bluuebunny/crossref_metadata_2025 huggingface dataset:
Turkey implementation model for the centre of excellence in healthcare services
Authors: Gökmen Kavak Demet , Can Ceren , İbrahim Halil Kayral , Çizmeci Şenel Figen
Published: April 2022

Today, in many countries, centres of excellence that can serve as a reference are determined in order to ensure easy access and quality healthcare services for patients whose diagnosis and treatment require advanced expertise, trained health human resource, experience, and high technology. Centres of excellence provide better health outcomes and equitable and easy access for patients. In addition, they provide very important advantages such as improving the quality of health services and health outcomes at the country level by increasing the provision of effective, efficient, high-quality health care services, increasing international competitiveness and health tourism potential in the field of health, and reducing catastrophic health expenditures. In 2018, a series of studies were initiated in cooperation with the Turkey Health Services Quality and Accreditation Institute and the Republic of Turkey Ministry of Health to identify centres of excellence in Turkey. The aim of this manuscript is to share the national implementation model that is being designed for Turkey for the studies of centers of excellence in health services.
The future of quality and accreditation surveys: Digital transformation and artificial intelligence
Authors: Cayirtepe Zuhal , Senel Figen Cizmeci
Published: April 2022

Accreditation is documented and reported by the external evaluation organization that the health facility provides services at certain standards. While on-site survey practices are being carried out by external evaluation organizations, there has been a trend toward new survey approaches using digital technologies as a result of the research carried out to ensure efficiency in surveys as well as improved effectiveness. With the emergence of the Covid-19 epidemic, external evaluation organization in all sectors has been forced to work remotely and adopt digital technology. Shared remote survey experience results reported its benefits as also some problems. The increase in the adaptation of digital technologies in quality and accreditation surveys showed that the use of technology in the survey structure will develop further in the future. Can artificial intelligence technologies be the next digital technology that will be adapted to surveys? In addition to the benefits of using artificial intelligence technologies, there are potential problems to consider and some requirements for using them. external evaluation organizations must be prepared to develop their organizational capacity to ensure that quality and accreditation surveys are responsive to changing industry needs and must make the necessary investments to make the data, which is the most important source of digital technologies, accessible and usable.

Graphical Abstract
Revealing the genetic basis of eyelid pigmentation in Hereford cattle
Authors: Jara Eugenio , Peñagaricano Francisco , Armstrong Eileen , Ciappesoni Gabriel , Iriarte Andrés , Navajas Elly Ana
Published: April 2022

Ocular squamous cell carcinoma and infectious keratoconjunctivitis are common ocular pathologies in Hereford cattle with considerable economic impact. Both pathologies have been associated with low eyelid pigmentation, and thus, genetic selection for higher eyelid pigmentation could reduce their incidence. The objective of the present study was to reveal the genetic basis of eyelid pigmentation in Hereford cattle. The analysis included a single-step genome-wide association study (ssGWAS) and a subsequent gene-set analysis in order to identify individual genes, genetic mechanisms, and biological pathways implicated in this trait. Data consisted of eyelid pigmentation records in 1,165 Hereford bulls and steers, visually assessed in five categories between 0% and 100%. Genotypic data for 774,660 single-nucleotide polymorphism markers were available for 886 animals with pigmentation records. Pedigree information of three generations of ancestors of animals with phenotype was considered in this study, with a total of 4,929 animals. Our analyses revealed that eyelid pigmentation is a moderately heritable trait, with heritability estimates around 0.41. The ssGWAS identified at least eight regions, located on BTA1, BTA3, BTA5, BTA14, BTA16, BTA18, BTA19, and BTA24, associated with eyelid pigmentation. These regions harbor genes that are directly implicated in melanocyte biology and skin pigmentation, such as ADCY8, PLD1, KITLG, and PRKCA. The gene-set analysis revealed several functional terms closely related to melanogenesis, such as positive regulation of melanocyte differentiation and regulation of ERK1 and ERK2 cascade. Overall, our findings provide evidence that eyelid pigmentation is a heritable trait influenced by many loci. Indeed, the ssGWAS detected several candidate genes that are directly implicated in melanocyte biology, including melanogenesis. This study contributes to a better understanding of the genetic and biological basis of eyelid pigmentation and presents novel information that could aid to design breeding strategies for reducing the incidence of ocular pathologies in cattle. Additional research on the genetic link between eyelid pigmentation and ocular pathologies is needed.
An Unusual Presentation of Pulmonary Edema During an Ice Dive at Altitude
Authors: Sanou Aliye Z , Murray Robert L , Hernandez Eli , Sherrier David
Published: April 2022

Military diving operations occur in a wide range of austere environments, including high-altitude environments and cold weather environments; however, rarely do both conditions combine. Ice diving at altitude combines the physiologic risks of diving, a hypothermic environment, and a high-altitude environment all in one. Careful planning and consideration of the potential injuries and disease processes affiliated with the aforementioned physiologic risks must be considered. In this case report, we describe a Navy diver who became obtunded secondary to hypoxia during an ice dive at 2,987 m (9,800 ft) elevation and was subsequently diagnosed with high-altitude pulmonary edema. Further consideration of the environment, activities, and history does not make this a clear case, and swimming-induced pulmonary edema which physiologically possesses many overlaps with high-altitude pulmonary edema may have contributed or been the ultimate causal factor for the diver’s acute response.
Helium line emissivities for nebular astrophysics
Authors: Del Zanna G , Storey P J
Published: April 2022

