Climate change exacerbates the environmental impacts of agriculture.

Agriculture's global environmental impacts are widely expected to continue expanding, driven by population and economic growth and dietary changes. This Review highlights climate change as an additional amplifier of agriculture's environmental impacts, by reducing agricultural productivity, reducing the efficacy of agrochemicals, increasing soil erosion, accelerating the growth and expanding the range of crop diseases and pests, and increasing land clearing. We identify multiple pathways through which climate change intensifies agricultural greenhouse gas emissions, creating a potentially powerful climate change-reinforcing feedback loop. The challenges raised by climate change underscore the urgent need to transition to sustainable, climate-resilient agricultural systems. This requires investments that both accelerate adoption of proven solutions that provide multiple benefits, and that discover and scale new beneficial processes and food products.

Anthocyanins in Vascular Health and Disease: Mechanisms of Action and Therapeutic Potential.

ABSTRACT: Unhealthy lifestyles have placed a significant burden on individuals' cardiovascular health. Anthocyanins are water-soluble flavonoid pigments found in a wide array of common foods and fruits. Anthocyanins have the potential to contribute to the prevention and treatment of cardiovascular disease by improving lipid profiles and vascular function, reducing blood glucose levels and blood pressure, and inhibiting inflammation. These actions have been demonstrated in numerous clinical and preclinical studies. At the cellular and molecular level, anthocyanins and their metabolites could protect endothelial cells from senescence, apoptosis, and inflammation by activating the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthases, silent information regulator 1 (SIRT1), or nuclear factor erythroid2-related factor 2 pathways and inhibiting the nuclear factor kappa B, Bax, or P38 mitogen-activated protein kinase pathways. Furthermore, anthocyanins prevent vascular smooth muscle cell from platelet-derived growth factor -induced or tumor necrosis factor-α-induced proliferation and migration by inhibiting the focal adhesion kinase and extracellular regulated protein kinases signaling pathways. Anthocyanins could also attenuate vascular inflammation by reducing the formation of oxidized lipids, preventing leukocyte adhesion and infiltration of the vessel wall, and macrophage phagocytosis of deposited lipids through reducing the expression of cluster of differentiation 36 and increasing the expression of ATP-binding cassette subfamily A member 1 and ATP-binding cassette subfamily G member 1. At the same time, anthocyanins could lower the risk of thrombosis by inhibiting platelet activation and aggregation through down-regulating P-selectin, transforming growth factor-1, and CD40L. Thus, the development of anthocyanin-based supplements or derivative drugs could provide new therapeutic approaches to the prevention and treatment of vascular diseases.

Cadaveric Study on the Safety of High-Flow Nasal Oxygen in Laser Microlaryngeal Surgery.

INTRODUCTION: High-flow nasal oxygen (HFNO), or transnasal humidified rapid-insufflation ventilatory exchange (THRIVE), is a technique providing apneic oxygenation and a degree of ventilation during microlaryngeal surgery. Its use with laser has been questioned due to concern for airway fire. For fire to occur, a triad of ignition source, oxidizer, and fuel source must be present. By using HFNO and eliminating an endotracheal tube (fuel source), it is hypothesized that airway fire risk is minimal. We tested this theory with human cadavers using HFNO with increasing levels of FiO2 while performing microlaryngeal laser surgery. METHODS: HFNO was placed on two cadavers, and oxygen was administered at incrementally increasing fraction of inspired oxygen (FiO2) concentrations (30%-100%). Laryngeal microsurgery was conducted with CO2 and KTP lasers applied for 30 s. Oxygen readings were taken at several anatomic locations along the body assessing oxygen concentrations in correlation with increasing FiO2 administration. RESULTS: The use of CO2 and KTP laser on cadaveric vocal folds produced char but no spark or airway fire at any of the tested oxygen concentrations. Apart from the mouth, there was minimal increase in oxygen levels at the surrounding anatomic sites despite elevating FiO2 levels. CONCLUSION: HFNO may be safe to use during microlaryngeal laser surgery. By eliminating the endotracheal tube as a fuel source, risk of airway fire may be negligible. Our study safely applied CO2 and KTP lasers for an uninterrupted 30 s with HFNO at 70 L/min and 100% FiO2 producing no spark or fire. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Prostate Cancer-related Events in Patients with Synchronous Metastatic Hormone-sensitive Prostate Cancer Treated with Androgen Deprivation Therapy with and Without Concurrent Radiation Therapy to the Prostate; Data from the HORRAD Trial.

