bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of severe‐to‐very severe chronic obstructive pulmonary disease on the prognosis of patients with non‐small cell lung cancer who received chemotherapy
Authors: Dong Weigang , Zhu Yaqian , Du Yan , Wang Lina , Feng Xue , Ma Shuping 
Published: December 2019

AbstractIntroductionChronic obstructive pulmonary disease (COPD) is associated with poor prognosis in non‐small cell lung cancer (NSCLC) patients. There are limited data about the impact of severe‐to‐very severe COPD on prognosis in patients with NSCLC receiving first‐line chemotherapy.ObjectivesTo investigate whether severe‐to‐very severe COPD impacted survival of patients with NSCLC receiving first‐line chemotherapy.MethodsA retrospective review was performed on 513 consecutive NSCLC patients receiving first‐line chemotherapy between February 2014 and May 2018. Prognostic impact of severe‐to‐very severe COPD was analysed using regression analyses.ResultsTotally 258 NSCLC patients (118 non‐COPD, 96 mild‐to‐moderate COPD and 44 severe‐to‐very severe COPD) were evaluated retrospectively. Kaplan‐Meier analysis showed that the median overall survival times in the severe‐to‐very severe COPD, mild‐to‐moderate COPD and non‐COPD groups were 14.0 months [95% confidence interval (CI): 11.0‐17.0], 18 months (95% CI: 14.8‐21.2) and 19 months (95% CI: 15.3‐22.7), respectively. The difference was significant between patients with severe‐to‐very severe COPD and those without COPD (χ2 = 6.8, P = 0.009) and between patients with severe‐to‐very severe COPD and those with mild‐to‐moderate COPD (χ2 = 4.0, P = 0.045). Multivariate analysis showed that survival time was significantly shorter in the severe‐to‐very severe COPD group than in the non‐COPD group (adjusted hazard ratio: 1.876, 95% CI: 1.161‐3.030, P = 0.01) and mild‐to‐moderate COPD group (adjusted hazard ratio: 1.782, 95% CI: 1.046‐3.034, P = 0.033).ConclusionSevere‐to‐very severe COPD may worsen the prognosis of NSCLC patients who received first‐line chemotherapy.
Blinatumomab vs historic standard‐of‐care treatment for minimal residual disease in adults with B‐cell precursor acute lymphoblastic leukaemia
Authors: Gökbuget Nicola , Dombret Hervé , Giebel Sebastian , Brüggemann Monika , Doubek Michael , Foa Robin , Hoelzer Dieter , Kim Christopher , Martinelli Giovanni , Parovichnikova Elena , Maria Ribera Josep , Schoonen Marieke , Tuglus Catherine , Zugmaier Gerhard , Bassan Renato 
Published: December 2019

AbstractObjectivesSurvival outcomes from a single‐arm phase 2 blinatumomab study in patients with minimal residual disease (MRD)‐positive B‐cell precursor (BCP)‐acute lymphoblastic leukaemia (ALL) were compared with those receiving standard of care (SOC) in a historic data set.MethodsThe primary analysis comprised adult Philadelphia chromosome (Ph)‐negative patients in first complete haematologic remission (MRD ≥ 10−3). Relapse‐free survival (RFS) and overall survival (OS) were compared between blinatumomab‐ and SOC‐treatment groups. Baseline differences between groups were adjusted by propensity scores.ResultsThe primary analysis included 73 and 182 patients from the blinatumomab and historic data sets, respectively. When weighted by age to the blinatumomab‐treatment group, median RFS was 7.8 months and median OS was 25.9 months in the SOC‐treated group. In the blinatumomab study, median RFS was 35.2 months; median OS was not evaluable. Propensity score weighting achieved balance with seven baseline prognostic factors. With adjustment for haematopoietic stem cell transplantation (HSCT) status, a 50% reduction in risk of relapse or death was observed with blinatumomab vs SOC. Median RFS, unadjusted for HSCT status, was 35.2 months with blinatumomab and 8.3 months with SOC.ConclusionsThese analyses suggest that blinatumomab improves RFS, and possibly OS, in adults with MRD‐positive Ph‐negative BCP‐ALL vs SOC.
Biotic resistance to invasion is ubiquitous across ecosystems of the United States
Authors: Beaury Evelyn M. , Finn John T. , Corbin Jeffrey D. , Barr Valerie , Bradley Bethany A. 
Published: December 2019