We present the results of several collisional-radiative models describing optically thin emissivities of the main lines in neutral helium formed by recombination, for a grid of electron temperatures and densities, typical of H ii regions and planetary nebulae. Accurate emissivities are required for example to measure the helium abundance in nebulae and as a consequence its primordial value. We compare our results with those obtained by previous models, finding significant differences, well above the target accuracy of 1 per cent. We discuss in some detail our chosen set of atomic rates and the differences with those adopted by previous models. The main differences lie in the treatment of electron and proton collision rates and we discuss which transitions are least sensitive to the choice of these rates and therefore best suited to high-precision abundance determinations. We have focused our comparisons on the case B approximation where only He and He+ are considered, but also present results of full models including the bare nuclei, photoexcitation, and photoionization, and either black-body or observed illuminating spectrum in the case of the Orion nebula, to indicate which spectral lines are affected by opacity. For those transitions, accurate radiative transfer calculations should be performed. We provide tables of emissivities for all transitions within n ≤ 5 and all those between the n ≤ 5 and n′ ≤ 25 states, in the log Te (K) = 103.0(0.1)4.6 and log Ne (cm−3) = 102(0.5)6 ranges, and a fortran code to interpolate to any Te, Ne within these ranges.
Atmosphere loss in oblique Super-Earth collisions
Authors: Denman Thomas R , Leinhardt Zoë M , Carter Philip J
Published: April 2022

Using smoothed particle hydrodynamics we model giant impacts of Super-Earth mass rocky planets between an atmosphere-less projectile and an atmosphere-rich target. In this work, we present results from head-on to grazing collisions. The results of the simulations fall into two broad categories: (1) one main post-collision remnant containing material from target and projectile; (2) two main post-collision remnants resulting from ‘erosive hit-and-run’ collisions. All collisions removed at least some of the target atmosphere, in contrast to the idealized hit-and-run definition in which the target mass is unchanged. We find that the boundary between ‘hit-and-run’ collisions and collisions that result in the projectile and target accreting/merging to be strongly correlated with the mutual escape velocity at the predicted point of closest approach. Our work shows that it is very unlikely for a single giant impact to remove all of the atmosphere. For all the atmosphere to be removed, head-on impacts require roughly the energy of catastrophic disruption (i.e. permanent ejection of half the total system mass) and result in significant erosion of the mantle. We show that higher impact angle collisions, which are more common, are less efficient at atmosphere removal than head-on collisions. Therefore, single collisions that remove all the atmosphere without substantially disrupting the planet are not expected during planet formation.
Finding quadruply imaged quasars with machine learning – I. Methods
Authors: Akhazhanov A , More A , Amini A , Hazlett C , Treu T , Birrer S , Shajib A , Liao K , Lemon C , Agnello A , Nord B , Aguena M , Allam S , Andrade-Oliveira F , Annis J , Brooks D , Buckley-Geer E , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Choi A , Conselice C , Costanzi M , da Costa L N , Pereira M E S , De Vicente J , Desai S , Dietrich J P , Doel P , Everett S , Ferrero I , Finley D A , Flaugher B , Frieman J , García-Bellido J , Gerdes D W , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kim A G , Kuehn K , Kuropatkin N , Lahav O , Lima M , Lin H , Maia M A G , March M , Menanteau F , Miquel R , Morgan R , Palmese A , Paz-Chinchón F , Pieres A , Plazas Malagón A A , Sanchez E , Scarpine V , Serrano S , Sevilla-Noarbe I , Smith M , Soares-Santos M , Suchyta E , Swanson M E C , Tarle G , To C , Varga T N , Weller J ,   (DES Collaboration)
Published: April 2022

Strongly lensed quadruply imaged quasars (quads) are extraordinary objects. They are very rare in the sky and yet they provide unique information about a wide range of topics, including the expansion history and the composition of the Universe, the distribution of stars and dark matter in galaxies, the host galaxies of quasars, and the stellar initial mass function. Finding them in astronomical images is a classic ‘needle in a haystack’ problem, as they are outnumbered by other (contaminant) sources by many orders of magnitude. To solve this problem, we develop state-of-the-art deep learning methods and train them on realistic simulated quads based on real images of galaxies taken from the Dark Energy Survey, with realistic source and deflector models, including the chromatic effects of microlensing. The performance of the best methods on a mixture of simulated and real objects is excellent, yielding area under the receiver operating curve in the range of 0.86–0.89. Recall is close to 100 per cent down to total magnitude i ∼ 21 indicating high completeness, while precision declines from 85 per cent to 70 per cent in the range i ∼ 17–21. The methods are extremely fast: training on 2 million samples takes 20 h on a GPU machine, and 108 multiband cut-outs can be evaluated per GPU-hour. The speed and performance of the method pave the way to apply it to large samples of astronomical sources, bypassing the need for photometric pre-selection that is likely to be a major cause of incompleteness in current samples of known quads.
Tracing stars in Milky Way satellites with a-sloth
Authors: Chen Li-Hsin , Magg Mattis , Hartwig Tilman , Glover Simon C O , Ji Alexander P , Klessen Ralf S
Published: April 2022

