bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying pathfinder elements for gold in bulk-rock geochemical data from the Cripple Creek Au–Te deposit: a statistical approach
Authors: Kadel-Harder Irene M. , Spry Paul G. , McCombs Audrey L. , Zhang Haozhe 
Published: October 2020

The Cripple Creek alkaline igneous rock-related, low-sulfidation epithermal gold telluride deposit, Colorado, is hosted in the 10 km wide Oligocene alkaline volcanic Cripple Creek diatreme in Proterozoic rocks. Gold occurs as native gold, Au-tellurides, and in the structure of arsenian pyrite, in potassically altered high-grade veins, and as disseminations in the host rocks.
Correlation coefficients, principal component analysis, hierarchical cluster analysis and random forests were used to analyse major and trace element compositions of 995 rock samples primarily from low-grade gold mineralization in drill core from three currently operating pits (Wild Horse Extension, Globe Hill and Schist Island) in the northwestern part of the Cripple Creek diatreme. These methods suggest that Ag, As, Bi, Te and W are the best pathfinders to gold mineralization in low-grade disseminated ore. Although Mo correlates with gold in other studies and is spatially related to gold veins, molybdenite post-dated the formation of gold and is likely related to a late-stage porphyry overprint. These elements, in conjunction with mineralogical studies, indicate that tellurides, fluorite, quartz, carbonates, roscoelite, tennantite-tetrahedrite, pyrite, sphalerite, muscovite, monazite, bastnäsite and hübnerite serve as exploration guides to ore.
Comparative Analysis of Visual Performance and Astigmatism Tolerance with Monofocal, Bifocal, and Extended Depth-of-Focus Intraocular Lenses Targeting Slight Myopia
Authors: Xu Jie , Zheng Tianyu , Lu Yi 
Published: October 2020

Purpose. To compare the visual performance and astigmatism tolerance of 3 intraocular lens (IOL) groups: monofocal, bifocal, and extended depth-of-focus (EDOF) IOLs targeting slight myopia. Methods. Overall, there were 60 cataract surgery eyes from 60 patients with implantation of a monofocal, bifocal, or EDOF IOL (20 eyes in each IOL group). The EDOF IOLs targeted slight myopia (−0.25 D to −0.75 D). Intragroup comparison of visual acuity, defocus curve, objective optical quality, contrast sensitivity, visual function questionnaire scores, patients’ overall satisfaction, and the astigmatism tolerance was performed 3 months after surgery. Results. The EDOF group provided equivalently excellent distance visual outcomes (0.06 ± 0.12) as the monofocal (0.06 ± 0.09) and bifocal (0.03 ± 0.09) groups

P
=
0.554

, better intermediate vision than the other 2 groups

P
<
0.05

, and similarly satisfactory near visual outcomes (0.23 ± 0.16 at 20 cm, and 0.17 ± 0.14 at 33 cm) as the bifocal group (0.28 ± 0.14 at 20 cm and 0.08 ± 0.10 at 33 cm)

P
>
0.05

. The contrast sensitivity of EDOF IOL was slightly decreased compared to that of monofocal IOL, but it was better than that of bifocal IOL. The EDOF group showed significantly higher satisfaction than the bifocal group did when preoperative corneal astigmatism was 0.75 D or greater

P
=
0.009

. A significant negative correlation between the corneal astigmatism and patient satisfaction was observed in only the bifocal group. Conclusions. The EDOF IOLs targeting slight myopia offered satisfactory visual outcomes at an extended range from far to near distances. The EDOF and monofocal IOLs showed a better tolerance to astigmatism than did the bifocal IOL.
Brain Tumor Stem Cell Dependence on Glutaminase Reveals a Metabolic Vulnerability through the Amino Acid Deprivation Response Pathway
Authors: Restall Ian J. , Cseh Orsolya , Richards Laura M. , Pugh Trevor J. , Luchman H. Artee , Weiss Samuel 
Published: October 2020

