bluuebunny/crossref_metadata_2025_split huggingface dataset:
Warming increases soil carbon input in aSibiraea angustata-dominated alpine shrub ecosystem
Authors: Liu Mei , Wen Jia-Hao , Chen Ya-Mei , Xu Wen-Juan , Wang Qiong , Ma Zhi-Liang 
Published: August 2021

AbstractPlant-derived carbon (C) inputs via foliar litter, root litter and root exudates are key drivers of soil organic C stocks. However, the responses of these three input pathways to climate warming have rarely been studied in alpine shrublands. By employing a 3-year warming experiment (increased by 1.3 °C), we investigated the effects of warming on the relative C contributions from foliar litter, root litter and root exudates from Sibiraea angustata, a dominant shrub species in an alpine shrubland on the eastern Qinghai-Tibetan Plateau. The soil organic C inputs from foliar litter, root litter and root exudates were 77.45, 90.58 and 26.94 g C m−2, respectively. Warming only slightly increased the soil organic C inputs from foliar litter and root litter by 8.04 and 11.13 g C m−2, but significantly increased the root exudate C input by 15.40 g C m−2. Warming significantly increased the relative C contributions of root exudates to total C inputs by 4.6% but slightly decreased those of foliar litter and root litter by 2.5% and 2.1%, respectively. Our results highlight that climate warming may stimulate plant-derived C inputs into soils mainly through root exudates rather than litter in alpine shrublands on the Qinghai-Tibetan Plateau.
Establishing new diffuse interstellar band correlations to identify common carriers
Authors: Smith Fraser M , Harriott Tina A , Majaess Daniel , Massa Lou , Matta Chérif F 
Published: August 2021

ABSTRACT
Observations from the Apache Point Observatory Catalog of Optical Diffuse Interstellar Bands (DIBs) were analysed to establish highly correlated pairs in terms of their equivalent widths (EWs) (r &gt; 0.95), which importantly facilitate the identification of common carriers. A total of 154 846 possible DIB pairs were originally examined, yet only those with a sufficient number of sightlines (n &gt; 9) that included EW uncertainties were subsequently investigated. The highest correlations for the resulting 56 893 DIB pairs are 6284.05–6203.58 Å (r = 0.990 ± 0.001), 6203.58–5780.64 Å (r = 0.986 ± 0.001), 6993.12–6269.89 Å (r = 0.984 ± 0.001), 6843.76–6792.51 Å (r = 0.984 ± 0.005), 6203.58–5487.64 Å (r = 0.983 ± 0.002), and 5061.50–4969.12 Å (r = 0.983 ± 0.009). The bands 5363.77, 5780.64, 6203.58, and 6284.05 Å appear most frequently. Novel relations linked to those DIBs and others warrant further research, in particular those pairs that involve one or both DIBs with low EWs (e.g. 5609.82, 6269.89, 6993.12, and 7224.16 Å). Numerous DIBs correlated with the prominent 4429.33 Å band were also discovered. The intriguing proposal of anionic hydrogen clusters as possible DIB carriers is also discussed.
Towards an advanced testing strategy for genotoxicity using image-based 2D and 3D HepG2 DNA damage response fluorescent protein reporters
Authors: ter Braak Bas , Niemeijer Marije , Wolters Liesanne , Le Dévédec Sylvia , Bouwman Peter , van de Water Bob 
Published: August 2021

