bluuebunny/crossref_metadata_2025 huggingface dataset:
Metformin inhibition of colorectal cancer cell migration is associated with rebuilt adherens junctions and FAK downregulation
Authors: Amable Gastón , Martínez‐León Eduardo , Picco María Elisa , Nemirovsky Sergio I. , Rozengurt Enrique , Rey Osvaldo
Published: April 2020

E‐cadherin, a central component of the adherens junction (AJ), is a single‐pass transmembrane protein that mediates cell–cell adhesion. The loss of E‐cadherin surface expression, and therefore cell–cell adhesion, leads to increased cell migration and invasion. Treatment of colorectal cancer (CRC)‐derived cells (SW‐480 and HT‐29) with 2.0 mM metformin promoted a redistribution of cytosolic E‐cadherin to de novo formed puncta along the length of the contacting membranes of these cells. Metformin also promoted translocation from the cytosol to the plasma membrane of p120‐catenin, another core component of the AJs. Furthermore, E‐cadherin and p120‐catenin colocalized with β‐catenin at cell–cell contacts. Western blot analysis of lysates of CRC‐derived cells revealed a substantial metformin‐induced increase in the level of p120‐catenin as well as E‐cadherin phosphorylation on Ser838/840, a modification associated with β‐catenin/E‐cadherin interaction. These modifications in E‐cadherin, p120‐catenin and β‐catenin localization suggest that metformin induces rebuilding of AJs in CRC‐derived cells. Those modifications were accompanied by the inhibition of focal adhesion kinase (FAK), as revealed by a significant decrease in the phosphorylation of FAK at Tyr397 and paxillin at Tyr118. These changes were associated with a reduction in the numbers, but an increase in the size, of focal adhesions and by the inhibition of cell migration. Overall, these observations indicate that metformin targets multiple pathways associated with CRC development and progression.
Matrix stiffness controls cardiac fibroblast activation through regulating YAP via AT1R
Authors: Niu Lele , Jia Yuanbo , Wu Mian , Liu Han , Feng Yanjing , Hu Yan , Zhang Xiaohui , Gao Dengfeng , Xu Feng , Huang Guoyou
Published: April 2020

Cardiac fibrosis is a common pathway leading to heart failure and involves continued activation of cardiac fibroblasts (CFs) into myofibroblasts during myocardium damage, causing excessive deposition of the extracellular matrix (ECM) and thus increases matrix stiffness. Increasing evidence has shown that stiffened matrix plays an important role in promoting CF activation and cardiac fibrosis, and several signaling factors mediating CF mechanotransduction have been identified. However, the key molecules that perceive matrix stiffness to regulate CF activation remain to be further explored. Here, we detected significantly increased expression and nuclear localization of Yes‐associated protein (YAP) in native fibrotic cardiac tissues. By using mechanically regulated in vitro cell culture models, we found that a stiff matrix‐induced high expression and nuclear localization of YAP in CFs, accompanied by enhanced cell activation. We also demonstrated that YAP knockdown decreased fibrogenic response of CFs and that YAP overexpression promoted CF activation, indicating that YAP plays an important role in mediating matrix stiffness‐induced CF activation. Further mechanistic studies revealed that the YAP pathway is an important signaling branch downstream of angiotensin II type 1 receptor in CF mechanotransduction. The findings help elucidate the mechanism of fibrotic mechanotransduction and may contribute to the development of new approaches for treating fibrotic diseases.
Retracted: HO‐1 overexpression alleviates senescence by inducing autophagy via the mitochondrial route in human nucleus pulposus cells
Authors: Yi Weiwei , Lan Haiyang , Wen Yafeng , Wang Yiyang , He Danshuang , Bai Zhibiao , Zhang Ye , Jiang Wei , Liu Bo , Shen Jieliang , Hu Zhenming
Published: April 2020

Intervertebral disc degeneration (IDD) is closely associated with aging. Our previous studies have confirmed that heme oxygenase‐1 (HO‐1) can inhibit nucleus pulposus (NP) cell apoptosis. However, whether or not HO‐1 is involved in NP cell senescence and autophagy is unclear. Our results indicated that HO‐1 expression was reduced in IDD tissues and replicative senescent NP cells. HO‐1 overexpression using a lentiviral vector reduced the NP cell senescence level, protected mitochondrial function, and promoted NP cell autophagy through the mitochondrial pathway. Autophagy inhibitor 3‐MA pretreatment reversed the anti‐senescent and protective effects on the mitochondrial function of HO‐1, which promoted the degradation of the extracellular matrix (ECM) in the intervertebral disc. In vivo, HO‐1 overexpression inhibited IDD and enhanced autophagy. In summary, these results suggested that HO‐1 overexpression alleviates NP cell senescence by inducing autophagy via the mitochondrial route.
PLS3 predicts poor prognosis in pancreatic cancer and promotes cancer cell proliferation via PI3K/AKT signaling
Authors: Xin Zechang , Li Duguang , Mao Feiyu , Du Yan , Wang Xiaodong , Xu Peng , Li Zhennan , Qian Jianjun , Yao Jie
Published: April 2020

