bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative characterization of single cells and engineered heart tissues from hiPSC-derived cardiomyocyte subtypes
Authors: Li J , Wiesinger A , Fokkert L , Boukens B , Verkerk A , Christoffels V , Boink G , Devalla H
Published: June 2022

Funding Acknowledgements

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research council starting grant 714866 and associated proof-of-concept grant 899422

ZonMW and the Dutch Heart foundation MKMD grant 114021512 and Dutch Heart Foundation Dekker fellowship 2020T023

Rationale: Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes represent an excellent in vitro platform to study cardiac development and model patient-specific diseases. However, their widespread application in drug discovery and regenerative approaches has not yet been realized at least in part due to limited comparative characterization of the available cardiomyocyte subtypes and lack of multicellular models that allow assessment of physiologically relevant parameters.

Objective

Perform comprehensive characterization of hiPSC-derived sinoatrial nodal cardiomyocytes (SANCM), atrial cardiomyocytes (ACM) and ventricular cardiomyocytes (VCM) from 2D and 3D cultures.

Methods

SANCM, ACM and VCM were generated using directed differentiation protocols. Electrophysiological analysis was performed by single cell patch-clamp. Subtype-specific differences were further characterized by response to neurohumoral agents noradrenaline, and carbachol and If blocker ivabradine. Next, we generated EHTs to evaluate the effect of 3D culturing on cardiomyocyte subtypes and performed optical mapping. To establish a model to study impulse initiation and propagation in vitro, we generated binary EHTs (BIN-EHTs) composed of heteropolar ends of SANCM and ACM.

Results

Gene expression analysis and single cell electrophysiology confirmed identities of respective cardiomyocyte subtypes. While response to noradrenaline and carbachol were as expected, ivabradine testing showed the functional presence of pacemaker current If in ACM, besides SANCM. After three weeks in culture as EHTs, cardiac structural genes were markedly upregulated in all groups. Optical mapping demonstrated a three-fold increase in conduction velocities in ACM and VCM while SANCM EHTs retained slower conduction velocities recapitulating in vivo differences. In BIN-EHTs, SANCM end of the EHT consistently paced the tissues under baseline conditions. Upon treatment with ivabradine, cycle length of BIN-EHTs increased and impulse initiation switched to ACM end in the majority of tissues.

Conclusions

We performed comprehensive characterization of hiPSC-cardiomyocyte subtypes, which recapitulated salient features of their in vivo counterparts. BIN-EHT constructs composed of SANCM and ACM are a valuable rudimentary model for investigating impulse formation and propagation in vitro.
Helium conditioning increases cardiac fibroblast migration which effect is not propagated via soluble factors or extracellular vesicles
Authors: Kovacshazi C , Jelemensky M , Ferenczyova K , Hofbauerova M , Kiss B , Pallinger E , Kittel A , Sayour V N , Gorbe A , Hambalko SZ , Kindernay L , Barancik M , Ferdinandy P , Bartekova M , Giricz Z
Published: June 2022

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Project was supported by the National Research, Development and Innovation Office of Hungary

Background

Helium inhalation induces cardioprotection against ischemia/reperfusion injury, of which cellular mechanism is not fully elucidated. Extracellular vesicles (EVs) are cell-derived, nano-sized membrane vesicles which play role in cardioprotective mechanisms, but their function in helium-conditioning (HeC) is not elucidated.

Purpose

To investigate, how HeC affects cardiac fibroblasts and if their HeC-induced EVs or other secreted factors mediates remodeling of the cardiac tissue.

Methods

Neonatal rat cardiac fibroblasts (NRCF) were exposed to glucose deprivation and HeC rendered by four cycles of 95% helium + 5% CO2 for one hour, followed by one hour of normal culturing conditions. 40 hours later, NRCF migration was analyzed and Western Blot and quantitative PCR were used to analyze the expression of fibroblast to myofibroblast transformation markers. From the cell supernatant, medium-sized extracellular vesicles (mEVs) were isolated with differential centrifugation and analyzed with WB, transmission electron microscopy and nanoparticle tracking analysis. Supernatant of HeC-treated NRCF was transferred to naïve NRCF or immortalized human umbilical vein endothelia cells (HUVEC/TERT2) and migration and in vitro angiogenesis assay was performed.

Results

HeC accelerated the migration of NRCF. Meanwhile, HeC did not increase the expression of myofibroblast markers. HeC tended to decrease mEV secretion of NRCFs, but supernatant of HeC-NRCF neither accelerate the migration of naïve NRCF, nor affect the angiogenic potential of HUVEC/TERT2.

Conclusion

Since HeC increased the migration of NRCF but HeC-NRCF mEVs did not affect the function of remote cells, HeC may exert its cardioprotective effect via NRCFs, but not affect cardiac remodeling remotely, via NRCF mEVs.
Diabetes impairs osteogenic differentiation of bone marrow mesenchymal stem cells
Authors: Chiva-Blanch G , Arderiu G , Vilahur G , Badimon L
Published: June 2022

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science and Innovation (MICINN)

Diabetes impairs osteogenic differentiation of bone marrow mesenchymal stem cells

Background

Diabetes is a severe metabolic condition that induces micro- and macrovascular disease, including atherosclerotic vascular disease, cutaneous lesions and bone necrosis. Whether it affects stem cell function is a matter of investigation. When the self-renewing capacity of mesenchymal stem cells (MSC) is compromised, their regenerative potential for cell therapy is impaired.