We study the stellar mass-to-halo mass (SMHM) relation at z = 0 in 30 Milky Way (MW)-like systems down to the ultrafaint ($M_{\rm *}\lt 10^5\, {\rm M}_\odot$) regime using the semi-analytic model a-sloth. A new model allows us to follow star formation (SF) and the stochastic stellar feedback from individually sampled Pop II stars. Our fiducial model produces consistent results with the SMHM relation derived from abundance matching and the observed cumulative stellar mass function above the observational completeness. We find a plateau in the SMHM relation in the ultrafaint regime. The stellar mass of this plateau tells us how many stars formed before supernovae occur and regulate further SF, which is determined by the Pop II SF efficiency. We also find that the number of luminous satellites increases rapidly as M* decreases until $M_{\rm *}\approx 10^4\, {\rm M}_\odot$. Finally, we find that the relative streaming velocity between baryons and dark matter at a high redshift is important in determining the number of ultrafaint dwarf galaxies at z = 0. The new model in a-sloth provides a framework to study the stellar properties and the formation history of metal-poor stars in MW and its satellites.
A survey of disc thickness and viscosity in circumbinary accretion: Binary evolution, variability, and disc morphology
Authors: Dittmann Alexander J , Ryan Geoffrey
Published: April 2022

Much of the parameter space relevant to the evolution of astrophysical circumbinary accretion discs remains unexplored. We have carried out a suite of circumbinary disc simulations surveying both disc thickness and kinematic viscosity, using both constant-ν and constant-α prescriptions. We focus primarily on disc aspect ratios between 0.1 and 0.033, and on viscosities between ν = 0.0005 and ν = 0.008 (in units of binary semimajor axis and orbital frequency), and specialize to circular equal-mass binaries. Both factors strongly influence the evolution of the binary semimajor axis: at ν = 0.0005, inspirals occur at aspect ratios ≲ 0.059, while at ν = 0.004 inspirals occur only at aspect ratios ≲ 0.04. Inspirals occur largely because of the increasingly strong negative torque on the binary by streams of material which lag the binary, with negligible contributions from resonant torques excited in the circumbinary disc. We find that reductions in accretion rate occur when simulations are initialized too far from the eventual quasi-steady state driven by interaction with the binary, rather than being intrinsically linked to the disc aspect ratio. We find not only that the cavity size increases as viscosity is decreased, but that thinner circumbinary discs become more eccentric. Our results suggest that supermassive black hole binaries should be driven, more rapidly than previous estimates, from ∼parsec separations to distances where gravitational waves drive their inspiral, potentially reducing the number of binaries observable by pulsar timing arrays.
Average bolometric corrections and optical to X-ray flux measurements as a function of accretion rate for X-ray binaries
Authors: Anastasopoulou K , Zezas A , Steiner J F , Reig P
Published: April 2022

In this paper, we use an RXTE library of spectral models from 10 black hole and 9 pulsar X-ray binaries, as well as model spectra available in the literature from 13 extra-galactic ultra-luminous X-ray sources (ULXs). We compute average bolometric corrections (BC = Lband/Lbol) for our sample as a function of different accretion rates. We notice the same behaviour between black hole and pulsar BCs only when ULX pulsars are included. These measurements provide a picture of the energetics of the accretion flow for an X-ray binary based solely on its observed luminosity in a given band. Moreover, it can be a powerful tool in X-ray binary population synthesis models. Furthermore, we calculate the X-ray (2–10 keV) to optical (V band) flux ratios originating from the disc/corona at different Eddington ratios for the black hole X-ray binaries in our sample. This provides a metric of the maximum contribution of the disc to the optical emission of a binary system and better constraints on its nature (donor type, etc.). We find that the optical to X-ray flux ratio shows very little variation as a function of accretion rate, but testing for different disc geometry scenarios we find that the optical contribution of the disc increases as the p value decreases [T(r) ∼ r−p]. Moreover, observational data are in agreement with a thicker disc scenario (p < 0.65), which could also possibly explain the lack of observed high-inclination systems.
Escaping the maze: a statistical subgrid model for cloud-scale density structures in the interstellar medium
Authors: Buck Tobias , Pfrommer Christoph , Girichidis Philipp , Corobean Bogdan
Published: April 2022

The interstellar medium (ISM) is a turbulent, highly structured multiphase medium. State-of-the-art cosmological simulations of the formation of galactic discs usually lack the resolution to accurately resolve those multiphase structures. However, small-scale density structures play an important role in the life cycle of the ISM, and determine the fraction of cold, dense gas, the amount of star formation, and the amount of radiation and momentum leakage from cloud-embedded sources. Here, we derive a statistical model to calculate the unresolved small-scale ISM density structure from coarse-grained, volume-averaged quantities such as the gas clumping factor, $\mathcal {C}$, and mean density 〈ρ〉V. Assuming that the large-scale ISM density is statistically isotropic, we derive a relation between the three-dimensional clumping factor, $\mathcal {C}_\rho$, and the clumping factor of the 4$\pi$ column density distribution on the cloud surface, $\mathcal {C}_\Sigma$, and find $\mathcal {C}_\Sigma =\mathcal {C}_\rho ^{2/3}$. Applying our model to calculate the covering fraction, i.e. the 4$\pi$ sky distribution of optically thick sightlines around sources inside interstellar gas clouds, we demonstrate that small-scale density structures lead to significant differences at fixed physical ISM density. Our model predicts that gas clumping increases the covering fraction by up to 30 per cent at low ISM densities compared to a uniform medium. On the other hand, at larger ISM densities, gas clumping suppresses the covering fraction and leads to increased scatter such that covering fractions can span a range from 20 per cent to 100 per cent at fixed ISM density. All data and example code are publicly available at GitHub.
A case of intestinal amoebiasis mimicking intestinal Behçet’s disease
Authors: Fukui Ayaka , Nakayama Yoichi , Yoshida Tsuneyasu , Murakami Kosaku , Kadoba Keiichiro , Onizawa Hideo , Akizuki Shuji , Nakashima Ran , Yoshifuji Hajime , Ohmura Koichiro , Sugimoto Akihiko , Yamamoto Shuji , Morinobu Akio
Published: April 2022

