bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo translational assessment of the GES genotype on the killing profile of ceftazidime, ceftazidime/avibactam and meropenem against Pseudomonas aeruginosa
Authors: Gill Christian M , Oliver Antonio , Fraile-Ribot Pablo Arturo , Nicolau David P 
Published: July 2022

Abstract

Objectives
To evaluate the in vivo killing profile of human-simulated exposures of ceftazidime, ceftazidime/avibactam and meropenem against GES-harbouring Pseudomonas aeruginosa in the murine thigh infection model.

Methods
Five P. aeruginosa isolates [three isogenic (GES-1, GES-5 and GES-15) and two clinical (GES-5 and GES-15)] were evaluated. MICs were determined using broth microdilution. Human-simulated regimens (HSRs) of ceftazidime 2 g IV q8h as a 2 h infusion, ceftazidime/avibactam 2.5 g IV q8h as a 2 h infusion and meropenem 2 g IV q8h as a 3 h infusion were administered. Change in bacterial burden relative to baseline was assessed.

Results
Modal MICs ranged from 8 to &gt;64 mg/L for ceftazidime, from 1 to 16 mg/L for ceftazidime/avibactam and from 1 to &gt;64 mg/L for meropenem. In vivo, for the isogenic strains, avibactam augmented ceftazidime activity against the GES-1- and GES-15-harbouring isolates. Both ceftazidime and ceftazidime/avibactam resulted in significant kill against the GES-5 isogenic isolate. The meropenem HSR produced &gt;1 log10 kill against each isogenic isolate (MICs of 1–4 mg/L). Against the GES-5 clinical isolate, ceftazidime and ceftazidime/avibactam resulted in &gt;1 log10 kill compared with bacterial growth with the meropenem HSR. In the clinical isolate harbouring GES-15, the elevated MICs of ceftazidime and ceftazidime/avibactam reduced the effectiveness of both compounds, while the observed reduction in meropenem MIC translated into in vivo efficacy of the HSR regimen, predictive of clinical efficacy.

Conclusions
In GES-harbouring P. aeruginosa, quantitative reductions in bacterial density observed with the translational murine model suggest that the phenotypic profile of ceftazidime, ceftazidime/avibactam and meropenem is predictive of clinical efficacy when using the evaluated dosing regimens.
Restriction in Program Algebra
Authors: Jackson Marcel , Stokes Tim 
Published: July 2022

Abstract
We provide complete classifications of algebras of partial maps for a significant swathe of combinations of operations not previously classified. Our focus is the many subsidiary operations that arise in recent considerations of the ‘override’ and ‘update’ operations arising in specification languages. These other operations turn out to have an older pedigree: domain restriction, set subtraction and intersection. All signatures considered include domain restriction, at least as a term. Combinations of the operations are classified and given complete axiomatizations with and without the presence of functional composition. Each classification is achieved by way of providing a concrete representation of the corresponding abstract algebras as partial maps acting on special kinds of filters determined with respect to various induced orders. In contrast to many negative results in the broader area, all of the considered combinations lead to finite axiomatizations.
Surgical repair of the medial head of the gastrocnemius: two case reports and review
Authors: Pereira Vitor Luis , Andreoli Carlos Vicente , Santos Rafaella Figueiredo Vieira , Belangero Paulo Santoro , Ejnisman Benno , Castro Pochini Alberto de 
Published: July 2022

Abstract
The gastrocnemius medial head distal musculotendinous junction injury is relatively common. Musculature contraction in an already stretched structure leads to muscle breakdown. Patients affected are often physically active middle-aged men. The typical presentation includes sudden pain, audible popping, bruising and localized tenderness. Occasionally, there is a palpable defect if the rupture is complete. Although the initial diagnosis can be made on the basis of a careful history and clinical examination, ultrasound or magnetic resonance imaging can be used to better describe the lesion. In complete ruptures, even when conservative treatment shows good results, it is common that the patient presents decreased muscle strength, difficulty returning to sports and permanent and visible gap. Considering surgical treatment in patients with complete ruptures and extensive injuries with a more than 5 cm gap may lead to better healing process, rapid rehabilitation and more efficient return to sports.
Coping with the COVID-19 Pandemic: How a Master’s in Clinical Laboratory Sciences Program Adapted Through the Modification of Existing Resources
Authors: Carbonaro Carol A , Isabella Debbie , Ronny Faisal Huq 
Published: July 2022

Abstract

Objective
Our aim was to describe the rapid adaption of a Master of Clinical Laboratory Sciences (MCLS) program to the abrupt suspension of classroom instruction and laboratory training at affiliated hospitals in compliance with the New York governor’s executive order in March 2020.