Purpose

We aimed to investigate the effects of diabetes on bone marrow- mesenchymal stem cells (BM-MSC) transcriptomics to evidence their potential for differentiation.

Methods

Bone marrow was extracted from femurs of Zucker rats, and BM-MSC were isolated by culturing adherent cells of extracted bone marrow in DMEM low glucose/ 20% FBS/ 1% P/S under hypoxic conditions (1% oxygen). After one week, MSC were characterized by flow cytometry.  Gene expression arrays were used to analyse the expression of BM-MSC of Zucker rats with diabetes (ZD) compared to those of lean-normoglycemic controls (ZC) with the same genetic background (n=6). Results were analysed in silico to identify significantly modified signalling pathways. In addition, BM-MSC differentiation into endothelial, adipogenic and osteogenic cells was investigated in vitro.

Results

95-99% of cells isolated from BM expressed CD90, a marker of MSC. Expression data analyses revealed a down-regulation of transcription factors related to the osteogenic pathway (Abcb1a, Adipoq, Fut1, Il1b, Kdr, Nes, Rhoa, Runx2, Tbx5, Tert and Tgfb3), and up-regulation of adipogenic- and angiogenic-related genes such as Bmp7, Casp3, Cd44, Csf2, Erbb2, Gdf7, Il10, Mcam, Nt5e, Pparg, Sox2, Vegfa and Vwf, in BM-MSC from animals with diabetes compared to lean controls. Concomitantly, BM-MSC from rats with diabetes showed impaired osteogenic differentiation in vitro compared to lean controls. No significant differences in adipogenesis or endothelial differentiation were observed between BM-MSC of rats with diabetes and lean controls.

Conclusions

Diabetes down-regulates several factors involved in the osteogenic differentiation pathway resulting in impaired osteogenesis. The imbalance in gene expression and MSC differentiation may partially explain the impaired regenerative capacity in diabetes.
Liraglutide treatment attenuates dysfunction-related changes in the cardiac and cerebral microvasculature in streptozotocin-induced diabetic rats
Authors: Korn A , Baylan U , Emmens RW , Schalkwijk CG , Niessen HWM , Krijnen PAJ , Simsek S
Published: June 2022

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): Novo Nordisk

Background

Diabetes mellitus (DM) induces cardiac and cerebral microvascular dysfunction via increased glycation, oxidative stress and endothelial activation. Liraglutide, a glucagon-like peptide-1 receptor analogue, inhibited the reactive oxygen species producing enzyme NOX2 and adhesion molecules in isolated endothelial cells. Here we have studied how Liraglutide affects advanced glycation, NOX expression and inflammatory status of the cardiac and cerebral microvasculature in vivo in diabetic rats.

Methods

DM was induced in Sprague Dawley rats (n=15) via intraperitoneal streptozotocin (STZ) injection (60 mg/kg body weight). 10 control rats remained non-diabetic. From day 9 post-STZ injection, Liraglutide (200 µg/kg bodyweight; n=7) or vehicle (n=8) was injected subcutaneously daily until termination on day 29. The advanced glycation end-product N-ε-(carboxymethyl)lysine (CML), NOX2, NOX4, ICAM-1 and VCAM-1 were subsequently analysed using immunohistochemistry and quantified to compare Liraglutide treatment to placebo.

Results

DM increased CML, NOX2, ICAM-1 and VCAM-1 in the intramyocardial vasculature, although not significant for NOX2. NOX4 was not significantly increased in the ventricles and absent in the atria. In the cerebral vasculature, CML, NOX2 and NOX4 were significantly increased, but not ICAM-1 and VCAM-1. Liraglutide significantly reduced the DM-associated CML accumulation and expression of NOX2, ICAM-1 and VCAM-1 in the intramyocardial, and CML, NOX2 and NOX4 in the cerebral vasculature. Liraglutide had these effects without changing blood glucose levels or body weight.

Conclusions

Our study implies that Liraglutide protects the cardiac and cerebral microvasculature against diabetes-induced dysfunction, independent of a blood glucose lowering effect in a type 1 diabetes rat model.
Hypoxia-inducible factors: roles in cardiovascular disease progression, prevention, and treatment
Authors: Semenza Gregg L
Published: June 2022

Hypoxia-inducible factors (HIF)-1 and HIF-2 are master regulators of oxygen homeostasis that regulate the expression of thousands of genes in order to match O2 supply and demand. A large body of experimental data links HIF activity to protection against multiple disorders affecting the cardiovascular system: ischemic cardiovascular disease (including coronary artery disease and peripheral artery disease), through collateral blood vessel formation and preconditioning phenomena; emphysema; lymphedema; and lung transplant rejection. In these disorders, strategies to increase the expression of one or both HIFs may be of therapeutic utility. Conversely, extensive data link HIFs to the pathogenesis of pulmonary arterial hypertension and drugs that inhibit one or both HIFs may be useful in treating this disease.
Heart in a shell—a cascade of classical findings: a case report
Authors: Khan Hafiz Muhammad Waqas , Munir Ahmad , Sud Anup , Moza Ankush
Published: June 2022

Background

Idiopathic chronic constrictive pericarditis (CP) is an uncommon yet very important clinical entity as prompt diagnosis and early treatment are affiliated with improved outcomes. We describe an uncommon case of CP with a series of textbook findings and received successful treatment with surgical pericardiectomy (SP).

