bluuebunny/crossref_metadata_2025_split huggingface dataset:
KL-1: HYPERTENSION: PAST PROGRESS, PRESENT CHALLENGES AND FUTURE PROMISES
Authors: Dzau Victor J. 
Published: January 2023

Hypertension has been long recognized as a major health challenge. Hypertension research and management have made important progress with considerable success in reducing cardiovascular morbidity and mortality. This progress is the result of basic and translational research in developing animal models, the fundamental understanding of physiology and biochemistry of blood pressure regulation, and the development of therapeutics. More recently, advances in genetics, genomics, molecular pathways, and emerging technology show much promise.
However, there remains substantial challenges. Hypertension is controlled in less than a fifth of patients worldwide. There are vast global disparities in hypertension awareness, treatment, and control, especially problematic in low- and middle-income countries. Challenges include early detection and follow-up that is dependent on cuff-based measurement and drug regimens, which are often not precise, and have side effects. In spite of recent scientific progress and numerous clinical research trials, recent research has not yielded major advances in hypertension control.
Transformation is urgently needed to reduce the global burden of hypertension. The future will depend on effective development of digital technologies, insights from data science and artificial intelligence for detection and management, new techniques such as genome editing which provide potential cures, and the importance of population science for global control.
PL-1: DECIPHERING THE MYSTERY OF SLEEP: TOWARD THE MOLECULAR SUBSTRATE FOR SLEEPINESS
Authors: Yanagisawa Masashi 
Published: January 2023

Although sleep is a ubiquitous behavior in animal species with central nervous systems, the neurobiology of sleep remain mysterious. Our discovery of orexin, a hypothalamic neuropeptide involved in the maintenance of wakefulness, has helped reveal neural pathways in the regulation of sleep/wakefulness. Orexin receptor antagonists, which specifically block the endogenous waking system, have been approved as a new drug to treat insomnia. Also, since the sleep disorder narcolepsy-cataplexy is caused by orexin deficiency, orexin receptor agonists are expected to provide mechanistic therapy for narcolepsy; they will likely be also useful for treating excessive sleepiness due to other etiologies.
Despite the fact that the executive neurocircuitry and neurochemistry for sleep/wake switching has been increasingly revealed in recent years, the mechanism for homeostatic regulation of sleep, as well as the neural substrate for “sleepiness” (sleep need), remains unknown. To crack open this black box, we have initiated a large-scale forward genetic screen of sleep/wake phenotype in mice based on true somnographic (EEG/EMG) measurements. We have so far screened > 10,000 heterozygous ENU-mutagenized founders and established a number of pedigrees exhibiting heritable and specific sleep/wake abnormalities. By combining linkage analysis and the next-generation whole exome sequencing, we have molecularly identified and verified the causal mutations in several of these pedigrees. Biochemical and neurophysiological analyses of these mutations are underway. Indeed, through a systematic cross-comparison of the Sleepy mutants (with a gain-of-function change in a serine/threonine kinase pathway) and sleep-deprived mice, we have found that the cumulative phosphorylation state of a specific set of mostly synaptic proteins may be the molecular substrate of sleep need.
FP-3: RESEARCH ON COMPLETE NUTRITION MEAL TO AVOID THE METABOLIC DOMINO EFFECT, REALIZING MIBYOU PREVENTION (DISEASE-FREE STATE)
Authors: Ando Noritaka 
Published: January 2023

While the modern diet has become richer and more abundant, many diet-related problems exist, including obesity due to excessive calories and hidden malnutrition due to inappropriate dieting. NISSIN FOOD PRODUCTS is engaged in research on Complete Nutrition Meals of the future, leveraging independent and cutting-edge food technologies cultivated through the development of instant foods and other products. Complete Nutrition Meals offer the same appearance and taste as regular means, but control calories, salt, sugar, fat, etc., embodying the concept of food that satisfies all necessary nutrient needs and referencing various nutritional perspectives. In pursuing Complete Nutrition Meals, NISSIN FOOD PRODUCTS aims to create a world where anyone can enjoy whatever they want, as much as they want, whenever they want.
In this presentation, we will introduce the background behind research on Complete Nutrition Meals and the results of clinical trials. We will also cover efforts aimed at preventing frailty and improving quality of life for hypertensive and diabetic patients through Complete Nutrition Meals.
ME-2: MR BLOCKERS AS THE POSSIBLE FIRST-LINE THERAPY IN HYPERTENSION
Authors: Shibata Hirotaka 
Published: January 2023

