bluuebunny/crossref_metadata_2025_split huggingface dataset:
Keeping older individuals cool in hot and moderately humid conditions: wetted clothing with and without an electric fan
Authors: Cramer Matthew N. , Huang Mu , Moralez Gilbert , Crandall Craig G. 
Published: February 2020

The present study evaluated whether wearing a water-soaked t-shirt, with or without electric fan use, mitigates thermal and cardiovascular strain in older individuals exposed to hot and moderately humid conditions. Nine healthy older individuals (68 ± 4 yr; five women) completed three 120-min heat exposures (42.4 ± 0.2°C, 34.2 ± 0.9% relative humidity) on separate days while wearing a dry t-shirt (CON), a t-shirt soaked with 500 ml of tap water (WET), or a t-shirt soaked with 500 ml of tap water while facing an electric fan (2.4 ± 0.4 m/s; WET+FAN). Measurements included core and skin temperatures, evaporative mass losses, heart rate, and blood pressure. In the WET condition, elevations in core temperature were attenuated compared with DRY from 30 to 120 min and compared with WET+FAN from 30 to 90 min ( P < 0.05). Evaporative mass losses (inclusive of sweat and water losses from the shirt) were greatest in WET+FAN, followed by WET, and then DRY ( P < 0.01). Sweat losses were lowest in WET, followed by DRY, and then WET+FAN ( P < 0.01). Heart rate was lower only at 60 min in WET versus DRY ( P = 0.01). No differences in mean arterial pressure were observed ( P = 0.51). In conclusion, wearing a water-soaked t-shirt without, but not with, electric fan use is an effective heat management strategy to mitigate thermal strain and lower sweat losses in older individuals exposed to hot and moderately humid conditions. NEW & NOTEWORTHY In older individuals exposed to hot and moderately humid environments, electric fan use coupled with a water-soaked t-shirt exacerbates sweat losses without mitigating heat strain compared with a dry t-shirt. However, wearing a water-soaked t-shirt without fan use reduces sweat losses and attenuates heat strain compared with a dry t-shirt and a fan/water-soaked t-shirt combination. These findings suggest wearing a water-soaked t-shirt is an effective heat-management strategy for older individuals during heat waves when air conditioning is inaccessible.
Reliability and agreement of human renal and segmental artery hemodynamics measured using Doppler ultrasound
Authors: Chapman Christopher L. , Johnson Blair D. , Hostler David , Lema Penelope C. , Schlader Zachary J. 
Published: February 2020

To optimize study design and data interpretation, there is a need to understand the reliability of Doppler ultrasound-derived measures of blood velocity (BV) measured in the renal and segmental arteries. Thus, this study tested the following two hypotheses: 1) renal and segmental artery BV measured over the current standard of three cardiac cycles have good agreement with measurements over nine cardiac cycles ( study 1); and 2) renal and segmental artery BV measurements have relatively poor day-to-day reliability ( study 2). In study 1, there was excellent agreement between measurements over three and nine cardiac cycles for BV in both the renal and segmental arteries, as evidenced by BV measurements that were not statistically different ( P ≥ 0.68), were highly consistent ( r ≥ 0.99, P < 0.01), had a coefficient of variation ≤2.5 ± 1.8%, and 97% (renal artery) and 92% (segmental artery) of the individual differences fell within the 95% limits of agreement. In study 2, there was relatively good day-to-day reliability in renal artery BV as evidenced by no differences between three separate days ( P ≥ 0.30), an intraclass correlation coefficient (ICC) of 0.92 (0.78, 0.98), and 7.4 ± 5.5% coefficient of variation. The day-to-day reliability was relatively poor in the segmental artery with an ICC of 0.77 (0.41, 0.93) and 9.0 ± 5.6% coefficient of variation. These findings support measuring renal and segmental artery hemodynamics over three cardiac cycles and the utility in reporting renal BV across days. However, because of the variation across days, hemodynamic responses in the segmental arteries should be reported as changes from baseline when making comparisons across multiple days. NEW & NOTEWORTHY The present study indicates that Doppler ultrasound-derived measures of renal and segmental artery hemodynamics over three cardiac cycles have excellent agreement with those over nine cardiac cycles. These findings support the current practice of measuring renal and segmental artery blood velocity over three cardiac cycles. This study also demonstrates that there is excellent day-to-day reliability for measures of renal artery blood velocity, which supports reporting absolute values of renal artery blood velocity across days. However, it was also found that the day-to-day reliability of segmental artery measurements is relatively poor. Thus, to account for this variability, we suggest that segmental artery hemodynamics be compared as relative changes from baseline across separate days.
Physiological response to fluid resuscitation with Ringer lactate versus Plasmalyte in critically ill burn patients
Authors: Chaussard Maïté , Dépret François , Saint-Aubin Oriane , Benyamina Mourad , Coutrot Maxime , Jully Marion , Oueslati Haikel , Fratani Alexandre , Cupaciu Alexandru , Poniard Alicia , Asehnoune Karim , Dimby Solohaja-Faniaha , Mebazaa Alexandre , Houze Pascal , Legrand Matthieu 
Published: February 2020

