bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-644a Disrupts Oncogenic Transformation and Warburg Effect by Direct Modulation of Multiple Genes of Tumor-Promoting Pathways
Authors: Ebron Jey S. , Shankar Eswar , Singh Jagjit , Sikand Kavleen , Weyman Crystal M. , Gupta Sanjay , Lindner Daniel J. , Liu Xiaoqi , Campbell Moray J. , Shukla Girish C. 
Published: February 2019

Abstract

Castration-resistant prostate cancer (CRPC) is defined by tumor microenvironment heterogeneity affecting intrinsic cellular mechanisms including dysregulated androgen signaling, aerobic glycolysis (Warburg effect), and aberrant activation of transcription factors including androgen receptor (AR) and c-Myc. Using in vitro, in vivo, and animal models, we find a direct correlation between miR-644a downregulation and dysregulation of essential cellular processes. MiR-644a downregulated expression of diverse tumor microenvironment drivers including c-Myc, AR coregulators, and antiapoptosis factors Bcl-xl and Bcl2. Moreover, miR-644a modulates epithelial–mesenchymal transition (EMT) by directly targeting EMT-promoting factors ZEB1, cdk6, and Snail. Finally, miR-644a expression suppresses the Warburg effect by direct targeting of c-Myc, Akt, IGF1R, and GAPDH expression. RNA sequencing analysis revealed an analogous downregulation of these factors in animal tumor xenografts. These data demonstrate miR-644a mediated fine-tuning of oncogenesis, stimulating pathways and resultant potentiation of enzalutamide therapy in CRPC patients.

Significance:
This study demonstrates that miR-644a therapeutically influences the CRPC tumor microenvironment by suppressing androgen signaling and additional genes involved in metabolism, proliferation, Warburg effect, and EMT, to potentiate the enzalutamide therapy.
Radiomics on Gadoxetic Acid–Enhanced Magnetic Resonance Imaging for Prediction of Postoperative Early and Late Recurrence of Single Hepatocellular Carcinoma
Authors: Kim Sungwon , Shin Jaeseung , Kim Do-Young , Choi Gi Hong , Kim Myeong-Jin , Choi Jin-Young 
Published: February 2019

Abstract

Purpose:
To evaluate the usefulness of the radiomic model in predicting early (≤2 years) and late (&gt;2 years) recurrence after curative resection in cases involving a single hepatocellular carcinoma (HCC) 2–5 cm in diameter using preoperative gadoxetic acid–enhanced magnetic resonance imaging (MRI), in comparison with the clinicopathologic model.

Experimental Design:
This retrospective study included 167 patients with surgically resected and pathologically confirmed single HCC 2–5 cm in diameter (n = 167, training set:validation set = 128:39) who underwent preoperative gadoxetic acid–enhanced MRI between January 2010 and December 2015. A radiomic model, a clinicopathologic model, and a combined clinicopathologic-radiomic (CCR) model were built using a random survival forest to predict disease-free survival (DFS) in the following conditions: early DFS versus late DFS, dynamic phases, and the peritumoral area included in the segmentation.

Results:
The radiomic model showed a prognostic performance comparable with the clinicopathologic model only with 3-mm peritumoral border extension [c-index difference (radiomic-clinicopathologic), −0.021, P = 0.758]. The CCR model with the 3-mm border extension showed the highest c-index value but no statistically significant improvement over the clinicopathologic model [CCR, 0.716 (0.627–0.799); clinicopathologic model, 0.696 (0.557–0.799)].

Conclusions:
The prognostic value of the preoperative radiomic model with 3-mm border extension showed comparable performance with that of the postoperative clinicopathologic model for predicting DFS of early recurrence of HCC using gadoxetic acid–enhanced MRI. This suggests the importance of including peritumoral changes in the radiomic analysis of HCC.
Urea Cycle Sustains Cellular Energetics upon EGFR Inhibition in EGFR-Mutant NSCLC
Authors: Pham-Danis Catherine , Gehrke Sarah , Danis Etienne , Rozhok Andrii I. , Daniels Michael W. , Gao Dexiang , Collins Christina , Paola José T. Di , D'Alessandro Angelo , DeGregori James 
Published: February 2019

