bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of a strong 6.6 keV emission feature from EXO 1745−248 after the superburst in 2011 October
Authors: Iwakiri Wataru B , Serino Motoko , Mihara Tatehiro , Gu Liyi , Yamaguchi Hiroya , Shidatsu Megumi , Makishima Kazuo
Published: August 2021

We discover an unidentified strong emission feature in the X-ray spectrum of EXO 1745−248 obtained by RXTE at 40 hr after the peak of a superburst. The structure was centered at 6.6 keV and significantly broadened with a large equivalent width of 4.3 keV, corresponding to a line photon flux of 4.7 × 10−3 ph cm−2 s−1. The 3–20 keV spectrum was reproduced successfully by a power-law continuum with narrow and broad (2.7 keV in full width at half maximum) Gaussian emission components. Alternatively, the feature can be described by four narrow Gaussians, centered at 5.5 keV, 6.5 keV, 7.5 keV, and 8.6 keV. Considering the strength and shape of the feature, it is unlikely to have originated from reflection of the continuum X-rays by some optically thick material, such as an accretion disk. Moreover, the intensity of the emission structure decreased significantly with an exponential time scale of 1 hr. The feature was not detected in an INTEGRAL observation performed 10 hr before the RXTE observation with a line flux upper limit of 1.5 × 10−3 ph cm−2 s−1. The observed emission structure is consistent with gravitationally redshifted charge exchange emission from Ti, Cr, Fe, and Co. We suggest that the emission results from a charge exchange interaction between a highly metal-enriched fall-back ionized burst wind and an accretion disk, at a distance of ∼60 km from the neutron star. If this interpretation is correct, the results provide new information on nuclear burning processes during thermonuclear X-ray bursts.
Public Management and Authentic Innovation
Authors: Frederickson H George
Published: August 2021

This is the last of four Last Lectures delivered by George Frederickson before his death in 2020. In “Public Management and Authentic Innovation,” Frederickson draws on key studies to demythologize the claims around the origins and diffusion of innovation in the private and nonprofit sectors. He compares and contrasts the managed innovation model with a sustaining innovation model and provides provocative insights into the relevant contributions and limitations of rankings, awards and report cards; strategic planning; and the iron cage.
Affirmative Action, Mismatch, and Economic Mobility after California’s Proposition 209
Authors: Bleemer Zachary
Published: August 2021

Proposition 209 banned race-based affirmative action at California public universities in 1998. Using a difference-in-differences research design and a newly constructed longitudinal database linking all 1994–2002 University of California applicants to their educational experiences and wages, I show that ending affirmative action caused underrepresented minority (URM) freshman applicants to cascade into lower-quality colleges. The “mismatch hypothesis” implies that this cascade would provide net educational benefits to URM applicants, but their degree attainment declined overall and in STEM fields, especially among less academically qualified applicants. URM applicants’ average wages in their twenties and thirties subsequently declined, driven by declines among Hispanic applicants. These declines are not explained by URM students' performance or persistence in STEM course sequences, which were unchanged after Prop 209. Ending affirmative action also deterred thousands of qualified URM students from applying to any UC campus. Complementary regression discontinuity and institutional value-added analyses suggest that affirmative action’s net educational and wage benefits for URM applicants exceed its net costs for on-the-margin white and Asian applicants.
Automated design and implementation of a NOR gate in Pseudomonas putida
Authors: Tas Huseyin , Grozinger Lewis , Goñi-Moreno Angel , de Lorenzo Victor
Published: August 2021

Boolean NOR gates have been widely implemented in Escherichia coli as transcriptional regulatory devices for building complex genetic circuits. Yet, their portability to other bacterial hosts/chassis is generally hampered by frequent changes in the parameters of the INPUT/OUTPUT response functions brought about by new genetic and biochemical contexts. Here, we have used the circuit design tool CELLO for assembling a NOR gate in the soil bacterium and the metabolic engineering platform Pseudomonas putida with components tailored for E. coli. To this end, we capitalized on the functional parameters of 20 genetic inverters for each host and the resulting compatibility between NOT pairs. Moreover, we added to the gate library three inducible promoters that are specific to P. putida, thus expanding cross-platform assembly options. While the number of potential connectable inverters decreased drastically when moving the library from E. coli to P. putida, the CELLO software was still able to find an effective NOR gate in the new chassis. The automated generation of the corresponding DNA sequence and in vivo experimental verification accredited that some genetic modules initially optimized for E. coli can indeed be reused to deliver NOR logic in P. putida as well. Furthermore, the results highlight the value of creating host-specific collections of well-characterized regulatory inverters for the quick assembly of genetic circuits to meet complex specifications.
Intra-specific leaf trait variability ofF. sylvatica,Q. petraeaandP. abiesin response to inter-specific competition and implications for forest functioning
Authors: Serrano-León Hernán , Nitschke Renate , Scherer-Lorenzen Michael , Forrester David I
Published: August 2021

