bluuebunny/crossref_metadata_2025_split huggingface dataset:
BiTE-ing into Prostate Cancer with Bispecific T-cell Engagers
Authors: Kamat Nikhil V. , Yu Evan Y. , Lee John K. 
Published: March 2021

Abstract
Targeting prostate-specific membrane antigen (PSMA) has important therapeutic ramifications, more recently including immune oncology. Data were recently presented on the preclinical efficacy of a half-life extended bispecific T-cell engager, AMG 160, which binds PSMA and CD3 to induce T-cell–driven cytolytic activity against prostate cancer.
See related article by Deegen et al., p. 2928
The Hippo Pathway Effector YAP Promotes Ferroptosis via the E3 Ligase SKP2
Authors: Yang Wen-Hsuan , Lin Chao-Chieh , Wu Jianli , Chao Pei-Ya , Chen Kuan , Chen Po-Han , Chi Jen-Tsan 
Published: March 2021

Abstract

Ferroptosis is a new form of regulated cell death resulting from the accumulation of lipid-reactive oxygen species. A growing number of studies indicate ferroptosis as an important tumor suppressor mechanism having therapeutic potential in cancers. Previously, we identified TAZ, a Hippo pathway effector, regulates ferroptosis in renal and ovarian cancer cells. Because YAP (Yes-associated protein 1) is the one and only paralog of TAZ, sharing high sequence similarity and functional redundancy with TAZ, we tested the potential roles of YAP in regulating ferroptosis. Here, we provide experimental evidence that YAP removal confers ferroptosis resistance, whereas overexpression of YAP sensitizes cancer cells to ferroptosis. Furthermore, integrative analysis of transcriptome reveals S-phase kinase-associated protein 2 (SKP2), an E3 ubiquitin ligase, as a YAP direct target gene that regulates ferroptosis. We found that the YAP knockdown represses the expression of SKP2. Importantly, the genetic and chemical inhibitions of SKP2 robustly protect cells from ferroptosis. In addition, knockdown of YAP or SKP2 abolishes the lipid peroxidation during erastin-induced ferroptosis. Collectively, our results indicate that YAP, similar to TAZ, is a determinant of ferroptosis through regulating the expression of SKP2. Therefore, our results support the connection between Hippo pathway effectors and ferroptosis with significant therapeutic implications.

Implications:
This study reveals that YAP promotes ferroptosis by regulating SKP2, suggesting novel therapeutic options for YAP-driven tumors.
RAF-Mutant Melanomas Differentially Depend on ERK2 Over ERK1 to Support Aberrant MAPK Pathway Activation and Cell Proliferation
Authors: Crowe Matthew S. , Zavorotinskaya Tatiana , Voliva Charles F. , Shirley Matthew D. , Wang Yanqun , Ruddy David A. , Rakiec Daniel P. , Engelman Jeffery A. , Stuart Darrin D. , Freeman Alyson K. 
Published: March 2021

Abstract

Half of advanced human melanomas are driven by mutant BRAF and dependent on MAPK signaling. Interestingly, the results of three independent genetic screens highlight a dependency of BRAF-mutant melanoma cell lines on BRAF and ERK2, but not ERK1. ERK2 is expressed higher in melanoma compared with other cancer types and higher than ERK1 within melanoma. However, ERK1 and ERK2 are similarly required in primary human melanocytes transformed with mutant BRAF and are expressed at a similar, lower amount compared with established cancer cell lines. ERK1 can compensate for ERK2 loss as seen by expression of ERK1 rescuing the proliferation arrest mediated by ERK2 loss (both by shRNA or inhibition by an ERK inhibitor). ERK2 knockdown, as opposed to ERK1 knockdown, led to more robust suppression of MAPK signaling as seen by RNA-sequencing, qRT-PCR, and Western blot analysis. In addition, treatment with MAPK pathway inhibitors led to gene expression changes that closely resembled those seen upon knockdown of ERK2 but not ERK1. Together, these data demonstrate that ERK2 drives BRAF-mutant melanoma gene expression and proliferation as a function of its higher expression compared with ERK1. Selective inhibition of ERK2 for the treatment of melanomas may spare the toxicity associated with pan-ERK inhibition in normal tissues.

