bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of autophagy induced by activation of the AMPK/ERK/mTOR signaling pathway after TRIM22-mediated DENV-2 infection of HUVECs
Authors: Wu Ning , Gou Xiaoqin , Hu Pan , Chen Yao , Ji Jinzhong , Wang Yuanying , Zuo Li 
Published: June 2022

Abstract
Background
Dengue virus type 2 (DENV-2) was used to infect primary human umbilical vein endothelial cells (HUVECs) to examine autophagy induced by activation of the adenosine monophosphate-activated protein kinase (AMPK)/extracellular signal-regulated kinase (ERK)/mammalian target of rapamycin (mTOR) signaling pathway following tripartite motif-containing 22 (TRIM22)-mediated DENV-2 infection to further reveal the underlying pathogenic mechanism of DENV-2 infection.
Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to screen putative interference targets of TRIM22 and determine the knockdown efficiency. The effect of TRIM22 knockdown on HUVEC proliferation was determined using the CCK8 assay. Following TRIM22 knockdown, transmission electron microscopy (TEM) was used to determine the ultrastructure of HUVEC autophagosomes and expression of HUVEC autophagy and AMPK pathway-related genes were measured by qRT-PCR. Moreover, HUVEC autophagy and AMPK pathway-related protein expression levels were determined by western blot analysis. Cell cycle and apoptosis were assessed by flow cytometry (FCM) and the autophagosome structure of the HUVECs was observed by TEM.
Results
Western blot results indicated that TRIM22 protein expression levels increased significantly 36 h after DENV-2 infection, which was consistent with the proteomics prediction. The CCK8 assay revealed that HUVEC proliferation was reduced following TRIM22 knockdown (P < 0.001). The TEM results indicated that HUVEC autolysosomes increased and autophagy was inhibited after TRIM22 knockdown. The qRT-PCR results revealed that after TRIM22 knockdown, the expression levels of antithymocyte globulin 7 (ATG7), antithymocyte globulin 5 (ATG5), Beclin1, ERK, and mTOR genes decreased (P < 0.01); however, the expression of AMPK genes (P < 0.05) and P62 genes (P < 0.001) increased. FCM revealed that following TRIM22 knockdown, the percentage of HUVECs in the G2 phase increased (P < 0.001) along with cell apoptosis. The effect of TRIM22 overexpression on HUVEC autophagy induced by DENV-2 infection and AMPK pathways decreased after adding an autophagy inhibitor.
Conclusions
In HUVECs, TRIM22 protein positively regulates autophagy and may affect autophagy through the AMPK/ERK/mTOR signaling pathway. Autophagy is induced by activation of the AMPK/ERK/mTOR signaling pathway following TRIM22-mediated DENV-2 infection of HUVECs.
Assessment of flooding impact on water supply systems: a comprehensive approach based on DSS
Authors: Barbetta Silvia , Bonaccorsi Bianca , Tsitsifli Stavroula , Boljat Ivana , Argiris Papakonstantinou , Reberski Jasmina Lukač , Massari Christian , Romano Emanuele 
Published: June 2022

Abstract
The assessment of flood impact on a Water Supply System (WSS) requires a comprehensive approach including several scales of analysis and models to capture dependencies between meteorological/hydrological forcing and WSS components. The flood risk on WSS should be managed in the Water Safety Plans (WSP), recommended in the EU Water Directive 2020/2184 to water utilities. Flood event can impact the quality of surface and ground water in multiple ways: contaminated water can enter groundwater through wells, overflow and contamination from sewerage systems can occur, extreme rainfall can increase loading of suspended sediments in surface waters. Flooding can also cause supply service interruption for damaged infrastructures. A comprehensive approach to address flood impact on WSS is not available, while only specific aspects were investigated. This work introduces an overall approach implemented in an informative tool named WAter Safety Planning Procedures Decision Support System (WASPP–DSS) developed in the context of MUHA (Multihazard framework for Water Related risks management) project. The tool is here applied and demonstrated for three case studies: Ridracoli dam (Italy), Larissa municipality (Greece), and area managed by Zadar water supply company (Croatia). The WASPP–DSS is found to be a valid support for the WSP development allowing the description of components and links, hazards identification and risk assessment and can be useful mainly for small water utilities for an early stage WSP development and implementation. Improvements are desirable, as including a specific section to consider the issue of loss of water resources from reservoirs due to overflow.
System archetypes underlying formal-informal urban water supply dynamics
Authors: Bano Rakhshinda , Khiadani Mehdi , Sebastian Yong 
Published: June 2022

