bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast Tumor Cellularity Assessment using Deep Neural Networks
Authors: Rakhlin Alexander , Tiulpin Aleksei , Shvets Alexey A. , Kalinin Alexandr A. , Iglovikov Vladimir I. , Nikolenko Sergey 
Published: May 2019

AbstractBreast cancer is one of the main causes of death world-wide. Histopathological cellularity assessment of residual tumors in post-surgical tissues is used to analyze a tumor’s response to a therapy. Correct cellularity assessment increases the chances of getting an appropriate treatment and facilitates the patient’s survival. In current clinical practice, tumor cellularity is manually estimated by pathologists; this process is tedious and prone to errors or low agreement rates between assessors. In this work, we evaluated three strong novel Deep Learning-based approaches for automatic assessment of tumor cellularity from post-treated breast surgical specimens stained with hematoxylin and eosin. We validated the proposed methods on the BreastPathQ SPIE challenge dataset that consisted of 2395 image patches selected from whole slide images acquired from 64 patients. Compared to expert pathologist scoring, our best performing method yielded the Cohen’s kappa coefficient of 0.69 (vs. 0.42 previously known in literature) and the intra-class correlation coefficient of 0.89 (vs. 0.83). Our results suggest that Deep Learning-based methods have a significant potential to alleviate the burden on pathologists, enhance the diagnostic workflow, and, thereby, facilitate better clinical outcomes in breast cancer treatment.
C. elegans RHY-1 and CYSL-1 act independently of HIF-1 to promote survival in hydrogen sulfide
Authors: Horsman Joseph W. , Heinis Frazer I. , Miller Dana L. 
Published: May 2019

AbstractHydrogen sulfide (H2S) is an endogenously produced signaling molecule that can be cytoprotective, especially in conditions of ischemia/reperfusion injury. However, exposure to exogenous H2S can be toxic, perhaps due to unregulated activation of endogenous H2S signaling pathways. We use the nematode C. elegans to define mechanisms that mediate the physiological effects of H2S in animals. We have previously shown that in C. elegans the hypoxia inducible factor (hif-1) coordinates the initial transcriptional response to H2S and is essential to survive exposure to low concentrations of H2S. In this study, we performed a forward genetic screen to identify mutations that suppress the lethality of hif-1 mutant animals in H2S. The mutations we recovered do not suppress embryonic lethality or reproductive arrest of hif-1 mutant animals in hypoxia, nor can they improve viability of hif-1 mutant animals exposed to hydrogen cyanide, indicating that these are specific for H2S. We found that the hif-1 suppressor mutations activate the skn-1/Nrf2 transcription factor. Activation of SKN-1 by hif-1 suppressor mutations increased the expression of a subset of H2S-responsive genes, consistent with our previous finding that skn-1 plays a role in the transcriptional response to H2S. Using transgenic rescue, we show a single gene, rhy-1, alone is sufficient to protect hif-1 mutant animals in H2S. Our data indicate that RHY-1 acts in concert with CYSL-1, an orthologue of human cystathionine β-synthase, to promote survival in H2S. The rhy-1 gene encodes a predicated O-acyltransferase enzyme that has previously been shown to negatively regulate HIF-1 activity. Our studies reveal a novel function of RHY-1, which is independent of hif-1, that protects against toxic effects of H2S.
Flow restoration and the impacts of multiple stressors on fish communities in regulated rivers
Authors: Göthe Emma , Degerman Erik , Sandin Leonard , Segersten Joel , Tamario Carl , Mckie Brendan G. 
Published: May 2019

Abstract

River regulation for hydropower is undertaken worldwide, causing profound alterations to hydrological regimes and running water habitats. Regulated catchments are often subjected to additional stressors, arising inter alia from agriculture, forestry and industry, which are likely to interact with impacts of river regulation on fish and other biota. Such interactions are poorly understood, hindering planning of effective mitigation and restoration.

We investigated fish responses to increased discharge (as a restoration measure) in regulated rivers in Sweden. We compiled electrofishing data from river channels downstream of hydropower dams, each of which either has or lacks a mandated minimum discharge corresponding to c. 5% of pre‐regulation discharge. We further analysed interactions between flow restoration and co‐occurring local and regional stressors.

