bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylene Blue-Mediated Photodynamic Therapy Induces Macrophage Apoptosis via ROS and Reduces Bone Resorption in Periodontitis
Authors: Jiang Chunlan , Yang Wenyi , Wang Chengyi , Qin Wei , Ming Jiajun , Zhang Manman , Qian Haixin , Jiao Ting 
Published: August 2019

Aim. To investigate whether methylene blue-mediated photodynamic therapy (MB-PDT) can affect the “fate” of macrophages in vitro or in periodontitis tissues and to explore the potential mechanism. Methods. For in vitro treatments, THP-1 macrophages were divided into three experimental groups: C/control, no treatment; MB, methylene blue treatment; and MB-PDT, MB and laser irradiation treatment. Then, apoptosis and apoptosis-related proteins were detected in each group. For in vivo treatments, periodontitis was ligature-induced in the first molars of the bilateral maxilla in 12 Sprague Dawley (SD) rats. After six weeks, the ligatures were removed and all the induced molars underwent scaling and root planning (SRP). Then, the rats were divided into three groups according to the following treatments: SRP, saline solution; MB, phenothiazinium dye; and MB-PDT, MB and laser irradiation. Apoptotic macrophages, inflammation levels, and alveolar bone resorption in the periodontal tissues of rats were analyzed in each group. Results. In vitro, flow cytometry analysis demonstrated that 10 μM MB and 40 J/cm2 laser irradiation maximized the apoptosis rate (34.74%) in macrophages. Fluorescence probe and Western blot analyses showed that MB-PDT induced macrophage apoptosis via reactive oxygen species (ROS) and the mitochondrial-dependent apoptotic pathway. Conversely, the addition of exogenous antioxidant glutathione (GSH) and the pan-caspase inhibitor Z-VAD-FMK markedly reduced the apoptotic response in macrophages. In vivo, immunohistochemistry, histology, radiographic, and molecular biology experiments revealed fewer infiltrated macrophages, less bone loss, and lower IL-1β and TNF-α levels in the MB-PDT group than in the SRP and MB groups (P<0.05). Immunohistochemistry analysis also detected apoptotic macrophages in the MB-PDT group. Conclusion. MB-PDT could induce macrophage apoptosis in vitro and in rats with periodontitis. This may be another way for MB-PDT to relieve periodontitis in addition to its antimicrobial effect. Meanwhile, MB-PDT induced apoptosis in THP-1 macrophages via the mitochondrial caspase pathway.
Prooxidative Activity of Celastrol Induces Apoptosis, DNA Damage, and Cell Cycle Arrest in Drug-Resistant Human Colon Cancer Cells
Authors: Moreira Helena , Szyjka Anna , Paliszkiewicz Kamila , Barg Ewa 
Published: August 2019

Cancer resistance to chemotherapy is closely related to tumor heterogeneity, i.e., the existence of distinct subpopulations of cancer cells in a tumor mass. An important role is assigned to cancer stem cells (CSCs), a small subset of cancer cells with high tumorigenic potential and capacity of self-renewal and differentiation. These properties of CSCs are sustained by the ability of those cells to maintain a low intracellular reactive oxygen species (ROS) levels, via upregulation of ROS scavenging systems. However, the accumulation of ROS over a critical threshold disturbs CSCs—redox homeostasis causing severe cytotoxic consequences. In the present study, we investigated the capacity of celastrol, a natural pentacyclic triterpenoid, to induce the formation of ROS and, consequently, cell death of the colon cancer cells with acquired resistant to cytotoxic drugs (LOVO/DX cell line). LOVO/DX cells express several important stem-like cell features, including a higher frequency of side population (SP) cells, higher expression of multidrug resistant proteins, overexpression of CSC-specific cell surface marker (CD44), increased expression of DNA repair gene (PARP1), and low intracellular ROS level. We found that celastrol, at higher concentrations (above 1 μM), significantly increased ROS amount in LOVO/DX cells at both cytoplasmic and mitochondrial levels. This prooxidant activity was associated with the induction of DNA double-strand breaks (DSBs) and apoptotic/necrotic cell death, as well as with inhibition of cell proliferation by S phase cell cycle arrest. Coincubation with NAC, a ROS scavenger, completely reversed the above effects. In summary, our results provide evidence that celastrol exhibits effective cytotoxic effects via ROS-dependent mechanisms on drug-resistant colon cancer cells. These findings strongly suggest the potential of celastrol to effectively kill cancer stem-like cells, and thus, it is a promising agent to treat severe, resistant to conventional therapy, colon cancers.
PARP1 Inhibition Radiosensitizes Models of Inflammatory Breast Cancer to Ionizing Radiation
Authors: Michmerhuizen Anna R. , Pesch Andrea M. , Moubadder Leah , Chandler Benjamin C. , Wilder-Romans Kari , Cameron Meleah , Olsen Eric , Thomas Dafydd G. , Zhang Amanda , Hirsh Nicole , Ritter Cassandra L. , Liu Meilan , Nyati Shyam , Pierce Lori J. , Jagsi Reshma , Speers Corey 
Published: August 2019

