bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B20: Repurposing of fenofibrate to prevent and treat PM-induced pulmonary fibroblast-mediated inflammation: Mechanism involved in SIRT1-SREBP1-PIR/NLRP3 inflammasome axis
Authors: Tien Chia-Ping , Chang Yu-Chan , Hung Shih-Chieh , Hsiao Michael 
Published: March 2020

Abstract
Particulate matter (PM) has been shown to have strong link with a variety of human morbidity and mortality. World Health Organization (WHO) recognizes air pollution as an invisible killer responsible for around 7 million global deaths per year, including 43% from chronic obstructive pulmonary disease (COPD), 29% from lung cancer, 25% from heart diseases, 24% from stroke, and 24% from pneumonia. Cardiopulmonary disease is considered as the leading PM-induced complication. The main mechanism involved in PM-induced cardiopulmonary disease is through upregulation of redox-sensitive signaling pathways, mediated by nuclear factor kappa B (NF-κB). We analyzed transcriptomics data by microarray chips in human pulmonary fibroblasts (HPF) after being treated by different doses of PM, and our result identified sterol regulatory element-binding protein 1 (SREBP1) as the top 1 transcription factor activated after PM exposure in HPF. Our analysis showed that Pirin (PIR), an iron-dependent redox regulator of NF-κB, was the most significantly and plausible transcriptional targets of SREBP1. Additionally, SREBP1, directly deacetylated and inhibited by Sirtuin 1 (SIRT1), increased the expression of inflammasome markers, e.g., NACHT, LRR and PYD domains containing protein 3 (NLPR3), Apoptosis-Associated Speck-Like Protein Containing CARD (ASC), and interleukin-1β (IL-1β), were documented. Our results further showed PM-induced inflammation could be reversed by inhibitors of SIRT1, SREBF1, and PIR. We concluded that SIRT1-SREBP1-PIR/NLRP3 inflammasome axis may play a key role in PM-induced sequel and may present new targets. Fenofibrate, clinically prescribed for dyslipidemia, prevented atrial fibrillation rabbits from atrial metabolic remodeling through the SIRT1-SREBP1 pathway. Moreover, in vivo fenofibrate was reported to regulate hyperglycemia-induced metabolic memory and reduce the inflammatory response via SIRT1-dependent suppression of NF-κB. On the basis of previous work and this study, we may repurpose fenofibrate as an anti-PM drug to prevent and treat PM-induced cardiopulmonary disease, which can be used in combination with COPD, heart disease, or anticancer medicines in future research.
Citation Format: Chia-Ping Tien, Yu-Chan Chang, Shih-Chieh Hung, Michael Hsiao. Repurposing of fenofibrate to prevent and treat PM-induced pulmonary fibroblast-mediated inflammation: Mechanism involved in SIRT1-SREBP1-PIR/NLRP3 inflammasome axis [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B20.
Abstract B79: PET CT might be better than CT scan when evaluating immune checkpoint inhibitor response
Authors: Choi JuWhan , Shin Hyun Seock , Oh Jee Youn , Lee Young Seok , Min Kyung Hoon , Shim Jae Jeong , Lee Sung Yong 
Published: March 2020

Abstract
Background: Immune checkpoint inhibitors (ICIs) are changing the paradigm of non-small cell lung cancer (NSCLC) treatment. However, in assessing tumor response, hyperprogression or pseudoprogression can cause difficulties in accurately identifying therapeutic response. We analyzed the usefulness of positron emission tomography-computed tomography (PET-CT) in treatment response assessment of ICI.
Methods: We retrospectively analyzed 12 advanced NSCLC patients who used ICI (pembrolizumab) as the first-line treatment. Chest CT was taken at two cycle intervals, and PET-CT was taken before ICI treatment and after the 2nd cycle. Comparison of response evaluation of tumor size was analyzed using chest CT, and the standardized uptake value (SUV) max was compared using PET-CT.
Results: Among 13 patients, eleven cases were male and one case was female. The mean age was 66.2 ± 6.7 years. Seven patients were treated with pembrolizumab monotherapy, and five patients were treated with pembrolizumab plus cytotoxic chemotherapy. 8 of the 12 patients received more than four cycles of treatment. The mean tumor size before treatment was 7.3 ± 3.3 cm and after treatment was 6.2 ± 3.7 cm, which was not statistically significant (P-value = 0.099). The mean SUV maximum value before treatment was 10.1 ± 3.3 and after treatment was 5.8 ± 2.6 cm, which was statistically significant (P-value = 0.004). SUV max showed a more pronounced trend than tumor size. Two of the five patients who showed stable disease in the first response assessment showed a partial response in the second response assessment. The mean SUV max value was decreased at 58.2% in these two patients.
Conclusion: In evaluating the response of ICIs, PET-CT showed more predictive change compared to CT scan. In predicting the therapeutic response of an ICIs, measuring the metabolic activity of a tumor may be more important than comparing tumor size. PET CT may be a useful tool in evaluating the treatment response of ICI.
Citation Format: JuWhan Choi, Hyun Seock Shin, Jee Youn Oh, Young Seok Lee, Kyung Hoon Min, Jae Jeong Shim, Sung Yong Lee. PET CT might be better than CT scan when evaluating immune checkpoint inhibitor response [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B79.
A new species of shieldtail snake (Reptilia: Squamata: Uropeltidae) from Kolli Hill complex, southern Eastern Ghats, peninsular India
Authors: Ganesh S.R. , Achyuthan N.S. 
Published: March 2020

