bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-P03-3: PREVALENCE OF HYPERTENSION IN NEPAL: RESULTS OF MAY MEASUREMENT MONTH 2020
Authors: Subedi Narayan , Acharya Pawan , Koirala Sweta , Soti Pabitra Babu , Sharma Sneha , Sapkota Abhisekh , Kafle Simrin , Paudel Kiran , Poudel Santosh , Neupane Dinesh 
Published: January 2023

Objective:
To increase public awareness on importance of blood pressure (BP) screening for hypertension prevention and management through a national campaign in Nepal.

Design:
Opportunistic BP screening campaign was carried out among people 18 years or more in the year 2020, following the COVID-19 safety measures. The study used a cross-sectional survey design.

Method:
Systolic and diastolic BP data of the participants were obtained from three consecutive measurements of which second and third measurements were used to estimate the mean. Hypertension was defined as the systolic BP more than or equal to 140 and/or diastolic BP more than or equal to 90 mmHg or currently taking antihypertensive medicine. The screening campaign was conducted in 25 sites of the country. Measurement was done using OMRON automatic monitors. Altogether, 115 volunteer research assistants with public health background used mobilized for data collection. Logistic regression analysis was used to identify the factors associated with hypertension.

Results:
In total, 11,481 people participated in the BP screening campaign of which more than half were females (57%, 6568/11,481). Mean age of the participants was 45 ± 17 years. Mean systolic and diastolic BP were 125.8 ± 18 and 81.6 ± 10.5 respectively. Nearly a third (31.1%, 3592/11,481) of participants were hypertensive of which only 40% (1444/3592) were aware about their hypertension status. However, only about 80% (1146/14444) hypertensive participants were talking medicines. High age-group, high body mass index and smoking were found associated with hypertension adjusting age, sex and body mass index and smoking status of the participants.

Conclusions:
Blood pressure screening campaign provided an important opportunity to identify undiagnosed hypertension and raise awareness on hypertension among the general population. Awareness raising programs at the population and targeted interventions are warranted for prevention and control of hypertension in Nepal among older, overweight, and obese people and smokers.
PS-P03-9: CONTENT AND DELIVERY PREFERENCES FOR INFORMATION TO SUPPORT THE MANAGEMENT OF HIGH BLOOD PRESSURE
Authors: Chapman Niamh , Marques Francine Z , Picone Dean S , Schultz Martin G , Mynard Jonathan P , Climie Rachel ED 
Published: January 2023

Blood pressure(BP) management interventions have been shown to be more effective when accompanied by appropriate patient education. As high BP remains poorly controlled, there may be gaps in patient knowledge and education. Therefore, this study aimed to identify specific content and delivery preferences for information to support BP management among Australian adults from the general public. Given that BP management is predominantly undertaken by general practitioners(GPs), information preferences to support BP management were also ascertained from a small sample of Australian GPs.
An online survey of adults was conducted to identify areas of concern for BP management to inform content preferences and preferred format for information delivery. A separate online survey was also delivered to GPs to determine preferred information sources to support BP management. Participants were recruited via social media.
General public participants (n = 465) were mostly female (68%), > 60 years (57%) and 49% were taking BP-lowering medications. The management of BP without medications, and role of lifestyle in BP management were of concern among 30% and 26% of adults respectively. Most adults(73%) preferred to access BP management information from their GP. 57% of GPs (total n = 23) preferred information for supporting BP management to be delivered via one-page summaries.
This study identified that Australian adults would prefer more information about the management of BP without medications and via lifestyle delivered by their GP. This could be achieved by providing GPs with one-page summaries on relevant topics to support patient education and ultimately improve BP management.
PS-P04-6: THE ROLE OF CUMULATIVE MEAN ARTERIAL PRESSURE IN FIRST STROKE EVENTS AMONG ADULTS WITH HYPERTENSION: A 10-YEAR PROSPECTIVE COHORT STUDY
Authors: Wang Dan , Wang Jiaqi , Liu Jiali , Qin Yu , Lou Peian , Zhang Yongqing , Zhang Yuqing , Xiang Quanyong 
Published: January 2023

Objective:
Mean arterial pressure (MAP) has been proved to be an independent risk factor for stroke. In this study, we explored whether cumulative exposure of MAP in patients with hypertension is more associated with the occurrence of stroke.