Intestinal amoebiasis is caused by Entamoeba histolytica (E. histolytica) and is characterised by cecal lesions, multiple lesions, aphthae, and multiple exudative erosions. Intestinal Behçet’s disease (BD) is a chronic inflammatory disorder that is characterised by multiple ulcers. Although the aetiologies of these two bowel diseases are unrelated, they are difficult to distinguish because they present similarly with inflammation and ulcers, especially if evidence of specific pathogens is not detected. Herein, we report a case of intestinal amoebiasis in a patient with BD. The patient underwent colonoscopy four times before intestinal amoebiasis was diagnosed. As intestinal BD was initially suspected, she received high-dose glucocorticoid therapy, which exacerbated her condition. Following exacerbation, she underwent colonoscopy, and E. histolytica was revealed. Deliberate care should be taken to distinguish between intestinal amoebiasis and intestinal BD, as the appropriate treatments for these diseases are entirely different.
Multivalent DNA and nucleosome acidic patch interactions specify VRK1 mitotic localization and activity
Authors: Budziszewski Gabrielle R , Zhao Yani , Spangler Cathy J , Kedziora Katarzyna M , Williams Michael R , Azzam Dalal N , Skrajna Aleksandra , Koyama Yuka , Cesmat Andrew P , Simmons Holly C , Arteaga Eyla C , Strauss Joshua D , Kireev Dmitri , McGinty Robert K
Published: April 2022

A key role of chromatin kinases is to phosphorylate histone tails during mitosis to spatiotemporally regulate cell division. Vaccinia-related kinase 1 (VRK1) is a serine–threonine kinase that phosphorylates histone H3 threonine 3 (H3T3) along with other chromatin-based targets. While structural studies have defined how several classes of histone-modifying enzymes bind to and function on nucleosomes, the mechanism of chromatin engagement by kinases is largely unclear. Here, we paired cryo-electron microscopy with biochemical and cellular assays to demonstrate that VRK1 interacts with both linker DNA and the nucleosome acidic patch to phosphorylate H3T3. Acidic patch binding by VRK1 is mediated by an arginine-rich flexible C-terminal tail. Homozygous missense and nonsense mutations of this acidic patch recognition motif in VRK1 are causative in rare adult-onset distal spinal muscular atrophy. We show that these VRK1 mutations interfere with nucleosome acidic patch binding, leading to mislocalization of VRK1 during mitosis, thus providing a potential new molecular mechanism for pathogenesis.
A histidine cluster determines YY1-compartmentalized coactivators and chromatin elements in phase-separated enhancer clusters
Authors: Wang Wenmeng , Qiao Shiyao , Li Guangyue , Cheng Jiahui , Yang Cuicui , Zhong Chen , Stovall Daniel B , Shi Jinming , Teng Chunbo , Li Dangdang , Sui Guangchao
Published: April 2022

As an oncogenic transcription factor, Yin Yang 1 (YY1) regulates enhancer and promoter connection. However, gaps still exist in understanding how YY1 coordinates coactivators and chromatin enhancer elements to assemble enhancers and super-enhancers. Here, we demonstrate that a histidine cluster in YY1’s transactivation domain is essential for its formation of phase separation condensates, which can be extended to additional proteins. The histidine cluster is also required for YY1-promoted cell proliferation, migration, clonogenicity and tumor growth. YY1-rich nuclear puncta contain coactivators EP300, BRD4, MED1 and active RNA polymerase II, and colocalize with histone markers of gene activation, but not that of repression. Furthermore, YY1 binds to the consensus motifs in the FOXM1 promoter to activate its expression. Wild-type YY1, but not its phase separation defective mutant, connects multiple enhancer elements and the FOXM1 promoter to form an enhancer cluster. Consistently, fluorescent in situ hybridization (FISH) assays reveal the colocalization of YY1 puncta with both the FOXM1 gene locus and its nascent RNA transcript. Overall, this study demonstrates that YY1 activates target gene expression through forming liquid-liquid phase separation condensates to compartmentalize both coactivators and enhancer elements, and the histidine cluster of YY1 plays a determinant role in this regulatory mechanism.
nMOWChIP-seq: low-input genome-wide mapping of non-histone targets
Authors: Liu Zhengzhi , Naler Lynette B , Zhu Yan , Deng Chengyu , Zhang Qiang , Zhu Bohan , Zhou Zirui , Sarma Mimosa , Murray Alexander , Xie Hehuang , Lu Chang
Published: April 2022

Genome-wide profiling of interactions between genome and various functional proteins is critical for understanding regulatory processes involved in development and diseases. Conventional assays require a large number of cells and high-quality data on tissue samples are scarce. Here we optimized a low-input chromatin immunoprecipitation followed by sequencing (ChIP-seq) technology for profiling RNA polymerase II (Pol II), transcription factor (TF), and enzyme binding at the genome scale. The new approach produces high-quality binding profiles using 1,000–50,000 cells. We used the approach to examine the binding of Pol II and two TFs (EGR1 and MEF2C) in cerebellum and prefrontal cortex of mouse brain and found that their binding profiles are highly reflective of the functional differences between the two brain regions. Our analysis reveals the potential for linking genome-wide TF or Pol II profiles with neuroanatomical origins of brain cells.
Evolutionarily Conserved and Non-Conserved Roles of Heterotrimeric Gα Proteins of Plants
Authors: Pandey Sona , Roy Choudhury Swarup , Ha Chien Van , Mohanasundaram Boominathan , Li Mao , Dodds Audrey
Published: April 2022

