bluuebunny/crossref_metadata_2025 huggingface dataset:
Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice
Authors: Lai Yumei , Zheng Wei , Qu Minghao , Xiao Christopher C. , Chen Sheng , Yao Qing , Gong Weiyuan , Tao Chu , Yan Qinnan , Zhang Peijun , Wu Xiaohao , Xiao Guozhi
Published: July 2022

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.
Thermally-curable nanocomposite printing for the scalable manufacturing of dielectric metasurfaces
Authors: Kim Wonjoong , Yoon Gwanho , Kim Joohoon , Jeong Heonyeong , Kim Yeseul , Choi Hojung , Badloe Trevon , Rho Junsuk , Lee Heon
Published: July 2022

Metasurfaces consisting of artificially designed meta-atoms have been popularized recently due to their advantages of amplitude and phase of light control. However, the electron beam lithography method for metasurface fabrication has high cost and low throughput, which results in a limitation for the fabrication of metasurfaces. In this study, nanocomposite printing technology is used to fabricate high-efficiency metasurfaces with low cost. To demonstrate the efficiency of the proposed fabrication method, a metahologram is designed and fabricated using a nanocomposite. The metahologram exhibits conversion efficiencies of 48% and 35% at wavelengths of 532 and 635 nm, respectively. The nanocomposite is composed of polymers with nanoparticles, so durability tests are also performed to evaluate the effects of temperature and humidity on the metasurfaces. The test verifies that at temperatures below the glass transition temperature of the base resin, the nanostructures do not collapse, so the efficiency of the metasurfaces remains almost the same. The surrounding humidity does not affect the nanostructures at all. Hence, the durability of the nanocomposite metasurfaces can be further enhanced by replacing the base resin, and this nanocomposite printing method will facilitate practical metasurface use at low cost.
Ets1 mediates sorafenib resistance by regulating mitochondrial ROS pathway in hepatocellular carcinoma
Authors: Vishnoi Kanchan , Ke Rong , Viswakarma Navin , Srivastava Piush , Kumar Sandeep , Das Subhasis , Singh Sunil Kumar , Principe Daniel R. , Rana Ajay , Rana Basabi
Published: July 2022

The incidence and mortality of hepatocellular carcinoma (HCC) are on a rise in the Western countries including US, attributed mostly to late detection. Sorafenib has been the first-line FDA-approved drug for advanced unresectable HCC for almost a decade, but with limited efficacy due to the development of resistance. More recently, several other multi-kinase inhibitors (lenvatinib, cabozantinib, regorafenib), human monoclonal antibody (ramucirumab), and immune checkpoint inhibitors (nivolumab, pembrolizumab) have been approved as systemic therapies. Despite this, the median survival of patients is not significantly increased. Understanding of the molecular mechanism(s) that govern HCC resistance is critically needed to increase efficacy of current drugs and to develop more efficacious ones in the future. Our studies with sorafenib-resistant (soraR) HCC cells using transcription factor RT2 Profiler PCR Arrays revealed an increase in E26 transformation–specific-1 (Ets-1) transcription factor in all soraR cells. HCC TMA studies showed an increase in Ets-1 expression in advanced HCC compared to the normal livers. Overexpression or knocking down Ets-1 modulated sorafenib resistance-related epithelial–mesenchymal transition (EMT), migration, and cell survival. In addition, the soraR cells showed a significant reduction of mitochondrial damage and mitochondrial reactive oxygen species (mROS) generation, which were antagonized by knocking down Ets-1 expression. More in-depth analysis identified GPX-2 as a downstream mediator of Ets-1-induced sorafenib resistance, which was down-regulated by Ets-1 knockdown while other antioxidant pathway genes were not affected. Interestingly, knocking down GPX2 expression significantly increased sorafenib sensitivity in the soraR cells. Our studies indicate the activation of a novel Ets-1–GPX2 signaling axis in soraR cells, targeting which might successfully antagonize resistance and increase efficacy.
Microbial autotrophic biorefineries: Perspectives for biopolymer production
Authors: Srisawat Pisanee , Higuchi-Takeuchi Mieko , Numata Keiji
Published: July 2022