Methods
Teaching modifications included greater emphasis on Zoom video conferencing, Media Lab assignments, independent self-study, and online testing.

Results
Instruction of academic coursework continued uninterrupted using previously established teaching modalities. Clinical training presented 2-fold concerns, credit hours needed for the master’s degree and clinical hours required for New York State licensing. The latter was delayed.

Conclusion
The real-time need to deliver laboratory science education during a time of statewide closure was fulfilled using available teaching modalities. The resulting uninterrupted academic and clinical training ensured the education of the incoming workforce of our clinical laboratories. This teaching strategy may be considered during new curricula development in preparation for times of future crises.
Patient and Treatment Characteristics Associated With Receipt of Core Patient-Reported Outcome Measures in VA Mental Health
Authors: Liebmann Edward P , Resnick Sandra G , Austin Karen L , Jedele Jenefer M 
Published: July 2022

ABSTRACT

Objective
Measurement-based care (MBC) has been implemented in Veterans Affairs since 2016 and is increasingly used in other mental health care organizations. Little quantitative research exists that assesses patient-level barriers and facilitators of MBC. This study examines correlates of receiving patient-reported outcome measures (PROMs) among veterans receiving both psychotherapy and pharmacotherapy (Both), psychotherapy only (Psychotherapy), and pharmacotherapy only (Pharmacotherapy).

Methods
Data on PROM administration were obtained for a 12-month period for 1,726,578 veterans who initiated outpatient mental health care during fiscal year 2019. Clinical, treatment, and PROM data were extracted from the electronic health record. Logistic regression was used to model the association between veteran and treatment characteristics and PROM administration.

Results
Thirty-two percent of veterans in Both, 26.0% in Psychotherapy, and 8.8% in Pharmacotherapy received at least one PROM. The probability of PROM administration was positively associated with the number of treatment encounters during the fiscal year 2019. Major depressive, generalized anxiety, and other depressive disorders were associated with an increased probability of PROM administration. Psychotic disorders, personality disorders, older age, dementia, and electronic health record suicide risk flag were associated with decreased odds of PROM administration across treatment types.

Conclusions
Rates of PROM administration differ depending on the type of treatment received. The probability of PROM administration is influenced by the frequency of encounters and, to a lesser extent, having a diagnosis congruent with symptoms assessed in the set of PROMs considered. Consistent with hypotheses from the MBC implementation literature, potential indicators of clinical severity and cognitive impairment decrease the likelihood of PROM utilization.
A fresh look at AGN spectral energy distribution fitting with the XMM-SERVS AGN sample
Authors: Marshall Adam , Auger-Williams Matthew W , Banerji Manda , Maiolino Roberto , Bowler Rebecca 
Published: July 2022

ABSTRACTWe perform spectral energy distribution (SED) fitting to 711 luminous X-ray AGN at 0.7 &lt; z &lt; 4.5 using 10-bands of optical and infra-red photometric data for objects within XMM-SERVS. This fitting provided 510 reliable (reduced χ2 &lt; 3) inferences on AGN and host galaxy properties. The AGN optical (3000 Å) luminosity inferred from SED-fitting is found to correlate with the measured X-ray (2–10 keV) luminosity, in good agreement with previous work. Using X-ray hardness as a proxy for AGN obscuration, we also study the differences in the host galaxy properties of obscured and unobscured AGNs. Both populations have consistent stellar masses (log10(M*/M⊙) = 10.88 $\pm 0.09\, {\rm M}_\odot$ and log10(M*/M⊙) = 10.8 $\pm 0.1\, {\rm M}_\odot$ for unobscured and obscured AGNs, respectively). We also find evidence for varying AGN emission line properties from a standard AGN template in 18.8 per cent of the sample with a reduced χ2 &lt; 3 where the inclusion of an additional emission line strength free parameter was found to improve the quality of the fit. Comparison of these fits to SDSS spectra showed that emission line properties inferred from broad-band photometry were consistent with the results from spectroscopy for 91 per cent of objects. We find that the presence of weaker, more blueshifted emission lines as inferred from the SED fits are associated with more negative values of αox. While the correlation between the hardness of the ionizing SED and the emission line properties has been known for some time, we are able to derive this correlation purely from broad-band photometry.
Dust masses for a large sample of core-collapse supernovae from optical emission line asymmetries: dust formation on 30-year time-scales
Authors: Niculescu-Duvaz Maria , Barlow M J , Bevan A , Wesson R , Milisavljevic D , De Looze I , Clayton G C , Krafton K , Matsuura M , Brady R 
Published: July 2022