River channels without a mandated minimum discharge were characterized by a low diversity of fish species with traits favouring persistence under unpredictable environmental conditions, including omnivory, short life cycles and small size. Additional stressors further reduced diversity and increased dominance by broad‐niched, opportunistic species.

Both the presence and magnitude of a mandated minimum discharge were positively related to fish diversity and density, and the relative density of three economically and recreationally valuable species. However, the size of these relationships frequently varied with the presence of additional stressors.

Increasing levels of hydrological degradation and reduced connectivity at the catchment scale reduced positive flow–ecology relationships and hindered the restoration of fish communities towards reference conditions. However, application of a mandated minimum discharge also assisted in mitigating impacts of some co‐occurring stressors, especially reduced riparian integrity.

Synthesis and applications. Additional stressors can strongly influence the outcomes of flow restoration for fish community diversity and composition. Our approach combining fish species and trait data from multiple flow restoration projects with information on additional stressors yielded valuable insights into factors affecting flow restoration success, useful for (a) identifying the systems most likely to benefit from mandated minimum flows, (b) modelling influences of multiple stressors on flow–ecology relationships, (c) prioritizing additional measures to manage co‐occurring stressors and enhance outcomes from flow restoration.
An empirical pipeline for choosing the optimal clustering threshold in RADseq studies
Authors: McCartney‐Melstad Evan , Gidiş Müge , Shaffer H. Bradley 
Published: May 2019

AbstractGenomic data are increasingly used for high resolution population genetic studies including those at the forefront of biological conservation. A key methodological challenge is determining sequence similarity clustering thresholds for RADseq data when no reference genome is available. These thresholds define the maximum permitted divergence among allelic variants and the minimum divergence among putative paralogues and are central to downstream population genomic analyses. Here we develop a novel set of metrics to determine sequence similarity thresholds that maximize the correct separation of paralogous regions and minimize oversplitting naturally occurring allelic variation within loci. These metrics empirically identify the threshold value at which true alleles at opposite ends of several major axes of genetic variation begin to incorrectly separate into distinct clusters, allowing researchers to choose thresholds just below this value. We test our approach on a recently published data set for the protected foothill yellow‐legged frog (Rana boylii). The metrics recover a consistent pattern of roughly 96% similarity as a threshold above which genetic divergence and data missingness become increasingly correlated. We provide scripts for assessing different clustering thresholds and discuss how this approach can be applied across a wide range of empirical data sets.
AeRobiology: The computational tool for biological data in the air
Authors: Rojo Jesús , Picornell Antonio , Oteros Jose 
Published: May 2019

Abstract

Aerobiological databases are constantly increasing. Many of them contain long and extensive time series of data which are very difficult and tedious to manage.

The development of new real‐time automatic sampling devices also requires new tools to reduce time of calculations and data management. In this sense, the AeRobiology r package has been implemented to accelerate and facilitate these tasks.

This package was structured in three sections based on (a) the checking of the database, (b) calculation of the main aerobiological indexes and (c) visualization of the results.

The AeRobiology package contains numerous functions which, in conjunction, solve the main general tasks that scientists must assume for the analysis of the biological data.

The package is freely distributed under GNU General Public License and can directly be installed from CRAN (http://cran.r-project.org/). The reference manual is available at https://cran.r-project.org/web/packages/AeRobiology. Contact: aerobiology.package@gmail.com.
Depletion of B cells rejuvenates the peripheral B‐cell compartment but is insufficient to restore immune competence in aging
Authors: Avivi Irit , Zisman‐Rozen Simona , Naor Shulamit , Dai Isabelle , Benhamou David , Shahaf Gitit , Tabibian‐Keissar Hilla , Rosenthal Noemie , Rakovsky Aviya , Hanna Ammuri , Shechter Arik , Peled Eli , Benyamini Noam , Dmitrukha Ekaterina , Barshack Iris , Mehr Ramit , Melamed Doron 
Published: May 2019

