bluuebunny/crossref_metadata_2025 huggingface dataset:
On-chip converter of waveguide polarization mode to free-space optical angular momentum mode
Authors: liu Aiping , Peng Wei , Li Zirui , Zhou Xingping , Ren Xi-Feng , Zou Chang-Ling , Wang Qin
Published: December 2022

An integrated photonic device for converting on-chip waveguide modes to free-space optical angular momentum beams is proposed, which is composed of a polarization splitter rotator and a waveguide surface holographic grating. The output orbital angular momentum (OAM) state can be manipulated by the input polarization state. Therefore, the superposition of OAM states can be realized by controlling the on-chip input. According to the numerical results, the conversion efficiency of the transverse-magnetic (transverse-electric) mode to the optical angular momentum mode with l=−1(+1) is above 14% (18%), with the highest fidelity up to 0.84 and a working bandwidth of approximately 40 nm for a fidelity above 0.8. The proposed device provides a feasible information channel between the integrated optics and the free space and holds the potential for applications including the on-chip detection of the optical angular momentum beam.
Energetic electrons and their contribution to the breakdown of a point-plane air gap with a positive nanosecond pulse
Authors: Li Yutai , Fu Yangyang , Liu Zhigang , Wang Peng , Zou Xiaobing , Wang Xinxin
Published: December 2022

It is found that the polarity reversal phenomenon occurs in the nanosecond pulse breakdown experiment. Two-dimensional axisymmetric particle-in-cell/Monte Carlo collisions’ calculation is used to observe energetic electrons at positive nanosecond pulse voltage in atmospheric air and compared with previous calculation results under negative polarity in an attempt to explain the polarity reversal phenomenon. During the evolution of the positive polarity discharge, the difference in spatial net charge distribution leads to distortion of the electric field, which makes the electric field in the area of the ionization channel head very high, exceeding the threshold at which electrons can enter the high-energy state. The simulation results show that although electrons travel in the opposite direction to the ionization channel, energetic electrons can also be generated during the positive polarity discharge’s evolution, which may differ from what some researchers expected. However, it is also found that the maximum energy of energetic electrons under positive nanosecond pulse voltage is lower than that under negative nanosecond pulse voltage (only about 1/4). This may be mainly because in the case of positive polarity, the energetic electrons in the head of the ionization channel will move to the low-field intensity region inside the ionization channel and cannot be accelerated continuously. However, it must be pointed out that in the case of positive polarity, energetic electrons still contribute significantly to the rapid breakdown of the air gap. This study provides a deeper understanding of the physics of nanosecond pulse discharge.
Precise spatial structure impacts antimicrobial susceptibility of
S. aureus
in polymicrobial wound infections
Authors: Ibberson Carolyn B. , Barraza Juan P. , Holmes Avery L. , Cao Pengbo , Whiteley Marvin
Published: December 2022

A hallmark of microbial ecology is that interactions between members of a community shape community function. This includes microbial communities in human infections, such as chronic wounds, where interactions can result in more severe diseases.
Staphylococcus aureus
is the most common organism isolated from human chronic wound infections and has been shown to have both cooperative and competitive interactions with
Pseudomonas aeruginosa
. Still, despite considerable study, most interactions between these microbes have been characterized using in vitro well-mixed systems, which do not recapitulate the infection environment. Here, we characterized interactions between
S. aureus
and
P. aeruginosa
in chronic murine wounds, focusing on the role that both macro- and micro-scale spatial structures play in disease. We discovered that
S. aureus
and
P. aeruginosa
coexist at high cell densities in murine wounds. High-resolution imaging revealed that these microbes establish a patchy distribution, only occupying 5 to 25% of the wound volume. Using a quantitative framework, we identified a precise spatial structure at both the macro (mm)- and micro (µm)-scales, which was largely mediated by
P. aeruginosa
production of the antimicrobial 2-heptyl-4-hydroxyquinoline N-oxide, while the antimicrobial pyocyanin had no impact. Finally, we discovered that this precise spatial structure enhances
S. aureus
tolerance to aminoglycoside antibiotics but not vancomycin. Our results provide mechanistic insights into the biogeography of
S. aureus
and
P. aeruginosa
coinfected wounds and implicate spatial structure as a key determinant of antimicrobial tolerance in wound infections.
Repurposing a tricyclic antidepressant in tumor and metabolism disease treatment through fatty acid uptake inhibition
Authors: Chu Qiaoyun , An Jing , Liu Ping , Song Yihan , Zhai Xuewei , Yang Ronghui , Niu Jing , Yang Chuanzhen , Li Binghui
Published: December 2022

Fatty acid uptake is essential for cell physiological function, but detailed mechanisms remain unclear. Here, we generated an acetyl-CoA carboxylases (ACC1/2) double-knockout cell line, which lacked fatty acid biosynthesis and survived on serum fatty acids and was used to screen for fatty acid uptake inhibitors. We identified a Food and Drug Administration–approved tricyclic antidepressant, nortriptyline, that potently blocked fatty acid uptake both in vitro and in vivo. We also characterized underlying mechanisms whereby nortriptyline provoked lysosomes to release protons and induce cell acidification to suppress macropinocytosis, which accounted for fatty acid endocytosis. Furthermore, nortriptyline alone or in combination with ND-646, a selective ACC1/2 inhibitor, significantly repressed tumor growth, lipogenesis, and hepatic steatosis in mice. Therefore, we show that cells actively take up fatty acids through macropinocytosis, and we provide a potential strategy suppressing tumor growth, lipogenesis, and hepatic steatosis through controlling the cellular level of fatty acids.
How decreasing T cell signaling unexpectedly results in autoimmunity
Authors: Yi Jaeu , Hsieh Chyi-Song
Published: December 2022

