bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of Updated Japanese Circulation Society Guidelines to Diagnose Isolated Cardiac Sarcoidosis
Authors: Sato Kimi , Kawamatsu Naoto , Yamamoto Masayoshi , Machino‐Ohtsuka Tomoko , Ishizu Tomoko , Ieda Masaki
Published: June 2022

Background

In the population with cardiac sarcoidosis (CS), approximately one third lacks extracardiac involvement and is considered to have isolated CS. Recently, the Japanese Circulation Society updated the diagnostic criteria for CS, providing a methodology for diagnosing isolated CS. We aimed to assess the characteristics of isolated CS diagnosed using a multimodal imaging approach according to the updated Japanese Circulation Society guidelines.

Methods and Results

We retrospectively identified 161 consecutive patients who underwent 18F‐fluorodeoxyglucose positron emission tomography for suspected CS between 2012 and 2019. According to the guidelines, patients were classified as having CS with extracardiac involvement, isolated CS, or no CS. We compared the characteristics of multimodality imaging and the prevalence of major adverse cardiovascular events. The Japanese Circulation Society criteria classified 28 patients (17%) as having CS with 4 (2%) with histological confirmation, 21 (13%) as isolated CS, and 112 (70%) as no CS. Compared with CS, isolated CS showed higher left ventricular volume and reduced left ventricular ejection fraction (
P
<0.01 for all). During the median follow‐up period of 522 days, 24 patients had major adverse cardiovascular events. Isolated CS (hazard ratio, 3.35; [95% CI, 1.08–10.39],
P
=0.036) was independently associated with major adverse cardiovascular events after adjusting for reduced left ventricular ejection fraction and steroid. In the subgroup of 41 patients with serial 18F‐fluorodeoxyglucose positron emission tomography evaluation, only updated CS criteria were associated with improvement in myocardial inflammation on 18F‐fluorodeoxyglucose positron emission tomography.

Conclusions

Isolated CS detected using the updated Japanese Circulation Society guidelines was associated with poor event‐free survival and should be managed with caution.
Inhibiting Succinate Release Worsens Cardiac Reperfusion Injury by Enhancing Mitochondrial Reactive Oxygen Species Generation
Authors: Milliken Alexander S. , Nadtochiy Sergiy M. , Brookes Paul S.
Published: June 2022

Background

The metabolite succinate accumulates during cardiac ischemia. Within 5 minutes of reperfusion, succinate returns to baseline levels via both its release from cells and oxidation by mitochondrial complex II. The latter drives reactive oxygen species (ROS) generation and subsequent opening of the mitochondrial permeability transition (PT) pore, leading to cell death. Targeting succinate dynamics (accumulation/oxidation/release) may be therapeutically beneficial in cardiac ischemia–reperfusion (IR) injury. It has been proposed that blocking MCT1 (monocarboxylate transporter 1) may be beneficial in IR injury, by preventing succinate release and subsequent engagement of downstream inflammatory signaling pathways. In contrast, herein we hypothesized that blocking MCT1 would retain succinate in cells, exacerbating ROS generation and IR injury.

Methods and Results

Using the mitochondrial ROS probe mitoSOX and a custom‐built murine heart perfusion rig built into a spectrofluorometer, we measured ROS generation in situ during the first moments of reperfusion. We found that acute MCT1 inhibition enhanced mitochondrial ROS generation at reperfusion and worsened IR injury (recovery of function and infarct size). Both of these effects were abrogated by tandem inhibition of mitochondrial complex II, suggesting that succinate retention worsens IR because it drives more mitochondrial ROS generation. Furthermore, using the PT pore inhibitor cyclosporin A, along with monitoring of PT pore opening via the mitochondrial membrane potential indicator tetramethylrhodamine ethyl ester, we herein provide evidence that ROS generation during early reperfusion is upstream of the PT pore, not downstream as proposed by others. In addition, pore opening was exacerbated by MCT1 inhibition.

Conclusions

Together, these findings highlight the importance of succinate dynamics and mitochondrial ROS generation as key determinants of PT pore opening and IR injury outcomes.
How the History of Changing Environments Affects Traits of Evolvable Robot Populations
Authors: Miras Karine , Eiben A. E.
Published: June 2022

The environment is one of the key factors in the emergence of intelligent creatures, but it has received little attention within the Evolutionary Robotics literature. This article investigates the effects of changing environments on morphological and behavioral traits of evolvable robots. In particular, we extend a previous study by evolving robot populations under diverse changing-environment setups, varying the magnitude, frequency, duration, and dynamics of the changes. The results show that long-lasting effects of early generations occur not only when transitioning from easy to hard conditions, but also when going from hard to easy conditions. Furthermore, we demonstrate how the impact of environmental scaffolding is dependent on the nature of the environmental changes involved.
The oldest fossil of the sawfly subfamily Nematinae (Hymenoptera: Tenthredinidae) from the Paleocene of Menat (France)
Authors: NEL ANDRÉ
Published: June 2022