AbstractAging is associated with increasing prevalence and severity of infections caused by a decline in bone marrow (BM) lymphopoiesis and reduced B‐cell repertoire diversity. The current study proposes a strategy to enhance immune responsiveness in aged mice and humans, through rejuvenation of the B lineage upon B‐cell depletion. We used hCD20Tg mice to deplete peripheral B cells in old and young mice, analyzing B‐cell subsets, repertoire and cellular functions in vitro, and immune responsiveness in vivo. Additionally, elderly patients, previously treated with rituximab healthy elderly and young individuals, were vaccinated against hepatitis B (HBV) after undergoing a detailed analysis for B‐cell compartments. B‐cell depletion in old mice resulted in rejuvenated B‐cell population that was derived from de novo synthesis in the bone marrow. The rejuvenated B cells exhibited a "young"‐like repertoire and cellular responsiveness to immune stimuli in vitro. Yet, mice treated with B‐cell depletion did not mount enhanced antibody responses to immunization in vivo, nor did they survive longer than control mice in "dirty" environment. Consistent with these results, peripheral B cells from elderly depleted patients showed a "young"‐like repertoire, population dynamics, and cellular responsiveness to stimulus. Nevertheless, the response rate to HBV vaccination was similar between elderly depleted and nondepleted subjects, although antibody titers were higher in depleted patients. This study proposes a proof of principle to rejuvenate the peripheral B‐cell compartment in aging, through B‐cell depletion. Further studies are warranted in order to apply this approach for enhancing humoral immune responsiveness among the elderly population.
Neuronal HMGB1 in nucleus accumbens regulates cocaine reward memory
Authors: Gao Shuang‐Qi , Zhang Hai , He Jin‐Gang , Zheng Hui‐Ling , Zhang Pei‐Wei , Xu Jun‐Feng , Shen Zu‐Cheng , Zhao Huan‐Huan , Wang Fang , Hu Zhuang‐Li , Chen Jian‐Guo 
Published: May 2019

AbstractCocaine is a common abused drug that can induce abnormal synaptic and immune responses in the central nervous system (CNS). High mobility group box 1 (HMGB1) is one kind of inflammatory molecules that is expressed both on neurons and immune cells. Previous studies of HMGB1 in the CNS have largely focused on immune function, and the role of HMGB1 in neurons and cocaine addiction remains unknown. Here, we show that cocaine exposure induced the translocation and release of HMGB1 in the nucleus accumbens (NAc) neurons. Gain and loss of HMGB1 in the NAc bidirectionally regulate cocaine‐induced conditioned place preference. From the nucleus to the cytosol, HMGB1 binds to glutamate receptor subunits (GluA2/GluN2B) on the membrane, which regulates cocaine‐induced synaptic adaptation and the formation of cocaine‐related memory. These data unveil the role of HMGB1 in neurons and provide the evidence for the HMGB1 involvement in drug addiction.
Transcriptome analysis of the endometrium from Chinese Erhualian sows that differ in calcium ion concentration and litter size
Authors: Ma X. , Li P. , Zhang Q. , He L. , Su G. , Huang Y. , Lu Z. , Hu W. , Ding H. , Huang R. 
Published: May 2019

SummaryEmbryonic survival rate, an important factor in the fecundity of sows, is affected by endometrium‐secreting histotroph. A higher concentration of calcium ion has been observed in the uterus of highly prolific Erhualian sows (EH) compared with those of less prolific (EL) sows. This suggests that EH sows have better establishment and maintenance of pregnancies, thus increasing embryonic survival rate during the peri‐implantation period. To understand the mechanisms of how the endometrium‐secreting histotroph affects embryonic survival rate during the Erhualian peri‐implantation period, the expression patterns of endometrial mRNA in the EH and EL sows on day 12 of gestation were analyzed using RNA sequencing technology. A total of 164 differentially expressed genes (DEGs) were identified (Padj < 0.05, |log2(FC)| ≥ 1), including 46 upregulated and 118 downregulated genes in EH compared to EL. Gene Ontology enrichment indicated that a subset of DEGs was involved in calcium ion binding and cell adhesion. Solute carrier family 8 member A3 and solute carrier family 24 member 4, identified as upregulated genes (Padj < 0.05) in EH, were considered key candidate genes expressed in the endometrium affecting embryonic survival rate during the peri‐implantation period. The results improve understanding of the genetic mechanism underlying the variation in litter size of Erhualian pigs during the peri‐implantation period.
Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care
Authors: Breiteneder Heimo , Diamant Zuzana , Eiwegger Thomas , Fokkens Wytske J. , Traidl‐Hoffmann Claudia , Nadeau Kari , O’Hehir Robyn E. , O’Mahony Liam , Pfaar Oliver , Torres Maria J. , Wang De Yun , Zhang Luo , Akdis Cezmi A. 
Published: May 2019