Abstract

Cancer cells can metabolize glutamine to replenish TCA cycle intermediates, leading to a dependence on glutaminolysis for cell survival. However, a mechanistic understanding of the role that glutamine metabolism has on the survival of glioblastoma (GBM) brain tumor stem cells (BTSC) has not yet been elucidated. Here, we report that across a panel of 19 GBM BTSC lines, inhibition of glutaminase (GLS) showed a variable response from complete blockade of cell growth to absolute resistance. Surprisingly, BTSC sensitivity to GLS inhibition was a result of reduced intracellular glutamate triggering the amino acid deprivation response (AADR) and not due to the contribution of glutaminolysis to the TCA cycle. Moreover, BTSC sensitivity to GLS inhibition negatively correlated with expression of the astrocytic glutamate transporters EAAT1 and EAAT2. Blocking glutamate transport in BTSCs with high EAAT1/EAAT2 expression rendered cells susceptible to GLS inhibition, triggering the AADR and limiting cell growth. These findings uncover a unique metabolic vulnerability in BTSCs and support the therapeutic targeting of upstream activators and downstream effectors of the AADR pathway in GBM. Moreover, they demonstrate that gene expression patterns reflecting the cellular hierarchy of the tissue of origin can alter the metabolic requirements of the cancer stem cell population.

Significance:
Glioblastoma brain tumor stem cells with low astrocytic glutamate transporter expression are dependent on GLS to maintain intracellular glutamate to prevent the amino acid deprivation response and cell death.
Activatable Zymography Probes Enable In Situ Localization of Protease Dysregulation in Cancer
Authors: Soleimany Ava P. , Kirkpatrick Jesse D. , Su Susan , Dudani Jaideep S. , Zhong Qian , Bekdemir Ahmet , Bhatia Sangeeta N. 
Published: October 2020

Abstract

Recent years have seen the emergence of conditionally activated diagnostics and therapeutics that leverage protease-cleavable peptide linkers to enhance their specificity for cancer. However, due to a lack of methods to measure and localize protease activity directly within the tissue microenvironment, the design of protease-activated agents has been necessarily empirical, yielding suboptimal results when translated to patients. To address the need for spatially resolved protease activity profiling in cancer, we developed a new class of in situ probes that can be applied to fresh-frozen tissue sections in a manner analogous to immunofluorescence staining. These activatable zymography probes (AZP) detected dysregulated protease activity in human prostate cancer biopsy samples, enabling disease classification. AZPs were leveraged within a generalizable framework to design conditional cancer diagnostics and therapeutics and showcased in the Hi-Myc mouse model of prostate cancer, which models features of early pathogenesis. Multiplexed screening against barcoded substrates yielded a peptide, S16, that was robustly and specifically cleaved by tumor-associated metalloproteinases in the Hi-Myc model. In situ labeling with an AZP incorporating S16 revealed a potential role of metalloproteinase dysregulation in proliferative, premalignant Hi-Myc prostatic glands. Systemic administration of an in vivo imaging probe incorporating S16 perfectly classified diseased and healthy prostates, supporting the relevance of ex vivo activity assays to in vivo translation. We envision AZPs will enable new insights into the biology of protease dysregulation in cancer and accelerate the development of conditional diagnostics and therapeutics for multiple cancer types.

Significance:
Visualization of protease activity within the native tissue context using AZPs provides new biological insights into protease dysregulation in cancer and guides the design of conditional diagnostics and therapeutics.
Transcriptomic Analysis of Diffuse Intrinsic Pontine Glioma (DIPG) Identifies a Targetable ALDH-Positive Subset of Highly Tumorigenic Cancer Stem-like Cells
Authors: Surowiec Rachel K. , Ferris Sarah F. , Apfelbaum April , Espinoza Carlos , Mehta Ranjit K. , Monchamp Karamoja , Sirihorachai Veerin R. , Bedi Karan , Ljungman Mats , Galban Stefanie 
Published: October 2020

Abstract

Understanding the cancer stem cell (CSC) landscape in diffuse intrinsic pontine glioma (DIPG) is desperately needed to address treatment resistance and identify novel therapeutic approaches. Patient-derived DIPG cells demonstrated heterogeneous expression of aldehyde dehydrogenase (ALDH) and CD133 by flow cytometry. Transcriptome-level characterization identified elevated mRNA levels of MYC, E2F, DNA damage repair (DDR) genes, glycolytic metabolism, and mTOR signaling in ALDH+ compared with ALDH−, supporting a stem-like phenotype and indicating a druggable target. ALDH+ cells demonstrated increased proliferation, neurosphere formation, and initiated tumors that resulted in decreased survival when orthotopically implanted. Pharmacologic MAPK/PI3K/mTOR targeting downregulated MYC, E2F, and DDR mRNAs and reduced glycolytic metabolism. In vivo PI3K/mTOR targeting inhibited tumor growth in both flank and an ALDH+ orthotopic tumor model likely by reducing cancer stemness. In summary, we describe existence of ALDH+ DIPGs with proliferative properties due to increased metabolism, which may be regulated by the microenvironment and likely contributing to drug resistance and tumor recurrence.

