bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility and Considerations for Remote Interviewing of Persons Living With Dementia: Adaptations for COVID-19
Authors: Yonashiro-Cho Jeanine , Avent Elizabeth , Mosqueda Laura , Gassoumis Zachary
Published: December 2021

The continuing COVID-19 pandemic has necessitated changes to research protocols and approaches to mitigate health risks to both study participants and researchers. This is particularly true of studies exploring the biopsychosocial well-being and personal perspectives of older adults and those at elevated risk of COVID-19 complications. While videoconferencing platforms have enabled remote work and social activities, reliance on them may potentially exclude some individuals (e.g., those without digital devices, access to high speed internet or proficiency with technology). Persons living with dementia (PLWD) may experience difficulties navigating videoconferencing systems and building rapport with interviewers, though the inclusion of PLWD in research is necessary to ensuring their equitable representation. This presentation disseminates promising practices and lessons learned from a longitudinal study conducting remote interviews on sensitive topics with PLWD and their care partners (CP). Findings are drawn from a case study of the Better Together Dementia Care Study, an 18-month longitudinal study of PLWD (N=8) and their CPs (N=13), which implemented remote interviewing in Summer 2020 to gather data on the quality-of-life, resilience, relationship quality, adverse childhood experiences, mistreatment, and health status of PLWD. Researchers were able to interview most enrolled PLWD (n=7) via videoconferencing. Paper surveys were mailed to phone-interviewed participants, enabling them to view questions and answer choices in concordance with verbal queries. Researchers also tested a protocol asking CPs to leave the room while PLWD answered questions on sensitive topics. Findings support the use of remote interviewing with PLWD and provide insights to guide replication of these approaches.
Long-time solutions of scalar hyperbolic reaction equations incorporating relaxation and the Arrhenius combustion nonlinearity
Authors: Leach J A , Bassom Andrew P
Published: December 2021

We consider an initial-value problem based on a class of scalar nonlinear hyperbolic reaction–diffusion equations of the general form $$\begin{align*} & u_{\tau\tau}+u_{\tau}=u_{{xx}}+\varepsilon (F(u)+F(u)_{\tau} ), \end{align*}$$in which ${x}$ and $\tau $ represent dimensionless distance and time, respectively, and $\varepsilon>0$ is a parameter related to the relaxation time. Furthermore, the reaction function, $F(u)$, is given by the Arrhenius combustion nonlinearity, $$\begin{align*} & F(u)=e^{-{E}/{u}}(1-u), \end{align*}$$in which $E>0$ is a parameter related to the activation energy. The initial data are given by a simple step function with $u({x},0)=1$ for ${x} \le 0$ and $u({x},0)=0$ for ${x}> 0$. The above initial-value problem models, under certain simplifying assumptions, combustion waves in premixed gaseous fuels; here, the variable $u$ represents the non-dimensional temperature. It is established that the large-time structure of the solution to the initial-value problem involves the evolution of a propagating wave front, which is of reaction–diffusion or reaction–relaxation type depending on the values of the problem parameters $E$ and $\varepsilon $.
Prognostic Nutritional Index and Major Adverse Cardiac Events After Burn Surgery: A Propensity Score Matching Analysis
Authors: Kim Hee Yeong , Yu Jihion , Kong Yu-Gyeong , Park Jun-Young , Shin Donghyeok , Seo Young Joo , Kim Young-Kug
Published: December 2021

Burn injuries can cause significant malnutrition, leading to cardiovascular impairments. The prognostic nutritional index (PNI) predicts postoperative complications. We evaluated the impact of preoperative PNI on major adverse cardiac events (MACE) after burn surgery. PNI was calculated using the equation, 10×(serum albumin level)+0.005×(total lymphocyte count). Multivariable logistic regression analysis was conducted to evaluate the predictors for MACE at 6 months after burn surgery. Receiver operating characteristic curve and propensity score matching analyses were conducted. Additionally, Kaplan–Meier analysis was conducted to compare postoperative 1-year mortality between MACE and non-MACE groups. MACE after burn surgery occurred in 184 (17.5%) of 1049 patients. PNI, age, American Society of Anesthesiologists physical status, and TBSA burned were significantly related to MACE. The area under the receiver operating characteristic curve of PNI was 0.729 (optimal cutoff value = 35). After propensity score matching, the incidence of MACE in the PNI <35 group was higher than that in the PNI ≥35 group (20.1% vs 9.6%, P < .001). PNI <35 was related to an increased incidence of MACE (odds ratio = 2.373, 95% confidence interval = 1.499–3.757, P < .001). The postoperative 1-year mortality was higher in the MACE group than in the non-MACE group (54.9% vs 9.1%, P < .001). Preoperative PNI was a predictor for MACE after burn surgery. PNI <35 was significantly related to an increased incidence of MACE. Moreover, MACE was related to higher postoperative 1-year mortality.
The TELPERION survey for distant [O iii] clouds around luminous and hibernating AGN
Authors: Keel William C , Moiseev Alexei , Kozlova D V , Ikhsanova A I , Oparin D V , Uklein R I , Smirnova A A , Eselevich M V
Published: December 2021

