the implemented position signal. This scheme completely avoids the use of traditional, specialized decoding chips. At the same time, in order to make the position decoding scheme applicable to different motor drive control platforms, a single-cycle partition average based pulse signal estimation method is proposed for converting the angle position into pulse signals similar to the output of an encoder's phases A, B, and Z, which are referred to as A/B/Z signals in the paper. In order to experimentally validate the proposed scheme, a software decoding platform based on the STM32F407 was built and compared with the decoding results of the chip. The effectiveness and accuracy of the proposed scheme were verified, and it can be effectively applied in the field of motor drive control.

Nrf-2 as a novel target in radiation induced lung injury.

Radiation-induced lung injury (RILI) is a common and fatal complication of chest radiotherapy. The underlying mechanisms include radiation-induced oxidative stress caused by damage to the deoxyribonucleic acid (DNA) and production of reactive oxygen species (ROS), resulting in apoptosis of lung and endothelial cells and recruitment of inflammatory cells and myofibroblasts expressing NADPH oxidase to the site of injury, which in turn contribute to oxidative stress and cytokine production. Nuclear factor erythroid 2-related factor 2 (Nrf-2) is a vital transcription factor that regulates oxidative stress and inhibits inflammation. Studies have shown that Nrf-2 protects against radiation-induced lung inflammation and fibrosis. This review discusses the protective role of Nrf-2 in RILI and its possible mechanisms.

Shanghai Community-Based Schizophrenia Cohort (SCS): a protocol for establishing a longitudinal cohort and research database of patients with schizophrenia receiving community-based mental health treatment.

INTRODUCTION: Drivers for remission, relapse and violence-related behaviour among patients with schizophrenia are the most complicated issue. METHODS AND ANALYSIS: This study aims to recruit a longitudinal cohort of patients with schizophrenia. Two suburban districts and two urban districts were randomly selected according to health service facilities, population, geographical region and socioeconomic status. Individuals (>18 years old) who received a diagnosis of schizophrenia following the International Classification of Diseases (10th edition) criteria within the past 3 years will be invited as participants. Assessments will be carried out in local community health centres. Data will be used to (1) establish a community-based schizophrenia cohort and biobank, (2) prospectively determine the course of multidimensional functional outcomes of patients with schizophrenia who are receiving community-based mental health treatment, and (3) map the trajectories of patients with schizophrenia and prospectively determine the course of multidimensional outcomes based on the differential impact of potentially modifiable moderators. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Human Research Ethics Committee of Shanghai Mental Health Center (2021-67). Results of the study will be disseminated through peer-reviewed journals. If effective, related educational materials will be released to the public.

Biohybrid Flexible Sperm-like Microrobot for Targeted Chemo-Photothermal Therapy.

Magnetic micro/nanorobots are promising platforms for targeted drug delivery, and their construction with soft and flexible features has received extensive attention for practical applications. Despite significant efforts in this field, facile fabrication of magnetic microrobots with flexible structures and versatility in targeted therapy remains a big challenge. Herein, we proposed a novel universal strategy to fabricate a biohybrid flexible sperm-like microrobot (BFSM) based on a Chlorella (Ch.) cell and artificial flagella, which showed great potential for targeted chemo-photothermal therapy for the first time. In this approach, microspherical Ch. cells were utilized to construct the microrobotic heads, which were intracellularly deposited with core-shell Pd@Au, extracellularly magnetized with Fe3O4, and further loaded with anticancer drug. The magnetic heads with excellent photothermal and chemotherapeutic capability were further assembled with flexible polypyrrole nanowires via biotin-streptavidin bonding to construct the BFSMs. Based on the exquisite head-to-tail structures, the BFSMs could be effectively propelled under precessing magnetic fields and move back and forth without a U-turn. Moreover, in vitro chemo-photothermal tests were conducted to verify their performance of targeted drug delivery toward localized HeLa cells. Due to this superior versatility and facile fabrication, the BFSMs demonstrated great potential for targeted anticancer therapy.

Synergistic improvement of humus formation in compost residue by fenton-like and effective microorganism composite agents.