Plastin‐3 plays a key role in cancer cell proliferation and invasion, but its prognostic value in pancreatic cancer (PACA) remains poorly defined. In this study, we show that PLS3 messenger RNA is overexpressed in PACA tissue compared with normal tissue. We accumulated 207 cases of PACA specimens to perform immunohistochemical analysis and demonstrated that PLS3 levels correlate with T‐classification (p < .001) and pathology (p < .001). Furthermore, overall survival rates (p < .001) in tumors with high PLS3 expression were poor, as assessed through Kaplan–Meier survival analysis. PLS3 was found to be an independent prognostic factor for PACA through multivariate Cox regression analysis. Moreover, we found that PLS3 enhances the proliferation and invasion of tumor cells as assessed through Cell Counting Kit‐8, wounding healing assays, and Transwell assays. The upregulation of PLS3 also led to enhanced phosphatidylinositol‐3 kinase/protein kinase B signaling in PACA cells. These data suggest that PLS3 is a biomarker to estimate PACA progression and represents a molecular target for PACA therapy.
TORS Base‐of‐Tongue Mucosectomy in Human Papilloma Virus‐Negative Carcinoma of Unknown Primary
Authors: Kubik Mark W. , Channir Hani I. , Rubek Niclas , Kim Seungwon , Ferris Robert L. , von Buchwald Christian , Duvvuri Umamaheswar
Published: April 2020

Objective

To analyze the role of transoral robotic base‐of‐tongue mucosectomy in a cohort of patients with human papilloma virus negative unknown primary carcinoma.

Study Design

Retrospective database analysis.

Methods

A retrospective database review from 2012 to 2018 was performed at two large tertiary centers to study patients with human papilloma virus (HPV)‐negative unknown primary carcinoma who underwent transoral robotic base‐of‐tongue mucosectomy. P16 testing was used as a surrogate for HPV status. Patients were included that had squamous cell carcinoma metastatic to the lateral neck based on fine needle aspiration or open biopsy. Preoperatively, all patients were classified as having an unknown primary based on normal clinical and flexible endoscopic exam, normal operative endoscopy, nonlocalizing imaging, and tonsillectomy. All patients underwent robotic base‐of‐tongue mucosectomy. The primary outcome measure was the incidence of pathologic identification of a mucosal primary.

Results

Twenty‐three patients with p16‐negative unknown primary carcinoma were identified and studied. All patients underwent transoral robotic base‐of‐tongue mucosectomy. Median age was 60 years at the time of diagnosis, and 18 of 23 (78.2%) were male. Pathologic analysis of the base‐of‐tongue specimens showed a primary tumor in only three of 23 (13.0%) of patients.

Conclusion

Despite prior evidence suggesting a high rate of primary site identification in HPV‐related disease, robotic base‐of‐tongue mucosectomy may not be indicated for HPV‐negative unknown primary carcinoma based on a low likelihood of finding the primary.

Level of Evidence

4 Laryngoscope, 131:78–81, 2021
Compartmental Surgery for Oral Tongue Cancer: Objective and Subjective Functional Evaluation
Authors: Grammatica Alberto , Piazza Cesare , Montalto Nausica , Del Bon Francesca , Frittoli Barbara , Mazza Monica , Paderno Alberto , Lancini Davide , Fior Milena , Deganello Alberto , Lombardi Davide , Nicolai Piero
Published: April 2020

Objective

To assess functional outcomes in patients treated by compartmental tongue surgery (CTS) and reconstruction for advanced oral tongue/floor‐of‐mouth cancer.

Study Design

Retrospective case series.

Methods

A retrospective cohort of patients (n = 48) treated by CTS and free flap reconstruction was prospectively evaluated concerning postoperative functional outcomes at different time points (6 months and 1 year). Swallowing was studied by videonasal endoscopic evaluation (VEES) and videofluoroscopy (VFS), testing various food consistencies and grading the results with the Donzelli scale. Speech articulation, lingual strength, and endurance were studied by phone call and Iowa Oral Performance Instrument (IOPI). Subjective tests (EORTC H&N35 and UWQOL) were administered.

Results

After 1 year, VEES showed a Donzelli scale of 67% level 1, 23% level 2, and 10% level 3. Vallecular pouch was present in 81% of patients. VFS showed levels 1, 2, and 3 in 42%, 25%, and 33%, respectively, with liquids (L); 48%, 19%, and 33%, with semi‐liquids (SL); and 54%, 33%, and 13%, with semi‐solids (SS). Vallecular pouch residue was present in 69% with L, 73% with SL, and 87% with SS. The mean number of words recognized at phone call was 56 of 75 (range, 27–74). IOPI showed a mean tongue strength of 19.2 kPa (range, 0–40), and a mean endurance of 16.2 seconds (range, 0–60).

Conclusion

CTS does not significantly affect speech. Sub‐clinical food aspiration and vallecular pouch are present in a significant proportion of patients, especially when adjuvant treatments are administered. Residual tongue strength is not affected when proper reconstruction is performed.

