bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell Spatial Proteomic Revelations on the Multiparametric MRI Heterogeneity of Clinically Significant Prostate Cancer
Authors: Pachynski Russell K. , Kim Eric H. , Miheecheva Natalia , Kotlov Nikita , Ramachandran Akshaya , Postovalova Ekaterina , Galkin Ilia , Svekolkin Viktor , Lyu Yang , Zou Qiong , Cao Dengfeng , Gaut Joseph , Ippolito Joseph E. , Bagaev Alexander , Bruttan Maria , Gancharova Olga , Nomie Krystle , Tsiper Maria , Andriole Gerald L. , Ataullakhanov Ravshan , Hsieh James J. 
Published: March 2021

Abstract

Purpose:
Multiparametric MRI (mpMRI) has become an indispensable radiographic tool in diagnosing prostate cancer. However, mpMRI fails to visualize approximately 15% of clinically significant prostate cancer (csPCa). The molecular, cellular, and spatial underpinnings of such radiographic heterogeneity in csPCa are unclear.

Experimental Design:
We examined tumor tissues from clinically matched patients with mpMRI-invisible and mpMRI-visible csPCa who underwent radical prostatectomy. Multiplex immunofluorescence single-cell spatial imaging and gene expression profiling were performed. Artificial intelligence–based analytic algorithms were developed to examine the tumor ecosystem and integrate with corresponding transcriptomics.

Results:
More complex and compact epithelial tumor architectures were found in mpMRI-visible than in mpMRI-invisible prostate cancer tumors. In contrast, similar stromal patterns were detected between mpMRI-invisible prostate cancer and normal prostate tissues. Furthermore, quantification of immune cell composition and tumor-immune interactions demonstrated a lack of immune cell infiltration in the malignant but not in the adjacent nonmalignant tissue compartments, irrespective of mpMRI visibility. No significant difference in immune profiles was detected between mpMRI-visible and mpMRI-invisible prostate cancer within our patient cohort, whereas expression profiling identified a 24-gene stromal signature enriched in mpMRI-invisible prostate cancer. Prostate cancer with strong stromal signature exhibited a favorable survival outcome within The Cancer Genome Atlas prostate cancer cohort. Notably, five recurrences in the 8 mpMRI-visible patients with csPCa and no recurrence in the 8 clinically matched patients with mpMRI-invisible csPCa occurred during the 5-year follow-up post-prostatectomy.

Conclusions:
Our study identified distinct molecular, cellular, and structural characteristics associated with mpMRI-visible csPCa, whereas mpMRI-invisible tumors were similar to normal prostate tissue, likely contributing to mpMRI invisibility.
Back from the Brink: EGFR Inhibition in Gastroesophageal Cancer
Authors: Openshaw Mark R. , Pinato David J. , Valeri Nicola 
Published: March 2021

Abstract
Gastroesophageal adenocarcinomas (GEA) remain difficult to treat with limited targeted therapeutics. Negative results from randomized trials of EGFR inhibitors (EGFRi) in patients with molecularly unselected GEA have hampered the development of EGFRi in the gastroesophageal cancer space. A recent study reopens the game.
See related article by Corso et al., p. 3126
Defects in Emerin–Nucleoskeleton Binding Disrupt Nuclear Structure and Promote Breast Cancer Cell Motility and Metastasis
Authors: Liddane Alexandra G. , McNamara Chelsea A. , Campbell Mallory C. , Mercier Isabelle , Holaska James M. 
Published: March 2021

