bluuebunny/crossref_metadata_2025_split huggingface dataset:
NRG1 fusion-positive lung cancers: Clinicopathologic profile and treatment outcomes from a global multicenter registry.
Authors: Duruisseaux Michaël , Liu Stephen V. , Han Ji-Youn , Gounant Valerie , Shih Jin-Yuan , Schram Alison M. , Schrock Alexa Betzig , Ali Siraj Mahamed , Magne Fanny , Monnet Isabelle , Moro-Sibilot Denis , Blum Torsten-Gerriet , Patil Tejas , Doebele Robert Charles , Camidge D. Ross , Muscarella Lucia Anna , Cadranel Jacques , Drilon Alexander E. 
Published: March 2020

9081 Background: NRG1 fusions are potentially actionable driver events enriched in NSCLCs, particularly invasive mucinous adenocarcinomas (IMAs). These fusions activate HER3/HER2, supporting the therapeutic use of HER3 and/or HER2 inhibitors, but optimal treatment strategies remain unclear. Methods: A global, multicenter network of thoracic oncologists (6 countries, 13 institutions) identified patients with pathologically confirmed NRG1 fusion-positive NSCLCs. Anonymized clinical/pathologic features and clinical outcomes were collected retrospectively. Best response to systemic therapy was determined (RECIST v1.1). PFS was calculated (Kaplan-Meier). Results: 80 NRG1 fusion-positive NSCLCs were identified. RNA-based sequencing identified 66% (n = 53/80), DNA-based sequencing 18% (n = 14/80), and FISH 16% (n = 13/80) of cases. The most common upstream partners were CD74 (45%), SLC3A2 (31%), and SDC (9%). Most patients were female (64%) and never smokers (58%). Histology was adenocarcinoma in 95% (IMA, 91%), squamous 4%, large cell neuroendocrine 1%. At diagnosis, most patients had non-metastatic disease (stage: I 33%, II 27%, III 18%, IV 22%). The lifetime frequency of brain metastases was 15%. 12 patients received the HER2 inhibitor afatinib for stage IV disease. PD was the best response in 55% (n = 6/11) of evaluable patients with 18% PR (n = 2/11) and SD 18% (n = 2/11); median PFS was 3.5 months (range 0.6-16.5 months). 19 patients received platinum-based chemotherapy; most patients had SD as their best response (47%, n = 8); PD 41% (n = 7), PR 12% (n = 2). PD-L1 was negative in the majority of tumors (79%, n = 26/33) and none had high PD-L1 expression (range 0-20%). No responses to single-agent anti-PD-1/L1 therapy were observed (PD n = 5/6, SD n = 1/6: nivolumab/atezolizumab). No responses to chemoimmunotherapy (carboplatin, pemetrexed, pembrolizumab) were observed (SD n = 4/5, PD n = 1/5). Conclusions: RNA-based testing is an important component of NRG1 fusion detection. Novel targeted therapeutic approaches are needed as overall outcomes with afatinib are poor. NRG1 fusion-positive NSCLCs do not highly express PD-L1 and outcomes with immunotherapy ± chemotherapy are poor.
Outcomes to first-line pembrolizumab in patients with non-small cell lung cancer and a PD-L1 tumor proportion score ≥90%.
Authors: Jimenez Aguilar Elizabeth , Ricciuti Biagio , Gainor Justin F. , Nishino Mizuki , Adeni Anika E. , Subegdjo Safiya , Khosrowjerdi Sara , Peterson Rachel , Digumarthy Subba , Liu Corinne , Sauter Jennifer L. , Rizvi Hira , Arbour Kathryn Cecilia , Carter Brett W. , Heymach John , Altan Mehmet , Hellmann Matthew David , Awad Mark M. 
Published: March 2020

