bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early plasma circulating tumor DNA (ctDNA) changes predict response to first-line pembrolizumab-based therapy in non-small cell lung cancer (NSCLC)
Authors: Ricciuti Biagio , Jones Greg , Severgnini Mariano , Alessi Joao V , Recondo Gonzalo , Lawrence Marissa , Forshew Tim , Lydon Christine , Nishino Mizuki , Cheng Michael , Awad Mark 
Published: March 2021

BackgroundCurrently available biomarkers are imperfect in their ability to predict responses to the multiple first-line treatment options available for patients with advanced non-small cell lung cancer (NSCLC). Having an early pharmacodynamic marker of treatment resistance may help redirect patients onto more effective alternative therapies. We sought to determine if changes in circulating tumor DNA (ctDNA) levels after initiation of first-line pembrolizumab±chemotherapy in NSCLC would enable early prediction of response prior to radiological assessment.MethodsPlasma collected from patients with advanced NSCLC prior to and serially after starting first-line pembrolizumab±platinum doublet chemotherapy was analyzed by next-generation sequencing using enhanced tagged-amplicon sequencing of hotspots and coding regions from 36 genes. Early change in ctDNA allele fraction (AF) was correlated with radiographic responses and long-term clinical outcomes.ResultsAmong 62 patients who received first-line pembrolizumab±platinum/pemetrexed and underwent ctDNA assessment, 45 had detectable ctDNA alterations at baseline. The median change in AF at the first follow-up (at a median of 21 days after treatment initiation) was −90.1% (range −100% to +65%) among patients who subsequently had a radiologic response (n=18), –19.9% (range: −100% to +1884%) among stable disease cases (n=15), and +28.8% (range: −100% to +410%) among progressive disease cases (n=12); p=0.003. In addition, there was a significant correlation between the percent change in ctDNA at the first follow-up and the percent change in tumor target lesions from baseline (R=0.66, p<0.001). AF decrease between the pretreatment and first on-treatment blood draw was associated with significantly higher response rate (60.7% vs 5.8%, p=0.0003), and significantly longer median progression-free survival (8.3 vs 3.4 months, HR: 0.29 (95% CI: 0.14 to 0.60), p=0.0007) and median overall survival (26.2 vs 13.2 months, HR: 0.34 (95% CI: 0.15 to 0.75), p=0.008) compared with cases with an AF increase.ConclusionIn patients with advanced NSCLC, rapid decreases in ctDNA prior to radiological assessment correlated with clinical benefit. These results suggest a potential role for ctDNA as an early pharmacodynamic biomarker of response or resistance to immunotherapies.
Assessment of post-trauma complications in eight million trauma cases over a decade in the USA
Authors: Jakobsen Rasmus Kirial , Bonde Alexander , Sillesen Martin 
Published: March 2021

BackgroundTrauma is associated with a significant risk of post-trauma complications (PTCs). These include thromboembolic events, strokes, infections, and failure of organ systems (eg, kidney failure). Although care of the trauma patient has evolved during the last decade, whether this has resulted in a reduction in specific PTCs is unknown. We hypothesize that the incidence of PTCs has been decreasing during a 10-year period from 2007 to 2017.MethodsThis is a descriptive study of trauma patients originating from level 1, 2, 3, and 4 trauma centers in the USA, obtained via the Trauma Quality Improvement Program (TQIP) database from 2007 to 2017. PTCs documented throughout the time frame were extracted along with demographic variables. Multiple regression modeling was used to associate admission year with PTCs, while controlling for age, gender, Glasgow Coma Scale score, and Injury Severity Score.ResultsData from 8 720 026 trauma patients were extracted from the TQIP database. A total of 366 768 patients experienced one or more PTCs. There was a general decrease in the incidence of PTCs during the study period, with the overall incidence dropping from 7.0% in 2007 to 2.8% in 2017. Multiple regression identified a slight decrease in incidence in all PTCs, although deep surgical site infection (SSI), deep venous thrombosis (DVT), and stroke incidences increased when controlled for confounders.DiscussionOverall the incidence of PTCs dropped during the 10-year study period, although deep SSI, DVT, stroke, and cardiac arrest increased during the study period. Better risk prediction tools, enabling a precision medicine approach, are warranted to identify at-risk patients.Level of evidenceIII.
Photon frequency shift in curvature-based Extended Theories of Gravity
Authors: Capozziello S. , Lambiase G. , Stabile A. , Stabile An. 
Published: March 2021