Level of Evidence

4 Laryngoscope, 131:E176–E183, 2021
Urban expansion or poor productivity: Explaining regional differences in cropland abandonment in China during the early 21st century
Authors: Qiu Bingwen , Yang Xin , Tang Zhenghong , Chen Chongcheng , Li Haiwen , Berry Joe
Published: April 2020

Cropland abandonment has long been recognized as a marginalization process in rural regions but recently also as a precursor to urbanization in peri‐urban regions. This study aimed to evaluate the relative importance of urbanization and poor productivity in cropland abandonment. A thorough investigation was conducted on 345 cities/towns at the prefecture level or higher in China using 500‐m annual maps for 2003–2016. Cropland abandonment was spatiotemporally coupled with the urbanization. At a national scale, approximately 0.55% of the total cropland area (approximately 862 km2 per year) has been abandoned. Cropland abandonment increased significantly until 2009, declined in the early 2010s, and then leveled off in recent years. In particular, the new first‐tier cities suffered the greatest abandonment per capita. However, cropland abandonment was increasingly shifted to lower‐tier cities, particularly the high‐quality cropland abandonment in the medium‐tier cities. Low‐quality cropland in rural regions of the medium‐ and lower‐tier cities experienced incessant abandonment. Results showed that the extent of cropland abandonment increased with city sizes described either by population/GDP or by built‐up area. High‐quality cropland abandonment was more closely related to the built‐up area than to population and GDP for total abandonment. Urbanization‐induced abandonment in peri‐urban areas was dominant for most cities, with exceptions only for a few small cities. Contrary to expectation, cropland abandonment for most cities/towns in rural regions was not more driven by poor productivity, compared to peri‐urban regions. Our study highlights that urbanization mainly accounted for the regional differences in cropland abandonment in China during the past two decades.
Multi‐level analysis of the learning health system: Integrating contributions from research on organizations and implementation
Authors: Harrison Michael I. , Shortell Stephen M.
Published: April 2020

Introduction

Organizations and systems that deliver health care may better adapt to rapid change in their environments by acting as learning organizations and learning health systems (LHSs). Despite widespread recognition that multilevel forces shape capacity for learning within care delivery organizations, there is no agreed‐on, comprehensive, multilevel framework to inform LHS research and practice.

Methods

We develop such a framework, which can enhance both research on LHSs and practical steps toward their development. We draw on existing frameworks and research within organization and implementation science and synthesize contributions from three influential frameworks: the Consolidated Framework for Implementation Research, the social‐ecological framework, and the organizational change framework. These frameworks come, respectively, from the fields of implementation science, public health, and organization science.

Results

Our proposed integrative framework includes both intraorganizational levels (individual, team, mid‐management, organization) and the operating and general environments in which delivery organizations operate. We stress the importance of examining interactions among influential factors both within and across system levels and focus on the effects of leadership, incentives, and culture. Additionally, we indicate that organizational learning depends substantially on internal and cross‐level alignment of these factors. We illustrate the contribution of our multilevel perspective by applying it to the analysis of three diverse implementation initiatives that aimed at specific care improvements and enduring system learning.

Conclusions

The framework and perspective developed here can help investigators and practitioners broadly scan and then investigate forces influencing improvement and learning and may point to otherwise unnoticed interactions among influential factors. The framework can also be used as a planning tool by managers and practitioners.
Porcine deltacoronavirus infection alters bacterial communities in the colon and feces of neonatal piglets
Authors: Li Hai‐Yan , Li Bing‐Xiao , Liang Qing‐Qing , Jin Xiao‐Hui , Tang Lei , Ding Qing‐Wen , Wang Zhi‐Xiang , Wei Zhan‐Yong
Published: April 2020

Porcine deltacoronavirus (PDCoV) is a novel enteropathogenic coronavirus that causes watery diarrhea in piglets. Little is known regarding the alteration of the gut microbiota in PDCoV‐induced diarrhea piglets. In this study, 5‐day‐old piglets were experimentally infected with PDCoV strain CH‐01, and all piglets developed typical clinical disease, characterized by acute and severe watery diarrhea. Histologic lesions were limited to the villous epithelium of the duodenum and ileum. Gut microbiota profiles in the colon and feces of piglets inoculated with PDCoV were investigated using 16S rRNA sequencing. The results showed that PDCoV infection reduced bacterial diversity and significantly altered the composition of the microbiota from the phylum to the genus level in the colon and feces of piglets. Firmicutes (phylum), Lactobacillaceae (family), and Lactobacillus (genus) were significantly increased (p < .01), while the abundance of Bacteroidetes (phylum) was markedly reduced in the colon and feces of the PDCoV‐infected piglets (p < .01) when compared to those of the healthy piglets. Furthermore, microbial function prediction indicated that the changes in the intestinal flora also affected the nucleotide transport and metabolism, defense, translation, and transcription function of the intestinal microbiota. The current study provides new insight into the pathology and physiology of PDCoV.
Solvability of the boundary value problems for the elastic beam equations with impulsive effects crossing resonance points
Authors: Chao Xiaoqian , Liu Wenbin , Shen Tengfei
Published: April 2020

In this paper, the existence of solutions is obtained for the boundary value problems to the elastic beam equations with simply supports and impulsive effects. By using the variational method and spectral structure, under the condition
is a positive integer) and other conditions, we give some new criteria to guarantee that the impulsive problems have solutions. This condition may make ratio
cross resonance points. Lastly, an example is presented to demonstrate the use of the main result.
Lepidiline A Improves the Balance of Endogenous Sex Hormones and Increases Fecundity by Targeting HSD17B1
Authors: Cheng Chuanjing , Shen Fukui , Ding Guoyu , Liu Aina , Chu Simeng , Ma Yuejiao , Hou Xiaotao , Hao Erwei , Wang Xiaoying , Hou Yuanyuan , Bai Gang
Published: April 2020

Scope

Maca (Lepidium meyenii), a well‐known plant from the Andean highlands of Peru, has been used widely as a nutritional supplement to increase sexual function and fecundity. However, the identity of its active ingredients and how they function remain unknown.