We present a narrow-band [O iii] imaging survey of 111 active galactic nucleus (AGN) hosts and 17 merging-galaxy systems, in search of distant extended emission-line regions (EELRs) around AGNs (either extant or faded). Our data reach deeper than detection from the broad-band SDSS data and cover a wider field than some early emission-line surveys used to study extended structure around AGNs. Spectroscopic follow-up confirms two new distant AGN-ionized clouds, in the merging systems NGC 235 and NGC 5514, projected at 26 and 75 kpc from the nuclei (respectively). We also recover the previously known region in NGC 7252. These results strengthen the connection between EELRs and tidal features; kinematically quiescent distant EELRs are virtually always photoionized tidal debris. We see them in ≈10 per cent of the galaxies in our sample with tidal tails. Energy budgets suggest that the AGN in NGC 5514 has faded by >3 times during the extra light traveltime ≈250 000 yr from the nucleus to the cloud and then to the observer; strong shock emission in outflows masks the optical signature of the AGN. For NGC 235 our data are consistent with but do not unequivocally require variation over ≈85 000 yr. In addition to these very distant ionized clouds, we find luminous and extensive line emission within four galaxies – IC 1481, ESO 362-G08, NGC 5514, and NGC 7679. Among these, IC 1481 shows apparent ionization cones, a rare combination with its LINER AGN spectrum. In NGC 5514, we measure a 7-kpc shell expanding at ≈370 km s−1 west of the nucleus.
Do quasar X-ray and UV flux measurements provide a useful test of cosmological models?
Authors: Khadka Narayan , Ratra Bharat
Published: December 2021

The recent compilation of quasar (QSO) X-ray and ultraviolet (UV) flux measurements include QSOs that appear to not be standardizable via the X-ray luminosity and UV luminosity (LX–LUV) relation and so should not be used to constrain cosmological model parameters. Here, we show that the largest of seven sub-samples in this compilation, the SDSS-4XMM QSOs that contribute about 2/3 of the total QSOs, have LX–LUV relations that depend on the cosmological model assumed and also on redshift, and is the main cause of the similar problem discovered earlier for the full QSO compilation. The second and third biggest sub-samples, the SDSS-Chandra and XXL QSOs that together contribute about 30 per cent of the total QSOs, appear standardizable, but provide only weak constraints on cosmological parameters that are not inconsistent with the standard spatially flat ΛCDM model or with constraints from better-established cosmological probes.
Transient quasi-periodic oscillations at γ-rays in the TeV blazar PKS 1510-089
Authors: Roy Abhradeep , Sarkar Arkadipta , Chatterjee Anshu , Gupta Alok C , Chitnis Varsha , Wiita P J
Published: December 2021

We present periodicity search analyses on the γ-ray light curve of the TeV blazar PKS 1510-089 observed by the Fermi Large Area Telescope. We report the detection of two transient quasi-periodic oscillations: A 3.6-d QPO during the outburst in 2009 that lasted five cycles (MJD 54906–54923); and a periodicity of 92 d spanning over 650 d from 2018 to 2020 (MJD 58200–58850), which lasted for seven cycles. We employed the Lomb–Scargle periodogram, Weighted Wavelet Z-transform, redfit, and the Monte Carlo light-curve simulation techniques to find any periodicity and the corresponding significance. The 3.6-d QPO was detected at a moderate significance of ∼3.5σ, while the detection significance of the 92-d QPO was ∼7.0σ. We explore a few physical models for such transient QPOs including a binary black hole system, precession of the jet, a non-axisymmetric instability rotating around the central black hole near the innermost stable circular orbit, the presence of quasi-equidistant magnetic islands inside the jet, and a geometric model involving a plasma blob moving helically inside a curved jet.
Intrinsic properties of the bars formed by the bar instability in flat stellar discs
Authors: Hozumi Shunsuke
Published: December 2021

The properties of the bars formed by the bar instability are examined for flat stellar discs. The initial mass models chosen are Kuzmin–Toomre discs, for which two types of exact equilibrium distribution function (DF) are employed in order to realize different distributions of Toomre’s Q values along the radius. First, the most linearly unstable, global two-armed modes (MLUGTAMs) of these disc models are determined by numerically solving the linearized collisionless Boltzmann equation. Next, we carry out N-body simulations whose models are constructed from the DFs adopted above. The latter simulations unravel that the MLUGTAMs corresponding to those obtained from the former modal calculations are excited in the early phases of evolution, finally being deformed into bars in the non-linear regime by the bar instability. We show that for simulated bars, the length increases and the axial ratio, in essence, decreases as the amplitude increases. These correlations are almost similar to those of the observed bars. In addition, we find that these bar properties are tightly correlated with the initial typical Q value, irrespective of the DF. In conclusion, a disc with a smaller typical Q value produces a bar which is smaller in amplitude, shorter in length, and rounder in shape. This finding might suggest that the Hubble sequence for barred galaxies is the sequence of decreasing Q from SBa to SBc or SBd. The implied correlations between the initial typical Q value and each of the bar properties are discussed on the basis of the characteristics of the MLUGTAMs.
High-fidelity KKH variant of Staphylococcus aureus Cas9 nucleases with improved base mismatch discrimination
Authors: Yuen Chaya T L , Thean Dawn G L , Chan Becky K C , Zhou Peng , Kwok Cynthia C S , Chu Hoi Yee , Cheung Maggie S H , Wang Bei , Chan Yee Man , Mak Silvia Y L , Leung Anskar Y , Choi Gigi C G , Zheng Zongli , Wong Alan S L
Published: December 2021