ABSTRACT
Modelling the red–blue asymmetries seen in the broad emission lines of core-collapse supernovae (CCSNe) is a powerful technique to quantify total dust mass formed in the ejecta at late times (&gt;5 yr after outburst) when ejecta dust temperatures become too low to be detected by mid-infrared (IR) instruments. Following our success in using the Monte Carlo radiative transfer code damocles to measure the dust mass evolution in SN 1987A and other CCSNe, we present the most comprehensive sample of dust mass measurements yet made with damocles, for CCSNe aged between 4 and 60 yr after outburst. Our sample comprises multi-epoch late-time optical spectra taken with the Gemini/Gemini Multi-Object Spectrographs (GMOS) and Very Large Telescope (VLT) X-Shooter spectrographs, supplemented by archival spectra. For the 14 CCSNe that we have modelled, we confirm a dust mass growth with time that can be fit by a sigmoid curve that is found to saturate beyond an age of ∼30 yr, at a mass of 0.23$^{+0.17}_{-0.12}$ M⊙. For an expanded sample including dust masses found in the literature for a further 11 CCSNe and six CCSN remnants, the dust mass at saturation is found to be 0.42$^{+0.09}_{-0.05}$ M⊙. Uncertainty limits for our dust masses were determined from a Bayesian analysis using the affine invariant Markov chain Monte Carlo ensemble sampler emcee with damocles. The best-fitting line profile models for our sample all required grain radii between 0.1 and 0.5 $\mu$m. Our results are consistent with CCSNe forming enough dust in their ejecta to significantly contribute to the dust budget of the Universe.
Spatially resolved gas-phase metallicity in FIRE-2 dwarfs: late-time evolution of metallicity relations in simulations with feedback and mergers
Authors: Porter Lori E , Orr Matthew E , Burkhart Blakesley , Wetzel Andrew , Ma Xiangcheng , Hopkins Philip F , Emerick Andrew 
Published: July 2022

ABSTRACT
We present an analysis of spatially resolved gas-phase metallicity relations in five dwarf galaxies ($\rm \mathit{M}_{halo} \approx 10^{11}\, {\rm M}_\odot$, $\rm \mathit{M}_\star \approx 10^{8.8}{-}10^{9.6}\, {\rm M}_\odot$) from the FIRE-2 (Feedback in Realistic Environments) cosmological zoom-in simulation suite, which include an explicit model for sub-grid turbulent mixing of metals in gas, near z ≈ 0, over a period of 1.4 Gyr, and compare our findings with observations. While these dwarf galaxies represent a diverse sample, we find that all simulated galaxies match the observed mass–metallicity (MZR) and mass–metallicity gradient (MZGR) relations. We note that in all five galaxies, the metallicities are effectively identical between phases of the interstellar medium (ISM), with 95 ${{\ \rm per\ cent}}$ of the gas being within ±0.1 dex between the cold and dense gas (T &lt; 500 K and nH &gt; 1 cm−3), ionized gas (near the H αT ≈ 104 K ridge-line), and nebular regions (ionized gas where the 10 Myr-averaged star formation rate is non-zero). We find that most of the scatter in relative metallicity between cold dense gas and ionized gas/nebular regions can be attributed to either local starburst events or metal-poor inflows. We also note the presence of a major merger in one of our galaxies, m11e, with a substantial impact on the metallicity distribution in the spatially resolved map, showing two strong metallicity peaks and triggering a starburst in the main galaxy.
LncRNA CTBP1-DT-encoded microprotein DDUP sustains DNA damage response signalling to trigger dual DNA repair mechanisms
Authors: Yu Ruyuan , Hu Yameng , Zhang Shuxia , Li Xincheng , Tang Miaoling , Yang Meisongzhu , Wu Xingui , Li Ziwen , Liao Xinyi , Xu Yingru , Li Man , Chen Suwen , Qian Wanying , Gong Li-Yun , Song Libing , Li Jun 
Published: July 2022