Heterotrimeric G-proteins modulate multiple signaling pathways in many eukaryotes. In plants, G-proteins have been characterized primarily from a few model angiosperms and a moss. Even within this small group, they seem to affect plant phenotypes differently: G-proteins are essential for survival in monocots, needed for adaptation but are nonessential in eudicots, and are required for life cycle completion and transition from the gametophytic to sporophytic phase in the moss Physcomitrium (Physcomitrella) patens. The classic G-protein heterotrimer consists of three subunits: one Gα, one Gβ and one Gγ. The Gα protein is a catalytically active GTPase and, in its active conformation, interacts with downstream effectors to transduce signals. Gα proteins across the plant evolutionary lineage show a high degree of sequence conservation. To explore the extent to which this sequence conservation translates to their function, we complemented the well-characterized Arabidopsis Gα protein mutant, gpa1, with Gα proteins from different plant lineages and with the yeast Gpa1 and evaluated the transgenic plants for different phenotypes controlled by AtGPA1. Our results show that the Gα protein from a eudicot or a monocot, represented by Arabidopsis and Brachypodium, respectively, can fully complement all gpa1 phenotypes. However, the basal plant Gα failed to complement the developmental phenotypes exhibited by gpa1 mutants, although the phenotypes that are exhibited in response to various exogenous signals were partially or fully complemented by all Gα proteins. Our results offer a unique perspective on the evolutionarily conserved functions of G-proteins in plants.
Development of a liquid argon detector with high light collection efficiency using tetraphenyl butadiene and a silicon photomultiplier array
Authors: Aoyama Kazutaka , Tanaka Masashi , Kimura Masato , Yorita Kohei
Published: April 2022

To increase the light collection efficiency of a liquid argon (LAr) detector, we optimized the evaporation technique of tetraphenyl butadiene (TPB) on the detector surface and tested the operability of a silicon photomultiplier at LAr temperature. TPB converts LAr scintillations (vacuum ultraviolet light) to visible light, which can be detected using high-sensitivity photosensors. Because the light collection efficiency depends on the deposition mass of TPB on the inner surface of the detector, we constructed a well-controlled TPB evaporator to ensure reproducibility and measured the TPB deposition mass using a quartz crystal microbalance sensor. After optimizing the deposition mass of TPB (30 $\rm \mu g/cm^2$ on the photosensor window and 42 $\rm \mu g/cm^2$ on the detector wall), the observed light yield was 12.8 ± 0.3 p.e./keVee using photomultiplier tubes with a quantum efficiency of approximately 30% for TPB-converted light. We also tested the low-temperature tolerance of the silicon photomultiplier, which has a high photon detection efficiency, in a LAr environment. It detected the LAr scintillations converted by TPB with a photon detection efficiency exceeding 50%.
Evaluation of loop formation dynamics in a chromatin fiber during chromosome condensation
Authors: Yokota Hiroshi , Tachikawa Masashi
Published: April 2022

Chromatin fibers composed of DNA and proteins fold into consecutive loops to form rod-shaped chromosomes in mitosis. Although the loop growth dynamics has been investigated in several studies, its detailed processes are unclear. Here, we describe the time evolution of the loop length for thermal-driven loop growth processes as an iterative map by calculating the physical quantities involved in the processes. We quantify the energy during the chromatin loop formation by calculating the free energies of unlooped and looped chromatins using the Domb–Joyce model of a lattice polymer chain incorporating the bending elasticity for thermal-driven loop growth processes. The excluded volume interaction among loops is integrated by employing the mean-field theory. We compare the loop formation energy with the thermal energy and evaluate the growth of the loop length via thermal fluctuation. By assuming the dependence of the excluded volume parameter on the loop length, we construct an iterative map for the loop growth dynamics. The map demonstrates that the growth length of the loop for a single reaction cycle decreases with time to reach the condensin size, where the loop growth dynamics can be less stochastic and be regarded as the direct power stroke of condensin as a kind of motor protein.
Assessment of Negative Symptoms in Clinical Trials of Acute Schizophrenia: Test of a Novel Enrichment Strategy
Authors: Hopkins Seth C , Tomioka Sasagu , Ogirala Ajay , Loebel Antony , Koblan Kenneth S , Marder Stephen R
Published: April 2022

Drug trials for negative symptoms in schizophrenia select patients based on the severity and stability of negative symptoms, using criteria that are not suitable for trials of acute exacerbation of schizophrenia. Here we present a method to prognostically enrich subjects having a predefined factor structure in PANSS and apply it to the measurement of negative symptoms specifically in trials of acute schizophrenia. A vector of 1335 elements based on between- and within-item variances, covariances, and differences of PANSS items was created to calculate an index of heterogeneity and to enrich for a predetermined symptom construct in PANSS. Using prerandomization PANSS scores across N = 4876 subjects in 13 trials of acute schizophrenia, we demonstrate an ability to select for a subpopulation having the greatest amount of variance explained across the 7-items of the Marder PANSS negative symptom (MPNS) construct. Network analyses on subjects enriched for MPNS construct confirm that negative symptoms were most influential in overall psychopathology, distinct from subjects without the MPNS construct. As expected for D2 antagonists, drug-placebo differences on negative symptoms with lurasidone were not specific to the subpopulation having the MPNS construct. In contrast, the novel TAAR1 agonist ulotaront demonstrated specific improvements in negative symptoms which were greatest in the MPNS subpopulation. These results demonstrate the utility of a novel prognostic enrichment strategy that can address heterogeneity in clinical trials, where patients can be selected on the basis of a greater likelihood of having the measured symptom construct (negative symptoms) related to the disorder (schizophrenia).