Improving the humification of compost through a synergistic approach of biotic and abiotic methods is of great significance. This study employed a composite reagent, comprising Fenton-like agents and effective microorganisms (EM) to improve humification. This composite reagent increased humic-acid production by 37.44 %, reaching 39.82 g kg-1, surpassing the control group. The composite reagent synergistically promoted micromolecular fulvic acid and large humic acid production. Collaborative mechanism suggests that Fenton-like agents contributed to bulk residue decomposition and stimulated the evolution of microbial communities, whereas EMs promoted highly aromatic substance synthesis and adjusted the microbial community structure. Sequencing analysis indicates the Fenton-like agent initiated compost decomposition by Firmicutes, and EM reduced the abundance of Virgibacillus, Lentibacillus, and Alcanivorax. Applied as an organic fertilizer in Brassica chinensis L. plantations, the composite reagent considerably improved growth and photosynthetic pigment content. This composite reagent with biotic and abiotic components provides a learnable method for promoting humification.

Enhancing psychiatric rehabilitation outcomes through a multimodal multitask learning model based on BERT and TabNet: An approach for personalized treatment and improved decision-making.

Evaluating the rehabilitation status of individuals with serious mental illnesses (SMI) necessitates a comprehensive analysis of multimodal data, including unstructured text records and structured diagnostic data. However, progress in the effective assessment of rehabilitation status remains limited. Our study develops a deep learning model integrating Bidirectional Encoder Representations from Transformers (BERT) and TabNet through a late fusion strategy to enhance rehabilitation prediction, including referral risk, dangerous behaviors, self-awareness, and medication adherence, in patients with SMI. BERT processes unstructured textual data, such as doctor's notes, whereas TabNet manages structured diagnostic information. The model's interpretability function serves to assist healthcare professionals in understanding the model's predictive decisions, improving patient care. Our model exhibited excellent predictive performance for all four tasks, with an accuracy exceeding 0.78 and an area under the curve of 0.70. In addition, a series of tests proved the model's robustness, fairness, and interpretability. This study combines multimodal and multitask learning strategies into a model and applies it to rehabilitation assessment tasks, offering a promising new tool that can be seamlessly integrated with the clinical workflow to support the provision of optimized patient care.

Insight into the status of plasma renin and aldosterone measurement: findings from 526 clinical laboratories in China.

OBJECTIVES: Accurate measurements of renin and aldosterone levels play an important role in primary aldosteronism screening, which is of great importance in the management and categorization of hypertension. The objective of this study is to investigate the current status of plasma renin and aldosterone measurements in China, which is achieved by analyzing the results of 526 clinical laboratories nationwide for three pooled fresh plasma samples derived from more than 2,000 patients. METHODS: Renin and aldosterone in three pooled plasma samples were measured four times in 526 laboratories employing various measurement systems. The inter- and intra-laboratory %CV were calculated and compared. To determine the source of the substantial inter-laboratory %CV, laboratories were categorized according to the measurement systems they are using, and both the inter- and intra-measurement-system %CV were calculated and compared. RESULTS: Regarding renin, the majority of laboratories use four primary commercial immunoassays. However, for aldosterone, in addition to commercial immunoassays, laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS) methods are also used by laboratories. The median values of intra-laboratory %CVs, intra-measurement-system %CVs, inter-laboratory %CVs, and inter-measurement systems %CVs varied between 1.6 and 2.6 %, 4.6 and 14.9 %, 8.3 and 25.7 %, and 10.0 and 34.4 % for renin, respectively. For aldosterone, these values ranged from 1.4 to 2.2 %, 2.5-14.7 %, 9.9-31.0 %, and 10.0-35.5 %, respectively. CONCLUSIONS: The precision within laboratories and measurement systems for plasma renin and aldosterone measurements is satisfactory. However, the comparability between laboratories using different measurement systems remains lacking, indicating the long way to achieve standardization and harmonization for these two analytes.

Association of intensive blood pressure management with cardiovascular outcomes in patients using multiple classes of antihypertensive medications: a post-hoc analysis of the STEP Trial.