AbstractNuclear envelope proteins play an important role in regulating nuclear size and structure in cancer. Altered expression of nuclear lamins are found in many cancers and its expression is correlated with better clinical outcomes. The nucleus is the largest organelle in the cell with a diameter between 10 and 20 μm. Nuclear size significantly impacts cell migration. Nuclear structural changes are predicted to impact cancer metastasis by regulating cancer cell migration. Here we show emerin regulates nuclear structure in invasive breast cancer cells to impact cancer metastasis. Invasive breast cancer cells had 40% to 50% less emerin than control cells, which resulted in decreased nuclear size. Overexpression of GFP-emerin in invasive breast cancer cells rescued nuclear size and inhibited migration through 3.0 and 8.0 μm pores. Mutational analysis showed emerin binding to nucleoskeletal proteins was important for its regulation of nuclear structure, migration, and invasion. Importantly, emerin expression inhibited lung metastasis by 91% in orthotopic mouse models of breast cancer. Emerin nucleoskeleton-binding mutants failed to inhibit metastasis. These results support a model whereby emerin binding to the nucleoskeleton regulates nuclear structure to impact metastasis. In this model, emerin plays a central role in metastatic transformation, because decreased emerin expression during transformation causes the nuclear structural defects required for increased cell migration, intravasation, and extravasation.Implications:Modulating emerin expression and function represents new targets for therapeutic interventions of metastasis, because increased emerin expression rescued cancer metastasis.
TAGLN Is Downregulated by TRAF6-Mediated Proteasomal Degradation in Prostate Cancer Cells
Authors: Wen Fuping , Sun Xiaochen , Sun Chenxia , Dong Zhenyang , Jia Gaozhen , Bao Wei , Yu Haolan , Yang Chenghua 
Published: March 2021

AbstractTransgelin (TAGLN, also named SM22) is an actin-associated protein and affects dynamics of actin filaments. Deregulation of TAGLN contributes to the development of different cancers, and it is commonly considered to be a tumor suppressor. TAGLN is usually downregulated in prostate cancer; however, the detailed functions of TAGLN in prostate cancer and how TAGLN is regulated remains unclear. In this study, we confirmed that TAGLN is downregulated in prostate cancer tissues and demonstrated that the downregulation of TAGLN occurs through proteasomal degradation. Next, we found that the expression level of TAGLN is inversely correlated with TRAF6. We screened more than 20 E2–E3 pairs by in vitro ubiquitination assay and found that the E2A–TRAF6 pair catalyzed mono ubiquitination of TAGLN. We then identified the ubiquitination sites of TAGLN to be on K89 or K108 residues and demonstrated that ubiquitination of TAGLN on K89/K108 are important for TRAF6-mediated proteasomal degradation. Furthermore, we investigated the function of TAGLN in prostate cancer cells. We found that ablation of TAGLN promoted prostate cancer cell proliferation and suppressed their migration via activation of NF-κB and Myc signaling pathways. Overall, our study provided new insights into the mechanisms underlying TAGLN expression and activity in prostate cancer.Implications:E3 ligase TRAF6 mediate mono-ubiquitination and degradation of TAGLN, which leads to activation of NF-κB and Myc signaling pathways in prostate cancer cells.
An IFNγ/STAT1/JMJD3 Axis Induces ZEB1 Expression and Promotes Aggressiveness in Lung Adenocarcinoma
Authors: Yang Jianjian , Wang Xue , Huang Bing , Liu Rong , Xiong Hui , Ye Fan , Zeng Chenxi , Fu Xiangning , Li Lequn 
Published: March 2021

AbstractActive IFNγ signaling is a common feature of tumors responding to PD-1 checkpoint blockade. IFNγ exhibits both anti- and protumor activities. Here, we show that the treatment of lung adenocarcinoma cells with IFNγ led to a rapid increase of ZEB1 expression and a significant change in epithelial-to-mesenchymal transition (EMT)-associated gene expression pattern. Moreover, functional analyses show that IFNγ promoted cell migration in vitro and metastasis in vivo. We demonstrate that ZEB1 is required for IFNγ-promoted EMT, cell migration, and metastasis, as RNAi-mediated knockdown of ZEB1 abrogated EMT, cell migration, and metastasis induced by IFNγ. We show that IFNγ induced upregulation of JMJD3 significantly reduced H3K27 trimethylation in the promoter of the ZEB1 gene, which led to activation of ZEB1 gene transcription. IFNγ-induced JMJD3 expression was JAK1/2-STAT1 dependent. Inhibition of JMJD3 abrogated IFNγ-induced ZEB1 expression. IFNγ-induced ZEB1 also reduced miR-200 expression. Downregulation of ZEB1 increased miR-200 expression, which led to a reduction of PD-L1 expression induced by IFNγ. It is worth noting that knockdown of ZEB1 did not affect IFNγ-mediated antiproliferation and induction of CXCL9 and CXCL10. Thus, downregulation of ZEB1 may prevent the protumor activity of IFNγ while retaining its antitumor function. This study expands our understanding of IFNγ-mediated signaling and helps to identify therapeutic targets to improve current immunotherapies.Implications:IFNγ increases ZEB1 expression in a STAT1-JMJD3 dependent manner, and consequently promotes cancer cell aggressiveness. This study provides a potential target to minimize the procancer effect of IFNγ while preserving its antitumor function.
Revisiting the taxonomy of Strobilanthes lawsonii and S. pushpangadanii (Acanthaceae), two endemic taxa of Western Ghats, India
Authors: Cherian Blessy , Prabhukumar K.M. , Jagadeesan R. , Kumar V.V. Naveen , Balachandran Indira 
Published: March 2021