The use of autotrophic microorganisms to fabricate biochemical products has attracted much attention in both academia and industry. Unlike heterotrophic microorganisms that require carbohydrates and amino acids for growth, autotrophic microorganisms have evolved to utilize either light (photoautotrophs) or chemical compounds (chemolithotrophs) to fix carbon dioxide (CO2) and drive metabolic processes. Several biotechnological approaches, including synthetic biology and metabolic engineering, have been proposed to harness autotrophic microorganisms as a sustainable/green production platform for commercially essential products such as biofuels, commodity chemicals, and biopolymers. Here, we review the recent advances in natural autotrophic microorganisms (photoautotrophic and chemoautotrophic), focusing on the biopolymer production. We present current state-of-the-art technologies to engineer autotrophic microbial cell factories for efficient biopolymer production.
A-site cation influence on the conduction band of lead bromide perovskites
Authors: Man Gabriel J. , Kamal Chinnathambi , Kalinko Aleksandr , Phuyal Dibya , Acharya Joydev , Mukherjee Soham , Nayak Pabitra K. , Rensmo Håkan , Odelius Michael , Butorin Sergei M.
Published: July 2022

Hot carrier solar cells hold promise for exceeding the Shockley-Queisser limit. Slow hot carrier cooling is one of the most intriguing properties of lead halide perovskites and distinguishes this class of materials from competing materials used in solar cells. Here we use the element selectivity of high-resolution X-ray spectroscopy and density functional theory to uncover a previously hidden feature in the conduction band states, the σ-π energy splitting, and find that it is strongly influenced by the strength of electronic coupling between the A-cation and bromide-lead sublattice. Our finding provides an alternative mechanism to the commonly discussed polaronic screening and hot phonon bottleneck carrier cooling mechanisms. Our work emphasizes the optoelectronic role of the A-cation, provides a comprehensive view of A-cation effects in the crystal and electronic structures, and outlines a broadly applicable spectroscopic approach for assessing the impact of chemical alterations of the A-cation on perovskite electronic structure.
Accelerated western European heatwave trends linked to more-persistent double jets over Eurasia
Authors: Rousi Efi , Kornhuber Kai , Beobide-Arsuaga Goratz , Luo Fei , Coumou Dim
Published: July 2022

Persistent heat extremes can have severe impacts on ecosystems and societies, including excess mortality, wildfires, and harvest failures. Here we identify Europe as a heatwave hotspot, exhibiting upward trends that are three-to-four times faster compared to the rest of the northern midlatitudes over the past 42 years. This accelerated trend is linked to atmospheric dynamical changes via an increase in the frequency and persistence of double jet stream states over Eurasia. We find that double jet occurrences are particularly important for western European heatwaves, explaining up to 35% of temperature variability. The upward trend in the persistence of double jet events explains almost all of the accelerated heatwave trend in western Europe, and about 30% of it over the extended European region. Those findings provide evidence that in addition to thermodynamical drivers, atmospheric dynamical changes have contributed to the increased rate of European heatwaves, with implications for risk management and potential adaptation strategies.
Neutralization capacity of antibodies elicited through homologous or heterologous infection or vaccination against SARS-CoV-2 VOCs
Authors: Bekliz Meriem , Adea Kenneth , Vetter Pauline , Eberhardt Christiane S. , Hosszu-Fellous Krisztina , Vu Diem-Lan , Puhach Olha , Essaidi-Laziosi Manel , Waldvogel-Abramowski Sophie , Stephan Caroline , L’Huillier Arnaud G. , Siegrist Claire-Anne , Didierlaurent Arnaud M. , Kaiser Laurent , Meyer Benjamin , Eckerle Isabella
Published: July 2022

Emerging SARS-CoV-2 variants raise questions about escape from previous immunity. As the population immunity to SARS-CoV-2 has become more complex due to prior infections with different variants, vaccinations or the combination of both, understanding the antigenic relationship between variants is needed. Here, we have assessed neutralizing capacity of 120 blood specimens from convalescent individuals infected with ancestral SARS-CoV-2, Alpha, Beta, Gamma or Delta, double vaccinated individuals and patients after breakthrough infections with Delta or Omicron-BA.1. Neutralization against seven authentic SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta and Omicron-BA.1) determined by plaque-reduction neutralization assay allowed us to map the antigenic relationship of SARS-CoV-2 variants. Highest neutralization titers were observed against the homologous variant. Antigenic cartography identified Zeta and Omicron-BA.1 as separate antigenic clusters. Substantial immune escape in vaccinated individuals was detected for Omicron-BA.1 but not Zeta. Combined infection/vaccination derived immunity results in less Omicron-BA.1 immune escape. Last, breakthrough infections with Omicron-BA.1 lead to broadly neutralizing sera.
Neutralization of ionic interactions by dextran-based single-chain nanoparticles improves tobramycin diffusion into a mature biofilm
Authors: Blanco-Cabra Núria , Movellan Julie , Marradi Marco , Gracia Raquel , Salvador Cristian , Dupin Damien , Loinaz Iraida , Torrents Eduard
Published: July 2022