Abstract
In vitro assessment of mutagenicity is an essential component in the chemical risk assessment. Given the diverse modes of action by which chemicals can induce DNA damage, it is essential that these in vitro assays are carefully evaluated for their possibilities and limitations. In this study, we used a fluorescent protein HepG2 reporter test system in combination with high content imaging. To measure induction of the DNA damage response (DDR), we used three different green fluorescent protein reporters for p53 pathway activation. These allowed for accurate quantification of p53, p21 and BTG2 (BTG anti-proliferation factor 2) protein expression and cell viability parameters at a single cell or spheroid resolution. The reporter lines were cultured as 2D monolayers and as 3D spheroids. Furthermore, liver maturity and cytochrome P450 enzyme expression were increased by culturing in an amino acid-rich (AAGLY) medium. We found that culture conditions that support a sustained proliferative state (2D culturing with normal DMEM medium) give superior sensitivity when genotoxic compounds are tested that do not require metabolisation and of which the mutagenic mode of action is dependent on replication. For compounds, which are metabolically converted to mutagenic metabolites, more differentiated HepG2 DDR reporters (e.g. 3D cultures) showed a higher sensitivity. This study stratifies how different culture methods of HepG2 DDR reporter cells can influence the sensitivity towards diverse genotoxicants and how this provides opportunities for a tiered genotoxicity testing strategy.
Kinetics of protein-assisted nucleic acid interconversion monitored by transient time resolved fluorescence in microfluidic droplets
Authors: Grytsyk Natalia , Cianfarani Damien , Crégut Olivier , Richert Ludovic , Boudier Christian , Humbert Nicolas , Didier Pascal , Mély Yves , Léonard Jérémie 
Published: August 2021

Abstract
Interconversions between nucleic acid structures play an important role in transcriptional and translational regulation and also in repair and recombination. These interconversions are frequently promoted by nucleic acid chaperone proteins. To monitor their kinetics, Förster resonance energy transfer (FRET) is widely exploited using ensemble fluorescence intensity measurements in pre-steady-state stopped-flow experiments. Such experiments only provide a weighted average of the emission of all species in solution and consume large quantities of materials. Herein, we lift these limitations by combining time-resolved fluorescence (TRF) with droplet microfluidics (DmF). We validate the innovative TRF-DmF approach by investigating the well characterized annealing of the HIV-1 (+)/(–) Primer Binding Sequences (PBS) promoted by a HIV-1 nucleocapsid peptide. Upon rapid mixing of the FRET-labelled (–)PBS with its complementary (+)PBS sequence inside microdroplets, the TRF-DmF set-up enables resolving the time evolution of sub-populations of reacting species and reveals an early intermediate with a ∼50 ps donor fluorescence lifetime never identified so far. TRF-DmF also favorably compares with single molecule experiments, as it offers an accurate control of concentrations with no upper limit, no need to graft one partner on a surface and no photobleaching issues.
Volatility Risk Pass-Through
Authors: Colacito Riccardo , Croce Mariano M , Liu Yang , Shaliastovich Ivan 
Published: August 2021

Abstract
We develop a novel measure of volatility pass-through to assess international propagation of output volatility shocks to macroeconomic aggregates, equity prices, and currencies. An increase in country’s output volatility is associated with a decrease in its output, consumption, and net exports. The average consumption pass-through is 50% (a 1% increase in output volatility increases consumption volatility by 0.5%) and it increases to 70% for shocks originating in smaller countries. The equity volatility pass-through is larger and in the order of 90%. A novel channel of risk sharing of volatility risks can explain our empirical findings.
Targeting of fibroblast activation protein in rheumatoid arthritis patients: imaging and ex vivo photodynamic therapy
Authors: Dorst Daphne N , Rijpkema Mark , Buitinga Mijke , Walgreen Birgitte , Helsen Monique M A , Brennan Evan , Klein Christian , Laverman Peter , Ramming Andreas , Schmidkonz Christian , Kuwert Torsten , Schett Georg , van der Kraan Peter M , Gotthardt Martin , Koenders Marije I 
Published: August 2021

Abstract

Objective
Activated synovial fibroblasts are key effector cells in RA. Selectively depleting these based upon their expression of fibroblast activation protein (FAP) is an attractive therapeutic approach. Here we introduce FAP imaging of inflamed joints using 68Ga-FAPI-04 in a RA patient, and aim to assess feasibility of anti-FAP targeted photodynamic therapy (FAP-tPDT) ex vivo using 28H1-IRDye700DX on RA synovial explants.