Case summary

A 58-year-old male presented to the emergency department with exertional dyspnoea and anasarca. The past medical history was negative for infections like tuberculosis, viral, etc., connective tissue disease, prior cardiac surgery, human immunodeficiency virus, or any radiation therapy. The vital signs were within normal limits except mild hypoxia while the physical examination was consistent with congestive heart failure. Further investigations with laboratory testing, imaging with chest X-ray, computed tomography, echocardiogram, and invasive study with right heart catheterization were all consistent with idiopathic chronic CP. The patient underwent successful SP with significant improvement in clinical condition.

Discussion

This case highlights the classical signs and symptoms along with important diagnostic features of CP. It is uncommon to see all the classical features of CP in one patient as described in the above case. Familiarity with these findings is crucial to make the diagnosis as early treatment is affiliated with improved outcomes.
Development of a Controlled Laboratory-scale Inoculation System to Study Vibrio parahaemolyticus-oyster Interactions
Authors: Hines Ian S , Smith Stephen A , Kuhn David D , Stevens Ann M
Published: June 2022

Prevalence of seafood-borne gastroenteritis caused by the human pathogen Vibrio parahaemolyticus is increasing globally despite current preventative measures. The United States Centers for Disease Control have designated V. parahaemolyticus as a reportable emerging human pathogen. The Eastern oyster (Crassostrea virginica) is a natural reservoir of the bacterium in marine environments, but little is actually known regarding interactions between oysters and V. parahaemolyticus. Therefore, a laboratory-scale Biosafety Level-2 (BSL2) inoculation system was developed wherein Chesapeake Bay region oysters harvested during summer or winter months, were exposed to the clinical RIMD2210633 strain carrying a chloramphenicol-selective marker (VP RIMDmC). Homogenized whole oyster tissues were spread on selective and differential agar medium to measure viable VP RIMDmC levels. Endogenous Vibrio spp. cell numbers were significantly reduced followed chloramphenicol treatment and this likely contributed to higher VP RIMDmC oyster-associated levels, especially using winter-harvested animals. Summer-harvested oysters had significantly higher existing Vibrio levels and a lower level of artificial oyster-associated VP RIMDmC. Thus, the pre-existing microbiome appears to afford some protection from an external V. parahaemolyticus challenge. Overall, this system successfully enabled controlled manipulation of parameters influencing V. parahaemolyticus–oyster interactions and will be useful in safely testing additional pertinent environmental variables and potential mitigation strategies.
Mantle dynamics of the North China Craton: new insights from mantle transition zone imaging constrained by P-to-S receiver functions
Authors: Liu Lin , Gao Stephen S , Liu Kelly H , Griffin William L , Li Sanzhong , Tong Siyou , Ning Jieyuan
Published: June 2022

Cratons are generally defined as stable continental blocks with a strong cratonic root that typically is at least ∼200 km thick. Many cratons have undergone little internal tectonism and destruction since their formation, but some of them, such as the eastern part of the North China Craton (NCC), the Dharwar Craton and the Wyoming Craton, have lost their thick cratonic root and become reactivated in recent geological history, leading to widespread Meso-Cenozoic volcanisms. The mechanisms responsible for such decratonization remain debated. To provide new constraints on models leading to decratonization, in this study we stack 612 854 source-normalized P-to-S conversions (receiver functions or RFs) from the 410 and 660 km discontinuities (d410 and d660, respectively) bordering the mantle transition zone (MTZ) recorded at 1986 stations in the NCC. Both the number of RFs and the number of stations are unprecedented in the study area. The average apparent depths of the d410 and d660 and the thickness of the MTZ are 413 ± 6, 669 ± 8 and 255 ± 6 km, respectively. A depression of up to 37 km and mean 11 km of the d660 are clearly observed beneath the eastern NCC, mainly caused by the possible existence of a relatively large amount of water in the MTZ. Our study provides strong observational evidence for geodynamic modelling that suggests water in the MTZ can be driven out into the upper mantle by poloidal mantle flow induced by the subduction and retreat of subducted oceanic slabs. The results are consistent with the weakening of the lithosphere beneath the eastern NCC by the release of water (in the form of structurally bound H/OH) brought down to the MTZ by subduction of the Pacific slab. Continuous slab dehydration and the ascent of fluids would have triggered intraplate volcanism and mantle upwelling in the eastern NCC, as evidenced by the spatial correspondence among the lower-than-normal upper-mantle seismic velocities, unusually large depressions of the d660, Cenozoic basaltic volcanism and thinning of the cratonic lithosphere.
Mobility of FLOWERING LOCUS T protein as a systemic signal in trifoliate orange and its low accumulation in grafted juvenile scions
Authors: Wu Yan-Mei , Ma Yu-Jiao , Wang Min , Zhou Huan , Gan Zhi-Meng , Zeng Ren-Fang , Ye Li-Xia , Zhou Jing-Jing , Zhang Jin-Zhi , Hu Chun-Gen
Published: June 2022

