bluuebunny/crossref_metadata_2025 huggingface dataset:
Systems analysis of protein signatures predicting cetuximab responses in KRAS, NRAS, BRAF and PIK3CA wild‐type patient‐derived xenograft models of metastatic colorectal cancer
Authors: Lindner Andreas U. , Carberry Steven , Monsefi Naser , Barat Ana , Salvucci Manuela , O'Byrne Robert , Zanella Eugenia R. , Cremona Mattia , Hennessy Bryan T. , Bertotti Andrea , Trusolino Livio , Prehn Jochen H. M.
Published: July 2020

Antibodies targeting the human epidermal growth factor receptor (EGFR) are used for the treatment of RAS wild‐type metastatic colorectal cancer. A significant proportion of patients remains unresponsive to this therapy. Here, we performed a reverse‐phase protein array‐based (phospho)protein analysis of 63 KRAS, NRAS, BRAF and PIK3CA wild‐type metastatic CRC tumours. Responses of tumours to anti‐EGFR therapy with cetuximab were recorded in patient‐derived xenograft (PDX) models. Unsupervised hierarchical clustering of pretreatment tumour tissue identified three clusters, of which Cluster C3 was exclusively composed of responders. Clusters C1 and C2 exhibited mixed responses. None of the three protein clusters exhibited a significant correlation with transcriptome‐based subtypes. Analysis of protein signatures across all PDXs identified 14 markers that discriminated cetuximab‐sensitive and cetuximab‐resistant tumours: PDK1 (S241), caspase‐8, Shc (Y317), Stat3 (Y705), p27, GSK‐3β (S9), HER3, PKC‐α (S657), EGFR (Y1068), Akt (S473), S6 ribosomal protein (S240/244), HER3 (Y1289), NF‐κB‐p65 (S536) and Gab‐1 (Y627). Least absolute shrinkage and selection operator and binominal logistic regression analysis delivered refined protein signatures for predicting response to cetuximab. (Phospo‐)protein analysis of matched pretreated and posttreated models furthermore showed significant reduction of Gab‐1 (Y627) and GSK‐3β (S9) exclusively in responding models, suggesting novel targets for treatment.
Profile and outcome of receptor conversion in breast cancer metastases: a nation‐wide multicenter epidemiological study
Authors: Yi Zong‐Bi , Yu Pei , Zhang Su , Wang Wen‐Na , Han Yi‐Qun , Ouyang Qu‐Chang , Yan Min , Wang Xiao‐Jia , Hu Xi‐Chun , Jiang Ze‐Fei , Huang Tao , Tong Zhong‐Sheng , Wang Shu‐Sen , Yin Yong‐Mei , Li Hui , Yang Run‐Xiang , Yang Hua‐Wei , Teng Yue‐E , Sun Tao , Cai Li , Li Hong‐Yuan , Chen Xi , He Jian‐Jun , Liu Xin‐Lan , Yang Shun‐E , Wang Jia‐Yu , Fan Jin‐Hu , Qiao You‐Lin , Xu Bing‐He
Published: July 2020

Although receptor status including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) of the primary breast tumors was related to the prognosis of breast cancer patients, little information is yet available on whether patient management and survival are impacted by receptor conversion in breast cancer metastases. Using data from the nation‐wide multicenter clinical epidemiology study of advanced breast cancer in China (NCT03047889), we report the situation of retesting ER, PR and HER2 status for breast cancer metastases and evaluate the patient management and prognostic value of receptor conversion. In total, 3295 patients were analyzed and 1583 (48.0%) patients retesting receptor status for metastasis. Discordance in one or more receptors between the primary and the metastatic biopsy was found in 37.7% of women. Patients who remained hormone receptor (HR) positive in their metastases had similar progression‐free survival of first‐line and second‐line treatment compared to patients with HR conversion (P > .05). In multivariate analysis, patients who showed ER conversion from negative to positive had longer disease‐free survival (DFS) than patients who remained negative in their metastases (hazard ratio, 2.05; 95% confidence interval [CI], 1.45‐2.90; P < .001). Patients with PR remained positive and had longer DFS than patients with PR conversion from negative to positive (hazard ratio, 0.56; 95% CI, 0.38‐0.83; P = .004). Patients with PR conversion have shorter overall survival than patients with PR remained positive or negative (P = .016 and P = .041, respectively). Our findings showed that the receptors' conversions were common in metastatic breast cancer, and the conversion impacted the survival.
hsa_circ_0000520 influences herceptin resistance in gastric cancer cells through PI3K‐Akt signaling pathway
Authors: Lv Xukun , Li Peizhe , Wang Jinkai , Gao Hengling , Hei Yingrui , Zhang Jianxian , Li Shuliang
Published: July 2020

Background

To investigate whether hsa_circ_0000520 affects Herceptin resistance in gastric cancer by regulating the PI3K‐AKT signaling.

Methods

The expression of hsa_circ_0000520 was detected by qRT‐PCR in gastric cancer tissues and cell lines. A Herceptin‐resistant gastric cancer cell was established. PcDNA and pcDNA‐hsa_circ_0000520 were transfected into NCI‐N87R cells and treated with Herceptin at a concentration of 10 μg/mL for 24 hours. MTT tested cell proliferation, and apoptosis was measured by flow cytometry. IGF‐1 treatment was used to activate PI3K‐Akt signaling. The expression levels of related proteins were detected.