Methods and results

Chemical substances in maca are identified by UPLC‐Q‐TOF, and the active ingredients are screened through HotMap coupled with an artificial neural network. Lepidiline A (LA), an imidazole alkaloid, is identified as the key active compound. LA affects the balance of endogenous sex hormones in mice and improves fecundity in Drosophila. Using a molecular LA probe, 17ß‐hydroxysteroid dehydrogenase type 1 (HSD17B1) is revealed to be the potential target of LA using a fishing‐rod strategy. It is demonstrated with experimental data that LA targets HSD17B1 to enhance the enzyme's activity and increases its bioconversion efficiency of actively formed sex hormones including estrogen to 17β‐estradiol and 4‐androsten‐3,7‐dione to testosterone, which ultimately improves reproductive activity.

Conclusion

LA improves the balance of endogenous sex hormones and increases fecundity by targeting HSD17B1. This underlying mechanism of action provides a useful insight into the application of maca in the regulation of dietary nutrition and healthy fertility.
Frequency‐dependent signal and noise in spectroscopic x‐ray imaging
Authors: Tanguay Jesse , Kim Jinwoo , Kim Ho Kyung , Iniewski Kris , Cunningham Ian A.
Published: April 2020

Purpose

We present a new framework for theoretical analysis of the noise power spectrum (NPS) of photon‐counting x‐ray detectors, including simple photon‐counting detectors (SPCDs) and spectroscopic x‐ray detectors (SXDs), the latter of which use multiple energy thresholds to discriminate photon energies.

Methods

We show that the NPS of SPCDs and SXDs, including spatio‐energetic noise correlations, is determined by the joint probability density function (PDF) of deposited photon energies, which describes the probability of recording two photons of two different energies in two different elements following a single‐photon interaction. We present an analytic expression for this joint PDF and calculate the presampling and digital NPS of CdTe SPCDs and SXDs. We calibrate our charge sharing model using the energy response of a cadmium zinc telluride (CZT) spectroscopic x‐ray detector and compare theoretical results with Monte Carlo simulations.

Results

Our analysis shows that charge sharing increases pixel signal‐to‐noise ratio (SNR), but degrades the zero‐frequency signal‐to‐noise performance of SPCDs and SXDs. In all cases considered, this degradation was greater than 10%. Comparing the presampling NPS with the sampled NPS showed that degradation in zero‐frequency performance is due to zero‐frequency noise aliasing induced by charge sharing.

Conclusions

Noise performance, including spatial and energy correlations between elements and energy bins, are described by the joint PDF of deposited energies which provides a method of determining the photon‐counting NPS, including noise‐aliasing effects and spatio‐energetic effects in spectral imaging. Our approach enables separating noise due to x‐ray interactions from that associated with sampling, consistent with cascaded systems analysis of energy‐integrating systems. Our methods can be incorporated into task‐based assessment of image quality for the design and optimization of spectroscopic x‐ray detectors.
Pulmonary nodule detection using hybrid two‐stage 3D CNNs
Authors: Tan Man , Wu Fa , Yang Bei , Ma Jinlian , Kong Dexing , Chen Zengsi , Long Dan
Published: April 2020

Purpose

Early detection of pulmonary nodules is an effective way to improve patients’ chances of survival. In this work, we propose a novel and efficient way to build a computer‐aided detection (CAD) system for pulmonary nodules based on computed tomography (CT) scans.

Methods

The system can be roughly divided into two steps: nodule candidate detection and false positive reduction. Considering the three‐dimensional (3D) nature of nodules, the CAD system adopts 3D convolutional neural networks (CNNs) in both stages. Specifically, in the first stage, a segmentation‐based 3D CNN with a hybrid loss is designed to segment nodules. According to the probability maps produced by the segmentation network, a threshold method and connected component analysis are applied to generate nodule candidates. In the second stage, we employ three classification‐based 3D CNNs with different types of inputs to reduce false positives. In addition to simple raw data input, we also introduce hybrid inputs to make better use of the output of the previous segmentation network. In experiments, we use data augmentation and batch normalization to avoid overfitting.

Results

We evaluate the system on 888 CT scans from the publicly available LIDC‐IDRI dataset, and our method achieves the best performance by comparing with the state‐of‐the‐art methods, which has a high detection sensitivity of 97.5% with an average of only one false positive per scan. An additional evaluation on 115 CT scans from local hospitals is also performed.