Variability in functional traits (FT) is increasingly used to understand the mechanisms behind tree species interactions and ecosystem functioning. In order to explore how FT differ due to interactions between tree species and its influence on stand productivity and other ecological processes, we examined the effects of tree species composition on the intra-specific variability of four widely measured FT: specific leaf area, leaf nitrogen content, leaf angle and stomatal conductance response to vapor pressure deficit. This study focused on three major central European tree species: European beech (Fagus sylvatica L.), Sessile oak (Quercus petraea Liebl.) and Norway spruce (Picea abies [L.] H. Karst.). Each species was examined in monoculture and two-species mixtures in the 13-year-old tree biodiversity experiment BIOTREE-Kaltenborn. Trait distributions and linear mixed models were used to analyze the effect of species mixing, tree size and stand variables on the intra-specific FT variability. A significant effect of branch height on most traits and species indicated a vertical gradient of foliar trait frequently related to light availability. Beech and oak showed a high overall trait variability and sensitivity to species mixing and stand basal area, while the trait variability of spruce was limited. Greater shifts in trait distributions due to mixing were found in specific leaf area for oak and leaf nitrogen content for beech. Thus intra-specific variability of key leaf traits was already influenced at this young development stage by inter-specific interactions. Finally, we used the 3-PG (Physiological Processes Predicting Growth) process-based forest growth model to show that the measured intra-specific variability on single FT values could influence stand productivity, light absorption and transpiration, although the net effect depends on the considered trait and the species composition of the mixture. The results of this study will aid better understanding of the effects of inter-specific competition on intra-specific FT variability, which has implications for the parameterization of process-based forest growth models and our understanding of ecosystem functioning.
Age-Related Human Resource Management Policies and Practices: Antecedents, Outcomes, and Conceptualizations
Authors: Boehm Stephan A , Schröder Heike , Bal Matthijs
Published: August 2021

Due to the demographic change in age, societies, firms, and individuals struggle with the need to postpone retirement while keeping up motivation, performance, and health throughout employees’ working life. Organizations, and specifically the Human Resource Management (HRM) practices they design and implement, take a central role in this process. Being influenced by macro-level trends such as new legislation, organizational HRM practices affect outcomes such as productivity and employability both at the firm and individual level of analysis. This editorial introduces the Special Issue on “Age-related Human Resource Management Policies and Practices” by conducting an interdisciplinary literature review. We offer an organizing framework that spans the macro-, meso-, and individual level and discusses major antecedents, boundary conditions, and outcomes of age-related HRM practices. Further, we propose a typology of HRM practices and discuss the role of individual HRM dimensions versus bundles of HRM practices in dealing with an aging and more age-diverse workforce. Building on these considerations, we introduce the eight articles included in this special issue. Finally, taking stock of our review and the new studies presented here, we deduct some recommendations for future research in the field of age-related HRM.
Loss of Nfat5 promotes lipid accumulation in vascular smooth muscle cells
Authors: Kappert Lena , Ruzicka Philipp , Kutikhin Anton , De La Torre Carolina , Fischer Andreas , Hecker Markus , Arnold Caroline , Korff Thomas
Published: August 2021

The nuclear factor of activated T‐cells 5 (NFAT5) is a transcriptional regulator of macrophage activation and T‐cell development, which controls stabilizing responses of cells to hypertonic and biomechanical stress. In this study, we detected NFAT5 in the media layer of arteries adjacent to human arteriosclerotic plaques and analyzed its role in vascular smooth muscle cells (VSMCs) known to contribute to arteriosclerosis through the uptake of lipids and transformation into foam cells. Exposure of both human and mouse VSMCs to cholesterol stimulated the nuclear translocation of NFAT5 and increased the expression of the ATP‐binding cassette transporter Abca1, required to regulate cholesterol efflux from cells. Loss of Nfat5 promoted cholesterol accumulation in these cells and inhibited the expression of genes involved in the management of oxidative stress or lipid handling, such as Sod1, Plin2, Fabp3, and Ppard. The functional relevance of these observations was subsequently investigated in mice fed a high‐fat diet upon induction of a smooth muscle cell‐specific genetic ablation of Nfat5 (Nfat5(SMC)−/−). Under these conditions, Nfat5(SMC)−/− but not Nfat5fl/fl mice developed small, focal lipid‐rich lesions in the aorta after 14 and 25 weeks, which were formed by intracellular lipid droplets deposited in the sub‐intimal VSMCs layer. While known for being activated by external stimuli, NFAT5 was found to mediate the expression of VSMC genes associated with the handling of lipids in response to a cholesterol‐rich environment. Failure of this protective function may promote the formation of lipid‐laden arterial VSMCs and pro‐atherogenic vascular responses.
A Vicious Cycle of Bias: Residents’ Perceptions of Leadership in Health Care
Authors: Ju Mindy , van Schaik Sandrijn M.
Published: August 2021

Purpose

Despite growing interest in shared leadership models, autocratic physician leadership remains the norm in health care. Stereotype and bias limit leadership by members of other professions. Furthermore, traditional views of effective clinical leadership emphasize agentic behaviors associated with male gender. To shift the prototypical concept of a leader from a male physician to a more inclusive prototype, a better understanding of prototype formation is needed. This study examines leader prototypes and their development among resident physicians through the lens of leadership categorization theory.

Method

One researcher conducted semistructured interviews with anesthesia and internal medicine residents at a single institution, asking participants to describe their ideal team leader and comment on the video-recorded performance of either a male or female nurse practitioner (NP) leading a simulated resuscitation. Interview questions explored participants’ perceptions of NPs as team leaders and how these perceptions developed. The researchers conducted deductive analysis to examine leadership prototypes and prototype formation, and inductive analysis to derive additional themes.