The speciose family Tenthredinidae has a scarce fossil record (Nel et al., 2022a, b), despite recent molecular-based phylogenetic analyses suggesting a Cretaceous age for the origin (ca. 100 Ma) and the diversification of the family into its modern subfamilies (Nyman et al., 2006, 2019; Niu et al., 2021). The lack of Mesozoic representative of this group remains unexplained because Nyman et al. (2006) dated its origin at 100 Ma. Cenozoic fossils are currently attributed to the subfamilies Allantinae, Heterarthrinae, Blennocampinae, and Nematinae (Taeger et al., 2010; Nel et al, 2022a, b).
A new species, Cylindroeme yunnanensis sp. nov. from China (Coleoptera, Cerambycidae, Cerambycinae)
Authors: LIN MEI-YING , LI KAI-QIN
Published: June 2022

A new species, Cylindroeme yunnanensis sp. nov., is described and illustrated from Yunnan Province of China. Cylindroeme vietnamica Vives, 2019 is recorded from China for the first time. A key to the species of Cylindroeme is provided.
Numerical and Linear Regression Analysis of Slip Effects on Magnetohydrodynamics (MHD) Convective Cu-Water Nanofluid Flow in a Channel with Stretchable Walls
Authors: Kalyan Chakravarthy Y. S. , Ram Prasad S. , Mallikarjuna B. , Suresh Babu R.
Published: June 2022

This paper is aimed to study the impact of 2nd order velocity and 2nd order thermal slip on the heat transfer flow of hydromagnetic nanofluid through the horizontal channel with stretching walls. The water-based Cu nanoparticle is considered to analyze the heat transfer enhancement.
The channel is considered to be fully developed with an incompressible nanofluid. A standard similarity transformation is used to non-dimensionalize and then solved by numerical technique. An admirable agreement has been noticed on correlating the present results with published results in
limiting cases. The profiles of velocity and temperature are discussed through plots for various non-dimensional parameters like magnetic parameter radiation parameter (Rd), solid volume fraction (Φ), Prandtl number (Pr) on fluid velocity and temperature profiles. One of the statistical
tools, linear regression has been used to analyze the drag coefficient and Nusselt number at the walls (between walls to the fluid) under various slip effects and magnetic force. It is observed that an augmentation in volume fraction lessens the velocity in all the cases (no slip, first and
slip of order of two). This study is mainly applicable in nuclear reactors and biomedical applications like nano-drug delivery, cancer therapeutics and, etc.
Suppression of Thermal Conductivity Enhancement in Carbon Nanofluids Caused by Surfactant High Concentration
Authors: Darabian Lyane Moreira , Darabian H. , Bell Maria José V. , Anjos Virgílio
Published: June 2022

In this study, structural and thermal properties of dispersed carbon nanomaterials such as single-wall carbon nanotubes and graphene in water are investigated. Carbon nanostructures are dispersed in the fluid through surfactant and ultrasonication treatment. Structural studies of the
samples are carried out by Raman spectroscopy which show that the dispersion process leads to the formation of two kind of nanofluids: nanostructured graphene based and single-wall carbon nanotubes ones. The first in the form of graphene dots. The thermal diffusivities of the samples are measured
by thermal lens technique. Contrary to what is normally expected our nanofluids show a considerable reduction in thermal conductivity. The reduction is stronger for graphene dots than for the carbon nanotubes. This peculiar behavior of the thermal conductivity is attributed to the high concentration
ratio of surfactant to dispersed particles, as well as, the formation of air layer or bubbles attached to the nanoparticles due to sonication process. To evaluate this hypothesis, simulation of the effective thermal conductivity based on Murshed model is conducted for spherical and cylindrical
particles surrounded by air layer. The simulation shows an effective decrease in thermal conductivity, which corroborates with the experimental trend.
Influence of the Ferro Particles on Convection Inside Inclined 2D Enclosure with Heat Conducting and Generating Body
Authors: Umadevi P. , Suganya M. , Prakash J.
Published: June 2022

The free convective flow of a Co-ferroparticle suspended nanofluid in a tilted square enclosure with various thermal boundaries including heat generating body is numerically investigated. A heat generating solid body is placed at the centre of the enclosure to study the effective rate
of heat transfer. The comprehensive analysis of the results suggests that the angle of inclination and addition of ferro particle have a considerable influence on the flow and heat transfer behaviour. The results are presented in the form of streamlines, isotherms and average Nusselt number
for the effect of inclination angle (0° ≤ Φ ≤ 90°), Rayleigh number (104 ≤ Ra ≤ 106) and solid volume fraction (Φ = 0.02, 0.1 and 0.2). Based on this investigation. It can be found that augmentation in Rayleigh number
increases the strength of the circular eddy due to induced buoyancy forces. Increase in size of the solid body suppresses the heat transfer effect. Also the temperature gradient show moderate nature until 45° angle of inclination and show the declination after 45°.
Entropy Generation Analysis on Magnetohydrodynamic Eyring-Powell Nanofluid Over a Stretching Sheet by Heat Source/Sink
Authors: Mishra S. R. , Baag S. , Parida S. K.
Published: June 2022