Implications:
BRAF-mutant melanomas overexpress and depend on ERK2 but not ERK1, suggesting that ERK2-selective inhibition may be toxicity sparing.
Intrinsic Immunogenicity of Small Cell Lung Carcinoma Revealed by Its Cellular Plasticity
Authors: Mahadevan Navin R. , Knelson Erik H. , Wolff Jacquelyn O. , Vajdi Amir , Saigí Maria , Campisi Marco , Hong Deli , Thai Tran C. , Piel Brandon , Han Saemi , Reinhold Bruce B. , Duke-Cohan Jonathan S. , Poitras Michael J. , Taus Luke J. , Lizotte Patrick H. , Portell Andrew , Quadros Victor , Santucci Alison D. , Murayama Takahiko , Cañadas Israel , Kitajima Shunsuke , Akitsu Aoi , Fridrikh Maya , Watanabe Hideo , Reardon Brendan , Gokhale Prafulla C. , Paweletz Cloud P. , Awad Mark M. , Van Allen Eliezer M. , Lako Ana , Wang Xi-Tao , Chen Benjamin , Hong Fangxin , Sholl Lynette M. , Tolstorukov Michael Y. , Pfaff Kathleen , Jänne Pasi A. , Gjini Evisa , Edwards Robin , Rodig Scott , Reinherz Ellis L. , Oser Matthew G. , Barbie David A. 
Published: March 2021

Abstract

Small cell lung carcinoma (SCLC) is highly mutated, yet durable response to immune checkpoint blockade (ICB) is rare. SCLC also exhibits cellular plasticity, which could influence its immunobiology. Here we discover that a distinct subset of SCLC uniquely upregulates MHC I, enriching for durable ICB benefit. In vitro modeling confirms epigenetic recovery of MHC I in SCLC following loss of neuroendocrine differentiation, which tracks with derepression of STING. Transient EZH2 inhibition expands these nonneuroendocrine cells, which display intrinsic innate immune signaling and basally restored antigen presentation. Consistent with these findings, murine nonneuroendocrine SCLC tumors are rejected in a syngeneic model, with clonal expansion of immunodominant effector CD8 T cells. Therapeutically, EZH2 inhibition followed by STING agonism enhances T-cell recognition and rejection of SCLC in mice. Together, these data identify MHC I as a novel biomarker of SCLC immune responsiveness and suggest novel immunotherapeutic approaches to co-opt SCLC's intrinsic immunogenicity.

Significance:
SCLC is poorly immunogenic, displaying modest ICB responsiveness with rare durable activity. In profiling its plasticity, we uncover intrinsically immunogenic MHC Ihi subpopulations of nonneuroendocrine SCLC associated with durable ICB benefit. We also find that combined EZH2 inhibition and STING agonism uncovers this cell state, priming cells for immune rejection.
This article is highlighted in the In This Issue feature, p. 1861
MIR503HG Loss Promotes Endothelial-to-Mesenchymal Transition in Vascular Disease
Authors: Monteiro João P. , Rodor Julie , Caudrillier Axelle , Scanlon Jessica P. , Spiroski Ana-Mishel , Dudnakova Tatiana , Pflüger-Müller Beatrice , Shmakova Alena , von Kriegsheim Alex , Deng Lin , Taylor Richard S. , Wilson-Kanamori John R. , Chen Shiau-Haln , Stewart Kevin , Thomson Adrian , Mitić Tijana , McClure John D. , Iynikkel Jean , Hadoke Patrick W.F. , Denby Laura , Bradshaw Angela C. , Caruso Paola , Morrell Nicholas W. , Kovacic Jason C. , Ulitsky Igor , Henderson Neil C. , Caporali Andrea , Leisegang Matthias S. , Brandes Ralf P. , Baker Andrew H. 
Published: March 2021

Rationale:
Endothelial-to-mesenchymal transition (EndMT) is a dynamic biological process involved in pathological vascular remodeling. However, the molecular mechanisms that govern this transition remain largely unknown, including the contribution of long noncoding RNAs (lncRNAs).

Objectives:
To investigate the role of lncRNAs in EndMT and their relevance to vascular remodeling.