ClinicalTrials.gov Identifiers: NCT0296938, NCT00088634, NCT00549718, NCT00615433, NCT00790192
Insomnia as a predictor of recurrent cardiovascular events in patients with coronary heart disease
Authors: Frøjd Lars Aastebøl , Dammen Toril , Munkhaugen John , Weedon-Fekjær Harald , Nordhus Inger Hilde , Papageorgiou Costas , Sverre Elise
Published: April 2022

Study Objectives

Insomnia is highly prevalent in patients with coronary heart disease (CHD). However, the potential effect of insomnia on the risk of recurrent major adverse cardiovascular events (MACE) remains uncertain.

Methods

This prospective cohort study included 1082 consecutive patients 2–36 (mean 16) months after myocardial infarction and/or coronary revascularization. Data on clinical insomnia, coronary risk factors, and comorbidity were collected at baseline. Clinical insomnia was assessed using the Bergen Insomnia Scale (BIS). The primary composite endpoint of MACE (cardiovascular death, hospitalization due to myocardial infarction, revascularization, stroke, or heart failure) was assessed with an average follow-up of 4.2 (SD 0.3) years after baseline. Data were analyzed using Cox proportional hazard regression models stratified by prior coronary events before the index event.

Results

At baseline, mean age was 62 years, 21% were females, and 45% reported clinical insomnia. A total of 346 MACE occurred in 225 patients during the follow-up period. For clinical insomnia, the relative risk of recurrent MACE was 1.62 (95% confidence interval [CI]: 1.24–2.11, p < .001) adjusted for age, gender, and previous coronary events. In a multi-adjusted analysis, including coronary risk factors, cardiovascular comorbidity, symptoms of anxiety, and depression, the relative risk was 1.41 (95% CI: 1.05–1.89, p = .023). Clinical insomnia accounted for 16% of the MACE in attributable risk fraction analyses, being third in importance after smoking (27%) and low physical activity (21%).

Conclusions

Clinical insomnia was associated with increased risk of recurrent MACE. These results emphasize the importance of identifying and managing insomnia in CHD outpatients.
Exploring leaf hydraulic traits to predict drought tolerance ofEucalyptusclones
Authors: Oliveira Leonardo A , Cardoso Amanda A , Andrade Moab T , Pereira Talitha S , Araújo Wagner L , Santos Gleison A , Damatta Fábio M , Martins Samuel C V
Published: April 2022

Ongoing changes in climate, and the consequent mortality of natural and cultivated forests across the globe, highlight the urgent need to understand the plant traits associated with greater tolerance to drought. Here, we aimed at assessing key foliar traits, with a focus on the hydraulic component, that could confer a differential ability to tolerate drought in three commercial hybrids of the most important Eucalyptus species utilized in tropical silviculture: E. urophyla, E. grandis and E. camaldulensis. All genotypes exhibited similar water potential when the 90% stomatal closure (Ψgs90) occurs with Ψgs90 always preceding the start of embolism events. The drought-tolerant hybrid showed a higher leaf resistance to embolism, but the leaf hydraulic efficiency was similar among all genotypes. Other traits presented by the drought-tolerant hybrid were a higher cell wall reinforcement, lower value of osmotic potential at full turgor and greater bulk modulus of elasticity. We also identified that the leaf capacitance after the turgor loss, the ratio between cell wall thickness (t) and lumen breadth (b) ratio (t/b)3, and the minimal conductance might be good proxies for screening drought-tolerant Eucalyptus genotypes. Our findings suggest that xylem resistance to embolism can be an important component of drought tolerance in Eucalyptus in addition to other traits aimed at delaying the development of high tensions in the xylem.

Highlight Drought tolerance in tropical Eucalyptus hybrids encompasses a high leaf resistance to embolism and a suite of traits aimed at delaying the development of high tensions in the xylem.
Circ_0009035 regulates the progression of cervical cancer by targeting miR-1305/CREBRF axis
Authors: Qu Xiangdong , Tao Junzhen , Xie Jirong
Published: April 2022

Circular RNAs (circRNAs) have a crucial role in the occurrence of many diseases, such as tumors. Yet the roles of circ_0009035 (circRACGAP1) in cervical cancer are not fully characterized. The expression levels of circRACGAP1, miR-1305 and cAMP-responsive element-binding protein 3 regulatory factor (CREBRF) were detected by using real-time quantitative PCR or western blot. Cell counting kit-8 assay, 5-ethynyl-2’-deoxyuridine, colony formation assay, transwell assay and tube formation assay were used to detect cell proliferation, migration and invasion and angiogenesis, respectively. Flow cytometry assay was used to analyze the cell apoptosis. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed to analyze the targeting about miR-1305 and circ_0009035 or CREBRF. Xenograft model was built to study the role of circ_0009035 in vivo. Immunohistochemistry was used to detect the expression of Ki67, epithelial cadherin and vimentin. First, we found that circ_0009035 expression was significantly upregulated in tumor cells and tissues; second, knockdown of circ_0009035 could inhibit cell proliferation, migration and invasion and promote cell apoptosis. Subsequently, circ_0009035 was found to be able to target miR-1305, and the expression of miR-1305 in tumor tissues and cells was significantly lower. MiR-1305 inhibitor could restore cell-related progression of cervical cancer inhibited by si-circ_0009035. Finally, miR-1305 could target CREBRF, and circ_0009035 could regulate CREBRF expression by targeting miR-1305, thereby affecting cervical cancer tumorigenesis. In summary, our study confirmed that circ_0009035 could influence the development of cervical cancer through the targeted regulation of miR-1305/CREBRF.
The Effect of Music Listening During Pulmonary or Cardiac Rehabilitation on Clinical Outcomes: A Systematic Review and Meta-analysis
Authors: Frank Hannah E. , Munro Prue E. , Clark Imogen , Lee Annemarie L.
Published: April 2022