The Cas9 nuclease from Staphylococcus aureus (SaCas9) holds great potential for use in gene therapy, and variants with increased fidelity have been engineered. However, we find that existing variants have not reached the greatest accuracy to discriminate base mismatches and exhibited much reduced activity when their mutations were grafted onto the KKH mutant of SaCas9 for editing an expanded set of DNA targets. We performed structure-guided combinatorial mutagenesis to re-engineer KKH-SaCas9 with enhanced accuracy. We uncover that introducing a Y239H mutation on KKH-SaCas9’s REC domain substantially reduces off-target edits while retaining high on-target activity when added to a set of mutations on REC and RuvC domains that lessen its interactions with the target DNA strand. The Y239H mutation is modelled to have removed an interaction from the REC domain with the guide RNA backbone in the guide RNA-DNA heteroduplex structure. We further confirmed the greatly improved genome-wide editing accuracy and single-base mismatch discrimination of our engineered variants, named KKH-SaCas9-SAV1 and SAV2, in human cells. In addition to generating broadly useful KKH-SaCas9 variants with unprecedented accuracy, our findings demonstrate the feasibility for multi-domain combinatorial mutagenesis on SaCas9’s DNA- and guide RNA- interacting residues to optimize its editing fidelity.
Deep near-infrared imaging observation of the faint X-ray point sources constituting the Galactic bulge X-ray emission
Authors: Morihana Kumiko , Tsujimoto Masahiro , Ebisawa Ken , Gandhi Poshak
Published: December 2021

The presence of the apparently extended hard (2–10 keV) X-ray emission along the Galactic plane has been known since the early 1980s. With a deep X-ray exposure using the Chandra X-ray Observatory of a slightly off-plane region in the Galactic bulge, most of the extended emission was resolved into faint discrete X-ray sources in the Fe K band (Revnivtsev et al. 2009, Nature, 458, 1142). The major constituents of these sources have long been considered to be X-ray active stars and magnetic cataclysmic variables (CVs). However, recent works including our near-infrared (NIR) imaging and spectroscopic studies (Morihana et al. 2013, ApJ, 766, 14; Morihana et al. 2016, PASJ, 68, 57) argue that other populations should be more dominant. To investigate this further, we conducted a much deeper NIR imaging observation at the center of the Chandra’s exposure field. We have used the MOIRCS on the Subaru telescope, reaching the limiting magnitude of ∼18 mag in the J, H, and Ks bands in this crowded region, and identified ${\sim}50\%$ of the X-ray sources with NIR candidate counterparts. We classified the X-ray sources into three groups (A, B, and C) based on their positions in the X-ray color–color diagram and characterized them based on the X-ray and NIR features. We argue that the major populations of the Group A and C sources are, respectively, CVs (binaries containing magnetic or non-magnetic white dwarfs with high accretion rates) and X-ray active stars. The major population of the Group B sources is presumably white dwarf (WD) binaries with low mass accretion rates. The Fe K equivalent width in the composite X-ray spectrum of the Group B sources is the largest among the three and comparable to that of the Galactic bulge X-ray emission. This leads us to speculate that there are numerous WD binaries with low mass accretion rates which are not recognized as CVs but are the major contributor of the apparently extended X-ray emission.
Exploring the Preference for Fatigue-avoidance Goals as a Mediator Between Pain Catastrophizing, Functional Impairment, and Walking Behavior in Women With Fibromyalgia
Authors: Velasco Lilian , López-Gómez Irene , Gutiérrez Lorena , Écija Carmen , Catalá Patricia , Peñacoba Cecilia
Published: December 2021

Objectives:

Along with the symptoms of pain and fatigue, pain catastrophizing and avoidance behaviors are highly prevalent and associated with functional impairment in fibromyalgia (FM) patients. Although pain and fatigue affect patients’ quality of life, research has been exclusively focused on how pain affects physical activity and exercise. The aim of this study was to analyze the role of pain catastrophizing and preference for fatigue-avoidance goals in walking behavior and functional impairment in women with FM.

Materials and Methods:

In this cross-sectional study the sample was composed of 76 participants aged 18 years and older (mean age=55.05, SD=7.70). The study evaluated pain catastrophizing, preference for fatigue-avoidance goals, functional impairment, and walking behavior along with sociodemographic variables and clinical data.

Results:

Pain catastrophizing was associated with preference for fatigue-avoidance goals and this preference was associated with greater functional impairment and less distance walked. Path analysis supported the mediating role of preference for fatigue-avoidance goals in the relationship between pain catastrophizing and walking behavior and between pain catastrophizing and functional impairment. Furthermore, pain catastrophizing predicted greater preference for fatigue-avoidance goals which predicted more problems in functioning and less distance walked.