Implications:
Characterization of ALDH+ DIPGs coupled with targeting MAPK/PI3K/mTOR signaling provides an impetus for molecularly targeted therapy aimed at addressing the CSC phenotype in DIPG.
SHOC2 Is a Critical Modulator of Sensitivity to EGFR–TKIs in Non–Small Cell Lung Cancer Cells
Authors: Terai Hideki , Hamamoto Junko , Emoto Katsura , Masuda Takeshi , Manabe Tadashi , Kuronuma Satoshi , Kobayashi Keigo , Masuzawa Keita , Ikemura Shinnosuke , Nakayama Sohei , Kawada Ichiro , Suzuki Yusuke , Takeuchi Osamu , Suzuki Yukio , Ohtsuki Sumio , Yasuda Hiroyuki , Soejima Kenzo , Fukunaga Koichi 
Published: October 2020

Abstract

EGFR mutation-positive patients with non–small cell lung cancer (NSCLC) respond well to treatment with EGFR–tyrosine kinase inhibitors (EGFR–TKI); however, treatment with EGFR–TKIs is not curative, owing to the presence of residual cancer cells with intrinsic or acquired resistance to this class of drugs. Additional treatment targets that may enhance the efficacy of EGFR–TKIs remain elusive. Using a CRISPR/Cas9-based screen, we identified the leucine-rich repeat scaffold protein SHOC2 as a key modulator of sensitivity to EGFR–TKI treatment. On the basis of in vitro assays, we demonstrated that SHOC2 expression levels strongly correlate with the sensitivity to EGFR–TKIs and that SHOC2 affects the sensitivity to EGFR–TKIs in NSCLC cells via SHOC2/MRAS/PP1c and SHOC2/SCRIB signaling. The potential SHOC2 inhibitor celastrol phenocopied SHOC2 depletion. In addition, we confirmed that SHOC2 expression levels were important for the sensitivity to EGFR–TKIs in vivo. Furthermore, IHC showed the accumulation of cancer cells that express high levels of SHOC2 in lung cancer tissues obtained from patients with NSCLC who experienced acquired resistance to EGFR–TKIs. These data indicate that SHOC2 may be a therapeutic target for patients with NSCLC or a biomarker to predict sensitivity to EGFR–TKI therapy in EGFR mutation-positive patients with NSCLC. Our findings may help improve treatment strategies for patients with NSCLC harboring EGFR mutations.

Implications:
This study showed that SHOC2 works as a modulator of sensitivity to EGFR–TKIs and the expression levels of SHOC2 can be used as a biomarker for sensitivity to EGFR–TKIs.
Timed Ang2-Targeted Therapy Identifies the Angiopoietin–Tie Pathway as Key Regulator of Fatal Lymphogenous Metastasis
Authors: Gengenbacher Nicolas , Singhal Mahak , Mogler Carolin , Hai Ling , Milde Laura , Pari Ashik Ahmed Abdul , Besemfelder Eva , Fricke Claudine , Baumann Daniel , Gehrs Stephanie , Utikal Jochen , Felcht Moritz , Hu Junhao , Schlesner Matthias , Offringa Rienk , Chintharlapalli Sudhakar R. , Augustin Hellmut G. 
Published: October 2020

Abstract

Recent clinical and preclinical advances have highlighted the existence of a previously hypothesized lymphogenous route of metastasis. However, due to a lack of suitable preclinical modeling tools, its contribution to long-term disease outcome and relevance for therapy remain controversial. Here, we established a genetically engineered mouse model (GEMM) fragment–based tumor model uniquely sustaining a functional network of intratumoral lymphatics that facilitates seeding of fatal peripheral metastases. Multiregimen survival studies and correlative patient data identified primary tumor–derived Angiopoietin-2 (Ang2) as a potent therapeutic target to restrict lymphogenous tumor cell dissemination. Mechanistically, tumor-associated lymphatic endothelial cells (EC), in contrast to blood vascular EC, were found to be critically addicted to the Angiopoietin–Tie pathway. Genetic manipulation experiments in combination with single-cell mapping revealed agonistically acting Ang2–Tie2 signaling as key regulator of lymphatic maintenance. Correspondingly, acute presurgical Ang2 neutralization was sufficient to prolong survival by regressing established intratumoral lymphatics, hence identifying a therapeutic regimen that warrants further clinical evaluation.

