bluuebunny/crossref_metadata_2025 huggingface dataset:
KUAKINI HHP CENTER FOR TRANSLATIONAL RESEARCH ON AGING: LATEST FINDINGS FROM MICE TO HUMANS
Authors: Willcox Bradley , Allsopp Richard , Martin Peter
Published: December 2022

Kuakini Medical Center (Kuakini) was funded by NIH in late 2019 to create an interdisciplinary Hawai’i-based, Center of Biomedical Research Excellence (COBRE), for translational research on aging. This Center is building upon Kuakini’s five-decades of prior NIH-funded research. These resources include clinical data from the 57-year ongoing Kuakini Honolulu Heart Program (HHP), Honolulu-Asia Aging Study, HHP Offspring Study and a large biorepository. The Center’s overarching aim is to increase infrastructure for collaborative aging research in Hawaii. The first step is to grow the Center’s faculty by hiring and mentoring research project leaders (RPLs) from diverse disciplines to become independent, R01-funded, investigators on aging. Our first RPL has graduated after obtaining R01-funded status. His project utilizes novel CRISPR methods to i) improve the safety and efficacy of delivering potentially therapeutic genes (such as FOXO3) to the mouse genome, and ii) test whether temporal enhancement of FOXO3 expression improves healthy aging in this mouse model - both key steps for potential translation to human clinical therapies. This work will be highlighted in the Program Overview session followed by current RPL findings. The first of these current RPL talks presents data on a potential relation between the FOXO3 gene and vascular dementia in elderly Japanese-American males. The second talk reports on how strong social networks mitigate risk for dementia in elderly Japanese-American males. The third talk will report a relation between FOXO3-associated resilience to hypertension and lower intracerebral hemorrhagic stroke risk in elderly Japanese-American males. Supported by NIGMS 5P20GM125526 and NIA R01AG027060.
FOXO3 LONGEVITY GENOTYPE MITIGATES THE IMPACT OF HYPERTENSION ON RISK OF INTRACEREBRAL HEMORRHAGE
Authors: Nakagawa Kazuma , Chen Randi , Greenberg Steven , Ross Webster , Willcox Bradley , Donlon Timothy , Morris Brian , Masaki Kamal
Published: December 2022

The longevity-associated FOXO3 G allele of SNP rs2802292 is associated with protection against mortality, however the impact of FOXO3 genotype on the association between hypertension and risk of intracerebral hemorrhage (ICH) has not been assessed. Therefore, we utilized the Kuakini Honolulu Heart Program (KHHP), a prospective population-based cohort of Japanese American men living in Hawaii that began in 1965 to study this relation. After excluding baseline prevalent stroke and those missing FOXO3 data, 6,469 men were included in the analysis. Age-adjusted prevalence of ICH by hypertension was assessed for the whole cohort after stratifying by FOXO3 genotype. Cox regression models, adjusted for age, cardiovascular risk factors, FOXO3 and APOE genotypes, were utilized to assess relative risk of hypertension on ICH. All models were created for the whole cohort and stratified by FOXO3 genotype, namely G allele carriers versus TT genotype. Overall, 183 subjects developed ICH over the 34-year follow-up period. Age-adjusted ICH prevalence was 0.90 versus 1.32 per 1,000 person-years follow-up in those without and with hypertension, respectively (p=0.002). After stratifying by FOXO3 genotype, this association was no longer significant in G allele carriers. In the whole cohort, hypertension was an independent predictor of ICH (RR=1.70, 95%CI 1.25, 2.32; p=0.0007). In stratified analyses, hypertension remained an independent predictor of ICH among the FOXO3 TT allele group (RR=2.02, 95% CI 1.33, 3.07; p=0.001), but not in FOXO3 G allele carriers (RR=1.39, 95% CI 0.88, 2.19; p=0.15). Thus, the longevity/resilience-associated FOXO3 G allele may mitigate the impact of hypertension on ICH risk in this population. Further study is needed in other populations.
EXPLORING THE NARRATIVE OF AGING THROUGH MUSIC
Authors: O'Neill Desmond
Published: December 2022

With increasing interest in exploring narratives of aging through literary/oral sources, a less prominent area of inquiry has been possibilities afforded by narratives inherent in music across the life-span and into later-life. Two possible areas of interest are the arc of development and change over the life-course, and inherent content of the music. The latter element is less prominent in narrative analysis, providing a potentially rich field of discovery. While popular song parallels these possibilities, further opportunities arise from instrumental, orchestral and operatic music, allied to strengths in musicological analysis. Later compositions whose elements provide insights into life course review (Shostakovich Viola Sonata and Metamorphosen, Richard Strauss) as well as romantic love in later life across generations (The Cunning Little Vixen, Leos Janáček). The analysis will seek to delineate to possible avenues of interpretation of musicological analysis in understanding the phenomenology and opportunities arising from aging.
ADULT TETANUS, DIPHTHERIA, AND PERTUSSIS VACCINATION AND INCIDENT DEMENTIA
Authors: Scherrer Jeffrey , Salas Joanne , Wiemken Timothy , Jacobs Christine , Morley John , Hoft Daniel
Published: December 2022