The metabolic consequences in vivo of various balanced solutions are poorly known in critically ill patients. The main objective of this study was to describe the metabolic consequences of Plasmalyte versus Ringer lactate (RL) in critically ill burn patients, with a special focus on the plasma clearance of buffer anions (i.e., gluconate, acetate, and lactate). We conducted a randomized trial between August 2017 and October 2018 in a tertiary teaching hospital in Paris, France. Patients with burn total body surface area >30% were randomized to receive Plasmalyte or RL. The primary end point was the base excess 24 h after inclusion. The secondary end points were acetate, gluconate, and lactate plasma concentration, the strong ion difference (SID). Twenty-eight patients were randomized. Twenty-four hours after inclusion, plasma BE was not significantly different in the Plasmalyte and RL groups {−0.9 [95% confidence interval (95% CI): −1.8–0.9] vs. −2.1 [95% CI: −4.6–0.6] mmol/L, respectively, P = 0.26}. Plasma gluconate concentration was higher in the Plasmalyte group ( P < 0.001), with a maximum level of 1.86 (95% CI: 0.98–4.0) mmol/L versus 0 (95% CI: 0–0.15) mmol/L. Plasma acetate and lactate were not significantly different. Ionized calcium level was lower in the Plasmalyte group ( P = 0.002). Hemodynamics did not differ between groups. To conclude, the alkalinizing effect of Plasmalyte was less important than expected with no difference in base excess compared with RL, in part due to gluconate accumulation. Acetate and lactate did not significantly accumulate. Plasmalyte led to significantly lower ionized calcium levels. NEW & NOTEWORTHY During fluid resuscitation in burns the alkalinizing effect of Plasmalyte was less important than expected, with no difference in base excess compared with Ringer lactate (RL), in part due to gluconate accumulation. Acetate and lactate did not significantly accumulate. Plasmalyte led to significantly lower ionized calcium levels.
Modeling Acquired Resistance to the Second-Generation Androgen Receptor Antagonist Enzalutamide in the TRAMP Model of Prostate Cancer
Authors: Cerasuolo Marianna , Maccarinelli Federica , Coltrini Daniela , Mahmoud Ali Mokhtar , Marolda Viviana , Ghedini Gaia Cristina , Rezzola Sara , Giacomini Arianna , Triggiani Luca , Kostrzewa Magdalena , Verde Roberta , Paris Debora , Melck Dominique , Presta Marco , Ligresti Alessia , Ronca Roberto 
Published: February 2020

Abstract
Enzalutamide (MDV3100) is a potent second-generation androgen receptor antagonist approved for the treatment of castration-resistant prostate cancer (CRPC) in chemotherapy-naïve as well as in patients previously exposed to chemotherapy. However, resistance to enzalutamide and enzalutamide withdrawal syndrome have been reported. Thus, reliable and integrated preclinical models are required to elucidate the mechanisms of resistance and to assess therapeutic settings that may delay or prevent the onset of resistance. In this study, the prostate cancer multistage murine model TRAMP and TRAMP-derived cells have been used to extensively characterize in vitro and in vivo the response and resistance to enzalutamide. The therapeutic profile as well as the resistance onset were characterized and a multiscale stochastic mathematical model was proposed to link the in vitro and in vivo evolution of prostate cancer. The model showed that all therapeutic strategies that use enzalutamide result in the onset of resistance. The model also showed that combination therapies can delay the onset of resistance to enzalutamide, and in the best scenario, can eliminate the disease. These results set the basis for the exploitation of this “TRAMP-based platform” to test novel therapeutic approaches and build further mathematical models of combination therapies to treat prostate cancer and CRPC.
Significance: Merging mathematical modeling with experimental data, this study presents the “TRAMP-based platform” as a novel experimental tool to study the in vitro and in vivo evolution of prostate cancer resistance to enzalutamide.
Cancer Cell–Derived Matrisome Proteins Promote Metastasis in Pancreatic Ductal Adenocarcinoma
Authors: Tian Chenxi , Öhlund Daniel , Rickelt Steffen , Lidström Tommy , Huang Ying , Hao Liangliang , Zhao Renee T. , Franklin Oskar , Bhatia Sangeeta N. , Tuveson David A. , Hynes Richard O. 
Published: February 2020