Significance:
Exploiting multiple mouse tumor models including a unique GEMM-derived allograft system in combination with preclinical therapy designs closely matching the human situation, this study provides fundamental insight into the biology of tumor-associated lymphatic EC and defines an innovative presurgical therapeutic window of migrastatic Ang2 neutralization to restrict lymphogenous metastasis.
This article is highlighted in the In This Issue feature, p. 211
Butterfly species richness and diversity in rural and urban areas of Sirajganj, Bangladesh
Authors: Shaburul Imam Sheikh Muhammad , Neogi Amit Kumer , Rahman M. Ziaur , Hasan M. Sabbir 
Published: October 2020

An appraisal of butterfly species diversity study was conducted in four selected parts of Sirajganj District, Bangladesh, as a part of an ecological research. The study was conducted from March 2015 to April 2016. A total of 19,343 butterflies belonging to five families and 12 subfamilies was recorded. A random sampling of forest, riverside rural, and urban areas in Sirajganj District revealed the presence of 65 butterfly species, dominated by Lycaenidae (37%) over Nymphalidae (33%) followed by Pieridae (19%), Hesperiidae (7%), and Papilionidae (4%). Butterfly fauna in Bangabandhu Sheikh Mujib Jamuna Ecopark (BJEP), compared with the percentage of other study sites, was very high (Hs= 4.03) and the percentage of hedge species was relatively higher (45%) than that of improved grassland and forest interior species. The relative abundance of the butterflies varied with the site, month, and family significantly. Considering the landscape of Sirajganj, steps to enhance riverside natural gardening should be adopted to maintain butterfly diversity and sustain the ecosystem services derived from them.
Elevational pattern and seasonality of avian diversity in Kaligandaki River Basin, central Himalaya
Authors: Neupane Juna , Khanal Laxman , Gyawali Basant , Chalise Mukesh Kumar 
Published: October 2020

This study explored bird diversity, seasonal variation, and associated factors along an elevational gradient in an important biodiversity area (IBA) of central Nepal: the Kaligandaki River basin of Annapurna Conservation Area. The field survey was carried out in 2019 over two seasons, winter (January and February) and summer (May and June) using the point count method. A total of 90 sampling plots were set up from elevations of 800m (Beni) to 3,800m (Muktinath). Data for variables including the number of fruiting trees (indicator of resource availability) and distance to the road (indicator of disturbance) were collected, and their influence on avian diversity were assessed. The results revealed a diverse assemblage of avian fauna in the study area with consistent species richness over the two seasons. A decline in species richness and diversity with increasing elevation was observed. Of the different habitat types within the study area, forest and shrubland habitats showed the strongest association with bird species distribution and richness. We emphasize the need for long-term monitoring programs with standardized sampling approaches to better understand the avifauna in the central Himalaya.
A frog that eats foam: predation on the nest of Polypedates sp. (Rhacophoridae) by Euphlyctis sp. (Dicroglossidae)
Authors: Pranoy Kishore Borah  , Ghosh Avrajjal , Sahoo Bikash , Aniruddha Datta-Roy  
Published: October 2020

Amphibians in terms of their predatory behaviour depend mainly upon the ambush technique. Other than predation, amphibians have also been recorded to scavenge to acquire food resources. This is an opportunistic observation of predatory behaviour of an amphibian species (Euphlyctis sp.) on the foam nest of another species (Polypedates sp.). The behaviour was recorded during a routine field sampling, which is broadly written in the body of this write up. Such an observation to our knowledge has not been reported earlier. This observation will have implications in terms of amphibian ecology, behavioural studies, and also diversity studies in the range of foraging behaviour.
A rare camera trap record of the Hispid Hare Caprolagus hispidus from Dudhwa Tiger Reserve, Terai Arc Landscape, India
Authors: Rastogi Sankarshan , Raj Ram Kumar , Chauhan Bridesh Kumar 
Published: October 2020