Methods
Remnant synovial tissue from RA patients was processed into 6 mm biopsies and, from several patients, into primary fibroblast cell cultures. Both were treated using FAP-tPDT. Cell viability was measured in fibroblast cultures and biopsies were evaluated for histological markers of cell damage. Selectivity of the effect of FAP-tPDT was assessed using flow cytometry on primary fibroblasts and co-cultured macrophages. Additionally, one RA patient intravenously received 68Ga-FAPI-04 and was scanned using PET/CT imaging.

Results
In the RA patient, FAPI-04 PET imaging showed high accumulation of the tracer in arthritic joints with very low background signal. In vitro, FAP-tPDT induced cell death in primary RA synovial fibroblasts in a light dose-dependent manner. An upregulation of cell damage markers was observed in the synovial biopsies after FAP-tPDT. No significant effects of FAP-tPDT were noted on macrophages after FAP-tPDT of neighbouring fibroblasts.

Conclusion
In this study the feasibility of selective FAP-tPDT in synovium of rheumatoid arthritis patients ex vivo is demonstrated. Furthermore, this study provides the first indication that FAP-targeted PET/CT can be used to image arthritic joints, an important step towards application of FAP-tPDT as a targeted locoregional therapy for RA.
Integrated application of metabolomics and RNA‐seq reveals thermogenic regulation in goat brown adipose tissues
Authors: Wang Yan , Chen Xingyue , Fan Wenli , Zhang Xujia , Zhan Siyuan , Zhong Tao , Guo Jiazhong , Cao Jiaxue , Li Li , Zhang Hongping , Wang Linjie 
Published: August 2021

AbstractBrown adipose tissue (BAT) plays an important role on no shivering thermogenesis during cold exposure to maintain animal body temperature and energy homeostasis. However, knowledge of the cellular transition from white adipose tissue (WAT) to BAT is still limited. In this study, we provided a comprehensive metabolomics and transcriptional signatures of goat BAT and WAT. A total of 157 metabolites were significantly changed, including 81 upregulated and 76 downregulated metabolites. In addition, we identified the citric acid cycle, fatty acid elongation, and degradation pathways as coordinately activated in BAT. Interestingly, five unsaturated fatty acids (Eicosadienoic Acid, C20:2; γ‐Linolenic acid, C20:3; Arachidonic Acid, C20:4; Adrenic acid, C22:4; Docosahexaenoic acid, C22:6), Succinate, L‐carnitine, and L‐palmitoyl‐carnitine were found to be abundant in BAT. Furthermore, L‐carnitine, an intermediate of fatty acid degradation, is required for goat brown adipocyte differentiation and thermogenesis through activating AMPK pathway. However, L‐carnitine decreased lipid accumulation through inducing lipolysis and thermogenesis in white adipocytes. These results revealed that there are the significant alterations in transcriptomic and metabolomic profiles between goat WAT and BAT, which may contribute to better understanding the roles of metabolites in BAT thermogenesis process.
Endothelium‐dependent contraction: The non‐classical action of endothelial prostacyclin, its underlying mechanisms, and implications
Authors: Liu Bin , Zhou Yingbi 
Published: August 2021

AbstractAlthough commonly thought to produce prostacyclin (prostaglandin I2; PGI2) that evokes vasodilatation and protects vessels from the development of diseases, the endothelial cyclooxygenase (COX)‐mediated metabolism has also been found to release substance(s) called endothelium‐derived contracting factor(s) (EDCF) that causes endothelium‐dependent contraction and implicates in endothelial dysfunction of disease conditions. Various mechanisms have been proposed for the process; however, the major endothelial COX metabolite PGI2, which has been classically considered to activate the I prostanoid receptor (IP) that mediates vasodilatation and opposes the effects of thromboxane (Tx) A2 produced by COX in platelets, emerges as a major EDCF in health and disease conditions. Our recent studies from genetically altered mice further suggest that vasomotor reactions to PGI2 are collectively modulated by IP, the vasoconstrictor Tx‐prostanoid receptor (TP; the prototype receptor of TxA2) and E prostanoid receptor‐3 (EP3; a vasoconstrictor receptor of PGE2) although with differences in potency and efficacy; a contraction to PGI2 reflects activities of TP and/or EP3 outweighing that of the concurrently activated IP. Here, we discuss the history of endothelium‐dependent contraction, evidences that support the above hypothesis, proposed mechanisms for the varied reactions to endothelial PGI2 synthesis as well as the relation of its dilator activity to the effect of another NO‐independent vasodilator mechanism, the endothelium‐derived hyperpolarizing factor. Also, we address the possible pathological and therapeutic implications as well as questions remaining to be resolved or limitations of our above findings obtained from genetically altered mouse models.
Two‐photon AMPK and ATP imaging reveals the bias between rods and cones in glycolysis utility
Authors: He Jiazhou , Yamamoto Masamichi , Sumiyama Kenta , Konagaya Yumi , Terai Kenta , Matsuda Michiyuki , Sato Shinya 
Published: August 2021

