bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paleoproterozoic metaluminous syenites synchronous with the
c.
2.21 Ga mafic dyke swarms from the Eastern Dharwar Craton, India: implications for alkaline magmatism associated with the breakup of supercraton Superia
Authors: Pandey Ashutosh , Rao N. V. Chalapathi , Rahaman Waliur , Seth Vikas , Sahoo Samarendra 
Published: January 2021

Abstract

The Eastern Dharwar Craton (EDC) hosts numerous Late Neoarchean to Paleoproterozoic syenites whose genesis remains unclear. Here we present a petrological and geochemical study on the syenites from Peddavaduguru, Danduvaripalle and Vannedoddi, towards the western margin of the Paleo-Mesoproterozoic Cuddapah Basin in the EDC. These syenite bodies constitute a part of the Paleoproterozoic (2210 ± 110 Ma) Dancherla alkaline complex and are contemporaneous with a mafic dyke swarm emplacement in the EDC. The Danduvaripalle and Vannedoddi syenites display geochemical affinities to adakites. The Peddavaduguru syenite shows a negative Eu anomaly and relatively gentle chondrite-normalized rare earth element (REE) pattern, suggesting an origin by a different process. The
ɛ
Nd
values range between 0.5 and 0.8 for the Peddavaduguru syenite, − 5.2 and − 4.2 for the Danduvaripalle syenite, and − 6.0 and − 1.0 for the Vannedoddi syenite. In tectonic discrimination diagrams, the Peddavaduguru syenite shows affinities to within-plate granitoids similar to syenites from the Deccan large igneous province whereas the others show geochemical similarities to arc-related alkaline rocks and volcanic arc granitoids. The adakitic syenites show deficiency of MgO, Ni, Cr and Sc, highly fractionated REE patterns and negative Nb–Ta–Ti anomalies along with low Nb/U and high Th/U ratios. These geochemical traits are compatible with their origin by the partial melting of a mafic crustal source that subsequently underwent fractionation of amphibole and garnet responsible to impart an adakitic character. We suggest that the crustal source of these syenites underwent partial melting by heat from the rising plume during the Paleoproterozoic extension of the Superia supercraton. The non-adakitic Peddavaduguru syenite, on the other hand, is suggested to have originated from direct fractionation of mafic magma.
Evasion of Innate Immunity Contributes to Small Cell Lung Cancer Progression and Metastasis
Authors: Zhu Mingrui , Huang Yi , Bender Matthew E. , Girard Luc , Kollipara Rahul , Eglenen-Polat Buse , Naito Yujiro , Savage Trisha K. , Huffman Kenneth E. , Koyama Shohei , Kumanogoh Atsushi , Minna John D. , Johnson Jane E. , Akbay Esra A. 
Published: January 2021

Abstract

Small cell lung cancer (SCLC) is a pulmonary neuroendocrine cancer with very poor prognosis and limited effective therapeutic options. Most patients are diagnosed at advanced stages, and the exact reason for the aggressive and metastatic phenotype of SCLC is completely unknown. Despite a high tumor mutational burden, responses to immune checkpoint blockade are minimal in patients with SCLC. This may reflect defects in immune surveillance. Here we illustrate that evading natural killer (NK) surveillance contributes to SCLC aggressiveness and metastasis, primarily through loss of NK-cell recognition of these tumors by reduction of NK-activating ligands (NKG2DL). SCLC primary tumors expressed very low level of NKG2DL mRNA and SCLC lines express little to no surface NKG2DL at the protein level. Chromatin immunoprecipitation sequencing showed NKG2DL loci in SCLC are inaccessible compared with NSCLC, with few H3K27Ac signals. Restoring NKG2DL in preclinical models suppressed tumor growth and metastasis in an NK cell–dependent manner. Likewise, histone deacetylase inhibitor treatment induced NKG2DL expression and led to tumor suppression by inducing infiltration and activation of NK and T cells. Among all the common tumor types, SCLC and neuroblastoma were the lowest NKG2DL-expressing tumors, highlighting a lineage dependency of this phenotype. In conclusion, these data show that epigenetic silencing of NKG2DL results in a lack of stimulatory signals to engage and activate NK cells, highlighting the underlying immune avoidance of SCLC and neuroblastoma.