BACKGROUND AND OBJECTIVE: A survival benefit was demonstrated for patients with low-volume synchronous metastatic hormone-sensitive prostate cancer (mHSPCa) when local radiotherapy to the prostate was added to androgen deprivation therapy. This study aims to determine the incidence of prostate cancer-related events and treatments in those who received and those who did not receive external beam radiotherapy for mHSPCa. METHODS: The HORRAD trial is a multicentre randomised controlled trial recruiting originally 432 patients with mHSPCa diagnosed between 2004 and 2014. In a second updated analysis, 328 patients were studied retrospectively for local and nonlocal prostate cancer-related events and treatments. Outcome measurements included the incidence and treatment of local (bladder outlet or ureter obstruction, catheterisation, surgical intervention, ureteric stents, and nephrostomy tubes) and nonlocal (blood transfusions, hospitalisations, and treatment for painful bone metastases) events. Differences between groups were compared using crude and adjusted logistic regression, while time to occurrence of local events was assessed with Kaplan-Meier curves and Cox regression analysis. KEY FINDINGS AND LIMITATIONS: A significant difference in the incidence of local events was observed: 30 events in the radiotherapy group versus 50 in the nonradiotherapy group (p = 0.04). Time to occurrence of local interventions was significantly longer in the radiotherapy group (hazard ratio 0.61, 95% confidence interval 0.37-0.99, p = 0.04). The study's limitations include its retrospective nature. CONCLUSIONS AND CLINICAL IMPLICATIONS: Local radiotherapy to the prostate prolongs local event-free survival significantly and reduces local prostate cancer-related interventions in patients with mHSPCa.

Reconciling opposing effects of emotion on relational memory: Behavioral, eye-tracking, and brain imaging investigations.

The effects of emotion on memory are wide-ranging and powerful, but they are not uniform. Although there is agreement that emotion enhances memory for individual items, how it influences memory for the associated contextual details (relational memory, RM) remains debated. The prevalent view suggests that emotion impairs RM, but there is also evidence that emotion enhances RM. To reconcile these diverging results, we carried out three studies incorporating the following features: (1) testing RM with increased specificity, distinguishing between subjective (recollection based) and objective (item-context match) RM accuracy, (2) accounting for emotion-attention interactions via eye-tracking and task manipulation, and (3) using stimuli with integrated item-context content. Challenging the prevalent view, we identified both enhancing and impairing effects. First, emotion enhanced subjective RM, separately and when confirmed by accurate objective RM. Second, emotion impaired objective RM through attention capturing, but it enhanced RM accuracy when attentional effects were statistically accounted for using eye-tracking data. Third, emotion also enhanced RM when participants were cued to focus on contextual details during encoding, likely by increasing item-context binding. Finally, functional magnetic resonance imaging data recorded from a subset of participants showed that emotional enhancement of RM was associated with increased activity in the medial temporal lobe (MTL) and ventrolateral prefrontal cortex, along with increased intra-MTL and ventrolateral prefrontal cortex-MTL functional connectivity. Overall, these findings reconcile evidence regarding opposing effects of emotion on RM and point to possible training interventions to increase RM specificity in healthy functioning, posttraumatic stress disorder, and aging, by promoting item-context binding and diminishing memory decontextualization. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Music alters heart rate and psychological responses but not muscle activation during light-intensity isometric exercise.

Listening to music manipulates attention to be more externally focused, which has the potential to improve muscular efficiency. This study aimed to determine the effect of listening to music on muscle activation during an isometric exercise task, and compare this effect to those of other attentional focus conditions. Apparently healthy subjects (n = â€‹35; 16 men/19 women) completed an isometric elbow flexion task for 1 â€‹min in three randomized and counterbalanced conditions: internal focus (INT), external focus with a simple distraction task (EXT), or listening to music (MUS). Muscle activation of the biceps and triceps brachii and heart rate (HR) were recorded throughout the exercise tasks. Ratings of perceived exertion (RPE), affective valence, and motivation were measured at the end of each trial. There was no difference in muscle activation measures among the three conditions. HR during MUS was lower than EXT at 15 â€‹s ([89.4 â€‹± â€‹11.8] beats/min vs. [93.1 â€‹± â€‹12.9] beats/min; p â€‹= â€‹0.018) and 30 â€‹s ([90.6 â€‹± â€‹12.4] beats/min vs. [94.2 â€‹± â€‹12.5] beats/min; p â€‹= â€‹0.026), and lower than INT at 60 â€‹s ([93.3 â€‹± â€‹13.3] beats/min vs. [96.7 â€‹± â€‹12.0] beats/min; p â€‹= â€‹0.016). Overall RPE was higher for INT (13.4 â€‹± â€‹2.2) than for MUS ([12.6 â€‹± â€‹2.0]; p â€‹= â€‹0.020) and EXT ([11.94 â€‹± â€‹2.22]; p â€‹< â€‹0.001). Affective valence was higher for MUS than for INT ([2.7 â€‹± â€‹1.4] vs. [2.1 â€‹± â€‹1.5]; p â€‹= â€‹0.011). Manipulating attentional focus did not alter muscle activation for a light-intensity isometric muscular endurance task, though MUS was reported as more positive and requiring less exertion to complete than INT. Using music can therefore be recommended during light-intensity isometric exercise based on the psychological benefits observed.