Purpose:

To determine the effects of music listening during pulmonary rehabilitation (PR) or cardiac rehabilitation (CR) or their corresponding maintenance programs on clinical outcomes in people with respiratory or cardiac conditions.

Methods:

Studies were identified from 4 electronic databases. Two reviewers independently reviewed randomized controlled or crossover studies examining the effects of music listening compared with no music listening in individuals undertaking PR or CR or corresponding maintenance programs. Methodologic quality was assessed using the Cochrane Risk of Bias tool.

Results:

Nine studies were included. Music listening during PR improved the incremental shuttle walk distance (mean difference [MD] of 73 m [95% CI 25.9–119.8]) compared with no music listening. This impact was absent in a CR maintenance program. When applied during PR programs, music listening had no effect on quality of life (standardized MD −4.6 points [95% CI −11.8 to 2.6]). Music listening had inconsistent effects on dyspnea and fatigue during PR and PR maintenance programs, but no impact on physical activity levels following CR or CR maintenance programs.

Conclusions:

Music listening during PR improved exercise capacity, but had no effect on quality of life. When applied during CR or CR maintenance, the impact on physical activity was negligible.
An Atypical Deep Penetrating Nevus With Mutations in Beta Catenin, BRAF V600E , and IDH1 R132C in an 8-Year-Old Boy
Authors: Ireland Amanda M. , Wood Benjamin A. , Whitfield Joseph , Amanuel Benhur , Harvey Nathan T. , Mesbah Ardakani Nima
Published: April 2022

Deep penetrating nevus (DPN) is a pigmented melanocytic tumor which typically displays a wedge-shaped deep penetrating architecture. Some cases show a coexisting component resembling conventional melanocytic nevus. These morphological attributes are correlated with the acquisition of genomic alterations in the Wnt pathway on a background of underlying activating MAPK pathway mutations. Lesions with features of DPN, but displaying expansile architecture, sheet-like arrangement of cells, cytological atypia, and/or more than rare mitotic activity have been described as “atypical deep penetrating nevus” or “deep penetrating melanocytoma.” The molecular correlates of these atypical morphological features are not well-established. In this case report, we describe a tumor in an 8-year-old boy with histological features of atypical DPN showing somatic BRAF

V600E
, beta catenin, and IDH1

R132C
mutations. The combination of abnormalities in MAPK and Wnt pathways with IDH1 mutations seems to be a reproducible feature in a subset of atypical DPNs. Whether this “three-hit” combination is associated with a significant risk of adverse outcome remains to be established.
MOC-31 Antibody Immunolabeling During Mohs Surgery
Authors: Bae Edward , Saap Liliana , Breen Catherine , Iwamoto Satori
Published: April 2022

BACKGROUND

Ber-EP4 is an antibody that labels basal cell carcinoma (BCC) by targeting epithelial cell adhesion molecule (Ep-CAM). MOC-31, a monoclonal mouse antibody, also targets Ep-CAM and is currently used to differentiate several extracutaneous epithelial tumors. However, the utility of MOC-31 has not been fully described in cutaneous tumors and in Mohs micrographic surgery (MMS).

OBJECTIVE

To evaluate MOC-31 labeling in BCC and other cutaneous tumors and to compare immunolabeling intensity of MOC-31 and Ber-EP4 in BCCs.

MATERIALS AND METHODS

Nineteen permanently fixed and 29 frozen BCC specimens and 23 other cutaneous tumors were labeled with MOC-31; labeling intensity of tumors, epidermis, and adnexal structures were recorded. In a separate study, a blinded dermatopathologist compared labeling intensities of 8 BCC specimens, each labeled with MOC-31 and Ber-EP4.4.

RESULTS

MOC-31 labeled all BCCs. Eccrine coils and follicular bulbs did label variably, although this did not detract utility of MOC-31. Five of thirteen cutaneous squamous cell carcinomas and one of two Merkel cell carcinomas demonstrated MOC-31 positivity. MOC-31 and Ber-EP4 labeled BCCs similarly.

CONCLUSION

MOC-31, an antibody directed against Ep-CAM, is sensitive for BCCs in frozen specimens encountered in MMS and permanently fixed specimen. In addition, MOC-31 demonstrated comparable immunolabeling characteristics with Ber-EP4 for BCCs.
A Multipollutant Approach to Estimating Causal Effects of Air Pollution Mixtures on Overall Mortality in a Large, Prospective Cohort
Authors: Traini Eugenio , Huss Anke , Portengen Lützen , Rookus Matti , Verschuren W. M. Monique , Vermeulen Roel C. H. , Bellavia Andrea
Published: April 2022

Background:

Several studies have confirmed associations between air pollution and overall mortality, but it is unclear to what extent these associations reflect causal relationships. Moreover, few studies to our knowledge have accounted for complex mixtures of air pollution. In this study, we evaluate the causal effects of a mixture of air pollutants on overall mortality in a large, prospective cohort of Dutch individuals.