Abstract
Sustained locoregional control of disease is a significant issue in patients with inflammatory breast cancer (IBC), with local control rates of 80% or less at 5 years. Given the unsatisfactory outcomes for these patients, there is a clear need for intensification of local therapy, including radiation. Inhibition of the DNA repair protein PARP1 has had little efficacy as a single agent in breast cancer outside of studies restricted to patients with BRCA mutations; however, PARP1 inhibition (PARPi) may lead to the radiosensitization of aggressive tumor types. Thus, this study investigates inhibition of PARP1 as a novel and promising radiosensitization strategy in IBC. In multiple existing IBC models (SUM-149, SUM-190, MDA-IBC-3), PARPi (AZD2281-olaparib and ABT-888-veliparib) had limited single-agent efficacy (IC50 &gt; 10 μmol/L) in proliferation assays. Despite limited single-agent efficacy, submicromolar concentrations of AZD2281 in combination with RT led to significant radiosensitization (rER 1.12–1.76). This effect was partially dependent on BRCA1 mutational status. Radiosensitization was due, at least in part, to delayed resolution of double strand DNA breaks as measured by multiple assays. Using a SUM-190 xenograft model in vivo, the combination of PARPi and RT significantly delays tumor doubling and tripling times compared with PARPi or RT alone with limited toxicity. This study demonstrates that PARPi improves the effectiveness of radiotherapy in IBC models and provides the preclinical rationale for the opening phase II randomized trial of RT ± PARPi in women with IBC (SWOG 1706, NCT03598257).
Effect of Blood Pressure Control on Long‐Term Risk of End‐Stage Renal Disease and Death Among Subgroups of Patients With Chronic Kidney Disease
Authors: Ku Elaine , Sarnak Mark J. , Toto Robert , McCulloch Charles E. , Lin Feng , Smogorzewski Miroslaw , Hsu Chi‐yuan 
Published: August 2019

Background

Our objective was to explore the effect of intensive blood pressure (
BP
) control on kidney and death outcomes among subgroups of patients with chronic kidney disease divided by baseline proteinuria, glomerular filtration rate, age, and body mass index.

Methods and Results

We included 840 MDRD (Modification of Diet in Renal Disease) trial and 1067 AASK (African American Study of Kidney Disease and Hypertension) participants. We used Cox models to examine whether the association between intensive
BP
control and risk of end‐stage renal disease (
ESRD
) or death is modified by baseline proteinuria (≥0.44 versus <0.44 g/g), glomerular filtration rate (≥30 versus <30 mL/min per 1.73 m
2
), age (≥40 versus <40 years), or body mass index (≥30 versus <30 kg/m
2
). The median follow‐up was 14.9 years. Strict (versus usual)
BP
control was protective against
ESRD
(hazard ratio [HR]
ESRD
, 0.77; 95%
CI
, 0.64–0.92) among those with proteinuria ≥0.44 g/g but not proteinuria <0.44 g/g. Strict (versus usual)
BP
control was protective against death (
HR
death
, 0.73; 95%
CI
, 0.59–0.92) among those with glomerular filtration rate <30 mL/min per 1.73 m
2
but not glomerular filtration rate ≥30 mL/min per 1.73 m
2
(
HR
death
, 0.98; 95%
CI
, 0.84–1.15). Strict (versus usual)
BP
control was protective against
ESRD
among those ≥40 years (

HR
ESRD

,
0.82; 95%
CI
, 0.71–0.94) but not <40 years. Strict (versus usual)
BP
control was also protective against
ESRD
among those with body mass index ≥30 kg/m
2
(

HR
ESRD

,
0.75; 95%
CI
, 0.61–0.92) but not body mass index <30 kg/m
2
.