Discussion:

The present study may help clarify the connection between the factors that stop individuals with FM from implementing beneficial behaviors such as walking, and thus, allowing for the design of psychological interventions that seek to maintain physical functioning despite experiencing fatigue.
Distal Humerus Traction Radiographs: Is the Interobserver and Intraobserver Reliability Comparable With Computed Tomography?
Authors: Galloway Joseph D. , Shymon Stephen J. , Adams Mark R. , Reilly Mark C. , Sirkin Michael S. , Hreha Jeremy , Jung Michael T. , Madi Naji , Siracuse Brianna L. , Ahmed Irfan , Vosbikian Michael M.
Published: December 2021

Objectives:

To compare the interobserver and intraobserver reliability of traction radiographs with 2-dimensional computed tomography (2D CT) in distal humerus fracture classification and characterization.

Design:

Randomized controlled radiographic review of retrospectively collected data.

Setting:

Academic Level 1 trauma center.

Patients/Participants:

Skeletally mature patients with intra-articular distal humerus fractures with both traction radiographs and CT scans were reviewed by 11 orthopaedists from different subspecialties and training levels.

Intervention:

The intervention involved traction radiographs and 2D CT.

Main Outcome Measurements:

The main outcome measurements included interobserver and intraobserver reliability of fracture classification by the OTA/AO and Jupiter–Mehne and determination of key fracture characteristics.

Results:

For the OTA/AO and Jupiter–Mehne classifications, we found a moderate intraobserver agreement with both 2D CT and traction radiographs (κ = 0.70–0.75). When compared with traction radiographs, 2D CT improved the interobserver reliability of the OTA/AO classification from fair to moderate (κ = 0.3 to κ = 0.42) and the identification of a coronal fracture from slight to fair (κ = 0.2 to κ = 0.34), which was more pronounced in a subgroup analysis of less-experienced surgeons. When compared with 2D CT, traction radiographs improved the intraobserver reliability of detecting stable affected articular fragments from fair to substantial (κ = 0.4 to κ = 0.67).

Conclusions:

Traction radiographs provide similar diagnostic characteristics as 2D CT in distal humerus fractures. For less-experienced surgeons, 2D CT may improve the identification of coronal fracture lines and articular comminution.
Symptomatic Postoperative Epidural Hematoma in the Lumbar Spine
Authors: Butler Alexander J. , Donnally Chester J. , Goz Vadim , Basques Bryce A. , Vaccaro Alexander R. , Schroeder Gregory D.
Published: December 2021

A symptomatic postoperative epidural hematoma (SPEH) in the lumbar spine is a complication with variable presentation and the potential to rapidly cause an irrecoverable neurological injury. Significant heterogeneity exists among current case series reporting SPEH in the literature. This review attempts to clarify the known incidence, risk factors, and management pearls. Currently, literature does not support the efficacy of subfascial drains in reducing the incidence of SPEHs and possibly suggests that medication for thromboembolism prophylaxis may increase risk. Acute back pain and progressing lower extremity motor weakness are the most common presenting symptoms of SPEH. Magnetic resonance imaging is the mainstay of diagnostic imaging necessary to confirm the diagnosis, but if not acutely available, an immediate return to the operative theater for exploration without advanced imaging is justified. Treatment of a SPEH consists of emergent hematoma evacuation as a delay in repeat surgery has a deleterious effect on neurological recovery. Outcomes are poorly defined, though a significant portion of patients will have lasting neurological impairments even when appropriately recognized and managed.
Effect of Quality of Caregiver–Adolescent Relationship on Sexual Debut, Transactional Sex, and on Age-Disparate Relationships Among Young Women in Rural South Africa Enrolled in HPTN 068
Authors: Shangase Nosipho , Edwards Jess , Pence Brian , Aiello Allison , Hussong Andrea , Gómez-Olivé Xavier , Kahn Kathleen , Stoner Marie , Pettifor Audrey
Published: December 2021

Background:

Adolescent girls and young women (AGYW) remain burdened by the HIV epidemic. Positive caregiver–child relationships are associated with safe sexual behaviors in young people; yet, this literature often highlights the role of parent–child communication and parental monitoring, neglecting the importance of emotional relationships between a caregiver and adolescent.

Setting:

We used longitudinal data from HIV Prevention Trial Network 068—conducted among 2533 AGYW (13–20 years) over a period of 5 years in Agincourt, South Africa.

Method:

Kaplan–Meier and Cox models were used to estimate the effect of quality of caregiver–adolescent relationships (caring and closeness) on sexual debut, and log-binomial models with generalized estimating equations were used to examine the relationship between our exposures and transactional sex and age-disparate relationships.

Results:

Sexual debut was delayed among those who reported high levels of caregiver caring [hazard ratio: 0.80, 95% confidence interval (CI): 0.69 to 0.93] and caregiver closeness (hazard ratio: 0.80, 95% CI: 0.68 to 0.95). AGYW who reported high quality caregiver–adolescent relationships had a lower risk of transactional sex [caring: risk ratio (RR): 0.67, 95% CI: 0.58 to 0.78; closeness: RR: 0.58; 95% CI: 0.50 to 0.67]. Similarly, those with high-quality caregiver–adolescent relationships were less likely to be in an age-disparate relationship (caring: RR: 0.68, 95% CI: 0.58 to 0.79; closeness: RR: 0.77, 95% CI: 0.66 to 0.90).

