bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of Computer Microscope Image Segmentation Model Based on Fourth-Order Partial Differential Equation Smoothing
Authors: Li Feng
Published: July 2022

In order to solve the problem of image noise, the author proposes a computer microscope image segmentation model based on the smoothing of fourth-order partial differential equations. On the basis of the functional describing the smoothness of the image by the directional curvature modulus, the author deduces a fourth-order partial differential equation (PDE) image noise reduction model, while effectively reducing noise, the edges are well preserved. The processing result of this method is a piecewise linear image, and there is a step in the gradient at the edge of the target. Taking advantage of this feature of the noise reduction results, the author proposes a new geodesic active contour model. The experimental results show that the reference method directly segments the results, iterates 10 times, and takes 160.721 seconds. Using the noise reduction model in the paper to preprocess and then using the reference method to segment the result, iterating 8 times, it takes 32.347 seconds. Conclusion. The new model is not only stable but also has strong contour extraction ability and fast convergence speed.
Serum Endocan Levels and Subclinical Atherosclerosis in Patients with Chronic Kidney and End-Stage Renal Diseases
Authors: El-Senosy Fatma M. , Abd El Aziz Rasha Elsayed Mohamed , Kasim Sammar Ahmed , Gad Lamia Abdulbary , Hassan Donia Ahmed , Sabry Seham , El mancy Ismail Mohamed , Shawky Taiseer Ahmed , Mohamed Ibrahim Ghounim Ramadan , Elmonier Rady , Kotb Essam , Abdul-Mohymen Abeer Mohammed
Published: July 2022

Background and Aim. Chronic kidney disease (CKD) and its final stage: end-stage renal disease (ESRD), are common clinical conditions. Endocan is a human endothelial cell-specific molecule produced by endothelial cells. Its production is related to activation of endothelium and angiogenesis. In this study, we assessed the relation between serum endocan levels and subclinical atherosclerosis (SCA) in CKD and hemodialysis (HD) patients. Subjects and Methods. The present case control study enrolled 30 patients on regular HD for at least 6 months, 30 patients with CKD, and 30 age and sex-matched healthy controls. All participants were subjected to careful history taking and thorough clinical examination. Laboratory investigations included complete blood count, kidney functions, and serum cholesterol, triglycerides, calcium, phosphorus, albumin, PTH, hsCRP, and endocan levels. Results. HD and CKD groups had significantly higher endocan levels when compared with control group (median (IQR): 519.0 (202.3–742.0) versus 409.0 (245.3–505.3) and 273.0 (168.0–395.5) ng/L, respectively). Also, HD patients had significantly higher endocan levels when compared with CKD levels. HD patients had significantly higher carotid intima-media thickness (CIMT) when compared with CKD patients (median (IQR): 0.80 (0.80–0.90) versus 0.75 (0.73–0.75) mm,

p
<
0.001

). HD patients had significantly higher frequency of SCA when compared with CKD patients (46.7% versus 13.3%,

p
=
0.005

). Patients with SCA had significantly higher hsCRP (median (IQR): 36.5 (26.8–43.5) versus 24.0 (15.8–29.0) mg/dl) and endocan levels (697.0 (528.3–974.8) versus 222.5 (158.8–565.8) ng/L) when compared with patients without SCA. ROC curve analysis of endocan for identification of SCA in HD patients showed that at a cutoff of 380.5 ng/L, endocan has an AUC of 0.862 with a sensitivity and specificity of 92.9% and 68.7%, respectively. Conclusions. Serum endocan levels are related to SCA in HD patients. In addition, it is associated with the hyperinflammatory state in those patients.
Estimating Daily Rice Crop Evapotranspiration in Limited Climatic Data and Utilizing the Soft Computing Algorithms MLP, RBF, GRNN, and GMDH
Authors: Aghelpour Pouya , Bahrami-Pichaghchi Hadigheh , Karimpour Farzaneh
Published: July 2022

Evapotranspiration represents the water requirement of plants during their growing season, and its accurate measurement at the farm is essential for agricultural water planners and managers. Field measurements of evapotranspiration have always been associated with many difficulties that have led researchers to seek a way to remotely measure this component in horticultural and agricultural areas. This study aims to investigate an indirect approach for daily rice crop evapotranspiration (ETc) measurement by machine learning (ML) techniques and the least available climatic variables. For this purpose, daily meteorological variables were obtained from three ground meteorological stations in rice cultivation regions of northern Iran during 2003–2016. The ETc rates were calculated by seven meteorological variables, the FAO‐56 Penman‐Monteith equation, and the regional calibrated rice crop coefficient and considered as the reference data. The MLs, including Multilayer Perceptron (MLP), Radial Basis Function (RBF), Generalized Regression Neural Network (GRNN), and Group Method of Data Handling (GMDH), were utilized for ETc modeling. Different input combinations were applied, based on the use of minimum effective variables as input. Results showed that the models showed the most accurate performances in the input combination of four climatic variables: sunshine duration, maximum temperature, relative humidity, and wind speed. Investigating the accuracy of models in rice growth phases showed that the least estimation error belonged to the initial growing stage, which increased during the mid‐season and late‐season growing stages. A comparison of the models showed that the GMDH model performed better against the other competitors. For this model, both the Nash‐Sutcliffe (NS) coefficient and R2 were greater than 0.98, and the Root Mean Square Error (RMSE) ranged between 0.214 and 0.234 mm per day in all stations. The current approach showed promising results in rice evapotranspiration modeling by only four common meteorological variables and can be reliably applied for indirect measurement of this variable over the rice farms. The studied approach will have research value for rice and other crops in similar/different climatic conditions.
Magnifying Chromoendoscopy with Flexible Spectral Imaging Color Enhancement, Indigo Carmine, and Crystal Violet in Predicting the Histopathology of Colorectal Polyps: Diagnostic Value in a Scare-Setting Resource
Authors: Pham Nguyen Binh , Vu Khanh Truong , Nguyen Nam Hoai , Doan Ha Thi-Ngoc , Tran Thanh Trung
Published: July 2022