Among 43 million hypertensive patients in Japan, blood pressure levels are controlled below 140/90mmHg in only a quarter of these patients. This fact may be due to poor adherence and inadequate lifestyles as well as “clinical inertia” (“diagnostic inertia” and “treatment inertia”) of health care providers.
Primary aldosteronism (PA) is the most common endocrine hypertension and often associated with resistant hypertension. Five to 10% of all people in hypertension and 20% of resistant hypertension is PA. Most importantly, PA presents with higher prevalence of cardiovascular diseases than essential hypertensive patients whose blood pressure levels are controlled to the similar levels. For the case-detection testing, high plasma aldosterone (PAC) to plasma renin activity (PRA) ratio is useful based on the clinical practice guideline of many countries. However, screening of PA is rarely done between 0.7% to 4.2% of hypertensive patients in daily clinical practice. This situation is a sad state of affairs (“diagnostic inertia”), and the screening of PA should be done at least once in all hypertensive patients. For treatment of PA, administration of a mineralocorticoid receptor blocker (MRB) is recommended in patients with bilateral PA as well as ones who do not willing to undergo surgery. It is therefore crucial to administer a MRB as a first-line therapy, although it is not included in the “first-line antihypertensives”.
In addition, since the PA screening test is done quantitatively, it may be insufficient to evaluate just “non-PA” when the ratio is lower than the cut-off values. It may be rather crucial to consider the pathogenesis as “borderline aldosteronism” or “mineralocorticoid receptor (MR)-associated hypertension” when the ratio is suboptimal, because a MR antagonist would be a better choice to control hypertension under such circumstances.
In diabetes mellitus and chronic kidney disease, MR may be directly overactivated by varied molecular mechanisms. In addition, under the treatment with angiotensin receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACEi) in patients with diabetes and chronic kidney disease, PAC is suppressed firstly, but re-elevated sometimes over baseline levels (“aldosterone breakthrough”). We therefore presume that combination treatment of a MRB with first-line antihypertensives (ARB/ACEi and calcium channel blocker) may resolve “treatment inertia” of hypertension. Considering the resolution of both “diagnostic and treatment inertia” for hypertension, it is conceivable that MRB should be included in the first-line therapy for hypertension.
SP-5: PRESENTATION ZEN: THE ART OF PRESENTING WITH IMPACT
Authors: Reynolds Garr 
Published: January 2023

Dynamic presentation skills are more important now than ever before for medical professionals. Effective and modern presentation skills are absolutely necessary, and having such skills can make a big difference in your professional effectiveness. Many medical professionals have teaching as a major aspect of their job. Increasingly, clinicians are required to construct presentations that facilitate real learning and not just a way to deliver loads of data and information. Delivering presentations with passion and enthusiasm will facilitate more effective learning and by extension may even impact patient care and outcomes.
Bullet-point filled slides with lots of text and small, poorly designed visuals become a barrier to good communication. We have become accustomed to visually busy and hard to see slides which cause a disconnect between the audience and the presenter. Many medical professionals are fed up with dense, hard to comprehend text-filled slides and presenters who just read a script and deliver a dull presentation. A presentation is a great opportunity for teaching and helping people to understand your findings and ideas so that they may make a change for the better. Presenters often unintentionally deliver their ideas in a way that is confusing for the audience. However, the presenter should ask themselves: How can I take this complicated topic and make it easy for the audience to understand and remember? Achieving this goal take creativity and an empathy for the audience.
I have been interested in multimedia and presentation since I was a child, and this interest is largely why I went to work for Apple in Silicon Valley. At Apple I was inspired by Steve Jobs presentation skills and became convinced that all professionals could become much better presenters by studying the arts of storytelling and visual communication.
The Presentation Zen approach challenges the conventional wisdom of making slide presentations today and encourages medical professionals to think differently and more creatively about the preparation, design, and delivery of presentations. Based on research from the cognitive sciences, combined with principles from the world of the Zen arts, graphic design and visual communications, Presentation Zen will dispel popular myths about what is an effective presentation and offer up effective alternatives and approaches for designing and delivering better presentations. All throughout the presentation, the common themes are (1) restraint and clarity in preparation, (2) simplicity in design, and (3) naturalness in delivery.
S-02-3: A REVIEW AND NEW INSIGHTS FROM THE SPRINT MIND TRIAL DATA
Authors: Williamson Jeff Douglas 
Published: January 2023