Pericardiocentesis: History, Current Practice, and Future Directions.

PURPOSE OF REVIEW: To discuss the evolution in the approach to pericardial effusions and drainage from a historical perspective, the present state, and pathways for future innovative therapies. RECENT FINDINGS: Incorporation of advanced imaging tools has dramatically improved the safety profile of pericardial interventions. Outcome data allow for refined approaches to management of pericardial disease in special populations, such as pulmonary arterial hypertension. Consideration of intrapericardial interventions and pharmacotherapy represent novel and promising approaches to management of pericardial effusions moving forward. Although the impact of excess or rapidly accumulating pericardial fluid on hemodynamics has been recognized for centuries, the therapeutic approaches have only recently become more refined with the routine incorporation of such tools as echocardiography and fluoroscopy. The most utilized approaches for pericardiocentesis include the apical, subxiphoid, and parasternal, and the most favorable approach is that in which the pericardial fluid is closest to the body surface, where intervening vital structures are least likely to be damaged. With the notable exception of patients with pre-existing pulmonary hypertension, complete decompression of pericardial fluid with careful drain management reduces likelihood of pericardial effusion recurrence. In addition, percutaneous balloon pericardiotomies have been demonstrated to reduce recurrence in nonmalignant effusions.

Routine Testing for Chlamydia trachomatis and Neisseria gonorrhoeae Infections within an HIV Pre-Exposure Prophylaxis Program in Hanoi, Vietnam: Implications for Low- and Middle-Income Countries.

Background: Data on Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections within HIV pre-exposure prophylaxis (PrEP) programs in low- and middle-income countries (LMICs) are limited. Our study reports the prevalence, anatomical distribution, and correlates of NG and CT infections within an HIV PrEP program in Hanoi, Vietnam. Methods: From January-December 2022, HIV PrEP program clients who were male at birth, ≥16 years old, reported ≥1 male sex partner in the prior 12 months, were enrolled. A questionnaire collected sociodemographics, sexual behaviors, and clinical data. CT/NG testing was performed on self-collected urine, rectal, and pharyngeal specimens. Multivariate logistic regression was used to identify factors associated with CT and NG infections. Results: There were 529 participants enrolled, the median age was 25.1 years. The overall prevalence of CT or NG was 28.9% (153/529). The prevalence of NG was 14.3% and highest for pharyngeal infections (11.7%), while for CT, the prevalence was 20.4% and highest for rectal infections (14.0%). Symptoms in the prior week were reported by 45.8% (70/153) of those with CT or NG infections. Condomless anal sex (aOR= 1.98; 95% CI: 1.27, 3.08) and sexualized drug use in the prior 6 months (aOR= 1.68; 95% CI: 1.07, 2.65) were associated with CT/NG infections. Conclusions: Our study found a high prevalence of NG and CT infections, including pharyngeal and rectal infections, within an HIV PrEP program in Hanoi, Vietnam. The findings underscore the need for further research on CT/NG prevention and the development of evidence-based guidelines for CT/NG screening in HIV PrEP programs in LMIC settings.

Education and Communication in Veterinary Clinical Practice.

Effective communication is a hallmark of successful veterinary clinical practice [...].

Multiparameter phenotyping of platelets and characterization of the effects of agonists using machine learning.