Background and Aims. Virtual magnifying chromoendoscopy with flexible spectral imaging color enhancement (FICE), image-enhanced endoscopy techniques, and dye-staining magnifying chromoendoscopy (with Indigo carmine and Crystal violet) have contributed to better visualization of the pit pattern and vascular structure of colorectal polyp. Therefore, magnifying chromoendoscopy is capable of predicting the histopathological results of colorectal polyp without biopsy and remains their diagnostic values over time, especially in scare-setting resources. This study compared the images of magnifying chromoendoscopy between FICE, Indigo carmine, and Crystal violet and then assessed their diagnostic values based on colorectal polyps’ histopathology as a gold standard. Methods. A total of 332 polyps of 266 patients were endoscopically evaluated from June 2016 to September 2019. After identified by white light endoscopy, polyps continued to be evaluated by virtual magnifying chromoendoscopy (×50-150 times) with FICE. The capillary-vessel pattern was divided into 5 subtypes according to the number, morphology, and distribution of the fine blood vessels according to Teixeira classification. Next, they were stained with Indigo carmine 0.2% and then Crystal violet 0.05% and were classified according to Kudo’s pit pattern classification. Finally, polyps were resected by endoscopy or surgery and biopsy and compared with histopathological results of either neoplastic or nonplastic polyp. Results. The number of neoplastic polyps was 278/332 with 231 adenoma polyps and 47 carcinoma polyps. Magnifying chromoendoscopy has high sensitivity and accuracy when compared with the histopathological results of colorectal polyps. The sensitivity, specificity, and accuracy of magnifying chromoendoscopy with Crystal violet are 97.2%, 72.2%, and 93.0%; with Indigo carmine are 96.0%, 72.2%, and 92.1%; and with FICE are 92.1%, 68.5%, and 88.3%.Conclusions. Among the three methods, Crystal violet has the highest sensitivity and accuracy in predicting histopathological results of colorectal polyps. FICE has shown its diagnostic value with reliable sensitivity and accuracy and should still be a reasonable endoscopic choice for physicians in scare-setting resources regardless its moderate specificity. Physicians should base on their facility and capability to determine an appropriate endoscopy technique.
HSPA5 Inhibitor Meliorate DSS-Induced Colitis through HSPA1A/CHIP
Authors: Gao Fei , Fan Heng , Xue Linping , Shou Zhexing , Zhu Feng , Yu Ting , Chu Si , Wei Chunzhu , Liu Chang , Zuo Dongbo , Zuo Dongmei
Published: July 2022

Objective. Ulcerative colitis (UC) is closely related to immune response, in which Treg cells (Tregs) suppress the autoimmune response of effector T cells to maintain homeostasis. As a marker of endoplasmic reticulum stress (ERS), HSPA5 was highly expressed in the colon tissue of UC patients. This study is aimed at evaluating the therapeutic effect of HSPA5 inhibitor (HA15) on dextran sulfate sodium- (DSS-) induced ulcerative colitis in mice and explored the effect and related mechanism of HSPA5 inhibitor on the differentiation and function of Tregs. Methods. Thirty-two C57BL/6 mice were randomly divided into four groups (8 mice per group): normal control group, DSS model group, HSPA5 inhibitor (HA15) group (intraperitoneal injection), and dexamethasone (DXM) group (intraperitoneal injection). Except for the blank control group, the other groups were induced with 3% DSS for 7 days and then given corresponding intervention therapy for 7 days. Results. The disease activity index (DAI) score, colon length, histopathological changes, and scores of DSS-induced mice show that HA15 could significantly improve the degree of inflammation in ulcerative colitis. Moreover, HA15 can better inhibit the expression of HSPA5, HSPA1A, and CHIP in the colon and increase the level of FOXP3 mRNA. Finally, the content of Treg cells and the levels of IL-10 and TGF-β1 were significantly increased, and the levels of IL-6 were significantly reduced. Conclusions. HA15 can improve the differentiation and function of Treg cells by inhibiting the HSPA1A/CHIP pathway, thereby improving ulcerative colitis. Therefore, inhibiting the expression of HSPA5 may serve as a new approach to treat ulcerative colitis.
Analysis of Cryptocurrency Market by Using q‐Rung Orthopair Fuzzy Hypersoft Set Algorithm Based on Aggregation Operators
Authors: Khan Salma , Gulistan Muhammad , Kausar Nasreen , Kousar Sajida , Pamucar Dragan , Addis Gezahagne Mulat
Published: July 2022

