bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefits of Aerosolized Phages for the Treatment of Pneumonia Due to Methicillin-ResistantStaphylococcus aureus: An Experimental Study in Rats
Authors: Prazak Josef , Valente Luca G , Iten Manuela , Federer Lea , Grandgirard Denis , Soto Sara , Resch Gregory , Leib Stephen L , Jakob Stephan M , Haenggi Matthias , Cameron David R , Que Yok-Ai 
Published: February 2021

AbstractBackgroundThe optimal method for delivering phages in the context of ventilator-associated pneumonia (VAP) is unknown. In the current study, we assessed the utility of aerosolized phages (aerophages) for experimental methicillin-resistant Staphylococcus aureus (MRSA) pneumonia.MethodsRats were ventilated for 4 hours before induction of pneumonia. Animals received one of the following: (1) aerophages; (2) intravenous (IV) phages; (3) a combination of IV and aerophages; (4) IV linezolid; or (5) a combination of IV linezolid and aerophages. Phages were administered at 2, 12, 24, 48, and 72 hours, and linezolid was administered at 2, 12, 24, 36, 48, 60, and 72 hours. The primary outcome was survival at 96 hours. Secondary outcomes were bacterial and phage counts in tissues and histopathological scoring of the lungs.ResultsAerophages and IV phages each rescued 50% of animals from severe MRSA pneumonia (P &lt; .01 compared with placebo controls). The combination of aerophages and IV phages rescued 91% of animals, which was higher than either monotherapy (P &lt; .05). Standard-of-care antibiotic linezolid rescued 38% of animals. However, linezolid and aerophages did not synergize in this setting (55% survival).ConclusionsAerosolized phage therapy showed potential for the treatment of MRSA pneumonia in an experimental animal model and warrants further investigation for application in humans.
Human Rights and Investor–State Dispute Settlement Reform: Fitting a Square Peg into a Round Hole?
Authors: Duggal Kabir A N , Diamond Nicholas J 
Published: February 2021

ABSTRACT
Investor–State dispute settlement (ISDS) is undergoing a seismic shift, not least regarding its relationship with human rights. We apply the three ‘generations’ of human rights framework to ISDS reform, underscoring fundamental tensions between ISDS and human rights considerations. The resultant tensions are as varied as calls for reform spanning, inter alia, permissive human rights provisions in international investment agreements, inconsistent State practices regarding human rights in model agreements, and case law that largely ignores human rights considerations. We acknowledge these tensions, noting where they persist, as well as where the seeds of reform have already been sewn. We contend that ongoing ISDS reform efforts provide opportunities to infuse the ISDS architecture with a newfound emphasis on all generations of human rights, thereby overcoming many of the persistent tensions that have previously encumbered efforts to develop synergies between ISDS and international human rights law.
A review of anti-tumour effects of ginsenoside in gastrointestinal cancer
Authors: Xu Jing , Pan Yunxia , Liu Yanyan , Na Sha , Zhou Hui , Li Lu , Chen Fengyuan , Song Hang 
Published: February 2021

Abstract

Objectives
Gastrointestinal cancer, one of the major causes of cancer-related deaths in the world, refers to malignant conditions of the gastrointestinal (GI) tract and other organs. Although conventional therapy has been successful to some extent in cancer treatment, drug resistance and cancer recurrence still limit the therapeutic efficacy. There is increasing evidence indicating that ginsenoside, as a kind of high nutritional value and widely used traditional Chinese medicine, could contribute to the promotion of treatment in GI cancer, which deserves further investigation.

Key findings
Based on previous studies, the possible mechanisms mainly include regulation of autophagy, apoptosis, proliferation, migration and angiogenesis. However, no studies recently have conducted a more in-depth review of the anti-cancer effects of ginsenoside in GI cancer.

Summary
Therefore, this review will summarise and analyse the latest developments in the anti-tumour effects of ginsenosides in GI cancer, thus may promote further research of the anti-tumour efficacy of ginsenoside.
Pulse Arrival Time Is Associated With Hemorrhagic Volume in a Porcine Model: A Pilot Study
Authors: Booth Gregory J , Cole Jacob , Geiger Phillip , Adams Jacob , Barnhill Joshua , Hughey Scott 
Published: February 2021

ABSTRACT

Background
Hemorrhage is a major cause of preventable death worldwide, and early identification can be lifesaving. Pulse wave contour analysis has previously been used to infer hemodynamic variables in a variety of settings. We hypothesized that pulse arrival time (PAT), a form of pulse wave contour analysis which is assessed via electrocardiography (ECG) and photoplethysmography (PPG), is associated with hemorrhage volume.