Design and Method:
In this prospective follow-up cohort study of hypertension from June 2010 to May 2020, 9,136 participants without previous stroke at recruitment were included, of whom 492 (5.4%) had a first incident stroke during the study period (418 ischemic strokes and 74 hemorrhagic strokes). The study exposure factor was cumulative MAP, and was quartered from low to high (Q1, Q2, Q3, Q4). We analyzed the risk of first stroke using multivariable adjusted Cox regression models, and used stratified analysis to further explore the risk of stroke in hypertensive patients with different characteristics.

Results:
Increased cumulative MAP in patients with hypertension were associated with risk for ischemic stroke (HR, Q2, 1.23 [95% CI, 0.91–1.67]; Q3, 1.35 [95% CI, 1.01–1.82]; Q4, 1.55 [95% CI, 1.15–2.10]; P = 0.035). furthermore, this trend persisted after stratified analysis in men (HR, Q3, 1.76[1.10–2.82]; Q4, 2.05[1.28–3.28]), aged 60 or above (HR, Q4, 1.63[1.13–2.35]) and higher body mass index (BMI) populations (HR, Q3, 1.48[1.02–2.14]; Q4, 1.59[1.09–2.32]). In contrast, cumulative MAP was not significantly associated with stroke in women, age under 60, and non-obese individuals.

Conclusions:
Increased cumulative MAP is an independent risk factor of ischemic stroke in patients with hypertension. Special attention should also be paid to men, aged 60 or older, or those with a higher BMI.
PS-BPB02-2: POLYMORPHISM OF DNA REPAIR GENE IS ASSOCIATED WITH HYPERTENSION-INDUCED LEFT VENTRICULAR HYPERTROPHY - ROLE OF DNA DAMAGE AND CELL SENESCENCE
Authors: Sakai Chiemi , Ishida Mari , Ariyandy Andi , Ishida Takafumi 
Published: January 2023

Objective:
Deficiency of X-ray repair cross-complementing protein 3 (XRCC3), a DNA-damage repair molecule, and 241Met variant of XRCC3 are prone to increase endoreduplication, resulting in pathological polyploidy. In this study we investigated the impact of XRCC3 polymorphism on the incidence of hypertension-induced left ventricular hypertrophy (LVH) and underlying mechanisms.

Design and method:
Patients under hemodialysis (n = 77) were genotyped for XRCC3 Thr241Met polymorphism. LVH was determined by echocardiography. To investigate the possible mechanisms for LVH, human XRCC3 cDNA of 241Thr or that of 241Met was introduced into cultured cells. The surface area of the cells was measured and spontaneous DNA double-strand breaks were detected by immunofluorescent study with anti-53BP1 antibody. The mRNA levels of basal and TNF-α-stimulated MCP-1 were quantified by real-time RT PCR. FACS analysis was performed to count the percentage of polyploidy.

Results:
In patients under hemodialysis, XRCC3 241Thr/Met genotype was more frequent in LVH (+) group than in LVH (-) group (42.3% vs. 13.7%, χ2 = 7.85, p = 0.0051). To investigate the possible mechanisms for LVH, following in vitro experiments were performed. The surface area of Chinese hamster ovary cells expressing XRCC3 241Met variant was larger than those expressing 241Thr. The accumulation of spontaneous DNA double-strand breaks (DSBs) was increased in NIH3T3 cells expressing 241Met (3T3–241Met) than those expressing 241Thr (3T3–241Thr). Ionizing radiation-induced cell senescence was significantly enhanced in 3T3–241Met than in 3T3–241Thr. The mRNA levels of basal and TNF-α-stimulated MCP-1 were higher in 3T3–241Met variant than 3T3–241Thr. Finally, FACS analysis revealed that the cell percentage in G2/M phase including polyploidy was significantly increased in 3T3–241Met compared with 3T3–241Thr. In addition, the basal mRNA level of MCP-1 was positively correlated with the cell percentage in G2/M phase and polyploidy.