The long juvenile period of perennial woody plants is a major constraint in breeding programs. FLOWERING LOCUS T (FT) protein is an important mobile florigen signal that induces plant flowering. However, whether FT can be transported in woody plants to shorten the juvenile period is unknown, and its transport mechanism remains unclear. In this study, trifoliate orange FT (ToFT) and Arabidopsis FT (AtFT, which has been confirmed to be transportable in Arabidopsis) as a control were transformed into tomato and trifoliate orange, and early flowering was induced in the transgenic plants. Long-distance and two-way (upward and downward) transmission of ToFT and AtFT proteins was confirmed in both tomato and trifoliate orange using grafting and western blot analysis. However, rootstocks of transgenic trifoliate orange could not induce flowering in grafted wild-type juvenile scions because of the low accumulation of total FT protein in the grafted scions. It was further confirmed that endogenous ToFT protein was reduced in trifoliate orange, and the accumulation of the transported ToFT and AtFT proteins was lower than that in grafted juvenile tomato scions. Furthermore, the trifoliate orange FT-INTERACTING PROTEIN1 homolog (ToFTIP1) was isolated by yeast two-hybrid analysis. The FTIP1 homolog may regulate FT transport by interacting with FT in tomato and trifoliate orange. Our findings suggest that FT transport may be conserved between the tomato model and woody plants. However, in woody plants, the transported FT protein did not accumulate in significant amounts in the grafted wild-type juvenile scions and induce the scions to flower.
Primary Microbial Succession in the Anchialine Ecosystem
Authors: Sterling James J , Sakihara Troy S , Brannock Pamela M , Pearson Zoe G , Maclaine Kendra D , Santos Scott R , Havird Justin C
Published: June 2022

Synopsis

When new land is created, initial microbial colonization lays the foundation for further ecological succession of plant and animal communities. Primary microbial succession of new aquatic habitats formed during volcanic activity has received little attention. The anchialine ecosystem, which includes coastal ponds in young lava flows, offers an opportunity to examine this process. Here, we characterized microbial communities of anchialine habitats in Hawaii that were created during volcanic eruptions in 2018. Benthic samples from three habitats were collected ∼2 years after their formation and at later time points spanning ∼1 year. Sequence profiling (16S and 18S) of prokaryotic and eukaryotic communities was used to test whether communities were similar to those from older, established anchialine habitats, and if community structure changed over time. Results show that microbial communities from the new habitats were unlike any from established anchialine microbial communities, having higher proportions of Planctomycetota and Chloroflexi but lower proportions of green algae. Each new habitat also harbored its own unique community relative to other habitats. While community composition in each habitat underwent statistically significant changes over time, they remained distinctive from established anchialine habitats. New habitats also had highly elevated temperatures compared to other habitats. These results suggest that idiosyncratic microbial consortia form during early succession of Hawaiian anchialine habitats. Future monitoring will reveal whether the early communities described here remain stable after temperatures decline and macro-organisms become more abundant, or if microbial communities will continue to change and eventually resemble those of established habitats. This work is a key first step in examining primary volcanic succession in aquatic habitats and suggests young anchialine habitats may warrant special conservation status.
Delirium prediction in the ICU: designing a screening tool for preventive interventions
Authors: Bhattacharyya Anirban , Sheikhalishahi Seyedmostafa , Torbic Heather , Yeung Wesley , Wang Tiffany , Birst Jennifer , Duggal Abhijit , Celi Leo Anthony , Osmani Venet
Published: June 2022

Introduction

Delirium occurrence is common and preventive strategies are resource intensive. Screening tools can prioritize patients at risk. Using machine learning, we can capture time and treatment effects that pose a challenge to delirium prediction. We aim to develop a delirium prediction model that can be used as a screening tool.

Methods

From the eICU Collaborative Research Database (eICU-CRD) and the Medical Information Mart for Intensive Care version III (MIMIC-III) database, patients with one or more Confusion Assessment Method-Intensive Care Unit (CAM-ICU) values and intensive care unit (ICU) length of stay greater than 24 h were included in our study. We validated our model using 21 quantitative clinical parameters and assessed performance across a range of observation and prediction windows, using different thresholds and applied interpretation techniques. We evaluate our models based on stratified repeated cross-validation using 3 algorithms, namely Logistic Regression, Random Forest, and Bidirectional Long Short-Term Memory (BiLSTM). BiLSTM represents an evolution from recurrent neural network-based Long Short-Term Memory, and with a backward input, preserves information from both past and future. Model performance is measured using Area Under Receiver Operating Characteristic, Area Under Precision Recall Curve, Recall, Precision (Positive Predictive Value), and Negative Predictive Value metrics.

Results

We evaluated our results on 16 546 patients (47% female) and 6294 patients (44% female) from eICU-CRD and MIMIC-III databases, respectively. Performance was best in BiLSTM models where, precision and recall changed from 37.52% (95% confidence interval [CI], 36.00%–39.05%) to 17.45 (95% CI, 15.83%–19.08%) and 86.1% (95% CI, 82.49%–89.71%) to 75.58% (95% CI, 68.33%–82.83%), respectively as prediction window increased from 12 to 96 h. After optimizing for higher recall, precision and recall changed from 26.96% (95% CI, 24.99%–28.94%) to 11.34% (95% CI, 10.71%–11.98%) and 93.73% (95% CI, 93.1%–94.37%) to 92.57% (95% CI, 88.19%–96.95%), respectively. Comparable results were obtained in the MIMIC-III cohort.