Conclusions

The
ESRD
and all‐cause mortality benefits of intensive
BP
lowering may not be uniform across all subgroups of patients with chronic kidney disease. But intensive
BP
lowering was not associated with increased risk of
ESRD
or death among any subgroups that we examined.
Collateral Circulation in Moyamoya Disease
Authors: Liu Zhi-wen , Han Cong , Zhao Feng , Qiao Peng-gang , Wang Hui , Bao Xiang-yang , Zhang Zheng-shan , Yang Wei-zhong , Li De-sheng , Duan Lian 
Published: August 2019

Background and Purpose—
Predicting the risk of stroke and determining intervention indications are highly important for patients with Moyamoya disease (MMD). Here, we evaluated a novel MMD grading system based on collateral circulation and Suzuki stage to evaluate symptoms and predict prognosis.

Methods—
In total, 301 idiopathic MMD patients were retrospectively analyzed between 2014 and 2016. A collateral circulation grading system with scores ranging from 1 to 12 was established: the anatomic extent of pial collateral blood flow from posterior cerebral artery to middle cerebral artery and anterior cerebral artery was scored from 1 to 6; perforator collateral and internal cerebral artery flow were scored as 6 to 1, which corresponded to Suzuki stages 1 to 6. Dynamic susceptibility contrast–magnetic resonance imaging was used to evaluate hemodynamic status. We assessed the association between the grading system and clinical characteristics.

Results—

We analyzed 364 symptomatic hemispheres of 301 patients (146 males, 28±16 years). Ischemic patients who presented with infarction were more likely to score <8 points (
P
<0.001), whereas those with ischemia symptoms (transient ischemic attack and headache) were more likely to score >8 points. Hemorrhagic patients who presented with intraparenchymal hemorrhage were more likely to score <8 points, whereas those who presented with intraventricular hemorrhage were more likely to score >8 points (
P
<0.001). According to dynamic susceptibility contrast–magnetic resonance imaging, lower scores were correlated with more severe time to peak delay (
P
<0.001) and worse relative cerebral blood volume ratio (
P
=0.016) and cerebral flow ratio (
P
=0.002). Encephaloduroarteriosynangiosis was performed in 348 symptomatic hemispheres. Patients who had collateral scores <4 points were more likely to have a postoperative stroke and a worse prognosis during the follow-up.

Conclusions—
This new MMD collateral grading system correlated well with clinical symptoms, hemodynamic status, and therapeutic prognosis and may facilitate risk stratification and prognosis predictions in patients with MMD.
Predicting Clinical Outcomes of Large Vessel Occlusion Before Mechanical Thrombectomy Using Machine Learning
Authors: Nishi Hidehisa , Oishi Naoya , Ishii Akira , Ono Isao , Ogura Takenori , Sunohara Tadashi , Chihara Hideo , Fukumitsu Ryu , Okawa Masakazu , Yamana Norikazu , Imamura Hirotoshi , Sadamasa Nobutake , Hatano Taketo , Nakahara Ichiro , Sakai Nobuyuki , Miyamoto Susumu 
Published: August 2019

Background and Purpose—
The clinical course of acute ischemic stroke with large vessel occlusion (LVO) is a multifactorial process with various prognostic factors. We aimed to model this process with machine learning and predict the long-term clinical outcome of LVO before endovascular treatment and to compare our method with previously developed pretreatment scoring methods.

Methods—
The derivation cohort included 387 LVO patients, and the external validation cohort included 115 LVO patients with anterior circulation who were treated with mechanical thrombectomy. The statistical model with logistic regression without regularization and machine learning algorithms, such as regularized logistic regression, linear support vector machine, and random forest, were used to predict good clinical outcome (modified Rankin Scale score of 0–2 at 90 days) with standard and multiple pretreatment clinical variables. Five previously reported pretreatment scoring methods (the Pittsburgh Response to Endovascular Therapy score, the Stroke Prognostication Using Age and National Institutes of Health Stroke Scale index, the Totaled Health Risks in Vascular Events score, the Houston Intra-Arterial Therapy score, and the Houston Intra-Arterial Therapy 2 score) were compared with these models for the area under the receiver operating characteristic curve.