In this communication, the analysis of the entropy generation on magnetohydrodynamic (MHD) Eyring-Powell nanofluid over a stretching sheet with the effects of heat source/sink is reported. The presence of thermophoresis and Brownian motion are responsible for the enhancement in the properties of heat transfer. With the help of suitable similarity transformation entity, the involved governing partially differential equations (PDEs) are converted into nonlinear coupled ordinary differential equations (ODEs). Further, converted differential equations are solved by numerical methods such as Runge-Kutta fourth order correlated with shooting technique. Influence of various pertinent physical parameters is discussed via velocity, temperature, concentration and entropy profiles. The effect of these variables on the quantities of engineering advance such as Nusselt and Sherwood number are furnished in illustrative form and discussed. Further, the major findings of the outcomes are laid down as follows; the Brownian motion of the particles enhances the fluid temperature whereas thermophoresis retards significantly. The entropy generation overshoots due to the increase in the Reynolds number. Nanofluids with high critical heat fluxes and high-power density have the potential to provide the required cooling effect in military ships, submarines, wave energy converters and high-power laser diodes.
Pulsating Hydromagnetic Flow of Chemically Reactive Oldroyd-B Nanofluid in a Channel with Brownian Motion, Thermophoresis, and Joule Heating
Authors: Venkatesan G. , Reddy A. Subramanyam , Srinivas S. , Jagadeshkumar K.
Published: June 2022

In the present study, the magnetohydrodynamic pulsating flow of chemically reacting Oldroyd-B nanoliquid via channel with the impressions of Ohmic heating, radiative heat and viscous dissipation is studied. The ruling PDEs (partial differential equations) are changed into ODEs (Ordinary
differential equations) by utilizing the perturbation procedure and numerically deciphered by adopting the 4th order Runge-Kutta approach with the aid of the shooting process. The novelty of the current work is to inspect the pulsating flow of Oldroyd-B nanoliquid via channel in the occurrence
of an applied magnetic field by deploying the Buongiorno nanofluid model. The application of the proposed physical model is energy production, heating and cooling processes, thermoelectric devices, bio-medical applications like brain tumours, cancer treatment, drug targeting. Detailed analysis
on the impacts of several pertinent parameters for velocity, temperature, nanoparticles concentration, rates of heat and mass transfer is done. The outcomes predict that the velocity of nanoliquid is improved with augmenting frequency parameter while it is reduced with acceleration in Hartmann
number. The temperature rises with an improvement of thermophoresis, viscous dissipation, and Brownian motion while it falls for a given rise in Hartmann number and thermal radiation. Further, the nanoparticle concentration rises with an increasing Brownian motion while it falls over rising
chemical reaction, thermophoresis, and Lewis number.
Investigation of Nonlinear Fluid Flow Equation in a Porous Media and Evaluation of Convection Heat Transfer Coefficient, by Taking the Forchheimer Term into Account
Authors: Shahnazari Mohammad Reza , Moosavi Mir Hedayat , Chamkha Ali J.
Published: June 2022

The steady-state fully developed fluid flow in a channel filled with porous media is known as one of the classical issues in the field of fluid mechanics. Darcy’s, Brinkman’s and Brinkman-Forchheimer’s laws are well-known models for describing this kind of fluid. Darcy
equation, as the most useful equations, is based on the description of fluid friction and porous matrix. In Brinkman equation, the term of viscosity similar to that of Laplacian in the Navier Stokes equation is added to the Darcy equation, and finally, Forchheimer term is able to account for
second-order drag term due to the impact of solid in the fluid. Adding the Forchheimer term to the Darcy-Brinkman equation causes the nonlinearity of the equation. In this research, an analytical solution for several flow models in a porous medium channel is provided. The simplicity of use
of the velocity profile, particularly for the study of the heat transfer problem and the exergy analysis of flow, is the most essential feature of the suggested approach. In addition to the analytical response of this equation, the convective heat transfer coefficient is estimated. The impacts
of all parameters on the the Nusselt number are evaluated. The findings reveal that when the Forchheimer coefficient rises, the Nusselt number falls; this downward trend is sharp in smaller Darcy numbers; hence Nusselt number tends to its asymptotic values. While, as Darcy number increase,
the downtrend is getting close to a linear one.
Evaluation of lung function and clinical features of interlaminar cervical epidural steroid injections: a randomized controlled trial
Authors: Chae Ji Seon , Kim Won-joong , Lee Gi Year , Choi Yong Ju
Published: June 2022

Objective

Interlaminar cervical epidural steroid injections (ICESIs) are commonly used to treat axial neck pain and cervical radicular pain. However, local anesthetics can spread to and block the phrenic nerve and upper segments of the thoracic spinal cord where the sympathetic innervation of the lungs emerges. Therefore, changes in lung function may occur following ICESIs.

Methods

The primary outcome measure was the pulmonary function test (PFT) result 30 minutes before and after ICESI with ropivacaine (0.1875% or 0.25%). The secondary outcome measure was the comparison of the pain scores and functional disability between the two concentrations of ropivacaine 4 weeks after the ICESIs.

Results

Fifty patients were randomly assigned to either the R1 (0.1875% ropivacaine) or R2 (0.25% ropivacaine) group. No significant difference was observed between the pre-ICESI and 30-minute post-ICESI PFT results within each group, and no difference was observed between the two groups. After 4 weeks of treatment, both groups showed a significant decrease in pain scores and functional disability; however, no significant differences were observed between the two groups.