Strobilanthes lawsonii was described by Gamble based on a collection made from Sispara Ghat of Nilgiri District, Tamil Nadu. Later researchers reported its distribution in Kerala, and S. gamblei and S. pushpangadanii, two endemic species of the Western Ghats, were synonymised with S. lawsonii during the genus revision in southern India in 2006. During a recent expedition to Muthikulam forest of Palakkad, Kerala the authors collected typical S. lawsonii. After comparing the new collections with S. gamblei and S. pushpangadanii, it was found that both taxa are distinct from S. lawsonii, with the most notable morphological differences being partially fused corolla lobes and exserted stamens. A detailed comparison of the three taxa is provided here, along with color photographs and a taxonomic key for easy species identification.
Catalogue of selected insect groups of Lalwan Community Reserve and Ranjit Sagar Conservation Reserve, Punjab, India
Authors: Singh Amar Paul , Chandra Agni , Uniyal Virendra Prasad , Adhikari Bhupendra Singh 
Published: March 2021

We present the first documentation of the insect fauna of Lalwan Community Reserve and Ranjit Sagar Conservation Reserve, Punjab. The survey was conducted in the months of May and June 2019. Selected insect groups were focused on for the rapid documentation of the entomofauna. Overall, we recorded 91 species of insects belonging to the orders Lepidoptera, Coleoptera, and Odonata. A total of 68 species including 46 species of order Lepidoptera, nine species of Odonata, and 13 species of Coleoptera were reported from Lalwan Community Reserve. Thirty-seven species consisting of 23 species of Odonata and 14 species of Lepidoptera were recorded from Ranjit Sagar Conservation Reserve, Punjab.
Relocation of a GPS collared conflict Sloth Bear Melursus ursinus (Mammalia: Carnivora) in Karnataka, India
Authors: Arun Attur Shanmugam , Shanmugavelu Swaminathan , Pannerselvam Yogaraj , Sharp Thomas Robert , Stephens Sydney , Satyanarayan Kartick , Seshamani Geeta 
Published: March 2021

The relocation of conflict bears has been a tool used widely across the United States and Canada with mixed results. It has also been used in India with Sloth Bears, though without follow-up it remains unknown how successful these relocation efforts have been. We documented the capture and relocation of a conflict female Sloth Bear from a rural area near Bangalore, Karnataka, India to Bannerghatta National Park roughly 30km away. This female bear, approximately six years old, was fitted with a VHF/GPS store-on-board collar, and her movements tracked. She did not attempt to return to her capture location but during the first two-month period after being released she did roam over an area roughly six times that of typical female Sloth Bear home range. Over the subsequent months the area over which she roamed continued to decline. She was least active mid-day and more active in the evening, night, and early morning. During her last few weeks in January, before she was killed by an explosive device just outside of the park, her movement pattern shrank considerably. The post-mortem examination showed that she had been pregnant when killed and would have given birth within the next two weeks. These reduced movements were consistent with those of periparturient female bears or potentially with a bear becoming more acclimated to her new surroundings. The relocation effort appeared successful up until the Sloth Bear was killed by poacher activity.
Implementation of a Myocardial Perfusion Imaging Risk Algorithm to Inform Appropriate Downstream Invasive Testing and Treatment
Authors: Kumar Anirudh , Patel Divyang R. , Harb Serge C. , Greenberg Neil L. , Bhargava Ajay , Menon Venu , Ellis Stephen G. , Kapadia Samir R. , Hachamovitch Rory , Jaber Wael A. , Cremer Paul C. 
Published: March 2021

Background:
To risk stratify patients undergoing single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in accordance with appropriate use criteria for referral to coronary angiography, we developed a risk classification algorithm incorporating appropriate use criteria–defined risk features. We evaluated the association between this algorithm with downstream angiography, revascularization, and all-cause mortality.