Adult vaccinations may reduce risk for dementia. We determined whether tetanus, diphtheria, pertussis (Tdap) vaccination is associated with lower risk for dementia. Analysis conducted with Veterans Health Affairs (VHA) administrative medical record data and replicated in private sector medical claims data. Patients were ≥65 years of age and free of dementia for 2 years prior to index date. Tdap vaccination in 2011 or 2012. Follow-up through 2018. Controls had no Tdap vaccination for the duration of follow-up. After controlling for confounding, patients with, compared to without Tdap vaccination, had a significantly lower risk for dementia in both cohorts (VHA: HR=0.58; 95%CI:0.54 - 0.63 and MarketScan: HR=0.58; 95%CI:0.48 - 0.70). Results were replicated in two cohorts with different clinical and sociodemographic characteristics. Several vaccine types are linked to decreased dementia risk, suggesting that these associations are due to nonspecific effects on inflammation rather than vaccine-induced pathogen-specific protective effects.
DIGITAL STORYTELLING AND INTERGENERATIONAL COLLABORATIONS: OLDER ADULTS AND COLLEGE STUDENTS
Authors: Lavery Angela
Published: December 2022

The use of digital storytelling can be a helpful tool within community work, health and social work research and policy. Digital storytelling refers to life-story telling that can be done in a variety of ways and used to encourage social change and transformation. This presentation will include experience on how this method was used in a study and an intergenerational project between older adults and university graduate and undergraduate students. This group of older adults specifically shared their experiences with equine interactions and activities, while the university students worked with the older adults to create a digital story. For this study and project, recruitment included students enrolled in different disciplines. Discussion on digital storytelling’s connection to the narrative method and critical gerontology framework will be noted. Challenges and barriers, including Institutional Review Board and ethical considerations while preparing for this method will also be discussed.
COMPARING EXERCISE DETERMINANTS BETWEEN BLACK AND WHITE OLDER ADULTS WITH HEART FAILURE
Authors: Kaushal Navin , Nemati Donya , Mann-Krzisnik Dylan , de la Colina Adrian Noriega
Published: December 2022

Heart Failure (HF) is a leading cause of mortality among older-adults (OA); however, engaging in moderate-to-vigorous intensity of physical activity (MVPA) improves survival rates. Limited research has applied behavior theory to understand determinants of MVPA among OA with HF and compared the effects between races. This study aimed to use the Health Belief Model (HBM) to compare MVPA determinants between Black and White OA diagnosed with HF.

Methods: The HF-ACTION Trial is a multi-site trial that helped facilitate physical activity among individuals with HF. The present study used structural equation modeling to test the change in HBM determinants and MVPA across 12 months among OA.

Results: Participants were OA 72.28 (SD= 5.41) years old, (Black: n= 230; White, n= 441). The model found MVPA to be facilitated by perceived benefits (Black: β=.27, p=.001; White: β=.28; p<.001), self-efficacy (Black: β=.20, p=.003; White: β=.24; p<.001) and deterred by perceived barriers (Black: β=-.25, p=.001; White β=-.24; p<.001). Perceived threats deterred Black OA (β=-.23; p=.002) but not White OA (β=-.07; p=.278) from MVPA. Experimental arm predicted the development of self-efficacy (Black: β=.21. p=.001; White: β=.23; p=.001), and perceived benefits (Black: β=.21. p=.001; White: β=.23; p=.001) but not barriers (p>.05) for both races.

Conclusions: Perceived barriers was a strong determinant to MVPA, and it was not resolved in the experimental arm for either race. The experimental arm did not resolve perceived threat, which was a deterrent for Black OA. Individual characteristics need to be considered when designing programs for HF patients to reduce health disparity.
POLYPHARMACY IN ASSISTED LIVING: WHERE ARE WE NOW AND EFFECTIVE APPROACHES TO IMPROVE MEDICATION MANAGEMENT
Authors: Resnick Barbara
Published: December 2022

There are many definitions for polypharmacy used within clinical practice and research and many factors contributing to this problem. Definitions vary from being based on the number of medications the older adult is taking to a more qualitative evaluation of the appropriateness of medication based on the benefit of the drug for a specific problem. For research purposes the definition is more commonly conceptualized as being equivalent to taking five or more medicines. Polypharmacy is noted to be presented in about 40% of older adults living in the community. Limited research has focused specifically on polypharmacy in assisted living settings. In addition to concerns about polypharmacy in assisted living there has also been a focus on the use of psychotropic medication and opioids in these settings as prevalence ranges from 53% to 68%. Although there are not regulations related to decreasing polypharmacy via deprescribing or to decrease use of psychotropics or opioids in assisted living, there are currently major initiatives in geriatrics to focus on these areas. This symposium will provide current data on medication use and polypharmacy among a large sample of 781 assisted living residents from 85 communities across three states and address the impact of a Function Focused Care approach on decreasing polypharmacy and use of psychotropics and opioids. Lastly data will be provided on the value of Deprescribing Networks to help decrease polypharmacy within these settings. The findings from this symposium will provide recommendations for future research as well as guidance for clinical practice.
POLYPHARMACY IN ASSISTED LIVING
Authors: Galik Elizabeth
Published: December 2022

The purpose of this study was to describe polypharmacy in assisted living settings, evaluate the factors that influence polypharmacy and the impact of polypharmacy on clinical outcomes. Baseline data from the study entitled, Dissemination and Implementation of Function Focused Care for Assisted Living Using the Evidence Integration Triangle (FFC-AL-EIT) was used. Total number of drugs taken daily among the 781 participants was 5.16 (SD=2.40) and over half (N=484, 62%) were exposed to polypharmacy. None of the predicted variables (age, gender, race, setting, diagnoses, and cognition) were associated with polypharmacy (Wald = .207, p=.65). Similarly, controlling for age, gender, race, setting, diagnoses, cognition, function, and physical activity, polypharmacy was not associated with falls, emergency room visits or hospitalizations. Factors not included in the data contributing to the high rate of polypharmacy in assisted living settings will be discussed and recommendations for further research and practice implications reviewed.
Integration of a Gaussian quadrature grid discretization approach with a generalized stiffness reduction method and a parallelized direct solver for 3-D frequency-domain seismic wave modelling in viscoelastic anisotropic media
Authors: Ma Guoqi , Zhou Bing , Greenhalgh Stewart , Liu Xu , Zemerly Jamal , Kamel Riahi Mohamed
Published: December 2022