Methods and Results:
To study EndMT in vitro, primary endothelial cells were treated with transforming growth factor-β2 and interleukin-1β. Single-cell and bulk RNA-seq (RNA-sequencing) were performed to investigate the transcriptional architecture of EndMT and identify regulated lncRNAs. The functional contribution of seven lncRNAs during EndMT was investigated based on a DsiRNA (dicer-substrate short interfering RNAs) screening assay. The loss of lncRNA MIR503HG was identified as a common signature across multiple human endothelial cell types undergoing EndMT in vitro. MIR503HG depletion induced a spontaneous EndMT phenotype, while its overexpression repressed hallmark EndMT changes, regulating 29% of its transcriptome signature. Importantly, the phenotypic changes induced by MIR503HG were independent of miR-424 and miR-503, which overlap the lncRNA locus. The pathological relevance of MIR503HG downregulation was confirmed in vivo using sugen/hypoxia–induced pulmonary hypertension in mice, as well as in human clinical samples, in lung sections and blood outgrowth endothelial cells from pulmonary arterial hypertension patients. Overexpression of human MIR503HG in sugen/hypoxia mice led to reduced mesenchymal marker expression, suggesting MIR503HG therapeutic potential. We also revealed that MIR503HG interacts with the PTBP1 (polypyrimidine tract binding protein 1) and regulates its protein level. PTBP1 regulation of EndMT markers suggests that the role of MIR503HG in EndMT might be mediated in part by PTBP1.

Conclusions:
This study reports a novel lncRNA transcriptional profile associated with EndMT and reveals the crucial role of the loss of MIR503HG in EndMT and its relevance to pulmonary hypertension.
Abstract P211: Stroke Recovery Navigator to Improve Post Stroke Recovery
Authors: Rindels Erin , Taylor Anna , Quigley Aurora ,   SRN Steering Committee
Published: March 2021

Social support impacts recovery after stroke. Patient centered navigation programs provide social support and have shown benefit with other patient populations. The purpose of this study is to determine if there is a difference in outcomes for stroke survivors and caregivers who receive navigation services post-discharge. The study used a multi-center quasi-experimental before-after design to examine the impact of a telephone-based stroke navigation. Selected recruitment sites were nine facilities without navigation programs. Facilities provided information to survivors and caregivers about Stroke Recovery Navigator (SRN) prior to discharge and made referrals to the program. Participants were randomized into control and intervention groups using a computer-generated coin flip. Navigators completed telephone assessments within a week of referral. Navigators received the following trainings: Patient Navigation Fundamentals, motivational interviewing, and mental health first aid. The Reintegration to Normal Living (RNLI) scale was completed by all survivors and the Zarit Caregiver Burden scale was completed by all caregivers. The control group completed the initial and final assessments using these tools. In addition to these assessments, the intervention group received an individualized navigation plan and weekly contact by the SRN. The study randomized 301 individuals (82 caregivers, 219 survivors), with completion rate of 32%. Caregiver demographic characteristics and baseline caregiver burden scores were not statistically significant. Caregiver burden in the intervention group were lower compared to the control group, but not statistically significant (p=0.25). Demographic characteristics for survivors were similar between groups. RNLI score for survivors was slightly higher for the intervention group (p<0.10). To achieve statistical significance additional participants were needed.
In conclusion differences in quality of life for survivors and caregivers were not statistically significant between the groups. Additional information on the benefits of an SRN program is needed to support its implementation. However, important lessons were learned to improve such program and its design.
China’s Public Diplomacy Goes Political
Authors: d’Hooghe Ingrid 
Published: March 2021

Summary
China’s growing confidence on the world stage under the leadership of President Xi Jinping is reflected in the country’s more active, vocal and, lately, even ‘wolf warrior’ diplomacy. It is also clearly visible in China’s public diplomacy approach, where priorities have shifted from advertising Chinese culture as the country’s major source of soft power to promoting China’s models of domestic and global governance. The Chinese government proudly presents policies such as the Belt and Road Initiative and, more recently China’s approach to the COVID-19 pandemic, as improvements in global governance or sometimes even as Chinese ‘gifts’ to the world. This article argues that under President Xi, the content and form of China’s public diplomacy have changed. China’s public diplomacy has hardened, it is more strongly controlled by the Chinese Communist Party and the content of China’s public diplomacy messages have become more political.
Kewatek, the Ikat Textiles from Adonara
Authors: Somi Kedan Petronela , Visser Leontine 
Published: March 2021

Abstract
Ikat textiles (kewatek) from Adonara, one of the Lesser Sunda Islands, are still seldom researched by textile specialists (Vatter 1984 [1932]; Barnes 1989). This article is the first account by a descendant from the island that builds on these studies to describe the social and cultural organization and taboos concerning ikat-dyeing and the weaving of kewatek in the twenty-first century. It also discusses recent government intervention and the actions of local NGO s to sustain Adonara textile identification and to stimulate the weaving of these sarongs for economic household purposes.
‘The Screaming Injustice of Colonial Relationships’
Authors: Hoogervorst Tom , Tarisa Melita 
Published: March 2021