Conclusion:
The current study suggests that XRCC3 241Met variant increases the risk of LVH via the accumulation of DNA damage, alteration of cell cycle progression, and induction of cell senescence and proinflammatory phenotype.
PS-BPB02-5: INHIBITION OF CALPAIN ALLEVIATES FERROPTOSIS IN DOXORUBICIN-INDUCED CARDIOMYOPATHY
Authors: Chen Zhiwei , Chen Ruizhen 
Published: January 2023

Rationale:
Maintaining iron homeostasis is essential for proper cardiac function. Although excessive activation of calpain plays a central role in cardiomyopathy and heart failure via complex mechanisms, the molecular function of calpain in iron homeostasis and cardiomyocyte ferroptosis remains unknown.

Objective:
To characterize the functional role of calpain in mediating cardiac iron homeostasis and heart disease.

Methods and Results:
Doxorubicin-induced cardiotoxicity (DIC) model with C57BL/6 mice was established and confirmed by transthoracic echocardiography examination. The induction of ferroptosis in the DOX-treated murine heart was confirmed by transmission electron microscopy, cardiac malondialdehyde (MDA) level, glutathione (GSH) level and Ptgs2 mRNA expression. We then investigate the role of calpain in DOX-induced cardiomyocytes ferroptosis. Both in vitro and in vivo experiments proved the upregulation of calpain-1 in DIC, which can be partially prevented with Lip-1 or Fer-1 treatment. Knock-down of calpain-1 in cell lines showed noteworthy protection to ferroptosis, while the overexpression of calpain-1sensitized cardiomyocytes to ferroptosis by DIC. Both in vitro and in vivo experiments proved PD150606, a specific inhibitor of calpain, inhibits lipid oxidation and DOX toxicity in DIC through promoting dihydroorotate dehydrogenase (DHODH) level, supporting calpain activation plays a central role in DOX-induced cardiomyocytes ferroptosis. Finally, we found that BAY-2402234, a novel DHODH inhibitor, undermined the protection effect of PD150606 in DIC.

Conclusion:
Our findings provide compelling evidence that calpain plays a major role in cardiac ferroptosis and subsequent cardiomyopathy, providing a potential treating target in preventing DIC by anti-ferroptosis.
PS-BPB04-1: DNA-APTAMER RAISED AGAINST RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS INHIBITS ATHEROSCLEROSIS
Authors: Terasaki Michishige , Mori Yusaku , Yashima Hironori , Saito Tomomi , Sotokawauchi Ami , Matsui Takanori , Hiromura Munenori , Osaka Naoya , Fukase Ayako , Kawakami Raichi , Shiraga Yoshie , Ohara Makoto , Fukui Tomoyasu , Yamagishi Shoichi 
Published: January 2023

Background and Aims:
Interaction of advanced glycation end products (AGEs) with the receptor RAGE could accelerate atherosclerotic plaque formation. However, effect of DNA-aptamer raised against RAGE on atherosclerosis remains unclear. In this study, we aimed to elucidate whether and how RAGE-aptamer could inhibit atherosclrotic lesions and oxidized-LDL uptake of macrophages derived from apolipoprotein E (ApoE)-null mice, a representative animal model of atherosclerosis. We also examined whether RAGE-aptamer could inhibit oxidized-LDL uptake in AGE-exposed mouse peripheral macrophages and human U937 cells.