Results

The majority of residents described a male physician as the ideal resuscitation team leader. Exposure to male physician leaders, and lack of exposure to NP leaders, contributed to this prototype formation. Residents described a vicious cycle in which bias against female and NP leaders diminished acceptance of their leadership by team members, resulting in decreased confidence and performance, further aggravating bias.

Conclusions

These results provide suggestions for interventions that can help shift the leadership prototype in health care and promote shared leadership models. These include increasing exposure to different professionals of either gender in leadership roles and increased representation in educational materials, education about effective leadership strategies to create awareness of the benefits of shared leadership, and reflection during team training to increase awareness of bias and the backlash effect faced by individuals whose behaviors counter established stereotypes.
Defining Successful Practice Within Health Systems Science Among Entering Residents: A Single-Institution Qualitative Study of Graduate Medical Education Faculty Observations
Authors: Ridinger Heather A. , Bonnet Kemberlee , Schlundt David G. , Tekian Ara , Riddle Janet , Lomis Kimberly D.
Published: August 2021

Purpose

The American Medical Association’s Accelerating Change in Medical Education consortium defined health systems science (HSS) as the study of how health care is delivered, how health care professionals work together to deliver that care, and how the health system can improve patient care and health care delivery. This framework is increasingly being incorporated into medical school curricula. Graduate medical education (GME) had previously elevated systems-based practice (SBP) as a core competency, but expectations are defined by specialty-specific milestones. The lack of a shared competency framework between undergraduate medical education (UME) and GME makes it challenging to ensure that entering residents are prepared to implement HSS/SBP concepts in the workplace. The authors explored GME faculty observations of residents exemplifying successful practice across HSS domains to inform targets for UME training and assessment.

Method

Authors performed a single-institution qualitative study using transcribed phone interviews with eligible Vanderbilt residency program directors, associate program directors, and core faculty. Participants described observations of successful residents within each HSS domain. Two researchers independently coded, discussed, and reconciled deidentified transcripts using inductive–deductive approaches to identify themes.

Results

Seventeen faculty participated across specialties (17/39, 45%). Faculty responses emphasize precurricular experiences including professional degrees, work experience, extracurriculars, and medical school exposure. Importantly, successful residents exhibit foundational core workforce characteristics including growth mindset, curiosity, and a desire to learn about systems. GME faculty identified HSS domain-specific skills, noting distinctions among learning environments. Outcomes resulting from residents’ application of HSS concepts include delivering high-quality, person-centered care and systems improvements.

Conclusions

Descriptions of successful practice within HSS domains highlight preparatory experiences and core workforce characteristics and outline entry-level HSS behaviors. Conceptualized in a logic model framework, these findings describe key inputs, learning activities, outputs, and outcomes for systems-prepared entering residents bridging the UME–GME transition.
Evaluation of a Tool for Measuring Temporal Modulation Detection
Authors: Landsberger David M. , Stupak Natalia
Published: August 2021

Objectives:

A software tool (EasyMDT) that measures temporal modulation detection thresholds of a broadband noise carrier is presented. EasyMDT is designed to be both easy and quick to promote the use in environments where testing time is limited, and testers may not have extensive technical expertise to use typical research software. In addition, by providing a standardized stimulus and protocol, data collected by all groups using the software can be compared directly. Details of EasyMDT, including a description of the protocol, stimuli, interface and how to obtain the software, are provided along with representative sample data from both normal-hearing listeners and cochlear implant (CI) users. Performance with the EasyMDT is compared with speech understanding metrics as well as a metric of spectral-temporal resolution.

Design:

A “Full Curve” of modulation detection thresholds is measured using a three-interval forced-choice adaptive task in a single block for 7 modulation frequencies (10, 50, 75, 100, 150, 200, and 300 Hz). Similarly, the modulation detection thresholds were measured for only one modulation frequency in a block (either 100 Hz or 150 Hz). Modulation detection thresholds and block duration were recorded. In addition, performance on speech recognition tasks (CNC words, consonant identification, vowel identification, and AzBio sentences in noise) and a spectral-temporal resolution task (SMRT; Aronoff and Landsberger) were measured. Modulation detection thresholds were measured for both normal-hearing listeners and CI users. Only CI users participated in the speech and spectral-temporal tests.

Results:

Modulation detection thresholds measured with EasyMDT were consistent with those previously reported from other laboratories. Modulation detection thresholds at a single modulation frequency (100 Hz or 150 Hz) were predictive of modulation detection thresholds measured as part of the Full Curve consisting of all 7 modulation frequencies. Testing durations for CI users dropped from an average of over 18 minutes for the Full Curve to under 3 minutes for either of the single modulation frequency measures. Modulation detection thresholds at 100 Hz correlated with CNC words, consonant identification, and AzBio sentences in noise, but not vowel identification. No correlations were found between modulation detection and spectral-temporal resolution.