9111 Background: In non-small cell lung cancers with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of ≥50%, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared to platinum-doublet chemotherapy. Whether higher PD-L1 expression levels within the TPS range of 50-100% predict for even greater benefit to pembrolizumab is currently unknown. Methods: In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment for advanced NSCLC with a PD-L1 TPS of ≥50%. Results: Among 196 patients with NSCLC treated with first-line pembrolizumab, the ORR was 43.8% (95%CI: 36.8-51.1). At a median follow-up of 12.6 months (95%CI: 11.6-13.7), the mPFS was 6.2 months (95% CI: 4.2-8.2) and the mOS was not reached. The median PD-L1 TPS among patients who experienced a response to pembrolizumab was significantly higher than in patients with stable or progressive disease (TPS 90% vs 70%, P < 0.001), so a TPS cut point of 90% was chosen for further analysis. Baseline clinicopathological characteristics were well-balanced between patients with a PD-L1 TPS of 50-89% vs 90-100%. Compared to patients with a PD-L1 TPS of 50-89% (N = 114, 58.2% of the cohort), patients with a TPS of 90-100% (N = 82, 41.8% of the cohort) had a significantly higher ORR (61.0% versus 31.6%, P < 0.001), a significantly longer mPFS (13.2 versus 3.7 months, HR: 0.48 [95% CI: 0.33-0.71], P < 0.001), and a significantly longer mOS (NR versus 16.0 months, HR: 0.38 [95% CI: 0.21-0.70], P = 0.002). After adjusting for ECOG performance status and smoking history, PD-L1 TPS of 90-100% was significantly associated with improved mPFS (HR: 0.51 [95% CI: 0.34-0.75], P < 0.001) and mOS (HR: 0.38 [95% CI: 0.21-0.70], P = 0.001). Conclusions: Among patients with NSCLC and a PD-L1 TPS ≥50%, clinical outcomes are improved in the subgroup of patients with a PD-L1 TPS of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.
Young Women With Breast Cancer in Mexico: Results of the Pilot Phase of the Joven & Fuerte Prospective Cohort
Authors: Villarreal-Garza Cynthia , Platas Alejandra , Miaja Melina , Fonseca Alan , Mesa-Chavez Fernanda , Garcia-Garcia Marisol , Chapman Judy-Anne , Lopez-Martinez Edna A. , Pineda Claudia , Mohar Alejandro , Galvez-Hernandez Carmen L. , Castro-Sanchez Andrea , Martinez-Cannon Bertha-Alejandra , Barragan-Carrillo Regina , Muñoz-Lozano Jose F. , Goss Paul , Bargallo-Rocha Juan E. , Aguilar Dione , Cardona Servando , Canavati Mauricio 
Published: March 2020

PURPOSE The pilot-phase report of the Joven & Fuerte prospective cohort broadly characterizes and assesses the needs of Mexican young women with breast cancer (YWBC). PATIENTS AND METHODS Women age ≤ 40 years with nonmetastatic primary breast cancer were consecutively accrued from 2 hospitals. Data were collected at the first/baseline oncology visit and 2 years later using a sociodemographic survey, European Organisation for Research and Treatment of Cancer Quality-of-Life (QOL) Questionnaire Core 30 (QLQ-C30) and Breast Cancer–Specific QOL Questionnaire (QLQ-BR23), Hospital Anxiety and Depression Scale (HADS), Female Sexual Functioning Index (FSFI), Sexual Satisfaction Inventory, and patients’ medical records. Pearson χ2 and 2-sided t tests were used for statistical analysis. An unadjusted P value < .05 was considered significant. RESULTS Ninety patients were included, all with government health care coverage. Most had low monthly household incomes (98%) and at least a high school education (59%). There was a considerable prevalence of unpartnered patients (36%) and unmet parity (25%). Patients’ most common initial symptom was a palpable mass (84%), and they were most frequently diagnosed with stage III disease (48%), with 51% having had a physician visit ≤ 3 months since detection but 39% receiving diagnosis > 12 months later. At baseline, 66% of patients were overweight/obese, and this proportion had significantly increased by 2 years ( P < .001). Compared with baseline, global QLQ-C30 had improved significantly by 2 years ( P = .004), as had HADS-Anxiety ( P < .001). However, both at baseline and at 2 years, nearly half of patients exhibited FSFI sexual dysfunction. CONCLUSION These preliminary findings demonstrate that YWBC in Mexico have particular sociodemographic and clinicopathologic characteristics, reinforcing the necessity to further describe and explore the needs of these young patients, because they may better represent the understudied and economically vulnerable population of YWBC in limited-resource settings.
Master Endurance Athletes and Cardiovascular Controversies
Authors: Tso Jason , Kim Jonathan H. 
Published: March 2020