AbstractWe study the frequency shift of photons generated by rotating gravitational sources in the framework of curvature-based Extended Theories of Gravity. The discussion is developed considering the weak-field approximation. Following a perturbative approach, we analyze the process of exchanging photons between Earth and a given satellite, and we find a general relation to constrain the free parameters of gravitational theories. Finally, we suggest the Moon as a possible laboratory to test theories of gravity by future experiments which can be, in principle, based also on other Solar System bodies.
IFNα Augments Clinical Efficacy of Regulatory T-cell Depletion with Denileukin Diftitox in Ovarian Cancer
Authors: Thibodeaux Suzanne R. , Barnett Brian B. , Pandeswara Srilakshmi , Wall Shawna R. , Hurez Vincent , Dao Vinh , Sun Lishi , Daniel Benjamin J. , Brumlik Michael J. , Drerup Justin , Padrón Álvaro , Whiteside Teresa , Kryczek Ilona , Zou Weiping , Curiel Tyler J. 
Published: March 2021

AbstractPurpose:Immunotherapy treats some cancers, but not ovarian cancer. Regulatory T cells (Tregs) impede anti-ovarian cancer immunity but effective human Treg-directed treatments are lacking. We tested Treg depletion with denileukin diftitox (DD) ± IFNα as ovarian cancer immunotherapy.Patients and Methods:Mice with syngeneic ID8 ovarian cancer challenge were treated with DD, IFNα, or both. The phase 0/I trial tested one dose-escalated DD infusion for functional Treg reduction, safety, and tolerability. The phase II trial added IFNα2a to DD if DD alone failed clinically.Results:DD depleted Tregs, and improved antitumor immunity and survival in mice. IFNα significantly improved antitumor immunity and survival with DD. IFNα did not alter Treg numbers or function but boosted tumor-specific immunity and reduced tumor Treg function with DD by inducing dendritic cell IL6. DD alone was well tolerated, depleted functional blood Tregs and improved immunity in patients with various malignancies in phase 0/I. A patient with ovarian cancer in phase 0/I experienced partial clinical response prompting a phase II ovarian cancer trial, but DD alone failed phase II. Another phase II trial added pegylated IFNα2a to failed DD, producing immunologic and clinical benefit in two of two patients before a DD shortage halt. DD alone was well tolerated. Adding IFNα increased toxicities but was tolerable, and reduced human Treg numbers in blood, and function through dendritic cell–induced IL6 in vitro.Conclusions:Treg depletion is clinically useful but unlikely alone to cure ovarian cancer. Rational treatment agent combinations can salvage clinical failure of Treg depletion alone, even when neither single agent provides meaningful clinical benefit.
L-Plastin Promotes Gastric Cancer Growth and Metastasis in a Helicobacter pylori cagA-ERK-SP1–Dependent Manner
Authors: Teng Yong-Sheng , Chen Wan-Yan , Yan Zong-Bao , Lv Yi-Pin , Liu Yu-Gang , Mao Fang-Yuan , Zhao Yong-Liang , Peng Liu-Sheng , Cheng Ping , Duan Mu-Bing , Chen Weisan , Wang Yu , Luo Ping , Zou Quan-Ming , Chen Jun , Zhuang Yuan 
Published: March 2021

Abstract

Actin cytoskeleton dynamic rearrangement is required for tumor cell metastasis and is a key characteristic of Helicobacter pylori (H. pylori)-infected host cells. Actin cytoskeleton modulation is coordinated by multiple actin-binding proteins (ABP). Through Kyoto encyclopedia of gene and genomes database, GEPIA website, and real-time PCR data, we found that H. pylori infection significantly induced L-plastin, a key ABP, in gastric cancer cells. We further explored the regulation and function of L-plastin in H. pylori–associated gastric cancer and found that, mechanistically, H. pylori infection induced gastric cancer cells to express L-plastin via cagA-activated ERK signaling pathway to mediate SP1 binding to L-plastin promoter. Moreover, this increased L-plastin promoted gastric cancer cell proliferation and migration in vitro and facilitated the growth and metastasis of gastric cancer in vivo. Finally, we detected the expression pattern of L-plastin in gastric cancer tissues, and found that L-plastin was increased in gastric cancer tissues and that this increase of L-plastin positively correlated with cagA+ H. pylori infection status. Overall, our results elucidate a novel mechanism of L-plastin expression induced by H. pylori, and a new function of L-plastin–facilitated growth and metastasis of gastric cancer, and thereby implicating L-plastin as a potential therapeutic target against gastric cancer.