AbstractMutations in oncogenes and tumor suppressor genes engender unique metabolic phenotypes crucial to the survival of tumor cells. EGFR signaling has been linked to the rewiring of tumor metabolism in non–small cell lung cancer (NSCLC). We have integrated the use of a functional genomics screen and metabolomics to identify metabolic vulnerabilities induced by EGFR inhibition. These studies reveal that following EGFR inhibition, EGFR-driven NSCLC cells become dependent on the urea cycle and, in particular, the urea cycle enzyme CPS1. Combining knockdown of CPS1 with EGFR inhibition further reduces cell proliferation and impedes cell-cycle progression. Profiling of the metabolome demonstrates that suppression of CPS1 potentiates the effects of EGFR inhibition on central carbon metabolism, pyrimidine biosynthesis, and arginine metabolism, coinciding with reduced glycolysis and mitochondrial respiration. We show that EGFR inhibition and CPS1 knockdown lead to a decrease in arginine levels and pyrimidine derivatives, and the addition of exogenous pyrimidines partially rescues the impairment in cell growth. Finally, we show that high expression of CPS1 in lung adenocarcinomas correlated with worse patient prognosis in publicly available databases. These data collectively reveal that NSCLC cells have a greater dependency on the urea cycle to sustain central carbon metabolism, pyrimidine biosynthesis, and arginine metabolism to meet cellular energetics upon inhibition of EGFR.Implications:Our results reveal that the urea cycle may be a novel metabolic vulnerability in the context of EGFR inhibition, providing an opportunity to develop rational combination therapies with EGFR inhibitors for the treatment of EGFR-driven NSCLC.
Lipid Uptake Is an Androgen-Enhanced Lipid Supply Pathway Associated with Prostate Cancer Disease Progression and Bone Metastasis
Authors: Tousignant Kaylyn D. , Rockstroh Anja , Taherian Fard Atefeh , Lehman Melanie L. , Wang Chenwei , McPherson Stephen J. , Philp Lisa K. , Bartonicek Nenad , Dinger Marcel E. , Nelson Colleen C. , Sadowski Martin C. 
Published: February 2019

AbstractDe novo lipogenesis is a well-described androgen receptor (AR)–regulated metabolic pathway that supports prostate cancer tumor growth by providing fuel, membrane material, and steroid hormone precursor. In contrast, our current understanding of lipid supply from uptake of exogenous lipids and its regulation by AR is limited, and exogenous lipids may play a much more significant role in prostate cancer and disease progression than previously thought. By applying advanced automated quantitative fluorescence microscopy, we provide the most comprehensive functional analysis of lipid uptake in cancer cells to date and demonstrate that treatment of AR-positive prostate cancer cell lines with androgens results in significantly increased cellular uptake of fatty acids, cholesterol, and low-density lipoprotein particles. Consistent with a direct, regulatory role of AR in this process, androgen-enhanced lipid uptake can be blocked by the AR-antagonist enzalutamide, but is independent of proliferation and cell-cycle progression. This work for the first time comprehensively delineates the lipid transporter landscape in prostate cancer cell lines and patient samples by analysis of transcriptomics and proteomics data, including the plasma membrane proteome. We show that androgen exposure or deprivation regulates the expression of multiple lipid transporters in prostate cancer cell lines and tumor xenografts and that mRNA and protein expression of lipid transporters is enhanced in bone metastatic disease when compared with primary, localized prostate cancer. Our findings provide a strong rationale to investigate lipid uptake as a therapeutic cotarget in the fight against advanced prostate cancer in combination with inhibitors of lipogenesis to delay disease progression and metastasis.Implications:Prostate cancer exhibits metabolic plasticity in acquiring lipids from uptake and lipogenesis at different disease stages, indicating potential therapeutic benefit by cotargeting lipid supply.
Current data on the reproduction of Four-horned Antelope Tetracerus quadricornis in zoological parks
Authors: Dubost Gérard , Labes Stéphane , Lutz Armelle 
Published: February 2019