We integrate three advanced numerical techniques—Gaussian quadrature grid (GQG) discretization, a new generalized stiffness reduction method and the latest version of an efficient parallelized direct solver to achieve accurate 3-D frequency-domain seismic wave modelling in viscoelastic anisotropic media. A GQG is employed to sample and interpolate both model parameters and wavefield quantities as well as to fit with arbitrary free-surface topography and subsurface interfaces of a geological model. A new version of the generalized stiffness reduction method is utilized to effectively remove the artificial boundary edge effects for which the common perfectly matched layer method fails. The most recent version of a multifrontal massively parallel direct solver is applied to tackle the notoriously expensive computation of frequency-domain 3-D wave modelling. We validate the 3-D modelling by comparing with the exact solutions for homogeneous viscoelastic isotropic, vertically transversely isotropic and orthorhombic media. All the results show very close matches between the numerical and analytical solutions. Then, we investigate the computational efficiency of the parallelized direct solver, compare its performance using different ordering schemes, in-core and out-of-core factorization modes and the block low-rank approximation in the factorization for different grid sizes. Our modelling results show that the ordering scheme of the so-called ‘Metis’ is the best for reducing computer memory and run time, and the parallelized direct solver is remarkably faster than iterative solvers for similar workloads but at the expense of higher memory requirements. The out-of-core factorization mode can effectively reduce the memory cost without a compromising on run time. The block low-rank approximation is able to significantly reduce the run time in both the factorization and solving process (up to 56 per cent in total), but will increase the memory cost when using the out-of-core factorization mode. Efficient application of this parallel direct solver should use ‘Metis’ as the ordering scheme and select the out-of-core factorization mode without the block low-rank approximation as the best scheme to save the memory cost, or the in-core factorization mode with the block low-rank approximation for the fastest computation. Finally, we demonstrate the excellent applicability of the 3-D wave modelling scheme for a practical and complex heterogeneous geological model.
Stage-Specific Brain Aging in First-Episode Schizophrenia and Treatment-Resistant Schizophrenia
Authors: Kim Woo-Sung , Heo Da-Woon , Shen Jie , Tsogt Uyanga , Odkhuu Soyolsaikhan , Kim Sung-Wan , Suk Heung-Il , Ham Byung-Joo , Rami Fatima Zahra , Kang Chae Yeong , Sui Jing , Chung Young-Chul
Published: December 2022

Background

Brain age is a popular brain-based biomarker that offers a powerful strategy for using neuroscience in clinical practice. We investigated the brain-predicted age difference (PAD) in patients with schizophrenia (SCZ), first-episode schizophrenia spectrum disorders (FE-SSDs), and treatment-resistant schizophrenia (TRS) using structural magnetic resonance imaging data. The association between brain-PAD and clinical parameters was also assessed.

Methods

We developed brain age prediction models for the association between 77 average structural brain measures and age in a training sample of controls (HCs) using ridge regression, support vector regression, and relevance vector regression. The trained models in the controls were applied to the test samples of the controls and 3 patient groups to obtain brain-based age estimates. The correlations were tested between the brain PAD and clinical measures in the patient groups.

Results

Model performance indicated that, regardless of the type of regression metric, the best model was support vector regression and the worst model was relevance vector regression for the training HCs. Accelerated brain aging was identified in patients with SCZ, FE-SSDs, and TRS compared with the HCs. A significant difference in brain PAD was observed between FE-SSDs and TRS using the ridge regression algorithm. Symptom severity, the Social and Occupational Functioning Assessment Scale, chlorpromazine equivalents, and cognitive function were correlated with the brain PAD in the patient groups.

Conclusions

These findings suggest additional progressive neuronal changes in the brain after SCZ onset. Therefore, pharmacological or psychosocial interventions targeting brain health should be developed and provided during the early course of SCZ.
Individual pulse emission from the diffuse drifter PSR J1401 − 6357 using the ultrawideband receiver on the Parkes radio telescope
Authors: Chen J L , Wen Z G , Duan X F , He D L , Wang N , Wang H G , Yuen R , Yuan J P , Yan W M , Wang Z , Lyu C B , Wang H , Cui S R
Published: December 2022

In this study, we report on a detailed single pulse analysis of the radio emission from the pulsar J1401 − 6357 (B1358 − 63) based on data observed with the ultrawideband low-frequency receiver on the Parkes radio telescope. In addition to a weak leading component, the integrated pulse profile features a single-humped structure with a slight asymmetry. The frequency evolution of the pulse profile is studied. Well-defined nulls, with an estimated nulling fraction greater than 2 per cent, are present across the whole frequency band. No emission is detected with significance above 3σ in the average pulse profile integrated over all null pulses. Using fluctuation spectral analysis, we reveal the existence of temporal-dependent subpulse drifting in this pulsar for the first time. A clear double-peaked feature is present at exactly the alias border across the whole frequency band, which suggests that the apparent drift sense changes during the observation. Our observations provide further confirmation that the phenomena of pulse nulling and subpulse drifting are independent of observing frequency, which suggest that they invoke changes on the global magnetospheric scale.
The size–mass and other structural parameter (n, μz, Rz) relations for local bulges/spheroids from multicomponent decompositions
Authors: Hon Dexter S -H , Graham Alister W , Sahu Nandini
Published: December 2022