AbstractThe biotic resistance hypothesis predicts that diverse native communities are more resistant to invasion. However, past studies vary in their support for this hypothesis due to an apparent contradiction between experimental studies, which support biotic resistance, and observational studies, which find that native and non‐native species richness are positively related at broad scales (small‐scale studies are more variable). Here, we present a novel analysis of the biotic resistance hypothesis using 24 456 observations of plant richness spanning four community types and seven ecoregions of the United States. Non‐native plant occurrence was negatively related to native plant richness across all community types and ecoregions, although the strength of biotic resistance varied across different ecological, anthropogenic and climatic contexts. Our results strongly support the biotic resistance hypothesis, thus reconciling differences between experimental and observational studies and providing evidence for the shared benefits between invasive species management and native biodiversity conservation.
Does rattling deter? The case of domestic dogs
Authors: Caine Nancy G. , Muñoz Rita , Mulholland Michele M. 
Published: December 2019

AbstractAlthough the rattling of rattlesnakes (Crotalus and Sistrurus) is widely accepted as being aposematic, the hypothesis that rattling deters approach from the snake's potentially dangerous adversaries has not been well tested. In a controlled study using rattling recorded from captive rattlesnakes (C. oreganus helleri) and a variety of comparison sounds or no‐sound controls, domestic dogs (Canis familiaris) showed no hesitation to approach camouflaged speakers projecting the recorded rattles. The dogs were equally likely to approach speakers projecting rattling as they were to approach speakers playing control sounds, or speakers that were silent. Furthermore, the dogs spent no less time in front of the speakers projecting the rattles than they did in front of speakers projecting control sounds or no sound. The dogs' reactions may not be representative of other species with whom rattlesnakes come into contact, but the data suggest a need for some circumspection about the role of rattling in the rattlesnake's defensive repertoire. Our results also suggest that dogs may be vulnerable to envenomation because they fail to react to the sound of rattling with avoidance.
Evolution‐guided engineering of non‐heme iron enzymes involved in nogalamycin biosynthesis
Authors: Nji Wandi Benjamin , Siitonen Vilja , Dinis Pedro , Vukic Vladimir , Salminen Tiina A. , Metsä‐Ketelä Mikko 
Published: December 2019

Microbes are competent chemists that are able to generate thousands of chemically complex natural products with potent biological activities. The key to the formation of this chemical diversity has been the rapid evolution of secondary metabolism. Many enzymes residing on these metabolic pathways have acquired atypical catalytic properties in comparison with their counterparts found in primary metabolism. The biosynthetic pathway of the anthracycline nogalamycin contains two such proteins, SnoK and SnoN, belonging to nonheme iron and 2‐oxoglutarate‐dependent mono‐oxygenases. In spite of structural similarity, the two proteins catalyze distinct chemical reactions; SnoK is a C2–C5″ carbocyclase, whereas SnoN catalyzes stereoinversion at the adjacent C4″ position. Here, we have identified four structural regions involved in the functional differentiation and generated 30 chimeric enzymes to probe catalysis. Our analyses indicate that the carbocyclase SnoK is the ancestral form of the enzyme from which SnoN has evolved to catalyze stereoinversion at the neighboring carbon. The critical step in the appearance of epimerization activity has likely been the insertion of three residues near the C‐terminus, which allow repositioning of the substrate in front of the iron center. The loss of the original carbocyclization activity has then occurred with changes in four amino acids near the iron center that prohibit alignment of the substrate for the formation of the C2–C5″ bond. Our study provides detailed insights into the evolutionary processes that have enabledStreptomycessoil bacteria to become the major source of antibiotics and antiproliferative agents.EnzymesEC number1.14.11.
Development of an in vitro screening assay for PIP5K1α lipid kinase and identification of potent inhibitors
Authors: Strätker Katja , Haidar Samer , Amesty Ángel , El‐Awaad Ehab , Götz Claudia , Estévez‐Braun Ana , Jose Joachim 
Published: December 2019