Results

The expression of hsa_circ_0000520 was reduced in gastric cancer tissues and cell lines, and hsa_circ_0000520 in NCI‐N87R cells was significantly lower than that of NCI‐N87 cells. Compared with the CON group, the cell viability of the Herceptin group was significantly reduced, the apoptosis rate was significantly increased, the level of Bax protein was significantly increased, and the levels of Bcl‐2, p‐PI3K, and p‐Akt protein were significantly reduced. Compared with the Herceptin + pcDNA group, the cell viability of the Herceptin + hsa_circ_0000520 group was significantly reduced, the apoptosis rate was significantly increased, the level of Bax protein was significantly increased, and the levels of p‐PI3K and p‐Akt proteins were significantly reduced. After IGF‐1 treatment, the cell viability was significantly increased, the apoptosis rate was significantly reduced, the level of Bax protein was significantly reduced, and the level of Bcl‐2 protein was significantly increased.

Conclusion

Hsa_circ_0000520 overexpression may reverse the Herceptin resistance of gastric cancer cells by inhibiting the PI3K‐Akt signaling pathway.
miR‐142a‐5p promoted osteoblast differentiation via targeting nuclear factor IA
Authors: Yuan Hairui , Li Mengyue , Feng Xue , Zhu Endong , Wang Baoli
Published: July 2020

miR‐142a‐5p plays critical roles in multiple biological processes and diseases, such as inflammation and tumorigenesis. However, it remains to be explored if and how miR‐142a‐5p contributes to osteoblast differentiation. In this study, our results showed that miR‐142a‐5p was highly expressed in bone tissue of mice and increased during osteogenesis in preosteoblast MC3T3‐E1 cells. Supplementing miR‐142a‐5p activity using miR‐142a‐5p agomir promoted osteogenic differentiation in stromal cell line ST2 and preosteoblastic line MC3T3‐E1. Conversely, miR‐142a‐5p antagomir, an inhibitor of endogenous miR‐142a‐5p, could reduce osteoblast differentiation in ST2 and MC3T3‐E1 cells. Nuclear factor IA (NFIA), a site‐specific transcriptional factor, was demonstrated to be directly targeted by miR‐142a‐5p. Overexpression of NFIA inhibited miR‐142a‐5p‐mediated osteoblast differentiation in ST2 cells. Furthermore, mechanism explorations revealed that Wnt/β‐catenin signaling transcriptionally regulated the expression of miR‐142a‐5p during osteogenic differentiation. β‐catenin binds to the T‐cell factor/lymphoid enhancer factor binding motif within the promoter of miR‐142 and positively regulates its transcriptional activity. Our findings suggested that miR‐142a‐5p promoted osteoblast differentiation via targeting NFIA.
Growth of Head Circumference and Body Length in Preterm Infants Receiving a Multicomponent vs a Soybean‐Based Lipid Emulsion: A Randomized Controlled Trial
Authors: Costa Simonetta , Cocca Carmen , Barone Giovanni , Catenazzi Piero , Gallini Francesca , Maggio Luca , Fusco Francesca Paola , Vento Giovanni
Published: July 2020

Background

The growth of very low‐birth‐weight (VLBW) infants relies, to a large extent, on parenteral nutrition (PN) during the early weeks of life. Despite the parenteral nutrients supply, extrauterine growth restriction remains the main concern for these infants. A parenteral multicomponent lipid emulsion (MLE) might improve growth and neurological outcomes, delivering fats for brain growth that the traditional soybean‐based lipid emulsion (SLE) fails to provide. We hypothesize that the use of an MLE in PN may reduce the loss of head circumference (HC) z‐score from birth to 36 weeks’ postmenstrual age (PMA) or at discharge compared with the use of an SLE in VLBW infants.

Methods

Infants with BW ≤1250 g, without malformations or chromosomal abnormalities, were randomly assigned to receive an MLE or an SLE. The primary outcome was the change in HC z‐score (HC Δ z‐score) from birth to 36 weeks’ PMA or at discharge. Secondary outcomes included the change in weight and length z‐score (W Δ z‐score and L Δ z‐score) as well as incidence of late‐onset sepsis and PN‐associated cholestasis (PNAC).

Results

Of the 128 infants randomized, 51 infants in the MLE group and 50 infants in the SLE group were analyzed. The MLE was significantly associated with a decreased loss in HC and length z‐scores from birth to 36 weeks’ PMA or at discharge.

Conclusions

This is the first randomized controlled trial providing the evidence that an MLE is associated with improved HC growth in comparison with a pure SLE.
High‐performance liquid chromatography–based fingerprint analysis with chemical pattern recognition for evaluation of Mahonia bealei (Fort.) Carr
Authors: Huang Yang , Wang Tiejie , Yin Guo , Wang Jue , Jiang Kun , Tu Jiasheng
Published: July 2020