We analyse the bulge/spheroid size–(stellar mass), Re, Sph − M*, Sph, relation and spheroid structural parameters for 202 local (predominantly $\lesssim 110~\rm Mpc$) galaxies spanning $M_*\sim 3\times 10^{9}\!-\!10^{12}~\rm M_{\odot }$ and $0.1 \lesssim R_\mathrm{e, Sph}\lesssim 32~\rm kpc$ from multicomponent decomposition. The correlations between the spheroid Sérsic index (nSph), central surface brightness (μ0, Sph), effective half-light radius (Re, Sph), absolute magnitude ($\mathfrak {M}_\mathrm{Sph}$), and stellar mass (M*, Sph) are explored. We also investigate the consequences of using different scale radii, $R_{z,\rm Sph}$, encapsulating a different fraction (z, from 0 to 1) of the total spheroid luminosity. The correlation strengths for projected mass densities, Σz and 〈Σ〉z, vary significantly with the choice of z. Spheroid size ($R_\mathrm{z, \rm Sph}$) and mass (M*, Sph) are strongly correlated for all light fractions z. We find $\log (R_\mathrm{e,Sph}/\rm kpc) = 0.88\log (M_\mathrm{*,Sph}/\rm M_{\odot })-9.15$ with a small scatter of $\Delta _{rms} = 0.24~\rm dex$ in the log (Re, Sph) direction. This result is discussed relative to the curved size–mass relation for early-type galaxies due to their discs yielding larger galaxy radii at lower masses. Moreover, the slope of our spheroid size–mass relation is a factor of ∼3, steeper than reported bulge size–mass relations, and with bulge sizes at M*, sph ∼3 × 109 M⊙ which are 2–3 times smaller. Our spheroid size–mass relation present no significant flattening in slope in the low-mass end ($M_{\rm *,sph}\sim 10^9 - 10^{10}\rm ~M_{\odot }$). Instead of treating galaxies as single entities, future theoretical and evolutionary models should also attempt to recreate the strong scaling relations of specific galactic components. Additional scaling relations, such as log (nSph) − log (M*, Sph), log (Σ0, Sph) − log (nSph), and log (nSph) − log (Re, Sph), are also presented. Finally, we show that the local spheroids align well with the size-mass distribution of quiescent galaxies at z ∼ 1.25–2.25. In essence, local spheroids and high-z quiescent galaxies appear structurally similar, likely dictated by the virial theorem.
Spectral analysis of the AMXP IGR J17591–2342 during its 2018 outburst
Authors: Manca A , Gambino A F , Sanna A , Jaisawal G K , Di Salvo T , Iaria R , Mazzola S M , Marino A , Anitra A , Bozzo E , Riggio A , Burderi L
Published: December 2022

The Accreting Millisecond X-ray Pulsar IGR J17591–2342 is a Low Mass X-ray Binary (LMXB) system that went in outburst on 2018 August and it was monitored by the NICER observatory and partially by other facilities. We aim to study how the spectral emission of this source evolved during the outburst by exploiting the whole X-ray data repository of simultaneous observations. The continuum emission of the combined broad-band spectra is on average well described by an absorbed Comptonization component scattering blackbody-distributed photons peaking at (0.8 ± 0.5) keV by a moderately optically thick corona (τ = 2.3 ± 0.5) with temperature of (34 ± 9) keV. A blackbody component with temperature and radial size of (0.8 ± 0.2) keV and (3.3 ± 1.5) km, respectively, is required by some of the spectra and suggests that part of the central emission, possibly a fraction of the neutron star surface, is not efficiently scattered by the corona. The continuum at low energies is characterized by significant residuals suggesting the presence of an absorption edge of O viii and of emission lines of Ne ix ions. Moreover, broad Fe i and Fe xxv Kα emission lines are detected at different times of the outburst, suggesting the presence of reflection in the system.
Importance of intracluster scattering and relativistic corrections from tSZ effect with cosmic infrared background
Authors: Acharya Sandeep Kumar , Chluba Jens
Published: December 2022

The Sunyaev–Zeldovich effect towards clusters of galaxies has become a standard probe of cosmology. It is caused by the scattering of photons from the cosmic microwave background (CMB) by the hot cluster electron gas. In a similar manner, other photon backgrounds can be scattered when passing through the cluster medium. This problem has been recently considered for the radio and the cosmic infrared background. Here, we revisit the discussion of the cosmic infrared background (CIB) including several additional effects that were omitted before. We discuss the intracluster scattering of the CIB and the role of relativistic temperature corrections to the individual cluster and all-sky averaged signals. We show that the all-sky CIB distortion introduced by the scattering of the photon field was underestimated by a factor of ≃1.5 due to neglecting the intracluster scattering contribution. The CIB photons can scatter with the thermal electrons of both the parent halo or another halo, meaning that there are two ways to gain energy. Therefore, energy is essentially transferred twice from the thermal electrons to the CIB. We carefully clarify the origin of various effects in the calculation of the average CIB and also scattered signals. The single-cluster CIB scattering signal also exhibits a clear redshift dependence, which can be used in cosmological analyses, as we describe both analytically and numerically. This may open a new way for cosmological studies with future CMB experiments.
Gravitationally lensed quasars in Gaia – IV. 150 new lenses, quasar pairs, and projected quasars
Authors: Lemon C , Anguita T , Auger-Williams M W , Courbin F , Galan A , McMahon R , Neira F , Oguri M , Schechter P , Shajib A , Treu T , Agnello A , Spiniello C
Published: December 2022