AbstractThe specialties of allergy and clinical immunology have entered the era of precision medicine with the stratification of diseases into distinct disease subsets, specific diagnoses, and targeted treatment options, including biologicals and small molecules. This article reviews recent developments in research and patient care and future trends in the discipline. The section on basic mechanisms of allergic diseases summarizes the current status and defines research needs in structural biology, type 2 inflammation, immune tolerance, neuroimmune mechanisms, role of the microbiome and diet, environmental factors, and respiratory viral infections. In the section on diagnostic challenges, clinical trials, precision medicine and immune monitoring of allergic diseases, asthma, allergic and nonallergic rhinitis, and new approaches to the diagnosis and treatment of drug hypersensitivity reactions are discussed in further detail. In the third section, unmet needs and future research areas for the treatment of allergic diseases are highlighted with topics on food allergy, biologics, small molecules, and novel therapeutic concepts in allergen‐specific immunotherapy for airway disease. Unknowns and future research needs are discussed at the end of each subsection.
Chronic adult‐onset of growth hormone/IGF‐I hypersecretion improves cognitive functions and LTP and promotes neuronal differentiation in adult rats
Authors: Martín‐Rodríguez Juan Francisco , Ramos‐Herrero Víctor Darío , Parras Gloria G. , Flores‐Martínez Álvaro , Madrazo‐Atutxa Ainara , Cano David A. , Gruart Agnès , Delgado‐García José María , Leal‐Cerro Alfonso , Leal‐Campanario Rocío 
Published: May 2019

AbstractAimBesides their metabolic and endocrine functions, the growth hormone (GH) and its mediated factor, the insulin‐like growth factor I (IGF‐I), have been implicated in different brain functions, including neurogenesis. Long‐lasting elevated GH and IGF‐I levels result in non‐reversible somatic, endocrine and metabolic morbidities. However, the subcutaneous implantation of the GH‐secreting (GH‐S) GC cell line in rats leads to the controllable over‐secretion of GH and elevated IGF‐I levels, allowing the experimental study of their short‐term effects on brain functions.MethodsAdult rats were implanted with GC cells and checked 10 weeks later, when a GH/IGF‐I‐secreting tumour was already formed.ResultsTumour‐bearing rats acquired different operant conditioning tasks faster and better than controls and tumour‐resected groups. They also presented better retentions of long‐term memories in the passive avoidance test. Experimentally evoked long‐term potentiation (LTP) in the hippocampus was also larger and longer lasting in the tumour bearing than in the other groups. Chronic adult‐onset of GH/IGF‐I hypersecretion caused an acceleration of early progenitors, facilitating a faster neural differentiation, maturation and integration in the dentate gyrus, and increased the complexity of dendritic arbours and spine density of granule neurons.ConclusionThus, adult‐onset hypersecretion of GH/IGF‐I improves neurocognitive functions, long‐term memories, experimental LTP and neural differentiation, migration and maturation.
Business ethics in the broiler industry
Authors: Beets S. Douglas 
Published: May 2019