The Four-horned Antelope Tetracerus quadricornis is currently facing numerous dangers throughout its natural range. The major threats include human overpopulation, deforestation, and degradation of its habitat. It is classified as Vulnerable on the IUCN Red List. Now, this species is rare or even absent in most zoos. Given the threats encountered by this species in the wild, its reproduction was analyzed from animal data obtained in European and Indian zoological parks during 39 consecutive years from 1977 to 2016. There was an average of 1.42 new-borns per litter. Twins were more numerous than singletons. Sexual maturity in females did not occur before 18–36 months of age. Most females, however, reproduced for the first time much later, on average at 6–7 years of age and more than half of females produced only one litter. In females that raised their young, new fertilization generally took place 101 days after the preceding birthing. In Indian zoos, where temperatures vary little between seasons, births were numerous in September–February, especially in September–November when rainfall decreases, contrary to deaths that occurred predominantly in June–August during peak rainfall. In European zoos, most litters occurred in December–February. Thus, Four-horned Antelopes maintain part of the birth season of their native countries, despite unfavourable local climate conditions. Deaths of individuals also occurred mainly in December–February in European parks, i.e., during the coldest season. Globally, more males than females died during the first month of life as in other species, but not so after that age. On the whole, there is a low reproductive success in populations of the Four-horned Antelope under managed care compared to other ruminant species. This could partly be due to husbandry and management procedures of individuals in these parks. This raises the question of the possibility of reintroducing individuals into the wild from ex situ livestock.
Avian survey in tourist sites near Putao in northern Myanmar
Authors: Scopin Alexey E. , Sotnikov Vladimir N. , Skumatov Dmitry V. , Sergeyev Alexey A. 
Published: February 2019

We present the results of short ornithological observations conducted in November–December 2014 and December 2015 in the territory near Putao in northern Myanmar at elevations below 1,500m. We recorded 105 species, which were mostly resident birds, and evaluated the species abundance with a relative scale along tourist walking routes in the area. The bird species richness in the Mali Hka River Valley was observed to be less than in the adjacent virgin mountain forests. Our results could be used for future bird monitoring fieldworks.
Butterflies of the myristica swamp forests of Shendurney Wildlife Sanctuary in the southern Western Ghats, Kerala, India
Authors: Sujitha Prabhakaran Chandrika , Prasad Gopal , Sadasivan Kalesh 
Published: February 2019

Myristica swamps are unique freshwater swamp forests characterised by predominance of tree species of the Myristicaceae family. There have been few published works on the flora and fauna of myristica swamps but studies on butterflies have been scanty. This work was done in the myristica swamps of Kattilapara in Shendurney Wildlife Sanctuary, Kollam district, Kerala, located in the northern aspect of the Agasthyamalai Hills of the southern Western Ghats. Data on the butterflies were collected over a period of two years supplemented with data from previous visits using Transect method. Butterflies were identified based on field photographs and relevant literature. We recorded 206 species of butterflies belonging to 6 families from the myristica swamps. This included 17 species of Papilionidae, 20 species of Pieridae, 65 species of Nymphalidae, 56 species of Lycaenidae, two species of Riodinidae and 46 species of Hesperiidae.Of the total, 19 species of butterflies were Western Ghat endemics. A checklist of butterflies of the myristica swamp, larval hostplants, status with respect to IUCN criteria, endemicity, and classification as per Indian Wildlife Protection Act (WPA) of 1972 are also provided. Eighty-two species of plants were listed as butterfly larval hosts in the myristica swamp ecosystem, with 27 species being new host records for Western Ghats. None of the butterflies recorded were using plants of Myristicaceae family as larval hosts. A simple index—the percentage occurrence—is proposed to delineate the habitat affinity of species.
Nuisance behaviors of macaques in Puerto Princesa Subterranean River National Park, Palawan, Philippines
Authors: Gamalo Lief Erikson , Baril Joselito , Dimalibot Judeline , Asis Augusto , Anas Brian , Puna Nevong , Paller Vachel Gay 
Published: February 2019

Different nuisance behaviors of macaques have been reported in different parts of the world where humans and macaques have been living in the same habitats and sharing the same resources. In this study, nuisance behaviors of Long-tailed Macaques were documented in Puerto Princesa Subterranean River National Park using direct observation, survey questionnaire and by visiting the complaint section database. The attitudes and practices of the locals towards the macaques were also investigated. From the result of the study, it was observed that the most common nuisance behavior of macaques in Central Park Station was littering, while according to the locals, eating of crops was the most common nuisance behavior. There was no existing tourist complaint about the macaques in the area, however, park personnel reported that aggressive tourist-macaque encounters sometimes happened. These nuisance behaviors were observed to be linked to food security of the animals which results in negative interaction. Meanwhile, it was also observed that the practices of most people towards macaques in the area are still relatively positive despite the nuisance behaviors of the macaques. Only a small percentage of respondents hunted macaques, experienced keeping macaques as pets or experienced eating macaque meat. The direct observations revealed that the degree of human-macaque interaction in the park was relatively mild compared to the reports in other countries, partly because of the positive human attitudes towards the animals and the effective management practices in the area.
Association Between Depression and Outcomes in Chinese Patients With Myocardial Infarction and Nonobstructive Coronary Arteries
Authors: Gu Xiao‐Hong , He Chao‐Jie , Shen Liang , Han Bin 
Published: February 2019