We report the spectroscopic follow-up of 175 lensed quasar candidates selected using Gaia Data Release 2 observations following Paper III of this series. Systems include 86 confirmed lensed quasars and a further 17 likely lensed quasars based on imaging and/or similar spectra. We also confirm 11 projected quasar pairs and 11 physical quasar pairs, while 25 systems are left as unclassified quasar pairs – pairs of quasars at the same redshift, which could be either distinct quasars or potential lensed quasars. Especially interesting objects include eight quadruply imaged quasars of which two have BAL sources, an apparent triple, and a doubly lensed LoBaL quasar. The source redshifts and image separations of these new lenses range between 0.65–3.59 and 0.78–6.23 arcsec, respectively. We compare the known population of lensed quasars to an updated mock catalogue at image separations between 1 and 4 arcsec, showing a very good match at z < 1.5. At z > 1.5, only 47 per cent of the predicted number are known, with 56 per cent of these missing lenses at image separations below 1.5 arcsec. The missing higher redshift, small-separation systems will have fainter lensing galaxies, and are partially explained by the unclassified quasar pairs and likely lenses presented in this work, which require deeper imaging. Of the 11 new reported projected quasar pairs, 5 have impact parameters below 10 kpc, almost tripling the number of such systems, which can probe the innermost regions of quasar host galaxies through absorption studies. We also report four new lensed galaxies discovered through our searches, with source redshifts ranging from 0.62 to 2.79.
Mutations in the non-codingRNU4ATACgene affect the homeostasis and function of the Integrator complex
Authors: Almentina Ramos Shidi Fatimat , Cologne Audric , Delous Marion , Besson Alicia , Putoux Audrey , Leutenegger Anne-Louise , Lacroix Vincent , Edery Patrick , Mazoyer Sylvie , Bordonné Rémy
Published: December 2022

Various genetic diseases associated with microcephaly and developmental defects are due to pathogenic variants in the U4atac small nuclear RNA (snRNA), a component of the minor spliceosome essential for the removal of U12-type introns from eukaryotic mRNAs. While it has been shown that a few RNU4ATAC mutations result in impaired binding of essential protein components, the molecular defects of the vast majority of variants are still unknown. Here, we used lymphoblastoid cells derived from RNU4ATAC compound heterozygous (g.108_126del;g.111G>A) twin patients with MOPD1 phenotypes to analyze the molecular consequences of the mutations on small nuclear ribonucleoproteins (snRNPs) formation and on splicing. We found that the U4atac108_126del mutant is unstable and that the U4atac111G>A mutant as well as the minor di- and tri-snRNPs are present at reduced levels. Our results also reveal the existence of 3’-extended snRNA transcripts in patients’ cells. Moreover, we show that the mutant cells have alterations in splicing of INTS7 and INTS10 minor introns, contain lower levels of the INTS7 and INTS10 proteins and display changes in the assembly of Integrator subunits. Altogether, our results show that compound heterozygous g.108_126del;g.111G>A mutations induce splicing defects and affect the homeostasis and function of the Integrator complex.
A versatile and convenient tool for regulation of DNA strand displacement and post-modification on pre-fabricated DNA nanodevices
Authors: Liao Yangwei , Hu Hao , Tang Xiaofeng , Qin Yang , Zhang Wei , Dong Kejun , Yan Bei , Mu Yaoqin , Li Longjie , Ming Zhihao , Xiao Xianjin
Published: December 2022

Toehold-mediated strand displacement and its regulatory tools are fundamental for DNA nanotechnology. However, current regulatory tools all need to change the original sequence of reactants, making the regulation inconvenient and cumbersome. More importantly, the booming development of DNA nanotechnology will soon promote the production of packaged and batched devices or circuits with specified functions. Regarding standardized, packaged DNA nanodevices, access to personalized post-modification will greatly help users, whereas none of the current regulatory tools can provide such access, which has greatly constrained DNA nanodevices from becoming more powerful and practical. Herein, we developed a novel regulation tool named Cap which has two basic functions of subtle regulation of the reaction rate and erasability. Based on these functions, we further developed three advanced functions. Through integration of all functions of Cap and its distinct advantage of working independently, we finally realized personalized tailor-made post-modification on pre-fabricated DNA circuits. A pre-fabricated dual-output DNA circuit was successfully transformed into an equal-output circuit, a signal-antagonist circuit and a covariant circuit according to our requirements. Taken together, Cap is easy to design and generalizable for all strand displacement-based DNA nanodevices. We believe the Cap tool will be widely used in regulating reaction networks and personalized tailor-made post-modification of DNA nanodevices.
Plasma endotrophin, reflecting tissue fibrosis, is associated with graft failure and mortality in KTRs: results from two prospective cohort studies
Authors: Kremer Daan , Alkaff Firas F , Post Adrian , Knobbe Tim J , Tepel Martin , Thaunat Olivier , Berger Stefan P , van den Born Jacob , Genovese Federica , Karsdal Morten A , Rasmussen Daniel G K , Bakker Stephan J L
Published: December 2022

Background

Fibrosis is a suggested cause of graft failure and mortality among kidney transplant recipients (KTRs). Accumulating evidence suggests that collagen type VI is tightly linked to fibrosis and may be a marker of systemic fibrosis and ageing. We studied whether plasma endotrophin, a pro-collagen type VI fragment, is associated with graft failure and mortality among KTRs.

Methods

In cohort A (57% male, age 53 ± 13 years), we measured plasma endotrophin in 690 prevalent KTRs ≥1 year after transplantation. The non-overlapping cohort B included 500 incident KTRs with serial endotrophin measurements before and after kidney transplantation to assess trajectories and intra-individual variation of endotrophin.

Results

In cohort A, endotrophin was higher in KTRs compared with healthy controls. Concentrations were positively associated with female sex, diabetes, cardiovascular disease, markers of inflammation and kidney injury. Importantly, endotrophin was associated with graft failure {hazard ratio [HR] per doubling 1.87 [95% confidence interval (CI) 1.07–3.28]} and mortality [HR per doubling 2.59 (95% CI 1.73–3.87)] independent of potential confounders. Data from cohort B showed that endotrophin concentrations strongly decrease after transplantation and remain stable during post-transplantation follow-up [intra-individual coefficient of variation 5.0% (95% CI 3.7–7.6)].