Abstract
As interest and participation in recreational endurance exercise has steadily increased, the number of masters level recreational endurance athletes also has increased. While the benefits of regular and moderate physical activity on cardiovascular health are well established, recent data have raised concern that long-term endurance exercise participation is associated with adverse cardiovascular outcomes. In this review, we discuss the supporting evidence and limitations of prior research focused on these recent controversies. Specifically, we address the association between extreme levels of endurance exercise and longevity, risk of atrial fibrillation, accelerated coronary artery atherosclerosis, and arrythmogenic cardiac remodeling. We aim to provide sports medicine practitioners with knowledge of these contemporary controversies in sports cardiology and will highlight the importance of shared decision making in situations of clinical uncertainty.
Drug Abuse and the Internet: Evidence from Craigslist
Authors: Liu Jiayi , Bharadwaj Anandhi 
Published: March 2020

The United States is in the midst of a drug overdose epidemic. Although the online availability of drugs has been a growing concern with considerable speculation that digital platforms are contributing to this epidemic, empirical assessments have been lacking. To quantify this impact, we rely on the phased rollout of Craigslist, a major online platform, as an experimental setup. Applying a difference-in-differences approach on a national panel data set for all counties in the United States from 1997 to 2008, we find a 14.9% increase in drug abuse treatment admissions, a 5.7% increase in drug abuse violations, and a 6.0% increase in drug overdose deaths after Craigslist’s entry. The impacts of Craigslist’s entry are larger among women, whites, Asians, and the more educated. Further, the unintended consequences of Craigslist are more likely to accrue in larger, wealthier areas with initially low levels of drug abuse. These findings raise the possibility that the marked growth in U.S. drug abuse may have partially stemmed from the wider availability of illicit drugs online at the very beginning of its evolution. This paper was accepted by David Simchi-Levi, information systems.
Keragaman Kondisi Salinitas Pada Lingkungan Tempat Tumbuh Mangrove di Teluk Kupang,NTT
Authors: Matatula Jeriels - 
Published: March 2020

Mangrove forest ecosystems are habitat of various types of microorganisms, but now, problems of mangrove forests experience are in quality and wealth. Efforts to rehabilitate activities mangrove forests againts had been carried out but the results shown had not been maximized, so it is need the correct strategies to achieve the success for rehabilitation activities. The studied was conducted in Teluk Kupang, East Nusa Tenggara, covered coastal areas of Kupang's mangrove forests and coastal mangrove forests in Kupang district. The method used in this studied was a systematic sampling method that was systematically distributed across all the mangrove forest areas. The method used for salinity measurement was method of transmission and Transect Line Plots. Measurements was made in straight line and the size of the plot is 10 m x 10 m, the distanced between lines was 50 meters so that total lane is 547 with the number of plots of observation 1641 plots. The value of measurement results was made into the spread of salinity used the interpolation method. The condition of the crossed of mangrove forest located on coastal panoramas of Kupang city shows a salinity value of 10,26 - 26.33%, while salinity conditions was on the coast of Kupang ten district 10-42.33 ‰. The salinity condition was formulation of the environmental conditions mangrove forest on coast of the island as well as attempts to support management of mangrove forest activities. The distribution of different mangrove forest conditions along the coastal zone of North Sumatra shows an environmental condition that supports mangrove growth even though in some places the salinity values are high. Results of this study of salinity conditions is a study of the environment of mangrove growth so that it can provide an overview for the government in conducting various activities to rehabilitate mangrove forests.
Evolution of mitochondrial protein import – lessons from trypanosomes
Authors: Schneider André 
Published: March 2020

Abstract
The evolution of mitochondrial protein import and the systems that mediate it marks the boundary between the endosymbiotic ancestor of mitochondria and a true organelle that is under the control of the nucleus. Protein import has been studied in great detail in Saccharomyces cerevisiae. More recently, it has also been extensively investigated in the parasitic protozoan Trypanosoma brucei, making it arguably the second best studied system. A comparative analysis of the protein import complexes of yeast and trypanosomes is provided. Together with data from other systems, this allows to reconstruct the ancestral features of import complexes that were present in the last eukaryotic common ancestor (LECA) and to identify which subunits were added later in evolution. How these data can be translated into plausible scenarios is discussed, providing insights into the evolution of (i) outer membrane protein import receptors, (ii) proteins involved in biogenesis of α-helically anchored outer membrane proteins, and (iii) of the intermembrane space import and assembly system. Finally, it is shown that the unusual presequence-associated import motor of trypanosomes suggests a scenario of how the two ancestral inner membrane protein translocases present in LECA evolved into the single bifunctional one found in extant trypanosomes.
The structure of the TOM core complex in the mitochondrial outer membrane
Authors: Bausewein Thomas , Naveed Hammad , Liang Jie , Nussberger Stephan 
Published: March 2020