In this issue of JEM, Tanaka et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20220386) advance our understanding of how genetic mutants that decrease T cell recognition of antigen, a critical event for immune activation to invading microbes and virus, paradoxically results in autoimmunity.
The wake of a rectangular flat plate
Authors: Montes Gomez E , Sumner D
Published: December 2022

The mean wake of a three-dimensional surface-mounted rectangular flat plate was studied experimentally in a low-speed wind tunnel for four different aspect (height-to-width) ratios, AR = 3, 2, 1, and 0.5. The Reynolds number based on the plate width was Re = 3.8 × 104 and the boundary layer thickness on the ground plane, relative to the plate width, was δ/W = 1.1. The incidence angle of the plate was varied from α = 0° (where the plate is normal to the flow) to α = 90° (where the plate is parallel to the flow). The mean velocity and vorticity fields in the wake were measured using a seven-hole pressure probe. At α = 0°, the length of the recirculation zone behind the plate becomes progressively shorter as the aspect ratio is lowered and follows the same tendency as that of a finite square prism. The wakes of the slenderer flat plates of AR = 3 and 2 are characterised by two pairs of streamwise vortices: a pair of tip vortices in the upper wake and a pair of ground-plane vortices on the lower edges of the wake. With increasing incidence angle, a single tip vortex comes to dominate the wake, secondary vorticity is induced at various locations, a ‘traffic light’ vortex pattern may form, and ultimately a familiar wing-tip (trailing) vortex develops. In contrast, flow downstream of the less slender flat plates of AR = 1 and 0.5 is characterised by a single pair of large streamwise vortices, which become asymmetric with increasing incidence. Close to the flat plate of AR = 0.5, and at small incidence angles only, a unique pair of small inner vorticity concentrations, of opposite sense of rotation to the main streamwise vortices, is found in the upper part of the wake.
Study on new process of electroless copper plating pretreatment on carbon fiber surface
Authors: Hui Wang Qing , Song Li Xue
Published: December 2022

In general, conventional carbon fiber surface pretreatment, with palladium, silver, and other precious metals as activators, increases its surface activity by initiating redox reactions for metallization, whereas it exhibits a high cost and poor economy. In this study, copper-nickel mixed colloids with low cost served as the activators, and sodium borohydride (NaBH4) and sodium hydroxide (NaOH) were employed as sensitizing reducing agents to successfully plate copper on the surface of carbon fibers. Subsequently, the morphology of the treated samples was characterized through SEM and XPS to explore the pretreatment process of the carbon fiber surface. The results indicated that the carbon fiber exhibited the optimal debinding effect at 55°C and the heating time was longer than 120 min. The result indicated that coarsening effect of 65% concentrated nitric acid was the optimal. The activation effect of copper-nickel mixed colloid was the optimal, and the surface quality of the coating was the optimal.
Building robust machine learning models for small chemical science data: the case of shear viscosity of fluids
Authors: Avula Nikhil V S , Veesam Shivanand Kumar , Behera Sudarshan , Balasubramanian Sundaram
Published: December 2022

Shear viscosity, though being a fundamental property of all fluids, is computationally expensive to calculate from equilibrium molecular dynamics simulations. Recently, machine learning (ML) methods have been used to augment molecular simulations in many contexts, thus showing promise to estimate viscosity too in a relatively inexpensive manner. However, ML methods face significant challenges—such as overfitting, when the size of the data set is small, as is the case with viscosity. In this work, we train seven ML models to predict the shear viscosity of a Lennard–Jones fluid, with particular emphasis on addressing issues arising from a small data set. Specifically, the issues related to model selection, performance estimation and uncertainty quantification were investigated. First, we show that the widely used performance estimation procedure of using a single unseen data set shows a wide variability—in estimating the errors on—small data sets. In this context, the common practice of using cross validation (CV) to select the hyperparameters (model selection) can be adapted to estimate the generalization error (performance estimation) as well. We compare two simple CV procedures for their ability to do both model selection and performance estimation, and find that k-fold CV based procedure shows a lower variance of error estimates. Also, these CV procedures naturally lead to an ensemble of trained ML models. We discuss the role of performance metrics in training and evaluation and propose a method to rank the ML models based on multiple metrics. Finally, two methods for uncertainty quantification—Gaussian process regression (GPR) and ensemble method—were used to estimate the uncertainty on individual predictions. The uncertainty estimates from GPR were also used to construct an applicability domain using which the ML models provided even more reliable predictions on an independent viscosity data set generated in this work. Overall, the procedures prescribed in this work, together, lead to robust ML models for small data sets.
Protein biosynthesis at the ER: finding the right accessories
Authors: Shao Sichen
Published: December 2022