Implications:
Our results elucidate a novel mechanism of L-plastin expression induced by H. pylori in gastric cancer, and a new function of L-plastin–facilitated gastric cancer growth and metastasis, implicating L-plastin as a potential therapeutic target against gastric cancer.
A Parathyroid–Gut Axis: Hypercalcemia and the Pathogenesis of Gastrinoma in Multiple Endocrine Neoplasia 1
Authors: Hackeng Wenzel M. , Dreijerink Koen M.A. , Offerhaus G. Johan A. , Brosens Lodewijk A.A. 
Published: March 2021

Abstract
Patients with multiple endocrine neoplasia 1 (MEN1) syndrome have a germline mutation in the MEN1 gene. Loss of the wild-type allele can initiate endocrine tumorigenesis. Microscopic and macroscopic pituitary, parathyroid, and pancreatic tumors (referred to as the 3 P's) show loss of the wild-type MEN1 allele up to 100%. In contrast, the duodenal gastrinoma pathogenesis in MEN1 syndrome follows a hyperplasia-to-neoplasia sequence. Gastrinomas have loss of heterozygosity of the MEN1 locus in &lt;50%, and invariably coincide with linear, diffuse, or micronodular gastrin-cell hyperplasia. The factor initiating the gastrin-cell hyperplasia-to-neoplasia sequence is unknown. In this perspective, we argue that hypercalcemia may promote the gastrin-cell hyperplasia-to-neoplasia sequence through the calcium sensing receptor. Hypercalcemia is present in almost all patients with MEN1 syndrome due to parathyroid adenomas. We propose a parathyroid-gut axis, which could well explain why patients with MEN1 syndrome are regularly cured of duodenal gastrinoma after parathyroid surgery, and might cause MEN1 syndrome phenocopies in MEN1-mutation negative individuals with parathyroid adenomas. This perspective on the pathogenesis of the gastrin-cell hyperplasia and neoplasia sequence sheds new light on tumorigenic mechanisms in neuroendocrine tumors and might open up novel areas of gastrinoma research. It may also shift focus in the treatment of MEN1 syndrome-related gastrinoma to biochemical prevention.
Decline of White-throated Bushchat Saxicola insignis Gray J.E. & J.R. Gray, 1847 (Aves: Passeriformes: Muscicapidae) in Nepal: implications on its global status
Authors: Baral Hem Sagar , Bhatt Tek Raj , Dhakal Bed Kumar , Chaudhary Dhiraj , Yadav Hemanta Kumar , Poudyal Laxman Prasad , Chaudhary Hathan , Joshi Pradeep Raj , Inskipp Carol , Amin Rajan 
Published: March 2021

The White-throated Bushchat, also known as Hodgson’s Bushchat, is a long-distance migratory and specialist grassland bird categorized as Vulnerable on the IUCN Red List. In Nepal, White-throated Bushchat winters in the lowlands, and has been primarily recorded in large Phantas (=open plains of grassland). We present the population status of the species in Shukla Phanta, the largest continuous lowland grassland in Nepal that is known to hold the largest wintering population of White-throated Bushchat in the Indian subcontinent. Our 2013–2014, 2016–2017, and 2017–2018 winter surveys for White-throated Bushchat followed the same method used in the 1997–1998 and 2007 surveys in Shukla Phanta for comparable assessment of the status of the species. Our study provided overwhelming evidence that the species has undergone a steep decline over the last two decades (probability of 92% for a decline greater than 5% per year). Shukla Phanta is dominated by the species’ preferred habitat of Imperata cylindrica, Narenga porphyrocoma, and Saccharum bengalensis. Grassland patches managed through controlled burning leaving enough reeds for perches, grazed at medium level of intensity by wildlife and within close distance to water were found to support higher numbers of White-throated Bushchat. Given the observed steep decline in the largest known wintering population of the species and similar declines observed in the wintering populations in India, its status warrants uplisting to Critically Endangered, and we recommend an urgent review of its global status.
A new species of braconid wasp Meteorus Haliday (Hymenoptera: Braconidae: Meteorinae) from India
Authors: Ahmed Zaheer , Hussain Mir Altaf , Shamim Mohammad 
Published: March 2021