Conclusions:

The EasyMDT is designed to be an easy-to-use tool that provides a nonlinguistic measure that can predict speech understanding. The test duration is short enough that it can be incorporated into clinical practice or as part of an experimental battery. The software is available for free download at https://www.ear-lab.org/software-downloads.html. The software is designed to have a minimum barrier of entry as well as provide a standardized protocol allowing direct comparison of modulation detection thresholds across studies and groups.
Changes in Orientation Behavior due to Extended High-Frequency (5 to 10 kHz) Spatial Cues
Authors: Whitmer William M. , McShefferty David , Levy Suzanne C. , Naylor Graham , Edwards Brent
Published: August 2021

Objectives:

Current hearing aids have a limited bandwidth, which limits the intelligibility and quality of their output, and inhibits their uptake. Recent advances in signal processing, as well as novel methods of transduction, allow for a greater useable frequency range. Previous studies have shown a benefit for this extended bandwidth in consonant recognition, talker-sex identification, and separating sound sources. To explore whether there would be any direct spatial benefits to extending bandwidth, we used a dynamic localization method in a realistic situation.

Design:

Twenty-eight adult participants with minimal hearing loss reoriented themselves as quickly and accurately as comfortable to a new, off-axis near-field talker continuing a story in a background of far-field talkers of the same overall level in a simulated large room with common building materials. All stimuli were low-pass filtered at either 5 or 10 kHz on each trial. To further simulate current hearing aids, participants wore microphones above the pinnae and insert earphones adjusted to provide a linear, zero-gain response.

Results:

Each individual trajectory was recorded with infra-red motion-tracking and analyzed for accuracy, duration, start time, peak velocity, peak velocity time, complexity, reversals, and misorientations. Results across listeners showed a significant increase in peak velocity and significant decrease in start and peak velocity time with greater (10 kHz) bandwidth.

Conclusions:

These earlier, swifter orientations demonstrate spatial benefits beyond static localization accuracy in plausible conditions; extended bandwidth without pinna cues provided more salient cues in a realistic mixture of talkers.
Mitral Regurgitation in the High-Risk Patient: Integrating an Expanding Armamentarium of Transcatheter Devices Into the Treatment Algorithm
Authors: Basman Craig , Johnson Joel , Pirelli Luigi , Patel Nirav C. , Reimers Carl , Singh Varinder P. , Scheinerman S. Jacob , Kliger Chad A.
Published: August 2021

Over the last decade, multiple transcatheter mitral valve repair and replacement strategies have emerged, yet there is only 1 US Food and Drug Administration approved device, the MitraClip (Abbott Vascular, Inc., Santa Clara, CA). Current guidelines support the use of the MitraClip in high or prohibitive surgical risk patients, but there are many patients that are not anatomically suited for the device. This review article discusses the approach to degenerative and functional mitral regurgitation in the high-prohibitive risk patient, how to choose transcatheter treatment options (both approved and investigational), and potential management for therapy failure.
Epidemiologic Trends in Oculoplastics-Related Emergency Department Visits in the United States, 2006–2015
Authors: Ahmad Meleha , Zhao Jiawei , Iftikhar Mustafa , Canner Joseph K. , Rajaii Fatemeh , Mahoney Nicholas , Zafar Sidra , Woreta Fasika
Published: August 2021

Purpose:

To characterize demographics and trends in oculoplastics-related emergency department (ED) visits.

Methods:

The authors conducted a retrospective, multiyear study of the nationwide ED sample database. The nationwide ED sample was queried for oculoplastics-related International Classification of Disease-ninth revision codes identified from a comprehensive list and categorized based on anatomic location, urgency, and trauma status. Demographics, clinical characteristics, procedure requirement, and cost data were analyzed. Variables associated with inpatient admission were assessed using univariate and multivariate logistic regression.

Results:

The authors identified an estimated 4.2 million ED visits in the United States with oculoplastics-related primary diagnoses, of which pathology was 80.8% eyelid/adnexal, 17.4% orbital, and 1.74% lacrimal. Overall, 31.3% of the visits were deemed to be nonurgent. Orbital pathology was more likely to be caused by trauma (70.6%), to be urgent (98.0%), and to require a procedure (45.6%) (p < 0.001). While less than 5% of all patients required hospitalization, predictors for inpatient admission were urgent diagnoses (odds ratio, 14.9; CI, 13.7–16.1), presentation to a level 1 trauma center (odds ratio, 3.19; CI, 2.7–3.79), and presence of orbital pathology (odds ratio, 6.09; CI 5.73–6.47). Incidence of ED visits decreased in all categories; however, total inflation-adjusted charges increased.

Conclusions:

Over half of oculoplastics-related ED visits are for trauma, with orbital pathology being less common but requiring a high level of care. Although trends show a potentially decreasing incidence of oculoplastics-related ED visits, increasing costs and high proportion of nonurgent visits pose an opportunity for mitigating periocular trauma and increasing outpatient access to care, respectively.
Etiology and risk factors of intracranial hemorrhage and ischemic stroke in young adults
Authors: Chen Chun-Yu , Lin Po-Tso , Wang Yun-Huei , Syu Ruei-Wun , Hsu Shao-Lun , Chang Li-Hsin , Tsai Jui-Yao , Huang Hui-Chi , Liu Tzu-Ching , Lin Chun-Jen , Tang Chih-Wei , Hsu Li-Chi , Chung Chih-Ping , Liu Hung-Yu , Chi Nai-Fang , Lee I-Hui
Published: August 2021

Background:

Young stroke incidence has increased worldwide with lifestyle changes. Etiology and risk factors for both ischemic and hemorrhagic stroke in young Asians remain underexplored.

Methods:

We retrospectively reviewed consecutive acute stroke patients aged 16–45 years admitted to the Taipei Veterans General Hospital between 2009 and 2019 to analyze etiologic subtypes, risk factors, and serial modified Rankin Scale scores for 1 year and compare the age groups of 16–30 and 31–45 years.