Abstract
Contrary to developed countries, developing countries have been observed to have increased reliance on a diversity of water supply options to meet their daily demands. Formal supply systems are incapable of delivering the daily needs of consumers. Informal supply systems, though filling the demand-supply gap, are increasingly being associated with issues of long-term sustainability, higher consumer cost, and inequity. Emerging formal-informal dynamics in developing countries require a thorough understanding of complex interactions for policy direction, in order to best support the advancement of urban water sustainability. Accordingly, system archetypes offer a platform to explain the behaviors of complex systems. This paper reviews existing literature on formal-informal dynamics and identifies common system archetypes that define urban waterscapes in the developing world. In this way, Causal Loop Diagrams (CLDs) are used to present the relationships and identify common archetypes that define the complexity of urban water supply systems in Hyderabad, Pakistan. These archetypes include ‘fixes that fail’, ‘shifting the burden’, ‘limits to growth/success’ and ‘growth and underinvestment’. Further, leverage points for each archetype are identified and discussed for policy direction.
Polarization-controlled multifunctional polarization conversion in bilayer chiral metamaterials
Authors: Luan Weimeng , Zhang Yihao , Gao Xinzhuo , Yan Xiaona , Jin Zuanming , Ma Guohong , Yao Jianquan 
Published: June 2022

Abstract
In this paper, a chiral metamaterial (MM) structure composed of bilayer twisted split-ring resonator (SRR) arrays is proposed and demonstrated to realize polarization-controlled, dual-directional, and multifunctional polarization conversion for terahertz (THz) waves. Simulated results show that the converter can selectively achieve linear-to-linear, or linear to left-handed circular, or linear to right-handed circular’s polarization conversion according to the polarization state and propagating direction of the incident THz wave. Stokes parameters, ellipticity, and polarized rotation angle are introduced to determine the polarization states of the output waves. The circular polarization transmission coefficients and surface current distributions at the resonance frequency points are simulated to explain and demonstrate the physical origin of polarization conversion. The proposed multifunctional converter can find potential applications in THz sensing, imaging and communication areas.
Energy-resolving large area X-ray imaging enabled by stacked metal halide scintillators
Authors: Ran Peng , Yang Lurong , Jiang tingming , Xu Xuehui , Hui Juan , Su Yirong , Kuang Cuifang , Liu Xu , Yang Yang 
Published: June 2022

Abstract
Conventional energy-integration black-white X-ray imaging lacks spectral information of X-ray photons. Although X-ray spectra (energy) can be distinguished by photon-counting technique typically with CdZnTe detectors, it is very challenging to be applied to large-area flat-panel X-ray imaging (FPXI). Herein, we design multi-layer stacked scintillators of different X-ray absorption capabilities and scintillation spectrums, in this scenario, the X-ray energy can be discriminated by detecting the emission spectra of each scintillator, therefore the spectral-resolving X-ray imaging can be easily obtained by color or multispectral visible-light camera in one single shot of X-ray. To verify this idea, stacked multilayer scintillators based on several emerging metal halides were fabricated in the cost-effective and scalable solution process, and proof-of-concept multi-energy FPXI was experimentally demonstrated. The energy-resolving X-ray image of a “bone-muscle” model clearly showed the details that were invisible in conventional energy-integration FPXI. By stacking four layers of specifically designed multilayer scintillators with appropriate thicknesses, a prototype FPXI with four energy channels was realized, proving its extendibility to multispectral or even hyperspectral X-ray imaging. This study provides a facile and effective strategy to realize energy-resolved flat-panel X-ray imaging.
Value of ypTNM stage in patients with rectal cancer
Authors: Chen Yue , Sun Zhe , Dong Xinxin , Liu Fang , Sun Deyu 
Published: June 2022