Conclusions

This study showed no significant change in lung function after ICESIs in either group and no local anesthetic concentration-based difference in the clinical efficacy of the ICESIs.
Deformation behavior of advanced high strength steel with different strain hardening exponents during tube hydroforging
Authors: Fischer Jeremy J , Nikhare Chetan P
Published: June 2022

Hydroforging is an innovative forming method used to form tubes with irregular cross-sections by using internal fluid pressure and axial force. Normally tube forming operations use solid mandrel to expand/bend the tube which does negative effect on tube or mandrel due to friction, buckling, and wrinkling. In this study, the tube material with various strain hardening exponents were hydroforged in a two-step numerical analysis with ramped fluid pressure and axial compression. The tube will be allowed to bulge with a ramped internal pressure and then shaped to a maximum expansion ratio by the axial compression in the shaping step. Some advanced materials exhibit the change in strain hardening exponent based on the plastic strain, the study focuses how the strain hardening exponent affects the deformation mechanics in tube hydroforging. It was found that the formability of tube during hydroforging is affected by the strain hardening exponent. The results show that tube can achieve a greater wall thickness reduction with increase in strain hardening exponent. Also, higher strain hardening exponent allowed tube to achieve a greater expansion ratio when axially compressed in the forging step. It was also observed that as the strain hardening exponent increases, the internal pressure requirements for the bulging and shaping steps decrease. The two model configurations of N01 and N02 failed from bursting and wrinkling, respectively, while every other model could form to the targeted disk-like shape. The forging step of the process showed that the die force for axial compression decreased as the strain hardening exponent increased for all successful models.
The cultural customization of TikTok: subaltern migrant workers and their digital cultures
Authors: Kaur-Gill Satveer
Published: June 2022

Migrant construction workers in Singapore produced TikTok videos sharing their structural, social, and health conditions during the pandemic. The platform's user-centered design presents opportunities for marginalized communities to participate in content production and distribution. The TikTok videos created by MCWs richly detailed the precarities they faced during the pandemic. Through the production of short videos, workers made visible their dormitory conditions, stringent medical surveillance of their bodies, the mental health anxieties they faced from confinement and isolation, and discussed the extensive mobility restrictions imposed on them. They also customized the platform's editability features to produce and edit vernacular content for entertainment and information-sharing, and digitally archived their precarities on the platform. Through user-generated content, workers responded to the exclusions they faced in the host country, undoing the mainstream discursive silencing of their lived experiences as subaltern workers in the city-state. Workers’ use of TikTok presents opportunities for activism and organizing that center voice and agency for greater digital mobilities.
The continuum of regaining one’s body: Childbirth and reproductive choice under beauty pressure in Taiwan
Authors: Keyser-Verreault Amélie
Published: June 2022

This article explores the phenomenon of regaining one’s body, by nuancing the Western feminist analysis of the cult of beauty and the ideal of the ‘yummy mummy’ in a non-Euro-American society, Taiwan. While existing studies of bouncing back after childbirth have focused mainly on losing weight during the postpartum period, this article examines a continuum of the beauty-related deliberations and different forms of aesthetic labor of Taiwanese women before, during and after pregnancy. Drawing on 62 in-depth interviews, my analysis shows that not only do women include the project of regaining their body in their plans for pregnancy and giving birth, but that beauty becomes a controlling claim that can compete with a child’s well-being or mother’s health. Moreover, this task should be viewed as a holistic and multidimensional concept because it involves not only body shape but also keeping desirability vibrant and dealing with delicate interpersonal relationships.
Tools for local health in all policies implementation: evidence from an explanatory case study of Kuopio, Finland
Authors: Guglielmin Maria , Shankardass Ketan , Bayoumi Ahmed , O’campo Patricia , Kokkinen Lauri , Muntaner Carles
Published: June 2022

Aims:

This paper describes the use of three governance tools for health in all policies utilised to facilitate implementation in the municipality of Kuopio, Finland: impact assessments, a city mandate (the Kuopio strategy), and shared budgets.

Methods:

An explanatory case study was used. Data sources included semistructured interviews with 10 government employees and scholarly literature. Realist scientific methods were used to reveal mechanisms underlying the use of tools in health in all policies.

Results:

Strong evidence was found supporting initial and new theory/hypotheses regarding the use of each tool in achieving positive implementation outcomes. Impact assessments facilitated health in all policies by enhancing understanding of health implications. The Kuopio strategy aided in implementation by giving credence to health in all policies work via formal authority. Shared budgets promoted intersectoral discussions and understanding, and a sense of ownership, in addition to allowing time to be spent on health in all policies work and not financial deliberation.

Conclusions:

Findings confirm the efficacious use of three governance tools in implementing health in all policies in Kuopio. Knowledge and evidence-based guidelines on local health in all policies implementation are needed as this policy approach continues to be recognised and adopted as a means to promote population health and health equity.
Grandviewite redefinition, new formula Cu3Al2(SO4)(OH)10⋅H2O, and crystal-structure determination
Authors: Sejkora Jiří , Steciuk Gwladys , Marquez-Zavalia Maria Florencia , Plášil Jakub , Dolníček Zdeněk
Published: June 2022