Conclusions:

Findings indicate high-quality caregiver–adolescent relationships are associated with delayed sexual debut, a lower risk of transactional sex, and having an older partner. Family-centered interventions are needed to improve relationships between AGYW and caregivers.
Conidiobolomycosis: a diagnostic challenge (case report)
Authors: Bhagia Vinita , Bansal Varun , Koparkar Vidyullata
Published: December 2021

Introduction and importance:

Conidiobolomycosis is a rare chronic granulomatous fungal infection affecting the rhino-facial region. It usually occurs in immunocompetent males with agricultural exposure. A high index of suspicion is required to achieve a timely diagnosis in such cases, as the infection usually responds well to early antifungal therapy.

Case presentation:

We share a case of this disease occurring in a 21-year-old male presenting with a right nasal mass and external nasal swelling. It could not be diagnosed correctly over 2 months at various hospitals before he visited our center, where we excised the mass via functional endoscopic sinus surgery and identified Conidiobolus coronatum as the causative agent based on histopathologic examination, and MALDI-TOF. The facial deformity resolved after 3 months of therapy with oral Voriconazole.

Clinical discussion:

In this report, we discuss the pathogenesis of Conidiobolomycosis, our diagnostic approach, and the use of functional endoscopic sinus surgery, which has not been reported extensively in the existing literature.

Conclusion:

In endemic regions, conidiobolomycosis should be considered amongst the differential diagnosis of a nasal mass associated with facial swelling. A multidisciplinary team approach is required to arrive at a timely diagnosis and begin early antifungal therapy.
Cold atoms meet lattice gauge theory
Authors: Aidelsburger Monika , Barbiero Luca , Bermudez Alejandro , Chanda Titas , Dauphin Alexandre , González-Cuadra Daniel , Grzybowski Przemysław R. , Hands Simon , Jendrzejewski Fred , Jünemann Johannes , Juzeliūnas Gediminas , Kasper Valentin , Piga Angelo , Ran Shi-Ju , Rizzi Matteo , Sierra Germán , Tagliacozzo Luca , Tirrito Emanuele , Zache Torsten V. , Zakrzewski Jakub , Zohar Erez , Lewenstein Maciej
Published: December 2021

The central idea of this review is to consider quantum field theory models relevant for particle physics and replace the fermionic matter in these models by a bosonic one. This is mostly motivated by the fact that bosons are more ‘accessible’ and easier to manipulate for experimentalists, but this ‘substitution’ also leads to new physics and novel phenomena. It allows us to gain new information about among other things confinement and the dynamics of the deconfinement transition. We will thus consider bosons in dynamical lattices corresponding to the bosonic Schwinger orZ2Bose–Hubbard models. Another central idea of this review concerns atomic simulators of paradigmatic models of particle physics theory such as the Creutz–Hubbard ladder, or Gross–Neveu–Wilson and Wilson–Hubbard models. This article is not a general review of the rapidly growing field—it reviews activities related to quantum simulations for lattice field theories performed by the Quantum Optics Theory group at ICFO and their collaborators from 19 institutions all over the world. Finally, we will briefly describe our efforts to design experimentally friendly simulators of these and other models relevant for particle physics.

This article is part of the theme issue ‘Quantum technologies in particle physics’.
Loop-free tensor networks for high-energy physics
Authors: Montangero Simone , Rico Enrique , Silvi Pietro
Published: December 2021

This brief review introduces the reader to tensor network methods, a powerful theoretical and numerical paradigm spawning from condensed matter physics and quantum information science and increasingly exploited in different fields of research, from artificial intelligence to quantum chemistry. Here, we specialize our presentation on the application of loop-free tensor network methods to the study of high-energy physics problems and, in particular, to the study of lattice gauge theories where tensor networks can be applied in regimes where Monte Carlo methods are hindered by the sign problem.

This article is part of the theme issue ‘Quantum technologies in particle physics’.
Quantum simulation of lattice gauge theories in more than one space dimension—requirements, challenges and methods
Authors: Zohar Erez
Published: December 2021

Over recent years, the relatively young field of quantum simulation of lattice gauge theories, aiming at implementing simulators of gauge theories with quantum platforms, has gone through a rapid development process. Nowadays, it is not only of interest to the quantum information and technology communities. It is also seen as a valid tool for tackling hard, non-perturbative gauge theory problems by particle and nuclear physicists. Along the theoretical progress, nowadays more and more experiments implementing such simulators are being reported, manifesting beautiful results, but mostly on

1
+
1

dimensional physics. In this article, we review the essential ingredients and requirements of lattice gauge theories in more dimensions and discuss their meanings, the challenges they pose and how they could be dealt with, potentially aiming at the next steps of this field towards simulating challenging physical problems in analogue, or analogue-digital ways.