AbstractIn vertebrates, retinal rod and cone photoreceptor cells rely significantly on glycolysis. Lactate released from photoreceptor cells fuels neighboring retinal pigment epithelium cells and Müller glial cells through oxidative phosphorylation. To understand this highly heterogeneous metabolic environment around photoreceptor cells, single‐cell analysis is needed. Here, we visualized cellular AMP‐activated protein kinase (AMPK) activity and ATP levels in the retina by two‐photon microscopy. Transgenic mice expressing a hyBRET‐AMPK biosensor were used for measuring the AMPK activity. GO‐ATeam2 transgenic mice were used for measuring the ATP level. Temporal metabolic responses were successfully detected in the live retinal explants upon drug perfusion. A glycolysis inhibitor, 2‐deoxy‐d‐glucose (2‐DG), activated AMPK and reduced ATP. These effects were clearly stronger in rods than in cones. Notably, rod AMPK and ATP started to recover at 30 min from the onset of 2‐DG perfusion. Consistent with these findings, ex vivo electroretinogram recordings showed a transient slowdown in rod dim flash responses during a 60‐min 2‐DG perfusion, whereas cone responses were not affected. Based on these results, we propose that cones surrounded by highly glycolytic rods become less dependent on glycolysis, and rods also become less dependent on glycolysis within 60 min upon the glycolysis inhibition.
Defusing aggressive behavior in the healthcare setting
Authors: Homotoff Kerry 
Published: August 2021

ABSTRACT
Up to 80% of healthcare professionals, particularly those working in emergency medicine, have experienced workplace violence. However, many clinicians lack proper training for handling these situations. Workplace violence is one factor contributing to burnout, job dissatisfaction, and mental health issues. This article describes how to identify and manage aggression and violence in the healthcare setting using simple interventions to de-escalate aggressive behaviors.
ICU survivorship
Authors: LaRosa Nicolette 
Published: August 2021

ABSTRACT
The number of people surviving critical illnesses is larger than ever. Many of these patients will rely on physician assistants (PAs) to facilitate their care after discharge from the ICU. As a result, PAs must be able to recognize and treat the numerous short- and long-term challenges this vulnerable population faces, especially given the recent surge of critically ill patients resulting from the COVID-19 pandemic.
Combination Therapy of Pulsed Dye Laser With Intense Pulsed Light in Port-Wine Stain Treatment: A Prospective Side-by-Side Comparison
Authors: Yu Wenxin , Cen Qingqing , Chen Yanyu , Zhu Jiafang , Lin Xiaoxi 
Published: August 2021

BACKGROUND
Pulsed dye laser (PDL) treatment currently represents the mainstream choice for port-wine stain (PWS) treatment in accordance with selective photothermolysis. However, most PWS lesions cannot be removed despite several treatments. Intense pulsed light (IPL) is reportedly an effective alternative to PDL for PWS treatment. No studies have thus far been reported on the combination therapy of PDL with IPL in PWS treatment.

OBJECTIVE
This study evaluated the efficacy and safety of PDL with IPL for PWS treatment.