Abstract
Sustaining DNA damage response (DDR) signalling via retention of DDR factors at damaged sites is important for transmitting damage-sensing and repair signals. Herein, we found that DNA damage provoked the association of ribosomes with IRES region in lncRNA CTBP1-DT, which overcame the negative effect of upstream open reading frames (uORFs), and elicited the novel microprotein DNA damage-upregulated protein (DDUP) translation via a cap-independent translation mechanism. Activated ATR kinase-mediated phosphorylation of DDUP induced a drastic ‘dense-to-loose’ conformational change, which sustained the RAD18/RAD51C and RAD18/PCNA complex at damaged sites and initiated RAD51C-mediated homologous recombination and PCNA-mediated post-replication repair mechanisms. Importantly, treatment with ATR inhibitor abolished the effect of DDUP on chromatin retention of RAD51C and PCNA, thereby leading to hypersensitivity of cancer cells to DNA-damaging chemotherapeutics. Taken together, our results uncover a plausible mechanism underlying the DDR sustaining and might represent an attractive therapeutic strategy in improvement of DNA damage-based anticancer therapies.
Insights into innate immune activation via PS-ASO–protein–TLR9 interactions
Authors: Pollak Adam J , Zhao Luyi , Vickers Timothy A , Huggins Ian J , Liang Xue-Hai , Crooke Stanley T 
Published: July 2022

Abstract
Non-CpG PS-ASOs can activate the innate immune system, leading to undesired outcomes. This response can vary—in part—as a function of 2′modifications and sequence. Here we investigated the molecular steps involved in the varied effects of PS-ASOs on the innate immune system. We found that pro-inflammatory PS-ASOs require TLR9 signaling based on the experimental systems used. However, the innate immunity of PS-ASOs does not correlate with their binding affinity with TLR9. Furthermore, the innate immune responses of pro-inflammatory PS-ASOs were reduced by coincubation with non-inflammatory PS-ASOs, suggesting that both pro-inflammatory and non-inflammatory PS-ASOs can interact with TLR9. We show that the kinetics of the PS-ASO innate immune responses can vary, which we speculate may be due to the existence of alternative PS-ASO binding sites on TLR9, leading to full, partial, or no activation of the pathway. In addition, we found that several extracellular proteins, including HMGB1, S100A8 and HRG, enhance the innate immune responses of PS-ASOs. Reduction of the binding affinity by reducing the PS content of PS-ASOs decreased innate immune responses, suggesting that PS-ASO–protein complexes may be sensed by TLR9. These findings thus provide critical information concerning how PS-ASOs can interact with and activate TLR9.
ERECTA regulates seed size independently of its intracellular domain via MAPK-DA1-UBP15 signaling
Authors: Wu Xuedan , Cai Xingbo , Zhang Baowen , Wu Shuting , Wang Ruiju , Li Na , Li Yunhai , Sun Yu , Tang Wenqiang 
Published: July 2022

AbstractSeed size is determined by the coordinated growth of the embryo, endosperm, and integument. Growth of the integument is initiated by signal molecules released from the developing endosperm or embryo. Although recent studies have identified many components that regulate seed size by controlling integument growth, the upstream signals and the signal transduction pathway that activate these components after double fertilization are unclear. Here, we report that the receptor-like kinase ERECTA (ER) controls seed size by regulating outer integument cell proliferation in Arabidopsis thaliana. Seeds from er mutants were smaller, while those from ER-overexpressing plants were larger, than those of control plants. Different from its role in regulating the development of other organs, ER regulates seed size via a novel mechanism that is independent of its intracellular domain. Our genetic and biochemical data show that a MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) signaling pathway comprising MAPK-KINASE 4/5, MAPK 3/6 (MPK3/6), DA1, and UBIQUITIN SPECIFIC PROTEASE 15 (UBP15) functions downstream of ER and modulates seed size. MPK3/6 phosphorylation inactivates and destabilizes DA1 to increase the abundance of UBP15, promoting outer integument cell proliferation and increasing seed size. Our study illustrates a nearly completed ER-mediated signaling pathway that regulates seed size and will help uncover the mechanism that coordinates embryo, endosperm, and integument growth after double fertilization.
Cooperative innovation and crises: Foreign subsidiaries, state-owned enterprises, and domestic private firms
Authors: García-Sánchez Antonio , Rama Ruth 
Published: July 2022