Results—
The area under the receiver operating characteristic curve of random forest, which was the worst among the machine learning algorithms, was significantly higher than those of the standard statistical model and the best model among the previously reported pretreatment scoring methods in the derivation (the area under the receiver operating characteristic curve were 0.85±0.07 for random forest, 0.78±0.08 for logistic regression without regularization, and 0.77±0.09 for Stroke Prognostication using Age and National Institutes of Health Stroke Scale) and validation cohorts (the area under the receiver operating characteristic curve were 0.87±0.01 for random forest, 0.56±0.07 for logistic regression without regularization, and 0.83±0.00 for Pittsburgh Response to Endovascular Therapy).

Conclusions—
Machine learning methods with multiple pretreatment clinical variables can predict clinical outcomes of patients with anterior circulation LVO who undergo mechanical thrombectomy more accurately than previously developed pretreatment scoring methods.
Multiple Soluble Components of the Glycocalyx Are Increased in Patient Plasma After Ischemic Stroke
Authors: DellaValle Brian , Hasseldam Henrik , Johansen Flemming F. , Iversen Helle K. , Rungby Jørgen , Hempel Casper 
Published: August 2019

Background and Purpose—
The GLX (glycocalyx) is a protein/polysaccharide meshwork at the cellular surface. Consisting largely of glycosaminoglycans and proteoglycans, the GLX can shed in response to stress. In this study, we assay 11 components of the GLX in plasma from patients with ischemic stroke from a longitudinal cohort.

Methods—
Plasma samples from healthy individuals (N=8), and patients with ischemic stroke day ≥3, day 7, and day 90 (N=9–14) were immunoassayed for diverse components of the GLX.

Results—
Median stroke severity was mild (National Institutes of Health Stroke Scale 2.0 (range, 0–6) at day ≤3). Three (keratan-chondroitin-heparan-sulfate) of 4 glycosaminoglycans and CD44 (proteoglycan) were increased at day 7 and returned to baseline at day 90. Proteoglycan syndecan (Syn)-3 increased and Syn-2 levels decreased, significantly.

Conclusions—
Individual GLX components are often assayed as stand-alone biomarkers for endothelial health. This study suggests a full assessment of GLX components is more indicative of the endothelial health of an individual and represents a complex GLX signature that may be valuable as a composite biomarker of disease.
Trend Analysis of Seasonal Precipitation (1960–2013) in Subregions of Hunan Province, Central South China Using Discrete Wavelet Transforms
Authors: Hu Qian , He Xinguang , Lu Xi-An , Zhang Xinping 
Published: August 2019

AbstractIn this study, trends of seasonal precipitation are investigated in subregions of Hunan Province in China over 1960–2013 by discrete wavelet transform (DWT) and Mann–Kendall (MK) tests. The main purpose of trend analysis is to detect the most dominant periodic components affecting the observed trends of seasonal precipitation in each subregion. For this purpose, the homogeneous precipitation regions are first delineated by combining rotated empirical orthogonal functions with agglomerative hierarchical clustering. Results suggest dividing the precipitation of Hunan Province into five subregions for winter and three subregions for spring, summer, and autumn. Delineated subregions for each season show strongly coherent spatial patterns, all of which are along the strip extending in the southwest–northeast direction. After regionalization, areal seasonal precipitation series in each subregion are decomposed into several detail and approximation component subseries, and then the decomposed subseries are analyzed by three types of MK tests. Results reveal that winter and summer precipitations experience an increasing trend in all of the divisions—winter precipitation in southeast-central and southern Hunan and summer precipitation in southwest-central Hunan especially exhibit a statistically significant tendency. However, spring and autumn precipitations show a nonsignificant decreasing trend in all of the divisions. Results from DWT and sequential MK analyses suggest that detail component 1 (plus approximation) of seasonal precipitations in all subregions is the most dominant periodic mode affecting their observed trends, except for summer precipitation in the subregion of southern Hunan, where detail component 2 is the most dominant one. Therefore, short-term periodicity (2–4 yr) is the most influential in affecting the observed trends of seasonal precipitation over Hunan Province.
A Diagnostic Equation for Tendency of Lapse-Rate-Tropopause Heights and Its Application
Authors: Kohma Masashi , Sato Kaoru 
Published: August 2019