More than 30% of eukaryotic proteins contain domains that must translocate across or integrate into the endoplasmic reticulum (ER) membrane. With few exceptions, protein translocation and transmembrane domain integration at the ER require the conserved Sec61 translocon. Decades of studies have established a clear mechanistic model for how the Sec61 translocon functions. The biosynthesis of distinct subsets of proteins at the ER also involves accessory factors that interact with the Sec61 translocon and translocating nascent proteins. However, assigning specific functions to many translocon accessory factors has been a persistent challenge in the field. This Perspective discusses recent insights into mechanisms that promote protein biosynthesis at the ER through accessory factors that directly regulate the Sec61 translocon or chaperone nascent proteins within the ER membrane. These translocon accessory factor functions, and more still to be discovered, are essential for producing a diverse and high-fidelity proteome at the ER.
The great compromise
Authors: Ritchie Donald A.
Published: December 2022

“The great compromise” examines how the constitutional convention shaped the nature of Congress. This resulted in a proportionally representative House of Representatives and an equality of the states in the Senate. Without this “Great Compromise” the framers of the Constitution would have been unable to progress and there would be no Constitution. The rejection of a parliamentary model and the way Congress has developed and the respective roles of the House of Representatives and the Senate are set in the context of the wider Constitution. Compromise, negotiation, and bipartisanship are all key elements in the life of the U.S. Congress.
Performance of a parasitic plant and its effects on hosts depends on the interactions between parasite seed family and host species
Authors: Moncalvillo Belén , Matthies Diethart
Published: December 2022

Root hemiparasitic plants act as keystone species influencing plant community composition through their differential suppression of host species. Their own performance also strongly depends on interactions with host species. However, little is known about the roles of parasite genetic variation vs. plasticity in these interactions. We grew plants from eight maternal families of the root hemiparasite Rhinanthus alectorolophus with six potential host species (two grasses, two legumes and two forbs) and without a host and measured fitness-related and morphological traits of the parasite, host biomass and overall productivity. Parasite biomass and other traits showed strong plastic variation in response to different host species, but were also affected by parasite maternal family. Parasite seed families responded differently to the hosts, indicating genetic variation that could serve as the basis for adaptation to different host plants. However, there were no negative correlations in the performance of families across different hosts, indicating that R. alectorolophus has plastic generalist genotypes and is not constrained in its use of different host species by trade-offs in performance. Parasite effects on host biomass (which may indicate virulence) and total productivity (host + parasite biomass) depended on the specific combination of parasite family and host species. Mean biomass of hosts with a parasite family and mean biomass of that family tended to be negatively correlated, suggesting selection for maximum resource extraction from the hosts. Specialization of generalist root hemiparasites may be restricted by a lack of trade-offs in performance across hosts, together with strong spatial and temporal variation in host species availability. The genetic variation in the effects on different hosts highlights the importance of genetic diversity of hemiparasites for their effects on plant community structure and productivity and for the success of using them to restore grassland diversity.
Efficient computation of contributional diversity metrics from microbiome data with FuncDiv
Authors: Douglas Gavin M , Kim Sunu , Langille Morgan G I , Shapiro B Jesse
Published: December 2022

Motivation

Microbiome datasets with taxa linked to the functions (e.g. genes) they encode are becoming more common as metagenomics sequencing approaches improve. However, these data are challenging to analyze due to their complexity. Summary metrics, such as the alpha and beta diversity of taxa contributing to each function (i.e. contributional diversity), represent one approach to investigate these data, but currently there are no straightforward methods for doing so.

Results

We addressed this gap by developing FuncDiv, which efficiently performs these computations. Contributional diversity metrics can provide novel insights that would be impossible to identify without jointly considering taxa and functions.

Availability and implementation

FuncDiv is distributed under a GNU Affero General Public License v3.0 and is available at https://github.com/gavinmdouglas/FuncDiv.

Supplementary information

Supplementary data are available at Bioinformatics online.
Reviewing knowledgebase and database grant proposals in the life sciences: the role of innovation
Authors: Karp Peter D
Published: December 2022

This article offers thoughts on reviewing grant proposals for biological knowledgebases and databases (KDs) in the hope of aiding grant reviewers and applicants in addressing the issue of innovation. Assessing such grant proposals involves a number of subtleties that are worthy of discussion, particularly for new reviewers and applicants. In part, this article is motivated by the release of two funding opportunity announcements by the US National Institutes of Health concerning KDs. We find that the amount of innovation required for different KD projects can vary significantly, particularly depending on where in its life cycle a given project is. Strong innovation is not necessarily required to have an impactful KD project. For example, PubMed has low innovation but high impact. The importance of innovation should be weighted differently for different KD projects depending on the challenges they face and their maturity. The score for the overall impact of a grant proposal might have little dependence on the innovation score, such as for a mature project that is already delivering strong impact.
Effectiveness and feasibility of cardiovascular disease personalized prevention on high polygenic risk score subjects: a randomized controlled pilot study
Authors: Viigimaa Margus , Jürisson Mikk , Pisarev Heti , Kalda Ruth , Alavere Helene , Irs Alar , Saar Aet , Fischer Krista , Läll Kristi , Kruuv-Käo Krista , Mars Nina , Widen Elisabeth , Ripatti Samuli , Metspalu Andres
Published: December 2022

Aims

The aim of this study was to evaluate the effect of the intervention by proactively sharing a patient’s high polygenic risk score (PRS) for coronary artery disease (CAD). Outcomes included: (i) reduction in cardiovascular disease (CVD) risk factors over 12 months; (ii) difference in purchased prescriptions of lipid-lowering and anti-hypertensive drugs between intervention group and control group subjects; and (iii) opinion of the participating physicians and subjects on PRS usefulness.