A simple and efficient high‐performance liquid chromatography method combined with chemical pattern recognition was established for quality evaluation of Mahonia bealei (Fort.) Carr. A common pattern of 30 characteristic peaks was applied for similarity analysis, hierarchical cluster analysis, principal component analysis, and partial least squares discriminant analysis in the 37 batches of M. bealei (Fort.) Carr. to discriminate wild M. bealei (Fort.) Carr., cultivated M. bealei (Fort.) Carr., and its substitutes. The results showed that partial least squares discriminant analysis was the most effective method for discrimination. Eight characteristics peaks with higher variable importance in projection values were selected for pattern recognition model. A permutation test and 26 batches of testing set samples were performed to validate the model that was successfully established. All of the training and testing set samples were correctly classified into three clusters (wild M. bealei (Fort.) Carr., cultivated M. bealei (Fort.) Carr., and its substitutes) based on the selected chemical markers. Moreover, 26 batches of unknown samples were used to predict the accuracy of the established model with a discrimination accuracy of 100%. The obtained results indicated that the method showed great potential application for accurate evaluation and prediction of the quality of M. bealei (Fort.) Carr.
Anal Sphincter Length as Determined by 3‐Dimensional Endoanal Ultrasound and Anal Manometry
Authors: Norderval Stig , Pedersen Torunn K. , Collinson Rowan J.
Published: July 2020

Objectives

The normal female external anal sphincter (EAS) is shorter anteriorly than laterally and posteriorly. Furthermore, the thickness of the very proximal part of the circular EAS is thinner than 50% of the lateral and posterior EAS thickness. The extent of these features is not fully explored. The aim of this prospective study was to assess the normal anal sphincter with 3‐dimensional (3D) endoanal ultrasound (EAUS) and to relate 3D EAUS length measurements to sphincter length determined by anal manometry.

Methods

Healthy premenopausal nulliparous women underwent anal manometry and 3D EAUS examinations. Two experienced colorectal surgeons independently assessed all scans, blinded to any patient data.

Results

A total of 43 women were included. Four scans were incomplete and excluded from the analysis. Interobserver agreement was fair to very good for the various length measurements. The mean length from the distal border of the puborectal muscle to the very proximal border of the anterior EAS (the anterior gap) was 4.4 (95% confidence interval, 3.9–4.9) mm, whereas the length to the level where the anterior EAS thickness was at least 50% of the lateral and posterior EAS thickness was 7.2 (95% confidence interval, 6.5–7.9) mm. Manometric sphincter length at rest did not correlate with any 3D EAUS length measurements.

Conclusions

In the normal anterior female anal canal, the EAS is not present or appears with less than 50% of the thickness of the lateral and posterior EAS for the first 7.2 mm below the distal border of the puborectal muscle.
Association Between Olfactory Impairment and Disease Severity and Duration in Parkinson's Disease
Authors: Sasaki Shoichi , Horie Yoshiharu
Published: July 2020

Background

The association between olfactory dysfunction and disease duration and severity in Parkinson's disease (PD) remains controversial.

Objective

The objective of this study was to examine the relationship between olfactory dysfunction and disease severity and duration in patients with recently diagnosed parkinsonism and patients with PD with a previous diagnosis.

Methods

Olfactory function was evaluated in 79 patients with recently diagnosed parkinsonism, 71 patients with PD with a previous diagnosis—with patients in both groups free of cognitive impairment—and 128 age‐matched controls. The Odor‐Stick Identification Test for Japanese score was counted as the numbers of correct answers, responses of indistinguishable, and responses of odorless. Parkinsonism was evaluated using the Movement Disorder Society Criteria, the Unified Parkinson Disease Rating Scale (UPDRS) Part III, and 123iodine‐labeled N‐(3‐fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐iodophenyl) nortropane single photon emission computed tomography (DaTscan).

Results

In the patients with recently diagnosed parkinsonism having the UPDRS Part III score ≥5 (mean [standard deviation: SD] score: 6.3 [1.9]) and with a positive DaTscan, the mean (SD) numbers of correct answers, responses of indistinguishable and responses of odorless were 4.3 (2.2), 1.6 (2.0), and 1.2 (2.2), respectively. In patients with PD with a previous diagnosis (mean [SD] UPDRS Part III score: 10.9 [3.2]), these numbers were 2.5 (2.2), 2.2 (2.5), and 3.8 (4.6), respectively. The patients with PD with a previous diagnosis showed more significant deterioration than the patients with recently diagnosed parkinsonism in the numbers of correct answers and responses of odorless (P < 0.0001). Olfaction in the combined patient group was significantly impaired compared with age‐matched controls in each category (P < 0.0001).

Conclusions

These findings imply a close association between olfactory dysfunction and disease severity and duration in PD.
Unique weak solutions of the d‐dimensional micropolar equation with fractional dissipation
Authors: Ben Said Oussama , Wu Jiahong
Published: July 2020

This article examines the existence and uniqueness of weak solutions to the d‐dimensional micropolar equations (d=2 or d=3) with general fractional dissipation (−Δ)αu and (−Δ)βw. The micropolar equations with standard Laplacian dissipation model fluids with microstructure. The generalization to include fractional dissipation allows simultaneous study of a family of equations and is relevant in some physical circumstances. We establish that, when
and
, any initial data (u0,w0) in the critical Besov space
and
yields a unique weak solution. For α ≥ 1 and β=0, any initial data
and
also leads to a unique weak solution as well. The regularity indices in these Besov spaces appear to be optimal and can not be lowered in order to achieve the uniqueness. Especially, the 2D micropolar equations with the standard Laplacian dissipation, namely, α=β=1, have a unique weak solution for
. The proof involves the construction of successive approximation sequences and extensive a priori estimates in Besov space settings.
Lactic Acidosis Secondary to Thiamin Deficiency Following Autologous Stem Cell Transplantation
Authors: Derespina Kim R , Kaushik Shubhi , Mahadeo Kris , McCabe Megan
Published: July 2020