The human phosphatidylinositol 4‐phosphate 5‐kinase type I α (hPIP5K1α) participates in the phosphoinositide‐3‐kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Despite the evidence that hPIP5K1α plays a role in the development of prostate cancer (PCa), only one inhibitor is known to date. With the aim of identifying new inhibitors, a nonradiometric assay for measurement of the hPIP5K1α enzyme activity was developed. The assay is based on the separation of the fluorescently labeled substrate phosphatidylinositol‐4‐phosphate (PI(4)P) and the resulting product phosphatidylinositol‐4,5‐bisphosphate (PIP2) by capillary electrophoresis (CE). Furthermore, an inactive mutant K261A of hPIP5K1α was generated by site‐directed mutagenesis and used as a control. Michaelis–Menten analysis revealed a Km value of 21.6 µm and Vmax of 0.65 pmol·min−1 for the cosubstrate ATP. The average Z’ value was determined to be 0.86, indicating a high reliability of the assay. An in silico screening of an in‐house compound library was performed employing the crystal structure of zebrafish PIP5K1α. By applying this strategy, three compounds with a 2‐amino‐3‐cyano‐4H‐pyranobenzoquinone scaffold were identified and tested using the CE‐based assay. These compounds inhibited hPIP5K1α to > 90% at a concentration of 50 µm. Subsequently, the inhibitory activity of all compounds with a pyranobenzoquinone scaffold (29) was tested on hPIP5K1α. Compound 4‐(2‐amino‐3‐cyano‐6‐hydroxy‐5,8‐dioxo‐7‐undecyl‐5,8‐dihydro‐4H‐chromen‐4‐yl)benzoic acid appeared to be the most potent inhibitor of hPIP5K1α identified so far with an IC50 value of 1.55 µm, exhibiting a substrate‐competitive mode of action. The effects of this compound on cell viability and the induction of apoptosis were investigated in LNCaP, DU145, and PC3 PCa cells.
Measuring fish catch and consumption: Practical methods for small‐scale fisheries based on length as an alternative to weight‐based approaches
Authors: Garaway Caroline , Arthur Robert 
Published: December 2019

AbstractSmall‐scale fisheries are recognised as making important contributions to nutrition and economic development despite a lack of accurate quantitative information on catches and consumption. While direct measurement remains the most appropriate way of collecting such data, it is impractical at large scales. Instead, household surveys based upon informant recall of fish caught and/or consumed are frequently used. However, the accuracy of weight recall by informants (even over short recall periods) has not been established. Using data from household surveys, the accuracy and precision of catch and consumption estimates derived from: (a) asking informants to recall weights of fish caught and (b) asking respondents to recall lengths of fish caught and converting to weight were tested. Length‐based methods, using visual aids to assist recall, were more accurate, precise and correctable. These methods could be useful for catch estimation, especially where fish are processed, sold or consumed shortly after capture.
Local climate determines vulnerability to camouflage mismatch in snowshoe hares
Authors: Zimova Marketa , Sirén Alexej P. K. , Nowak Joshua J. , Bryan Alexander M. , Ivan Jacob S. , Morelli Toni Lyn , Suhrer Skyler L. , Whittington Jesse , Mills L. Scott 
Published: December 2019