Methods and results

This randomized controlled trial was conducted among middle-aged subjects with a top 20% CAD PRS in a family medicine setting. Participants were selected from 26 953 Estonian Biobank cohort participants. Subjects were informed and counselled about their PRS score and CAD risk using the visual tool at baseline (Visit I), counselling session (Visit II), and on the final Visit III at 12 months. The primary endpoint was not significantly different. However, the intervention group participants had a significantly higher probability of initiating statin treatment compared with the controls. Their levels of LDL-cholesterol (LDL-C) were significantly decreased compared with baseline on Visit III and significantly lower than in the control group. The vast majority of participating family physicians believe that finding out about genetic risks will affect the subject’s lifestyle and medication compliance.

Conclusion

Most of our outcome measures were in favour of this intervention. Participants achieved larger changes in cholesterol and blood pressure values. The vast majority (98.4%) of family physicians are interested in continuing to use genetic risk assessment in practice.
66 MYOCARDIAL EDEMA CONTRIBUTES TO INTERSTITIAL EXPANSION AND ASSOCIATES WITH MECHANICAL AND ELECTROCARDIOGRAPHIC CHANGES IN TAKOTSUBO SYNDROME: A CMR T1 AND T2 MAPPING STUDY
Authors: Arcari Luca , Camastra Giovanni , Ciolina Federica , Limite Luca Rosario , Danti Massimiliano , Ansalone Gerardo , Musumeci Beatrice , Sclafani Matteo , Sbarbati Stefano , Cacciotti Luca
Published: December 2022

Background

myocardial edema has a central role in takotsubo syndrome (TTS). Relationships between edema, mechanical and electrical abnormalities in TTS are still elusive.

Methods

n=32 hospitalized TTS patients and n=23 controls were analyzed. We performed cardiac magnetic resonance (CMR) with tissue mapping for the assessment of edema and interstitial expansion, global longitudinal (GLS) and circumferential strain (GCS) were evaluated by CMR feature-tracking. Twelve-lead ECGs were recorded at the time of CMR in TTS patients, aVR voltage, negative T-wave voltage and QTc length were calculated.

Results

mean age of the TTS cohort was 72±12-year-old, 94% women, undergoing CMR at a median of 4 days (interquartile range 2, 6) after hospital admission. Compared with controls, patients had increased LV mass (55±11 g/m2 vs 46±8 g/m2, p<0.001), worse left ventricular ejection fraction (LVEF), GLS and GCS (all p<0.001), higher septal native T1 (1116±73 msec vs 970±23 msec, p<0.001), T2 (56±5 msec vs 46±2 msec, p<0.001) and extra-cellular volume (ECV) fraction (32±5% vs 24±1%, p<0.001). TTS patients had higher apicobasal gradient of T2 values (12±6 msec vs 2±6 msec, p<0.001), basal LV wall displayed higher native T1, T2 and ECV (all p<0.002) but similar circumferential strain against controls (-23±3% vs -24±4%, p=0.351). In the TTS cohort, septal T2 value showed significant correlations with native T1 (r=0.609, p<0.001), ECV (r=0.689, p<0.001), LVEF (r=-0.459, p=0.008) and aVR voltage (r=-0.437, p<0.05). Negative T waves voltage and QTc length significantly correlated with apicobasal T2 mapping gradient (r=0.499, p=0.007 and r=0.372, p=0.047 respectively) but not with other tissue mapping measurements.

Conclusions

CMR T1 and T2 mapping demonstrated increased myocardial water content conditioning interstitial expansion in acute TTS. Myocardial edema was detected even outside areas of abnormal wall motion, its burden and distribution associated with mechanical and electrocardiographic changes, making it a potential prognostic marker and therapeutic target in TTS.
839 DAPAGLIFOZIN AND INTIMA-MEDIA TICKNESS IN TYPE II DIABETIC PATIENTS
Authors: Lamaida Norman , Cerciello Antonio
Published: December 2022

Background

Carotid Doppler ultrasonography (USG) is widely used to measure haemodynamic parameters, such as Intima–Media Thickness (IMT) and blood flow velocities (i.e. Peak–Systolic Velocity [PSV], End–Diastolic Velocity [EDV], and Resistive Index [RI]). Dapaglifozin (SGLT2i) have been shown to reduce the risk of cardiovascular disease in type 2 diabetes (T2DM) patients. SGLT2i is a sodium–glucose co–transporter 2 inhibitor that reduces renal glucose reabsorption, thus increasing urinary glucose excretion. This leads to sustained systolic and diastolic blood pressure reduction, through natriuresis. We hypothesized that this agent would also reduce arterial stiffness. AIM: The purpose of this study was to evaluate cardiovascular disease risk indirectly through USG of carotid artery vascular markers in T2DM patients using dapagliflozin.

Methods and Results

40 patients presenting to our clinic between march 2019 and march 2021 and diagnosed with T2DM were included in the study. These were divided into two groups : 1) a dapagliflozin group of 20 patients and 2) 20 patients non–dapagliflozin control group. Velocity parameters were: peak–systolic velocity (PSV), end–diastolic velocity (EDV), pulsatility index (PI), resistive index (RI). Examination was performed on distal portion of CCA, and we took the mean of both CCA. The mean duration of follow–up was 2.0 years. Mean ages were 55 ± 10 years in the dapagliflozin group and 50 ± 10 in the control group. Common carotid artery, PSV, and EDV parameters were higher while RI was lower (p < 0.01), in the dapagliflozin group than in the control group. Vascular resistance was lower in the group using dapagliflozin for diabetes management. In addition In the dapagliflozin group, the IMT decreased after dapagliflozin therapy (P < 0.01).