Background: Platelet function is driven by the expression of specialized surface markers. The concept of distinct circulating subpopulations of platelets has emerged in recent years, but their exact nature remains debatable. Objectives: To design a spectral flow cytometry-based phenotyping workflow to provide a more comprehensive characterization, at a global and individual level, of surface markers in resting and activated healthy platelets, and to apply this workflow to investigate how responses differ according to platelet age. Methods: A 14-marker flow cytometry panel was developed and applied to vehicle- or agonist-stimulated platelet-rich plasma and whole blood samples obtained from healthy volunteers, or to platelets sorted according to SYTO-13 (Thermo Fisher Scientific) staining intensity as an indicator of platelet age. Data were analyzed using both user-led and independent approaches incorporating novel machine learning-based algorithms. Results: The assay detected differences in marker expression in healthy platelets, at rest and on agonist activation, in both platelet-rich plasma and whole blood samples, that are consistent with the literature. Machine learning identified stimulated populations of platelets with high accuracy (>80%). Similarly, machine learning differentiation between young and old platelet populations achieved 76% accuracy, primarily weighted by forward scatter, cluster of differentiation (CD) 41, side scatter, glycoprotein VI, CD61, and CD42b expression patterns. Conclusion: Our approach provides a powerful phenotypic assay coupled with robust bioinformatic and machine learning workflows for deep analysis of platelet subpopulations. Cleavable receptors, glycoprotein VI and CD42b, contribute to defining shared and unique subpopulations. This adoptable, low-volume approach will be valuable in deep characterization of platelets in disease.

Informing Decision-making for Transected Margin Reresection in Intraductal Papillary Mucinous Neoplasm-derived PDAC: An International Multicenter Study.

OBJECTIVE: To assess the prognostic impact of margin status in patients with resected intraductal papillary mucinous neoplasms (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) and to inform future intraoperative decision-making on handling differing degrees of dysplasia on frozen section. SUMMARY BACKGROUND DATA: The ideal oncologic surgical outcome is a negative transection margin with normal pancreatic epithelium left behind. However, the prognostic significance of reresecting certain degrees of dysplasia or invasive cancer at the pancreatic neck margin during pancreatectomy for IPMN-derived PDAC is debatable. METHODS: Consecutive patients with resected and histologically confirmed IPMN-derived PDAC (2002-2022) from six international high-volume centers were included. The prognostic relevance of a positive resection margin (R1) and degrees of dysplasia at the pancreatic neck margin were assessed by log-rank test and multivariable Cox-regression for overall survival (OS) and recurrence-free survival (RFS). RESULTS: Overall, 832 patients with IPMN-derived PDAC were included with 322 patients (39%) having an R1-resection on final pathology. Median OS (mOS) was significantly longer in patients with an R0 status compared to those with an R1 status (65.8 vs. 26.3 mo P<0.001). Patients without dysplasia at the pancreatic neck margin had similar OS compared to those with low-grade dysplasia (mOS: 78.8 vs. 66.8 months, P=0.344). However, high-grade dysplasia (mOS: 26.1 mo, P=0.001) and invasive cancer (mOS: 25.0 mo, P<0.001) were associated with significantly worse OS compared to no or low-grade dysplasia. Patients who underwent conversion of high-risk margins (high-grade or invasive cancer) to a low-risk margin (low-grade or no dysplasia) after intraoperative frozen section had significantly superior OS compared to those with a high-risk neck margin on final pathology (mOS: 76.9 vs. 26.1 mo P<0.001). CONCLUSIONS: In IPMN-derived PDAC, normal epithelium or low-grade dysplasia at the neck have similar outcomes while pancreatic neck margins with high-grade dysplasia or invasive cancer are associated with poorer outcomes. Conversion of a high-risk to low-risk margin after intraoperative frozen section is associated with survival benefit and should be performed when feasible.

Tailoring Mechanical and Optical Properties of Sputtered SiNx/BN Coatings.

The swift evolution of contemporary electronics products, such as flexible screens and wearable electronic devices, highlights the significance of flexible protective coatings, which combine superior mechanical and optical properties. Even though the recently developed polymer protective coatings can satisfy requirements for flexibility and transparency, their intrinsic nature often results in a hardness below 1 GPa, rendering them susceptible to scratches. On the other hand, traditional inorganic coatings, known for their high hardness and transparency, fall short of meeting flexibility requirements. In the present study, a SiNx/BN periodical nanolayered coatings (PNCs) structure has been tailored to achieve high mechanical durability, transparency, and flexibility. In SiNx/BN PNCs, the optical and mechanical properties of the single-layer SiNx film are crucial to the overall performance of the PNCs. Therefore, pulse direct current (DC) magnetron sputtering was optimized first to enhance the ionization efficiency of Si and N, thereby promoting their reaction and diminishing the presence of elemental silicon in SiNx. The effects of the pulse frequency and duty cycle on SiNx were evaluated. Additionally, the influence of the thickness ratio and modulation periods on the overall performance of the SiNx/BN PNCs was investigated. As a result, a SiNx/BN coating with sapphire-grade hardness, almost no optical absorption in the visible-near-infrared (vis-NIR) range, high wear resistance, and exceptional flexibility was demonstrated.