Conclusions

Experimental results demonstrate that our method is highly suited for the detection of pulmonary nodules.
Response of Out-Migrating Adult American Shad Guided by Spill and Ultrasound as They Approach Rivière-des-Prairies Hydroelectric Generating Station (Québec, Canada)
Authors: Caumartin Jean , Verdon Richard , Desrochers Denis , Guindon Alexandre , Lafleur François , Guay Frédéric
Published: April 2020

Fish entrainment and mortality at hydropower generating stations constitute a major concern for power producers and government agencies. The American Shad Alosa sapidissima is particularly at risk at higher latitudes because of the large percentage of repeat spawners and the vulnerability of many populations. Total or partial turbine shutdowns at powerhouses and concurrent increased spillage are generally considered an effective way to enable fish to bypass the turbines and to reduce associated mortality, but this strategy is unappealing to hydropower producers because of the loss of power generation revenue. Two approaches were tested to repel out-migrating adult American Shad from the turbine intakes of the Rivière-des-Prairies Generating Station powerhouse and guide them toward the adjacent spillway. The first approach consisted of shutting down the powerhouse and increasing spillage. The second approach consisted of testing the effectiveness of an ultrasonic field to deter American Shad from getting close to turbine intakes and to guide them toward the partially opened spillway. On average, fish density observed in front of the 54-MW powerhouse was reduced by 93% as a result of a powerhouse shutdown lasting about 1 h and a concurrent spillage increase. Similarly, our results showed a decrease in shad abundance of 78–90% in front of the turbine intakes when a pulsed ultrasonic field (125 kHz) was activated. Measurements of sound pressure levels (SPLs) in the forebay suggested that the deterrent effect could be perceived by American Shad more than 100 m away, before they could sense higher water velocities near the powerhouse intakes. These results indicate that the combination of high-SPL pulsed ultrasounds (125 kHz) and the concurrent opening of adjacent spillway gates could guide postspawn American Shad away from powerhouse intakes.
Advantages of Outpatient Treatment with Long‐Acting Lipoglycopeptides for Serious Gram‐Positive Infections: A Review
Authors: Krsak Martin , Morrisette Taylor , Miller Matthew , Molina Kyle , Huang Misha , Damioli Laura , Pisney Larissa , Wong Megan , Poeschla Eric
Published: April 2020

Treatment of serious gram‐positive infections presents multiple challenges. Treatment often results in prolonged hospitalization for administration of intravenous antimicrobials and presents an inefficient use of hospital resources. Prolonged hospitalization is typically also unfavorable to patient preferences and potentially subjects patients to additional health care‐associated complications. Current strategies of transition to outpatient settings—outpatient parenteral antimicrobial therapy and use of oral antibiotics—often do not adequately serve vulnerable populations for whom there is often no alternative to inpatient therapy. Specifically, people who use drugs, those who cannot reliably adhere to unsupervised treatment (poor mental or physical health), people with complicating life circumstances (e.g., homelessness, incarceration, rural location), and those with inadequate health insurance remain hospitalized for weeks longer than persons without such conditions. We suspected that long‐acting lipoglycopeptides (laLGP), such as dalbavancin and oritavancin, may be useful in patient transitions to outpatient settings. Thus, we conducted a search of the peer‐reviewed literature using the PubMed, Google Scholar, and MEDLINE databases. Based on accumulating literature, it appears that laLGPs offer a reliable alternative therapeutic strategy that addresses many of the personal and systemic barriers to the traditional transitioning approaches. Current evidence also suggests that these agents may be cost‐effective from patient, payer, and hospital perspectives. Barriers to broader use of laLGPs include, among others, a relative lack of prospective data regarding efficacy in serious infections, a narrow United States Food and Drug Administration–approved indication restricted to only acute bacterial skin and skin structure infections, and lack of reimbursement infrastructure for inpatient settings.
Anti‐Atherogenic Effect of Stem Cell Nanovesicles Targeting Disturbed Flow Sites
Authors: Yoon Jeong‐Kee , Kim Dae‐Hyun , Kang Mi‐Lan , Jang Hyeon‐Ki , Park Hyun‐Ji , Lee Jung Bok , Yi Se Won , Kim Hye‐Seon , Baek Sewoom , Park Dan Bi , You Jin , Lee Seong‐Deok , Sei Yoshitaka , Ahn Song Ih , Shin Young Min , Kim Chang Soo , Bae Sangsu , Kim YongTae , Sung Hak‐Joon
Published: April 2020

Atherosclerosis development leads to irreversible cascades, highlighting the unmet need for improved methods of early diagnosis and prevention. Disturbed flow formation is one of the earliest atherogenic events, resulting in increased endothelial permeability and subsequent monocyte recruitment. Here, a mesenchymal stem cell (MSC)‐derived nanovesicle (NV) that can target disturbed flow sites with the peptide GSPREYTSYMPH (PREY) (PMSC‐NVs) is presented which is selected through phage display screening of a hundred million peptides. The PMSC‐NVs are effectively produced from human MSCs (hMSCs) using plasmid DNA designed to functionalize the cell membrane with PREY. The potent anti‐inflammatory and pro‐endothelial recovery effects are confirmed, similar to those of hMSCs, employing mouse and porcine partial carotid artery ligation models as well as a microfluidic disturbed flow model with human carotid artery‐derived endothelial cells. This nanoscale platform is expected to contribute to the development of new theragnostic strategies for preventing the progression of atherosclerosis.
The Nanomaterial Metabolite Corona Determined Using a Quantitative Metabolomics Approach: A Pilot Study
Authors: Chetwynd Andrew J. , Zhang Wei , Thorn James A. , Lynch Iseult , Ramautar Rawi
Published: April 2020