Grandviewite is redefined on the basis of a reinvestigation of the holotype specimen from the Grandview mine, Arizona, USA, and additional specimens found in the Restauradora vein at the Capillitas mine, northwestern Argentina. Grandviewite from the Capillitas mine forms globular masses up to a couple of millimetres in diameter, formed by very thin platy to acicular lath-like crystals, greenish-pale blue in colour, pleochroic (X = colourless, Y = very pale blue and Z = greenish-pale blue), with pale blue streak and silky to a satiny lustre. Results of an electron-microprobe study and crystal-structure determination lead to the new ideal formula Cu3Al2(SO4)(OH)10⋅H2O, which requires (in wt.%) CuO 45.13, Al2O3 19.28, SO3 15.14, and H2O 20.45, total 100.00. Its empirical formulas are (Cu2.96Mn0.01)Σ2.97Al2.03(SO4)0.97(SiO4)0.03(AsO4)0.01(OH)9.97Cl0.01⋅H2O (Grandview mine) and Cu2.97(Al2.03Fe0.01)Σ2.04(SO4)0.95(SiO4)0.03(AsO4)0.01(PO4)0.01(OH)9.97Cl0.01⋅H2O (Capillitas mine). Grandviewite is triclinic, P$\bar{1}$, with unit-cell parameters refined from powder X-ray diffraction data: a = 5.713(2), b = 10.1374(8), c = 10.9791(9) Å, α = 72.240(6)°, β = 82.79(2)°, γ = 86.07(2)°, V = 600.5(3) Å3 and Z = 2 (Grandview mine); and a = 5.749(3), b = 10.1388(13), c = 10.9656(16) Å, α = 72.344(1)°, β = 82.83(4)°, γ = 86.77(3)°, V = 604.2(3) Å3 and Z = 2 (Capillitas mine). The crystal structure of grandviewite from the Capillitas mine was solved by 3-dimensional electron diffraction analysis (R(obs)/wR(obs) = 0.1304/0.1316 for 6401/31007 observed reflections with I ≥ 3σ(I). Grandviewite contains infinite AlO6–Cu1–AlO6 slabs along a connected on both ends to Cu2 [4 + 1]–SO4 chains. The SO4 tetrahedra form a disordered chain along a connected to the Cu2 pyramids on one side and are otherwise stabilised by strong hydrogen bonds to surrounding units. The Raman and infrared spectra for samples from both occurrences are identical. The redefinition (new chemical formula and triclinic symmetry) has been approved by the Commission on New Minerals, Nomenclature and Classification of the International Mineralogical Association (number 21-K).
STAT1 is essential for HSC function and maintains MHCIIhi stem cells that resist myeloablation and neoplastic expansion
Authors: Li Juan , Williams Matthew J. , Park Hyun Jung , Bastos Hugo P. , Wang Xiaonan , Prins Daniel , Wilson Nicola K. , Johnson Carys , Sham Kendig , Wantoch Michelle , Watcham Sam , Kinston Sarah J. , Pask Dean C. , Hamilton Tina L. , Sneade Rachel , Waller Amie K. , Ghevaert Cedric , Vassiliou George S. , Laurenti Elisa , Kent David G. , Göttgens Berthold , Green Anthony R.
Published: June 2022

Adult hematopoietic stem cells (HSCs) are predominantly quiescent and can be activated in response to acute stress such as infection or cytotoxic insults. STAT1 is a pivotal downstream mediator of interferon (IFN) signaling and is required for IFN-induced HSC proliferation, but little is known about the role of STAT1 in regulating homeostatic hematopoietic stem/progenitor cells (HSPCs). Here, we show that loss of STAT1 altered the steady state HSPC landscape, impaired HSC function in transplantation assays, delayed blood cell regeneration following myeloablation, and disrupted molecular programs that protect HSCs, including control of quiescence. Our results also reveal STAT1-dependent functional HSC heterogeneity. A previously unrecognized subset of homeostatic HSCs with elevated major histocompatibility complex class II (MHCII) expression (MHCIIhi) displayed molecular features of reduced cycling and apoptosis and was refractory to 5-fluorouracil–induced myeloablation. Conversely, MHCIIlo HSCs displayed increased megakaryocytic potential and were preferentially expanded in CALR mutant mice with thrombocytosis. Similar to mice, high MHCII expression is a feature of human HSCs residing in a deeper quiescent state. Our results therefore position STAT1 at the interface of stem cell heterogeneity and the interplay between stem cells and the adaptive immune system, areas of broad interest in the wider stem cell field.
GGCX mutants that impair hemostasis reveal the importance of processivity and full carboxylation to VKD protein function
Authors: Rishavy Mark A. , Hallgren Kevin W. , Wilson Lee A. , Hiznay James M. , Runge Kurt W. , Berkner Kathleen L.
Published: June 2022