Methods
Yorkshire-Cross swine were randomized to hemorrhage (30 mL/kg over 20 minutes) vs. control. Continuous ECG and PPG waveforms were recorded with a novel monitoring device, and algorithms were developed to calculate PAT and PAT variability throughout the respiratory cycle, termed “PAT index” or “PAT_I.” Mixed effects models were used to determine associations between blood loss and PAT and between blood loss and PAT_I to account for clustering within subjects and investigate inter-subject variability in these relationships.

Results
PAT and PAT_I data were determined for ∼150 distinct intervals from five subjects. PAT and PAT_I were strongly associated with blood loss. Mixed effects modeling with PAT alone was substantially better than PAT_I alone (R2 0.93 vs. 0.57 and Akaike information criterion (AIC) 421.1 vs. 475.5, respectively). Modeling blood loss with PAT and PAT_I together resulted in slightly improved fit compared to PAT alone (R2 0.96, AIC 419.1). Mixed effects models demonstrated significant inter-subject variability in the relationships between blood loss and PAT.

Conclusions
Findings from this pilot study suggest that PAT and PAT_I may be used to detect blood loss. Because of the simple design of a single-lead ECG and PPG, the technology could be packaged into a very small form factor device for use in austere or resource-constrained environments. Significant inter-subject variability in the relationship between blood loss and PAT highlights the importance of individualized hemodynamic monitoring.
20 yr of observations of PM 1-188: its chemical abundances and extraordinary kinematics
Authors: Peña Miriam , Hernández-Martínez Liliana , Ruiz-Escobedo Francisco 
Published: February 2021

ABSTRACT
The analysis of 20 yr of spectrophotometric data of the double-shell planetary nebula (PN) PM 1-188 is presented, aiming to determine the time evolution of the emission lines and the physical conditions of the nebula, as a consequence of the systematic fading of its [WC 10] central star whose brightness has declined by about 10 mag in the past 40 yr. Our main results include that the [O iii], [O ii], and [N ii] line intensities are increasing with time in the inner nebula as a consequence of an increase in electron temperature from 11 000 K in 2005 to more than 14 000 K in 2018, due to shocks. The intensities of the same lines are decreasing in the outer nebula, due to a decrease in temperature, from 13 000 to 7000 K, in the same period. The chemical compositions of the inner and outer shells are derived and they are similar. Both nebulae present subsolar O, S, and Ar abundances, while they are He, N, and Ne rich. For the outer nebula, the values are 12 + log He/H = 11.13 ± 0.05, 12 + log O/H = 8.04 ± 0.04, 12 + log N/H = 7.87 ± 0.06, 12 + log S/H = 7.18 ± 0.10, and 12 + log Ar = 5.33 ± 0.16. The O, S, and Ar abundances are several times lower than the average values found in disc non-Type I PNe, and are reminiscent of some halo PNe. From high-resolution spectra, an outflow in the N–S direction was found in the inner zone. Position–velocity diagrams show that the outflow expands at velocities in the −150 to 100 km s−1 range, and both shells have expansion velocities of about 40 km s−1.
A machine learning approach to measuring the quenched fraction of low-mass satellites beyond the Local Group
Authors: Baxter Devontae C , Cooper M C , Fillingham Sean P 
Published: February 2021

ABSTRACT
Observations suggest that satellite quenching plays a major role in the build-up of passive, low-mass galaxies at late cosmic times. Studies of low-mass satellites, however, are limited by the ability to robustly characterize the local environment and star formation activity of faint systems. In an effort to overcome the limitations of existing data sets, we utilize deep photometry in Stripe 82 of the Sloan Digital Sky Survey, in conjunction with a neural network classification scheme, to study the suppression of star formation in low-mass satellite galaxies in the local Universe. Using a statistically driven approach, we are able to push beyond the limits of existing spectroscopic data sets, measuring the satellite quenched fraction down to satellite stellar masses of ∼107 M⊙ in group environments (Mhalo = 1013−14 h−1 M⊙). At high satellite stellar masses (≳1010 M⊙), our analysis successfully reproduces existing measurements of the quenched fraction based on spectroscopic samples. Pushing to lower masses, we find that the fraction of passive satellites increases, potentially signalling a change in the dominant quenching mechanism at M⋆ ∼ 109 M⊙. Similar to the results of previous studies of the Local Group, this increase in the quenched fraction at low satellite masses may correspond to an increase in the efficacy of ram-pressure stripping as a quenching mechanism in groups.
Complex structure of a proto-brown dwarf
Authors: Riaz B , Machida M N 
Published: February 2021