Materials and Methods:
Seventeen-week-old male ApoE-null mice were subcutaneously infused with RAGE-aptamer (10 pmoL/g/day) or control-aptamer by osmotic pump for 4 weeks. Peritoneal macrophages were extracted from mice at 21 weeks of age just after intraperitoneal injection of thioglycollate broth. The entire aortae and cross-sections of the aortic roots were stained with Oil Red O or MOMA-2 for the assessment of atherosclerotic lesions or macrophage infiltration. Mouse macrophages and human U937 cells were incubated with 100 μg/mL AGE-bovine serum albumin (AGE-BSA) or non-glycated BSA for 24 hours. Then the cells were treated with RAGE-aptamer or control-aptamer for 18 hours. Oxidized-LDL uptake was determined by Dil-oxidized-LDL fluorescent intensity using immunohistochemistry. Quantitative RT-PCR analysis was performed using TaqMan-based probes and SYBR-based primers.

Results:
Atherosclerotic lesions and infiltration of macrophages in the aortae isolated from ApoE-null mice infused subcutaneously with RAGE-aptamer were significantly suppressed compared with control-aptamer-treated mice. Oxidized-LDL uptake, and cyclin-dependent kinase 5 (Cdk5) and CD36 gene expression in macrophages extracted from ApoE-null mice infused with RAGE-aptamer were attenuated in comparison to those from mice infused with control-aptamer. Furthermore, RAGE-aptamer significantly inhibited oxidized-LDL uptake, and Cdk5 and CD36 gene expression in mouse macrophages and human U937 cells compared with those exposed with control-aptamer. Gene expression level of Cdk5 in mouse or human U937 cells was correlated with that of CD36.

Conclusion:
Our present findings suggest that RAGE-aptamer could play a protective role against atherosclerosis through the inhibition of macrophage foam cell formation via Cdk5-CD36 pathway in mice and human, which may be caused by attenuating the harmful effects of AGEs.
PS-BPB05-9: DUAL DELETION OF GUANYLYL CYCLASE-A AND P38 MAPK IN PODOCYTES WITH ALDOSTERONE ADMINISTRATION CAUSES GLOMERULAR INTRACAPILLARY THROMBI
Authors: Sugioka Sayaka , Yamada Hiroyuki , Ishii Akira , Kato Yukiko , Mori Keita P , Ohno Shoko , Handa Takaya , Ikushima Akie , Ishimura Takuya , Tokudome Takeshi , Matsusaka Taiji , Nebreda Angel R , Yanagita Motoko , Yokoi Hideki 
Published: January 2023

Objective:
Previously, we demonstrated that uninephrectomized aldosterone-infused, high salt-fed podocyte-specific guanylyl cyclase-A (GC-A) conditional KO (pod-GC-A cKO) mice exhibit glomerular injury and that pharmacological inhibition of p38 MAPK ameliorates podocyte damage. However, the effects of genetic deletion of p38 MAPK in podocytes of pod-GC-A cKO mice have been unknown. By generating podocyte-specific p38 MAPK and GC-A double cKO mice, the study investigated the effects of p38 MAPK deletion in podocytes on glomerular injury with aldosterone and a high salt diet in mice.

Design and method:
We generated p38 MAPK(fl/fl);Nephrin-Cre (pod-p38 MA- PK cKO) mice and p38 MAPK(fl/fl);GC-A(fl/fl);Nephrin-Cre (pod-p38MAPK/GC-A double cKO) mice. For induction of glomerular injury, we treated them with aldosterone and high salt at 2 months of age for 3 weeks without nephrectomy (B-ALDO). In vitro, firstly, we examined human podocytes which p38 MAPK was deleted by Crispr/Cas9 system and GC-A was suppressed by siRNA. Secondly, we used a transwell co-culture system to investigate changes of wild-type human umbilical vein endothelial cells (HUVEC) mRNA in the lower layer culture with immortalized p38 MAPK-null podocytes transfected with si-GC-A in the upper layer.