We describe a new species of shieldtail (uropeltid) snake, Uropeltis rajendrani sp. nov., from the Kolli Hill complex of the southern Eastern Ghats in Tamil Nadu, India. The new species belongs to the U. ceylanica group and is differentiated from related species in having 16–17:16–17:15–16 dorsal scale rows; 145–158 ventral scales; 8–11 pairs of subcaudals; dorsum uniform brown, anteriorly powdered with yellow mottling; venter brown, scales outlined with yellow. This endemic species with a restricted range is known only from atop Kolli Hill complex, inhabiting higher elevation (> 900m) evergreen forests, where it is the only known member of this genus.
Allopatric species, endemism, isolated massif, Uropeltis rajendrani sp. nov., Western Ghats.
FVIIa (Factor VIIa) Induces Biased Cytoprotective Signaling in Mice Through the Cleavage of PAR (Protease-Activated Receptor)-1 at Canonical Arg41 (Arginine41) Site
Authors: Kondreddy Vijay , Pendurthi Usha R. , Xu Xiao , Griffin John H. , Rao L. Vijaya Mohan 
Published: March 2020

Objective:
Recent studies showed that FVIIa (factor VIIa), upon binding to EPCR (endothelial cell protein C receptor), elicits endothelial barrier stabilization and anti-inflammatory effects via activation of PAR (protease-activated receptor)-1–mediated signaling. It is unknown whether FVIIa induces PAR1-dependent cytoprotective signaling through cleavage of PAR1 at the canonical site or a noncanonical site, similar to that of APC (activated protein C).

Approach and Results:
Mouse strains carrying homozygous R41Q (canonical site) or R46Q (noncanonical site) point mutations in PAR1 (QQ41-PAR1 and QQ46-PAR1 mice) were used to investigate in vivo mechanism of PAR1-dependent pharmacological beneficial effects of FVIIa. Administration of FVIIa reduced lipopolysaccharide-induced inflammation, barrier permeability, and VEGF (vascular endothelial cell growth factor)-induced barrier disruption in wild-type (WT) and QQ46-PAR1 mice but not in QQ41-PAR1 mice. In vitro signaling studies performed with brain endothelial cells isolated from WT, QQ41-PAR1, and QQ46-PAR1 mice showed that FVIIa activation of Akt (protein kinase B) in endothelial cells required R41 cleavage site in PAR1. Our studies showed that FVIIa cleaved endogenous PAR1 in endothelial cells, and FVIIa-cleaved PAR1 was readily internalized, unlike APC-cleaved PAR1 that remained on the cell surface. Additional studies showed that pretreatment of endothelial cells with FVIIa reduced subsequent thrombin-induced signaling. This process was dependent on β-arrestin1.

Conclusions:
Our results indicate that in vivo pharmacological benefits of FVIIa in mice arise from PAR1-dependent biased signaling following the cleavage of PAR1 at the canonical R41 site. The mechanism of FVIIa-induced cytoprotective signaling is distinctly different from that of APC. Our data provide another layer of complexity of biased agonism of PAR1 and signaling diversity.
A Critical Role for Estrogen-Related Receptor Signaling in Cardiac Maturation
Authors: Sakamoto Tomoya , Matsuura Timothy R. , Wan Shibiao , Ryba David M. , Kim J`unil , Won Kyoung Jae , Lai Ling , Petucci Christopher , Petrenko Nataliya , Musunuru Kiran , Vega Rick B. , Kelly Daniel P. 
Published: March 2020

Rationale:
The heart undergoes dramatic developmental changes during the prenatal to postnatal transition, including maturation of cardiac myocyte energy metabolic and contractile machinery. Delineation of the mechanisms involved in cardiac postnatal development could provide new insight into the fetal shifts that occur in the diseased heart and unveil strategies for driving maturation of stem cell–derived cardiac myocytes.