Conclusions

Our model performed comparably to contemporary models using fewer variables. Using techniques like sliding windows, modification of threshold to augment recall and feature ranking for interpretability, we addressed shortcomings of current models.
Complications and surgical treatment after pathological fracture associated to HIV secondary disease. A case report
Authors: Fuentes-Sánchez Jorge , Gómez-Barrena Enrique
Published: June 2022

Due to advances in retroviral treatment, human immunodeficiency virus (HIV)-related disease may become chronic and the patient survival has substantially increased. Osteoarticular disease in those patients include multifocal osteonecrosis and its complications. Pain and functional limitation may be due to these complications, frequently underdiagnosed, including pathological fractures. Its prompt management may require a different approach than osteosynthesis. We present a long-term chronic HIV patient with severe pain and limitation. A tibial plateau pathological fracture associated to multifocal osteonecrosis was identified and treated with osteonecrosis debridement and total knee arthroplasty (TKA). Acute periprosthetic joint infection developed and required debridement, antibiotic and implant retention. The contralateral knee, also with multiple osteonecrosis foci, was managed with early TKA. We highlight the importance of timely surgical reconstruction to avoid serious limitation and complications.
Stellar graveyards: clustering of compact objects in globular clusters NGC 3201 and NGC 6397
Authors: Vitral Eduardo , Kremer Kyle , Libralato Mattia , Mamon Gary A , Bellini Andrea
Published: June 2022

We analyse Gaia EDR3 and re-calibrated HST proper motion data from the core-collapsed and non-core-collapsed globular clusters NGC 6397 and NGC 3201, respectively, with the Bayesian mass-orbit modelling code MAMPOSSt-PM. We use Bayesian evidence and realistic mock data sets constructed with Agama to select between different mass models. In both clusters, the velocities are consistent with isotropy within the extent of our data. We robustly detect a dark central mass (DCM) of roughly $1000\, \rm M_\odot$ in both clusters. Our MAMPOSSt-PM fits strongly prefer an extended DCM in NGC 6397, while only presenting a mild preference for it in NGC 3201, with respective sizes of a roughly one and a few per cent of the cluster effective radius. We explore the astrophysics behind our results with the CMC Monte Carlo N-body code, whose snapshots best matching the phase space observations lead to similar values for the mass and size of the DCM. The internal kinematics are thus consistent with a population of hundreds of massive white dwarfs in NGC 6397, and roughly 100 segregated stellar-mass black holes in NGC 3201, as previously found with CMC. Such analyses confirm the accuracy of both mass-orbit modelling and Monte Carlo N-body techniques, which together provide more robust predictions on the DCM of globular clusters (core-collapsed or not). This opens possibilities to understand a vast range of interesting astrophysical phenomena in clusters, such as fast radio bursts, compact object mergers, and gravitational waves.
Mapping the aliphatic hydrocarbon content of interstellar dust in the Galactic plane
Authors: Günay B , Burton M G , Afşar M , Schmidt T W
Published: June 2022

We implement a new observational method for mapping the aliphatic hydrocarbon content in the solid phase in our Galaxy, based on spectrophotometric imaging of the 3.4 $\mu$m absorption feature from interstellar dust. We previously demonstrated this method in a field including the Galactic Centre cluster. We applied the method to a new field in the Galactic Centre where the 3.4 $\mu$m absorption feature has not been previously measured and we extended the measurements to a field in the Galactic plane to sample the diffuse local interstellar medium, where the 3.4 $\mu$m absorption feature has been previously measured. We have analysed 3.4 $\mu$m optical depth and aliphatic hydrocarbon column density maps for these fields. Optical depths are found to be reasonably uniform in each field, without large source-to-source variations. There is, however, a weak trend towards increasing optical depth in a direction towards b = 0° in the Galactic Centre. The mean value of column densities and abundances for aliphatic hydrocarbon were found to be about several $\rm \times 10^{18} \, cm^{-2}$ and several tens × 10−6, respectively for the new sightlines in the Galactic plane. We conclude that at least 10–20 per cent of the carbon in the Galactic plane lies in aliphatic form.
Observational signatures of black hole accretion: rotating versus spherical flows with tilted magnetic fields
Authors: Jia(贾 赫) He , White Christopher J , Quataert Eliot , Ressler Sean M
Published: June 2022

We study the observational signatures of magnetically arrested black hole accretion with non-rotating inflow on to a rotating black hole; we consider a range of angles between the black hole spin and the initial magnetic field orientation. We compare the results of our general relativistic magneto-hydrodynamic simulations to more commonly used rotating initial conditions and to the Event Horizon Telescope (EHT) observations of M87. We find that the mm intensity images, polarization images, and synchrotron emission spectra are very similar among the different simulations when post-processed with the same electron temperature model; observational differences due to different electron temperature models are significantly larger than those due to the different realizations of magnetically arrested accretion. The orientation of the mm synchrotron polarization is particularly insensitive to the initial magnetic field orientation, the electron temperature model, and the rotation of the inflowing plasma. The largest difference among the simulations with different initial rotation and magnetic tilt is in the strength and stability of the jet; spherical inflow leads to kink-unstable jets. We discuss the implications of our results for current and future EHT observations and for theoretical models of event-horizon-scale black hole accretion.
Relic jet activity in ‘Hanny’s Voorwerp’ revealed by the LOFAR two metre sky survey
Authors: Smith D J B , Krause M G , Hardcastle M J , Drake A B
Published: June 2022

We report new observations of ‘Hanny’s Voorwerp’ (hereafter HV) taken from the second data release of the LOFAR Two-metre Sky Survey (LoTSS). HV is a highly-ionized region in the environs of the galaxy IC2497, first discovered by the Galaxy Zoo project. The new 150 MHz observations are considered in the context of existing multi frequency radio data and archival narrow-band imaging from the Hubble Space Telescope, centred on the [O iii] emission line. The combined sensitivity and spatial resolution of the LoTSS data – which far exceed what was previously available at radio frequencies – reveal clear evidence for large-scale extended emission emanating from the nucleus of IC2497. The radio jet appears to have punched a hole in the neutral gas halo, in a region co-located with HV. The new 150 MHz data, alongside newly-processed archival 1.64 GHz eVLA data, reveal that the extended emission has a steep spectrum, implying an age >108 yr. The jet supplying the extended 150 MHz structure must have ‘turned off’ long before the change in X-ray luminosity reported in recent works. In this picture, a combination of jet activity and the influence of the radiatively efficient active galactic nucleus are responsible for the unusual appearance of HV.
The musca molecular cloud: The perfect ‘filament’ is still a sheet
Authors: Tritsis A , Bouzelou F , Skalidis R , Tassis K , Enßlin T , Edenhofer G
Published: June 2022