One of the most important innovations brought by digitization is the cryptocurrency, also called virtual or digital currency, which has been discussed in recent years and in particular is a new platform for investors. Different types of cryptocurrencies such as Bitcoin, Ethereum, Binance Coin, and Tether do not depend on a central authority. Decision making is complicated by categorization and transmission of uncertainty, as well as verification of digital currency. The weighted average and weighted geometric aggregation operators are used in this article to define a multi‐attribute decision‐making approach. This work investigates the uniqueness of q‐rung orthopair fuzzy hypersoft sets (q‐ROFHSS), which respond to instabilities, uncertainty, ambiguity, and imprecise information. This research also covers some fundamental topics of q‐ROFHSS. The model offered here is the best option for learning about electronic currency. This study validates the complexity of decision‐making problems with different attributes and subattributes to obtain an optimal choice. We conclude that Bitcoin has a diverse set of applications and that crypto assets are well positioned to become an important asset class in decision making.
Analysis and Research on the Rehabilitation Effect of Physical Exercise on College Students’ Mental Depression Based on Multidimensional Data Mining
Authors: Zou Wen
Published: July 2022

In order to explore the physical exercise and psychological changes of college students, this study adopts the method of multidimensional data mining, taking 23,146 undergraduates from a university in Guangzhou, Guangdong Province, as the research object. On the basis of summarizing and analyzing the previous research literature, this study expounds the development background, current situation, and future challenges of multidimensional data mining technology. This paper introduces the methods and principles of sample selection and multidimensional assessment of the physical and mental depression of college students, analyzes the physical health status of college students, summarizes the psychological changes of college students before and after the intervention, and discusses the relationship between physical exercise and mental health of college students. In addition, this paper analyzes the influencing factors and psychological changes of college students’ physical exercise and puts forward suggestions for improving the physical and mental health of college students. The results of this study show that with increasing age, college students have a lower risk of moderate anxiety and mild depression; girls are more prone to mild depression than boys; rural college students are more prone to mild, moderate anxiety; college students with nonmedical backgrounds were more likely to experience moderate anxiety than college students with medical backgrounds. During the intervention control period, continuous connection with others may encourage college students to actively use internal resources to actively cope with obstacles and setbacks, and as a protective factor, psychological resilience can appropriately weaken the association between risk factors in life and anxiety and relieve anxiety. The results of this study can provide a reference for further research on the physical exercise and psychological changes of college students.
Design and Application of Smart City Internet of Things Service Platform Based on Fuzzy Clustering Algorithm
Authors: Yin Qi
Published: July 2022

The development of the city is dependent on various information technologies, the core of which is the Internet of Things technology. The traditional multisource information collaboration mode of urban system is relatively single, with low collaboration efficiency and lack of effective measurement of collaboration structure. In this paper, a design scheme of IoT (Internet of Things) service platform for smart cities is proposed, and a multisource information collaborative difference measurement model with a given confidence interval is constructed based on a fuzzy clustering algorithm to meet the needs of developing IoT energy management application services and “smart city” energy management in different environments. In the experiment of participating in the fusion, the number of participating nodes is reduced to about 50 from the third iteration, which is reduced by half. In the traditional algorithm, almost all nodes participate in every fusion process. However, the improved algorithm can greatly reduce the number of participating nodes, thus greatly reducing the computational requirements of the algorithm. The experimental results show that the fuzzy clustering algorithm is effective. The system can be used in vehicle networking, geological disaster prevention, environmental monitoring, and other fields.
Making Hematochezia of Unknown Origin Known: A Retrospective Analysis
Authors: Tanaka Takanao , Tominaga Keiichi , Yamamiya Akira , Sugaya Takeshi , Kanazawa Mimari , Kondo Masayuki , Abe Keiichiro , Kanamori Akira , Iijima Makoto , Goda Kenichi , Haruyama Yasuo , Irisawa Atsushi
Published: July 2022

Introduction: Hematochezia is observed frequently in daily practice. However, natural hemostasis often prevents identification of the bleeding source during observations. This study was conducted to clarify risk factors related to rebleeding in hematochezia patients without an identified cause of bleeding. Methods: We analyzed patients who were admitted to Dokkyo Medical University Hospital during April 1, 2009, through March 31, 2015, with the chief complaint of hematochezia. Main outcome measures included the rebleeding rate and the period until rebleeding in hematochezia patients without an identified bleeding source. Results: We selected 159 patients for analyses. Rebleeding was observed in 46 (28.9%) of 159 patients. The median period until first rebleeding was 166 days (2–3,046 days). Univariate analysis indicated that risk factors for rebleeding were male gender (p = 0.029), higher age (p = 0.023), antithrombotic medicines (p = 0.047), lower hemoglobin on admission (p = 0.024), and the presence of diverticula (p = 0.002). Multivariate analysis indicated the presence of diverticula (p = 0.023) and male gender (p = 0.043) as rebleeding risk factors. Discussion/Conclusion: In patients with hematochezia of unknown origin, risk factors for rebleeding indicated in this study, especially the presence of diverticula and male gender, should be given particular attention by physicians.
Longitudinal Changes in Cardiac Structure and Function in Pediatric Kidney Transplant Recipients
Authors: de Verteuil Isabel , Fitzpatrick Jessica , Alvarez Elias Ana Catalina , Banh Tonny , Vasilevska-Ristovska Jovanka , Browne Jordan , Bondi Bianca C. , Hui Wei , Slorach Cameron , Wei Teoh Chia , Langlois Valerie , Mertens Luc , Parekh Rulan S.
Published: July 2022

Background:

Cardiovascular disease results in increased morbidity and mortality in pediatric kidney transplant recipients. Longitudinal changes in cardiac structure and function and the association with blood pressure control over time in pediatric kidney transplant recipients are unknown.