Results:
Unexpectedly, aldosterone-infused, and high salt-fed (B-ALDO)-treated pod-p38 MAPK/GC-A double cKO mice resulted in significant elevation of serum Cr (0.29 ± 0.04 mg/dL), massive albuminuria (42,0541 ± 8,493 μg/mgCr) and severe foot process effacement in addition to intracapillary fibrin thrombi which indicated endothelial damage. In vitro, knockout of p38 MAPK and suppression of GC-A in human cultured podocytes induced podocyte damage. Deletion of p38 MAPK and inhibition of GC-A in podocytes in the upper layer upregulated TGFB1 and FN1 in the HUVEC in the lower layer, indicating that some humoral factors derived from podocytes could work as cell-to-cell mediators, especially for HUVEC.

Conclusions:
Genetic dual deletion of p38 MAPK and GC-A in podocytes accelerates both podocyte and endothelium injuries, suggesting that p38 MAPK in podocytes has an essential role in maintaining podocyte-endothelial interactions, especially under diseased conditions.
PS-BPB09-7: ENDOTHELIAL CNP-GC-B SYSTEM PLAYS A PROTECTIVE ROLE IN THE DEVELOPMENT OF PULMONARY HYPERTENSION
Authors: Yanagisawa Hiromu , Nakagawa Yasuaki , Nishikimi Toshio , Kuwahara Kouichirou 
Published: January 2023

Background:
Pulmonary hypertension (PH) is a disease with a poor prognosis despite the development of various treatments, and a further therapeutic agent is required. C-type natriuretic peptide (CNP), one of the natriuretic peptide family, affects vasorelaxation and inhibition of vascular remodeling through its receptor guanylyl cyclase-B (GC-B). However, the beneficial effect of CNP on PH is still controversial. In this study, we examined the role of the CNP-GC-B pathway in the pathogenesis of PH.

Methods and Results:
To clarify the effect of the endogenous CNP-GC-B system on PH, we evaluated two types of PH models (monocrotaline pyrrole-induced and hypoxia-induced PH models) by using endothelial cell-specific CNP knockout mice (ecCNP-cKO), endothelial cell-specific GC-B knockout mice (ecGC-B-cKO), and smooth muscle cell-specific CG-B knockout mice (smGC-B-cKO). In both PH models, ecGC-B-cKO and ecCNP-cKO mice exacerbated PH compared to control cre-mice. Besides, mRNA levels of Edn1, IL6 and Ccl2 of the lung were significantly increased in the PH models of these mice. However, PH models of smGC-B-cKO mice showed no significant difference compared to those of control cre-mice. In cultured pulmonary arterial endothelial cells, synthesised CNP significantly attenuated PDGF- or hypoxia-induced increase in mRNA expression of Edn1, IL-6, and Ccl2. Moreover, continuous subcutaneous administration of synthesised CNP by osmotic mini-pump significantly ameliorated PH in PH model mice.

Conclusion:
CNP plays a protective role in the development of PH via endothelial GC-B through inhibiting endothelin-1 and inflammatory signals involvement. These data suggest CNP could be a novel therapeutic agent for PH.
PS-BPB10-2: MOLECULAR INSIGHT INTO SALT-SENSITIVITY; THE ROLE OF ATF3 AND THE GENERATION OF TUBULAR SPECIFIC KO MICE. (1)
Authors: Machida Kosuke , Mouri Satoshi , Maeda Kazuki , Matsumoto Kento , Kino Tabito , Saigo Sae , Uchida Kotaro , Chen Lin , Minegishi Shintaro , Arakawa Kentaro , Sugiyama Michio , Tamura Koichi , Ishigami Tomoaki 
Published: January 2023

Objectives:
Current research including ours suggested pivotal roles of expressions of and regulations of tubular ion transporters for developments of sodium sensitivity and hypertension. Orlov et al. demonstrated using rat cardiomyocytes three different genes which are activated according to the elevation of intra-cellular Na ion concentration. (2015) To elucidate detailed biological roles of these genes in tubules, we performed current experiments.