This article is part of the theme issue ‘Quantum technologies in particle physics’.
Proteomic study of the effect of metformin on C. albicans
Authors: Mascaraque Victoria , Navas Cristina , Hernaéz María Luisa , Gil Concha , Molero Gloria
Published: December 2021

Fungal infections are a global health problem. Of them, those produced by Candida albicans are the most important, with a reduced arsenal of antifungals and an increasing problem of antifungal resistance. Thus, the discovery of new antifungal targets and drugs remains interesting. Metformin is a biguanide administered as a first-line treatment for Type II Diabetes Mellitus and it has recently been published its anti-Candida action, especially against C. glabrata, and its synergistic effect with other antifungals. Our studies of the effect of metformin on C. albicans have revealed an inhibition of growth, filamentation and other phenotypes important for virulence. Although metformin has been described as an AMPK agonist, its mechanism of action is partly unknown. To deepen into the anti-Candida mechanism of action, we have addressed the differential proteomic study. A set-up of the conditions for the proteomic study has been carried out, fixing a concentration of 50mM of metformin, 6 h of treatment at 37°C in RPMI medium and with 60 rpm of agitation. The proteomic study using the Labelfree technique and 4 biological replicas, allowed the identification and quantification of a total of 1899 proteins, 206 of them presenting differences in abundance due to metformin exposure. Of these, 127 increased and 79 decreased due to the action of the drug. The most relevant functions of these proteins are related to antifungal response, filamentation, biofilm formation and metabolism, being 9 essential proteins for the microorganism that could be new antifungal targets.
Nocardia acididurans sp. nov., an acid-tolerant actinobacterium isolated from bio-fertilizer of Musa species
Authors: Sirireung Narissara , Duangupama Thitikorn , Suriyachadkun Chanwit , Thawai Chitti
Published: December 2021

A novel acid-tolerant actinobacterium (strain LPG 2T), which formed fragmented substrate mycelia, was isolated from bio-fertiliser of Musa spp. collected from Lampang Province, Thailand. Its morphological and chemotaxonomic properties, e.g., the presence of mycolic acid and MK-8 (H4ω-cycl) in the cells, showed that strain LPG 2T was a member of the genus

Nocardia

. 16S rRNA gene sequence analysis revealed that this strain was closely related to

Nocardia otitidiscaviarum

NBRC 14405T (98.7 %). The low average nucleotide identity–blast and digital DNA–DNA hybridization values (<78.6 and <24.0 %, respectively), and several phenotypic differences between strain LPG 2T and its related

Nocardia

type strains, indicated that the strain merits classification as representing a novel species of the genus

Nocardia

, for which we propose the name Nocardia acididurans sp. nov. The type strain is LPG 2T (=TBRC 11242T=NBRC 114293T).
Spontaneous Neuronal Oscillations in the Human Insula are Hierarchically Organized Traveling Waves
Authors: Das Anup , Myers John , Mathura Raissa , Shofty Ben , Metzger Brian , Bijanki Kelly , Wu Chengyuan , Jacobs Joshua , Sheth Sameer A.
Published: December 2021

The insula plays a fundamental role in a wide range of adaptive human behaviors, but its electrophysiological dynamics are poorly understood. Here we used human intracranial electroencephalographic recordings to investigate the electrophysiological properties and hierarchical organization of spontaneous neuronal oscillations within the insula. We analyzed the neuronal oscillations of the insula directly and found that rhythms in the theta and beta frequency oscillations are widespread and spontaneously present. These oscillations are largely organized along the anterior–posterior axis of the insula. Both the left and right insula showed anterior-to-posterior decreasing gradients for the power of oscillations in the beta frequency band. The left insula also showed a posterior-to-anterior decreasing frequency gradient and an anterior-to-posterior decreasing power gradient in the theta frequency band. In addition to measuring the power of these oscillations, we also examined the phase of these signals across simultaneous recording channels and found that the insula oscillations in the theta and beta bands are traveling waves. The strength of the traveling waves in each frequency was positively correlated with the amplitude of each oscillation. However, the theta and beta traveling waves were uncoupled to each other in terms of phase and amplitude, which suggested that insula traveling waves in the theta and beta bands operate independently. Our findings provide new insights into the spatiotemporal dynamics and hierarchical organization of neuronal oscillations within the insula, which, given its rich connectivity with widespread cortical regions, indicates that oscillations and traveling waves have an important role in intra- and inter-insula communication.
A Mathematical Model of Mitochondria in Proximal Tubule and Thick Ascending Limb Cells
Authors: Bell William , Layton Anita T.
Published: December 2021

Mitochondria are a key player in several kinds of tissue injury, and are even the ultimate cause of certain diseases. In this work we introduce new models of mitochondrial ATP generation in multiple tissues, including liver hepatocytes and the medullary thick ascending limb in the kidney. Using this model, we predict these tissues’ responses to hypoxia, uncoupling, ischemia-reperfusion, and oxidative phosphorylation dysfunction. Our results suggest mechanisms explaining differences in robustness of mitochondrial function across tissues.The medullary thick ascending limb and proximal tubule in the kidney both experience a high metabolic demand, while having lower baseline activity of oxidative phosphorylation relative to the liver. These factors make these tissues susceptible to dysfunction of ComplexIII. A lower baseline oxygen tension observed in the thick ascending limb makes it susceptible to Complex IV. On the other hand, since the liver lacks these risk factors, and has higher baseline rates of glycolysis, it is less susceptible to all kinds of oxidative phosphorylation dysfunction.
Clinical genetics laboratories use divergent demographic frameworks across countries: comparing data structures for ‘race’, ‘ethnicity’, and ‘ancestry’ on test requisition forms
Authors: Popejoy Alice B. , Mayol Julia Gimbernat , Anderson Katherine , Hooker Gillian
Published: December 2021

Purpose

The goal of this study is to investigate how population groups are represented on requisition forms for clinical genetic testing in different laboratories.