Background:
Proven treatments for reducing the risk of mild cognitive impairment (MCI) and dementia have been lacking. The impact of intensive treatment of hypertension on the incidence of Mild Cognitive Impairment (MCI) and dementia was tested in the Systolic Blood Pressure Intervention Trial (SPRINT-MIND) by prospectively assessing the effect of intensive blood pressure control to a target systolic blood pressure of <120 mmHg versus a standard target (<140 mmHg). This presentation reviews the SPRINT results demonstrating a reduction in risk of developing dementia and MCI and presents additional data on the reliability of the MCI and dementia diagnosis. We will also provide preliminary evidence for differential cognitive benefit from specific antihypertensive medicines and evidence for lack of benefit after onset of cognitive impairment

Results:
At one year, mean systolic blood pressure was 121.4 mmHg in the intensive-treatment group and 136.2 mmHg in the standard-treatment group. Treatment was stopped on 8/20/2015 due to CVD benefit after a median follow up of 3.26 years, but cognitive assessment continued. Participant mean age was 67.9 years (35.6% women) and 8,626 (92.1%) completed at least one follow-up cognitive assessment. There was a significantly lower rate of adjudicated incident MCI (HR 0.81, CI 0.67–0.97) and a non-significant reduction in probable dementia (HR 0.83, CI 0.69–1.04). The combined outcome of MCI plus probable all cause dementia was significantly lower (HR 0.85, CI 0.74–0.97) in the intensive versus standard treatment group. Most cases occurred in persons over age 70. At 2 years, MCI classification was 10X more likely to transition to dementia than normal cognition and 30% of classified as MCI reverted to normal, consistent with other large epidemiologic studies of MCI trajectory

Conclusions:
Among ambulatory adults at increased risk for CVD but without diabetes, treating to a SBP target < 120 mmHg compared to a target of < 140 mmHg reduces the risk of incident MCI and combined MCI/probable dementia. Reduction of dementia risk by cardiovascular interventions is feasible in the elderly population.
S-04-2: AUTOMATED OFFICE BLOOD PRESSURE IN RESEARCH VERSUS CLINICAL PRACTICE
Authors: Myers Martin G. 
Published: January 2023

A white coat response which increases BP when recorded in clinical practice has been recognized as a cause of apparent hypertension. Automated office (AO) BP measurement was developed to improve the accuracy of office BP. By recording multiple readings using an automated sphygmomanometer with the patient resting quietly alone, the white coat response which averaged 15 mmHg was eliminated, with AOBP being similar to the awake ambulatory (A) BP. In a Spanish study of 27,211 patients in the community, the difference between awake ambulatory BP and routine office BP was even greater (25 mmHg). Based on these studies, Canadian and American guidelines now recommend AOBP as the preferred method for recording BP in the office.
However, European guidelines continue to focus on improving the accuracy of office BP by stricter adherence to proper BP measurement technique. AOBP is considered to be impractical, with concerns that readings take too long, require a dedicated room and lack support from longitudinal outcome studies. In reality, none of these criticisms are valid. Guidelines on the proper measurement of BP in the office have been published as far back as 1939, yet, there has never been a meta-analysis showing that routine office BP is as good a predictor of cardiovascular outcome as the BP recorded under research conditions.
Awake ABP is a gold standard for determining the risk of future cardiovascular morbidity and mortality. In 19 research studies, mean systolic AOBP was only 0.3 mmHg different from the mean awake ABP. When data comparing attended versus unattended AOBP in research studies were analysed, the mean systolic attended AOBP was still 6 mmHg higher. The presence of office staff appears to be sufficient to increase office BP.
AOBP has been criticized for being too variable. In a recent study comparing AOBP to home BP readings, both types of measurements exhibited similar degrees of variability, yet only home BP is recommended as an alternative to 24-hour ABPM. This conclusion ignores data showing mean AOBP, home BP and awake ABP being similar.
Guidelines for clinical practice should be evidence-based. It may not be possible to record AOBP on every patient. However, AOBP readings should be recommended as the optimum method for recording BP in routine clinical practice, whenever it is feasible to do so.
S-04-3: VALIDATION OF BLOOD PRESSURE DEVICES AS PER 2020 WHO TECHNICAL SPECIFICATIONS: A SCOPING REVIEW OF GLOBAL LITERATURE
Authors: Murthy Shruti , Rajwar Eti , Johnson Rosemol , Shrivastava Krati , Kamath Prashanthi , Rahman Rinsy , Devaria Abhinav , Ismavel Vijay Anand , Vetter Beatrice , John Oommen 
Published: January 2023