Nanomaterials (NMs) are promptly coated with biomolecules in biological systems leading to the formation of the so‐called corona. To date, research has predominantly focused on the protein corona and how it affects NM uptake, distribution, and bioactivity by conferring a biological identity to NMs enabling interactions with receptors to mediate cellular responses. Thus, protein corona studies are now integral to nanosafety assessment. However, a larger class of molecules, the metabolites, which are orders of magnitude smaller than proteins (<1000 Da) and regulate metabolic pathways, has been largely overlooked. This hampers the understanding of the bio–nano interface, development of computational predictions of corona formation, and investigations into uptake or toxicity at the cellular level, including identification of molecular initiating events triggering adverse outcome pathways. Here, a capillary electrophoresis–mass spectrometry based metabolomics approach reveals that pure polar ionogenic metabolite standards differentially adsorb to a range of 6 NMs (SiO2, 3 TiO2 with different surface chemistries, and naïve and carboxylated polystyrene NMs). The metabolite corona composition is quantitatively compared using protein‐free and complete plasma samples, revealing that proteins in samples significantly change the composition of the metabolite corona. This key finding provides the basis to include the metabolite corona in future nanosafety endeavors.
Transparent Electrodes Consisting of a Surface‐Treated Buffer Layer Based on Tungsten Oxide for Semitransparent Perovskite Solar Cells and Four‐Terminal Tandem Applications
Authors: Park Helen Hejin , Kim Jincheol , Kim Geunjin , Jung Hyunmin , Kim Songhee , Moon Chan Su , Lee Seon Joo , Shin Seong Sik , Hao Xiaojing , Yun Jae Sung , Green Martin A. , Ho‐Baillie Anita W. Y. , Jeon Nam Joong , Yang Tae‐Youl , Seo Jangwon
Published: April 2020

For semitransparent devices with n‐i‐p structures, a metal oxide buffer material is commonly used to protect the organic hole transporting layer from damage due to sputtering of the transparent conducting oxide. Here, a surface treatment approach is addressed for tungsten oxide‐based transparent electrodes through slight modification of the tungsten oxide surface with niobium oxide. Incorporation of this transparent electrode technique to the protective buffer layer significantly recovers the fill factor from 70.4% to 80.3%, approaching fill factor values of conventional opaque devices, which results in power conversion efficiencies over 18% for the semitransparent perovskite solar cells. Application of this approach to a four‐terminal tandem configuration with a silicon bottom cell is demonstrated.
Socio‐environmental confounders of safe water interventions
Authors: Smiley Sarah L. , Stoler Justin
Published: April 2020

The international development community spends billions of dollars annually on safe drinking water projects globally in low‐ and middle‐income settings. These projects are driven by the World Health Organization's Joint Monitoring Programme metrics that rely on indirect measurements of water insecurity via water source and fetching time, with tacit acknowledgment of price inelasticity. But the success of water interventions, as framed by these metrics, is often tempered by the reality that people do not always use the safest, nearest, or least expensive water source. Drinking water interventions are confounded by diverse social and environmental factors that shape household water seeking behaviors in unexpected or underappreciated ways. These caveats to human water‐related behaviors are littered throughout the drinking water literature—often as an anecdote to a given study's primary findings—and present significant barriers to providing universal safe water as outlined by Sustainable Development Goal 6. We review and categorize these socio‐environmental confounders into six themes at multiple scales: social relations, water properties, intermittency, affordability, fetching practices, and physical and mental health. We illustrate how efforts to mitigate drinking water insecurity are complicated by the interaction of these social and physical processes. We highlight emerging metrics that enable a richer assessment of household water insecurity, and emphasize the importance of transdisciplinary approaches to improve the effectiveness of clean water interventions.

This article is categorized under:

Engineering Water > Planning Water

Engineering Water > Sustainable Engineering of Water

Human Water > Water as Imagined and Represented

Human Water > Value of Water
Using Ultrasonic Acoustics to Detect Cryptic Flying Squirrels: Effects of Season and Habitat Quality
Authors: Diggins Corinne A. , Gilley L. Michelle , Kelly Christine A. , Ford W. Mark
Published: April 2020

New technologies allow for more efficient and effective monitoring of rare or elusive species. However, standardizing protocol to ensure high detection rates is important prior to widespread use of a new technique. The use of ultrasonic acoustic detectors to survey for flying squirrels (Glaucomys spp.) is a novel method that is more efficient than traditional methods. However, certain methodologies for this technique still need to be refined. During 2015, we conducted a seasonal and habitat quality study on the endangered Carolina northern flying squirrel (G. sabrinus coloratus) in western North Carolina, USA. Our seasonal study examined differences in probability of detection (POD) and latency to detection (LTD) at 30 high‐quality sites across 10 survey nights in spring, summer, and autumn. The habitat quality study focused on POD and LTD among 15 sites with varying habitat quality (5 High, 5 Medium, 5 Low) across 20 survey nights. We found POD similar between seasons, with POD 15–20% greater during spring. The LTD was comparable among seasons. We found that POD and LTD varied at sites with different habitat quality. The POD was similar between High and Medium sites (0.26 ± 0.04 SE and 0.29 ± 0.05, respectively), but greater than Low sites (0.02 ± 0.02). The LTD was not different among sites with differing habitat quality, although LTD at High sites was 2.7 and 4.5 times lower than Medium and Low sites, respectively. Trill calls, the most distinctive species‐specific call type produced by species of flying squirrels, was recorded at greater rates in spring versus other times of the year. Our results indicate flying squirrels can be surveyed during any season, although habitat quality needs to be considered when determining survey length. For Carolina northern flying squirrel, the optimal time to perform acoustic surveys is during the spring season for 6–10 survey nights at sites with high or medium habitat quality. © 2020 The Wildlife Society.
Relative scales of the GUT and twin sectors in an F-theory model
Authors: Clemens C. Herbert , Raby Stuart
Published: April 2020