The true three-dimensional (3D) morphology of the Musca molecular cloud is a topic that has received significant attention lately. Given that Musca does not exhibit intense star-formation activity, unveiling its shape has the potential to also reveal crucial information regarding the physics that dictates the formation of the first generation of stars within molecular clouds. Here, we revisit the shape of Musca and we present a comprehensive array of evidence pointing towards a shape that is extended along the line-of-sight dimension: (a) 3D maps of differential extinction; (b) new non-local thermodynamic equilibrium radiative transfer simulations of CO rotational transitions from a sheet-like, magnetically dominated simulated cloud; (c) an effective/critical density analysis of available CO observations; and (d) indirect consequences that a filamentary structure would have had, from a theoretical star-formation perspective. We conclude that the full collection of observational evidence strongly suggests that Musca has a sheet-like geometry.
Receipt of Baseline Laboratory Testing Recommended by the HIV Medicine Association for People Initiating HIV Care, United States, 2015–2019
Authors: Weiser John , Tie Yunfeng , Lu Jen-Feng , Colasanti Jonathan A , Fanfair Robyn Neblett , Beer Linda
Published: June 2022

Background

The HIV Medicine Association of the Infectious Disease Society of America publishes Primary Care Guidance for Persons with Human Immunodeficiency Virus. We assessed receipt of recommended baseline tests among newly diagnosed patients initiating HIV care.

Methods

The Medical Monitoring Project is a Centers for Disease Control and Prevention survey designed to produce nationally representative estimates of behavioral and clinical characteristics of adults with diagnosed HIV in the United States. We analyzed data for 725 participants in the 2015–2019 data collection cycles who received an HIV diagnosis within the past 2 years and had ≥1 HIV provider visit. We estimated the prevalence of having recommended tests after the first HIV provider visit and between 3 months before and 3/6 months after the first HIV provider visit and estimated prevalence differences of having 4 combinations of tests by sociodemographic and clinical characteristics.

Results

Within 6 months of care initiation, HIV monitoring tests were performed for 91.3% (95% CI, 88.7%–93.8%) of patients; coinfection blood tests, 27.5% (95% CI, 22.5%–32.4%); site-based STI tests, 59.7% (95% CI, 55.4%–63.9%); and blood chemistry and hematology tests, 50.8% (95% CI, 45.8%–55.8%). Patients who were younger, gay, or bisexual were more likely to receive site-based STI tests, and patients receiving care at Ryan White HIV/AIDS Program (RWHAP)–funded facilities were more likely than patients at non-RWHAP-funded facilities to receive all test combinations.

Conclusions

Receipt of recommended baseline tests among patients initiating HIV care was suboptimal but was more likely among patients at RWHAP-funded facilities. Embedding clinical decision support in HIV provider workflow could increase recommended baseline testing.
Outcomes of Cytomegalovirus Viremia Treatment in Critically Ill Patients With COVID-19 Infection
Authors: Schoninger Scott , Dubrovskaya Yanina , Marsh Kassandra , Altshuler Diana , Prasad Prithiv , Louie Eddie , Weisenberg Scott , Hochman Sarah , Fridman David , Trachuk Polina
Published: June 2022

Background

Patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU) have poor outcomes and frequently develop comorbid conditions, including cytomegalovirus (CMV) reactivation. The implications of CMV reactivation in this setting are unknown. We aimed to investigate if treatment of CMV viremia improved in-hospital mortality in ICU patients with COVID-19.

Methods

In this single-center retrospective study, we analyzed clinical outcomes in patients diagnosed with COVID-19 pneumonia and CMV viremia admitted to an ICU from March 1, 2020, to April 30, 2021, who either received treatment (ganciclovir and/or valganciclovir) or received no treatment. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were total hospital length of stay (LOS), ICU LOS, requirement for extracorporeal membrane oxygenation (ECMO) support, duration of mechanical ventilation (MV), and predictors of in-hospital mortality.

Results

A total of 80 patients were included, 43 patients in the treatment group and 37 in the control group. Baseline characteristics were similar in both groups. CMV-treated patients were more likely to test positive for CMV earlier in their course, more likely to be on ECMO, and received higher total steroid doses on average. In-hospital mortality was similar between the 2 groups (37.2% vs 43.2.0%; P = .749). There was no significant difference in hospital LOS, though CMV-treated patients had a longer ICU LOS.