Abstract

The prognosis for pancreatic ductal adenocarcinoma (PDAC) remains poor despite decades of effort. The abundant extracellular matrix (ECM) in PDAC comprises a major fraction of the tumor mass and plays various roles in promoting resistance to therapies. However, nonselective depletion of ECM has led to poor patient outcomes. Consistent with that observation, we previously showed that individual matrisome proteins derived from stromal cells correlate with either long or short patient survival. In marked contrast, those derived from cancer cells correlate strongly with poor survival. Here, we studied three cancer cell–derived matrisome proteins that are significantly overrepresented during PDAC progression, AGRN (agrin), SERPINB5 (serine protease inhibitor B5), and CSTB (cystatin B). Using both overexpression and knockdown experiments, we demonstrate that all three are promoters of PDAC metastasis. Furthermore, these proteins operate at different metastatic steps. AGRN promoted epithelial-to-mesenchymal transition in primary tumors, whereas SERPINB5 and CSTB enhanced late steps in the metastatic cascade by elevating invadopodia formation and in vivo extravasation. All three genes were associated with a poor prognosis in human patients and high levels of SERPINB5, secreted by cancer cells and deposited in the ECM, correlated with poor patient prognosis. This study provides strong evidence that cancer cell–derived matrisome proteins can be causal in promoting tumorigenesis and metastasis and lead to poor patient survival. Therefore, compared with the bulk matrix, mostly made by stromal cells, precise interventions targeting cancer cell–derived matrisome proteins, such as AGRN, SERPINB5, and CSTB, may represent preferred potential therapeutic targets.

Significance:
This study provides insights into the biological roles of cancer cell–derived matrisome proteins in PDAC and supports the notion that these proteins are protumorigenic and better therapeutic targets.
Propranolol: What is BLOCKing Its Clinical Investigation in Breast Cancer?
Authors: Blaes Anne H. , Domingo-Musibay Evidio , Kalinsky Kevin 
Published: February 2020

Abstract

Presurgical propranolol modulates biomarkers associated with breast cancer progression. β-adrenergic signaling promotes invasion, epithelial-to-mesenchymal transition phenotype, and immune cell infiltration into the tumor microenvironment. Blockade of the β-adrenergic receptor signaling with propranolol, along with potential future combinatorial strategies, holds promise for reducing breast cancer progression and metastasis.
See related article by Hiller et al., p. 1803
c-Src Phosphorylates and Inhibits the Function of the CIC Tumor Suppressor Protein
Authors: Bunda Severa , Heir Pardeep , Li Annie Si Cong , Mamatjan Yasin , Zadeh Gelareh , Aldape Kenneth 
Published: February 2020

Abstract

Capicua (CIC) is a transcriptional repressor that counteracts activation of genes in response to receptor tyrosine kinase (RTK)/Ras/ERK signaling. Following activation of RTK, ERK enters the nucleus and serine-phosphorylates CIC, releasing it from its targets to permit gene expression. We recently showed that ERK triggers ubiquitin-mediated degradation of CIC in glioblastoma (GBM). In this study, we examined whether another important downstream effector of RTK/EGFR, the non-RTK c-Src, affects CIC repressor function in GBM. We found that c-Src binds and tyrosine-phosphorylates CIC on residue 1455 to promote nuclear export of CIC. On the other hand, CIC-mutant allele (CIC-Y1455F), that escapes c-Src–mediated tyrosine phosphorylation, remains localized to the nucleus and retains strong repressor function against CIC targets, the oncogenic transcription factors ETV1 and ETV5. Furthermore, we show that the orally available Src family kinase inhibitor, dasatinib, which prevents EGF-mediated tyrosine phosphorylation of CIC and attenuates elevated ETV1 and ETV5 levels, reduces viability of GBM cells and glioma stem cells (GSC), but not of their control cells with undetectable c-Src activity. In fact, GBM cells and GSC expressing the tyrosine-defective CIC mutant (Y1455F) lose sensitivity to dasatinib, further endorsing the effect of dasatinib on Src-mediated tyrosine phosphorylation of CIC. These findings elucidate important mechanisms of CIC regulation and provide the rationale to target c-Src alongside ERK pathway inhibitors as a way to fully restore CIC tumor suppressor function in neoplasms such as GBM.