Hispid Hare Caprolagus hispidus, member of family Leporidae, is a highly elusive species. Now restricted to grasslands of north India, southern Nepal and parts of Bhutan, this lagomorph was historically known to be found upto south Bangladesh in Dhaka. There are currently a very few photographic evidences of this rare and threatened lagomorph as it inhabits dense tall grasslands. Here, we present a photographic evidence of the Hispid Hare from the grasslands of Dudhwa Tiger Reserve, Uttar Pradesh, India. The hare was camera-trapped in January 2020 as part of an ongoing study on ungulates in floodplain Terai grasslands of the park. Although we found signs of Hispid Hare in multiple grasslands, we only photo documented it in one of our sampling sites. Intensive sampling efforts are needed to get an estimate of the hare in the park, and to assess the immediate threats to this lagomorph and its habitats to plan better conservation measures.
Recurrent Admissions for Acute Decompensated Heart Failure Among Patients With and Without Peripheral Artery Disease: The ARIC Study
Authors: Chunawala Zainali , Chang Patricia P. , DeFilippis Andrew P. , Hall Michael E. , Matsushita Kunihiro , Caughey Melissa C. 
Published: October 2020

Background
Peripheral artery disease (PAD) is both a common comorbidity and a contributing factor to heart failure. Whether PAD is associated with hospitalization for recurrent decompensation among patients with established heart failure is uncertain.

Methods and Results

Since 2005, the ARIC (Atherosclerosis Risk in Communities) study has conducted active surveillance of hospitalized acute decompensated heart failure (ADHF), with events verified by physician review. From 2005 to 2016, 1481 patients were hospitalized with ADHF and discharged alive (mean age, 78 years; 69% White). Of these, 207 (14%) had diagnosis of PAD. Those with PAD were more often men (55% versus 44%) and smokers (17% versus 8%), with a greater prevalence of coronary artery disease (72% versus 52%). Patients with PAD had an increased risk of at least 1 ADHF readmission, both within 30 days (11% versus 7%) and 1 year (39% versus 28%) of discharge from the index hospitalization. After adjustments, PAD was associated with twice the hazard of ADHF readmission within 30 days (HR, 2.02; 95% CI, 1.14–3.60) and a 60% higher hazard of ADHF readmission within 1 year (HR, 1.60; 95% CI, 1.25–2.05). The 1‐year hazard of ADHF readmission associated with PAD was stronger with heart failure with reduced ejection fraction (HR, 2.01; 95% CI, 1.29–3.13) than preserved ejection fraction (HR, 1.04; 95% CI, 0.69–1.56);
P
for interaction=0.05.

Conclusions
Patients with ADHF and concomitant PAD have a higher likelihood of ADHF readmission. Strategies to prevent ADHF readmissions in this high‐risk group are warranted.
Synchronous and Metachronous Thoracic Aortic Aneurysms in Patients With Abdominal Aortic Aneurysms: A Systematic Review and Meta‐Analysis
Authors: Gouveia e Melo Ryan , Silva Duarte Gonçalo , Lopes Alice , Alves Mariana , Caldeira Daniel , Fernandes e Fernandes Ruy , Mendes Pedro Luís 
Published: October 2020

Background
The prevalence of thoracic aortic aneurysms (TAA) in patients with known abdominal aortic aneurysms (AAA) is not well known and understudied. Our aim was to conduct a systematic review and meta‐analysis of the overall prevalence of synchronous and metachronous TAA (SM‐TAA) in patients with a known AAA and to understand the characteristics of this sub‐population.

Methods and Results
We searched MEDLINE, EMBASE, and CENTRAL (Cochrane Central Register of Controlled Trials) from inception to November 2019 for all population‐based studies reporting on the prevalence of SM‐TAAs in a cohort of patients with AAA. Article screening and data extraction were performed by 2 authors and data were pooled using a random‐effects model of proportions using Freeman‐Tukey double arcsine transformation. The main outcome was the prevalence of SM‐TAAs in patients with AAAs. Secondary outcomes were the prevalence of synchronous TAAs, metachronous TAAs, prevalence of TAAs in patients with AAA according to the anatomic location (ascending, arch, and descending) and the differences in prevalence of these aneurysms according to sex and risk factors. Six studies were included. The pooled‐prevalence of SM‐TAA in AAA patients was 19.2% (95% CI, 12.3–27.3). Results revealed that 15.2% (95% CI, 7.1–25.6) of men and 30.7% (95% CI, 25.2–36.5) of women with AAA had an SM‐TAA. Women with AAA had a 2‐fold increased risk of having an SM‐TAA than men (relative risk [RRs], 2.16; 95% CI, 1.32–3.55). Diabetes mellitus was associated with a 43% decreased risk of having SM‐TAA (RRs, 0.57; 95% CI, 0.41–0.80).

Conclusions
Since a fifth of AAA patients will have an SM‐TAA, routine screening of SM‐TAA and their clinical impact should be more thoroughly studied in patients with known AAA.