Significance:
This study discovers in SCLC and neuroblastoma impairment of an inherent mechanism of recognition of tumor cells by innate immunity and proposes that this mechanism can be reactivated to promote immune surveillance.
The Use of Serial Circulating Tumor DNA to Detect Resistance Alterations in Progressive Metastatic Breast Cancer
Authors: Jacob Saya , Davis Andrew A. , Gerratana Lorenzo , Velimirovic Marko , Shah Ami N. , Wehbe Firas , Katam Neelima , Zhang Qiang , Flaum Lisa , Siziopikou Kalliopi P. , Platanias Leonidas C. , Gradishar William J. , Behdad Amir , Bardia Aditya , Cristofanilli Massimo 
Published: January 2021

Abstract

Purpose:
Circulating tumor DNA (ctDNA) is a promising tool for noninvasive longitudinal monitoring of genomic alterations. We analyzed serial ctDNA to characterize genomic evolution in progressive metastatic breast cancer.

Experimental Design:
This was a retrospective cohort between 2015 and 2019 obtained under an Institutional Review Board–approved protocol at Northwestern University (Chicago, IL). ctDNA samples were analyzed with Guardant360 next-generation sequencing (NGS) assay. A total of 86 patients had at least two serial ctDNA collections with the second drawn at first post-NGS progression (PN1) by imaging and clinical assessment. A total of 27 participants had ctDNA drawn at second post-NGS clinical progression (PN2). We analyzed alterations, mutant allele frequency (MAF), number of alterations (NOA), and sites of disease on imaging in close proximity to ctDNA evaluation. Matched pairs' variations in MAF, NOA, and alterations at progression were tested through Wilcoxon test. We identified an independent control cohort at Massachusetts General Hospital (Boston, MA) of 63 patients with serial ctDNA sampling and no evidence of progression.

Results:
We identified 44 hormone receptor–positive, 20 HER2+, and 22 triple-negative breast cancer cases. The significant alterations observed between baseline and PN1 were TP53 (P &lt; 0.0075), PIK3CA (P &lt; 0.0126), AR (P &lt; 0.0126), FGFR1 (P &lt; 0.0455), and ESR1 (P &lt; 0.0143). Paired analyses revealed increased MAF and NOA from baseline to PN1 (P = 0.0026, and P &lt; 0.0001, respectively). When compared with controls without progression, patients with ctDNA collection at times of progression were associated with increased MAF and NOA (P = 0.0042 and P &lt; 0.0001, respectively).

Conclusions:
Serial ctDNA testing identified resistance alterations and increased NOA and MAF were associated with disease progression. Prospective longitudinal ctDNA evaluation could potentially monitor tumor genomic evolution.
Clinical Responsiveness to All-trans Retinoic Acid Is Potentiated by LSD1 Inhibition and Associated with a Quiescent Transcriptome in Myeloid Malignancies
Authors: Tayari Mina M. , Santos Helena G. Dos , Kwon Deukwoo , Bradley Terrence J. , Thomassen Amber , Chen Charles , Dinh Yvonne , Perez Aymee , Zelent Arthur , Morey Lluis , Cimmino Luisa , Shiekhattar Ramin , Swords Ronan T. , Watts Justin M. 
Published: January 2021

Abstract

Purpose:
In preclinical studies, the lysine-specific histone demethylase 1A (LSD1) inhibitor tranylcypromine (TCP) combined with all-trans retinoic acid (ATRA) induces differentiation and impairs survival of myeloid blasts in non-acute promyelocytic leukemia acute myeloid leukemia (AML). We conducted a phase I clinical trial (NCT02273102) to evaluate the safety and activity of ATRA plus TCP in patients with relapsed/refractory AML and myelodysplasia (MDS).

Patients and Methods:
Seventeen patients were treated with ATRA and TCP (three dose levels: 10 mg twice daily, 20 mg twice daily, and 30 mg twice daily).

Results:
ATRA-TCP had an acceptable safety profile. The MTD of TCP was 20 mg twice daily. Best responses included one morphologic leukemia-free state, one marrow complete remission with hematologic improvement, two stable disease with hematologic improvement, and two stable disease. By intention to treat, the overall response rate was 23.5% and clinical benefit rate was 35.3%. Gene expression profiling of patient blasts showed that responding patients had a more quiescent CD34+ cell phenotype at baseline, including decreased MYC and RARA expression, compared with nonresponders that exhibited a more proliferative CD34+ phenotype, with gene expression enrichment for cell growth signaling. Upon ATRA-TCP treatment, we observed significant induction of retinoic acid–target genes in responders but not nonresponders. We corroborated this in AML cell lines, showing that ATRA-TCP synergistically increased differentiation capacity and cell death by regulating the expression of key gene sets that segregate patients by their clinical response.