Results:

Among 670 young Taiwanese patients (mean age at onset 37.5 ± 7.0 years; male 65.1%), there were 366 nontraumatic spontaneous hemorrhagic stroke (including 259 intracerebral hemorrhage [ICH] and 107 subarachnoid hemorrhage, SAH), 292 ischemic stroke and 12 cerebral venous thromboses. Notably, ICH was more prevalent in patients aged 16–30 than in those aged 31–45 (54.8% vs 36.8%). Specifically, structural vasculopathy (e.g., arteriovenous malformation, cavernoma) was the most common etiologic subtype in patients aged 16–30 (p < 0.001), whereas hypertensive ICH was the most common subtype in patients aged 31–45 (p < 0.001). On the other hand, the top ischemic subtype for both age groups was other determined diseases (e.g., arterial dissection, autoimmune diseases, moyamoya disease, etc.) rather than large artery atherosclerosis. Hyperlipidemia, diabetes, and cigarette smoking were more common risk factors for infarction than ICH. Familial stroke patients whose first- or second-degree relatives had a stroke by age 80 (n = 104, 15.5%) had more infarctions than those without a familial stroke history. In multivariate analyses, initial stroke severity, and infarction type were important predictors of favorable outcomes after 3 months. At the 1-year follow-up, patients with ICH and SAH had worse functional outcomes and survival rates than those with infarction.

Conclusion:

An aggressive approach to elucidate the etiology of stroke is indicated because structural vasculopathy-induced ICH and other determined infarction are distinctively prevalent in young adults, particularly those aged 16–30.
Neutrophil-to-lymphocyte ratio in predicting neurologic outcome of patients with acute ischemic stroke treated with intravenous thrombolytics
Authors: Chen Chung-Ting , Li Li-Hua , Su Pei-Ying , Chang Yu-Chin , Lee I-Hui , Yen David Hung-Tsang , How Chorng-Kuang
Published: August 2021

Background:

Recombinant tissue plasminogen activator (rtPA) is currently the most standard treatment for patients with acute ischemic stroke (AIS). However, rtPA treatment may further enhance the immune response poststroke. This study is to investigate the clinical utility of white blood–based inflammatory biomarkers in predicting neurologic outcomes among AIS patients receiving rtPA.

Methods:

A retrospective observational cohort study of 100 patients with AIS treated with intravenous rtPA was conducted in an urban tertiary hospital in Taiwan. Favorable neurological outcome defined as modified Rankin Scale (mRS) score 0 to 2 in poststroke follow-up was the primary outcome measure. Baseline and post-rtPA neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were investigated for potential predictors.

Results:

These patients had a mean age of 71.3 ± 13.7 years and the average of initial National Institute of Health Stroke Scale was 12.7 ± 6.5. Using multiple regression analysis, PLR was not an independent factor; however, both baseline and post-rtPA NLR were independent factors predicting favorable neurological outcome at 3, 6, 12 months after a stroke. The area under the receiver operating characteristic curve for baseline and post-rtPA NLR were 0.645 (95% confidence interval [CI], 0.537-0.753) and 0.769 (95% CI, 0.676-0.862) (Z score = 2.086) in 3-month, 0.645 (95% CI, 0.537-0.752) and 0.791 (95% CI, 0.701-0.880) (Z score = 2.471) in 6-month, and 0.646 (95% CI, 0.538-0.754) and 0.813 (95% CI, 0.728-0.898) (Z score = 2.857) in 12-month poststroke follow-up.

Conclusion:

For AIS patients treated with rtPA, both lower baseline and post-rtPA NLR levels were independently associated with a favorable neurologic outcome in serial mid- and long-term follow-up. Post-rtPA NLR was superior to baseline NLR in discriminative performance for neurologic prognosis.
Novel Innovations for Ventricular Assist Device Infection
Authors: Polycarpou Andreas , Pahwa Siddharth , Blackmon Shanda H. , Stulak John M.
Published: August 2021

Device infection is a major potential complication following ventricular assist device implantation and can lead to devastating consequences. The treatment options are few and often challenging to implement. The most durable option may require device exchange to obtain adequate source control. Due to the prolonged support times offered by the new left ventricular assist devices (LVADs), there is concern that the number of patients that will eventually require repeated device exchanges for device infection will increase. The benefit of medical antibiotic therapy alone is limited and is frequently unsuccessful. Surgical treatment strategies that improve outcomes by eliminating the infection and by preventing infection recurrence are needed. We report a case of a third-time LVAD exchange (4th device implant) for device infection within eight years of the index implant, and we briefly discuss the role of the greater omentum in the surgical treatment of this complication.
Total Artificial Heart Computational Fluid Dynamics: Modeling of Stator Bore Design Effects on Journal-Bearing Performance
Authors: Khelghatibana Maryam , Goodin Mark S. , Yaksh Michael , Horvath David J. , Kuban Barry D. , Fukamachi Kiyotaka , Karimov Jamshid H.
Published: August 2021