Abstract
An insensitive poem published in 1935 sparked a wave of outrage among the Indies Chinese students in the Netherlands. Titled The yellow peril, it had started as an inside joke among Leiden’s Indologists, yet quickly aroused the fury of both moderates and radicals. Their anti-colonial activism flared up for months, attracting numerous allies and eventually taking hold in the Netherlands Indies. After the Indologists had apologized, the number of activists willing to push for more structural change dwindled. As such, this microhistory lays bare some broader dynamics of anti-racism. We argue that ethnic Chinese, who continue to be portrayed as an unobtrusive model minority, have a longer legacy of activism than they are usually given credit for. This is particularly relevant in the present, when Covid-induced Sinophobia, anti-Black racism, and a reassessment of the colonial past are inspiring new movements and forging new anti-racist solidarities.
Filaments in Time and Space: Lien Heng’s Elegant Words and the Linguistic Ecology of Taiwan in the 1930s
Authors: McConaghy Mark 
Published: March 2021

Abstract
This article revisits the debate which occurred in the early 1930s regarding ‘Taiwanese Language Writing’ to argue that these discussions represented an extended interrogation of the linguistic ecology of the island: how written scripts and spoken sounds functioned in Taiwan to make meaning in relation to a larger environmental, animistic, and social whole. Set against the backdrop of this debate, the 1932 work Elegant Words by the famed intellectual Lien Heng stands out as an important text. Lien Heng’s vision of Minnan as a historically grounded yet broadly cosmopolitan language was a particularly enabling expression of Taiwanese consciousness, which presented an island that could face many directions at once, absorbing the textual signs of a deep Sinographic past while remaining vitally open to a complex and increasingly integrated world. Lien Heng’s cultural criticism presaged many of the debates about language, history, and identity that would take place in subsequent decades in Taiwan, and as such his work continues to have resonance today for thinking critically about Taiwan’s place in the modern world.
A Surplus of Fish: Language, Literature, and Cultural Ecologies in Ng Kim Chew’s Fiction
Authors: Rojas Carlos 
Published: March 2021

Abstract
This essay uses an examination of intertwined thematics of fish and text in the fiction of the ethnically Malaysian Chinese author Ng Kim Chew in order to reflect on a broader set of ecological concerns, including issues relating to the natural ecology of the Southeast Asian regions depicted in Ng’s works, together with the overlapping literary ecosystems within which his works are embedded. In particular, the essay is concerned with the ways in which Ng’s fiction reflects on the relationship between the field of Southeast Asian Sinophone literature and the partially overlapping ecosystem of world literature.
Diastylis uniplicata sp. nov. (Crustacea: Cumacea: Diastylidae) a new Korean cumacean
Authors: KIM SUNG-HYUN , LEE CHANG-MOK 
Published: March 2021

A new species of cumacean belonging to the genus Diastylis Say, 1818 was collected from the Nokdo Island, Korea. The new species, Diastylis uniplicata sp. nov., can be distinguished from all other Diastylis species by the combination of the smooth carapace surface with a transverse ridge and a pair of oblique ridges, and telson 1.7 times as long as pleonite 6, with 5–6 short stout simple setae laterally. Full illustrations of the new species, including the mouthparts, are given in this paper. Also, a key to the Korean species of Diastylis is provided.
Advancements and Characteristics of Gauge Ingest and Quality Control within the Multi-Radar Multi-Sensor System
Authors: Martinaitis Steven M. , Cocks Stephen B. , Simpson Micheal J. , Osborne Andrew P. , Harkema Sebastian S. , Grams Heather M. , Zhang Jian , Howard Kenneth W. 
Published: March 2021