Abstract

In this note we analyze the relative scales for the GUT and twin sectors in the F-theory model discussed in ref. [1]. There are a number of volume moduli in the model. The volume of the GUT surface in the visible sector (1) (with the Wilson line GUT breaking) defines the GUT scale M

G

∼ 2 × 1016
GeV as the unification scale with precise gauge coupling unification of SU(3) × SU(2) × U(1)
Y
. We choose the GUT coupling constant,

$$ {\alpha}_G^{-1} $$

α
G

−
1

∼ 24. We are then free to choose the ratio α

G
(2)/α

G
(1) = m
1
/m
2 with m
1 and m
2 independent volume moduli associated with the directions perpendicular to the two asymptotic GUT surfaces. We then analyze the effective field theory of the twin sector (2), which may lead to a SUSY breaking gaugino condensate. Of course, all these results are subject to the self-consistent stabilization of the moduli.
Matter coupling in massive gravity
Authors: Falkowski Adam , Isabella Giulia
Published: April 2020

Abstract

We discuss the dRGT massive gravity interacting with spin-0, spin-1/2, or spin-1 matter. The effective theory of a massive spin-2 particle coupled to matter particles is constructed directly at the amplitude level. In this setting we calculate the gravitational Compton scattering amplitudes and study their UV properties. While the Compton am- plitudes generically grow with energy as O(E
6), we identify regions of the parameter space where they are softened to O(E
4) or even O(E
3), which allows for a larger validity range of the effective theory. In these regions, both positivity and beyond-positivity of the forward Compton amplitudes are fulfilled, and the equivalence principle automatically emerges.
Rainstorm effects on the biocontrol efficacy of the decay fungus Chondrostereum purpureum against birch sprouting in boreal forests
Authors: Hamberg Leena , Saarinen Veli-Matti , Rantala Markku , Hantula Jarkko , Seiskari Pekka , Saksa Timo
Published: April 2020

In forest regeneration areas, alongside roads and railways, under electric power lines and above gas pipe lines, there is a need for regular sprout control. A biocontrol method against broadleaved sprouting with formulations including the decay fungus Chondrostereum purpureum (Pers. Ex Fr.) Pouzar has been shown to be effective. Yet, heavy rain during spreading of this fungal inoculum on freshly cut stumps may affect the efficacy of the treatment, i.e., stump mortality during the following years. Thus, we performed an experiment where freshly cut birch stump surfaces (Betula pendula Roth and Betula pubescens Ehrh.) were treated with fungal inoculum under heavy irrigation and without it. Furthermore, two different adjuvants which aimed to fix the fungal inoculum to freshly cut stumps during irrigation and to protect against solar radiation were tested. Our results revealed that the artificial rainstorm treatment caused a delay in the efficacy of C. purpureum, but after three growing seasons, there was no significant difference in the mortality of birch stumps treated under irrigation or without it (stump mortalities 74 and 86%, respectively). Adjuvants did not improve the efficacy in stumps treated under irrigation nor in those treated without irrigation.

Key Points

• Heavy rain delayed the sprout control efficacy of a fungus Chondrostereum purpureum.

• Final efficacy of formulations was the same in wet and dry conditions.

• No additional adjuvants are needed to improve formulations.
Lower limb peripersonal space and the desire to amputate a leg
Authors: Stone Kayla D. , Kornblad Clara A. E. , Engel Manja M. , Dijkerman H. Chris , Blom Rianne M. , Keizer Anouk
Published: April 2020

Body integrity identity disorder (BIID) is a rare condition defined by a persistent desire to amputate or paralyze a healthy limb (usually one or both of the legs). This desire arises from experiencing a mismatch between the internal body model and the actual physical/functional boundaries of the body. People with BIID show an abnormal physiological response to stimuli approaching the affected (unwanted) but not the unaffected leg, which might suggest a retracted peripersonal space (PPS: a multisensory integration zone near the body) around the unwanted limb. Thus, using a visuo-tactile interaction task, we examined leg PPS in a group of healthy men and three men with BIID who desired unilateral leg amputation. PPS size (~ 70 cm) around the unwanted BIID legs did not differ from that of healthy controls. Although the leg feels foreign in BIID, it still seems to maintain a PPS, presumably to protect it and facilitate interactions within the surrounding environment.
Comparative genomic profiling of glandular bladder tumours
Authors:   for the German study group of bladder cancer, Maurer Angela , Ortiz-Bruechle Nadina , Guricova Karolina , Rose Michael , Morsch Ronja , Garczyk Stefan , Stöhr Robert , Bertz Simone , Golz Reinhard , Reis Henning , Bremmer Felix , Zimpfer Annette , Siegert Sabine , Kristiansen Glen , Schwamborn Kristina , Gassler Nikolaus , Knuechel Ruth , Gaisa Nadine T.
Published: April 2020