AbstractThis article studies whether foreign subsidiaries (FSs) are able to cooperate for innovation with local partners during good and harsh economic times. It also enquires as to whether these companies and different types of domestic firms displayed similar cooperative behaviour during 2004–16. The period is divided into three sub-periods (boom, downturn, and recovery), and three logit models with panel data of a representative sample of Spanish firms are proposed. The ability of FSs to cooperate for innovation is maintained throughout the business cycle. These firms are better at cooperating than are unaffiliated firms but not significantly better than domestic business groups. State-owned enterprises strongly outperform both FSs and domestic private firms during the boom, the downturn, and the recovery. Unaffiliated domestic firms manage to cooperate during the boom and the recovery but not during the downturn. Predictors of cooperative innovation vary throughout the business cycle. The results contain policy implications.
Leading nutrient foraging strategies shaping by root system characteristics along the elevations in rubber (Hevea brasiliensis) plantations
Authors: Duan Mengcheng , Li Liang , Ding Gaigai , Ma Zeqing 
Published: July 2022

Abstract
When it comes to root and mycorrhizal associations that define resource acquisition strategy, there is a need to identify the leading dimension across root physiology, morphology, architecture and whole plant biomass allocation to better predict the plant’s responses to multiple environmental constraints. Here, we developed a new framework for understanding the variation in roots and symbiotic fungi by quantifying multiple-scale characteristics, ranging from anatomy to the whole plant. We chose the rubber (Hevea brasiliensis) grown at three elevations to test our framework and to identify the key dimensions for resource acquisition. Results showed that the quantities of absorptive roots and root system architecture, rather than single root traits, played the leading role in belowground resource acquisition. As the elevation increased from the low to high elevation, root length growth, productivity and root mass fraction (RMF) increased by 2.9-, 2.3- and 13.8-fold, respectively. The contribution of RMF to the changes in total root length was 3.6-fold that of specific root length (SRL). Root architecture exhibited higher plasticity than anatomy and morphology. Further, mycorrhizal colonization was highly sensitive to rising elevations with a non-monotonic pattern. By contrast, both leaf biomass and specific leaf area (traits) co-varied with increasing elevation. In summary, rubber trees changed root system architecture by allocating more biomass and lowering the reliance on mycorrhizal fungi rather than improving single root efficiency in adapting to high elevation. Our framework is instructive for traits-based ecology; accurate assessments of forest carbon cycling in response to resource gradient should account for the leading dimension of root system architecture.
Methylation-mediated silencing of PTPRD induces pulmonary hypertension by promoting pulmonary arterial smooth muscle cell migration via the PDGFRB/PLCγ1 axis
Authors: Xu Junhua , Zhong Yanfeng , Yin Haoyang , Linneman John , Luo Yixuan , Xia Sijian , Xia Qinyi , Yang Lei , Huang Xingtao , Kang Kang , Wang Jun , Niu Yanqin , Li Li , Gou Deming 
Published: July 2022

Objective:
Pulmonary hypertension is a lethal disease characterized by pulmonary vascular remodeling and is mediated by abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Platelet-derived growth factor BB (PDGF-BB) is the most potent mitogen for PASMCs and is involved in vascular remodeling in pulmonary hypertension development. Therefore, the objective of our study is to identify novel mechanisms underlying vascular remodeling in pulmonary hypertension.

Methods:
We explored the effects and mechanisms of PTPRD downregulation in PASMCs and PTPRD knockdown rats in pulmonary hypertension induced by hypoxia.

Results:
We demonstrated that PTPRD is dramatically downregulated in PDGF-BB-treated PASMCs, pulmonary arteries from pulmonary hypertension rats, and blood and pulmonary arteries from lung specimens of patients with hypoxic pulmonary arterial hypertension (HPAH) and idiopathic PAH (iPAH). Subsequently, we found that PTPRD was downregulated by promoter methylation via DNMT1. Moreover, we found that PTPRD knockdown altered cell morphology and migration in PASMCs via modulating focal adhesion and cell cytoskeleton. We have demonstrated that the increase in cell migration is mediated by the PDGFRB/PLCγ1 pathway. Furthermore, under hypoxic condition, we observed significant pulmonary arterial remodeling and exacerbation of pulmonary hypertension in heterozygous PTPRD knock-out rats compared with the wild-type group. We also demonstrated that HET group treated with chronic hypoxia have higher expression and activity of PLCγ1 in the pulmonary arteries compared with wild-type group.

Conclusion:
We propose that PTPRD likely plays an important role in the process of pulmonary vascular remodeling and development of pulmonary hypertension in vivo.