Conclusions

Plasma endotrophin is strongly associated with graft failure and mortality among KTRs. These findings suggest a key role of abnormal extracellular matrix turnover and fibrosis in graft and patient prognosis among KTRs and highlight the need for (interventional) studies targeting the profibrotic state of KTRs. The intra-individual stability after transplantation indicates potential use of endotrophin as a biomarker and outcome measure of fibrosis.

Trial registration

ClinicalTrials.gov NCT02811835.
Efficacy and safety of interleukin-1 blockers in kidney transplant recipients with familial Mediterranean fever: a propensity score–matched cohort study
Authors: Mirioglu Safak , Dirim Ahmet Burak , Bektas Murat , Demir Erol , Tor Yavuz Burak , Ozluk Yasemin , Kilicaslan Isin , Oto Ozgur Akin , Yalcinkaya Yasemin , Caliskan Yasar , Artim-Esen Bahar , Yazici Halil , Inanc Murat , Turkmen Aydin , Gul Ahmet , Sever Mehmet Sukru
Published: December 2022

Background

Data on use of interleukin (IL)-1 blockers in kidney transplant recipients (KTRs) with familial Mediterranean fever (FMF) are very limited. We aimed to evaluate the efficacy and safety of anakinra and canakinumab in the transplantation setting.

Methods

In this retrospective cohort study, we included KTRs who suffered from AA amyloidosis caused by FMF and treated with anakinra or canakinumab (study group, n = 36). Using propensity score matching, we selected 36 patients without FMF or amyloidosis from our database of 696 KTRs as the control group. Primary outcomes were patient and graft survival. Biopsy-confirmed graft rejection, changes in estimated glomerular filtration rate (eGFR), high-sensitivity CRP (hsCRP), erythrocyte sedimentation rate (ESR), proteinuria and number of monthly attacks were secondary outcomes.

Results

All KTRs with FMF began IL-1 blocker therapy with anakinra and nine (25%) were switched to canakinumab. Overall death was more frequent in the study group (19.4% vs 0%) (P = .005); however, overall graft loss was comparable between study (27.8%) and control groups (36.1%) (P = .448). Five- and 10-year graft survival rates were significantly higher in the study group (94.4% and 83.3%, respectively) than in the control group (77.8% and 63.9%, respectively) (P = .014 and P < .001, respectively). Rejections were numerically lower in study group (8.3% vs 25%), but it did not reach to statistical significance (P = .058). When compared with the pre-treatment period, with IL-1 blockers, the number of attacks per month (P < .001), and eGFR (P = .004), hsCRP (P < .001) and ESR (P = .026) levels were lower throughout the follow-up, whereas proteinuria levels were not.

Conclusions

Anakinra and canakinumab are effective in KTRs suffering from FMF; however, the mortality rate may be of concern.
Hepatic Resection vs Particle Therapy as an Initial Treatment for Single Hepatocellular Carcinoma: Bi-Institutional Propensity Score-Matched Analysis
Authors: Omiya Satoshi , Komatsu Shohei , Terashima Kazuki , Yamasaki Nobuaki , Matsuo Yoshiro , Toyama Hirochika , Tokumaru Sunao , Okimoto Tomoaki , Fukumoto Takumi
Published: December 2022

Background:

Curative treatment for hepatocellular carcinoma (HCC) is limited to hepatic resection (HR), radiofrequency ablation, and liver transplantation, while the value of particle therapy (PT) as an initial treatment remains unclear. This study aimed to compare the outcomes of HR and PT for single HCC.

Study Design:

A total of 554 patients with single HCC without vascular invasion were enrolled from January 2000 to December 2015. Patients underwent either HR (n = 279) or PT (n = 275) as initial treatments. A one-to-one propensity score matching (PSM) analysis was performed to evaluate the overall survival (OS) and progression-free survival (PFS) after dividing patients according to liver function as assessed by the modified albumin-bilirubin (mALBI) grade.

Results:

The median OS (130 vs. 85 month, p = 0.001) and PFS (47 vs. 30 month, p = 0.004) of HR were also significantly better than that of PT in the PSM cohort with mALBI grade 1/2a (n = 145 per group). Meanwhile, in a PSM cohort with mALBI grade 2b/3 (n = 53 per group), there were no significant differences in median OS and PFS between HR and PT.

Conclusion:

HR may be preferable as an initial treatment for patients with single HCC without vascular invasion, especially those with preserved liver function. PT can be an acceptable alternative to HR for patients without surgical indication and/or impaired liver function.
Proposal to reclassify Aquiflexum aquatile into a novel genus as Cognataquiflexum aquatile gen. nov., comb. nov., and description of Cognataquiflexum nitidum sp. nov. and Cognataquiflexum rubidum sp. nov., isolated from freshwater lakes on the Tibetan Plateau
Authors: Gao Peixin , Lu Huibin , Phurbu Dorji , Wu Qinglong , Xing Peng
Published: December 2022

Thousands of lakes harbouring different characteristics (pH, salinity, temperature) are located on the Tibetan Plateau, and the mining of microbial resources inhabited in these lakes has great value. Two Gram-stain-negative, aerobic, rod-shaped, non-motile strains (LQ15WT and AIY15WT) were isolated from freshwater lakes on the Tibetan Plateau. Comparisons based on the 16S rRNA gene sequences showed that both strains LQ15WT and AIY15WT share 16S rRNA gene sequence similarities 98.4 % with