Conclusions:
These data indicate that LSD1 inhibition sensitizes AML cells to ATRA and may restore ATRA responsiveness in subsets of patients with MDS and AML.
TNIK Is a Therapeutic Target in Lung Squamous Cell Carcinoma and Regulates FAK Activation through Merlin
Authors: Torres-Ayuso Pedro , An Elvira , Nyswaner Katherine M. , Bensen Ryan C. , Ritt Daniel A. , Specht Suzanne I. , Das Sudipto , Andresson Thorkell , Cachau Raul E. , Liang Roger J. , Ries Amy L. , Robinson Christina M. , Difilippantonio Simone , Gouker Brad , Bassel Laura , Karim Baktiar O. , Miller Chad J. , Turk Benjamin E. , Morrison Deborah K. , Brognard John 
Published: January 2021

Abstract

Lung squamous cell carcinoma (LSCC) is the second most prevalent type of lung cancer. Despite extensive genomic characterization, no targeted therapies are approved for the treatment of LSCC. Distal amplification of the 3q chromosome is the most frequent genomic alteration in LSCC, and there is an urgent need to identify efficacious druggable targets within this amplicon. We identify the protein kinase TNIK as a therapeutic target in LSCC. TNIK is amplified in approximately 50% of LSCC cases. TNIK genetic depletion or pharmacologic inhibition reduces the growth of LSCC cells in vitro and in vivo. In addition, TNIK inhibition showed antitumor activity and increased apoptosis in established LSCC patient-derived xenografts. Mechanistically, we identified the tumor suppressor Merlin/NF2 as a novel TNIK substrate and showed that TNIK and Merlin are required for the activation of focal adhesion kinase. In conclusion, our data identify targeting TNIK as a potential therapeutic strategy in LSCC.

Significance:
Targeted therapies have not yet been approved for the treatment of LSCC, due to lack of identification of actionable cancer drivers. We define TNIK catalytic activity as essential for maintaining LSCC viability and validate the antitumor efficacy of TNIK inhibition in preclinical models of LSCC.
This article is highlighted in the In This Issue feature, p. 1307
Performance analysis of power generation by wood and woody biomass gasification in a downdraft gasifier
Authors: Safarian Sahar , Unnthorsson Runar , Richter Christiaan 
Published: January 2021

An equilibrium simulation model was developed by applying Aspen Plus to evaluate the performance of 28 wood and woody biomass (W&amp;WB) gasification in a downdraft gasifier integrated with power production unit. The developed simulation model does not focus the gasification process as a closed box, it considers important processes in gasification like drying, pyrolysis, combustion, gasification and integrated with power production plant (combustion chamber plus gas turbine). The results for the 28 W&amp;WB alternatives show that the net power produced from 1-ton feedstock entering to the gasification system is between the interval [0-400 kW/ton] and among them, gasification system derived from Tamarack bark biomass significantly outranks all other systems by producing 363 kW/ton, owing to the favorable results obtained in the performance analysis. Moreover, effect of various operating parameters such as gasification temperature and air to fuel ratio (AFR) on the system performance was carried out. Finally, the developed model is applied as an effective tool to assess the impact of so many biomasses and operating parameters on output power.
Good Clinical Outcome Decreases With Number of Retrieval Attempts in Stroke Thrombectomy
Authors: Flottmann Fabian , Brekenfeld Caspar , Broocks Gabriel , Leischner Hannes , McDonough Rosalie , Faizy Tobias D. , Deb-Chatterji Milani , Alegiani Anna , Thomalla Götz , Mpotsaris Anastasios , Nolte Christian H. , Fiehler Jens , Maros Máté E. , Boeckh-Behrens Tobias , Wunderlich Silke , Wiesmann Martin , Ernemann Ulrike , Hauser Till-Karsten , Siebert Eberhard , Zweynert Sarah , Bohner Georg , Ludolph Alexander , Henn Karl-Heinz , Pfeilschifter Waltraud , Wagner Marlis , Röther Joachim , Eckert Bernd , Berrouschot Jörg , Bormann Albrecht , Gerloff Christian , Hattingen Elke , Petzold Gabor , Thonke Sven , Bangard Christopher , Kraemer Christoffer , Dichgans Martin , Wollenwebe Frank , Kellert Lars , Dorn Franziska , Herzberg Moriz , Psychogios Marios , Liman Jan , Petersen Martina , Stögbauer Florian , Kraft Peter , Pham Mirko , Braun Michael , Hamann Gerhard F. , Kastrup Andreas , Roth Christian , Gröschel Klaus , Uphaus Timo , Limmroth Volker 
Published: January 2021

Background and Purpose:
Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. Often, more than one retrieval attempt is needed to achieve reperfusion. We aimed to quantify the influence of endovascular therapy on clinical outcome depending on the number of retrievals needed for successful reperfusion in a large multi-center cohort.