Primary glandular bladder tumours (bladder adenocarcinoma [BAC], urachal adenocarcinoma [UAC], urothelial carcinoma with glandular differentiation [UCg]) are rare malignancies with histological resemblance to colorectal adenocarcinoma (CORAD) in the majority of this subgroup. Definite case numbers are very low, molecular data are limited and the pathogenesis remains poorly understood. Therefore, this study was designed to complement current knowledge by in depth analysis of BAC (n = 12), UAC (n = 13), UCg (n = 11) and non-invasive glandular lesions (n = 19). In BAC, in addition to known alterations in TP53, Wnt, MAP kinase and MTOR pathway, mutations in SMAD4, ARID1A and BRAF were identified. Compared to published data on muscle invasive bladder cancer (BLCA) and CORAD, UCg exhibited frequent “urothelial” like alterations while BAC and UAC were characterised by a more “colorectal” like mutational pattern. Immunohistochemically, there was no evidence of DNA mismatch repair deficiency or PD-L1 tumour cell positivity in any sample. Depending on the used antibody 0–45% of BAC, 0–30% of UCg and 0% UAC cases exhibited PD-L1 expressing tumour associated immune cells. A single BAC (9%, 1/11) showed evidence of ARID1A protein loss, and two cases of UCg (20%, 2/10) showed loss of SMARCA1 and PBRM1, respectively. Taken together, our data suggest at least in part involvement of similar pathways driving tumourigenesis of adenocarcinomas like BAC, UAC and CORAD independent of their tissue origin. Alterations of TERT and FBXW7 in single cases of intestinal metaplasia further point towards a possible precancerous character in line with previous reports.
Identification of intrinsic and reflexive contributions to trunk stabilization in patients with low back pain: a case–control study
Authors: Griffioen M. , van Drunen P. , Maaswinkel E. , Perez R. S. G. M. , Happee R. , van Dieën J. H.
Published: April 2020

Purpose

The goal of this study was to assess differences in low back stabilization and underlying mechanisms between patients with low back pain (LBP) and healthy controls. It has been hypothesized that inadequate trunk stabilization could contribute to LBP through high tissue strains and/or impingement. Evidence to support this is inconsistent, and not all methods that have been used to study trunk stabilization are equally suitable. We have recently developed a method to assess intrinsic and reflexive contributions to trunk stabilization, which aims to circumvent the limitations of previous studies.

Methods

Forty-nine participants suffering from chronic LBP and a control group of fifty healthy subjects participated in this study. Trunk stabilization was measured using force-controlled perturbations directly applied to the trunk. The actuator displacement and contact force between the actuator and subject were measured as well as electromyography (EMG) of the M. Longissimus. Underlying mechanisms were characterized using system identification.

Results

LBP patients showed lower admittance, i.e., less displacement per unit of force applied, mainly due to higher position, velocity and acceleration feedback gains. Among patients, lower trunk admittance and higher reflex gains were associated with more negative pain-related cognitions.

Conclusion

Trunk stabilization differs between LBP patients and controls, with the same perturbations causing less trunk movement in patients, due to stronger reflexes. We interpret these changes as reflecting protective behavior.

Graphic abstract

These slides can be retrieved under Electronic Supplementary Material.
New CAP Delivery Model, Old Issues
Authors: Lovec Marko , Šumrada Tanja , Erjavec Emil
Published: April 2020

The proposed Common Agricultural Policy (CAP) for the period 2021–2027 will be more flexible and, presumably, more effective. To provide for sufficient ambition and prevent a race to the bottom, national strategic plans will be introduced with quantitative targets covering both policy pillars. This article argues that since formal requirements and the evaluation model are weak on actual long-term impact, substantial improvements are unlikely. To test this, programming rules are experimentally evaluated on the implementation of CAP 2014–2020 in Slovenia. The experiment shows that while measures and resources broadly correspond to policy objectives, the specific relevance of measures is generally weak and has potential effects dispersed among several objectives, resulting in high costs for individual objectives at best. Without the effective inclusion of an impact assessment, the outcome will rely on the capacity and benevolence of national governance systems.
Benchmarking inference methods for water quality monitoring and status classification
Authors: Jung Hoseung , Senf Cornelius , Jordan Philip , Krueger Tobias
Published: April 2020

River water quality monitoring at limited temporal resolution can lead to imprecise and inaccurate classification of physicochemical status due to sampling error. Bayesian inference allows for the quantification of this uncertainty, which can assist decision-making. However, implicit assumptions of Bayesian methods can cause further uncertainty in the uncertainty quantification, so-called second-order uncertainty. In this study, and for the first time, we rigorously assessed this second-order uncertainty for inference of common water quality statistics (mean and 95th percentile) based on sub-sampling high-frequency (hourly) total reactive phosphorus (TRP) concentration data from three watersheds. The statistics were inferred with the low-resolution sub-samples using the Bayesian lognormal distribution and bootstrap, frequentistttest, and face-value approach and were compared with those of the high-frequency data as benchmarks. Thettest exhibited a high risk of bias in estimating the water quality statistics of interest and corresponding physicochemical status (up to 99% of sub-samples). The Bayesian lognormal model provided a good fit to the high-frequency TRP concentration data and the least biased classification of physicochemical status (< 5% of sub-samples). Our results suggest wide applicability of Bayesian inference for water quality status classification, a new approach for regulatory practice that provides uncertainty information about water quality monitoring and regulatory classification with reduced bias compared to frequentist approaches. Furthermore, the study elucidates sizeable second-order uncertainty due to the choice of statistical model, which could be quantified based on the high-frequency data.