A 22‐month‐old female with high‐risk neuroblastoma completed 5 cycles of chemotherapy then underwent high‐dose chemotherapy with autologous stem cell rescue (ASCR). Parenteral nutrition was administered from day +2 following ASCR, as she was unable to tolerate nasogastric feeds because of grade IV mucositis and vomiting. On day +12, she developed worsening metabolic acidosis with above reportable levels of lactic acid. Given the patient's well clinical appearance and paucity of evidence of end‐organ dysfunction on physical examination and on laboratory studies, there was high suspicion that the patient's lactic acidosis did not result from tissue hypoxia and was, in fact, a type B lactic acidosis. Thiamin was empirically administered, with rapid improvement in lactic acidosis. Thiamin deficiency was later confirmed by laboratory studies drawn prior to thiamin administration.
Holocene pore‐ice δ18O and δ2H records from drained thermokarst lake basins in the Old Crow Flats, Yukon, Canada
Authors: Bandara Sasiri , Froese Duane , Porter Trevor J. , Calmels Fabrice
Published: July 2020

Thermokarst lakes form following the thaw of ice‐rich permafrost and drain after a few decades to millennia. Drained thermokarst lake basins (DTLBs) become epicenters for peat accumulation and re‐aggradation of ice‐rich permafrost. This re‐aggradation of permafrost may be interrupted by subsequent thermokarst lake formation with sufficient disturbance. Thermokarst lakes and DTLBs are abundant near Old Crow, Yukon, Canada, but little is known about their evolution through the Holocene. In this study, we investigate the hydrology and drainage histories of seven DTLBs from the Old Crow Flats on the basis of cryostratigraphy, radiocarbon dating, and pore‐ice δ18O and δ2H records. Cryostratigraphic evidence implies only one of the seven studied DTLBs underwent multiple thermokarst cycles. Radiocarbon age–depth models demonstrate a slowdown in the rate of post‐drainage peat accumulation with time. Pore‐ice isotope analyses reveal a spectrum of possible post‐drainage isotopic histories resulting from spatial variability in permafrost, vegetation, and hydrology. Unlike lacustrine silt, post‐drainage peat contains relatively constant pore‐ice isotope trends. In light of our findings, we propose that syngenetic peat permafrost in DTLBs preserve a warm‐season sampling of local meteoric waters. These pore‐ice δ18O and δ2H records may aid millennial‐scale paleoclimate investigations, as we demonstrate through our reconstruction of Holocene climate change in northern Yukon.
Ensemble model for the degradation prediction of proton exchange membrane fuel cell stacks
Authors: Wang Fu‐Kwun , Huang Chang‐Yi , Mamo Tadele , Cheng Xiao‐Bin
Published: July 2020

Proton exchange membrane fuel cell (PEMFC) stacks are widely used in mobile and portable applications due to their clean and efficient model of operation. We propose an ensemble model based on a stacked long short‐term memory model that combines three machine‐learning models, including long short‐term memory with attention mechanism, support vector regression, and random forest regression, to improve the degradation prediction of a PEMFC stack. The prediction intervals can be derived using the dropout technique. The proposed model is compared with some existing models using two PEMFC stacks. The results show that the proposed model outperforms the other models in terms of mean absolute percentage error and root mean square error. Regarding the remaining useful life prediction, the proposed model with the sliding window approach can provide better results.
A conceptual framework for barriers of circular supply chains for sustainability in the textile industry
Authors: Kazancoglu Ipek , Kazancoglu Yigit , Yarimoglu Emel , Kahraman Aysun
Published: July 2020

Circular economy is a contemporary concept including usage of renewable materials and technologies. The transition to the circular economy creates value through closed‐loop systems, reverse logistics, eco‐design, product life cycle management, and clean production. The aim of the study was to propose a holistic conceptual framework for barriers of circular supply chain for sustainability in the textile industry. Within this aim, an in‐depth literature review on barriers was conducted by covering all supply chain stages and circular initiatives in textile industry. Then, a focus group study was implemented. In the focus group study, barriers related to supply chains that prevent companies to implement the circular economy were discussed and validated. As a result, a total of 25 barriers were classified under nine main categories such as (a) management and decision‐making, (b) labour, (c) design challenges, (d) materials, (e) rules and regulations, (f) lack of knowledge and awareness, (g) lack of integration and collaboration, (h) cost, and (i) technical infrastructure.
Art‐on‐a‐Chip: Preserving Microfluidic Chips for Visualization and Permanent Display
Authors: Soffe Rebecca , Mach Albert J. , Onal Sevgi , Nock Volker , Lee Luke P. , Nevill J. Tanner
Published: July 2020

“After a certain high level of technical skill is achieved, science and art tend to coalesce in aesthetics, plasticity, and form. The greatest scientists are always artists as well.” said Albert Einstein. Currently, photographic images bridge the gap between microfluidic/lab‐on‐a‐chip devices and art. However, the microfluidic chip itself should be a form of art. Here, novel vibrant epoxy dyes are presented in combination with a simple process to fill and preserve microfluidic chips, to produce microfluidic art or art‐on‐a‐chip. In addition, this process can be used to produce epoxy dye patterned substrates that preserve the geometry of the microfluidic channels—height within 10% of the mold master. This simple approach for preserving microfluidic chips with vibrant, colorful, and long‐lasting epoxy dyes creates microfluidic chips that can easily be visualized and photographed repeatedly, for at least 11 years, and hence enabling researchers to showcase their microfluidic chips to potential graduate students, investors, and collaborators.
Development and validation of HPLC methodology for quantitative estimation of Efinaconazole in topical pharmaceutical formulation prepared in‐house for the treatment of onychomycosis
Authors: Patani Nikesh , Patel Mrunali , Patel Rashmin
Published: July 2020