Objective:
To delineate transcriptional drivers of cardiac maturation.

Methods and Results:

We hypothesized that ERR (estrogen-related receptor) α and γ, known transcriptional regulators of postnatal mitochondrial biogenesis and function, serve a role in the broader cardiac maturation program. We devised a strategy to knockdown the expression of ERRα and γ in heart after birth (pn-csERRα/γ [postnatal cardiac-specific ERRα/γ]) in mice. With high levels of knockdown, pn-csERRα/γ knockdown mice exhibited cardiomyopathy with an arrest in mitochondrial maturation. RNA sequence analysis of pn-csERRα/γ knockdown hearts at 5 weeks of age combined with chromatin immunoprecipitation with deep sequencing and functional characterization conducted in human induced pluripotent stem cell–derived cardiac myocytes (hiPSC-CM) demonstrated that ERRγ activates transcription of genes involved in virtually all aspects of postnatal developmental maturation, including mitochondrial energy transduction, contractile function, and ion transport. In addition, ERRγ was found to suppress genes involved in fibroblast activation in hearts of pn-csERRα/γ knockdown mice. Disruption of
Esrra
and
Esrrg
in mice during fetal development resulted in perinatal lethality associated with structural and genomic evidence of an arrest in cardiac maturation, including persistent expression of early developmental and noncardiac lineage gene markers including cardiac fibroblast signatures. Lastly, targeted deletion of
ESRRA
and
ESRRG
in hiPSC-CM derepressed expression of early (transcription factor 21 or TCF21) and mature (periostin, collagen type III) fibroblast gene signatures.

Conclusions:
ERRα and γ are critical regulators of cardiac myocyte maturation, serving as transcriptional activators of adult cardiac metabolic and structural genes, an.d suppressors of noncardiac lineages including fibroblast determination.
Focal Cerebral Arteriopathy in Young Adult Patients With Stroke
Authors: McKenna Mary Clare , Fanning Noel , Cronin Simon 
Published: March 2020

Background and Purpose—
Focal cerebral arteriopathy is monophasic inflammatory stenosis of the distal internal carotid artery or the proximal segment of the middle cerebral artery. It is one of the most common causes of acute arterial ischemic stroke in young children but is a less familiar entity for adult neurologists.

Methods—
We retrospectively reviewed stroke service radiology records at a tertiary referral center from January 2013 to December 2014. Focal cerebral arteriopathy was defined as nonprogressive unifocal and unilateral stenosis/irregularity of the distal internal carotid artery or its proximal branches. Only patients aged 16 to 55 years with stroke were included.

Results—
There were 5 cases of focal cerebral arteriopathy: 2 males and 3 females. Three cases were from the cohort of 123 acute presentations of young stroke, and 2 cases were outpatient referrals. The mean age (range) was 43 (32–55) years. The majority presented with recurrent transient ischemic attacks/minor strokes within a single vascular territory over days to weeks. All cases had characteristic radiological features. Interval imaging demonstrated resolution in 1 case and improvement in 3 cases. Functional outcome was excellent with discharge modified Rankin Scale score ranging from 0 to 1. Recurrence occurred in 1 case.

Conclusions—
Focal cerebral arteriopathy is a rare cause of arterial ischemic stroke in young adults. Follow-up intracranial imaging is essential to differentiate from progressive arteriopathies. Evidence-based treatment warrants further investigation. Prognosis is favorable.
PERK (Protein Kinase RNA-Like ER Kinase) Branch of the Unfolded Protein Response Confers Neuroprotection in Ischemic Stroke by Suppressing Protein Synthesis
Authors: Wang Ya-chao , Li Xuan , Shen Yuntian , Lyu Jingjun , Sheng Huaxin , Paschen Wulf , Yang Wei 
Published: March 2020

Background and Purpose—
Ischemic stroke impairs endoplasmic reticulum (ER) function, causes ER stress, and activates the unfolded protein response. The unfolded protein response consists of 3 branches controlled by ER stress sensor proteins, which include PERK (protein kinase RNA-like ER kinase). Activated PERK phosphorylates eIF2α (eukaryotic initiation factor 2 alpha), resulting in inhibition of global protein synthesis. Here, we aimed to clarify the role of the PERK unfolded protein response branch in stroke.