Implications:
c-Src tyrosine-phosphorylates CIC exports to cytoplasm and inactivates its repressor function in GBM.
Museus e Desenvolvimento Sustentável
Authors: Oliveira Mariana Rodrigues de Almeida Espel de 
Published: February 2020

O presente estudo tem o objetivo de demonstrar a aplicação dos indicadores de Desenvolvimento Sustentável sugeridos pela OCDE (Organização para Cooperação e Desenvolvimento Econômico) para Museus. Esta aplicação tem o intuito de demonstrar como é possível reconhecer o nível de sustentabilidade dos Museus. Para isso foram realizadas pesquisas bibliográficas que evidenciam a importância de se organizar tais parâmetros, com base nas características do País em que o Museu está instalado e que demonstram a efetiva contribuição destas organizações no que se refere aos objetivos do Desenvolvimento Sustentável. Neste estudo preliminar, foram realizadas recolha de dados em dois museus da Região Centro de Portugal. A recolha de dados teve como referência Indicadores de Sustentabilidade sugeridos e publicados pela OCDE em 2018. Estes parâmetros foram a base da recolha de dados, que resultou em uma análise do nível de sustentabilidade desses dois museus, seguindo as referências OCDE. O resultado demonstrou uma efetiva possibilidade de medição dos níveis de sustentabilidade dos museus e mostra também, a potencialidade dos museus para cooperação nos objetivos delineados pela Agenda 2030 do Desenvolvimento Sustentável, elaborado pela Organização das Nações Unidas.
Impaired SMAD1/5 Mechanotransduction and Cx37 (Connexin37) Expression Enable Pathological Vessel Enlargement and Shunting
Authors: Peacock Hanna M. , Tabibian Ashkan , Criem Nathan , Caolo Vincenza , Hamard Lauriane , Deryckere Astrid , Haefliger Jacques-Antoine , Kwak Brenda R. , Zwijsen An , Jones Elizabeth A.V. 
Published: February 2020

Objective:
Impaired ALK1 (activin receptor–like kinase-1)/Endoglin/BMP9 (bone morphogenetic protein 9) signaling predisposes to arteriovenous malformations (AVMs). Activation of SMAD1/5 signaling can be enhanced by shear stress. In the genetic disease hereditary hemorrhagic telangiectasia, which is characterized by arteriovenous malformations, the affected receptors are those involved in the activation of mechanosensitive SMAD1/5 signaling. To elucidate how genetic and mechanical signals interact in AVM development, we sought to identify targets differentially regulated by BMP9 and shear stress.

Approach and Results:

We identify Cx37 (Connexin37) as a differentially regulated target of ligand-induced and mechanotransduced SMAD1/5 signaling. We show that stimulation of endothelial cells with BMP9 upregulated Cx37, whereas shear stress inhibited this expression. This signaling was SMAD1/5-dependent, and in the absence of SMAD1/5, there was an inversion of the expression pattern. Ablated SMAD1/5 signaling alone caused AVM-like vascular malformations directly connecting the dorsal aorta to the inlet of the heart. In yolk sacs of mouse embryos with an endothelial-specific compound heterozygosity for
SMAD1/5
, addition of TNFα (tumor necrosis factor-α), which downregulates Cx37, induced development of these direct connections bypassing the yolk sac capillary bed. In wild-type embryos undergoing vascular remodeling, Cx37 was globally expressed by endothelial cells but was absent in regions of enlarging vessels. TNFα and endothelial-specific compound heterozygosity for
SMAD1/5
caused ectopic regions lacking Cx37 expression, which correlated to areas of vascular malformations. Mechanistically, loss of Cx37 impairs correct directional migration under flow conditions.