The purpose of this research work was to design, develop, and optimize new high‐performance liquid chromatography method for quantitative estimation of Efinaconazole in topical pharmaceutical formulation developed in‐house for the treatment of onychomycosis. Based on the outcomes of preliminary investigation, optimized high‐performance liquid chromatography conditions were reverse phase column (Luna C18) as stationary material, with simple isocratic mobile phase comprising mixture of water and acetonitrile (20:80 v/v), flow rate 1 mL/min, column oven temperature 30°C, injection volume 10 µL, detection wavelength of 230 nm, and total run time of 10 min. The optimized method was successfully validated as per International Council for Harmonization guideline Q2(R1), and statistical analysis proved that the method is specific (peak purity ≥ 0.999), accurate (99.21–99.63% w/w), precise (% relative standard deviation < 2.0), and sensitive (limit of detection = 9.26 µg and limit of quantitation = 28.05 µg). As a result, this research work provides a new and simple high‐performance liquid chromatography methodology with optimized chromatographic parameters for quantitation of Efinaconazole as a routine assay purpose, contributing to the technological and scientific domain and guaranteeing a safe and effective use of Efinaconazole for the treatment of onychomycosis.
An innovative infill wall utilizing light expanded clay aggregate: An experimental and numerical study
Authors: Ghamari Ali , Khaloo Alireza
Published: July 2020

Past earthquakes had shown vulnerability of infill walls especially under out of plane (OOP) loading. Although some new infill walls show a good OOP performance, generally, they do not have the right economic justification or have complexity in construction. Therefore, in this paper, an innovative economical infill wall is presented that is not complicated in construction. The proposed wall constructed by light expanded clay aggregate in especial shape that reinforced with side plates, top, and bottom rebars. Experimental and numerical studies were carried out to investigate its seismic performance. Experimental results showed a high continuity between blocks of wall due to its especial shape that is increased ultimate OOP strength and ultimate OOP displacement of the wall. Numerical results indicated, because the infill wall is isolated from boundary frame, no drift is imposed to infill wall from boundary frame. Therefore, the infill wall only suffered OOP seismic acceleration. Due to light weight of the infill wall, low OOP load that corresponds to seismic acceleration is applied to the infill wall. In the infill wall, no separation is made even up to drift frame of 2.5%. The relations to design of the proposed infill wall were also presented.
The scattering amplitude of stringy hadrons: strings with opposite charges on their endpoints
Authors: Sonnenschein Jacob , Weissman Dorin , Yankielowicz Shimon
Published: July 2020

Abstract

In this note we describe hadrons: mesons and baryons as strings with electric charges on their endpoints. We consider here only the neutral system with opposite charges, coupled to an external constant electromagnetic field. We derive certain classical solutions including rotating folded open strings. We write down the mode expansion and canonically quantize the system. The OPEs associated with such strings are determined. We rederive the non-commutativity of the zero modes and the fact that the charges modify the spacetime metric. We show that the quantum worldsheet energy momentum tensor on the boundary is affected by the endpoint charges and differs from the corresponding Noether current. We determine the generalization of the Veneziano scattering amplitude for such strings in the critical dimension. Phenomenological implications are addressed and in particular we show that the external magnetic field can be tuned so that the amplitude vanishes for particular kinematic setups. We discuss the generalization of such strings to non-critical four dimensional spacetime. In particular we renormalize the divergence of the Polchinski-Strominger effective action associated with the rotating folded string.
Changes in positive associations among vertebrate predators at South Georgia during winter
Authors: Monier Samantha A. , Veit Richard R. , Manne Lisa L.
Published: July 2020

We studied positive associations among seabirds and marine mammals at South Georgia on research cruises during the Austral winters of 1985, 1991 and 1993 and found statistically significant differences. We collected data on abundance and distribution, providing a critical reference for sub-Antarctic conservation in anticipation of future environmental changes. We found significant changes in the abundance of 29% of species surveyed and a consequent change in species diversity. We postulate that the resulting altered community composition may have previously unanticipated population effects on the component species, due to changes in positive interactions among species which use each other as cues to the presence of prey. We found a near threefold reduction in spatial overlap among vertebrate predators, associated with warming sea temperatures. As the strength and opportunity for positive associations decreases in the future, feeding success may be negatively impacted. In this way, environmental changes may disproportionately impact predator abundances and such changes are likely already underway, as Southern Ocean temperatures have increased substantially since our surveys. Of course the changes we describe are not solely due to changing sea temperature or any other single cause—many factors are important and we do not claim to have removed these from consideration. Rather, we report previously undocumented changes in positive associations among species, and argue these changes may continue into the future, given near-certain continued increases in climate-related changes.
Self-tuning serverless task farming using proactive elasticity control
Authors: Kehrer Stefan , Zietlow Dominik , Scheffold Jochen , Blochinger Wolfgang
Published: July 2020