γ-Glutamyl carboxylase (GGCX) generates multiple carboxylated Glus (Glas) in vitamin K–dependent (VKD) proteins that are required for their functions. GGCX is processive, remaining bound to VKD proteins throughout multiple Glu carboxylations, and this study reveals the essentiality of processivity to VKD protein function. GGCX mutants (V255M and S300F) whose combined heterozygosity in a patient causes defective clotting and calcification were studied using a novel assay that mimics in vivo carboxylation. Complexes between variant carboxylases and VKD proteins important to hemostasis (factor IX [FIX]) or calcification (matrix Gla protein [MGP]) were reacted in the presence of a challenge VKD protein that could potentially interfere with carboxylation of the VKD protein in the complex. The VKD protein in the complex with wild-type carboxylase was carboxylated before challenge protein carboxylation occurred and became fully carboxylated. In contrast, the V255M mutant carboxylated both forms at the same time and did not completely carboxylate FIX in the complex. S300F carboxylation was poor with both FIX and MGP. Additional studies analyzed FIX- and MGP-derived peptides containing the Gla domain linked to sequences that mediate carboxylase binding. The total amount of carboxylated peptide generated by the V255M mutant was higher than that of wild-type GGCX; however, the individual peptides were partially carboxylated. Analysis of the V255M mutant in FIX HEK293 cells lacking endogenous GGCX revealed poor FIX clotting activity. This study shows that disrupted processivity causes disease and explains the defect in the patient. Kinetic analyses also suggest that disrupted processivity may occur in wild-type carboxylase under some conditions (eg, warfarin therapy or vitamin K deficiency).
The identification of TCF1+ progenitor exhausted T cells in THRLBCL may predict a better response to PD-1/PD-L1 blockade
Authors: Tabanelli Valentina , Melle Federica , Motta Giovanna , Mazzara Saveria , Fabbri Marco , Agostinelli Claudio , Calleri Angelica , Del Corvo Marcello , Fiori Stefano , Lorenzini Daniele , Cesano Alessandra , Chiappella Annalisa , Vitolo Umberto , Derenzini Enrico , Griffin Gabriel K. , Rodig Scott J. , Vanazzi Anna , Sabattini Elena , Tarella Corrado , Sapienza Maria Rosaria , Pileri Stefano A.
Published: June 2022

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare and aggressive variant of diffuse large B-cell lymphoma (DLBCL) that usually affects young to middle-aged patients, with disseminated disease at presentation. The tumor microenvironment (TME) plays a key role in THRLBCL due to its peculiar cellular composition (<10% neoplastic B cells interspersed in a cytotoxic T-cell/histiocyte-rich background). A significant percentage of THRLBCL is refractory to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP)-based regimens and to chimeric antigen receptor T-cell therapy; thus, the development of a specific therapeutic approach for these patients represents an unmet clinical need. To better understand the interaction of immune cells in THRLBCL TME and identify more promising therapeutic strategies, we compared the immune gene expression profiles of 12 THRLBCL and 10 DLBCL samples, and further corroborated our findings in an extended in silico set. Gene coexpression network analysis identified the predominant role of the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis in the modulation of the immune response. Furthermore, the PD-1/PD-L1 activation was flanked by the overexpression of 48 genes related to the functional exhaustion of T cells. Globally, THRLBCL TME was highly interferon-inflamed and severely exhausted. The immune gene profiling findings strongly suggest that THRLBCL may be responsive to anti–PD-1 therapy but also allowed us to take a step forward in understanding THRLBCL TME. Of therapeutic relevance, we validated our results by immunohistochemistry, identifying a subset of TCF1+ (T cell–specific transcription factor 1, encoded by the TCF7 gene) progenitor exhausted T cells enriched in patients with THRLBCL. This subset of TCF1+ exhausted T cells correlates with good clinical response to immune checkpoint therapy and may improve prediction of anti–PD-1 response in patients with THRLBCL.
Refining the migration and engraftment of short-term and long-term HSCs by enhancing homing-specific adhesion mechanisms
Authors: Al-Amoodi Asma S. , Li Yanyan , Al-Ghuneim Arwa , Allehaibi Hanaa , Isaioglou Ioannis , Esau Luke E. , AbuSamra Dina B. , Merzaban Jasmeen S.
Published: June 2022

In contrast to the short-term (ST) CD34+ stem cells, studies have suggested that long-term (LT) hematopoietic stem cells (HSCs) found in the CD34− stem cell pool have trouble migrating and engrafting when introduced through IV. To understand why these deficiencies exist, we set out to fully elucidate the adhesion mechanisms used by ST and LT-HSCs to migrate to the bone marrow(BM). Specifically focusing on murine ST-HSCs (Flk2−CD34+) and LT-HSCs (Flk2−CD34−), we observed a distinctive expression pattern of BM homing effectors necessary for the first step, namely sialyl Lewis-X (sLex) (ligand for E-selectin), and the second step, namely CXCR4 chemokine receptor (receptor for SDF-1). sLex expression was higher on Flk2−CD34+ ST-HSCs (>60%) compared with Flk2−CD34− LT-HSCs (<10%), which correlated to binding to E-selectin. Higher concentrations of CXCR4 were observed on Flk2−CD34+ ST-HSCs compared with Flk2−CD34− LT-HSCs. Interestingly, the expression of CD26, a peptidase known to deactivate chemokines (ie, SDF-1), was higher on Flk2−CD34− LT-HSCs. Given that both E-selectin–binding and CXCR4-mediated migration are compromised in Flk2−CD34− LT-HSCs, we aimed to enhance their ability to migrate using recombinant human fucosyltransferase 6 (rhFTVI) and the CD26 inhibitor, Dip A (diprotin A). To this end, we observed that although LT-HSCs expressed low concentrations of sLex, they were able to engraft when transplanted into recipient mice. Moreover, although both CD26 inhibition and fucosylation enhanced migration of both HSC populations in vitro, only pretreatment of LT-HSCs with Dip A enhanced engraftment in vivo after transplantation into recipient mice. Remarkably, fucosylation of Flk2−CD34+ ST-HSCs consistently led to their ability to transplant secondary recipients. These data suggest that using fucosylation and Dip A to overcome the molecular disparity in adhesion mechanisms among ST-HSCs and LT-HSCs differentially influences their abilities to migrate and engraft in vivo and promotes the ability of ST-HSCs to engraft secondary recipient mice, the gold standard for testing functionality of LT-HSCs.
Upregulated lncARAT in Schwann cells promotes axonal regeneration by recruiting and activating proregenerative macrophages
Authors: Yin Gang , Lin Yaofa , Wang Peilin , Zhou Jun , Lin Haodong
Published: June 2022