Conclusions

haemodynamic parameters were better performing in the group using dapagliflozin for diabetes management. Finally SGLT2i can decrease the IMT in patients with T2DM, which is closely related to cardiovascular benefit in patients with T2DM.
3 SAFETY OF NOVEL ORAL ANTICOAGULANTS COMPARED TO VITAMIN K ANTAGONISTS IN THE TREATMENT OF VENOUS THROMBOEMBOLISM: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Ridolfi Lorenzo , Masini Gabriele , Castiglione Vincenzo , Gentile Francesco , Favilli Marco , Mazzola Matteo , Lepone Attilio , Scalera Silvia Teresa , Italiano Andrea , Negro Francesco , Guarini Giacinta , Ricci Fabrizio , Renda Giulia , De Caterina Raffaele , Morrone Doralisa
Published: December 2022

Background

Individual randomized controlled trials (RCTs) enrolling patients with venous thromboembolism (VTE) have demonstrated that novel oral anticoagulants (NOACs) are comparable to vitamin K antagonists (VKAs) in reducing the risk of recurrent VTE but hold a safer bleeding profile. Nonetheless, pooled data from RCTs on the safety of NOACs versus VKAs in patients with VTE are still scarce.

Purpose

We aimed to compare the effect of NOACs versus VKA on the risk of fatal bleeding, major bleeding, clinically relevant non-major bleeding (CRNMB) and any bleeding in patients with VTE through a meta-analysis of RCTs.

Methods

We performed a systematic review of the literature, from January 1970 to December 2021, using PubMed database with four independent reviewers (L.R.; G.M.; V.C.; F.G.). Discrepancies were solved by consensus with a senior researcher (D.M.). Phase 3 randomized controlled trials comparing NOACs versus VKAs, either as an acute treatment or as an extended therapy, in patients with pulmonary embolism or deep vein thrombosis were selected. We performed a meta-analysis using a random-effects model with the Mantel–Haenszel method for each safety endpoint. Study outcomes were expressed as odd ratios (OR) with 95% confidence interval (CI) and illustrated in a Forest plot diagram. A two-sided p-value <0.05 was considered statistically significant. Heterogeneity was tested using the I2-statistic.

Results

Seven trials were included (n=29,879 patients), either investigating the direct thrombin inhibitor dabigatran (RE-COVER, RE-COVER II and RESONATE trials) or the factor Xa inhibitors rivaroxaban (EINSTEIN-DVT and EINSTEIN-PE studies), apixaban (AMPLIFY study) and edoxaban (Hokusai-VTE study). Compared to VKAs, treatment with NOACs was associated with lower risk of fatal bleeding (OR 0.35; 95% CI 0.16-0.81), major bleeding (OR 0.60; 95% CI 0.45-0.80), and any bleeding (OR 0.62; 95% CI 0.54-0.72) - fig. 1. There was no significant difference between the two groups concerning the risk of CRNMB.

Conclusions

In patients with VTE, treatment with NOACs was associated with fewer bleeding complications compared with VKAs.
Lipomatous metaplasia prolongs repolarization and increases repolarization dispersion within post-infarct ventricular tachycardia circuit cites
Authors: Xu Lingyu , Zahid Sohail , Khoshknab Mirmilad , Moss Juwann , Berger Ronald D , Chrispin Jonathan , Callans David , Marchlinski Francis E , Zimmerman Stefan L , Han Yuchi , Desjardins Benoit , Trayanova Natalia , Nazarian Saman
Published: December 2022

Aims

Post-infarct myocardium contains viable corridors traversing scar or lipomatous metaplasia (LM). Ventricular tachycardia (VT) circuitry has been separately reported to associate with corridors that traverse LM and with repolarization heterogeneity. We examined the association of corridor activation recovery interval (ARI) and ARI dispersion with surrounding tissue type.

Methods and results

The cohort included 33 post-infarct patients from the prospective Intra-Myocardial Fat Deposition and Ventricular Tachycardia in Cardiomyopathy (INFINITY) study. We co-registered scar and corridors from late gadolinium enhanced magnetic resonance, and LM from computed tomography with intracardiac electrogram locations. Activation recovery interval was calculated during sinus or ventricular pacing, as the time interval from the minimum derivative within the QRS to the maximum derivative within the T-wave on unipolar electrograms. Regional ARI dispersion was defined as the standard deviation (SD) of ARI per AHA segment (ARISD). Lipomatous metaplasia exhibited higher ARI than scar [325 (interquartile range 270–392) vs. 313 (255–374), P < 0.001]. Corridors critical to VT re-entry were more likely to traverse through or near LM and displayed prolonged ARI compared with non-critical corridors [355 (319–397) vs. 302 (279–333) ms, P < 0.001]. ARISD was more closely associated with LM than with scar (likelihood ratio χ2 50 vs. 12, and 4.2-unit vs. 0.9-unit increase in 0.01*Log(ARISD) per 1 cm2 increase per AHA segment). Additionally, LM and scar exhibited interaction (P < 0.001) in their association with ARISD.