Methods:
For this observational cohort study, 2611 patients from the prospective German Stroke Registry included between June 2015 and April 2018 were analyzed. Patients who received endovascular therapy for acute anterior circulation stroke with known admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction score, and number of retrievals were included. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. The primary outcome was defined as functional independence (modified Rankin Scale score of 0–2) at day 90. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers and confounders.

Results:
The inclusion criteria were met by 1225 patients. The odds of good clinical outcome decreased with every retrieval attempt required for successful reperfusion: the first retrieval had the highest odds of good clinical outcome (adjusted odds ratio, 6.45 [95% CI, 4.0–10.4]), followed by the second attempt (adjusted odds ratio, 4.56 [95% CI, 2.7–7.7]), and finally the third (adjusted odds ratio, 3.16 [95% CI, 1.8–5.6]).

Conclusions:
Successful reperfusion within the first 3 retrieval attempts is associated with improved clinical outcome compared with patients without reperfusion. We conclude that at least 3 retrieval attempts should be performed in endovascular therapy of anterior circulation strokes.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03356392.
Biology teachers’ conceptions of Humankind Origin across secular and religious countries: an international comparison
Authors: Silva Heslley Machado , Oliveira Alandeon W. , Belloso Gabriela Varela , Díaz Martín Andrés , Carvalho Graça S. 
Published: January 2021

AbstractStriving toward a better understanding of how the global spread of creationist ideology may impact biology teachers and teaching worldwide, this study comparatively examines how biology teachers from three Latin American countries (Argentina, Brazil, and Uruguay) conceive the origin of humankind. It is reported that teachers from Uruguay (the most secular country) and Argentina (a country with intermediate religiosity) more frequently associated humankind origin with scientific terms Evolution, Natural selection, and Australopithecus. In contrast, Brazilian teachers stood out as those most frequently associating humankind’s origin to the religious term “God” alongside scientific terms. This study underscores the importance of the interplay of social factors (societal religiosity) and psychological factors (e.g., personal commitment) when considering the impact of teacher exposure to creationist ideology. It also highlights the need for biology teachers (particularly those in more religious countries) to undergo professional development.
Effects of exposure to low-dose ionizing radiation on changing platelets: a prospective cohort study
Authors: Liu Ning , Peng Yang , Zhong Xinguang , Ma Zheng , He Suiping , Li Ying , Zhang Wencui , Gong Zijun , Yao Zhenjiang 
Published: January 2021

AbstractBackgroundNumerous studies have concentrated on high-dose radiation exposed accidentally or through therapy, and few involve low-dose occupational exposure, to investigate the correlation between low-dose ionizing radiation and changing hematological parameters among medical workers.MethodsUsing a prospective cohort study design, we collected health examination reports and personal dose monitoring data from medical workers and used Poisson regression and restricted cubic spline models to assess the correlation between changing hematological parameters and cumulative radiation dose and determine the dose-response relationship.ResultsWe observed that changing platelet of 1265 medical workers followed up was statistically different among the cumulative dose groups (P= 0.010). Although the linear trend tested was not statistically significant (Ptrend= 0.258), the non-linear trend tested was statistically significant (Pnon-linear= 0.007). Overall, there was a correlation between changing platelets and cumulative radiation dose (a change of βa0.008 × 109/L during biennially after adjusting for gender, age at baseline, service at baseline, occupation, medical level, and smoking habits; 95% confidence interval [CI] = 0.003,0.014 × 109/L). Moreover, we also found positive first and then negative dose-response relationships between cumulative radiation dose and changing platelets by restricted cubic spline models, while there were negative patterns of the baseline service not less than 10 years (− 0.015 × 109/L, 95% CI = − 0.024, − 0.007 × 109/L) and radiation nurses(− 0.033 × 109/L, 95% CI = − 0.049, − 0.016 × 109/L).ConclusionWe concluded that although the exposure dose was below the limit, medical workers exposed to low-dose ionizing radiation for a short period of time might have increased first and then decreased platelets, and there was a dose-response relationship between the cumulative radiation dose and platelets changing.
Decreased Vascular Bundle 1 affects mitochondrial and plant development in rice
Authors: Zhang Lisha , Feng Ping , Deng Yao , Yin Wuzhong , Wan Yingchun , Lei Ting , He Guanghua , Wang Nan 
Published: January 2021