Conclusions

Treatment of CMV viremia did not decrease in-hospital mortality in ICU patients with COVID-19, but the sample size was limited. CMV viremia was significantly associated with total steroid dose received and longer ICU stay.
Are Patients and Their Providers Talking About Long-Acting Injectable Antiretroviral Therapy? Penetration into Clinical Encounters at Three U.S. Care Sites
Authors: Christopoulos Katerina A , Colasanti Jonathan , Johnson Mallory O , Diaz Tsuzuki Manami , Erguera Xavier A , Flores Rey , Kerman Jared , Dance Kaylin , Sauceda John A , Neilands Torsten B , Dilworth Samantha E , Koester Kimberly A , Gutierrez Jose , Schneider John A , Montgomery Elizabeth , McNulty Moira C
Published: June 2022

Use of long-acting injectable antiretroviral therapy depends on patient awareness, provider discussion, and patient willingness to use. We conducted a postvisit survey with patients at 3 HIV clinics in San Francisco, Chicago, and Atlanta in May 2021 to assess for inequities in these early implementation phases.
Habitat edges influence the distribution of nest predators for Seaside Sparrows, but not nest placement or success
Authors: Newsome Corina D , Hunter Elizabeth A
Published: June 2022

Nest failure for coastal marsh bird species is primarily caused by predation and nest flooding. As sea level rise makes nest flooding more likely, the threat of nest predation will constrain the potential adaptive responses of marsh nesting species. Thus, understanding the predictors of nest predation is important for the conservation of salt marsh-dwelling bird species, such as the Seaside Sparrow (Ammospiza maritima). Predator activity may be influenced by landscape features (particularly habitat edges), potentially making nest predation predictable. We aimed to understand the predictability of Seaside Sparrow nest predation relative to two major landscape features: roads and tidal rivers, as both of these edges may be entryways or attractants for predators in marshes. In coastal Georgia, USA, we assessed mammalian predator activity relative to the two features of interest, and hypothesized that mammalian predator activity would be greater close to roads and tidal rivers. We also recorded Seaside Sparrow nest locations and nest predation events and hypothesized that nest predation events would increase with increasing predator activity. Consistent with our first hypothesis, mammalian predator activity increased close to roads and tidal rivers, but mammalian predator distribution did not explain the spatial variation in Seaside Sparrow nest predation thus not supporting our second hypothesis. Seaside Sparrows also placed their nests in locations with high mammalian predator activity, indicating that the ability to avoid nesting in high-risk areas may be constrained by habitat or resource limitations. Additionally, mammals may not be the primary nest predators, as we found that one bird species—Marsh Wren (Cistothorus palustris)—contributed substantially to nest predation rates. Understanding the predictability of mammalian predator distribution can allow for focused predator management efforts, such as exclusion, to habitat edges where we found the highest mammalian predator activity, which could relax the constraint of nest predation on Seaside Sparrow’s ability to respond to the intensifying threat of sea level rise.
Defining resistance and tolerance traits in Covid-19: towards a stratified medicine approach
Authors: Russell C D , Clohisey Hendry S
Published: June 2022

Successful host defence against infectious disease involves resistance (reduce pathogen load) and tolerance (reduce tissue damage associated with pathogen presence). Integration of clinical, immunologic, genetic and therapeutic discoveries has identified defects in both of these responses in the progression from SARS-CoV-2 infection to life-threatening coronavirus disease 2019 (Covid-19) lung injury. Early after infection with SARS-CoV-2, resistance can be compromised by a failed type 1 interferon (IFN-I) response, due to direct viral antagonism of induction and signalling, deleterious host genetic variants (IFNAR2, IFNA10, TYK2 and PLSCR1), and neutralizing auto-antibodies directed against IFN-I (predominantly IFN-α). Later in the disease, after pathogen sensing has activated a pro-inflammatory response, a failure to appropriately regulate this response compromises tolerance resulting in virus-independent immunopathology involving the lung and reticuloendothelial system. Monocytes are activated in the periphery (involving M-CSF, GM-CSF, IL-6, NLRP1 inflammasomes, TYK2 and afucosylated anti-spike IgG) then recruited to the lung (involving CCR2::MCP-3/MCP-1 and C5a::C5aR1 axes) as pro-inflammatory monocyte-derived macrophages, resulting in inflammatory lung injury. Phenotypic and genotypic heterogeneity is apparent in all these responses, identifying ‘treatable traits’ (therapeutically relevant components of inter-individual variation) which could be exploited to achieve a stratified medicine approach to Covid-19. Overall, Covid-19 pathogenesis re-affirms the importance of resistance in surviving an infectious disease and highlights that tolerance is also a central pillar of host defence in humans and can be beneficially modified using host-directed therapies.
Changes on chest HRCT in systemic sclerosis-related interstitial lung disease after autologous haematopoietic stem cell transplantation
Authors: Pugnet Grégory , Petermann Antoine , Collot Samia , Otal Philippe , Lansiaux Pauline , Ait Abdallah Nassim , Lorillon Gwenaëlle , Resche-Rigon Mathieu , Borel Cécile , Marjanovic Zora , Farge Dominique ,   for the MATHEC-SFGM-TC network
Published: June 2022

Objective

To evaluate extent of interstitial lung disease (ILD) and oesophageal involvement using high-resolution computed tomography (HRCT) in early diffuse SSc patients after autologous haematopoietic stem cell transplantation (aHSCT).

Methods

Overall chest HRCT, lung function and skin score changes were evaluated in 33 consecutive diffuse SSc patients before and after aHSCT during yearly routine follow-up visits between January 2000 and September 2016. Two independent radiologists blindly assessed the ILD extent using semi-quantitative Goh and Wells method, the widest oesophageal diameter (WOD) and the oesophageal volume (OV) on HRCT. Patients were retrospectively classified as radiological responders or non-responders, based on achieved stability or a decrease of 5% or more of HRCT-ILD at 24 months post-aHSCT.