Methods:
We tested expressions of three genes for cDNA from kidneys of Nedd4 2 C2 KO mice using quantitative RT PCR methods. Subsequently, we performed crossbreeding experiments between floxed target gene mice (generous gift from Prof. Kitamura, Tokyo Medical and Dental University) and Ksp-cre mice (Jackson Laboratory), which cre-recombinase expresses specifically along urinary tubules to generate mice with cre+, flox/flox genotype.

Results:
We found expressions of Atf3 are significantly changed due to oral sodium intake and diuretics treatment in Nedd4–2 C2 KO mice. We successfully generated mice with cre+, Atf3 flox/flox mice for current experiments. Under normal salt diet, we could not find any significant differences between cre + and minus mice in terms of systolic blood pressure, water intake, urine volume, urinary sodium excretions, urinary pH, and urinary osmotic pressures using metabolic cage experiments. We found, under high salt intake, gene expressions of both classic renin and tubular alternative renin are significantly suppressed for 30 to 70% in KO mice by quantitative RT PCR and immunohistochemistry imaging.

Conclusions:
Tubular epithelial Atf3 genes are involved in regulations of renin gene expressions in accordance with intracellular Na ion concentrations. Therefore, there are possibilities that tubular specific Atf3 KO mice shows blood pressure change under various salt intake and diuretics treatment.
PS-BPC01-6: DEEP LEARNING IS USEFUL FOR THE PATHOLOGICAL ANALYSES OF HUMAN KIDNEY BIOPSY IMAGES
Authors: Matsui Isao , Matsumoto Ayumi , Imai Atsuhiro , Okushima Hiroki , Katsuma Yusuke , Yasuda Seiichi , Inoue Kazunori , Isaka Yoshitaka 
Published: January 2023

Objective:
The kidney plays a pivotal role in the maintenance of blood pressure. Non-neoplastic kidney biopsy images yield a great deal of diagnostic information, however, several studies have shown that there is room for improvement in pathological diagnostic reproducibility. Recently, deep learning has made major breakthroughs in various tasks. Therefore, we tried to analyze human kidney biopsy images using deep learning.

Design and Method:
We analyzed 5002 non-neoplastic kidney biopsy whole slide images (WSIs) obtained from 24 facilities in Japan using deep learning. Images of periodic acid-Schiff stained kidney sections were analyzed.

Results:
WSIs have billions of pixels, and deep neural networks (NNs) cannot accept such a huge image as an input. Therefore, we prepared 88 μm square 6,125,990 patch images (PIs) from the WSIs, and trained NNs with these PIs. We manually selected 259,682 typical PIs from the whole set of PIs, and annotated them into 56 classes. Using these annotated PIs, we trained EfficientNets B0-B7, whose network depth and width are carefully balanced for various input resolutions (224 to 600 pixels), and found that EfficientNetB4 (hereafter referred to CNN_Man) achieved the best F1 score. Using histological parameters obtained from renal biopsy reports made by nephrologists and pathologists at each facility, we confirmed the reliability of CNN_Man-based prediction. We also finely visualized histological features of WSIs based on CNN_Man prediction (Figure). In addition to these supervised histological analyses, we tried to extract disease features in a loosely supervised manner. In this loosely supervised learning, we tried to extract disease-related rather than histology-related glomerular features by training EfficientNetB4 using final diagnosis as true labels. It is noteworthy that the final-diagnosis-based training is not typical supervised learning because each disease class contains patch images with various histological features to varying degrees. We extracted glomerulus-related PIs by using CNN_Man, and then labeled these PIs into 20 final-diagnosis categories. EfficientNetB4 (hereafter CNN_Diag) was trained with the 20 class images in a 5-fold cross-validation manner. Using UMAP, we visualized the final layer parameters of CNN_Diag corresponding to each PI. This approach divided PIs from IgA nephropathy into many clusters, and each cluster reflected blood pressure, renal function, age, etc., even though they were not explicitly given as teacher labels.

Conclusions:
The analysis of kidney biopsy images using deep learning may be useful for the classification of renal diseases based on new perspectives.