Abstract
In the past three decades, significant advances have been made in providing the biochemical background of TOM (translocase of the outer mitochondrial membrane)-mediated protein translocation into mitochondria. In the light of recent cryoelectron microscopy-derived structures of TOM isolated from Neurospora crassa and Saccharomyces cerevisiae, the interpretation of biochemical and biophysical studies of TOM-mediated protein transport into mitochondria now rests on a solid basis. In this review, we compare the subnanometer structure of N. crassa TOM core complex with that of yeast. Both structures reveal remarkably well-conserved symmetrical dimers of 10 membrane protein subunits. The structural data also validate predictions of weakly stable regions in the transmembrane β-barrel domains of the protein-conducting subunit Tom40, which signal the existence of β-strands located in interfaces of protein-protein interactions.
Modular assembly of yeast mitochondrial ATP synthase and cytochrome oxidase
Authors: Franco Leticia Veloso Ribeiro , Su Chen Hsien , Tzagoloff Alexander 
Published: March 2020

Abstract
The respiratory pathway of mitochondria is composed of four electron transfer complexes and the ATP synthase. In this article, we review evidence from studies of Saccharomyces cerevisiae that both ATP synthase and cytochrome oxidase (COX) are assembled from independent modules that correspond to structurally and functionally identifiable components of each complex. Biogenesis of the respiratory chain requires a coordinate and balanced expression of gene products that become partner subunits of the same complex, but are encoded in the two physically separated genomes. Current evidence indicates that synthesis of two key mitochondrial encoded subunits of ATP synthase is regulated by the F1 module. Expression of COX1 that codes for a subunit of the COX catalytic core is also regulated by a mechanism that restricts synthesis of this subunit to the availability of a nuclear-encoded translational activator. The respiratory chain must maintain a fixed stoichiometry of the component enzyme complexes during cell growth. We propose that high-molecular-weight complexes composed of Cox6, a subunit of COX, and of the Atp9 subunit of ATP synthase play a key role in establishing the ratio of the two complexes during their assembly.
Syntheticity and Recent Metaphysical Readings of Kant’sCritique of Pure Reason
Authors: Gurofsky Simon R. 
Published: March 2020

AbstractMetaphysical readings of Kant’s theoretical philosophy in the Critical period are ascendant. But their possibility assumes the possibility of existence- and real-possibility-judgments about things in themselves. I argue that Kant denies the latter possibility, so metaphysical readings have dubious prospects. First, I show that Kant takes existence- and real-possibility-judgments, as necessarily synthetic, to require a relation to sensible intuition. Second, I show that the most promising metaphysical readings can ultimately neither satisfy nor explain away that requirement for existence- and real-possibility-judgments about things in themselves. I conclude with pessimistic reflections on the prospects for the metaphysical interpretive project.
Kant über das Recht des Privatgebrauchs des Erdbodens
Authors: Wolff Michael 
Published: March 2020

AbstractAs is well known, § 6 of Kant’s Metaphysical First Principles of the Doctrine of Right contains five paragraphs that do not belong there. The article shows that their correct location is at the end of § 16. This sheds some new light on Kant’s theory of property and its significance for Kant’s doctrine of cosmopolitan right.
The typology of sound symbolism: Defining macro-concepts via their semantic and phonetic features
Authors: Erben Johansson Niklas , Anikin Andrey , Carling Gerd , Holmer Arthur 
Published: March 2020