The cloud evolved into an attractive execution environment for parallel applications, which make use of compute resources to speed up the computation of large problems in science and industry. Whereas Infrastructure as a Service (IaaS) offerings have been commonly employed, more recently, serverless computing emerged as a novel cloud computing paradigm with the goal of freeing developers from resource management issues. However, as of today, serverless computing platforms are mainly used to process computations triggered by events or user requests that can be executed independently of each other and benefit from on-demand and elastic compute resources as well as per-function billing. In this work, we discuss how to employ serverless computing platforms to operate parallel applications. We specifically focus on the class of parallel task farming applications and introduce a novel approach to free developers from both parallelism and resource management issues. Our approach includes a proactive elasticity controller that adapts the physical parallelism per application run according to user-defined goals. Specifically, we show how to consider a user-defined execution time limit after which the result of the computation needs to be present while minimizing the associated monetary costs. To evaluate our concepts, we present a prototypical elastic parallel system architecture for self-tuning serverless task farming and implement two applications based on our framework. Moreover, we report on performance measurements for both applications as well as the prediction accuracy of the proposed proactive elasticity control mechanism and discuss our key findings.
Coffee consumption and overall and cause-specific mortality: the Norwegian Women and Cancer Study (NOWAC)
Authors: Lukic Marko , Barnung Runa Borgund , Skeie Guri , Olsen Karina Standahl , Braaten Tonje
Published: July 2020

Coffee consumption has previously been reported to reduce overall and cause-specific mortality. We aimed to further investigate this association by coffee brewing methods and in a population with heavy coffee consumers. The information on total, filtered, instant, and boiled coffee consumption from self-administered questionnaires was available from 117,228 women in the Norwegian Women and Cancer (NOWAC) Study. We used flexible parametric survival models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause, cardiovascular, and cancer mortality by total coffee consumption and brewing methods, and adjusted for smoking status, number of pack-years, age at smoking initiation, alcohol consumption, body mass index, physical activity, and duration of education. During 3.2 million person-years of follow-up, a total of 16,106 deaths occurred. Compared to light coffee consumers (≤ 1 cup/day), we found a statistically significant inverse association with high-moderate total coffee consumption (more than 4 and up to 6 cups/day, HR 0.89; 95% CI 0.83–0.94) and all-cause mortality. The adverse association between heavy filtered coffee consumption (> 6 cups/day) and all-cause mortality observed in the entire sample (HR 1.09; 95% CI 1.01–1.17) was not found in never smokers (HR 0.85; 95% CI 0.70–1.05). During the follow-up, both high-moderate total and filtered coffee consumption were inversely associated with the risk of cardiovascular mortality (HR 0.79; 95% CI 0.67–0.94; HR 0.80; 95% CI 0.67–0.94, respectively). The association was stronger in the analyses of never smokers (> 6 cups of filtered coffee/day HR 0.20; 95% CI 0.08–0.56). The consumption of more than 6 cups/day of filtered, instant, and coffee overall was found to increase the risk of cancer deaths during the follow-up. However, these associations were not statistically significant in the subgroup analyses of never smokers. The data from the NOWAC study indicate that the consumption of filtered coffee reduces the risk of cardiovascular deaths. The observed adverse association between coffee consumption and cancer mortality is most likely due to residual confounding by smoking.
Hoxd10 Is Required Systemically for Secretory Activation in Lactation and Interacts Genetically with Hoxd9
Authors: Landua John D. , Moraes Ricardo , Carpenter Ellen M. , Lewis Michael T.
Published: July 2020

Targeted disruption of the murineHoxd10gene(ΔHoxd10)leads to a high frequency of localized (gland-to-gland or regionally within a gland) lactation impairment in homozygous mutant mice as a single gene mutation. The effect ofHoxd10disruption was enhanced by simultaneous disruption ofHoxd9 (ΔHoxd9/d10), a mutation shown previously to have no effect on mammary function as a single gene alteration. Mammary glands of homozygousΔHoxd10andΔHoxd9/d10females were indistinguishable from those of wild type littermate and age-matched control mice in late pregnancy. However, in lactation, 47% of homozygousΔHoxd10females, and 100% of homozygousΔHoxd9/d10females, showed localized or complete failure of two or more glands to undergo lactation-associated morphological changes and to secrete milk. Affected regions ofΔHoxd10andΔHoxd9/d10mutants showed reduced prolactin receptor expression, reduced signal transducer and activator transcription protein 5 (STAT5) phosphorylation, reduced expression of downstream milk proteins, mislocalized glucose transporter 1 (GLUT1), increased STAT3 expression and phosphorylation, recruitment of leukocytes, altered cell cycle status, and increased apoptosis relative to unaffected regions and wild type control glands. Despite these local effects on alveolar function, transplantation results and hormone analysis indicate thatHoxd10primarily has systemic functions that confer attenuated STAT5 phosphorylation on both wild type andΔHoxd10transplants when placed inΔHoxd10hosts, thereby exacerbating an underlying propensity for lactation failure in C57Bl/6 mice.
Dissolution behavior of metal oxide nanomaterials in cell culture medium versus distilled water
Authors: Avramescu Mary-Luyza , Chénier Marc , Palaniyandi Srijanani , Rasmussen Pat E.
Published: July 2020