AbstractBackgroundMitochondria are vital regulators of plant growth and development, constitute the predominant source of ATP, and participate in multiple anabolic and catabolic metabolic pathways. But the mechanism by which dysfunctional mitochondria affect plant growth remains unknown, and more mitochondria-defective mutants need to be identified.ResultsA mitochondria-defective mutantdecreased vascular bundle 1(dvb1) was isolated from rice mutant library mutagenized by EMS (ethylmethane sulfonate), which shows dwarfism, narrow leaves, short branches, few vascular bundles, and low fertility. Map-based cloning, genetic complementation, and phylogenetic analysis revealed thatDVB1encodes a structural protein classified in the Mic10 family and is required for the formation of cristae in mitochondria, and was primarily expressed in vascular bundles. The DVB1 protein is partially localized in the mitochondria and capable of forming dimers and polymers. Comparing with the wild type, disruption of amino acid metabolism and increased auxin synthesis were observed indvb1mutant which also showed increased sensitivity to the mitochondrial electron transport inhibitors.ConclusionsDVB1 belongs to Mic10 family and DVB1 is partially localized in the mitochondria. Further studies indicated that DVB1 is important for mitochondrial and plant development in rice.
Comparison of different shock wave frequencies on stone disintegration in extracorporeal shock wave lithotripsy; 60, 80 and 100/min
Authors: Taher Mohamed Ahmed Mohamed El , Reda A. , Latif A. M. Abdel , Gammal M. A. El 
Published: January 2021

Abstract
Background
We know that SWL started on February 07, 1980, by Christian Chaussy with a wide range of indications. Complication rate has always remained very low and usually limited to minor side effects and complications. This study shows the impact of different shock wave release frequencies 60, 80 & 100/min on disintegration of renal stones.

Methods
A total number of 210 patients with mean age (40 ± 15) years with renal stone who were candidate for SWL divided into 3 groups each are 70 patients on rate 60,80 and 100 per min), Chi-Square test, Fisher’s exact test used in the study.

Results
Complete stone clearance( defined as complete stone free) was obtained in 184 patients 87.6% after one session, the highest success rate 94.3% were obtained in the second group of patients ( with shock wave frequency 80/min) followed by the first group 87.1% (with shock wave frequency 60/min), and patients with highest frequency (100/min) had the lowest success rate 81.4%.

Conclusions
The best option is using intermediate shock wave rate 80/min to obtain highest success rate and mild pain. Using high rate 100/min is not favorable due to least disintegration rate with highest pain. Using rate 60/min shows less success than rate 80/min despite it less painful.
Toxicity and risk of plant-produced alkaloids to Daphnia magna
Authors: Griffiths Megan R. , Strobel Bjarne W. , Hama Jawameer R. , Cedergreen Nina 
Published: January 2021

Abstract
Background
Many plants contain phytotoxic alkaloids to deter herbivorous pests and grazing animals. Alkaloids include quinolizidine and indole alkaloids found in the lupin (Lupinus spp.), an ornamental flower and emerging protein crop, as well as pyrrolizidine alkaloids in the ragwort (Senecio jacobaea), an invasive, weed-like flower. When lupins and ragworts are present in large densities in fields, there is a concern that alkaloids may leach into freshwater environments in amounts that may affect non-target organisms, such as Daphnia magna. This study aimed to investigate (i) the acute toxicity of alkaloids (gramine, heliotrine, lupanine, lupinine, monocrotaline, monocrotaline N-oxide, senecionine and sparteine) in D. magna, (ii) the contribution of these individual alkaloids to lupin plant extract toxicity, (iii) the longer term reproductive effects of a representative alkaloid, sparteine, and conclude with (iv) a tentative risk assessment for the sum of alkaloids measured in soil and surface waters.

Results
The alkaloids exhibited toxicity, with 48 h EC50 values in the range of 5.6 to > 100 mg/L. The 48 h EC50 of the Lupinus angustifolius plant extract was 1.38 mg/L, which was far more toxic than the simulated extract where lethality was < 10% at 10 mg/L after 48 h. Hence, non-measured compounds may have contributed to the joint toxicity. Daphnid mothers exposed to > 2.5 mg/L sparteine produced significantly fewer and smaller offspring during the 21-day exposure, making chronic effects occur at concentrations approximately 10-fold lower than the 48 h EC50 for sparteine. The risk assessment of cumulated alkaloids measured in drain, running and pond waters showed a potential risk, particularly for stagnant pond water, where concentrations were severalfold higher than in the drain and running waters.

Conclusions
The results highlight that natural toxins may contribute to poor chemical quality of natural waters, and that natural toxins from upcoming crops or invasive weeds should be considered in aquatic risk assessments.