A new species of braconid wasp, Meteorus rubrum Ahmed & Shamim sp. nov. (Hymenoptera: Braconidae: Meteorinae), is described from India. The new species is closely related with M. dichomeridis (Wilkinson, 1930) and M. kotanni (Maeto, 1986).
Sandracottus vijayakumari (Coleoptera: Dytiscidae), a new aquatic beetle species from landslide hit area of Nelliyampathy Forest Range, Western Ghats, Kerala, India
Authors: Anand P.P. , Ashiq P.P. , Smitha M. , Adithya M. , Tibin T. , Suresh V. 
Published: March 2021

The present study deals with the description of a new species Sandracottus vijayakumari from Nelliyampathy forest range, southern Western Ghats, Kerala, India with a comparative key of closely related species S. dejeani Aube, 1838. Only one species is known from the genus Sandracottus Sharp, 1882, from southern Western Ghats, Kerala. The Nelliyampathy forest areas are hilly and the altitude of the hills range 40–1,530 m. The region experiences several types of landslides especially during the monsoon (August to September 2018). The new species was discovered in one of the worst landslide hits area in Nelliyampathy forest, Kundrachola region. The new aquatic beetle species is moderately large in size and often very attractively marked dorsally with complex maculations. Additionally, the new species shows a strong synapomorphy along with Eretini, Hydaticini, and Aubehydrini tribes.
Freshwater medusae Limnocnida indica Annandale, 1911 in the Cauvery Wildlife Sanctuary, Dubare Reserve Forest and Shivanasamudram in Karnataka, India, with a commentary note on the exotic Craspedacusta sowerbii Lankester, 1880
Authors: Sreenivasan Naren , Barton Joshua 
Published: March 2021

Fifty years after the first report of freshwater medusae (Limnocnida indica) from Cauvery River in Krishanrajasagar Reservoir, there has been only one other published report of its occurrence in the Cauvery Basin at Hemavathi Reservoir, Kodagu District. Recent interest in freshwater photography has revealed three more locations in the Cauvery Basin where medusae are found. Medusae are often observed at these locations but are erroneously identified as invasive species. According to published literature, this is true of Craspedacusta sowerbii, a cosmopolitan species with only three confirmed reports from India. All these reports were from artificial structures such as ponds and aquaria. The native Limnocnida and exotic Craspedacusta can be distinguished from each other visually and with respect to temporal variation in the occurrence of their free swimming medusae. This short note is intended to shed light on the status, distribution, and field identification of L. indica, a species endemic to the Western Ghats of India.
A rapid assessment of waterbirds and the mangrove status in the Menabe Antimena Protected Area, Madagascar
Authors: Zöckler Christoph , Razanamahenina Solofo Ndrina , Markolf Matthias 
Published: March 2021

Mangroves are of great ecological importance that provide multiple ecosystem services, shelter, and habitat for many threatened waterbird species. The mangroves of the Menabe Antimena Protected Area (MANAP) in western Madagascar are among the most extensive remaining on the island. The remaining dryland forests of the MANAP have been subjected to immense deforestation in recent years. Although remote sensing studies indicate that the mangrove forest loss is considerably lower than the dryland forest loss, little is known about the mangroves’ degradation status. Furthermore, detailed information on bird diversity and numbers is scattered, and previous surveys focused on northern parts of the MANAP, recently designated as the Wetlands of the Tsiribihina RAMSAR site. This study aims to assess bird diversity and abundance, as well as the status of mangroves in the MANAP. We conducted a rapid survey using direct observations at three sites along the coastal regions of the MANAP from 24 Sep–2 Oct 2019. We recorded 71 species of birds in the mangroves and coastal wetlands. High numbers of individuals were counted for several species. Numbers of the Madagascar Plover Charadrius thoracicus and the Madagascar Teal Anas bernieri fulfill criteria for important bird areas at single survey sites and the site is likely to be of importance for Madagascar Sacred Ibis Threskiornis bernieri; these three species are all globally threatened. Mangrove degradation is still limited, but numerous threats to mangroves are present. Our results highlight the importance of the mangroves of the MANAP for several endemic bird species in Madagascar. We provide recommendations for conservation management and future research.
Structure-informed functional connectivity driven by identifiable and
state-specific control regions
Authors: Chiêm Benjamin , Crevecoeur Frédéric , Delvenne Jean-Charles 
Published: March 2021