AbstractAimPhenological mismatches, when life‐events become mistimed with optimal environmental conditions, have become increasingly common under climate change. Population‐level susceptibility to mismatches depends on how phenology and phenotypic plasticity vary across a species’ distributional range. Here, we quantify the environmental drivers of colour moult phenology, phenotypic plasticity, and the extent of phenological mismatch in seasonal camouflage to assess vulnerability to mismatch in a common North American mammal.LocationNorth America.Time period2010–2017.Major taxa studiedSnowshoe hare (Lepus americanus).MethodsWe used > 5,500 by‐catch photographs of snowshoe hares from 448 remote camera trap sites at three independent study areas. To quantify moult phenology and phenotypic plasticity, we used multinomial logistic regression models that incorporated geospatial and high‐resolution climate data. We estimated occurrence of camouflage mismatch between hares’ coat colour and the presence and absence of snow over 7 years of monitoring.ResultsSpatial and temporal variation in moult phenology depended on local climate conditions more so than on latitude. First, hares in colder, snowier areas moulted earlier in the fall and later in the spring. Next, hares exhibited phenotypic plasticity in moult phenology in response to annual variation in temperature and snow duration, especially in the spring. Finally, the occurrence of camouflage mismatch varied in space and time; white hares on dark, snowless background occurred primarily during low‐snow years in regions characterized by shallow, short‐lasting snowpack.Main conclusionsLong‐term climate and annual variation in snow and temperature determine coat colour moult phenology in snowshoe hares. In most areas, climate change leads to shorter snow seasons, but the occurrence of camouflage mismatch varies across the species’ range. Our results underscore the population‐specific susceptibility to climate change‐induced stressors and the necessity to understand this variation to prioritize the populations most vulnerable under global environmental change.
No Gastrointestinal Dysmotility in Transgenic Mouse Models of Migraine
Authors: Sprouse Blum Adam S. , Lavoie Brigitte , Haag Melody , Mawe Seamus M. , Tolner Else A. , van den Maagdenberg Arn M.J.M. , Chen Shih‐Pin , Eikermann‐Haerter Katharina , Ptáček Louis , Mawe Gary M. , Shapiro Robert E. 
Published: December 2019

ObjectiveTo determine whether transgenic mouse models of migraine exhibit upper gastrointestinal dysmotility comparable to those observed in migraine patients.BackgroundThere is considerable evidence supporting the comorbidity of gastrointestinal dysmotility and migraine. Gastrointestinal motility, however, has never been investigated in transgenic mouse models of migraine.MethodsThree transgenic mouse strains that express pathogenic gene mutations linked to monogenic migraine‐relevant phenotypes were studied: CADASIL (Notch3‐Tg88), FASP (CSNK1D‐T44A), and FHM1 (CACNA1A‐S218L). Upper gastrointestinal motility was quantified by measuring gastric emptying and small intestinal transit in mutant and control animals. Gastrointestinal motility was measured at baseline and after pretreatment with 10 mg/kg nitroglycerin (NTG).ResultsNo significant differences were observed for gastric emptying or small intestinal transit at baseline for any of the 3 transgenic strains when compared to appropriate controls or after pretreatment with NTG when compared to vehicle.ConclusionsWe detected no evidence of upper gastrointestinal dysmotility in mice that express mutations in genes linked to monogenic migraine‐relevant phenotypes. Future studies seeking to understand why humans with migraine experience delayed gastric emptying may benefit from pursuing other modifiers of gastrointestinal motility, such as epigenetic or microbiome‐related factors.
Acquired perforating dermatosis: clinicopathologic study of a 10‐year period at a tertiary teaching hospital
Authors: Garrido Pedro Miguel , Queirós Catarina , Borges‐Costa João , Soares‐Almeida Luís , Filipe Paulo 
Published: December 2019

AbstractBackgroundAcquired perforating dermatosis (APD) comprises an uncommon group of skin disorders that develop in adulthood in association with systemic diseases. The aim of this study was to characterize clinicopathologic features and treatment outcomes in a series of patients diagnosed with APD.MethodsRetrospective study of all patients diagnosed with an APD over a 10‐year period (2009–2018) at a tertiary teaching hospital in Lisbon, Portugal.ResultsFifty‐seven patients with APD were identified. Thirty‐five patients presented lesions in multiple anatomic areas (61.4%), and the lower limbs were the most common location. Forty‐six patients reported pruritus (80.7%), which was classified as severe in 21 of them (36.8%). An underlying systemic disease was identified in 53 patients (93.0%). Diabetes mellitus (DM) and chronic kidney disease (CKD) were the most common associated systemic diseases, but psychiatric disorders, malignancies, and chronic infections were present in a significant number of patients. The combination of topical steroids with antihistamines was the most prescribed initial treatment, but only 37.8% of the patients had a complete response. Acitretin, systemic steroids, and phototherapy were the treatments associated with the best outcome.ConclusionAcquired perforating dermatosis can be associated with many systemic disorders that have pruritus as a common factor. Chronic viral infections and an occult malignancy should be sought, particularly in the absence of DM and CKD. The management of APD is challenging and is best achieved with the control of the underlying systemic diseases.
Intentional (Nation‐)States: A Group‐Agency Problem for the State’s Right to Exclude
Authors: Joseph Matthew R. 
Published: December 2019