Prevalence of self-reported voice and swallowing complaints in an outpatient geriatric population.

Background: Older adults suffer from increased rates of dysphagia and dysphonia, both of which have a profound effect on quality of life and are often underdiagnosed. We sought to better understand the prevalence of these complaints and the potential utility of a patient-reported screening program in a geriatrics clinic. Methods: Using an IRB-approved cross-sectional survey and retrospective cohort design, we recruited participants from a population of new patients seeking care at an academic geriatrics clinic. We used three validated questionnaires to assess self-reported dysphagia, dysphonia, and pill dysphagia: the Eating-Assessment Tool-10 (EAT-10), the Voice Handicap Index-10 (VHI-10), and the PILL-5. Patients who screened positive on any questionnaire were offered referral to a laryngologist for additional evaluation. Patients who screened positive on the PILL-5 were also offered referral to our geriatric pharmacist. Results: Among our 300 patients surveyed, the mean age was 76 (SD 8.46). A total of 82 (27.3%) patients screened positive (73 on EAT-10, 10 on PILL-5, 13 on VHI-10) and were offered referral, of which 36 accepted. These positive screening patients took more prescription medications (p = .024) and had a higher GDS score (p < .001) when compared to the patients who screened negative. Conclusions: Many new patients seeking generalized care at our center screened positively for dysphagia and/or dysphonia on validated questionnaires. Geriatric patients may benefit from integrating screening for these disorders to identify the need of further evaluation. It is unknown if these survey tools are appropriate in a non-otolaryngology clinic. Level of evidence: III.

Divergent Evolution in Bilateral Prostate Cancer: a Case Study.

Multifocal prostate cancer is a prevalent phenomenon, with most cases remaining uncharacterized from a genomic perspective. A patient presented with bilateral prostate cancer. On systematic biopsy, two indistinguishable clinicopathologic lesions were detected. Whole-genome sequencing displayed somatically unrelated tumours with distinct driver CNA regions, suggesting independent origins of the two tumors. We demonstrated that similar clinicopathologic multifocal tumours, which might be interpreted as clonal disease, can in fact represent independent cancers. Genetic prognostics can prevent mischaracterization of multifocal disease to enable optimal patient management.

Differential MYC and PROM1 mRNA isoform expression in breast invasive carcinoma as biomarkers for subtyping and prognosis.

BACKGROUND: Cancer stem cells are a subpopulation of tumor cells with the ability to self-renew; evidence suggests that cancer stem cells are responsible for recurrence, metastasis, and resistance to therapy. MYC and CD133 (PROM1 gene) are clinical biomarkers for cancer stem cells, and their dysregulation is involved in the progression of many cancers. Alternative splicing of these genes may contribute to cancer stem cell differentiation. METHODS: Transcriptional and clinical data of PROM1 and MYC mRNA isoforms in breast cancer samples were downloaded from the TCGA Splicing Variants Database site, a web-tool to explore mRNA alternative-splicing based on TCGA samples. Data include RSEM isoform expression, clinical sample types, survival data, and clinical receptor expression. Breast cancer subtypes (luminal A, luminal B, Her2 positive, triple negative) were assigned on the basis of estrogen, progesterone, and HER2 expression. RESULTS: Expression of MYC isoforms uc003ysh.1 and uc003ysi.3 was significantly greater in triple-negative breast cancer compared with all other breast cancer subtypes (P < .001). Isoform uc003ysi.3 was associated with greater 5-year survival in luminal A breast cancer (hazard ratio, 0.79; 95% confidence interval, 0.65-0.96; P = .02). PROM1 isoforms uc003gop.2, uc003goq.3, uc003gos.2, and uc003gou.2 were expressed greatest in triple-negative breast cancer (P < .001). PROM1 isoform uc003gou.2 was associated with better 5-year survival in luminal A breast cancer (hazard ratio, 0.79; 95% confidence interval, 0.65-0.97; P = .02). CONCLUSIONS: MYC and PROM1 isoforms are differentially expressed in breast cancer subtypes. Certain isoforms confer better survival prognosis. Further work should be done to study alternative splicing in cancer stem cells.