Methods:

To determine the influence of blood pressure control on cardiac changes following pediatric kidney transplant, we conducted a retrospective cohort study of children who received their first kidney transplant at the Hospital for Sick Children from 2004 to 2015. Children were followed until transfer to adult care or censoring in July 2018. Cardiac structure and function parameters were collected from clinical echocardiograms and assessed using standardized scores. Blood pressure control was determined by systolic blood pressure
Z
scores (above or below the 90th percentile) in combination with antihypertensive medications. A segmented mixed-effects model assessed
Z
scores of interventricular septum thickness, left ventricular end-diastolic dimension, and left ventricular posterior wall dimension.

Results:

Of 142 children included, 58% were men, mean age at transplant was 11 (±4.5) years, and average follow-up time was 4 (±3) years. All cardiac structural
Z
scores improved during follow-up. Interventricular septum thickness normalized at 4.0 years post-transplant. Left ventricular end-diastolic dimension normalized at 1.5 years post-transplant. Left ventricular posterior wall dimension normalized at 6.3 years post-transplant. Left ventricular mass index showed sustained improvement up to 12 years post-transplant. Individuals with uncontrolled blood pressure had increased left ventricular mass (β=2.97 [95% CI, 0.77–5.16]).

Conclusions:

Cardiac structural abnormalities improve following kidney transplantation and normalize within 7 years, especially with controlled blood pressure. Strict blood pressure control is critical after pediatric kidney transplantation.
Identification of a Gut Commensal That Compromises the Blood Pressure-Lowering Effect of Ester Angiotensin-Converting Enzyme Inhibitors
Authors: Yang Tao , Mei Xue , Tackie-Yarboi Ethel , Akere Millicent Tambari , Kyoung Jun , Mell Blair , Yeo Ji-Youn , Cheng Xi , Zubcevic Jasenka , Richards Elaine M. , Pepine Carl J. , Raizada Mohan K. , Schiefer Isaac T. , Joe Bina
Published: July 2022

Background:

Despite the availability of various classes of antihypertensive medications, a large proportion of hypertensive individuals remain resistant to treatments. The reason for what contributes to low efficacy of antihypertensive medications in these individuals is elusive. The knowledge that gut microbiota is involved in pathophysiology of hypertension and drug metabolism led us to hypothesize that gut microbiota catabolize antihypertensive medications and compromised their blood pressure (BP)-lowering effects.

Methods and Results:

To test this hypothesis, we examined the BP responses to a representative ACE (angiotensin-converting enzyme) inhibitor quinapril in spontaneously hypertensive rats (SHR) with or without antibiotics. BP-lowering effect of quinapril was more pronounced in the SHR+antibiotics, indicating that gut microbiota of SHR lowered the antihypertensive effect of quinapril. Depletion of gut microbiota in the SHR+antibiotics was associated with decreased gut microbial catabolism of quinapril as well as significant reduction in the bacterial genus
Coprococcus
.
C. comes
, an anaerobic species of
Coprococcus
, harbored esterase activity and catabolized the ester quinapril in vitro. Co-administration of quinapril with
C. comes
reduced the antihypertensive effect of quinapril in the SHR. Importantly,
C. comes
selectively reduced the antihypertensive effects of ester ramipril but not nonester lisinopril.

Conclusions:

Our study revealed a previously unrecognized mechanism by which human commensal
C. comes
catabolizes ester ACE inhibitors in the gut and lowers its antihypertensive effect.
Effects of Blood Pressure According to Age on End-Stage Renal Disease Development in Patients With Diabetes: A Nationwide Population-Based Cohort Study
Authors: Bae Eun Hui , Lim Sang Yeob , Kim Bongseong , Oh Tae Ryom , Song Su Hyun , Suh Sang Heon , Choi Hong Sang , Yang Eun Mi , Kim Chang Seong , Ma Seong Kwon , Han Kyung-Do , Kim Soo Wan
Published: July 2022

Background:

Recent hypertension guidelines have recommended lower blood pressure (BP) targets in high-risk patients. However, there are no specific guidelines based on age or systolic and diastolic blood pressure (SBP and DBP, respectively). We aimed to assess the effects of age-related BP on development of end-stage renal disease (ESRD) in patients with diabetes.

Methods:

A total of 2 563 870 patients with diabetes aged >20 years were selected from the Korean National Health Screening Program from 2009 to 2012 and followed up until the end of 2019. Participants were categorized into age and BP groups, and the hazard ratios for ESRD were calculated.

Results:

During a median follow-up of 7.15 years, the incidence rates of ESRD increased with increasing SBP and DBP. The hazard ratio for ESRD was the highest in patients younger than 40 years of age with DBP≥100 mm Hg. The effect of SBP and DBP on ESRD development was attenuated with age (interaction
P
was <0.0001 for age and SBP, and 0.0022 for age and DBP). The subgroup analysis for sex, antihypertension medication, and history of chronic kidney disease showed higher hazard ratios for ESRD among males, younger than 40 years, not taking antihypertension medications and chronic kidney disease compared to those among females, older than 40 years, antihypertension medication, and nonchronic kidney disease groups.