Conclusions:
Our data demonstrate that Cx37 expression is differentially regulated by shear stress and SMAD1/5 signaling, and that reduced Cx37 expression is permissive for capillary enlargement into shunts.
Redefining Hematoma Expansion With the Inclusion of Intraventricular Hemorrhage Growth
Authors: Yogendrakumar Vignan , Ramsay Tim , Fergusson Dean A. , Demchuk Andrew M. , Aviv Richard I. , Rodriguez-Luna David , Molina Carlos A. , Silva Yolanda , Dzialowski Imanuel , Kobayashi Adam , Boulanger Jean-Martin , Gubitz Gord , Srivastava Padma , Roy Jayanta , Kase Carlos S. , Bhatia Rohit , Hill Michael D. , Goldstein Joshua N. , Dowlatshahi Dar ,   for the PREDICT/Sunnybrook CTA Study Group
Published: February 2020

Background and Purpose—
Definitions of significant hematoma expansion traditionally focus on changes in intraparenchymal volume. The presence of intraventricular hemorrhage (IVH) is a predictor of poor outcome, but current definitions of hematoma expansion do not include IVH expansion. We evaluated whether including IVH expansion to current definitions of hematoma expansion improves the ability to predict 90-day outcome.

Methods—
Using data from the PREDICT-ICH study (Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT), we compared a standard definition of hematoma expansion (≥6 mL or ≥33%) to revised definitions that includes new IVH development or expansion (≥6 mL or ≥33% or any IVH; ≥6 mL or ≥33% or IVH expansion ≥1 mL). The primary outcome was poor clinical outcome (modified Rankin Scale score, 4–6) at 90 days. Diagnostic accuracy measures were calculated for each definition, and C statistics for each definition were compared using nonparametric methods.

Results—

Of the 256 patients eligible for primary analysis, 127 (49.6%) had a modified Rankin Scale score of 4 to 6. Sensitivity and specificity for the standard definition (n=80) were 45.7% (95% CI, 36.8–54.7) and 82.9% (95% CI, 75.3–88.9), respectively. The revised definition, ≥6 mL or ≥33% or any IVH (n=113), possessed a sensitivity of 63.8% (95% CI, 54.8–72.1) and specificity of 75.2% (95% CI, 66.8–82.4). Overall accuracy was significantly improved with the revised definition (
P
=0.013) and after adjusting for relevant covariates, was associated with a 2.55-fold increased odds (95% CI, 1.31–4.94) of poor outcome at 90 days. A second revised definition, ≥6 mL or ≥33% or IVH expansion ≥1 mL, performed similarly (sensitivity, 56.7% [95% CI, 47.6–65.5]; specificity, 78.3% [95% CI, 40.2–85.1]; aOR, 2.40 [95% CI, 1.23–4.69]).

Conclusions—
In patients with mild-to-moderate ICH, including IVH expansion to the definition of hematoma expansion improves sensitivity with only minimal decreases to specificity and improves overall prediction of 90-day outcome.
Aphelenchoides smolae n. sp. (Tylenchina: Aphelenchoididae) found in Lilium orientalis imported into China from The Netherlands
Authors: Cai Jingjing , Gu Jianfeng , Wang Xuan , Fang Yiwu , Li Hongmei 
Published: February 2020

Summary
Aphelenchoides smolae n. sp. isolated in Ningbo Port, China, from medium soil and tissues of Lilium orientalis bulbs imported from The Netherlands, is described. It is characterised by the female body length of 826 (672-1002) μm and male body length of 785 (683-844) μm, lateral field with four lines (three bands), stylet 13.0-14.9 μm long with small basal swellings, excretory pore situated slightly posterior to nerve ring, vulval flap absent, post-vulval uterine sac well developed and extending for ca 35.7-62.4% of vulva to anus distance, conical tail with terminus bearing a single mucron with many tiny nodular protuberances under SEM, males common, with spicules 25.7-29.8 μm long (median curved line), the condylus and rostrum rounded, well developed, the dorsal limb with a hook-like tip, and tail bearing three pairs (2 + 2 + 2) of caudal papillae and a sharply pointed mucron. The new species belongs to the Group 2 category of Aphelenchoides species sensu Shahina. Phylogenetic analysis based on 18S, 28S D2-D3 of rDNA and COI mtDNA further characterised the new species.