Background

Axonal regeneration following peripheral nerve injury (PNI) depends on the complex interaction between Schwann cells (SCs) and macrophages, but the mechanisms underlying macrophage recruitment and activation in axonal regeneration remain unclear.

Methods

RNA sequencing (RNA-seq) was conducted to identify differentially expressed long noncoding RNAs (DElncRNAs) between crushed sciatic nerves and intact contralateral nerves. The putative role of lncRNAs in nerve regeneration was analyzed in vitro and in vivo.

Results

An lncRNA, called axon regeneration-associated transcript (lncARAT), was upregulated in SCs and SC-derived exosomes (SCs-Exo) after sciatic nerve injury. LncARAT contributed to axonal regeneration and improved motor function recovery. Mechanistically, lncARAT epigenetically activated C–C motif ligand 2 (CCL2) expression by recruiting KMT2A to CCL2 promoter, resulting in increased histone 3 lysine 4 trimethylation (H3K4me3) and CCL2 transcription in SCs. CCL2 facilitated the infiltration of macrophages into the injured nerves. Meanwhile, lncARAT-enriched exosomes were released from SCs and incorporated into macrophages. LncARAT functioned as an endogenous sponge to adsorb miRNA-329-5p in macrophages, resulting in increased suppressor of cytokine signaling (SOCS) 2 expression, which induced a proregenerative function of macrophages through a signal transducer and activator of transcription (STAT) 1/6-dependent pathway.

Conclusions

LncARAT may represent a promising therapeutic avenue for peripheral nerve repair.
DeepPN: a deep parallel neural network based on convolutional neural network and graph convolutional network for predicting RNA-protein binding sites
Authors: Zhang Jidong , Liu Bo , Wang Zhihan , Lehnert Klaus , Gahegan Mark
Published: June 2022

Background

Addressing the laborious nature of traditional biological experiments by using an efficient computational approach to analyze RNA-binding proteins (RBPs) binding sites has always been a challenging task. RBPs play a vital role in post-transcriptional control. Identification of RBPs binding sites is a key step for the anatomy of the essential mechanism of gene regulation by controlling splicing, stability, localization and translation. Traditional methods for detecting RBPs binding sites are time-consuming and computationally-intensive. Recently, the computational method has been incorporated in researches of RBPs. Nevertheless, lots of them not only rely on the sequence data of RNA but also need additional data, for example the secondary structural data of RNA, to improve the performance of prediction, which needs the pre-work to prepare the learnable representation of structural data.

Results

To reduce the dependency of those pre-work, in this paper, we introduce DeepPN, a deep parallel neural network that is constructed with a convolutional neural network (CNN) and graph convolutional network (GCN) for detecting RBPs binding sites. It includes a two-layer CNN and GCN in parallel to extract the hidden features, followed by a fully connected layer to make the prediction. DeepPN discriminates the RBP binding sites on learnable representation of RNA sequences, which only uses the sequence data without using other data, for example the secondary or tertiary structure data of RNA. DeepPN is evaluated on 24 datasets of RBPs binding sites with other state-of-the-art methods. The results show that the performance of DeepPN is comparable to the published methods.

Conclusion

The experimental results show that DeepPN can effectively capture potential hidden features in RBPs and use these features for effective prediction of binding sites.
Age-related differences of vastus lateralis muscle morphology, contractile properties, upper body grip strength and lower extremity functional capability in healthy adults aged 18 to 70 years
Authors: Jacob Isobel , Johnson Mark I. , Jones Gareth , Jones Ashley , Francis Peter
Published: June 2022

Background

There is a lack of of cross-sectional research that has investigated muscle morphology, function, and functional capability in all age-bands of healthy adults. The primary aim of this study was to evaluate age-related differences in indices of vastus lateralis (VL) muscle morphology, function and functional capability in a sample of healthy males and females aged 18-70yrs. Secondary aims were to evaluate relationships between age and VL muscle morphology and function and functional capability.

Methods

B mode Ultrasonography and Tensiomyography were used to measure VL muscle thickness, pennation angle, fascicle length, and contractile properties in 274 healthy adults aged 18-70yrs. Measurements of grip strength and functional capability (1-min chair rise test) were also taken. Data analysis included descriptive statistics, correlations, one-way ANOVAs, and multiple regressions.

Results

Negative correlations were found between age and muscle thickness (rs = -.56), pennation angle (rs = -.50), fascicle length (rs = -.30), maximal displacement (rs = -.24), grip strength (rs = -.27) and the 1-min chair rise test (rs = -.32). Positive correlations were observed between age and the echo intensity of the muscle (rs = .40) and total contraction time (rs = .20). Differences in the indices of muscle health were noticeable between the 18–29 age band and the 50–59 and 60–70 age bands (p < 0.05). The interaction of age and level of physical activity predicted changes in the variables (r2 = .04—.32).