Conclusions:

Higher SBP and DBP increase the risk of developing ESRD in patients with diabetes, and in particular, younger individuals face greater risk. Therefore, intensive BP management is warranted in younger patients to prevent ESRD.
Evidence From Human Placenta, Endoplasmic Reticulum–Stressed Trophoblasts, and Transgenic Mice Links Transthyretin Proteinopathy to Preeclampsia
Authors: Cheng Shibin , Huang Zheping , Banerjee Sayani , Jash Sukanta , Buxbaum Joel N. , Sharma Surendra
Published: July 2022

Background:

We have demonstrated that protein aggregation plays a pivotal role in the pathophysiology of preeclampsia and identified several aggregated proteins in the circulation of preeclampsia patients, the most prominent of which is the serum protein TTR (transthyretin). However, the mechanisms that underlie protein aggregation remain poorly addressed.

Methods:

We examined TTR aggregates in hypoxia/reoxygenation-exposed primary human trophoblasts (PHTs) and the preeclampsia placenta using complementary approaches, including a novel protein aggregate detection assay. Mechanistic analysis was performed in hypoxia/reoxygenation-exposed PHTs and
Ttr
transgenic mice overexpressing transgene-encoded wild-type human TTR or
Ttr
−/−
mice. High-resolution ultrasound analysis was used to measure placental blood flow in pregnant mice.

Results:

TTR aggregation was inducible in PHTs and the TCL-1 trophoblast cell line by endoplasmic reticulum stress inducers or autophagy-lysosomal disruptors. PHTs exposed to hypoxia/reoxygenation showed increased intracellular BiP (binding immunoglobulin protein), phosphorylated IRE1α (inositol-requiring enzyme-1α), PDI (protein disulfide isomerase), and Ero-1, all markers of the unfolded protein response, and the apoptosis mediator caspase-3. Blockade of IRE1α inhibited hypoxia/reoxygenation-induced upregulation of Ero-1 in PHTs. Excessive unfolded protein response activation was observed in the early-onset preeclampsia placenta. Importantly, pregnant human TTR mice displayed aggregated TTR in the junctional zone of the placenta and severe preeclampsia-like features. High-resolution ultrasound analysis revealed low blood flow in uterine and umbilical arteries in human TTR mice compared with control mice. However,
Ttr
−/−
mice did not show any pregnancy-associated abnormalities.

Conclusions:

These observations in the preeclampsia placenta, cultured trophoblasts, and
Ttr
transgenic mice indicate that TTR aggregation is an important causal contributor to preeclampsia pathophysiology.
Isolated Diastolic Hypertension and Risk of Cardiovascular Disease: Controversies in Hypertension - Pro Side of the Argument
Authors: Yano Yuichiro , Kim Hyeon Chang , Lee Hokyou , Azahar Nazar , Ahmed Sabrina , Kitaoka Kaori , Kaneko Hidehiro , Kawai Fujimi , Mizuno Atsushi , Viera Anthony J.
Published: July 2022

Isolated diastolic hypertension (IDH), defined as diastolic blood pressure in the hypertensive range but systolic blood pressure not in the hypertensive range, is not uncommon (<20%) among adults with hypertension. IDH often manifests in concurrence with other cardiovascular risk factors. Individuals with IDH tend to have lower awareness of their hypertension compared with those with both systolic and diastolic hypertension. IDH appears to be a largely underrated risk factor for cardiovascular disease events, which may be explained by inconsistent association of IDH with cardiovascular disease events. The inconsistency suggests that IDH is heterogeneous. One size does not seem to fit all in the clinical management of individuals with IDH. Rather than treating IDH as a monolithic low-risk condition, detailed phenotyping in the context of individual comprehensive cardiovascular risk would seem to be most useful to assess an individual’s expected net benefit from therapy. In this review, we highlight that the clinical relevance of IDH differs by individual clinical characteristics, and elucidate groups of individuals with IDH that should be wary of cardiovascular disease risks.
Cathepsin K Deficiency Prevented Kidney Damage and Dysfunction in Response to 5/6 Nephrectomy Injury in Mice With or Without Chronic Stress
Authors: Yue Xueling , Piao Limei , Wang Hailong , Huang Zhe , Meng Xiangkun , Sasaki Takeshi , Inoue Aiko , Nakamura Kae , Wan Ying , Xu Shengnan , Shi Guo-Ping , Kim Weon , Murohara Toyoaki , Kuzuya Masafumi , Cheng Xian Wu
Published: July 2022

Background:

Chronic psychological stress is a risk factor for kidney disease, including kidney dysfunction and hypertension. Lysosomal CatK (cathepsin K) participates in various human pathobiologies. We investigated the role of CatK in kidney remodeling and hypertension in response to 5/6 nephrectomy injury in mice with or without chronic stress.

Methods:

Male 7-week-old WT (wild type; CatK
+/+
) and CatK-deficient (CatK
−/−
) mice that were or were not subjected to chronic stress underwent 5/6 nephrectomy. At 8 weeks post-stress/surgery, the stress was observed to have accelerated injury-induced glomerulosclerosis, proteinuria, and blood pressure elevation.