Cleveland Clinic’s continuous-flow total artificial heart (CFTAH) is a double-ended centrifugal blood pump that has a single rotating assembly with an embedded magnet, which is axially and radially suspended by a balance of magnetic and hydrodynamic forces. The key to the radial suspension is a radial offset between the stator bearing bore and the magnet’s steel laminations. This offset applies a radial magnetic force, which is balanced by a hydrodynamic force as the rotating assembly moves to a “force-balanced” radial position. The journal-bearing blood passage is a narrow flow path between the left and right impellers. The intent of this study was to determine the impact of the stator-bearing bore radius on the journal-bearing hydraulic performance while satisfying the geometric design constraints imposed by the pump and motor configuration. Electromagnetic forces on the journal bearing were calculated using the ANSYS EMAG program, Version 18 (ANSYS, Canonsburg, PA). ANSYS CFX Version 19.2 was then used to model the journal-bearing flow paths of the most recent design of the CFTAH. A transient, moving mesh approach was used to locate the steady state, force-balanced position of the rotating assembly. The blood was modeled as a non-Newtonian fluid. The computational fluid dynamics simulations showed that by increasing stator bore radius, rotor power, stator wall average shear stress, and blood residence time in journal-bearing decrease, while blood net flow rate through the bearing increases. The results were used to select a new bearing design that provides an improved performance compared with the baseline design. The performance of the new CFTAH-bearing design will be confirmed through upcoming in vitro and in vivo testing.
Proposal of Streptomyces aureorectus (ex Taig et al. 1969) Taig and Solovieva 1986 as a later heterotypic synonym of Streptomyces calvus Backus et al. 1957 (Approved Lists 1980) on the basis of a polyphasic taxonomic approach
Authors: Li Kaiqin , Hu Siren , Wang Yinfeng , Guo Yihui , Zhou Meiliang , Tang Xinke , Gao Jian
Published: August 2021

As two separate genomic species,

Streptomyces calvus

and

Streptomyces aureorectus

were approved in 1980 and 1986, respectively. However, recently, it has been found that the average nucleotide identity and digital DNA–DNA hybridization values between

S. calvus

JCM 4326T and

S. aureorectus

DSM 41692T were 99.19 and 92.70 %, respectively, much higher than 95–96 and 70  % cut-off points proposed and the generally accepted species boundaries. These data indicated that they should be classified as the same genomic species. Furthermore, this result was also supported by a comprehensive comparison of phenotypic, chemotaxonomic and physio-biochemical characteristics between the two type strains. All these data indicated that

S. calvus

and

S. aureorectus

had the same taxonomic position. In accordance with the principle of priority, it is proposed that

S. aureorectus

is a later heterotypic synonyms of

S. calvus

.
Photochemical changes during rehydration of an intertidal cyanobacterial mat exposed to variations in salinity and light intensity
Authors: Fleming Erich D. , Bebout Brad M. , Castenholz Richard W.
Published: August 2021

This study focuses on a

Lyngbya

cf. aestuarii dominated mat community from the intertidal zone of the Laguna Ojo de Liebre, Baja California Sur. In this environment, the mat is desiccated for several days between spring tides. While the mats were desiccated, photosynthetic activity was absent but recovered rapidly (~3 h) upon rehydration. It has been shown previously that the rate of photosynthetic recovery is dependent on both light intensity and salinity. In the current study, photosynthetic recovery was measured based on chlorophyll a fluorescence using pulse amplitude modulated (PAM) fluorometry. Upon the addition of water, photosystem II (PSII) complexes recovered the capacity for reaction centre excitation. However, these functional centres were initially closed. Respiratory activity early in recovery probably reduced the plastoquinone pool through the shared use of part of the photosynthetic transport chain, thus temporarily blocking electron transport downstream of PSII. The time that PSII complexes remained closed increased with light intensities above saturation. This condition is potentially damaging to the cyanobacteria since the exposure of closed PSII centres to high light intensities can lead to the production of singlet oxygen. After this initial lag period, PSII centres opened rapidly indicating an increase in the flow of electrons from PSII to PSI. The rate of photosynthetic recovery appeared to be limited primarily by the relatively slow return of functional PSII. Photosynthetic recovery rates were slower in salinities greater than those that naturally occur in the intertidal zone.
Relationship between astrocyte reactivity, using novel11C-BU99008 PET, and glucose metabolism, grey matter volume and amyloid load in cognitively impaired individuals
Authors: Livingston Nicholas R , Calsolaro Valeria , Hinz Rainer , Nowell Joseph , Raza Sanara , Gentleman Steve , Tyacke Robin J , Myers Jim , Venkataraman Ashwin V , Perneczky Robert , Gunn Roger N , Rabiner Eugenii A , Parker Christine A , Murphy Philip S , Wren Paul B , Nutt David J , Matthews Paul M , Edison Paul
Published: August 2021