Aquiflexum aquatile

Z0201T, but only about 95.0 % with

Aquiflexum balticum

DSM 16537T. The 16S rRNA gene sequence similarity between strains LQ15WT and AIY15WT was 98.9 %. The phylogenetic tree reconstructed based on 16S rRNA gene sequences also showed that strains LQ15WT and AIY15WT take

A. aquatile

Z0201T as their closest neighbour and these three strains form a tight cluster. In the phylogenomic tree, the genus

Aquiflexum

was splited into two clusters by

Mariniradius saccharolyticus

. Strains LQ15WT, AIY15WT and

A. aquatile

Z0201T still formed a close cluster, and

A. balticum

DSM 16537T and

Aquiflexum lacus

CUG 91378T formed another cluster. The calculated OrthoANIu, average amino acid identity and digital DNA–DNA hybridization values among strains LQ15WT, AIY15WT,

A. aquatile

Z0201T,

A. balticum

DSM 16537T and

A. lacus

CUG 91378T were less than 91.0, 92.9 and 42.1 %, respectively. The major respiratory quinones of both strains LQ15WT and AIY15WT were MK-7 (32 %) and MK-8 (68 %), and their major fatty acids were iso-C15 : 0, C18 : 1
 ω9c, summed feature 3 and summed feature 9. The predominant polar lipids of both strains were phosphatidylethanolamine, unidentified aminophospholipids, unidentified phospholipids and lipids. Strain AIY15WT also contained phosphatidylglycerol and unidentified glycolipid. Considering the distinct phylogenetic relationships and chemotaxonomic characteristics between strains

A. aquatile

Z0201T and

A. balticum

DSM 16537T, it is proposed to reclassify

A. aquatile

into a novel genus Cognataquiflexum gen. nov. as Cognataquiflexum aquatile comb. nov., and strains LQ15WT and AIY15WT should represent two independent novel species of the genus Cognataquiflexum, for which the names Cognataquiflexum nitidum sp. nov. (type strain: LQ15WT=CICC 24711T=JCM 34222T) and Cognataquiflexum rubidum sp. nov. (type strain: AIY15WT=CICC 24708T=JCM 34612T) are proposed.
Actinotalea soli sp. nov., isolated from Kubuqi Desert soil
Authors: Du Jie , Ping Weiwei , Chen Ya , Pang Huancheng , Bai Pengze , Cui Siqi , Zhang Jianli
Published: December 2022

A Gram-stain positive, facultatively anaerobic, motile rod-shaped strain, BY-33T, was isolated from a soil sample obtained from the Kubuqi Desert, PR China. Phylogenetic analysis based on 16S rRNA gene sequence similarity revealed that strain BY-33T was most closely related to the genus

Actinotalea

, including

Actinotalea ferrariae

CF5-4T (98.2 % similarity), ‘Actinotalea subterranea’ HO-Ch2T (98.0 %),

Actinotalea solisilvae

THG-T121T (97.6 %), ‘Actinotalea bogoriensis’ 69B4T (97.5 %),

Actinotalea fermentans

MT (97.3 %) and ‘Actinotalea carbonis’ T26T (97.0 %). The strain grew at 0‒37 °C (optimum, 28–30 °C) and pH 6.0–11.0 (optimum, pH 9.0–10.0) and with 0‒8.0 % (w/v) NaCl (optimum, 3.0%) on tryptic soy agar. It had catalase activity, but no oxidase activity. The polar lipids of strain BY-33T contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, and phosphatidylinositol mannosides. The major respiratory quinone of strain BY-33T was MK-10 (H4). Its major fatty acids were anteiso-C15 : 0, anteiso-C15 : 1 A and C16 : 0. The genomic DNA G+C content of strain BY-33T was 73.0 mol% based on total genome calculations. The average nucleotide identity scores between the genomic sequences of strain BY-33T and the other species of the genus

Actinotalea

were found to be low (ANIm <85.0 %, ANIb <77.0 % and OrthoANIu <78.0 %). Furthermore, the digital DNA–DNA hybridization and average amino acid identity values between strain BY-33T and the closely related species ranged from 20.5 to 21.0% and from 62.2 to 72.2 %, respectively. Based on the results of phylogenetic, phenotypic, genotypic and chemotaxonomic analyses, it is concluded that strain BY-33T represents a novel species within the genus

Actinotalea

, for which the name Actinotalea soli sp. nov. is proposed. The type strain is BY-33T (=CGMCC 1.17460T=KCTC 49362T).
Predicting Adverse Events in the Cardiothoracic Surgery Intensive Care Unit Using Machine Learning: Results and Challenges
Authors: Amal Saeed , Kramer Robert , Sawyer Douglas , Rabb Jaime B , Maurais Alanna S , Ross Cathy S. , Iribarne Alexander , Winslow Raimond L
Published: December 2022

It is highly important to anticipate impending problems in patients in the cardiothoracic intensive care unit (CTICU) and be proactive with respect to prediction of adverse events, enabling interventions to prevent them. In order to develop models that predict the occurrence of adverse events after cardiac surgery, a dataset of 9,237 patients was constructed of a single center’s Society of Thoracic Surgeons (STS) internal database. 1,383 of those patients had developed at least one of seven defined adverse events for this analysis. For the control set, we randomly picked 1,383 patients from the group who did not develop any adverse event. The ensemble learning algorithm, random forest, was applied and outperformed the best reported logistic regression models for similar task (c-statistic of ∼0.81), by achieving an AUC of 0.86 with a 95% CI of [0.81-0.90], specificity of 0.72, sensitivity of 0.82, PPV of 0.78 and NPV of 0.77. In the future, we plan to run a similar evaluation process on a multicenter dataset, and then use this static prediction model as a context for using time-evolving data to develop algorithms for real-time feedback to care teams. In acute care settings, such as the operating room and intensive care unit, the ability to anticipate potentially fatal complications will be enhanced by using supervised machine learning algorithms.
Identifying the neurodevelopmental and psychiatric signatures of genomic disorders associated with intellectual disability
Authors: Donnelly Nicholas A , Cunningham Adam C , Bracher-Smith Matthew , Chawner Samuel , Stochl Jan , Ford Tamsin , Raymond F Lucy , Escott-Price Valentina , van den Bree Marianne BM
Published: December 2022