ABSTRACT
We present ALMA 12CO (2–1), 13CO (2–1), C18O (2–1) molecular line observations of a very young proto-brown dwarf system, ISO-OPH 200. We have conducted physical+chemical modelling of the complex internal structure for this system using the core collapse simulations for brown dwarf formation. The model at an age of ∼6000 yr can provide a good fit to the observed kinematics, spectra, and reproduce the complex structures seen in the moment maps. Results from modelling indicate that 12CO emission is tracing an extended (∼1000au) molecular outflow and a bright shock knot, 13CO is tracing the outer (∼1000 au) envelope/pseudo-disc, and C18O is tracing the inner (∼500 au) pseudo-disc. The source size of ∼8.6 au measured in the 873-μm image is comparable to the inner Keplerian disc size predicted by the model. A 3D model structure of ISO-OPH 200 suggests that this system is viewed partially through a wide outflow cavity resulting in a direct view of the outflow and a partial view of the envelope/pseudo-disc. We have argued that ISO-OPH 200 has been mis-classified as a Class Flat object due to the unusual orientation. The various signatures of this system, notably, the young ∼616-yr outflow dynamical age and high outflow rate (∼1 × 10−7 M⊙ yr−1), silicate absorption in the 10-$\rm{\mu m}$ mid-infrared spectrum, pristine ISM-like dust in the envelope/disc, comparable sizes of the extended envelope and outflow, indicate that ISO-OPH 200 is an early Class 0 stage system formed in a star-like mechanism via gravitational collapse of a very low mass core.
Description of a new Late Cretaceous species ofBulimulusLeach, 1814 (Orthalicoidea: Bulimulidae) using geometric morphometric analysis
Authors: Cabrera Fernanda , Breure Abraham S H , Norbis Walter , Martínez Sergio 
Published: February 2021

ABSTRACTIn the Late Cretaceous fossil record of Uruguay, three morphotypes of Bulimulus (Bulimulidae) have been recorded: Bulimulus klappenbachi and two undescribed ones. A geometric morphometric analysis was conducted to show whether the three morphotypes represent one or more species. With this aim, the three fossils were compared with three extant species of the same genus: Bulimulus bonariensis, B. guadalupensis and B. rushi. Variability within and among these three well-known extant species was tested to evaluate differences in the fossil morphotypes. Twenty-eight landmarks were selected (9 permanent landmarks and 19 semi-landmarks) and principal component analysis and canonical variate analysis were performed. Results indicate that only one of the unnamed morphotypes can be described as a new species and that the other is a variant of B. klappenbachi. The latter fossil species is described as Bulimulus frenguellii n. sp.
Incidence of hyperaccumulation and tissue-level distribution of manganese, cobalt, and zinc in the genus Gossia (Myrtaceae)
Authors: Abubakari Farida , Nkrumah Philip Nti , Fernando Denise R , Brown Gillian K , Erskine Peter D , Echevarria Guillaume , van der Ent Antony 
Published: February 2021

Abstract
The rare phenomenon of plant manganese (Mn) hyperaccumulation within the Australian flora has previously been detected in the field, which suggested that the tree genus Gossia (Myrtaceae) might contain new Mn hyperaccumulators. We conducted the first growth experiment on Gossia using a multi-factorial dosing trial to assess Mn, cobalt (Co), and zinc (Zn) (hyper)accumulation patterns in selected Gossia species (G. fragrantissima and G. punctata) after a systematic assessment of elemental profiles on all holdings of the genus Gossia at the Queensland Herbarium using handheld X-ray fluorescence spectroscopy. We then conducted detailed in situ analyses of the elemental distribution of Mn, Co, Zn and other elements at the macro (organ) and micro (cellular) levels with laboratory- and synchrotron-based X-ray fluorescence microscopy (XFM). Gossia pubiflora and Gossia hillii were newly discovered to be Mn hyperaccumulator plants. In the dosing trial, G. fragrantissima accumulated 17 400 µg g−1 Mn, 545 µg g−1 Co, and 13 000 µg g−1 Zn, without signs of toxicity. The laboratory-based XFM revealed distinct patterns of accumulation of Co, Mn, and Zn in G. fragrantissima, while the synchrotron XFM showed their localization in foliar epidermal cells, and in the cortex and phloem cells of roots. This study combined novel analytical approaches with controlled experimentation to examine metal hyperaccumulation in slow-growing tropical woody species, thereby enabling insight into the phenomenon not possible through field studies.
Oligomeric quaternary structure of Escherichia coli and Mycobacterium smegmatis Lhr helicases is nucleated by a novel C-terminal domain composed of five winged-helix modules
Authors: Warren Garrett M , Wang Juncheng , Patel Dinshaw J , Shuman Stewart 
Published: February 2021