Objective:
To (1) identify and summarize the global research literature on validation of automated non-invasive blood pressure measurement devices (BPMD) with upper arm cuff, (2) develop a repository of validated BPMD in compliance 2020 WHO technical specifications (3) identify challenges and gaps in evidence base on validated BPMD and develop novel strategies to address them.

Design and method:
A scoping review was conducted according to the Joanna Briggs Institute methodology using ‘Population, Concept, Context’ concept. Empirical studies validating BPMD complying with the 2020 WHO technical specifications (i.e. semi-automated/automated non-invasive with upper arm cuff), published in English between 2000 and 2022 were eligible for inclusion in the review. We searched MEDLINE, Web of Science, Scopus, EMBASE, CINAHL, CENTRAL, ProQuest and daBL website. We snowballed references from website reports. Title-abstract, full-text screening, and data extraction was conducted in duplicate by four reviewers (PICOPortal, MS Excel). Descriptive data analysis was performed on MS Excel and Tableau.

Results:
Of 11,825 identified records, we included 269 studies that fulfilled the inclusion criteria. A total of 251 BPMD from 89 manufacturers were assessed for validation methods. Omron (29%), Microlife (10%) and A&D Company (8%) were the top three BPMD manufacturers that underwent validations. China (20%), UK (13%) and USA (12%) were the top three countries where these validations were undertaken. The three most frequently used validation protocols were (Figure1): European Society of Hypertension-International protocol (ESH-IP) 2002 (27%), ESH-IP 2010 (25%) and Modified British Hypertension Society 1993 (16%). Nearly 50%, 40% and 48% of the validated BPMD were intended for use in clinical- and home/self-measurement, and for general adults, respectively. Of the 55% studies that were funded, 72% received support (finances/ BPMD) from device manufacturers. The publications did not reveal details about the following: device manufacturer (13%), country of validation (26%), settings for intended BPMD use (29%), and the target population for BPMD use (22%).

Conclusions:
While most (89%) of the BPMD included in the review fulfilled the validation criteria, there are considerable gaps in terms of the settings and countries of validation. In designing validation studies, research methods should focus on validating BPMD for specific target population and conditions (e.g. pregnancy or children), and take range of arm circumferences into considerations. Finally, we call for improvement in quality of reporting the validation studies to improve transparency and comparability. This could be best achieved by initiating a dialogue with all stakeholders in blood pressure research and practice.
S-06-3: EMERGENT BLOOD PRESSURE LOWERING WITH INTRAVENOUS NICARDIPINE FOR JAPANESE PATIENTS WITH ACUTE INTRACEREBRAL HEMORRHAGE: AN INDIVIDUAL PARTICIPANT DATA ANALYSIS
Authors: Toyoda Kazunori , Yoshimura Sohei , Doi Mayumi Fukuda , Qureshi Adnan I. , Koga Masatoshi 
Published: January 2023

Objective:
Intensive lowering of elevated blood pressure is one of the few promising therapies for acute intracerebral hemorrhage. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine for Japanese patients with acute intracerebral hemorrhage on clinical outcomes were determined.