Background

Myocardial infarction with nonobstructive coronary arteries (
MINOCA
) occurs in ≈10% of all patients with myocardial infarction. Studies on effects of depression on
MINOCA
outcomes are lacking. Therefore, the aim of this study was to examine the association of depression with clinical outcomes in Chinese patients with
MINOCA
.

Methods and Results

We conducted a prospective cohort study of 633 participants with
MINOCA
and followed up for 3 years. End points were defined as all‐cause mortality and cardiovascular events. Diagnosis of depression was ascertained using the psychiatric interview based on the
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐5)
. During the follow‐up period, all‐cause death occurred in 93 individuals and cardiovascular events developed in 170 individuals. Kaplan‐Meier curves showed a significant association of depression with all‐cause mortality (log‐rank
P
<0.001) and cardiovascular events (log‐rank
P
<0.001). Multiple Cox regression identified the new diagnosis of depression as an independent prognostic factor for all‐cause mortality as well as cardiovascular events (adjusted hazard ratio, 7.250; 95% CI, 4.735–11.100;
P
<0.001; and hazard ratio, 3.411; 95%
CI
, 2.490–4.674;
P
<0.001, respectively).

Conclusions
The new diagnosis of depression at the time of myocardial infarction is associated with increased risk of adverse clinical outcomes in patients with MINOCA.
Ultrastructural Changes of the Right Ventricular Myocytes in Pulmonary Arterial Hypertension
Authors: Shults Nataliia V. , Kanovka Sergey S. , Ten Eyck Jennifer E. , Rybka Vladyslava , Suzuki Yuichiro J. 
Published: February 2019

Background

Pulmonary arterial hypertension (
PAH
) is a serious disease without cure. Elevated pulmonary vascular resistance puts strain on the right ventricle (
RV
) and patients die of
RV
failure. Subjecting Sprague–Dawley rats to
SU
5416 injection and hypoxia promotes severe
PAH
with pulmonary vascular lesions similar to human disease and has been well utilized to investigate pulmonary vascular pathology. However, despite exhibiting severe
RV
fibrosis, these rats do not die. Recently, subjecting Fischer (
CDF
) rats to the same treatment to promote
PAH
was found to result in mortality. Thus, the present study performed detailed morphological characterizations of Fischer rats with
PAH
.

Methods and Results

Rats were subjected to
SU
5416 injection and hypoxia for 3 weeks, followed by maintenance in normoxia. More than 90% of animals died within 6 weeks of the
SU
5416 injection. Necropsy revealed the accumulation of fluid in the chest cavity, right ventricular hypertrophy and dilatation, hepatomegaly, and other indications of congestive heart failure. Time course studies demonstrated the progressive thickening of pulmonary arteries with the formation of concentric lamellae and plexiform lesions as well as
RV
fibrosis in
PAH
rats. Transmission electron microscopy demonstrated the destruction of the myofilaments, T‐tubules, and sarcoplasmic reticulum.
RV
mitochondrial damage and fission were found in Fischer rats, but not in Sprague–Dawley rats, with
PAH
.

Conclusions

These results suggest that the destruction of
RV
mitochondria plays a role in the mechanism of
PAH
‐induced death. The
SU
5416/hypoxia model in Fischer rats should be useful for further investigating the mechanism of
RV
failure and finding effective therapeutic agents to increase the survival of
PAH
patients.
Development and Validation of a Novel Risk Score for In‐Hospital Major Bleeding in Acute Myocardial Infarction:—The SWEDEHEART Score
Authors: Simonsson Moa , Winell Henric , Olsson Henrik , Szummer Karolina , Alfredsson Joakim , Hall Marlous , Dondo Tatendashe B. , Gale Chris P , Jernberg Tomas 
Published: February 2019

Background
Bleeding risk stratification in acute coronary syndrome is of highest clinical interest but current risk scores have limitations. We sought to develop and validate a new in‐hospital bleeding risk score for patients with acute myocardial infarction.

