bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid improvement of lake acid–base status in Atlantic Canada following steep decline in precipitation acidity
Authors: Houle Daniel , Augustin Fougère , Couture Suzanne 
Published: July 2022

Policy measures resulted in reductions in acidic emission of sulfur and nitrogen in North America. Here, we conducted trend analyses on a 37-year database for atmospheric depositions and lake ( n = 78) chemistry in the provinces of Nova Scotia, New Brunswick, and Newfoundland and Labrador, in Canada. Sulfate, and particularly nitrate deposition, began to decrease strongly around the year 2000, resulting in strong pH increases in precipitation. Recovery was observed in most lakes with significant increases in pH and Gran alkalinity (AlcG). A piecewise regression approach detected coherent breaks and overlapping confidence intervals in the break years for precipitation pH and lake AlcG (to a lesser extent for lake pH), suggesting a rapid lake response to the sudden changes in acidic inputs. However, an increase in organic acid after 2000 decreases the rate of acid neutralizing capacity recovery nearly by half in about a third of the studied lakes. Despite the positive pH and AlcG trends, a significant proportion of lakes still have pH and calcium values below the recommended thresholds for aquatic life.
$$H_0$$ tension or M overestimation?
Authors: Mazo Brayan Yamid Del Valle , Romano Antonio Enea , Quintero Maryi Alejandra Carvajal 
Published: July 2022

AbstractThere is a strong discrepancy between the value of the Hubble parameter $$H_0^P$$

H
0
P

obtained from large scale observations such as the Planck mission, and the small scale value $$H_0^R$$

H
0
R

, obtained from low redshift supernovae (SNe). The value of the absolute magnitude $$M^{Hom}$$

M

Hom

used as prior in analyzing observational data is obtained from low-redshift SNe, assuming a homogeneous Universe, but the distance of the anchors used to calibrate the SNe to obtain M would be affected by a local inhomogeneity, making it inconsistent to test the Copernican principle using $$M^{Hom}$$

M

Hom

, since M estimation itself is affected by local inhomogeneities. We perform an analysis of the luminosity distance of low redshift SNe, using different values of M, $$\{M^P,M^R\}$$

{

M
P

,

M
R

}

, corresponding to different values of $$H_0$$

H
0

, $$\{H_0^P,H_0^R\}$$

{

H
0
P

,

H
0
R

}

, obtained from the model independent consistency relation between $$H_0$$

H
0

and M which can be derived from the definition of the distance modulus. We find that the value of M can strongly affect the evidence of a local inhomogeneity. We analyze data from the Pantheon catalog, finding no significant statistical evidence of a local inhomogeneity using the parameters $$\{M^R,H_0^R\}$$

{

M
R

,

H
0
R

}

, confirming previous studies, while with $$\{M^P,H_0^P\}$$

{

M
P

,

H
0
P

}

we find evidence of a small local void, which causes an overestimation of $$M^R$$

M
R

with respect to $$M^P$$

M
P

. An inhomogeneous model with the parameters $$\{M^P,H_0^P\}$$

{

M
P

,

H
0
P

}

fits the data better than a homogeneous model with $$\{M^R,H_0^R\}$$

{

M
R

,

H
0
R

}

, resolving the apparent $$H_0$$

H
0

tension. Using $$\{M^P,H_0^P\}$$

{

M
P

,

H
0
P

}

, we obtain evidence of a local inhomogeneity with a density contrast $$-0.140 \pm 0.042 $$

-
0.140
±
0.042

, extending up to a redshift of $$z_v =0.056 \pm 0.0002$$

z
v

=
0.056
±
0.0002

, in good agreement with recent results of galaxy catalogs analysis (Wong et al. in The local hole: a galaxy under-density covering 90 mpc, 2021).
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.
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.