Post mortemneuropathology suggests that astrocyte reactivity may play a significant role in neurodegeneration in Alzheimer’s disease. We explored thisin vivousing multimodal PET and MRI imaging. Twenty subjects (11 older, cognitively impaired subjects and 9 age-matched healthy controls) underwent brain scanning using the novel reactive astrocyte PET tracer11C-BU99008,18F-FDG and18F-florbetaben PET, and T1-weighted MRI. Differences between cognitively impaired subjects and healthy controls in voxel-wise levels of astrocyte reactivity, glucose metabolism and grey matter volume were explored, and their relationship to each other was assessed using Biological Parametric Mapping (BPM). Aβ-positive cognitively impaired subjects showed greater brain astrocyte reactivity, except in the temporal lobe, with further increased astrocyte reactivity in Mild Cognitive Impairment compared to Alzheimer’s subjects in the cingulate cortices. BPM correlations revealed regions which showed reduced11C-BU99008 uptake in Aβ-positive cognitively impaired subjects, such as the temporal lobe, also showed reduced18F-FDG uptake and grey matter volume. BPM analysis also revealed a regionally-dynamic relationship between astrocyte reactivity and amyloid uptake: increased amyloid load in cortical association areas of the temporal lobe and cingulate cortices was associated withreducedastrocyte reactivity, whilst increased amyloid uptake in primary motor and sensory areas (in which amyloid load occurs later) was associated withincreasedastrocyte reactivity. These novel observations add to the hypothesis that while astrocyte reactivity may be triggered by early Aβ-deposition, sustained pro-inflammatory astrocyte reactivity with greater amyloid deposition may lead to astrocyte dystrophy and amyloid-associated neuropathology such as grey matter atrophy and glucose hypometabolism.
The individual and global impact of copy number variants on complex human traits
Authors: Auwerx Chiara , Lepamets Maarja , Sadler Marie C. , Patxot Marion , Stojanov Miloš , Baud David , Mägi Reedik , Porcu Eleonora , Reymond Alexandre , Kutalik Zoltán
Published: August 2021

Copy number variations (CNVs) have been involved in multiple genomic disorders but their impact on complex traits remains understudied. We called CNVs in the UK Biobank and performed genome-wide association scans (GWASs) between the copy-number of CNV-proxy probes and 57 continuous traits, revealing 131 signals spanning 47 phenotypes. Our analysis recapitulated well-known associations (1q21 and height), revealed the pleiotropy of recurrent CNVs (26 traits for 16p11.2-BP4-BP5), and suggested new gene functionalities (MARF1in female reproduction). Forty CNV signals overlapped known GWAS loci (RHDdeletion and hematological traits). Conversely, others overlapped Mendelian disorder regions, suggesting variable expressivity and a broad impact of these loci, as illustrated by signals mapping to Rotor syndrome (SLCO1B1/3), renal cysts and diabetes (HNF1B), or Charcot-Marie-Tooth (PMP22) loci. The total CNV burden negatively impacted 35 traits, leading to increased adiposity, liver/kidney damage, and decreased intelligence and physical capacity. Thirty traits remained burden-associated after correcting for CNV-GWAS signals, pointing to a polygenic CNV-architecture. The burden negatively correlated with socio-economic indicators, parental lifespan, and age (survivorship proxy), suggesting that CNVs contribute to decreased longevity. Together, our results showcase how studying CNVs can reveal new biological insights, emphasizing the critical role of this mutational class in shaping complex traits.
Potential autoimmunity resulting from molecular mimicry between SARS-CoV-2 Spike and human proteins
Authors: Nunez-Castilla Janelle , Stebliankin Vitalii , Baral Prabin , Balbin Christian A , Sobhan Masrur , Cickovski Trevor , Mondal Ananda Mohan , Narasimhan Giri , Chapagain Prem , Mathee Kalai , Siltberg-Liberles Jessica
Published: August 2021

SARS-CoV-2 causes COVID-19, a disease curiously resulting in varied symptoms and outcomes, ranging from asymptomatic to fatal. Autoimmunity due to cross-reacting antibodies resulting from molecular mimicry between viral antigens and host proteins may provide an explanation. We computationally investigated molecular mimicry between SARS-CoV-2 Spike and known epitopes. We discovered molecular mimicry hotspots in Spike and highlight two examples with tentative autoimmune potential and implications for understanding COVID-19 complications. We show that a TQLPP motif in Spike and thrombopoietin shares similar antibody binding properties. Antibodies cross-reacting with thrombopoietin may induce thrombocytopenia, a condition observed in COVID-19 patients. Another motif, ELDKY, is shared in multiple human proteins such as PRKG1 and tropomyosin. Antibodies cross-reacting with PRKG1 and tropomyosin may cause known COVID-19 complications such as blood-clotting disorders and cardiac disease, respectively. Our findings illuminate COVID-19 pathogenesis and highlight the importance of considering autoimmune potential when developing therapeutic interventions to reduce adverse reactions.
N-dihydrogalactochitosan reduces mortality in a lethal mouse model of SARS-CoV-2
Authors: Weiss Christopher M. , Liu Hongwei , Ball Erin E. , Hoover Ashley R. , Wong Talia S. , Wong Chun Fung , Lam Samuel , Hode Tomas , Keel M. Kevin , Levenson Richard M. , Chen Wei R. , Coffey Lark L.
Published: August 2021

The rapid emergence and global dissemination of SARS-CoV-2 that causes COVID-19 continues to cause an unprecedented global health burden resulting in nearly 7 million deaths. While multiple vaccine countermeasures have been approved for emergency use, additional treatments are still needed due to sluggish vaccine rollout, vaccine hesitancy, and inefficient vaccine-mediated protection. Immunoadjuvant compounds delivered intranasally can guide non-specific innate immune responses during the critical early stages of viral replication, reducing morbidity and mortality. N- dihydrogalactochitosan (GC) is a novel mucoadhesive immunostimulatory polymer of β- 0-4-linked N-acetylglucosamine that is solubilized by the conjugation of galactose glycans with current applications as a cancer immunotherapeutic. We tested GC as a potential countermeasure for COVID-19. GC was well-tolerated and did not produce histopathologic lesions in the mouse lung. GC administered intranasally before and after SARS-CoV-2 exposure diminished morbidity and mortality in humanized ACE2 receptor expressing mice by up to 75% and reduced infectious virus levels in the upper airway. Fluorescent labeling of GC shows that it is confined to the lumen or superficial mucosa of the nasal cavity, without involvement of adjacent or deeper tissues. Our findings demonstrate a new application for soluble immunoadjuvants such as GC for preventing disease associated with SARS-CoV-2 and may be particularly attractive to persons who are needle-averse.