Methods and Results

From the nationwide
SWEDEHEART
(Swedish Web‐System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) register, 97,597 patients with acute myocardial infarction enrolled from 2009 until 2014 were selected. A full model with 23 predictor variables and 8 interaction terms was fitted using logistic regression. The full model was approximated by a model with 5 predictors and 1 interaction term. Calibration, discrimination, and clinical utility was evaluated and compared with the
ACTION
(Acute Coronary Treatment and Intervention Outcomes Network) and
CRUSADE
(Can Rapid Risk Stratification of Unstable Angina Patients Suppress
Ad
verse Outcomes With Early Implementation of the
ACC
/AHA Guidelines) scores. Internal and temporal validity was assessed. In‐hospital major bleeding, defined as fatal, intracranial, or requiring surgery or blood transfusion, occurred in 1356 patients (1.4%). The 5 predictors in the approximate model that constituted the
SWEDEHEART
score were hemoglobin, age, sex, creatinine, and C‐reactive protein. The
ACTION
and
CRUSADE
scores were poorly calibrated in the derivation cohort and therefore were recalibrated. The
SWEDEHEART
score showed higher discriminative ability than both recalibrated scores, overall (
C
‐index 0.80 versus 0.73/0.72) and in all predefined subgroups. Decision curve analysis demonstrated consistently positive and higher net benefit for the
SWEDEHEART
score compared with both recalibrated scores across all clinically relevant decision thresholds. The original
ACTION
and
CRUSADE
scores showed negative net benefit.

Conclusions

The 5‐item
SWEDEHEART
score discriminates in‐hospital major bleeding in patients with acute myocardial infarction and has superior model performance compared with the recalibrated
ACTION
and
CRUSADE
scores.
The genus Echinolittorina Habe, 1956 (Gastropoda: Littorinidae) in the eastern Atlantic Ocean and Mediterranean Sea
Authors: REID DAVID G. 
Published: February 2019

This is the last in a series of systematic accounts of the 60 worldwide species of the littorinid genus Echinolittorina. The taxonomy and distributions of molluscs in the eastern Atlantic are poorly known and littorinids are no exception. Recent molecular studies have clarified the number of species and their relationships, and are used as the basis of this systematic account. Detailed morphological descriptions are provided here for the eight known living species in the tropical and warm temperate eastern Atlantic, from the Mediterranean to Namibia, including the islands of Cape Verde, Canaries, São Tomé, Ascension and St Helena. The descriptions give details of shell, operculum, pigmentation of headfoot, reproductive anatomy, spermatozoa, egg capsules and radulae. Diagnoses include reference to mitochondrial gene sequences (COI). A key is based on shell, penial shape, pallial oviduct and geographical distribution, and includes all other littorinid species (members of genera Tectarius, Afrolittorina, Littoraria, Melarhaphe and Littorina) found in the eastern Atlantic region. Three new species are described: E. peregrinator, E. caboverdensis and E. soroziczac. One name change is proposed: Littorina lemniscata Philippi, 1846 was formerly listed as a junior synonym of E. miliaris from Ascension Island, but examination of types has shown this to be a senior synonym of E. galapagiensis (Stearns, 1892) from the tropical eastern Pacific, which should now be called E. lemniscata. Full synonymies are given for all taxa, and the taxonomic, evolutionary and ecological literature reviewed. Distribution maps are based on examination of 312 samples and on reliable literature records. These reveal close correspondence with the biogeographic division of the region into three provinces (Lusitanian; West African; St Helena and Ascension). The allopatry of sister taxa is maintained by barriers of ocean currents, river deltas and distribution of continental and oceanic conditions. The eight species belong to four clades (E. peregrinator; E. soroziczac; E. punctata group; E. granosa group), each of which is sister to one or more species from the western Atlantic or belongs to a clade with western Atlantic and eastern Pacific distribution. This supports trans-Atlantic dispersal from the west, estimated to have occurred in the Early Miocene and in the Plio-Pleistocene.