Conclusion

Lipomatous metaplasia is closely associated with prolonged local action potential duration of corridors and ARI dispersion, which may facilitate the propensity of VT circuit re-entry.
Mixed origin of juvenile Atlantic cod (Gadus morhua) along the Swedish west coast
Authors: Henriksson Simon , Pereyra Ricardo T , Sodeland Marte , Ortega-Martinez Olga , Knutsen Halvor , Wennhage Håkan , André Carl
Published: December 2022

Cryptic population structure in exploited fishes poses a major challenge for fisheries management. In Atlantic cod, sympatric ecotypes are well-known, for instance off the coast of northern Norway. Recently, two sympatric cod ecotypes have also been documented in the Skagerrak and Kattegat, where adult cod has declined dramatically. One ecotype has an apparent offshore origin and displays a more migratory lifestyle than the other, which is generally resident at the coast throughout its life. To investigate their relative abundances along the Swedish west coast, juvenile cod were collected at high spatial resolution along the coast and genetically assigned to ecotypes. The results reveal large proportions of the coastal ecotype in the southern Kattegat, Öresund, and inshore Swedish Skagerrak, whereas the offshore ecotype dominates in offshore areas. A regression model comparison suggests that differences in bottom depth, rather than distance from the open sea, explain the heterogeneous spatial distribution of the two ecotypes. In addition, the two ecotypes display genetic differences suggesting adaptation to different environments. The results underline that successful fisheries management requires identification and consideration of locally adapted sympatric ecotypes.
Recognizing the Diverse Faces of Later Life: Old Age as a Category of Intersectional Analysis in Medical Ethics
Authors: Weßel Merle , Schweda Mark
Published: December 2022

Public and academic medical ethics debates surrounding justice and age discrimination often proceed from a problematic understanding of old age that ignores the diversity of older people. This article introduces the feminist perspective of intersectionality to medical ethical debates on aging and old age in order to analyze the structural discrimination of older people in medicine and health care. While current intersectional approaches in this field focus on race, gender, and sexuality, we thus set out to introduce aging and old age as an additional category that is becoming more relevant in the context of longer life expectancies and increasing population aging. We analyze three exemplary cases on the individual, institutional, and public health level, and argue that considering the intersections of old age with other social categories helps to accommodate the diverse identities of older people and detect inequality and structural discrimination.
Neuropathologic findings in a young woman 4 years following declaration of brain death: case analysis and literature review
Authors: Folkerth Rebecca D , Crary John F , Shewmon D Alan
Published: December 2022

Brain death (death by neurologic criteria) is declared in 2% of all in-hospital deaths in the United States. Published neuropathology studies of individuals maintained on cardiorespiratory support are generally decades old, and notably include only 3 cases with long intervals between brain and “somatic” death (68 days, 101 days, 20 years). Here, we share our observations in a young woman supported for nearly 4½ years following declaration of brain death after oropharyngeal surgery. While limited by tissue availability and condition, we found evidence of at least partial perfusion of the superficial cerebral and cerebellar cortices by external carotid and vertebral arteries (via meningeal and posterior pharyngeal branches), characterized by focal cellular reaction and organization. Dural venous sinuses had thrombosis and recanalization, as well as iron deposition. In nonperfused brain areas, tissue “mummification,” akin to that seen in certain postmortem conditions, including macerated stillbirths and saponification (adipocere formation), was identified, and are reviewed herein. Unfortunately, correlation with years-earlier clinical and radiographic observations was not possible. Nevertheless, we feel that our careful neuropathologic inspection of this case expands the understanding of the spectrum of human brain tissue alterations possible in a very rarely seen set of conditions.
X-shooter survey of young intermediate-mass stars – I. Stellar characterization and disc evolution
Authors: Iglesias Daniela P , Panić Olja , van den Ancker Mario , Petr-Gotzens Monika G , Siess Lionel , Vioque Miguel , Pascucci Ilaria , Oudmaijer René , Miley James
Published: December 2022

Intermediate-mass stars (IMSs) represent the link between low-mass and high-mass stars, and cover a key mass range for giant planet formation. In this paper, we present a spectroscopic survey of 241 young IMS candidates with IR-excess, the most complete unbiased sample to date within 300 pc. We combined VLT/X-Shooter spectra with BVR photometric observations and Gaia DR3 distances to estimate fundamental stellar parameters such as Teff, mass, radius, age, and luminosity. We further selected those stars within the intermediate-mass range 1.5 ≤ M⋆/M⊙ ≤ 3.5, and discarded old contaminants. We used 2MASS and WISE photometry to study the IR-excesses of the sample, finding 92 previously unidentified stars with IR-excess. We classified this sample into ‘protoplanetary’, ‘hybrid candidates’, and ‘debris’ discs based on their observed fractional excess at 12 $\mu$m, finding a new population of 17 hybrid disc candidates. We studied inner disc dispersal time-scales for $\lambda < 10 \,\mu$m and found very different trends for IMSs and low-mass stars (LMSs). IMSs show excesses dropping fast during the first 6 Myr independently of the wavelength, while LMSs show consistently lower fractions of excess at the shortest wavelengths, and increasingly higher fractions for longer wavelengths with slower dispersal rates. In conclusion, this study demonstrates empirically that IMSs dissipate their inner discs very differently than LMSs, providing a possible explanation for the lack of short period planets around IMSs.
New stellar velocity substructures from Gaia DR3 proper motions
Authors: Mikkola Daniel , McMillan Paul J , Hobbs David
Published: December 2022