METHODS
A total of 33 PWS lesions underwent 3 treatment sessions. Each PWS was divided into IPL + PDL, PDL, and untreated sites. Therapeutic outcomes were evaluated by visual assessment and chromametric assessment 3 months after the final treatment.

RESULTS
The overall average blanching rates were 36.2% and 32.6% at the sites treated with IPL + PDL and PDL, respectively (p > .05). No permanent side effects were reported.

CONCLUSION
In this laser setting, although IPL + PDL is a safe and effective PWS treatment, no significant improvement in the efficacy was observed using IPL + PDL in contrast to PDL alone.
Dexmedetomidine Exerts a Negative Chronotropic Action on Sinoatrial Node Cells Through the Activation of Imidazoline Receptors
Authors: Ishihara Mariko , Kojima Akiko , Ding Wei-Guang , Kitagawa Hirotoshi , Matsuura Hiroshi 
Published: August 2021

Abstract:
Dexmedetomidine (DEX), an α2-adrenoreceptor (α2-AR) and imidazoline receptor agonist, is most often used for the sedation of patients in the intensive care unit. Its administration is associated with an increased incidence of bradycardia; however, the precise mechanism of DEX-induced bradycardia has yet to be fully elucidated. This study was undertaken to examine whether DEX modifies pacemaker activity and the underlying ionic channel function through α2-AR and imidazoline receptors. The whole-cell patch-clamp techniques were used to record action potentials and related ionic currents of sinoatrial node cells in guinea pigs. DEX (≥10 nM) reduced sinoatrial node automaticity and the diastolic depolarization rate. DEX reduced the amplitude of hyperpolarization-activated cation current (I
f or I
h) the pacemaker current, even within the physiological pacemaker potential range. DEX slowed the I
f current activation kinetics and caused a significant shift in the voltage dependence of channel activation to negative potentials. In addition, efaroxan, an α2-AR and imidazoline I1 receptor antagonist, attenuated the inhibitory effects of DEX on sinoatrial node automaticity and I
f current activity, whereas yohimbine, an α2-AR–selective antagonist, did not. DEX did not affect the current activities of other channels, including rapidly and slowly activating delayed rectifier K+ currents (I
Kr and I
Ks), L-type Ca2+ current (I
Ca,L), Na+/Ca2+ exchange current (I
NCX), and muscarinic K+ current (I
K,ACh). Our results indicate that DEX, at clinically relevant concentrations, induced a negative chronotropic effect on the sinoatrial node function through the downregulation of I
f current through an imidazoline I1 receptor other than the α2-AR in the clinical setting.
The Etiology of Childhood Pneumonia in Bangladesh
Authors: Brooks W. Abdullah , Zaman Khalequ , Goswami Doli , Prosperi Christine , Endtz Hubert P. , Hossain Lokman , Rahman Mustafizur , Ahmed Dilruba , Rahman Mohammed Ziaur , Banu Sayera , Shikder Arif Uddin , Jahan Yasmin , Nahar Kamrun , Chisti Mohammod Jobayer , Yunus Mohammed , Khan Muhammad Alfazal , Matin Fariha Bushra , Mazumder Razib , Shahriar Bin Elahi Mohammad , Saifullah Muhammad , Alam Muntasir , Bin Shahid Abu Sadat Mohammad Sayeem , Haque Fahim , Sultana Sabiha , Higdon Melissa M. , Haddix Meredith , Feikin Daniel R. , Murdoch David R. , Hammitt Laura L. , O’Brien Katherine L. , Deloria Knoll Maria 
Published: August 2021

Background:
Pneumonia remains the leading infectious cause of death among children <5 years, but its cause in most children is unknown. We estimated etiology for each child in 2 Bangladesh sites that represent rural and urban South Asian settings with moderate child mortality.

Methods:
As part of the Pneumonia Etiology Research for Child Health study, we enrolled children 1–59 months of age with World Health Organization–defined severe and very severe pneumonia, plus age-frequency-matched controls, in Matlab and Dhaka, Bangladesh. We applied microbiologic methods to nasopharyngeal/oropharyngeal swabs, blood, induced sputum, gastric and lung aspirates. Etiology was estimated using Bayesian methods that integrated case and control data and accounted for imperfect sensitivity and specificity of the measurements.