Methods—

Neuron-specific and tamoxifen-inducible PERK conditional knockout (cKO) mice were generated by cross-breeding Camk2a-CreERT2 with
Perk

f/f

mice. Transient middle cerebral artery occlusion was used to induce stroke. Short- and long-term stroke outcomes were evaluated. Protein synthesis in the brain was assessed using a surface-sensing-of-translation approach.

Results—

After tamoxifen-induced deletion of
Perk
in forebrain neurons was confirmed in PERK-cKO mice, PERK-cKO and control mice were subjected to transient middle cerebral artery occlusion and 3 days or 3 weeks recovery. PERK-cKO mice had larger infarcts and worse neurological outcomes compared with control mice, suggesting that PERK-induced eIF2α phosphorylation and subsequent suppression of translation protects neurons from ischemic stress. Indeed, better stroke outcomes were observed in PERK-cKO mice that received postischemic treatment with salubrinal, which can restore the ischemia-induced increase in phosphorylated eIF2α in these mice. Finally, our data showed that post-treatment with salubrinal improved functional recovery after stroke.

Conclusions—
Here, we presented the first evidence that postischemic suppression of translation induced by PERK activation promotes recovery of neurological function after stroke. This confirms and further extends our previous observations that recovery of ER function impaired by ischemic stress critically contributes to stroke outcome. Therefore, future research should include strategies to improve stroke outcome by targeting unfolded protein response branches to restore protein homeostasis in neurons.
Too big to fly? An engineering evaluation of the fossil biology of the giant birds of the Miocene in relation to their flight limitations, constraining the minimum air pressure at about 1.3 bar
Authors: Cannell Alan E.R. 
Published: March 2020

Abstract
The fossil biology of flight is one of the few options available for obtaining information on the density of past atmospheres. The giant birds of the Miocene, the 70 kg teratorn Argentavis magnificens and the giant Pelagornithidae with wingspans of 6.5 m or more, have long intrigued bird specialists, leading one researcher, Colin Pennycuick, to hypothesize that a higher air density may have been necessary for these birds to fly. To test this hypothesis, previous mass estimates and wing shapes of these birds are reviewed and the revised values used in the Flight 1.25 bird simulation program to investigate and quantify in engineering terms the limitations of flight in the present atmosphere as well as in hypothetical higher densities. The results indicate that Pennycuick was probably right: the available takeoff power for a gorged teratorn in an atmosphere of 1 bar is too low and attempts at level takeoff could involve a high risk of injury; The giant Pelagornithidae would have had enough power for takeoff, but flapping bone stress at 1 bar would also have been critical. Simulations indicate that for both birds, power and bone stress constraints are overcome at about 1.3 bar, also enhancing the dynamic soaring of the Pelagornithidae. This level of atmospheric pressure would imply a different climate than the present, but is consistent with the data on average global temperatures for the Miocene before the Late Cooling Events, as well as with the polar to equator temperature gradient.
Mean-Flow Damping Forms the Buffer Zone of the Quasi-Biennial Oscillation: 1D Theory
Authors: Match Aaron , Fueglistaler Stephan 
Published: March 2020

AbstractThe quasi-biennial oscillation (QBO) is a descending pattern of alternating easterly and westerly winds in the tropical stratosphere. Upwelling is generally understood to counteract the descent of the QBO. The upwelling hypothesis holds that where upwelling exceeds the intrinsic descent rate of the QBO, the QBO cannot descend and a buffer zone forms. Descent-rate models of the QBO, which represent a highly simplified evolution of a QBO wind contour, support the upwelling hypothesis. Here, we show that the upwelling hypothesis and descent-rate models only correctly describe buffer zone formation in the absence of wave dissipation below critical levels. When there is wave dissipation below critical levels, the 1D QBO response to upwelling can be either to 1) reform below the upwelling, 2) undergo period-lengthening collapse, or 3) expand a preexisting buffer zone. The response depends on the location of the upwelling and the lower boundary condition. Mean-flow damping always forms a buffer zone. A previous study of reanalyses showed that there is mean-flow damping in the buffer zone due to horizontal momentum flux divergence. Therefore, the 1D model implicates lateral terms in buffer zone formation that it cannot self-consistently include.
Greenhouse Effect: The Relative Contributions of Emission Height and Total Absorption
Authors: Dufresne Jean-Louis , Eymet Vincent , Crevoisier Cyril , Grandpeix Jean-Yves 
Published: March 2020