Methods:
We studied consecutive patients who underwent SPECT-MPI from January 1, 2015, to December 31, 2017, and assigned a scan risk of low, intermediate, high, or indeterminate. With this stratification, we assessed referral for angiography and revascularization within 3 months of SPECT-MPI and intermediate-term mortality.

Results:

Among 12 799 patients, the mean age was 66 years, and a majority were men (56.8%). Most patients were low risk (83.6%) followed by intermediate (9.9%) and high risk (5.2%). Compared with low-risk patients, intermediate- and high-risk patients were more frequently referred for angiography (14.8% and 13.6% versus 2.0%;
P
<0.001) and revascularization (7.7% and 6.8% versus 0.7%;
P
<0.001). In 1008 propensity-matched patients, scan risk was independently associated with angiography after adjustment for ischemia, scar, or stress ejection fraction. At a mean follow-up of 2.3 years, mortality was higher with increased scan risk (high, 10.4%; intermediate, 7.1%; low, 4.1%;
P
<0.001). Compared with low scan risk, intermediate (hazard ratio, 1.37 [95% CI, 1.09–1.72];
P
=0.008) and high scan risk (hazard ratio, 1.98 [95% CI, 1.53–2.56];
P
<0.001) were associated with mortality in multivariable analysis. Similar findings were observed for those undergoing pharmacological and exercise SPECT-MPI with comparatively worse prognosis among pharmacological patients.

Conclusions:
This appropriate use criteria–derived risk classification algorithm for SPECT-MPI guided referral for coronary angiography and revascularization and was significantly associated with mortality. This algorithm may serve as an important tool to reaffirm appropriate use criteria and direct management of patients with stable ischemic heart disease undergoing stress testing.
Humility and Influence
Authors: Oleas-Mogollón Isabel 
Published: March 2021

Abstract
In June 1773 Doña Luisa García de Medina filed a lawsuit against the Spanish colonial government demanding the return of her generous donation to the confraternity of Saint Rosalia in Cuenca (Audiencia of Quito). This dispute provides a clear testimony of the influence of religious devotion and the power of female self-fashioning and agency. Doña Luisa’s piety, her promotion of the cult of Saint Rosalia, and her substantial donation allowed her to establish associations with leading local institutions and shape Cuenca’s sacred landscape and its inhabitants’ religious experience. Doña Luisa’s control of the processional route also identified her oratory as a space for spiritual introspection, self-representation, and social exchange. This article illustrates the importance of humility in the advancement of female agency in the colonial period. This research also proves that the study of religious confraternities supports a more inclusive construction of Spanish American history and shows the impact of female patronage in the civic space.
“When You Stop Pretending That You Know”
Authors: DeCoste D. Marcel 
Published: March 2021

Abstract
Increasingly addressing the religious dimension of Cormac McCarthy’s work, critics have frequently rooted it in a Gnosticism which holds, first, that the world is a place of evil and suffering and, second, that salvation is attained through knowledge made available only to the elect. The Stonemason, however, seems intent on refuting just such a thesis. Focusing on Ben and his grandfather Papaw, a centenarian stonemason, the play presents Ben as seeking, through mastery of the mason’s secrets, to become custodian to knowledge that will unlock the mysteries not just of a trade but of the cosmos. Yet this Gnostic quest fosters in him a moral negligence that leads to the deaths of two family members. Indeed, Ben’s tragedy stems precisely from his Gnostic prizing of secret lore and indifference to the Christian lessons Papaw himself most values—lessons not in god-like knowledge but in the practice of faith, humility, and love.
Studying the Bible in the “Post-Truth” Era
Authors: Brisman Leslie 
Published: March 2021

Abstract
When Jesus tells Pilate “my kingdom is not of this world” (John 18:36), he may be reassuring Pilate that Jesus and his followers pose no political threat. In our time, however, the secular idea of “alternate facts” has become something of a new religion and affects both our politics and our academic study. The difficult questions of what constitutes facts or credible critical interpretation of literary facts is particularly vexed when there is a question of citation. This article does not deal with questionable abbreviations of citation (such as “The Lord is merciful and compassionate” Exod. 34:6 without the deflected punishment clauses) or expanded citation (such as “You have heard it said, ‘Love your neighbor and hate your enemies’ ” [Matt. 5:43]). It concerns rather some instances where a verse may or may not be a citation and where extra-biblical ideology can interfere with the interpretation of what is being quoted, if it is being quoted. “The poor you have always with you” (Mark 14:7, possibly citing Deut. 15:11) is one such example.
Environmental and Collective Rights: Differences between Indigenous and Non-Indigenous ngo s Involved with the United Nations Human Rights Council
Authors: Hallward Maia , Butcher Charity , Downs Jonathan Taylor , Cook Emily 
Published: March 2021