AbstractSound symbolism emerged as a prevalent component in the origin and development of language. However, as previous studies have either been lacking in scope or in phonetic granularity, the present study investigates the phonetic and semantic features involved from a bottom-up perspective. By analyzing the phonemes of 344 near-universal concepts in 245 language families, we establish 125 sound-meaning associations. The results also show that between 19 and 40 of the items of the Swadesh-100 list are sound symbolic, which calls into question the list’s ability to determine genetic relationships. In addition, by combining co-occurring semantic and phonetic features between the sound symbolic concepts, 20macro-conceptscan be identified, e. g. basic descriptors, deictic distinctions and kinship attributes. Furthermore, all identified macro-concepts can be grounded in four types of sound symbolism: (a) unimodal imitation (onomatopoeia); (b) cross-modal imitation (vocal gestures); (c) diagrammatic mappings based on relation (relative); or (d) situational mappings (circumstantial). These findings show that sound symbolism is rooted in the human perception of the body and its interaction with the surrounding world, and could therefore have originated as a bootstrapping mechanism, which can help us understand the bio-cultural origins of human language, the mental lexicon and language diversity.
LINC00152 knock-down suppresses esophageal cancer by EGFR signaling pathway
Authors: Ding Yan , Guo Hai , Zhu Liangjun , Xu Li , Pei Qingyu , Cao Youjun 
Published: March 2020

Abstract

Aim
This study aims to explain the role and mechanism of lncRNA LINC00152 in esophageal cancer.

Methods
The 30 pairs of esophageal cancer and adjacent normal tissues were collected and measuring the lncRNA LINC00152 expression by ISH and RT-qPCR assay. In the next cell experiment, Eca 109 and Kyse 150 cells were divided into 3 groups: NC group were treated with non-treatment; BL group were transfected with empty vector and lncRNA group were transfected with lncRNA LINC00152. The cells proliferation were measured by MTT assay; the cells apoptosis and cell cycle were evaluated by flow cytometry. The relative proteins expressions were measured by WB assay.

Results
Compared with NC groups, the cell proliferation rate of lncRNA groups were significantly suppressed (P<0.05, respectively); the cell apoptosis and G1 phase rates were significantly enhanced in the lncRNA groups (P<0.05, respectively). In the proteins expressions, the EGFR, PI3K and AKT proteins expressions of lncRNA group were significantly inhibited and the P21 proteins expressions were significantly stimulated in the lncRNA groups compared with those of NC groups in Eca 109 and Kyse 150 cells.

Conclusion
The lncRNA LINC00152 had anti-tumor effects on esophageal cancer in the Eca 109 and Kyse 150 cells, the mechanisms were relative with EGFR pathway.
Diversity and biogeography of picoplankton communities from the Straits of Malacca to the South China Sea
Authors: Jiang Zhao-Yu , Sun Fu-Lin 
Published: March 2020

Abstract
Marine picoplankton, including prokaryotic and eukaryotic picoplankton, drive many biogeochemical processes, such as carbon, nitrogen and sulfur cycles, making them crucial to the marine ecosystem. Despite the fact that picoplankton is prevalent, its diversity and spatial distribution from the Straits of Malacca (SM) to the South China Sea (SCS) remain poorly investigated. This work explores the phylogenetic diversity and community structure of picoplankton in relation to environmental factors from the SM to the SCS. To this end, the Illumina MiSeq sequencing technique was applied to 16S and 18S rRNA genes. The results showed significant differences in the dynamics of picoplankton between the open sea and the strait region. Proteobacteria and Cyanobacteria constituted a larger part of the prokaryotic group. Within Cyanobacteria, the abundance of Prochlorococcus in the open sea was significantly higher than that of Synechococcus, while the opposite trend was observed in the strait. Dinoflagellata, Cnidaria, Retaria, Tunicata, and Arthropoda dominated among the eukaryotic taxa. High-throughput sequencing data indicated that salinity, temperature and NO2-N were the key factors determining the prokaryotic community structure, while temperature and dissolved oxygen determined the eukaryotic community structure in the studied region. The network analysis demonstrated that the cooperation and competition were also important factors affecting the picoplankton community.
An algebraic model for the propagation of errors in matrix calculus
Authors: Van Tran Nam , van den Berg Imme 
Published: March 2020

AbstractWe assume that every element of a matrix has a small, individual error, and model it by an external number, which is the sum of a nonstandard real number and a neutrix, the latter being a convex (external) additive group. The algebraic properties of external numbers formalize common error analysis, with rules for calculation which are a sort of mellowed form of the axioms for real numbers.We model the propagation of errors in matrix calculus by the calculus of matrices with external numbers, and study its algebraic properties. Many classical properties continue to hold, sometimes stated in terms of inclusion instead of equality. There are notable exceptions, for which we give counterexamples and investigate suitable adaptations. In particular we study addition and multiplication of matrices, determinants, near inverses, and generalized notions of linear independence and rank.