Abstract
Describing how the brain anatomical wiring contributes to the emergence of coordinated neural activity underlying complex behavior remains challenging. Indeed, patterns of remote coactivations that adjust with the ongoing task-demand do not systematically match direct, static anatomical links. Here, we propose that observed coactivation patterns, known as functional connectivity (FC), can be explained by a controllable linear diffusion dynamics defined on the brain architecture. Our model, termed structure-informed FC, is based on the hypothesis that different sets of brain regions controlling the information flow on the anatomical wiring produce state-specific functional patterns. We thus introduce a principled framework for the identification of potential control centers in the brain. We find that well-defined, sparse, and robust sets of control regions, partially overlapping across several tasks and resting state, produce FC patterns comparable to empirical ones. Our findings suggest that controllability is a fundamental feature allowing the brain to reach different states.
KEPLER: A Unified Model for Knowledge Embedding and Pre-trained Language Representation
Authors: Wang Xiaozhi , Gao Tianyu , Zhu Zhaocheng , Zhang Zhengyan , Liu Zhiyuan , Li Juanzi , Tang Jian 
Published: March 2021

Abstract
Pre-trained language representation models (PLMs) cannot well capture factual knowledge from text. In contrast, knowledge embedding (KE) methods can effectively represent the relational facts in knowledge graphs (KGs) with informative entity embeddings, but conventional KE models cannot take full advantage of the abundant textual information. In this paper, we propose a unified model for Knowledge Embedding and Pre-trained LanguagERepresentation (KEPLER), which can not only better integrate factual knowledge into PLMs but also produce effective text-enhanced KE with the strong PLMs. In KEPLER, we encode textual entity descriptions with a PLM as their embeddings, and then jointly optimize the KE and language modeling objectives. Experimental results show that KEPLER achieves state-of-the-art performances on various NLP tasks, and also works remarkably well as an inductive KE model on KG link prediction. Furthermore, for pre-training and evaluating KEPLER, we construct Wikidata5M1 , a large-scale KG dataset with aligned entity descriptions, and benchmark state-of-the-art KE methods on it. It shall serve as a new KE benchmark and facilitate the research on large KG, inductive KE, and KG with text. The source code can be obtained from https://github.com/THU-KEG/KEPLER.
Practicing the Passion of Pentecost
Authors: Rice Monte Lee 
Published: March 2021

Abstract
Scholars are steadily situating pentecostal studies within the embodiment turn, recognizing its foci as imperative to ongoing twenty-first-century pentecostal/charismatic studies. Yet this enjoins greater movement beyond the earlier “linguistic turn,” which too often overlooked the crucial perspectival role of human flesh. For from the horizons of incarnation and Pentecost, Christian faith propagates God’s turn toward flesh. This suggest that pentecostal spirituality generates an eschatological urgency. Fostering this “urgency” into the twenty-first century, however, requires recasting its source and expression within pentecostal spirituality. Drawing from Acts 2:17 (“I will pour out my Spirit on all flesh”), this essay explores how this turn to the flesh might aptly ground and generate eschatological fervor. Doing so, however, exposes deficiencies with pentecostal sacramentality, recognizing links between it and eschatology. The essay addresses this by engaging Kearney’s “anatheistic sacramentality.” It concludes with several implications with particular attention to the violent tragedy of world hunger.
Different Levels of Ethnic Kinship: The Next Step in Cross-Border Minority Issues?
Authors: Ruda Darius 
Published: March 2021

Abstract
This article serves as a comprehensive literature review on cross-border minority issues in Europe, and after a thorough analysis, we discuss the role of ethnic kinship in such matters. After exploring the literature, we conclude that the theoretical frameworks deployed so far seem to be appropriate in cases of direct ethnic kinship (i.e. when the observed groups are, ethnologically speaking, the same, except for obvious regional differences), but they are insufficient for indirect ethnic kinship (i.e. when the observed groups are, ethnologically speaking, differentiated, but remain ideologically attached because of various reasons related to common history, linguistic background, identity or ancient ancestry). We provide some examples of indirect kinship, explain why the levels of political legitimation are different for all actors involved and present a new theoretical framework to study ethnic kinship not as binary, but as a phenomenon with different levels.