Local stellar motions are expected, and have been shown, to include signatures of the Galaxy’s past dynamical evolution. These are typically divided into the disc, which shows the dynamical effects of spiral arms and the bar, and the stellar halo, with structures thought to be debris from past mergers. We use Gaia Data Release 3 to select large samples of these populations without limiting them to sources with radial velocities. We apply a penalized maximum likelihood method to these samples to determine the full 3D velocity distribution in Cartesian (U, V, and W) or spherical (vr, vϕ, and vθ) coordinates. We find that the disc population is dominated by four moving groups and also detect a new moving group at (U, V) = (−10, −15) km s−1 which we call MMH-0. For the stellar halo, we isolate the accreted component with cuts in transverse velocity and the colour–magnitude diagram. In this component, we find several known structures believed to be caused by past mergers, particularly one around (vr, vϕ, vθ) = (−150, −300, and −100) km s−1 appears more prominent than previously claimed. Furthermore, we also identify two new structures near (vr, vϕ, and vθ) = (225, 25, and 325) km s−1 and (0, 150, and −125) km s−1, which we refer to as MMH-1 and MMH-2, respectively. These results give new insights into local stellar motions and shows the potential of using samples that are not limited to stars with measured line-of-sight velocities, which is key to providing large samples of stars, necessary for future studies.
Detailed analysis of the variable star population in the globular cluster NGC 7006
Authors: Arellano Ferro A , Rojas Galindo F C , Bustos Fierro I H , Muneer S , Yepez M A , Giridhar Sunetra
Published: December 2022

A 5-yr CCD photometric VI time series of NGC 7006 is employed to perform a detailed analysis of the known population of variable stars. In the process, we have corrected inconsistent classifications, sky coordinates and found 10 new cluster member variables. An independent reddening estimate with a value E(B−V) = 0.08 ± 0.05 is made. Using Fourier decompositions of RR Lyrae light curves and well-established calibrations, the cluster mean metallicity and distance [Fe/H]ZW = −1.53 ± 0.15 and 41.2 ± 1.4 kpc are estimated based on an extended sample of cluster member RRab stars. Using the Gaia DR3 data, we performed an extensive membership analysis that leads to a clean colour–magnitude diagram, and hence to the identification of variables that are likely field stars, and to considerations on the variable distribution in the horizontal branch (HB). A double-mode RR Lyrae and three CW stars are discussed. The origin of CW stars from precursors in the blue tail of the HB with very thin (∼0.06 ± 0.01 M⊙) envelopes is argued. Our models indicate that the main-sequence predecessor of RR Lyrae stars had a mass of 0.82–0.85 M⊙ and lost about 25–35 per cent of its mass during the red giant branch events before settling in the HB some 12–13.5 Gyr later.
869. Oral Encochleated Amphotericin B for Cryptococcal Meningitis: a Phase II Randomized Trial
Authors: Atukunda Mucunguzi , Kagimu Enock , Rutakingirwa Morris K , Tugume Lillian , Nsangi Laura , Musubire Abdu , Gakuru Jane , Mugabi Timothy , Akampurira Andrew , Ssebambulidde Kenneth , Kasibante John , Ellis Jayne , Mpoza Edward , Williams Darlisha A , Fieberg Ann M , Skipper Caleb , Abassi Mahsa , Hullsiek Kathy Huppler , Meya David , Boulware David R
Published: December 2022

Background

Intravenous (IV) amphotericin B is the gold standard treatment of severe mycoses. A new orally absorbed, less-toxic formulation of amphotericin has been developed (Matinas Biopharma). We evaluated the efficacy of this novel anti-fungal agent amongst adults with cryptococcal meningitis.

Methods

We conducted a phase II randomized clinical trial testing oral encochleated amphotericin B (cAMB) versus IV amphotericin B for first episode cryptococcal meningitis in Kampala, Uganda from December 2020 to August 2021. Participants were HIV-positive, CSF cryptococcal antigen (CrAg) positive, and had the capacity to consent and take oral medications (GCS=15). Participants in the experimental arm received two loading doses of either IV deoxycholate amphotericin B 1.0 mg/kg/day or liposomal amphotericin 3 mg/kg/day, followed by 1.8g oral cAMB daily in 6 divided doses through 2 weeks with flucytosine (5FC) at 100mg/kg/day, and thereafter cAMB at 1.2g daily in 4 divided doses through 6 weeks. Participants in the control arm received 7 days of IV amphotericin B (deoxycholate or liposomal) with 5FC, then 7 days of fluconazole 1200mg/day. After 14 days, all participants received fluconazole 800mg/day through 10 weeks and thereafter a maintenance dose of 200mg/day.

Results

We randomized 40 participants to oral cAMB + 5FC and 30 control participants to IV amphotericin + 5FC. With cAMB the 30-day survival was 97.5% (39/40) and 18-week survival was 90% (36/40) compared with 87% (26/30) 18-week survival in IV amphotericin controls.

The CSF Early Fungicidal Activity (EFA) was lower with oral cAMB (mean EFA = 0.42 log10Cryptococcus CFU/mL/day; 95%CI, 0.29 to 0.54) versus IV amphotericin (mean EFA = 0.52 log10 CFU/mL/day; 95%CI, 0.39 to 0.66). Among those CSF culture positive at baseline, CSF sterility was achieved by 2 weeks in 65% (24/37) of cAMB participants and 68% (17/25) of controls.