Results

Using a linear mixed model, the regressions of the extent of ILD and of ground glass opacities were significant at 12 months (ILD P = 0.001; ground glass opacities P = 0.0001) and at 24 months (ILD P = 0.007; ground glass opacities P = 0.0008) after aHSCT, with 18 patients classified as radiological responders (probability of response 0.78 [95% CI 0.58, 0.90]). Meanwhile the WOD and the OV increased significantly at 12 months (WOD P = 0.03; OV P = 0.34) and at 24 months (WOD P = 0.002; OV P = 0.007). Kaplan–Meier analyses showed a trend towards better 5-year survival rates (100% vs 60%; hazard ratio 0.23 [95% CI 0.03, 1.62], P = 0.11) among radiological responders vs non-responders at 24 month follow-up after aHSCT.

Conclusion

Real-world data analysis confirmed significant improvement in extent of HRCT SSc-ILD 24 months after aHSCT, although oesophageal dilatation worsened requiring specific attention.
The BILAG-2004 index is associated with development of new damage in SLE
Authors: Yee Chee-Seng , Gordon Caroline , Akil Mohammed , Lanyon Peter , Edwards Christopher J , Isenberg David A , Rahman Anisur , Teh Lee-Suan , Tosounidou Sofia , Stevens Robert , Prabu Athiveeraramapandian , Griffiths Bridget , McHugh Neil , Bruce Ian N , Ahmad Yasmeen , Khamashta Munther A , Farewell Vernon T
Published: June 2022

Objective

To determine whether BILAG-2004 index is associated with the development of damage in a cohort of SLE patients. Mortality and development of damage were examined.

Methods

This was a multicentre longitudinal study. Patients were recruited within 12 months of achieving fourth ACR classification criterion for SLE. Data were collected on disease activity, damage, SLE-specific drug exposure, cardiovascular risk factors, antiphospholipid syndrome status and death at every visit. This study ran from 1 January 2005 to 31 December 2017. Descriptive statistics were used to analyse mortality and development of new damage. Poisson regression was used to examine potential explanatory variables for development of new damage.

Results

A total of 273 SLE patients were recruited with total follow-up of 1767 patient-years (median 73.4 months). There were 6348 assessments with disease activity scores available for analysis. During follow-up, 13 deaths and 114 new damage items (in 83 patients) occurred. The incidence rate for development of damage was higher in the first 3 years before stabilizing at a lower rate. Overall rate for damage accrual was 61.1 per 1000 person-years (95% CI: 50.6, 73.8). Analysis showed that active disease scores according to BILAG-2004 index (systems scores of A or B, counts of systems with A and BILAG-2004 numerical score) were associated with development of new damage. Low disease activity (LDA) states [BILAG-2004 LDA and BILAG Systems Tally (BST) persistent LDA] were inversely associated with development of damage.

Conclusions

BILAG-2004 index is associated with new damage. BILAG-2004 LDA and BST persistent LDA can be considered as treatment targets.
Care to Persist: A Campaign to Ensure Nursing Student Success During A Time of Crisis
Authors: DeVaughn Valerie , Minnick Amy , Sherer Amy
Published: June 2022

Student persistence is crucial for preparing nurses to meet the demands of an ever-changing health care environment. The RN to BSN Online Degree Completion Option at a large for-profit university implemented the Care to Persist campaign in 2018 to support student persistence. This campaign evolved during the COVID-19 pandemic and has been a critical component in ensuring students’ success. First-term session-to-session persistence rates improved from 81.2 percent in May 2019 to 85.2 percent in May 2021. The campaign has been a beneficial strategy to care for students and ensure academic progression both before and during the pandemic.
Rapid Transition to Virtual Assessment and Treatment in an Interdisciplinary Randomized Clinical Trial for Youth With Chronic Pain
Authors: Shear Deborah , Harrison Lauren E. , O’Brien Shannon , Khazendar Zeena , Lyons Samuel , Morgan Jeffery J. , Chan Salinda K. , Feinstein Amanda B. , Simons Laura E.
Published: June 2022

Objectives:

COVID-19 abruptly halted in-person clinical care and research requiring a shift to virtual assessment and treatment. This unexpected transition of a 2-arm randomized controlled trial (RCT) examining interdisciplinary graded exposure treatment (GET Living) compared with multidisciplinary pain management for youth with chronic pain provided an opportunity to implement the first remotely delivered exposure treatment and remotely delivered biomechanical assessment for pediatric chronic pain. Here we describe these new approaches and provide lessons learned to inform future efforts in digital health care.

Methods:

A total of 68 youth (M=14.2 y; 80.9% female) were enrolled in the RCT (n=31 in-person, n=5 hybrid, n=32 virtual, n=9 withdrew). Of those withdrawn, n=3 withdrew due to COVID-19 related reasons. Some RCT elements required slight modification (eg, e-consent, actigraphy deployment, recruitment, and screening), while others were significantly altered (eg, session format and lab-based biomechanical assessment). Data from exit interviews were also examined to assess perspectives on the virtual format transition.

Results:

Results showed an increased enrollment rate when virtual care was an option (70.7%) compared with in-person (44.3%). Equivalent rates of completion for daily assessment (in-person, 72.8%; virtual, 73.3) were also observed, and participants described enhanced experience when able to complete exercises and exposures in their home environment during session (vs. a rehabilitation gym) allowing for genuine in vivo exposures (eg, household chores, riding bicycles).

Discussion:

Overall, our data demonstrate acceptability, feasibility, and equivalent patient engagement to virtual treatment. Novel methods implemented in this RCT can inform trial design and measures of clinical endpoints for future digital health interventions.