AbstractThe chicken meat, or broiler, business in the United States is a vertically integrated industry in which integrator corporations control all aspects of the business. Primarily through a series of business acquisitions, an industry duopoly has evolved. The two dominant integrator corporations, Pilgrim's Pride and Tyson Foods, are profitable, and their officers and stockholders benefit from the corporations’ financial success. The multitude of local growers who nurture the chickens to maturity for the integrators, however, benefit minimally from the financial success of the integrators, as the growers face a myriad of financial, environmental, community, and health problems. Many growers have difficulty in extracting themselves from an occupation that requires their initial, personal expenditure, or debt of hundreds of thousands of dollars. Additionally, many who live in regions or states of broiler growing facilities suffer from gases emitted by these facilities and correspondingly lower property values. Several demographic, economic, education, health, and quality of life metrics were analyzed for the 50 U.S. states to provide insights regarding the ethics of the broiler industry and why some states produce significantly more broilers than others.
Pharmacokinetic and haemodynamic interactions between amlodipine and losartan in human beings
Authors: Park Jin‐Woo , Kim Kyoung‐Ah , Il Kim Yong , Park Ji‐Young 
Published: May 2019

AbstractThe combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety. Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. The potential pharmacokinetic interactions between amlodipine and losartan were assessed. An open‐label, three‐period, fixed‐sequence trial was conducted. Amlodipine, losartan and combined amlodipine and losartan were administered to 24 healthy male participants during periods 1, 2 and 3, respectively, for 9 days each. The pharmacokinetics of amlodipine, losartan and EXP‐3174, an active metabolite of losartan, were assessed at steady‐state. Twenty participants completed the study without serious adverse events. Losartan did not influence the exposure of amlodipine at steady‐state (AUCτ, 165.15 ng h/mL [amlodipine alone] vs 172.36 ng h/mL [combination], P = 0.389) [geometric mean ratio (GMR) (90% confidence interval [CI]), 1.060 (0.954‐1.178)]. In addition, the exposure of EXP‐3174 was not affected by amlodipine (AUCτ, 1159.46 ng h/mL vs 1105.10 ng h/mL, P = 0.295) (GMR [90% CI], 0.957 [0.891‐1.027]). However, amlodipine significantly decreased the exposure of losartan at steady‐state (AUCτ, 1241.50 ng h/mL vs 1082.02 ng h/mL, P = 0.006) (GMR [90% CI], 0.875 [0.813‐0.942]) and increased oral clearance of losartan (84.65 L/h vs 97.26 L/h, P = 0.002). Combination use of two drugs caused additive haemodynamic changes compared to treatment of amlodipine or losartan alone. The co‐administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction, even though losartan disposition was affected. Combination use of the two drugs caused additive haemodynamic changes compared to monotherapy of amlodipine or losartan.
Examining the psychological well‐being of refugee children and the role of friendship and bullying
Authors: Samara Muthanna , El Asam Aiman , Khadaroo Ameerah , Hammuda Sara 
Published: May 2019

BackgroundRefugee children might have experienced violent and traumatic events before settling into a new country. In the United Kingdom, the number of refugee children is increasing; however, little is known about their psycho‐social and physical well‐being.AimThis study aims to investigate the psychological well‐being and behaviour of refugee children compared to British‐born children on a number of psychological, social, behavioural, and health‐related issues and to investigate the role of friendship as a protective factor.SamplesThis study utilized a sample of 149 refugee children recruited from two charities, 79 of which are children aged 6–10 years and 70 older refugee children aged 11–16 years. The study also included 120 non‐refugee children recruited from primary schools aged 6–10 years.MethodsThis is a cross‐sectional study that investigates the psycho‐social well‐being of refugee children compared to non‐refugee British‐born children. The study explored symptoms of posttraumatic stress disorder, emotional and behavioural problems (Strengths and Difficulties Questionnaire), self‐esteem, friendships and popularity, bullying and victimization, physical health, and psychosomatic problems.ResultsYoung refugee children reported more peer problems, functional impairment, physical health, and psychosomatic problems compared to the control children and older refugee children groups. On the other hand, older refugee children had lower self‐esteem (academic and social self‐peers) compared to the younger refugee children group. The differences between the groups were explained by friendship quality, number of friends, peer bullying/victimization, or sibling bullying/victimization except for physical health and psychosomatic problems.ConclusionsWhile refugee children were found to be at risk on various levels, the findings also point to the fact that social relationships including friendship quality and number of friends played an essential protective role. Conversely, bullying was a risk factor that explained many of the refugees’ problems. These findings pave the way for future research to further probe into the well‐being of refugee children in the United Kingdom while also targeting relevant intervention schemes specifically tailored to address their needs.