Grade >=3 laboratory adverse events were more common with IV amphotericin. Grade 3–4 anaemia occurred in 10% (n=4) with cAMB versus 37% (n=11) with IV amphotericin. Grade 3 hypokalaemia (< 3mEq/L) occurred in 5% (n=2) with cAMB versus 27% (n=8) with IV amphotericin.

Conclusion

Novel oral cAMB appears to be a safe agent with promising efficacy for HIV-related cryptococcal meningitis.

Disclosures

All Authors: No reported disclosures.
1223. The Impact of the COVID-19 Pandemic on the Prevalence of Multidrug-resistant Organisms in Veterans Affairs Nursing Homes
Authors: Sajib Monirul I , Ford Florence M , Psevdos George
Published: December 2022

Background

Multidrug-resistant organisms (MDRO) in long-term care facilities are prevalent and pose a major health concern for their residents. During the COVID-19 pandemic, infection control measures were justifiably heightened in every aspect of health care, including nursing homes. There are reports depicting decreasing prevalence of MDRO in hospital settings during the pandemic. We compared the prevalence of MDRO in our facility’s nursing homes in the two-year period before vs. the two years of the pandemic.

Methods

Northport Veterans Affairs Medical Center provides long-term nursing home care structured as community living centers including mental health and hospice care; a 139 total bed capacity. A retrospective review of culture data collected by infection control preventionists comparing the prevalence of MDROs between 1 March 2018 to 28 February 2022 was performed. Data included: Nasopharyngeal MRSA swabs, urine, wound, blood, sputum cultures, C. difficile toxin and PCR assays. MDRO included ESBL E. coli, K. pneumoniae, P. mirabilis, MDR Pseudomonas spp (resistance to 2/3 antibiotics: cefepime/piperacillin-tazobactam/ciprofloxacin), carbapenem-resistant Pseudomonas spp, and vancomycin-resistant Enterococcus spp.

Results

There were 75209 bed days of care from 1 March 2018 to 28 February 2020 vs. 77531 from 1 March 2020 to 28 February 2022. The MRSA rate per 1000 patient days decreased from 4.98 pre-COVID to 2.70 during-COVID, P < 0.001. Similarly, there was a decrease in C. difficile 0.69 vs. 0.13, P< 0.001, ESBL E. coli 0.53 vs. 0.51, P< 0.001 and S. maltophilia (no cases during COVID). There was an increase in ESBL K. pneumoniae 0.51 vs. 0.63, P< 0.001, MDR Pseudomonas 0.05 vs. 0.49, P< 0.001, carbapenem-resistant Pseudomonas 0.026 vs. 0.077, P< 0.001 and VRE 0.22 vs. 0.31, P< 0.001. There were no Candida auris or Acinetobacter spp detected in the study period.

MDRO occurrences before and during COVID-19 pandemic

Conclusion

While increased awareness and implementation of infection control measures during the years of the COVID-19 pandemic led to decrease in certain infections in our nursing homes, like C. difficile, a surprising uptick in ESBL K. pneumoniae and MDR Pseudomonas was noted. This is a concerning trend that merits further study to identify molecular factors and increase stewardship efforts in diligent use of carbapenems.

Disclosures

All Authors: No reported disclosures.
1834. Evaluation of De-Escalation Options after Combination Daptomycin and Ceftaroline Therapy for Persistent MRSA Bacteremia
Authors: Carroll Ryan D , Brown Matthew L , Edwards William S , Stripling Joshua
Published: December 2022

Background

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia carries high mortality with limited treatment options. Studies over the last decade support glycolipopeptide and beta-lactam combination therapy with daptomycin (DAP) and ceftaroline (CFT) combination gaining prominence. While data supports de-escalation to monotherapy after bacteremia clearance it does not guide the choice of agent. With barriers including accessibility, cost, and tolerability of these agents, data is needed to optimize treatment. This study aims to evaluate de-escalation options after combination DAP/CFT therapy for persistent MRSA bacteremia.

Methods

A single-center, retrospective review of cases of persistent MRSA bacteremia (defined as greater than 72 hours on appropriate therapy) requiring escalation to DAP/CFT between 2014 and 2021 was performed. Details of bacteremia, source of infection, and comorbidities were assessed, and outcomes including recurrence of infection, infection-associated mortality, and tolerability were compared using exact Chi-square testing and univariant analysis.

Results

Sixty-six cases were identified of which 7 were de-escalated to vancomycin (VAN), 48 to DAP, 4 to CFT, and 7 continued DAP/CFT combination. Demographics and details of bacteremia such as prior anti-MRSA therapy, duration prior to DAP/CFT therapy, and source identification were similar between groups. Differences included higher rates of hemodialysis patients in the VAN group, higher rates of immunocompromised hosts in the DAP group, higher average Pitt bacteremia score in the DAP/CFT group, and lower rates of source control in the VAN group. Recurrence of infection (29% VAN, 13% DAP, 25% CFT) and infection-related mortality (14% VAN, 8% DAP) were higher in the VAN group (p=0.0452). In the DAP group 23% required change in therapy during their course. Univariant analysis assessing for confounding from comorbidities and source control yielded no significant associations.

Conclusion

This study is limited by small, uneven sample sizes but the results identify a trend of increased recurrence rates and mortality with de-escalation to VAN but tolerability concerns with DAP. More study is needed to guide clinical care and this data provides framework for future research.

Disclosures

All Authors: No reported disclosures.