Methods:

We evaluated 86,882 individuals from the LIFEWORK study, assessing overall mortality between 2013 and 2017 through national registry linkage. We predicted outdoor concentration of five air pollutants (PM2.5, PM10, NO2, PM2.5 absorbance, and oxidative potential) with land-use regression. We used logistic regression and mixture modeling (weighted quantile sum and boosted regression tree models) to identify potential confounders, assess pollutants' relevance in the mixture–outcome association, and investigate interactions and nonlinearities. Based on these results, we built a multivariate generalized propensity score model to estimate the causal effects of pollutant mixtures.

Results:

Regression model results were influenced by multicollinearity. Weighted quantile sum and boosted regression tree models indicated that all components contributed to a positive linear association with the outcome, with PM2.5 being the most relevant contributor. In the multivariate propensity score model, PM2.5 (OR=1.18, 95% CI: 1.08–1.29) and PM10 (OR=1.02, 95% CI: 0.91–1.14) were associated with increased odds of mortality per interquartile range increase.

Conclusion:

Using novel methods for causal inference and mixture modeling in a large prospective cohort, this study strengthened the causal interpretation of air pollution effects on overall mortality, emphasizing the primary role of PM2.5 within the pollutant mixture.
EVALUATION OF RETINAL DISPLACEMENT FOLLOWING PRIMARY SCLERAL BUCKLING FOR MACULA-INVOLVING RHEGMATOGENOUS RETINAL DETACHMENT
Authors: Rohowetz Landon J. , Shaheen Abdulla R. , Russell Jonathan F. , Ashkenazy Noy , Iyer Prashanth G. , Sridhar Jayanth , Flynn Harry W. , Yannuzzi Nicolas A.
Published: April 2022

Purpose:

To evaluate the incidence and degree of retinal displacement following scleral buckling surgery for macula-involving rhegmatogenous retinal detachment.

Methods:

Retrospective interventional case series comprised of patients treated with primary scleral buckling procedure without gas tamponade for macula-involving rhegmatogenous retinal detachment and imaged postoperatively with fundus autofluorescence imaging between June 1, 2016 and July 25, 2021. Clinical notes, operative reports, fundus autofluorescence photographs, and optical coherence tomography images were reviewed. The presence and degree of retinal displacement were recorded.

Results:

Twelve eyes of 11 patients were included. One (8%) eye with an epiretinal membrane demonstrated 0.1 mm of retinal displacement along the superior arcade and in the superotemporal periphery. The remainder of eyes (92%) did not show any identifiable signs of retinal displacement.

Conclusion:

Retinal displacement does not seem to be a frequent complication of primary scleral buckling surgery for macula-involving rhegmatogenous retinal detachment.
Emergence of Congenital Chagas Disease in Ireland
Authors: Stone Roy G. , Gavin Patrick , Chiodini Peter , Nolder Debbie , McGettrick Padraig , Keogh Anna , Mc Entagart Noel , Drew Richard , Lambert Jack , Ferguson Wendy
Published: April 2022

Chagas disease (CD) is an under-diagnosed tropical disease that is increasingly being observed outside of Latin America. We describe the first 2 infants with congenital Chagas Disease (cCD) in Ireland. Clinicians in nonendemic countries need to be aware of the potential for cCD due to the migration of women from countries of high prevalence.
Autophagy reprogramming stem cell pluripotency and multiple-lineage differentiation
Authors: Yang Yi-Ping , Lai Wei-Yi , Lin Tzu-Wei , Lin Yi-Ying , Chien Yueh , Tsai Yi-Ching , Tai Hsiao-Yun , Wang Chia-Lin , Liu Yung-Yang , Huang Pin-I , Chen Yi-Wei , Lo Wen-Liang , Wang Chien-Ying
Published: April 2022

The cellular process responsible for the degradation of cytosolic proteins and subcellular organelles in lysosomes was termed “autophagy.” This process occurs at a basal level in most tissues as part of tissue homeostasis that redounds to the regular turnover of components inside cytoplasm. The breakthrough in the autophagy field is the identification of key players in the autophagy pathway, compounded under the name “autophagy-related genes” (ATG) encoding for autophagy effector proteins. Generally, the function of autophagy can be classified into two divisions: intracellular clearance of defective macromolecules and organelles and generation of degradation products. Therapeutic strategies using stem cell–based approach come as a promising therapy and develop rapidly recently as stem cells have high self-renewability and differentiation capability as known as mesenchymal stem cells (MSCs). They are defined as adherent fibroblast-like population with the abilities to self-renew and multi-lineage differentiate into osteogenic, adipogenic, and chondrogenic lineage cells. To date, they are the most extensively applied adult stem cells in clinical trials. The properties of MSCs, such as immunomodulation, neuroprotection, and tissue repair pertaining to cell differentiation, processes to replace lost, or damaged cells, for aiding cell repair and revival. Autophagy has been viewed as a remarkable mechanism for maintaining homeostasis, ensuring the adequate function and survival of long-lived stem cells. In addition, authophagy also plays a remarkable role in protecting stem cells against cellular stress when the stem cell regenerative capacity is harmed in aging and cellular degeneration. Understanding the under-explored mechanisms of MSC actions and expanding the spectrum of their clinical applications may improve the utility of the MSC-based therapeutic approach in the future.