Results:

Compared with the nonstressed mice, the stressed mice showed increased levels of TLR (Toll-like receptor)-2/4, p22
phox
, gp91
phox
, CatK, MMP (matrix metalloproteinase)-2/9, collagen type I and III genes, PPAR-γ (peroxisome proliferator-activated receptor-gamma), NLRP-3 (NOD-like receptor thermal protein domain associated protein 3), p21, p16, and cleaved caspase-8 proteins, podocyte foot process effacement, macrophage accumulation, apoptosis, and decreased levels of Bcl-2 (B cell lymphoma 2) and Sirt1, as well as decreased glomerular desmin expression in the kidneys. These harmful changes were retarded by the genetic or pharmacological inhibition of CatK. Consistently, CatK inhibition ameliorated 5/6 nephrectomy–related kidney injury and dysfunction. In mesangial cells, CatK silencing or overexpression, respectively, reduced or increased the PPAR-γ and cleaved caspase-8 protein levels, providing evidence and a mechanistic explanation of CatK’s involvement in PPAR-γ/caspase-8–mediated cell apoptosis in response to superoxide and stressed serum.

Conclusions:

These results demonstrate that CatK plays an essential role in kidney remodeling and hypertension in response to 5/6 nephrectomy or stress, possibly via a reduction of glomerular inflammation, apoptosis, and fibrosis, suggesting a novel therapeutic strategy for controlling kidney injury in mice under chronic psychological stress conditions.
SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients
Authors: Mone Pasquale , Varzideh Fahimeh , Jankauskas Stanislovas S. , Pansini Antonella , Lombardi Angela , Frullone Salvatore , Santulli Gaetano
Published: July 2022

Background:

Frailty is a multidimensional condition often diagnosed in older adults with hypertension and diabetes, and both these conditions are associated with endothelial dysfunction and oxidative stress. We investigated the functional role of the SGLT2 (sodium glucose cotransporter 2) inhibitor empagliflozin in frail diabetic and hypertensive older adults.

Methods:

We studied the effects of empagliflozin in consecutive hypertensive and diabetic older patients with frailty presenting at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, from March 2021 to January 2022. Moreover, we performed in vitro experiments in human endothelial cells to measure cell viability, permeability, mitochondrial Ca
2+
, and oxidative stress.

Results:

We evaluated 407 patients; 325 frail elders with diabetes successfully completed the study. We propensity-score matched 75 patients treated with empagliflozin and 75 with no empagliflozin. We observed a correlation between glycemia and Montreal Cognitive Assessment (MoCA) score and between glycemia and 5-meter gait speed (5mGS). At 3-month follow-up, we detected a significant improvement in the MoCA score and in the 5mGS in patients receiving empagliflozin compared with non-treated subjects. Mechanistically, we demonstrate that empagliflozin significantly reduces mitochondrial Ca
2+
overload and reactive oxygen species production triggered by high glucose in human endothelial cells, attenuates cellular permeability, and improves cell viability in response to oxidative stress.

Conclusions:

Taken together, our data indicate that empagliflozin reduces frailty in diabetic and hypertensive patients, most likely by decreasing the mitochondrial generation of reactive oxygen species in endothelial cells.
Racial and Ethnic Disparities in Incidence and Prognosis of Perioperative Stroke Among Pediatric Cardiac Transplant Recipients
Authors: Lehman Laura L. , Mostofsky Elizabeth , Salia Soziema , Gupta Suruchi , Barrera Francisco J. , Liou Lathan , Mittleman Murray A.
Published: July 2022

Background

In the general population, Black children have a higher incidence of stroke and all‐cause mortality after stroke than White children. Beginning 6 months following cardiac transplantation, Black children have higher mortality than White children. However, whether there are racial and ethnic disparities in incidence and all‐cause mortality following perioperative stroke among pediatric cardiac transplant recipients is unknown.

Methods and Results

Using the Scientific Registry of Transplant Recipients, we studied children who underwent their first heart transplant in the United States between January 1994 and September 2019. Using multivariable logistic regression, we assessed the association between race and ethnicity and perioperative stroke. We used multivariable piecewise Cox regression to examine the association between race and ethnicity and mortality among survivors of perioperative stroke. Among 8224 children who had a first cardiac transplant, 255 (3%) had a perioperative stroke. Black children had 32% lower odds of perioperative stroke compared with White children (adjusted odds ratio, 0.68 [95% CI, 0.46–0.996]). Following perioperative stroke, mortality rates were similar for Black and White children in the first 6 months (adjusted hazard ratio [HR], 0.99 [95% CI, 0.44–2.26]). However, Black children had a higher mortality rate than White children beyond 6 months (adjusted HR, 3.36 [95% CI, 1.22–9.22]).