Abstract
In the current NCCN guidelines, the prognosis and adjuvant chemotherapy regimen of patients who underwent neoadjuvant chemoradiotherapy, which are based on pre-radiotherapy clinical TNM stage or neoadjuvant pathologic TNM stage, are not clearly described. This retrospective study investigated the significance of neoadjuvant pathologic TNM stage and the value of the adjuvant chemotherapy regimens in different neoadjuvant pathologic TNM stages. Between 2010 and 2015, a total of 316 rectal cancer patients who underwent neoadjuvant chemoradiotherapy, followed by radical resection, were included for analysis. Our findings revealed that neoadjuvant pathologic TNM stage was a more important prognostic factor than clinical TNM stage. In different neoadjuvant pathologic TNM stages, adjuvant chemotherapy played important roles in stage-II and -III disease, but played no significant role in pCR and stage-I disease. We concluded that neoadjuvant pathologic TNM stage, rather than clinical TNM stage, was a more important prognostic factor. The intensity of adjuvant chemotherapy might need to be strengthened with the increase of ypTNM stage.
“A disembodied voice over the telephone”: A qualitative study of healthcare practitioners’ experiences in geriatric medicine
Authors: Brown Frankie , Sanders Isabella , Watkins Ross , Grey Elisabeth , Smith Paula , Springett Daniella , Welsh Tomas , Gillison Fiona 
Published: June 2022

Abstract
Objectives
This study explored the experience of delivering care remotely among practitioners in a UK geriatric medicine clinic.
Methods
Nine semi-structured interviews were conducted with consultants (n = 5), nurses (n = 2), a speech and language and an occupational therapist, and thematically analysed.
Results
Three themes developed; Rapport Building; Setting and Context; Patient-Professional relationships.
Discussion
Participants felt that rapport and trust had been more feasible to develop remotely than they had anticipated, although this was more challenging for new patients and those with cognitive or sensory impairments. While practitioners identified advantages of remote consultations, including involving relatives, saving time, and reducing anxiety, they also experienced disadvantages such as consultations feeling like a ‘production line’, missing visual cues and reduced privacy. Some participants felt their professional identity was threatened by the lack of face-to-face contact, linked to feeling that remote consultations are not suitable for frail older adults or those with cognitive deficits.
Is increased arterial stiffness an additional link between obesity and organ damage?
Authors: Piko Nejc , Bevc Sebastjan , Hojs Radovan , Petreski Tadej , Ekart Robert 
Published: June 2022

Abstract
Background.
Obesity is associated with several neurohumoral changes that play an important role in organ damage. Increased arterial stiffness causes functional vessel wall changes and can therefore lead to accelerated target organ damage as well. Whether obesity causes an independent increase in central arterial stiffness is, however, not yet fully known.
Methods.
133 patients (63.2% male) were included. BMI was defined as body weight in kilograms, divided by the square of body height in meters. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine 2009 equation was used to estimate glomerular filtration rate (eGFR). Non-invasive applanation tonometry was used for arterial stiffness measurements (Sphygmocor Atcor Medical, Sydney, Australia). All patients underwent coronarography.
Results.
The mean age of our patients was 65.0 ± 9.2 years. Their mean BMI was 28.5 ± 4.4 kg/m2, eGFR 75.5 ± 17.2 ml/min/1.73 m2 and ankle-brachial index (ABI) 1.0 ± 0.1. Their arterial stiffness measurements showed mean carotid-femoral pulse wave velocity (cfPWV) 10.3 ± 2.7 m/s, subendocardial viability ratio (SEVR) 164.4 ± 35.0%, and pulse pressure (PP) 47.8 ± 14.5 mmHg. Spearman's correlation test revealed statistically significant correlation between BMI and SEVR (r=-0.193; p = 0.026), BMI and cfPWV (r = 0.417; p < 0.001) and between BMI and PP (r = 0.227; p = 0.009). Multiple regression analysis confirmed an independent connection between BMI and cfPWV (B = 0.303; p < 0.001) and between BMI and SEVR (B=-0.186; p = 0.040). There was no association between BMI and kidney function, ABI, or coronary artery disease.
Conclusion.
Increased BMI is independently associated with augmented central arterial stiffness and reduced subendocardial perfusion, but not with coronary artery disease, kidney function, or ABI.
Single-base precision design of CRISPR-Cas13b enables systematic silencing of oncogenic fusions
Authors: Hu Wenxin , Kumar Amit , Qi Shijiao , Sadras Teresa , Casan Joshua , Ma David , Brown Lauren , Haber Michelle , Voskoboinik Ilia , Trapani Joseph , Ekert Paul , Fareh Mohamed 
Published: June 2022