Abstract
Mycobacterium smegmatis Lhr (MsmLhr; 1507-aa) is the founder of a novel clade of bacterial helicases. MsmLhr consists of an N-terminal helicase domain (aa 1–856) with a distinctive tertiary structure (Lhr-Core) and a C-terminal domain (Lhr-CTD) of unknown structure. Here, we report that Escherichia coli Lhr (EcoLhr; 1538-aa) is an ATPase, translocase and ATP-dependent helicase. Like MsmLhr, EcoLhr translocates 3′ to 5′ on ssDNA and unwinds secondary structures en route, with RNA:DNA hybrid being preferred versus DNA:DNA duplex. The ATPase and translocase activities of EcoLhr inhere to its 877-aa Core domain. Full-length EcoLhr and MsmLhr have homo-oligomeric quaternary structures in solution, whereas their respective Core domains are monomers. The MsmLhr CTD per se is a homo-oligomer in solution. We employed cryo-EM to solve the structure of the CTD of full-length MsmLhr. The CTD protomer is composed of a series of five winged-helix (WH) modules and a β-barrel module. The CTD adopts a unique homo-tetrameric quaternary structure. A Lhr-CTD subdomain, comprising three tandem WH modules and the β-barrel, is structurally homologous to AlkZ, a bacterial DNA glycosylase that recognizes and excises inter-strand DNA crosslinks. This homology is noteworthy given that Lhr is induced in mycobacteria exposed to the inter-strand crosslinker mitomycin C.
Discovery and engineering of small SlugCas9 with broad targeting range and high specificity and activity
Authors: Hu Ziying , Zhang Chengdong , Wang Shuai , Gao Siqi , Wei Jingjing , Li Miaomiao , Hou Linghui , Mao Huilin , Wei Yanyan , Qi Tao , Liu Hongmao , Liu Dong , Lan Feng , Lu Daru , Wang Hongyan , Li Jixi , Wang Yongming 
Published: February 2021

Abstract
The compact CRISPR/Cas9 system, which can be delivered with their gRNA and a full-length promoter for expression by a single adeno-associated virus (AAV), is a promising platform for therapeutic applications. We previously identified a compact SauriCas9 that displays high activity and requires a simple NNGG PAM, but the specificity is moderate. Here, we identified three compact Cas9 orthologs, Staphylococcus lugdunensis Cas9 (SlugCas9), Staphylococcus lutrae Cas9 (SlutrCas9) and Staphylococcus haemolyticus Cas9 (ShaCas9), for mammalian genome editing. Of these three Cas9 orthologs, SlugCas9 recognizes a simple NNGG PAM and displays comparable activity to SaCas9. Importantly, we generated a SlugCas9-SaCas9 chimeric nuclease, which has both high specificity and high activity. We finally engineered SlugCas9 with mutations to generate a high-fidelity variant that maintains high specificity without compromising on-target editing efficiency. Our study offers important minimal Cas9 tools that are ideal for both basic research and clinical applications.
A ProQ/FinO family protein involved in plasmid copy number control favours fitness of bacteria carryingmcr-1-bearing IncI2 plasmids
Authors: Yang Jun , Wang Hai-Hong , Lu Yaoyao , Yi Ling-Xian , Deng Yinyue , Lv Luchao , Burrus Vincent , Liu Jian-Hua 
Published: February 2021