IMPORTANCE

The ongoing COVID-19 pandemic necessitates new approaches to reduce disease caused by SARS-CoV-2. We tested the immunoadjuvant N-dihydrogalactochitosan (GC), used previously as an immunostimulant for tumor therapy and adjuvant for viral vaccines, as a potential COVID-19 countermeasure. When GC was administered before and after inoculation of a lethal dose of SARS-CoV-2 into the nose of humanized mice expressing an entry receptor for the virus, fewer mice showed weight loss and died compared to mice that received only the vehicle but no GC. GC-treated mice also had lower levels of infectious SARS-CoV-2 in their upper airway. These results suggest that GC may be a candidate to prevent or treat COVID-19.

Single Sentence Summary

The immunoadjuvant N-dihydrogalactochitosan diminishes SARS-CoV-2 disease in humanized ACE2 mice, representing a new countermeasure against COVID-19.
Performance of Core Genome Multilocus Sequence Typing Compared to Capillary-Electrophoresis PCR Ribotyping and SNP Analysis ofClostridioides difficile
Authors: Baktash A , Corver J , Harmanus C , Smits WK , Fawley W , Wilcox MH , Kumar N , Eyre DW , Indra A , Mellmann A , Kuijper EJ
Published: August 2021

Clostridioides difficileis the most common cause of antibiotic-associated gastrointestinal infections. Capillary-electrophoresis (CE)-PCR ribotyping is currently the gold standard forC. difficiletyping but lacks discriminatory power to study transmission and outbreaks in detail. New molecular methods have the capacity to differentiate better, but backward compatibility with CE-PCR ribotyping must be assessed. Using a well-characterized collection of diverse strains (N=630; 100 unique ribotypes [RTs]), we aimed to investigate PCR ribotyping prediction from core genome multilocus sequence typing (cgMLST). Additionally, we compared the discriminatory power of cgMLST (SeqSphere & EnteroBase) and whole genome MLST (wgMLST) (EnteroBase) with single nucleotide polymorphism (SNP) analysis). A unique cgMLST profile (>6 allele differences) was observed in 82/100 ribotypes, indicating sufficient backward compatibility. Intra-RT allele difference varied per ribotype and MLST clade. Application of cg/wgMLST and SNP analysis in two outbreak settings with ribotypes RT078 and RT181 (known with a low intra-ribotype allele difference) showed no distinction between outbreak- and non-outbreak strains, in contrast to wgMLST and SNP analysis. We conclude that cgMLST has the potential to be an alternative to CE-PCR ribotyping. The method is reproducible, easy to standardize and offers higher discrimination. However, in some ribotype complexes adjusted cut-off thresholds and epidemiological data are necessary to recognize outbreaks. We propose to decrease the current threshold of 6 to 3 alleles to better identify outbreaks.
Defining the pig microglial transcriptome reveals their core signature, regional heterogeneity, and similarity with humans
Authors: Shih Barbara B , Brown Sarah M , Lefevre Lucas , Mabbott Neil A , Priller Josef , Thompson Gerard , Lawrence Alistair B , McColl Barry W
Published: August 2021

Microglia play key roles in brain homeostasis as well as responses to neurodegeneration and neuroinflammatory processes caused by physical disease and psychosocial stress. The pig is a physiologically-relevant model species for studying human neurological disorders, many of which are associated with microglial dysfunction. Furthermore, pigs are an important agricultural species, and there is a need to understand how microglial function affects their welfare. As a basis for improved understanding to enhance biomedical and agricultural research, we sought to characterise pig microglial identity at genome-wide scale and conduct inter-species comparisons.

We isolated pig hippocampal tissue and microglia from frontal cortex, hippocampus and cerebellum, as well as alveolar macrophages from the lungs and conducted RNA-sequencing (RNAseq). By comparing the transcriptomic profiles between microglia, macrophages, and hippocampal tissue, we derived a set of 365 highly-enriched genes defining the porcine core microglial signature. We found brain regional heterogeneity based on 215 genes showing significant (adjusted p<0.01) regional variations and that cerebellar microglia were most distinct. We compared normalized gene expression for microglia from human, mice and pigs using microglia signature gene lists derived from each species and demonstrated that a core microglial marker gene signature is conserved across species, but that species-specific expression subsets also exist. Importantly, pig and human microglia shared greater similarity than pig and murine microglia.

Our data provide a valuable resource defining the pig microglial transcriptome signature that highlights pigs as a useful large animal species bridging between rodents and humans in which to study the role of microglia during homeostasis and disease.

Main Points

- Defined a pig microglial transcriptome signature comprising 365 genes.

- Demonstrated regional variance in the pig microglial transcriptome across the brain.

- Revealed greater similarity between pig and human microglia than mouse.