Solubility is a key criterion used in the hazard assessment of metal oxide–engineered nanomaterials (ENMs). The present study investigated solubility of CuO, NiO, and TiO2ENMs compared with their bulk analogues in two aqueous media: water and Dulbecco’s modified Eagle’s medium (DMEM). Particle size distributions were characterized using dynamic light scattering (DLS) and tunable resistive pulse sensing (TRPS). After centrifugal separation, the dissolved metal fraction was quantified using inductively coupled plasma optical emission spectroscopy (ICP-OES). Overall, solubility of the metal oxides decreased in the order CuO ≥ NiO > TiO2in both media, with each ENM displaying higher solubility than its bulk analogue. However, the metal oxide ENMs responded differently to the two aqueous media, when comparing their solubility using a low initial concentration (10 mg/L) versus a high initial concentration (100 mg/L). In DMEM, both nano-CuO and nano-NiO displayed increased solubility at the higher initial concentration by 3.8-fold and 1.4-fold, respectively. In water, this trend was reversed, with both nano-CuO and nano-NiO displaying increased solubility at the lower initial concentration by 3.3-fold and 1.2-fold, respectively. Interestingly, solubility trends displayed by nano-TiO2were the opposite of those displayed by nano-CuO and nano-NiO. In DMEM, nano-TiO2displayed decreased solubility at the higher initial concentration (0.3-fold), whereas in water, nano-TiO2displayed increased solubility at the higher initial concentration (5.5-fold). These results show the importance of evaluating the solubility of ENMs in biologically relevant fluids at concentrations that correspond to toxicity assays, for the purposes of read-across and grouping ENMs.
Suitability of 2D modelling to evaluate flow properties in 3D porous media
Authors: Marafini Ester , La Rocca Michele , Fiori Aldo , Battiato Ilenia , Prestininzi Pietro
Published: July 2020

The employment of 2D models to investigate the properties of 3D flows in porous media is ubiquitous in the literature. The limitations of such approaches are often overlooked. Here, we assess to which extent 2D flows in porous media are suitable representations of 3D flows. To this purpose, we compare representative elementary volume (REV) scales obtained by 2D and 3D numerical simulations of flow in porous media. The stationarity of several quantities, namely porosity, permeability, mean and variance of velocity, is evaluated in terms of both classical and innovative statistics. The variance of velocity, strictly connected to the hydrodynamic dispersion, is included in the analysis in order to extend conclusions to transport phenomena. Pore scale flow is simulated by means of a Lattice Boltzmann model. The results from pore scale simulations point out that the 2D approach often leads to inconsistent results, due to the profound difference between 2D and 3D flows through porous media. We employ the error in the evaluation of REV as a quantitative measure for the reliability of a 2D approach. Moreover, we show that the acceptance threshold for a 2D representation to be valid strongly depends on which flow/transport quantity is sought.
Red cell differential width (RDW) as a predictor of survival outcomes with palliative and adjuvant chemotherapy for metastatic penile cancer
Authors: Patel Reena , English Louise , Liu Wing K. , Tree Alison C. , Ayres Benjamin , Watkin Nick , Pickering Lisa M. , Afshar Mehran
Published: July 2020

Purpose

Red cell distribution width (RDW) measures red cells’ size variability. Metastatic penile cancer displays poor chemotherapy response. As no validated prognostic predictor exists, we investigated whether RDW correlates independently with survival outcomes in metastatic penile cancer treated by chemotherapy.

Methods

Electronic chemotherapy files of patients with metastatic penile cancer (M1 or N3) from a large academic supra-regional centre were retrospectively analysed between 2005 and 2018. Patients were stratified into RDW > 13.9% and < 13.9%, as per published data on RDW in renal cell carcinoma. Survival time was calculated from the date of chemotherapy initiation until the date of death.

Results

58 patients were analysed. The RDW-high group (n = 31) had a poorer survival than the RDW-low group (n = 27). Median overall survival (mOS) in all patients was 19.0 months (95% CI 13.1–24.9). mOS for RDW-high was 15.0 months (95% CI 10.1–19.9) and 37.0 months (95% CI 32.3–43.1) for RDW-low. Kaplan–Meier curves showed a clear disparity in survival (log rank p = 0.025). Cox proportional hazard ratio for death, corrected for T-stage, grade, age and deprivation score was 0.43 (p = 0.04). Sub-analysis of the M1 patients showed mOS in RDW-high of 17 m (95% CI 11.6–22.4) vs. NR; HR for death of 0.42. N3 patients’ mOS in RDW-high cohort was 30 months (95% CI 4.5–55.9) vs. 13 months (95% CI 1.8–24.2) in RDW-low; HR for death was 0.30.

Conclusion

RDW correlates independently with survival outcomes in metastatic penile cancer and may act as a potential predictor of survival outcomes for patients with metastatic penile cancer receiving chemotherapy.
Granzyme B PET Imaging of Immune Checkpoint Inhibitor Combinations in Colon Cancer Phenotypes
Authors: Goggi J. L. , Tan Y. X. , Hartimath S. V. , Jieu B. , Hwang Y. Y. , Jiang L. , Boominathan R. , Cheng P. , Yuen T. Y. , Chin H. X. , Tang J. R. , Larbi A. , Chacko A. M. , Renia L. , Johannes C. , Robins Edward G.
Published: July 2020

Purpose

Immune checkpoint inhibitor (ICI) monotherapy and combination regimens are being actively pursued as strategies to improve durable response rates in cancer patients. However, the biology surrounding combination therapies is not well understood and may increase the likelihood of immune-mediated adverse events. Accurate stratification of ICI response by non-invasive PET imaging may help ensure safe therapy management across a wide number of cancer phenotypes.