Metapipeline-DNA: A Comprehensive Germline & Somatic Genomics Nextflow Pipeline.

Summary: DNA sequencing is becoming more affordable and faster through advances in high-throughput technologies. This rise in data availability has contributed to the development of novel algorithms to elucidate previously obscure features and led to an increased reliance on complex workflows to integrate such tools into analyses pipelines. To facilitate the analysis of DNA sequencing data, we created metapipeline-DNA, a highly configurable and extensible pipeline. It encompasses a broad range of processing including raw sequencing read alignment and recalibration, variant calling, quality control and subclonal reconstruction. Metapipeline-DNA also contains configuration options to select and tune analyses while being robust to failures. This standardizes and simplifies the ability to analyze large DNA sequencing in both clinical and research settings. Availability: Metapipeline-DNA is an open-source Nextflow pipeline under the GPLv2 license and is freely available at https://github.com/uclahs-cds/metapipeline-DNA.

Predicting Long-Term Clinical Outcomes of Patients With Recurrent Pericarditis.

BACKGROUND: Recurrent pericarditis (RP) is a complex condition associated with significant morbidity. Prior studies have evaluated which variables are associated with clinical remission. However, there is currently no established risk-stratification model for predicting outcomes in these patients. OBJECTIVES: We developed a risk stratification model that can predict long-term outcomes in patients with RP and enable identification of patients with characteristics that portend poor outcomes. METHODS: We retrospectively studied a total of 365 consecutive patients with RP from 2012 to 2019. The primary outcome was clinical remission (CR), defined as cessation of all anti-inflammatory therapy with complete resolution of symptoms. Five machine learning survival models were used to calculate the likelihood of CR within 5 years and stratify patients into high-risk, intermediate-risk, and low-risk groups. RESULTS: Among the cohort, the mean age was 46 ± 15 years, and 205 (56%) were women. CR was achieved in 118 (32%) patients. The final model included steroid dependency, total number of recurrences, pericardial late gadolinium enhancement, age, etiology, sex, ejection fraction, and heart rate as the most important parameters. The model predicted the outcome with a C-index of 0.800 on the test set and exhibited a significant ability in stratification of patients into low-risk, intermediate-risk, and high-risk groups (log-rank test; P < 0.0001). CONCLUSIONS: We developed a novel risk-stratification model for predicting CR in RP. Our model can also aid in stratifying patients, with high discriminative ability. The use of an explainable machine learning model can aid physicians in making individualized treatment decision in RP patients.

Serial Changes in Ventricular Strain in Symptomatic Obstructive Hypertrophic Cardiomyopathy Treated With Mavacamten: Insights From the VALOR-HCM Trial.

BACKGROUND: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy, VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) demonstrated that mavacamten reduces the need for septal reduction therapy with sustained improvement in left ventricular (LV) outflow tract gradients and symptoms. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function. In VALOR-HCM, we assessed serial changes in LV and right ventricular (RV) strain. METHODS: VALOR-HCM included 112 patients with symptomatic obstructive hypertrophic cardiomyopathy (mean, 60 years; 51% male; LV ejection fraction, 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo (n=52) transitioned to mavacamten from weeks 16 to 56 (40-week exposure). LV-GLS and RV-GLS assessment was performed using a vendor-neutral software. Non-foreshortened apical (4-, 3-, and 2-chamber) views were used to obtain peak LV-GLS. RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable. RESULTS: At baseline, the mean LV-GLS, RV 4-chamber, and free wall strain values were -14.7%, -22.2%, and -16.8%, respectively (all worse than reported normal means). In the total study sample, LV-GLS significantly improved from baseline to week 56 (P=0.02). Twelve patients had transient reduction in LV ejection fraction (<50%) requiring temporary drug interruption (including 3 permanent discontinuations). The LV-GLS in this subgroup was worse at baseline versus total study population (-11.4%), with no significant worsening from baseline through week 56 (P=0.64). Both free wall and 4-chamber RV-GLS remained unchanged from baseline to week 56 (P=0.62 and P=0.56, respectively). CONCLUSIONS: In VALOR-HCM, treatment with mavacamten improved LV-GLS from baseline through week 56 (with no significant worsening of LV-GLS in patients with a reduction in LV ejection fraction ≤50%), suggesting a favorable long-term impact on regional LV systolic function. Additionally, there was no detrimental impact on RV systolic function. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04349072.