Introduction

Genomic conditions can be associated with developmental delay, intellectual disability and physical and mental health symptoms, but are individually rare and variable, which limits the use of standard clinical guidelines. A simple screening tool to identify young people with genetic conditions associated with neurodevelopmental disorders (ND-GC) who could benefit from further support would be of considerable value. We used machine learn approaches to address this question.

Methods

A total of 489 individuals were included: 376 with a ND-GC, mean age=9.33, 63% male) and 113 unaffected siblings; mean age=10.35, 50% male). Primary carers completed detailed assessments of behavioural, neurodevelopmental and psychiatric symptoms and physical health conditions. Machine learning techniques (elastic net regression, random forests, support vector machines and artificial neural networks) were used to develop classifiers of ND-GC status using a limited set of variables. Exploratory Graph Analysis was used to understand associations within the final variable set.

Results

We identified a set of 30 variables best discriminating between ND-GC carriers and control individuals, which formed 4 dimensions: Anxiety, Motor Development, Insomnia and Depression. All methods showed high discrimination accuracy with Linear Support Vector machines outperforming other methods (AUROC between 0.959 and 0.971).

Conclusions

In this study we developed models that identified a compact set of psychiatric and physical health measures that differentiate individuals with a ND-GC from controls and highlight the structure within these measures. This work is a step toward developing of a screening instrument to select young people with ND-GCs who might benefit from further specialist assessment.
Babesia microti with multiple resistance mutations detected in an immunocompromised patient receiving atovaquone prophylaxis
Authors: Holbrook Nolan R. , Klontz Erik H. , Adams Gordon C. , Schnittman Samuel R. , Issa Nicolas C. , Bond Sheila A. , Branda John A. , Lemieux Jacob E.
Published: December 2022

We reportBabesia microtigenomic sequences with multiple mutations in the atovaquone-target region of cytochrome b and the azithromycin-associated ribosomal protein L4, including newly identified mutations. The parasite was sequenced from an immunocompromised patient on prophylactic atovaquone forPneumocystispneumonia for several weeks before the diagnosis of babesiosis.
Predicting transcription factor activity using prior biological information
Authors: Estabrook Joseph , Yashar William M. , Holly Hannah D. , Somers Julia , Nikolova Olga , Barbur Özgün , Braun Theodore P. , Demir Emek
Published: December 2022

Transcription factors are critical regulators of cellular gene expression programs. Disruption of normal transcription factor regulation is associated with a broad range of diseases. In order to understand the mechanisms that underly disease pathogenesis, it is critical to detect aberrant transcription factor activity. We have developed Priori, a computational method to predict transcription factor activity from RNA sequencing data. Priori has several key advantages over existing methods. Priori utilizes literature-supported regulatory relationship information to identify known transcription factor target genes. Using these transcriptional relationships, Priori uses linear models to determine the impact and direction of transcription factor regulation on the expression of its target genes. In our work, we evaluated the ability of Priori and 16 other methods to detect aberrant activity from 124 single-gene perturbation experiments. We show that Priori identifies perturbed transcription factors with greater sensitivity and specificity than other methods. Furthermore, our work demonstrates that Priori can be used to discover significant determinants of survival in breast cancer as well as identify mediators of drug response in leukemia from primary patient samples.
Aberrant miR-29 is a predictive feature of severe phenotypes in pediatric Crohn’s disease
Authors: Shumway Alexandria J. , Shanahan Michael T. , Hollville Emilie , Chen Kevin , Beasley Caroline , Villanueva Jonathan W. , Albert Sara , Lian Grace , Cure Moises R. , Schaner Matthew , Zhu Lee-Ching , Bantumilli Surekha , Deshmukh Mohanish , Furey Terrence S. , Sheikh Shehzad Z. , Sethupathy Praveen
Published: December 2022

Crohn’s disease (CD) is a chronic inflammatory gut disorder. Molecular mechanisms underlying the clinical heterogeneity of CD remain poorly understood. MicroRNAs (miRNAs) are important regulators of gut physiology and several have been implicated in the pathogenesis of adult CD. However, there is a dearth of large-scale miRNA studies for pediatric CD. We hypothesized that specific miRNAs uniquely mark pediatric CD. We performed small RNA-sequencing of patient-matched non-inflamed colon and ileum biopsies from treatment-naïve pediatric patients with CD (n=169) and a control cohort (n=108). Comprehensive miRNA analysis revealed 58 miRNAs altered in pediatric CD. Notably, multinomial logistic regression analysis revealed that index levels of ileal miR-29 are strongly predictive of severe inflammation and stricturing. Transcriptomic analyses of transgenic mice overexpressing miR-29 show a significant reduction of the tight junction protein genePmp22and classic Paneth cell markers. The dramatic loss of Paneth cells was confirmed by histologic assays. Moreover, we also found that pediatric CD patients with elevated miR-29 exhibit significantly lower Paneth cell counts, increased inflammation scores, and reduced levels ofPMP22. These findings strongly indicate that miR-29 up-regulation is a distinguishing feature of pediatric CD, highly predictive of severe phenotypes, and associated with inflammation and Paneth cell loss.