Results:
We enrolled 525 cases and 772 controls over 24 months. Of the cases, 9.1% had very severe pneumonia and 42.0% (N = 219) had infiltrates on chest radiograph. Three cases (1.5%) had positive blood cultures (2 Salmonella typhi, 1 Escherichia coli and Klebsiella pneumoniae). All 4 lung aspirates were negative. The etiology among chest radiograph–positive cases was predominantly viral [77.7%, 95% credible interval (CrI): 65.3–88.6], primarily respiratory syncytial virus (31.2%, 95% CrI: 24.7–39.3). Influenza virus had very low estimated etiology (0.6%, 95% CrI: 0.0–2.3). Mycobacterium tuberculosis (3.6%, 95% CrI: 0.5–11.0), Enterobacteriaceae (3.0%, 95% CrI: 0.5–10.0) and Streptococcus pneumoniae (1.8%, 95% CrI: 0.0–5.9) were the only nonviral pathogens in the top 10 etiologies.

Conclusions:
Childhood severe and very severe pneumonia in young children in Bangladesh is predominantly viral, notably respiratory syncytial virus.
The Etiology of Pneumonia in HIV-1-infected South African Children in the Era of Antiretroviral Treatment
Authors: Moore David P. , Baillie Vicky L. , Mudau Azwifarwi , Wadula Jeannette , Adams Tanja , Mangera Shafeeka , Verwey Charl , Sipambo Nosisa , Liberty Afaaf , Prosperi Christine , Higdon Melissa M. , Haddix Meredith , Hammitt Laura L. , Feikin Daniel R. , O’Brien Katherine L. , Deloria Knoll Maria , Murdoch David R. , Simões Eric A. F. , Madhi Shabir A. 
Published: August 2021

Background:HIV-1 infection predisposes to an increased burden of pneumonia caused by community-acquired and opportunistic pathogens.Methods:Within the context of the Pneumonia Etiology Research for Child Health case-control study of under 5 pneumonia, we investigated the etiology of World Health Organization-defined severe/very severe pneumonia requiring hospitalization in South African HIV-infected children. Nasopharyngeal-oropharyngeal swabs and blood, collected from cases and age- and season-matched HIV-infected controls attending outpatient antiretroviral therapy (ART) clinics, were analyzed using molecular diagnostic methods. Cases were also investigated for tuberculosis. Etiologic fractions among cases with radiologically confirmed pneumonia were derived using Bayesian analytic techniques.Results:Of 115 HIV-infected cases, 89 (77.4%) had radiologically confirmed pneumonia. Severe immunosuppression (adjusted odds ratio, 32.60; 95% confidence interval, 7.25–146.64) was significantly associated with radiologically confirmed pneumonia. Cotrimoxazole prophylaxis (46.4% vs. 77.4%) and ART (28.2% vs. 83.1%) coverage were significantly lower in cases compared with ART-clinic controls. An etiologic agent was identified in 99.0% of the radiologically confirmed cases. The ‘top 4’ pathogens associated with radiologically confirmed pneumonia werePneumocystis jirovecii[23.0%; 95% credible interval (CrI), 12.4%–31.5%],Staphylococcus aureus(10.6%; 95% CrI, 2.2%–20.2%), pneumococcus (9.5%; 95% CrI, 2.2%–18.0%) and respiratory syncytial virus (9.3%; 95% CrI, 2.2%–14.6%). Bacteremia (6.7%) and in-hospital death (10.1%) were frequent among those with radiologically confirmed disease.Conclusions:Pneumocystis jirovecii,S. aureus, pneumococcus and respiratory syncytial virus contribute a considerable burden of radiologically confirmed pneumonia in South African HIV-infected children under 5 years. Expediting access to ART and cotrimoxazole prophylaxis would decrease the burden of pneumonia in these children.