Abstract
Scholarship on human rights and environmental justice suggests that organizations vary in their messaging regarding outcomes related to environmental protection and sustainability, differences often found in the divide between the Global North and Global South. The literature also suggests that Indigenous organizations represent groups that traditionally focus on issues of sovereignty, while grappling with unique problems related to assimilation, cultural preservation, and oppression. This study utilizes empirical data gathered from 333 non-governmental organizations affiliated with the United Nations Human Rights Council to explore whether Indigenous and non-Indigenous organizations, which share many aspects of their mission with one another at the transnational level, differ on issues related to environment sustainability and collective identity rights. Our results indicate that Indigenous organizations take a more holistic approach in addressing the relationship between humans and the natural world, centring marginalized perspectives through restorative justice and the needs of current and future generations.
Use of Integrated Global Climate Model Simulations and Statistical Time Series Forecasting to Project Regional Temperature and Precipitation
Authors: Lai Yuchuan , Dzombak David A. 
Published: March 2021

AbstractAn integrated technique combining global climate model (GCM) simulation results and a statistical time series forecasting model [the autoregressive integrated moving average (ARIMA) model] was developed to bring together the climate change signal from GCMs to city-level historical observations as an approach to obtain location-specific temperature and precipitation projections. This approach assumes that regional temperature and precipitation time series reflect a combination of an underlying climate change signal series and a regional-deviation-from-the-signal series. An ensemble of GCMs is used to describe and provide the climate change signal, and the ARIMA model is used to model and project the regional deviation. Qualitative and quantitative assessments were conducted for evaluating the projection performance of the hybrid GCM-ARIMA (G-ARIMA) model. The results indicate that the G-ARIMA model can provide projected city-specific daily temperature and precipitation series comparable to historical observations and can have improved projection accuracy for several assessed annual indices compared to a commonly used downscaled projection product. The G-ARIMA model is subject to some limitations and uncertainties from the GCM-provided climate change signal. A notable feature of the G-ARIMA model is the efficiency with which projections can be updated when new observations become available, thus facilitating updating of regional temperature and precipitations projections. Given the increasing need for and use of location-specific climate projections in practical engineering applications, the G-ARIMA model is an option for regional temperature and precipitation projection for such applications.
The Terminal Velocity of Axisymmetric Cloud Drops and Raindrops Evaluated by the Immersed Boundary Method
Authors: Ong Chia Rui , Miura Hiroaki , Koike Makoto 
Published: March 2021

AbstractThe terminal velocity of cloud drops and raindrops used in numerical model calculations can significantly affect weather predictions. Current formulations rely on laboratory experiments made in the 1940s and 1960s. Because these experiments were performed only at typical environmental conditions of 20°C and 1013 hPa, parameterizations have been introduced to deduce the terminal velocity aloft without rigorous evaluation. In this study, an incompressible two-phase flow direct numerical simulation model is used to calculate the free-falling motion of axisymmetric drops with diameters between 0.025 and 0.5 mm to study the terminal fall velocity. Simulated terminal fall velocities of free-falling drops at 20°C and 1013 hPa agree within 3.2% with the previous empirical parameterization (Beard formula), and 4.5% with existing laboratory data in the diameter range between 0.3 and 0.5 mm. The velocities converge to the analytic Hadamard–Rybczynski solution within 2% for small Reynolds numbers, demonstrating the robustness of our simulations. Simulations under various atmospheric conditions show that existing empirical parameterizations that account for the air density dependence of the terminal velocity have errors up to 11.8% under the conditions examined in this study. We propose a new empirical formula that describes the air density dependence of the terminal velocity. It is also shown that the falling speed of a small drop is not sensitive to shape oscillation, and the terminal velocity decreases by only less than 1.3% when the axis ratio increases by 12% with reduced surface tension. Internal circulation within falling drops is also presented and compared with previous studies.