Conclusion

Age-related differences in muscle health are noticeable at 50 years of age, and age-related differences are larger in females compared to males. It was suggested that the thickness of the VL changed the most with age across the adult lifespan and that physical activity likely acts to abate detrimental change.
Why do older adults living alone in cities cease seeking assistance? A qualitative study in China
Authors: Du Qianqian , Gong Ni , Hu Qin , Chen Guicheng , Xie Jingyue , Luo Lan , Cheng Yu , Zhang Meifen
Published: June 2022

Background

Against the background of an aging population, older adults living alone in cities are increasingly dependent. However, their use of home and community-based services in China is unsatisfactory. This study attempted to figure out why older adults living alone in cities do not actively seek assistance in China.

Methods

In-depth interviews were conducted. A total of 29 older adults were recruited. Content analysis was used to analyze the interview data.

Results

Three themes were identified. (1) Desire for independence, despite hardship: The lives of older adults involve many inconveniences, but they preferred to solve problems by themselves, instead of asking for help; (2) Desire to not overburden jiaren (meaning family in Chinese): older adults did not want to disturb families or burden children with caring responsibilities. Moreover, previous experience of failing to obtain care made them reluctant to seek help from jiaren; (3) Desire to not bother wairen (meaning people other than family in Chinese): The lack of trust caused by being unfamiliar with wairen, and the fear of being a burden to others if they were not able to reciprocate, made older adults reluctant to seek help from wairen.

Conclusions

Changes in social, economic, and demographic structures have led to gradual failure of family care. Older adults accustomed to an “acquaintance society” have not yet adapted to seeking help from the community. When addressing the problem of care for older adults living alone in cities, it is important to focus on the profound impact of social change.
Psychiatric disorders and associated risk factors in a sample of adolescents in Gaborone, Botswana: a cross-sectional study
Authors: Olashore Anthony A. , Brooks Wendy , Roy Hlanganiso , Adebayo Fatai Adewole , Chiliza Bonginkosi
Published: June 2022

Background

Despite the high proportion of adolescents living with mental health issues in low- to middle-income countries (LMICs), especially in Botswana, there is a significant deficit of local research to guide an increase in prevention and treatment. We, therefore, aimed to assess the prevalence and associated risk factors of psychiatric disorders (PD) in a sample of secondary school students in Botswana.

Methods

This cross-sectional study included 750 students from the 13 public secondary schools in Gaborone using a multi-stage sampling technique. The Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) was used to screen for PDs.

Results

The participant’s mean age was 15.26 and SD 1.57 years, with 53.6% being female. Approximately 34% had a PD, with depression being the commonest, of whom 35% were neither receiving treatment nor aware of the available services. Perinatal complications (AOR = 4.29; 95%CI: 1.04–17.70), a family history of mental illness (AOR = 2.19; 95%CI: 1.17–4.11) and substance-related problems (AOR = 1.80; 95% CI:1.22–2.65) predicted the likelihood of developing PD.

Conclusions

Our findings revealed that adolescents in Botswana have many mental health issues which may affect their developmental phases. A multi-sectoral collaboration is needed for the timely detection of identified risk factors and initiation of the necessary prevention and treatment measures.
Associations between children’s physical literacy and well-being: is physical activity a mediator?
Authors: Melby Paulina S. , Nielsen Glen , Brønd Jan Christian , Tremblay Mark S. , Bentsen Peter , Elsborg Peter
Published: June 2022

Background

Physical literacy (PL) is a multi-dimensional concept that provides a holistic understanding of movement and physical activity. PL contains an affective, a physical, and a cognitive domain, which together lay the foundation for the individual’s capacity and the tendency for participating in physical activities currently and throughout life. PL is increasingly regarded as a ‘cause of the causes’ to health promotion. Cross-sectional studies have shown associations between children’s PL, physical activity behaviours, and well-being. This study aims to examine the associations between Danish children’s PL and their physical and psychosocial well-being and whether the associations are mediated by moderate- to vigorous intensity physical activity (MVPA).

Methods

Cross-sectional data from Danish schoolchildren aged 7–13 years were collected in Jan-Dec 2020 in the Danish Assessment of Physical Literacy (DAPL) project. PL was assessed with the DAPL which measures the affective, cognitive, and physical domains of PL. MVPA (min/day) was measured with accelerometers (Axivity), psychosocial well-being was measured with The Strengths and Difficulties Questionnaire, and physical well-being was measured with the KIDSCREEN questionnaire. Structural equation models were constructed with PL and MVPA as predictors of physical well-being and four aspects of psychosocial well-being.

Results

A positive moderate association between PL and physical well-being, partly mediated by MVPA was observed. PL was positively associated with the positive aspects of psychosocial well-being and negatively associated with the negative aspects (behaviour problems). None of the associations between PL and aspects of psychosocial well-being were mediated by MVPA.

Conclusions

The study contributes to evidence on the link between PL, physical activity, and health outcomes. The study found beneficial relations between PL and physical and psychosocial well-being. MVPA mediated part of the relationship between PL and physical well-being but not psychosocial well-being.