Design and method:
A systematic review and individual participant data analysis of articles before October 1, 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving adults developing hyperacute intracerebral hemorrhage who were treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale were eligible. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4–6, and hematoma expansion, defined as an increase 6 mL or more from baseline to 24-h computed tomography. In this study, data on Japanese patients were extracted. The study is registered with PROSPERO (CRD42020213857).

Results:
Three studies, ATACH-1, ATACH-2, and SAMURAI-ICH, met the eligibility criteria. Of 1,271 patients enrolled, 500 were registered from Japan, and all of these were Japanese. A patient with available data on the hourly blood pressures only for < 4 timepoints was excluded, and the other 449 patients (age 64.9 ± 11.8 years, 183 women, initial BP 203.5v± 18.3 / 109.1 ± 17.2 mmHg) were studied. Death or disability occurred in 35.6%, and hematoma expansion occurred in 15.6%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio 1.26, 95% confidence interval 1.04–1.53 per 10 mmHg) and hematoma expansion (1.47, 1.17–1.85). These odds ratios were relatively high as compared to the reported ones for global patients of this individual participant data analysis [1.12 (95% confidence interval 1.00–1.26) and 1.16 (1.02–1.32), respectively] (Toyoda K, et al: Int J Stroke 2021).

Conclusions:
Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h was associated with lower risks of hematoma expansion and 90-day death or disability in Japanese patients with hyperacute intracerebral hemorrhage. The impact of systolic blood pressure lowering on better outcome seemed to be stronger in Japanese patients than the global ones.
S-07-5: ASPROSIN INDUCES VASCULAR ENDOTHELIAL- TO-MESENCHYMAL TRANSITION IN DIABETIC LOWER EXTREMITY PERIPHERAL ARTERY DISEASE
Authors: You Mei , Liu Yushuang , Wang Bowen , Yan Zhencheng 
Published: January 2023

Objective:
Altered adipokine secretion in dysfunctional adipose tissue facilitates the development of atherosclerotic diseases including lower extremity peripheral artery disease (PAD). Asprosin is a recently identified adipokine and displays potent regulatory role in metabolism, but the relationship between asprosin and lower extremity PAD remains uninvestigated. In this study, we investigated the effect of asprosin accounting for the lower extremity vascular injury in diabetic patients based on the metabolic profiles of PAD.

Design and method:
33 type 2 diabetes mellitus (T2DM) patients (DM), 51 T2DM patients with PAD (DM+PAD) and 30 healthy normal control (NC) volunteers were recruited and the blood samples were collected for detecting the circulatory asprosin level and metabolomic screening. RNA sequencing was performed using the aorta tissues from the type 2 diabetic db/db mice and its control db/m mice. Moreover, human umbilical vein endothelial cells (HUVECs) were treated with asprosin to determine its impact on the endothelial-to-mesenchymal transition (EndMT).

Results:
The circulating levels of asprosin in DM+PAD group were significantly higher than that of NC group and the DM group. Circulating asprosin level was remarkably negatively correlated with ankle-brachial index (ABI), even after adjusting for age, sex, body mass index (BMI) and other traditional risk factors of PAD (P = 0.049). Logistic regression analysis revealed that asprosin is an independent risk factor for PAD (OR:3.944, 95%CI:1.656 − 9.393, P = 0.002) and receiver-operator characteristic (ROC) curve determined a cut-off value at 188.70 ng/ml with a good sensitivity (74.5%) and specificity (74.6%) of asprosin to distinguish PAD (Area under curve:0.788, 95%CI:0.694 − 0.863, P < 0.001). Data from metabolomics displayed a typical characteristics of de novo amino acid synthesis in collagen protein production by myofibroblasts in which TGF-beta signaling pathway might plays a critical role in patients with PAD. In addition, activation of TGF-beta signaling pathway also appeared in the aortic tissue of db/db mice, suggesting a causal relationship between TGF-beta signaling pathway and artery injury. Asprosin directly induces EndMT in HUVECs in a TGF-beta-dependent manner as TGF-beta signaling pathway inhibitor SB431542 erased the promotional effect of asprosin on EndMT.

Conclusions:
Elevated circulatory asprosin level is an independent risk factor of lower extremity PAD and might serve as a diagnostic marker. Mechanistically, asprosin directly induces EndMT that participates in vascular injury via activation of TGF-beta signaling pathway.