Conclusions

Among pediatric cardiac transplant recipients, Black children have a lower incidence of perioperative stroke than White children. Among survivors of perioperative stroke, mortality is initially similar by race and ethnicity, but beyond 6 months, Black children have over a 3‐fold higher mortality rate than White children. Identifying and intervening on potential differences in care is essential to addressing these disparities.
Effect of
NOTCH3
EGFr Group, Sex, and Cardiovascular Risk Factors on CADASIL Clinical and Neuroimaging Outcomes
Authors: Hack Remco J. , Cerfontaine Minne N. , Gravesteijn Gido , Tap Stephan , Hafkemeijer Anne , van der Grond Jeroen , Witjes-Ané Marie-Noëlle , Baas Frank , Rutten Julie W. , Lesnik Oberstein Saskia A.J.
Published: July 2022

Background:

A retrospective study has shown that EGFr (epidermal growth factor–like repeat) group in the
NOTCH3
gene is an important cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) disease modifier of age at first stroke and white matter hyperintensity (WMH) volume. No study has yet assessed the effect of other known CADASIL modifiers, that is, cardiovascular risk factors and sex, in the context of
NOTCH3
EGFr group. In this study, we determined the relative disease-modifying effects of
NOTCH3
EGFr group, sex and cardiovascular risk factor on disease severity in the first genotype-driven, large prospective CADASIL cohort study, using a comprehensive battery of CADASIL clinical outcomes and neuroimaging markers.

Methods:

Patients with CADASIL participated in a single-center, prospective cohort study (DiViNAS [Disease Variability in NOTCH3 Associated Small Vessel Disease]) between 2017 and 2020. The study protocol included a clinical assessment, neuropsychological test battery and brain magnetic resonance imaging on a single research day. Multivariable linear, logistic and Cox regression models were used to cross-sectionally assess the effect of CADASIL modifiers on clinical severity (stroke, disability, processing speed) and neuroimaging markers (WMH volume, peak width of skeletonized mean diffusivity, lacune volume, brain volume, cerebral microbleed count).

Results:

Two hundred patients with CADASIL participated, of which 103 harbored a
NOTCH3
EGFr 1–6 variant and 97 an EGFr 7–34 variant.
NOTCH3
EGFr 1–6 group was the most important modifier of age at first stroke (hazard ratio, 2.45 [95% CI, 1.39–4.31];
P
=0.002), lacune volume (odds ratio, 4.31 [95% CI, 2.31–8.04];
P
=4.0×10
-6
), WMH volume (B=0.81 [95% CI, 0.60–1.02];
P
=1.1×10
-12
), and peak width of skeletonized mean diffusivity (B=0.65 [95% CI, 0.44–0.87];
P
=1.6×10
-8
). EGFr 1–6 patients had a significantly higher WMH volume in the anterior temporal lobes and superior frontal gyri and a higher burden of enlarged perivascular spaces. After
NOTCH3
EGFr group, male sex and hypertension were the next most important modifiers of clinical outcomes and neuroimaging markers.

Conclusions:

NOTCH3
EGFr group is the most important CADASIL disease modifier not only for age at first stroke and WMH volume but also strikingly so for a whole battery of clinically relevant disease measures such as lacune volume and peak width of skeletonized mean diffusivity.
NOTCH3
EGFr group is followed in importance by sex, hypertension, diabetes, and smoking.
Texture Features of Magnetic Resonance Images Predict Poststroke Cognitive Impairment: Validation in a Multicenter Study
Authors: Betrouni Nacim , Jiang Jiyang , Duering Marco , Georgakis Marios K. , Oestreich Lena , Sachdev Perminder S. , O’Sullivan Michael , Wright Paul , Lo Jessica W. , Bordet Régis ,   on behalf of the Stroke and Cognition (STROKOG) Collaboration
Published: July 2022

Background:

Imaging features derived from T1-weighted (T1w) images texture analysis were shown to be potential markers of poststroke cognitive impairment, with better sensitivity than atrophy measurement. However, in magnetic resonance images, the signal distribution is subject to variations and can limit transferability of the method between centers. This study examined the reliability of texture features against imaging settings using data from different centers.

Methods:

Data were collected from 327 patients within the Stroke and Cognition Consortium from centers in France, Germany, Australia, and the United Kingdom. T1w images were preprocessed to normalize the signal intensities and then texture features, including first- and second-order statistics, were measured in the hippocampus and the entorhinal cortex. Differences between the data led to the use of 2 methods of analysis. First, a machine learning modeling, using random forest, was used to build a poststroke cognitive impairment prediction model using one dataset and this was validated on another dataset as external unseen data. Second, the predictive ability of the texture features was examined in the 2 remaining datasets by ANCOVA with false discovery rate correction for multiple comparisons.

Results:

The prediction model had a mean accuracy of 90% for individual classification of patients in the learning base while for the validation base it was ≈ 77%. ANCOVA showed significant differences, in all datasets, for the kurtosis and inverse difference moment texture features when measured in patients with cognitive impairment and those without.

Conclusions:

These results suggest that texture features obtained from routine clinical MR images are robust early predictors of poststroke cognitive impairment and can be combined with other demographic and clinical predictors to build an accurate prediction model.
Defining “Cosmology” in the Early Modern System of Knowledge, 1530–1621
Authors: Tessicini Dario
Published: July 2022

This article seeks to revise the common scholarly assumption that in early modern Europe there was no single word for the study of the universe as a whole until the word “cosmology” appeared in Christian Wolff’s Cosmologia generalis methodo scientifica pertractata (1731). In fact, the term “cosmology” had circulated in both Latin and European languages since at least the 1530s in the context of critical appraisals of the largely dominant Aristotelian and scholastic frameworks. The aim of this study is to unearth the earliest attempts to define cosmology as a philosophical discipline and, thereby, to highlight the lasting authority of traditional disciplinary boundaries.
Resources of Intellectual Legitimacy in Italian Cosmological Affairs: Cremonini and Bellarmine’s Authority Conflict (c.1616)
Authors: Omodeo Pietro Daniel
Published: July 2022