Abstract
Precision oncology programs can rapidly identify oncogenic gene fusions in individual patients1–3. However, despite their established oncogenic status, the vast majority of gene fusions remain ‘undruggable’ due to the lack of specific inhibitory molecules4,5. Here, we establish PspCas13b, a poorly characterized programmable RNA nuclease, as a versatile tool to silence various oncogenic fusion transcripts. Our Single-Base Tiled crRNA screens (SiBTil), unbiased computational analysis, and comprehensive spacer-target mutagenesis revealed key determinants of PspCas13b activity. De novo design of crRNAs harbouring basepaired or mismatched guanosine bases at key spacer positions greatly enhances the silencing efficacy of otherwise inefficient crRNAs, expanding the targeting spectrum of this enzyme. We also reveal the interface between mismatch tolerance and intolerance, which unlocks an unexpected single-base precision targeting capability of this RNA nuclease. Notably, our de novo design principles enable potent and selective silencing of various gene fusion transcripts and their downstream oncogenic networks, without off-targeting of non-translocated variants that share extensive sequence homology. We demonstrate that PspCas13b targeting the breakpoint of fusion transcripts enables efficient suppression of ancestral and single-nucleotide mutants (e.g. BCR-ABL1 T315I) that often drive clinical cancer relapse. Collectively, this study provides new design principles for PspCas13b programming to specifically recognise and degrade any ‘undruggable’ fusion oncogenic transcript, thus providing a new conceptual framework for personalized oncology.
Tipping points in polymer life cycle greenhouse gas emissions
Authors: Walker Stuart , Ryan Anthony , Rothman Rachael 
Published: June 2022

Abstract
For decades, polymers have offered a unique combination of low cost and high durability, and are the material of choice for a huge range of applications. In the current energy system, such polymers require the combustion of fossil resources to provide process heat and electricity for manufacture, and release emissions from embodied resources when incinerated. Polymers which are biodegradable or based on biological feedstock avoid some of this resource use, but in some cases have greater energy requirements than fossil polymer equivalents. This work compares life cycle greenhouse gas emissions for pairs of fossil- and biologically-based polymers under various UK electricity, heat and end-of-life treatment scenarios between 2019 and 2040. As specific emissions from electricity and heat supply reduce over the period, life cycle emissions of all polymers fall. Polylactic acid was found to already have lower emissions than polystyrene in most scenarios. Low-density polyethylene was found to have lower emissions than poly(butylene adipate‐co‐terephthalate) in all cases to 2040. Both bio-based high density polyethylene and bio-based polyethylene terephthalate were found to have lower emissions than their fossil equivalents at some point between 2019 and 2040, depending on energy and end-of-life scenarios. Identifying and acting on these crossover points offers a route to significant reductions in the emissions of polymers, and even suggests that polymers with net negative emissions can be manufactured by 2040, offering the possibility of greenhouse gas sequestration through polymers made from agricultural waste.
Maddening intermittence of rain and two types of critical transitions to monsoon
Authors: Surovyatkina Elena , George Nitin Babu 
Published: June 2022

Abstract
According to folk knowledge, in some years, monsoon comes as a thundering elephant, while in others, it enters gently, like a deer, or sets foot erratic like a chicken. The "elephant" brings good continuous rains and prosperity, while the "deer" or the "chicken" bode a dry spell and a ruinous planting season for farmers. The classical understanding of monsoon onset implies a sudden increase in precipitation and sustainable rains that only fit the "elephant" case. Here, we show that there are two types of critical transitions to monsoon: a direct transition, with a sudden increase in precipitation, and a two/multiple-step transition, with a dry spell after initial rain. We present evidence that 70$\%$ of the last 47 years show two/multiple-step transition, which went overlooked. We uncover that the cause of rainfall cessation is the hidden phenomenon of intermittence emerging between two successive phase transitions. Remarkably, the second type of transition prevails under climate change. Our discovery fills the gap in understanding the transition to monsoon and paves the way to explore its climate resilience in India and other tropical countries.
Novel modification of Luminex assay for characterization of extracellular vesicle populations in biofluids
Authors: Volpert Olga , Gershun Eve , Elgart Katia , Erden Eren , Kapogiannis Dimitrios , Verma Ajay , Levin Amir , Kalia Vrinda , Wu Haotian , Baccarelli Andrea , Eitan Erez 
Published: June 2022