Methods

Clinical laboratory test requisition forms (RFs) were obtained from 70 laboratories in the US, Canada, Europe, and Australia. Details about the laboratories and how RFs represent patient demographics were extracted and analyzed for trends between forms in the U.S. (N=213) and other countries (N=203).

Results

Clinical genetics laboratories included in the analysis vary widely regarding the format of demographic data collected on test requisition forms. US-based laboratory RFs are more likely than those from other countries to include ‘race’ or ‘ethnicity’. These are most often represented as categorical data, with multiple-choice options. RFs from laboratories in other countries do not include ‘race’, and those that include ‘ethnicity’ most often provide a blank space for open-ended responses.

Conclusions

These results are consistent with existing research on heterogeneity in the nomenclature and number of categories used to describe patient populations across clinical genetics laboratories in the US. It also suggests systemic differences in the way measures of diversity are conceptualized in the US compared to other countries.
A Model of Mitochondria in the Rat Hepatocyte
Authors: Bell William , Layton Anita T.
Published: December 2021

Mitochondria are a key player in several kinds of tissue injury, and are even the ultimate cause of certain diseases. In this work we introduce a new model of mitochondrial ATP generation in liver hepatocytes of the rat. Ischemia-reperfusion is an intriguing example of a non-equilibrium behaviour driven by a change in tissue oxygen tension. Ischemia involves prolonged hypoxia, followed by the sudden return of oxygen during reperfusion. During reperfusion, we predict that the build up of succinate causes the electron transport chain in the liver to temporarily be in a highly reduced state. This can lead to the production of reactive oxygen species. We accurately predict the timescale on which the electron transport chain is left in a reduced state, and we observe levels of reduction likely to lead to reactive oxygen species production. Aside from the above, we predict thresholds for ATP depletion from hypoxia, and we predict the consequences for oxygen consumption of uncoupling.
Optimizing Dosage-Specific Treatments in a Multi-Scale Model of a Tumor Growth
Authors: Ponce-de-Leon Miguel , Montagud Arnau , Akasiadis Charilaos , Schreiber Janina , Ntiniakou Thaleia , Valencia Alfonso
Published: December 2021

The emergence of cell resistance in cancer treatment is a complex phenomenon that emerges from the interplay of processes that occur at different scales. For instance, molecular mechanisms and population-level dynamics such as competition and cell-cell variability have been described as playing a key role in the emergence and evolution of cell resistances. Multi-scale models are a useful tool to study biology at a very different time and spatial scales, as they can integrate different processes that take place at the molecular, cellular and intercellular levels. In the present work, we use an extended hybrid multi-scale model of 3T3 fibroblast spheroid to perform a deep exploration of the parameter space of effective treatment strategies based on TNF pulses. To explore the parameter space of effective treatments in different scenarios and conditions, we have developed an HPC-optimized model exploration workflow based on EMEWS. We first studied the effect of the cells spatial distribution in the values of the treatment parameters by optimizing the supply strategies in 2D monolayers and 3D spheroids of different sizes. We later study the robustness of the effective treatments when heterogeneous populations of cells are considered. We found that our model exploration workflow can find effective treatments in all the studied conditions. Our results show that cells’ spatial geometry, as well as, population variability should be considered when optimizing treatment strategies in order to find robust parameter sets.
Air Pollution Particles Hijack Peroxidasin to Disrupt Immunosurveillance and Promote Lung Cancer
Authors: Wang Zhenzhen , Zhai Ziyu , Chen Chunyu , Tian Xuejiao , Xing Zhen , Xing Panfei , Yang Yushun , Zhang Junfeng , Wang Chunming , Dong Lei
Published: December 2021

Although fine particulate matter (FPM) in air pollutants and tobacco smoke is recognized as a strong carcinogen and global threat to public health, its biological mechanism for inducing lung cancer remains unclear. Here, by investigating FPM’s bioactivities in lung carcinoma mice models, we discover that these particles promote lung tumor progression by inducing aberrant thickening of tissue matrix and hampering migration of anti-tumor immunocytes. Upon inhalation into lung tissue, these FPM particles abundantly adsorb peroxidasin (PXDN) – an enzyme mediating type IV collagen (Col IV) crosslinking – onto their surface. The adsorbed PXDN exerts abnormally high activity to crosslink Col IV via increasing the formation of sulfilimine bonds at the NC1 domain, leading to an overly dense matrix in the lung tissue. This disordered structure decreases the mobility of cytotoxic CD8+ T lymphocytes into the lung and consequently impairs the local immune surveillance, enabling the flourish of nascent tumor cells. Meanwhile, inhibiting the activity of PXDN effectively abolishes the tumor-promoting effect of FPM, indicating the key impact of aberrant PXDN activity on tumorigenic process. In summary, our finding elucidates a new mechanism for FPM-induced lung tumorigenesis and identifies PXDN as a potential target for treatment or prevention of the FPM-relevant biological risks.