This essay deals with two seventeenth-century intellectuals, the Aristotelian philosopher at Padua, Cesare Cremonini, and the Jesuit controversist, Robert Bellarmine. In the years of the cosmological affair of 1616, both defended their cosmological conceptions by relying on the principle of authority. However, they embraced different sources of legitimation in matters of natural philosophy. While the Padua professor stick to (what he considered to be) the letter of Aristotle, basically a secular interpretation of his world conception, Cardinal and Inquisitor Bellarmine understood the cosmos against a theological background. In particular, Bellarmine subordinated natural philosophy to exegesis and the authority of the Scriptures, and this allowed him to depart from Aristotle to some extent (for instance on the fluidity and possibly the corruptibility of the heavens). Yet, the two thinkers also shared the criticism of the major astronomical novelty of their time, namely the planetary system of Copernicus and his followers. But their objections rested on different worldviews and authorities (Aristotle and the Scriptures, respectively). Cremonini also supported a vision of celestial animation which was received with much preoccupation by religious authorities as they feared that his views might revive forms of astral worshipping. This essay discusses the manner in which Cremonini and Bellarmine received geocentrism and cosmology in very different, even opposite, manners, especially concerning the relation between natural philosophy and theology, and the reconcilability of cosmology with the Scriptures.
Discussing Tides Before and After Newton: Roger Joseph Boscovich’sDe aestu maris
Authors: Akopyan Ovanes
Published: July 2022

The causes of tidal motions were widely debated from antiquity up to the eighteenth century. These discussions got a second wind in the early modern period, in the wake of a growing number of cosmological alternatives that challenged the dominant Aristotelian-Ptolemaic stance. The 1687 publication of Isaac Newton’s Principia Mathematica was a defining moment in the discussions and consequently made universal gravitation the most credible and generally accepted explanation. This paper investigates the aftermath of Newton’s discovery and demonstrates how his understanding of tidal motion crowded out competing theories within a broader European context. My main point of reference is Roger Boscovich’s De aestu maris (1747). In his work, the leading Jesuit scholar of the time contrasted Newton’s interpretation to those of other major authorities, namely Johannes Kepler, Galileo Galilei, and René Descartes, and went on to claim the superiority of the British scientist’s achievements over anything written prior to the Principia. As this essay argues, alongside a significant body of literature produced under the umbrella of the Jesuit order, Boscovich’s De aestu maris subsequently contributed to the formation of the popular image of Newton as a “scientific hero.”
Slowing Down Society? Theoretical Reflections on Social Deceleration in Pandemic Times (and Beyond)
Authors: Torres Felipe , Gros Alexis
Published: July 2022

The COVID-19 pandemic has caused a major change in everyday life and also reinvigorated the theoretical and political discussion on the temporal rhythms of social existence. Taking the situation of the coronavirus crisis as a starting point, the present paper attempts to provide the outlines of a theoretical account of social deceleration, a topic that has been hitherto barely explored in the field of social studies of time. In view of the complexity of the phenomenon, a distinction is made between two ways of theoretically approaching it, namely, a descriptive and a normative perspective. The paper proceeds in three steps: First, upon adopting a descriptive perspective, it advances a definition of social deceleration and proposes a typology of its different manifestations. The second step analyzes the coronavirus crisis as a process of partial deceleration of social life. The final step gives an overview of the current normative, i.e., ethical-political, disputes over social speed.
Calendar Poems: Variances in Vernacular Versified Calendars as Expressions of Individual Perceptions of Time
Authors: DuBois Raoul
Published: July 2022

Cisiojanus is what we call a medieval mnemonic device designed to provide temporal orientation by transforming the sequence of immovable religious feast days into a short and memorable poem. Mapping the sacred calendar onto a textual surface enabled its user to determine dates by counting the poem’s syllables, words or lines. As an integral part of elementary education, the cisiojanus is believed to have been one of the most popular poems of the Middle Ages. It survived in hundreds of copies all over Europe and was translated into numerous languages. While the cisiojanus formed what could be one of the largest premodern, text-based temporal communities, it also adapted to the requirements of its users, leading to an astonishing amount of nearly identical, yet significally different poems. This article explores different cisiojani as individual perspectives on time. While some make adjustments for regional and local variants of the calendar, some even bear witness to personal interpretations of the calendar.
Praying in the Streets: Re-Traditionalisation of Public Spaces in Contemporary Spain
Authors: Chanzà Josep Almudéver
Published: July 2022

This paper contributes to the scant ethnographic literature dedicated to understanding the phenomenon of re-sacralisation. The article appraises lay Catholics’ lived experiences of everyday religion, charting the demographic dynamics and social and spiritual demands of those who are revitalising public expressions of Catholicism on the ground. Through theoretical frameworks that foreground memory, identity and gender, the fate and work of lay Catholic organisations is explored vis-à-vis priestly notions of faith. The current return and reinvention of Catholic traditions in Spain is explored through ethnographic study, seeking the reasons for the return and reinvention of Catholic festive traditions and asking what this phenomenon means when the faithful devise their own modes of devotion and faith-based identity away from priestly demands.