Abstract
Most approaches to extracellular vesicle (EV) characterization are size based and provide few clues regarding EV origin, composition, and function. New methods to define EV surface proteins may aid understanding of their origin, physiological role, and biomarker potential. Recently developed highly sensitive immunoassays for intact EV using ELISA, NanoView, SIMOA and MesoScale platforms have limited multiplexing capabilities, whereas MACSPlex enables the detection of multiple EV surface proteins, but the requirement for large amounts of purified EVs limits its diagnostic usage. Here, we describe a Luminex-based immunoassay, which combines multiplexing capabilities with high sensitivity. The lack of enrichment and purification steps that makes it applicable to low sample volumes. We demonstrate assay’s specificity for EV surface proteins via multiple EV depletion techniques, EV of known cellular origin, and by co-localization with established EV markers. Our novel approach elucidates the differences in tetraspanin profiles of neuronal and erythrocytic EV. Using size exclusion chromatography, we show that plasma EVs of neuronal origin differ in size from EV derived from erythrocytes, released by cutlured cells. In conclusion, our novel multiplexed assay differentiates between EV distinct tissue origins and has the potential to enable characterization of EV surface proteome and thus address EV molecular heterogeneity.
Outbreak.info Research Library: A standardized, searchable platform to discover and explore COVID-19 resources
Authors: Hughes Laura , Tsueng Ginger , Mullen Julia , Alkuzweny Manar , Cano Marco , Rush Benjamin , Haag Emily , Latif Alaa Abdel , Zhou Xinghua , Qian Zhongchao , Hufbauer Emory , Zeller Mark , Andersen Kristian , Wu Chunlei , Su Andrew , Gangavarapu Karthik 
Published: June 2022

Abstract
To combat the ongoing COVID-19 pandemic, scientists have been conducting research at breakneck speeds, producing over 52,000 peer-reviewed articles within the first year. To address the challenge in tracking the vast amount of new research located in separate repositories, we developed outbreak.info Research Library, a standardized, searchable interface of COVID-19 and SARS-CoV-2 resources. Unifying metadata from fourteen repositories, we assembled a collection of over 270,000 publications, clinical trials, datasets, protocols, and other resources as of May 2022. We used a rigorous schema to enforce consistency across different sources and resource types and linked related resources. Researchers can quickly search the latest research across data repositories, regardless of resource type or repository location, via a search interface, public API, and R package. Finally, we discuss the challenges inherent in combining metadata from scattered and heterogeneous resources and provide recommendations to streamline this process to aid scientific research.
Infants with Macrosomia and Infants of Diabetic Mothers Have Increased Carotid Artery Intima- Media Thickness in Childhood
Authors: Yapicioglu Hacer , Seckin Sultan Ceren , Yontem Ahmet , Yildizdas Dincer 
Published: June 2022

Abstract
Purpose: Incidence of diabetes during pregnancy is increasing worldwide, and intrauterine hyperglycemia exposure may have long-term adverse effects on the cardiovascular health of children. We investigated risk of atherosclerosis and carotid intima-media thickness (CIMT) in infants born macrosomic and in infants of diabetic mothers (IDM) at the age of 8–9 years.Method: 49 infants of diabetic mothers (IDM group) and 13 macrosomic infants (Macrosomic group) were included in the study. They were compared with 26 age-matched healthy children with birth weight appropriate for gestational age born to non-diabetic mothers (Control group). Anthropometric measurements, atherosclerosis risk factors and CIMT measurements were performed. Results: There was no significant difference between the groups in terms of age, gender, actual anthropometric measurements, blood pressure measurements, laboratory parameters or atherosclerosis risk factors. Gestational age was lower in the IDM group (p<0.001), while birth weight was higher in the Macrosomic group (p<0.001). High-density lipoprotein cholesterol level was lower in the IDM group than the other groups. Duration of exclusive and total breastfeeding were lower in IDM group than in Control group (p<0.001 for both). Body mass index, skinfold thickness, waist-to-hip ratio and waist-to-height ratio were higher in those breastfed for less than 6 months in the IDM group. The CIMT values were statistically higher in IDM [0.43±.0.047 (0.34-0.60)] and Macrosomic [0.40±0.055 (0.33-0.50)] groups than Control group [0.34±0.047 (0.26-0.45)]. Conclusion, CIMT values were higher in IDM and Macrosomic groups. This indicates intrauterine exposure in both groups. Breastfeeding seems very important for IDMs.