AbstractMost philosophical defences of the state’s right to exclude immigrants derive their strength from the normative importance of self‐determination. If nation‐states are taken to be the political institutions of a people, then the state’s right to exclude is the people’s right to exclude – and a denial of this right constitutes an abridgement of self‐determination. In this article, I argue that this view of self‐determination does not cohere with a group‐agency view of nation‐states. On the group‐agency view that I defend, a nation‐state is the kind of group‐agent that does not supervene on the intentionality of member/citizens. If we think that a nation‐state is an intentional group‐agent in its own right, then we should think that self‐determination resides with the institutions of the state rather than with the citizens. If nation‐states do not supervene on the intentionality of citizens, then it is unclear why citizens might have the right to control membership in the state as a feature of self‐determination.
Financial resources and decisions to avoid information about environmental perils
Authors: Losee Joy E. , Shepperd James A. , Webster Gregory D. 
Published: December 2019

AbstractEnvironmental perils pose threats that require mitigation. Mitigation requires knowledge of the threat. Ironically, people may opt to avoid information about an environmental peril, especially if they lack resources to respond and the mitigation burden is high or costly. Three experiments (N = 845) examined how available resources and the resource burden of responding to an environmental peril affect the perceived of burden of taking action, and how perceiving burden, in turn, affects avoidance of information about the threat. Experiments 1a and 1b revealed that lower perceived likelihood of taking action and low income predicted a greater tendency to avoid hurricane risk information among Florida residents. Experiment 2 examined receptivity to information about home radon levels and manipulated the burden required to make repairs ($200 vs. $2,000). Having low income and learning repairs were costly corresponded with greater perceived burden of taking action, which predicted a lower likelihood to repair and greater information avoidance. These findings demonstrate that facing a high mitigation burden and lacking resources can lead to remaining uninformed about risks posed by environmental perils. Remaining uninformed is problematic because it may increase people's vulnerability to damage from these threats. However, these findings also identify a potential pathway for intervention. Reminding people of resources they may be unaware of will likely increase their likelihood of preparation and decrease information avoidance.
Diversification is decoupled from biome fidelity: Acacia – a case study
Authors: Dale Esther E. , Larcombe Matthew J. , Lee William G. , Higgins Steven I. 
Published: December 2019

AbstractAimTo investigate species and clade biome occupancy patterns of Australian Acacia to test for within‐biome diversification, which indicate biome conservatism.LocationAustralia.TaxonAcacia (Fabaceae).MethodsSpecies distributions were predicted for 481 Australian Acacia using the Thornley Transport Resistance Species Distribution Model and mapped across four biome typologies. Within Acacia 19 clades were identified. The number of biomes occupied and niche size was quantified for every species and clade using the range area projected by the distribution model. Relationships between clade species richness, niche size and biomes occupied were tested using phylogenetic least squares regression models.ResultsOnly 9% of the Acacia 481 species and no clades were biome specialists. There were most specialist taxa in the Crisp Biome classification (8.7%), followed by WWF Biomes (6.2%), González–Orozco Biomes (5.0%) then Functional Biomes (1.2%). On average Acacia species occupied four WWF Biomes, seven Functional Biomes, three Crisp Biomes and three González–Orozco Biomes (out of 7, 13, 5 or 6 biomes respectively). Clades were also distributed across multiple biomes (2–13) with a significant positive relationship between clade species richness and the number of biomes occupied for all biome typologies. Species richness had positive linear relationships with biome area for all biome concepts except the González–Orozco Biomes. Larger clades had larger niche sizes.Main conclusionsAcacia diversification occurred across biome boundaries and was not associated with biome specialization. Species and clades mainly occurred in multiple biomes, and there were typically few biome specialists. Diversification in Acacia appears to be decoupled from biome conservatism, associated with expanding niche size across biome boundaries. Major ecological–environmental units such as biomes may constrain adaptive radiation processes via biome conservatism in many groups, but this study leads us to hypothesize that for some lineages biome boundaries are permeable.