Abstract
The tropopause is the boundary between the troposphere and stratosphere and is normally defined by the temperature lapse rate. Previous studies have noted that synoptic-scale and planetary-scale disturbances bring about lapse-rate-tropopause (LRT) height fluctuations on time scales from several days to several years. In the present study, a diagnostic expression for the tendency of LRT height is derived by assuming that the LRT can be characterized as a discontinuity in the vertical gradient of the potential temperature. In addition, the contribution from each term in the thermodynamic equation to the LRT height is quantified. The derived equation is validated by examining the time variation of the LRT height associated with baroclinic waves in an idealized numerical calculation, that of the zonal-mean LRT height in GPS radio occultation data, and that of the LRT height in reanalysis data.
Response of Orographic Precipitation to Subsaturated Low-Level Layers
Authors: Fu Shizuo , Rotunno Richard , Xue Huiwen 
Published: August 2019

AbstractIn orographic precipitation events, there are times when subsaturated low-level layers are observed to be below saturated, nearly moist-neutral, upper-level layers. By performing a series of idealized two-dimensional simulations, this study investigates the response of orographic precipitation to subsaturated low-level layers. When the nondimensional parameter N2zt/U, where N2 and zt are, respectively, the dry Brunt–Väisälä frequency and depth of the subsaturated low-level layer, and U the cross-mountain wind speed, exceeds a critical value, the decelerated region on the upwind side of the mountain moves upwind, resulting in weak surface precipitation near the mountain peak. The critical value determined from the simulations is close to that derived from linear theory. When N2zt/U is less than the critical value, increasing zt has two competing effects: 1) the vapor-transport effect, meaning that increasing zt decreases the amount of vapor transported to the mountain, and hence tends to decrease surface precipitation; and 2) the updraft-width effect, meaning that increasing zt enhances flow blocking, producing a wider updraft over the upwind slope, and hence tends to increase surface precipitation. When the vapor-transport effect dominates, surface precipitation decreases with zt. When the updraft-width effect dominates, surface precipitation increases with zt. Increasing the maximum mountain height hm or U generally increases surface precipitation. However, for certain combinations of hm and U, the simulations produce lee waves, which substantially reduce surface precipitation. Finally, the response of orographic precipitation in the simulations with both liquid-phase and ice-phase microphysics is similar to that in the simulations with only liquid-phase microphysics.
Addressing Fractional Dimensionality in the Application of Weather Index Insurance and Climate Risk Financing in Agricultural Development: A Dynamic Triggering Approach
Authors: Turvey Calum G. , Shee Apurba , Marr Ana 
Published: August 2019

AbstractClimate risk financing programs in agriculture have caught the attention of researchers and policy makers over the last decade. Weather index insurance has emerged as a promising market-based risk financing mechanism. However, to develop a suitable weather index insurance mechanism it is essential to incorporate the distribution of underlying weather and climate risks to a specific event model that can minimize intraseasonal basis risk. In this paper we investigate the erratic nature of rainfall patterns in Kenya using Climate Hazards Group Infrared Precipitation with Station Data (CHIRPS) rainfall data from 1983 to 2017. We find that the patterns of rainfall are fractional, both erratic and persistent, which is consistent with the Noah and Joseph effects that are well known in mathematics. The erratic nature of rainfall emerges from the breakdown of the convergence to a normal distribution. Instead we find that the distribution about the average is approximately lognormal, with an almost 50% higher chance of deficit rainfall below the mean than adequate rainfall above the mean. We find that the rainfall patterns obey the Hurst law and that the measured Hurst coefficients for seasonal rainfall pattern across all years range from a low of 0.137 to a high above 0.685. To incorporate the erratic and persistent nature of seasonal rainfall, we develop a new approach to weather index insurance based upon the accumulated rainfall in any 21-day period falling below 60% of the long-term average for that same 21-day period. We argue that this approach is more satisfactory to matching drought conditions within and between various phenological stages of growth.