Graphical abstract
Structure prediction of the druggable fragments in SARS-CoV-2 untranslated regions
Authors: Gumna Julita , Antczak Maciej , Adamiak Ryszard W. , Bujnicki Janusz M. , Chen Shi-Jie , Ding Feng , Ghosh Pritha , Li Jun , Mukherjee Sunandan , Nithin Chandran , Pachulska-Wieczorek Katarzyna , Ponce-Salvatierra Almudena , Popenda Mariusz , Sarzynska Joanna , Wirecki Tomasz , Zhang Dong , Zhang Sicheng , Zok Tomasz , Westhof Eric , Szachniuk Marta , Miao Zhichao , Rybarczyk Agnieszka
Published: December 2021

The outbreak of the COVID-19 pandemic has led to intensive studies of both the structure and replication mechanism of SARS-CoV-2. In spite of some secondary structure experiments being carried out, the 3D structure of the key function regions of the viral RNA has not yet been well understood. At the beginning of COVID-19 breakout, RNA-Puzzles community attempted to envisage the three-dimensional structure of 5′- and 3′-Un-Translated Regions (UTRs) of the SARS-CoV-2 genome. Here, we report the results of this prediction challenge, presenting the methodologies developed by six participating groups and discussing 100 RNA 3D models (60 models of 5′-UTR and 40 of 3′-UTR) predicted through applying both human experts and automated server approaches. We describe the original protocol for the reference-free comparative analysis of RNA 3D structures designed especially for this challenge. We elaborate on the deduced consensus structure and the reliability of the predicted structural motifs. All the computationally simulated models, as well as the development and the testing of computational tools dedicated to 3D structure analysis, are available for further study.
Evaluation of the effects of nicotine on the friction of the articular cartilage and the reversion of the estrogen in vitro
Authors: Li Huiqin , Tang Jiaxin , Zhang Ying , Han Yao
Published: December 2021

Background

Osteoarthritis is a severe disease for menopausal women, especially for those who exposed in the smoking and second hand-smoking. This study investigated the effect of the nicotine and estrogen on the articular cartilage.

Methods

The articular cartilages were treated by nicotine and estrogen in vitro. Then the frictional properties and morphology on the surface were investigated using atomic force microscope. Proteoglycan 4(PRG4), as the key boundary lubricant of articular cartilage was characterized.

Results

Nicotine down-regulates the friction coefficient and secretion of PRG4 significantly and then the estrogen increase them again. The adhesion forces also showed the same trend due to the content of anti-adhesive PRG4.

Discussion

This study demonstrated that the present concentration nicotine has a negative effect on the articular cartilage and the estrogen has a better protecting effect. This may provide a potential guide for OA prevention and treatment.
Identification of CDRH3 Loops in the B Cell Receptor Repertoire that Can Be Engaged by Candidate Immunogens
Authors: Swanson Olivia , Beem Joshua S. Martin , Rhodes Brianna , Wang Avivah , Barr Maggie , Chen Haiyan , Parks Robert , Saunders Kevin O. , Haynes Barton F. , Wiehe Kevin , Azoitei Mihai L.
Published: December 2021

A major goal for the development of vaccines against rapidly mutating viruses, such as influenza or HIV, is to elicit antibodies with broad neutralization capacity. However, B cell precursors capable of maturing into broadly neutralizing antibodies (bnAbs) can be rare in the immune repertoire. Due to the stochastic nature of B cell receptor (BCR) rearrangement, a limited number of third heavy chain complementary determining region (CDRH3) sequences are identical between different individuals. Thus, in order to successfully engage broadly neutralizing antibody precursors that rely on their CDRH3 loop for antigen recognition, immunogens must be able to tolerate sequence diversity in the B cell receptor repertoire across an entire vaccinated population. Here, we present a combined experimental and computational approach to identify BCRs in the human repertoire with CDRH3 loops predicted to be engaged by a target immunogen. For a given antibody/antigen pair, deep mutational scanning was first used to measure the effect of CDRH3 loop substitution on binding. BCR sequences, isolated experimentally or generatedin silico, were subsequently evaluated to identify CDRH3 loops expected to be bound by the candidate immunogen. We applied this method to characterize two HIV-1 germline-targeting immunogens and found differences in the frequencies with which they are expected to engage target B cells, thus illustrating how this approach can be used to evaluate candidate immunogens towards B cell precursors engagement and to inform immunogen optimization strategies for more effective vaccine design.
A neuronal prospect theory model in the brain reward circuitry
Authors: Imaizumi Yuri , Tymula Agnieszka , Tsubo Yasuhiro , Matsumoto Masayuki , Yamada Hiroshi
Published: December 2021

Prospect theory, arguably the most prominent theory of choice, is an obvious candidate for neural valuation models. How the activity of individual neurons, a possible computational unit, reflects prospect theory remains unknown. Here, we show with theoretical accuracy equivalent to that of human neuroimaging studies that single-neuron activity in four core reward-related cortical and subcortical regions represents the subjective valuation of risky gambles in monkeys. The activity of individual neurons in monkeys passively viewing a lottery reflects the desirability of probabilistic rewards, parameterized as a multiplicative combination of a utility and probability weighting functions in the prospect theory framework. The diverse patterns of valuation signals were not localized but distributed throughout most parts of the reward circuitry. A network model aggregating these signals reliably reconstructed risk preferences and subjective probability perceptions revealed by the animals’ choices. Thus, distributed neural coding explains the computation of subjective valuations under risk.