High medication burden is associated with poor treatment effect and high risk of cardiovascular outcomes. This study aimed to investigate the association between the antihypertensive medication burden and cardiovascular outcomes in the STEP trial. This post-hoc analysis of the STEP trial enrolled 8511 participants, including 8041 with low burden and 470 with high burden. High antihypertensive medication burden was defined as being treated with ≥3 different classes of prescribed antihypertensive medications. The primary outcome was a composite of cardiovascular outcomes. Fine-Gray model was used in this study. Among all participants, high antihypertensive medication burden was associated with a higher risk of the primary outcome compared with low medication burden (HR, 1.52; 95% CI, 1.03-2.24), which was consistent in the standard group (HR, 1.95; 95% CI, 1.20-3.18) and the intensive group (HR, 1.10; 95% CI, 0.57-2.13; Pinteraction = 0.18). The beneficial effects of intensive systolic blood pressure (SBP) control on the primary outcome remained significant in the high burden group (HR, 0.42; 95% CI, 0.19-0.95) and the low burden group (HR, 0.79; 95% CI, 0.63-0.98; Pinteraction = 0.18). At 24 months, the percentage of participants achieving the target SBP was lower in the high medication burden group (risk ratio, 0.93; 95% CI, 0.89-0.98). In both standard and intensive treatment groups, participants with a high medication burden were harder to achieve the target SBP (Pinteraction = 0.65). High antihypertensive medication burden was associated with worse SBP control and a greater risk of cardiovascular events. Intensive SBP control showed cardiovascular benefits in both medication burden groups. Trial registration: STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

The Association between Serum Level of Vitamin D and Inflammatory Biomarkers in Hospitalized Adult Patients: A Cross-Sectional Study Based on Real-World Data.

Objective: The association between vitamin D status and inflammation remains unclear in hospitalized patients. Materials and Methods: We performed the current study based on real-world data from two teaching hospitals. Serum level of vitamin D (assessed by 25-hydroxyvitamin D) was evaluated within 2 days after admission. All the patients were further classified into three groups: deficiency (<12 ng/mL), insufficiency (12-20 ng/mL), and adequate (≥20 ng/mL). White blood cell (WBC) count, serum level of C-reactive protein (CRP), and procalcitonin were also measured and used to evaluate inflammation. Other potential covariates were abstracted from medical records. Charlson comorbidity index (CCI) was calculated to assess the severity of disease. Results: A total number of 35,528 hospitalized adult patients (21,171 men and 14,357 women) were included. The average age and BMI were 57.5 ± 16.2 years and 23.4 ± 3.7 kg/m2, respectively, while medium vitamin D level was 16.1 ng/mL (interquartile range: 11.4 ng/mL, 21.6 ng/mL) and median CCI was one point (interquartile range: 0 point, two points). The prevalence of deficiency and insufficiency was 28.0% and 40.5%. Multivariate linear regression model showed that serum level of vitamin D was significantly associated with WBC and CRP but not associated with procalcitonin. Each standard deviation (≈7.4 ng/mL) increase in vitamin D was associated with a decrease in WBC by 0.13 × 109/mL (95% CI: 0.2 × 109/mL, 0.06 × 109/mL) and 0.62 mg/L (95% CI: 0.88 mg/L, 0.37 mg/L) for CRP. Subgroup analysis and sensitivity analysis (excluding those whose eGFR <60 ml/min/1.73 m2, those whose daily calorie intake <1,000 kcal, and those who were recruited from Xin Hua hospital) generated similar results. Conclusions: The deficiency and insufficiency of vitamin D in the hospitalized adult patients was very common. However, the results should be interpreted with caution for limited representation of the whole inpatients. Low level of vitamin D was associated with inflammatory biomarkers, which provide the evidences to early intervention for lower the risk of infection.

Modeling and optimization of sporulation by Bacillus licheniformis BF-002 based on dynamics and recurrent neural networks.