Procedures

We have assessed the ability of a fluorine-labelled peptide, [18F]AlF-mNOTA-GZP, targeting granzyme B, to stratify ICI response in two syngeneic models of colon cancer, CT26 and MC38. In vivo tumour uptake of [18F]AlF-mNOTA-GZP following ICI monotherapy, or in combination with PD-1 was characterised and correlated with changes in tumour-associated immune cell populations.

Results

[18F]AlF-mNOTA-GZP showed good predictive ability and correlated well with changes in tumour-associated T cells, especially CD8+ T cells; however, overall uptake and response to monotherapy or combination therapies was very different in the CT26 and MC38 tumours, likely due to the immunostimulatory environment imbued by the MSI-high phenotype in MC38 tumours.

Conclusions

[18F]AlF-mNOTA-GZP uptake correlates well with changes in CD8+ T cell populations and is able to stratify tumour response to a range of ICIs administered as monotherapies or in combination. However, tracer uptake can be significantly affected by preexisting phenotypic abnormalities potentially confusing data interpretation.
Hybride Organisationen führen – das Beispiel Hochschule
Authors: Busse Stefan
Published: July 2020

Hybridität ist ein organisationssoziologisch etabliertes Konzept, dass die Multirationalität moderner Organisationen abbildet. Hybride Organisation spiegelt die komplexen und widersprüchlichen Beziehungen zu unterschiedlichen gesellschaftlichen Sektoren wider. Exemplarisch wird dies an der Organisation Hochschule skizziert. Der Ausganspunkt ist der seit 2008 durch das Centrum für Hochschulentwicklung (CHE) prämierte Hochschulmanager/in des Jahres. Hier werden Führungskompetenzen prämiert, die im Beitrag zu den Anforderungen eines multirationalen Managens und hybriden Führens in Beziehung gesetzt werden. Daraus ergeben sich interessante Anknüpfungspunkte für Beratungsbedarfe (Coaching und Supervision) in Hochschulen als hybride Organisationen.
Recovery on the Pitch: Street Football as a Means of Social Inclusion
Authors: Ogundipe Esther , Borg Marit , Thompson Tommy , Knutsen Tor , Johansen Cathrine , Karlsson Bengt
Published: July 2020

The study contributes to the existing literature on the value of street football teams in recovery, by exploring how persons with mental health and/or substance abuse problems experience participation in street football teams. In total,
51 persons experiencing mental health and/or substance abuse challenges who played in street football teams, in Norway, participated in focus group interviews. The interviews were recorded and transcribed verbatim. Data were analyzed using thematic content analysis, and resulted in three major themes: (1) The spirit of the football team, (2) More than just a pitch, and (3) The country’s best follow-up system. Overall, our findings highlighted the importance of community and communal efforts through acts of citizenship, in facilitating and promoting social inclusion for persons in challenging life situations. Street football is one measure than can be helpful in this context. Communities, policy makers and funders need to acknowledge and gain more insight and understanding of the value that street football teams represent. There is also a need for further studies exploring what contributes to community in our highly individualistic society.
How Does a Mathematician Fit in? A Mixed-Methods Analysis of University Students’ Sense of Belonging in Mathematics
Authors: Lahdenperä Juulia , Nieminen Juuso Henrik
Published: July 2020

University mathematics has been described as a setting that has challenges in inviting everyone to be part of the mathematics community. Thus, university mathematics offers an important context for research on belonging. For this study, we utilised a mixed-methods approach to investigate the various ways mathematics students belong or do not belong to the mathematics community. Based on both quantitative and qualitative analyses, three student profiles were identified: Members of the Scientific Community, Members of the Social Community, and Non-Members. The first profile highlights students’ belonging to the scientific community, the second profile emphasises belonging to the social community of students, and in the third profile students’ responses reflected various ways of not belonging to the mathematics community. In addition, we elaborate on how university mathematics learning environments both promote and hinder students’ sense of belonging. Overall, the study broadens the understanding of the ways of belonging in the mathematics context and provides suggestions for teaching to address the issues of exclusion that are currently present in the culture of university mathematics.
Negative-pressure pneumatic separator: a new solution for hard-coal beneficiation
Authors: Stańczyk Kamil , Bajerski Andrzej , Łączny Marian J.
Published: July 2020

Hard coal is an important source of energy worldwide. Owing to the imperfections of excavation technology, most run-of-mine coals must be processed before they can be utilised as fuel. In this study, tests on the dry separation process were performed with numerous different raw hard coal and coal waste material samples, using a newly designed and constructed negative-pressure pneumatic separator (NPPS). The experiments revealed the effects of the feed-material properties and material processing conditions. These experiments were preceded by additional tests for evaluating the influence of each device operating parameter on the process, to determine the optimal method of supplying the feed material. The calorific value of the processed materials was improved by 5%–40%, while a minimal output yield of products (60%–70%) was maintained. The trials indicated that in coal material processing, the developed NPPS can be used for not only raw coal enrichment but also coal recovery from materials stored at coal-waste dumps. The main advantages of the device are its mobility, low material processing cost, and lack of water consumption during operation.

Graphic abstract