AbstractThis study describes recent advancements in the Multi-Radar Multi-Sensor (MRMS) automated gauge ingest and quality control (QC) processes. A data latency analysis for the combined multiple gauge collection platforms provided guidance for a multiple-pass generation and delivery of gauge-based precipitation products. Various advancements to the gauge QC logic were evaluated over a 21-month period, resulting in an average of 86% of hourly gauge observations per hour being classified as useful. The fully-automated QC logic was compared to manual human QC for a limited domain, which showed a > 95% agreement in their QC reasoning categories. This study also includes an extensive evaluation of various characteristics related to the gauge observations ingested into the MRMS system. Duplicate observations between gauge collection platforms highlighted differences in site coordinates; moreover, errors in Automated Surface Observing System (ASOS) station site coordinates resulted in > 79% of sites being located in a different MRMS 1-km grid cell. The ASOS coordinate analysis combined with examinations of other limitations regarding gauge observations highlight the need for robust and accurate metadata to further enhance the quality control of gauge data.
Chest and Pelvis X-Rays as a Screening Tool for Abdominal Injury in Geriatric Blunt Trauma Patients
Authors: Leede Emily , Cardenas Tatiana C. P. , Emigh Brent J. , Brown Lawrence H. , Teixeira Pedro G. , Trust Marc D. , Coopwood Ben , Aydelotte Jayson , Ali Sadia , Brown Carlos V. R. 
Published: March 2021

Background This study evaluates the utility of chest (CXR) and pelvis (PXR) X-ray, as adjuncts to the primary survey, in screening geriatric blunt trauma (GBT) patients for abdominal injury or need for laparotomy. Methods We performed a retrospective analysis of patients 65-89 years in the 2014 National Trauma Data Bank. X-ray injuries were identified by ICD9 codes and defined as any injury felt to be readily detectable by a non-radiologist. X-ray findings were dichotomized as “both negative” (no injury presumptively apparent on CXR or PXR) or “either positive” (any injury presumptively apparent on CXR or PXR). Rates of abdominal injuries and laparotomy were compared and used to calculate sensitivity and specificity. The primary outcomes were abdominal injury and laparotomy. The secondary outcomes included mortality, ventilator days, and hospital days. Results A total of 202 553 patients met criteria. Overall, 9% of patients with either positive X-rays had abdominal injury and 2% laparotomy vs. 1.1% and .3% with both negative ( P < .001). The specificity for any positive X-ray was 79% for abdominal injury and 78% for laparotomy. The sensitivity was 69% for abdominal injury and laparotomy. The either positive group had fewer ventilator days (.3 vs. .8, P < .0001), longer length of stay (7 vs. 5, P < .0001), and higher mortality (6% vs. 4%, P < .0001) vs both negative. Conclusion CXR and PXR can be used to assess for intra-abdominal injury and need for laparotomy. GBT patients with either positive X-rays should continue workup regardless of mechanism due to the high specificity of this tool for abdominal injury and need for laparotomy.
Role and Growth of Independent Medicare‐Billing Otolaryngologic Advanced Practice Providers
Authors: Patel Rahul A. , Torabi Sina J. , Kasle David A. , Pivirotto Allison , Manes R. Peter 
Published: March 2021

ObjectiveTo evaluate the role and growth of independently billing otolaryngology (ORL) advanced practice providers (APPs) within a Medicare population.Study DesignRetrospective cross‐sectional study.SettingMedicare Provider Utilization and Payment Data: Physician and Other Supplier Data Files, 2012‐2017.MethodsThis retrospective review included data and analysis of independent Medicare‐billing ORL APPs. Total sums and medians were gathered for Medicare reimbursements, services performed, number of patients, and unique Current Procedural Terminology (CPT) codes used, along with geographic and sex distributions.ResultsThere has been near‐linear growth in number of ORL APPs (13.7% to 18.4% growth per year), with a 115.4% growth from 2012 to 2017. Similarly, total Medicare‐allowed reimbursement (2012: $15,568,850; 2017: $35,548,446.8), total number of services performed (2012: 313,676; 2017: 693,693.7), and total number of Medicare fee‐for‐service (FFS) patients (2012: 108,667; 2017: 238,506) increased. Medians of per APP number of unique CPT codes used, Medicare‐allowed reimbursement, number of services performed, and number of Medicare FFS patients have remained constant. There were consistently more female APPs than male APPs (female APP proportion range: 71.3%‐76.7%). Compared to ORL physicians, there was a significantly greater proportion of APPs practicing in a rural setting as opposed to urban settings (2017: APP proportion 13.6% vs ORL proportion 8.4%; P <. 001).ConclusionAlthough their scope of practice has remained constant, independently billing ORL APPs are rapidly increasing in number, which has led to increased Medicare reimbursements, services, and patients. ORL APPs tend to be female and are used more heavily in regions with fewer ORL physicians.