Bacillus licheniformis is widely utilized in disease prevention and environmental remediation. Spore quantity is a critical factor in determining the quality of microbiological agents containing vegetative cells. To improve the understanding of Bacillus licheniformis BF-002 strain culture, a hybrid model integrating traditional dynamic modeling and recurrent neural network was developed. This model enabled the optimization of carbon/nitrogen source feeding rates, pH, temperature and agitation speed using genetic algorithms. Carbon and nitrogen source consumption in the optimal duplicate batches showed no significant difference compared to the control batch. However, the spore quantity in the broth increased by 16.2% and 35.2% in the respective duplicate batches. Overall, the hybrid model outperformed the traditional dynamic model in accurately tracking the cultivation dynamics of Bacillus licheniformis, leading to increased spore production when used for optimizing cultivation conditions.

First-line sintilimab with pegaspargase, gemcitabine, and oxaliplatin in advanced extranodal natural killer/T cell lymphoma (SPIRIT): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Programmed cell death protein 1 (PD-1) inhibitor sintilimab is effective in relapsed and refractory extranodal natural killer/T cell lymphoma (ENKTL), nasal type. We aimed to assess the safety and activity of sintilimab plus P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) in the first-line setting for advanced ENKTL. METHODS: The multicentre, single-arm, phase 2 trial was done at three medical centres in China. Patients aged 18-75 years with treatment-naive pathologically confirmed advanced ENKTL and an with Eastern Cooperative Oncology Group performance status score of 0-2 were eligible. Patients received intravenous sintilimab (200 mg on day 1), intramuscular pegaspargase (2000 U/m2 on day 1), intravenous gemcitabine (1 g/m2 on days 1 and 8), and intravenous oxaliplatin (130 mg/m2 on day 1) every 3 weeks for six cycles, followed by intravenous sintilimab (200 mg) every 3 weeks for up to 2 years or until disease progression or unacceptable toxicities. The primary endpoint was the complete response rate in the intention-to-treat population. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival. This trial is registered with ClinicalTrials.gov, NCT04127227. Enrolment has been completed, and follow-up is ongoing. FINDINGS: Between Nov 29, 2019, and Sept 7, 2022, 34 eligible patients were enrolled (median age 39 years [IQR 32-55]; 25 [74%] of 34 patients were male; nine [26%] were female; and all were of Asian ethnicity). At the data cutoff (July 20, 2023), the median follow-up was 21 months (IQR 13-32). The complete response rate was 85% (29 of 34 patients, 95% CI 70-94). Five patients (15%; 95% CI 7-30) attained partial response and the ORR was 100% (34 of 34 patients). 24-month PFS was 64% (95% CI 48-86), 24-month DFS was 72% (54-95), and 36-month overall survival was 76% (52-100). The most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anaemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in one (3%) patient that caused treatment termination. No severe adverse events occurred. There were three deaths: one due to haemophagocytic syndrome, one due to disease progression, and one due to unknown cause, which were not considered to be treatment related. INTERPRETATION: Combination of sintilimab with P-GEMOX seems to be an active and safe first-line regimen for patients with advanced ENKTL. FUNDING: National Key Research and Development Program and National Natural Science Foundation of China, Guangzhou Science and Technology Program and the Clinical Oncology Foundation of Chinese Society of Clinical Oncology.

Incidence and prognosis of cardiac conduction system diseases in hypertension: the STEP trial.

Patients with cardiac conduction system diseases (CSD) may have increased incidence and mortality of cardiovascular events. Here we report a post hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) randomized clinical trial (ClinicalTrials.gov number, NCT03015311) concerning the effect of intensive blood pressure (BP) control on the incidence of new-onset CSD and the prognostic implications of preexisting or new-onset CSD. The incidence of new-onset CSD was similar in the intensive (n = 205, 6.42%) and standard (n = 188, 5.94%) treatment arms. Participants with preexisting CSD had a higher risk for acute decompensated heart failure. Increased age, male sex and increased body mass index were independently associated with increased risk for new-onset CSD. Our results suggest that intensive BP control may not reduce the incidence of new-onset CSD compared with standard BP control.