AbstractThe plasmid-encoded colistin resistance gene mcr-1 challenges the use of polymyxins and poses a threat to public health. Although IncI2-type plasmids are the most common vector for spreading the mcr-1 gene, the mechanisms by which these plasmids adapt to host bacteria and maintain resistance genes remain unclear. Herein, we investigated the regulatory mechanism for controlling the fitness cost of an IncI2 plasmid carrying mcr-1. A putative ProQ/FinO family protein encoded by the IncI2 plasmid, designated as PcnR (plasmid copy number repressor), balances the mcr-1 expression and bacteria fitness by repressing the plasmid copy number. It binds to the first stem-loop structure of the repR mRNA to repress RepA expression, which differs from any other previously reported plasmid replication control mechanism. Plasmid invasion experiments revealed that pcnR is essential for the persistence of the mcr-1-bearing IncI2 plasmid in the bacterial populations. Additionally, single-copy mcr-1 gene still exerted a fitness cost to host bacteria, and negatively affected the persistence of the IncI2 plasmid in competitive co-cultures. These findings demonstrate that maintaining mcr-1 plasmid at a single copy is essential for its persistence, and explain the significantly reduced prevalence of mcr-1 following the ban of colistin as a growth promoter in China.
Serum biomarkers of iron stores are associated with worse physical health-related quality of life in nondialysis-dependent chronic kidney disease patients with or without anemia
Authors: Guedes Murilo , Muenz Daniel , Zee Jarcy , Lopes Marcelo Barreto , Waechter Sandra , Stengel Bénédicte , Massy Ziad A , Speyer Elodie , Ayav Carole , Finkelstein Fredric , Sesso Ricardo , Pisoni Ronald L , Robinson Bruce M , Pecoits-Filho Roberto 
Published: February 2021

Abstract

Background
Iron deficiency (ID) is a common condition in nondialysis-dependent chronic kidney disease (NDD-CKD) patients that is associated with poorer clinical outcomes. However, the effect of ID on health-related quality of life (HRQoL) in this population is unknown. We analyzed data from a multinational cohort of NDD-CKD Stages 3–5 patients to test the association between transferrin saturation (TSAT) index and ferritin with HRQoL.

Methods
Patients from Brazil (n = 205), France (n = 2015) and the USA (n = 293) in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps, 2013–2019) were included. We evaluated the association of TSAT and ferritin (and functional and absolute ID, defined as TSAT ≤20% and ferritin ≥300 or &lt;50 ng/mL) on pre-specified HRQoL measures, including the 36-item Kidney Disease Quality of Life physical component summary (PCS) and mental component summary (MCS) as the primary outcomes. Models were adjusted for confounders including hemoglobin (Hb).

Results
TSAT ≤15% and ferritin &lt;50 ng/mL and ≥300 ng/mL were associated with worse PCS scores, but not with MCS. Patients with composite TSAT ≤20% and ferritin &lt;50 or ≥300 ng/mL had lower functional status and worse PCS scores than those with a TSAT of 20–30% and ferritin 50–299 ng/mL. Patients with a lower TSAT were less likely to perform intense physical activity. Adjustment for Hb only slightly attenuated the observed effects.

Conclusions
Low TSAT levels, as well as both low TSAT with low ferritin and low TSAT with high ferritin, are associated with worse physical HRQoL in NDD-CKD patients, even after accounting for Hb level. Interventional studies of iron therapy on HRQoL among NDD-CKD individuals are needed to confirm these findings.
Increased risk of ischaemic heart disease after kidney donation
Authors: Haugen Anders J , Hallan Stein , Langberg Nina E , Dahle Dag Olav , Pihlstrøm Hege , Birkeland Kåre I , Reisæter Anna V , Midtvedt Karsten , Hartmann Anders , Holdaas Hallvard , Mjøen Geir 
Published: February 2021

Abstract

Background
Previous reports suggest increased risk of hypertension and cardiovascular mortality after kidney donation. In this study we investigate the occurrence of ischaemic heart disease and cerebrovascular disease, diabetes and cancer in live kidney donors compared with healthy controls eligible for donation.

Methods
Different diagnoses were assessed in 1029 kidney donors and 16 084 controls. The diagnoses at follow-up were self-reported for the controls and registered by a physician for the donors. Stratified logistic regression was used to estimate associations with various disease outcomes, adjusted for gender, age at follow-up, smoking at baseline, body mass index at baseline, systolic blood pressure at baseline and time since the donation.

Results
The mean observation time was 11.3 years [standard deviation (SD) 8.1] for donors versus 16.4 years (SD 5.7) for controls. The age at follow-up was 56.1 years (SD 12.4) in donors versus 53.5 years (SD 11.1) in controls and 44% of donors were males versus 39.3% in the controls. At follow-up, 35 (3.5%) of the donors had been diagnosed with ischaemic heart disease versus 267 (1.7%) of the controls. The adjusted odds ratio for ischaemic heart disease was 1.64 (confidence interval 1.10–2.43; P = 0.01) in donors compared with controls. There were no significant differences for the risks of cerebrovascular disease, diabetes or cancer.

Conclusions
During long-term follow-up of kidney donors, we found an increased risk of ischaemic heart disease compared with healthy controls. This information may be important in the follow-up and selection process of living kidney donors.