AbstractSince the 1970s, results from radiative transfer models unambiguously show that an increase in the carbon dioxide (CO2) concentration leads to an increase of the greenhouse effect. However, this robust result is often misunderstood and often questioned. A common argument is that the CO2 greenhouse effect is saturated (i.e., does not increase) as CO2 absorption of an entire atmospheric column, named absorptivity, is saturated. This argument is erroneous first because absorptivity by CO2 is currently not fully saturated and still increases with CO2 concentration and second because a change in emission height explains why the greenhouse effect may increase even if the absorptivity is saturated. However, these explanations are only qualitative. In this article, we first propose a way of quantifying the effects of both the emission height and absorptivity and we illustrate which one of the two dominates for a suite of simple idealized atmospheres. Then, using a line-by-line model and a representative standard atmospheric profile, we show that the increase of the greenhouse effect resulting from an increase of CO2 from its current value is primarily due (about 90%) to the change in emission height. For an increase of water vapor, the change in absorptivity plays a more important role (about 40%) but the change in emission height still has the largest contribution (about 60%).
On the Stationarity of Annual Precipitation over China (1959–2018)
Authors: Wang Hong , Sun Fubao 
Published: March 2020

AbstractStationarity is an assumption that permeates training and practice in water-resource engineering. However, with global change, the validity of stationarity as well as uncertainty of nonstationarity in water-resource planning are being questioned; thus, it is critical to evaluate the stationarity of climate variables, especially precipitation. Based on the continuous observation data of precipitation from 1427 stations across China, 593 efficient grid cells (1° × 1°) are constructed, and the annual precipitation stationarities from 1959 to 2018 are analyzed. The evaluated autocorrelation stationarity indicates that 92.24%–96.12% of the grid cells for an autocorrelation coefficient of lag 1–8 years of precipitation are indistinguishable from 0 [90% confidence level (CL)]. The mean stationarity indicates that 97.47% of the grid cells have a stable mean for 30 years (90% CL); beyond the confidence limits, they are mainly located in the northwest of China, where annual precipitation is less, and the average exceeding range is ±3.78 mm. The long-term observation of annual precipitation in Beijing (1819–2018) and Shanghai (1879–2018) also yields autocorrelation and mean stationarities. There is no significant difference in the annual precipitations between the past 20 years (1999–2018) and the past 60 years (1959–2018) over China. Therefore, the annual precipitation in China exhibits a weak stationary behavior that is indistinguishable from the stationary stochastic process. The average variation in precipitation is ±9.55% between 30 successive years and 16.53% between 10 successive years. Therefore, it is valuable and feasible to utilize the historical data of annual precipitation as the basis of water-resources application.
Visualizing the autonomic and somatic innervation of the female pelvis with 3D MR neurography: a feasibility study
Authors: De Paepe Katja N , Higgins David M , Ball Iain , Morgan Veronica A , Barton Desmond P , deSouza Nandita M 
Published: March 2020

Background Treatment of female pelvic malignancies often causes pelvic nerve damage. Magnetic resonance (MR) neurography mapping the female pelvic innervation could aid in treatment planning. Purpose To depict female autonomic and somatic pelvic innervation using a modified 3D NerveVIEW sequence. Material and Methods Prospective study in 20 female volunteers (n = 6 normal, n = 14 cervical pathology) who underwent a modified 3D short TI inversion recovery (STIR) turbo spin-echo (TSE) scan with a motion-sensitive driven equilibrium (MSDE) preparation radiofrequency pulse and flow compensation. Modifications included offset independent trapezoid (OIT) pulses for inversion and MSDE refocusing. Maximum intensity projections (MIP) were evaluated by two observers (Observer 1, Observer 2); image quality was scored as 2 = high, 1 = medium, or 0 = low with the sciatic nerve serving as a reference. Conspicuity of autonomic superior (SHP) and bilateral inferior hypogastric plexuses (IHP), hypogastric nerves, and somatic pelvic nerves (sciatic, pudendal) was scored as 2 = well-defined, 1 = poorly defined, or 0 = not seen, and inter-observer agreement was determined. Results Images were of medium to high quality according to both observers agreeing in 15/20 (75%) of individuals. SHP and bilateral hypogastric nerves were seen in 30/60 (50%) of cases by both observers. Bilateral IHP was seen in 85% (34/40) by Observer 1 and in 75% (30/40) by Observer 2. Sciatic nerves were well identified in all cases, while pudendal nerves were seen bilaterally by Observer 1 in 65% (26/40) and by Observer 2 in 72.5% (29/40). Agreement between observers for scoring nerve conspicuity was in the range of 60%–100%. Conclusion Modified 3D NerveVIEW renders high-quality images of the female autonomic and pudendal nerves.