The extracellular matrix protects biofilm cells by reducing diffusion of antimicrobials. Tobramycin is an antibiotic used extensively to treatP. aeruginosabiofilms, but it is sequestered in the biofilm periphery by the extracellular negative charge matrix and loses its efficacy significantly. Dispersal of the biofilm extracellular matrix with enzymes such as DNase I is another promising therapy that enhances antibiotic diffusion into the biofilm. Here, we combine the charge neutralization of tobramycin provided by dextran-based single-chain polymer nanoparticles (SCPNs) together with DNase I to break the biofilm matrix. Our study demonstrates that the SCPNs improve the activity of tobramycin and DNase I by neutralizing the ionic interactions that keep this antibiotic in the biofilm periphery. Moreover, the detailed effects and interactions of nanoformulations with extracellular matrix components were revealed through time-lapse imaging of theP. aeruginosabiofilms by laser scanning confocal microscopy with specific labeling of the different biofilm components.
A multiplex implantable microdevice assay identifies synergistic combinations of cancer immunotherapies and conventional drugs
Authors: Tatarova Zuzana , Blumberg Dylan C. , Korkola James E. , Heiser Laura M. , Muschler John L. , Schedin Pepper J. , Ahn Sebastian W. , Mills Gordon B. , Coussens Lisa M. , Jonas Oliver , Gray Joe W.
Published: July 2022

Systematically identifying synergistic combinations of targeted agents and immunotherapies for cancer treatments remains difficult. In this study, we integrated high-throughput and high-content techniques—an implantable microdevice to administer multiple drugs into different sites in tumors at nanodoses and multiplexed imaging of tumor microenvironmental states—to investigate the tumor cell and immunological response signatures to different treatment regimens. Using a mouse model of breast cancer, we identified effective combinations from among numerous agents within days. In vivo studies in three immunocompetent mammary carcinoma models demonstrated that the predicted combinations synergistically increased therapeutic efficacy. We identified at least five promising treatment strategies, of which the panobinostat, venetoclax and anti-CD40 triple therapy was the most effective in inducing complete tumor remission across models. Successful drug combinations increased spatial association of cancer stem cells with dendritic cells during immunogenic cell death, suggesting this as an important mechanism of action in long-term breast cancer control.
Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements
Authors: Baranasic Damir , Hörtenhuber Matthias , Balwierz Piotr J. , Zehnder Tobias , Mukarram Abdul Kadir , Nepal Chirag , Várnai Csilla , Hadzhiev Yavor , Jimenez-Gonzalez Ada , Li Nan , Wragg Joseph , D’Orazio Fabio M. , Relic Dorde , Pachkov Mikhail , Díaz Noelia , Hernández-Rodríguez Benjamín , Chen Zelin , Stoiber Marcus , Dong Michaël , Stevens Irene , Ross Samuel E. , Eagle Anne , Martin Ryan , Obasaju Oluwapelumi , Rastegar Sepand , McGarvey Alison C. , Kopp Wolfgang , Chambers Emily , Wang Dennis , Kim Hyejeong R. , Acemel Rafael D. , Naranjo Silvia , Łapiński Maciej , Chong Vanessa , Mathavan Sinnakaruppan , Peers Bernard , Sauka-Spengler Tatjana , Vingron Martin , Carninci Piero , Ohler Uwe , Lacadie Scott Allen , Burgess Shawn M. , Winata Cecilia , van Eeden Freek , Vaquerizas Juan M. , Gómez-Skarmeta José Luis , Onichtchouk Daria , Brown Ben James , Bogdanovic Ozren , van Nimwegen Erik , Westerfield Monte , Wardle Fiona C. , Daub Carsten O. , Lenhard Boris , Müller Ferenc
Published: July 2022

Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental functional genomic data. Our data coordination center (https://danio-code.zfin.org) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals.
Longitudinal dynamics of clonal hematopoiesis identifies gene-specific fitness effects
Authors: Robertson Neil A. , Latorre-Crespo Eric , Terradas-Terradas Maria , Lemos-Portela Jorge , Purcell Alison C. , Livesey Benjamin J. , Hillary Robert F. , Murphy Lee , Fawkes Angie , MacGillivray Louise , Copland Mhairi , Marioni Riccardo E. , Marsh Joseph A. , Harris Sarah E. , Cox Simon R. , Deary Ian J. , Schumacher Linus J. , Kirschner Kristina , Chandra Tamir
Published: July 2022

Clonal hematopoiesis of indeterminate potential (CHIP) increases rapidly in prevalence beyond age 60 and has been associated with increased risk for malignancy, heart disease and ischemic stroke. CHIP is driven by somatic mutations in hematopoietic stem and progenitor cells (HSPCs). Because mutations in HSPCs often drive leukemia, we hypothesized that HSPC fitness substantially contributes to transformation from CHIP to leukemia. HSPC fitness is defined as the proliferative advantage over cells carrying no or only neutral mutations. If mutations in different genes lead to distinct fitness advantages, this could enable patient stratification. We quantified the fitness effects of mutations over 12 years in older age using longitudinal sequencing and developed a filtering method that considers individual mutational context alongside mutation co-occurrence to quantify the growth potential of variants within individuals. We found that gene-specific fitness differences can outweigh inter-individual variation and, therefore, could form the basis for personalized clinical management.
Resurrecting extinct cephalopods with biomimetic robots to explore hydrodynamic stability, maneuverability, and physical constraints on life habits
Authors: Peterman David J. , Ritterbush Kathleen A.
Published: July 2022

Externally shelled cephalopods with coiled, planispiral conchs were ecologically successful for hundreds of millions of years. These animals displayed remarkable morphological disparity, reflecting comparable differences in physical properties that would have constrained their life habits and ecological roles. To investigate these constraints, self-propelling, neutrally buoyant, biomimetic robots were 3D-printed for four disparate morphologies. These robots were engineered to assume orientations computed from virtual hydrostatic simulations while producingNautilus-like thrusts. Compressed morphotypes had improved hydrodynamic stability (coasting efficiency) and experienced lower drag while jetting backwards. However, inflated morphotypes had improved maneuverability while rotating about the vertical axis. These differences highlight an inescapable physical tradeoff between hydrodynamic stability and yaw maneuverability, illuminating different functional advantages and life-habit constraints across the cephalopod morphospace. This tradeoff reveals there is no single optimum conch morphology, and elucidates the success and iterative evolution of disparate morphologies through deep time, including non-streamlined forms.
Stable isotope analysis confirms substantial changes in the fatty acid composition of bacteria treated with antimicrobial random peptide mixtures (RPMs)
Authors: Wiedmaier-Czerny Nina , Schroth Dorothee , Krauß Stephanie , Topman-Rakover Shiri , Brill Aya , Burdman Saul , Hayouka Zvi , Vetter Walter
Published: July 2022

Resistance of plant-pathogenic bacteria to classic antibiotics has prompted the search for suitable alternative antimicrobial substances. One promising strategy could be the use of purposely synthesized random peptide mixtures (RPMs). Six plant-pathogenic bacteria were cultivated and treated with two RPMs previously found to show antimicrobial activity mainly by bacterial membrane disruption. Here, we show that bacteria treated with RPMs showed partly remarkable changes in the fatty acid pattern while those unaffected did not. Quantitative changes could be verified by compound specific isotope analysis of δ13C values (‰). This technique was employed due to the characteristic feature of stronger bonds between heavier isotopes in (bio)chemical reactions. As a proof of concept, the increase in abundance of a fatty acid group after RPM treatment was accompanied with a decrease in the 13C content and vice versa. We propose that our findings will help designing and synthesizing more selective antimicrobial peptides.
Suitability of the global forest cover change map to assess climatic megadisturbance impacts on remote tropical forests
Authors: Geler Roffe Tatiana , Couturier Stéphane , García-Romero Arturo
Published: July 2022

The occurrence and combination of extreme meteorological events may lead to severe (megadisturbance) impacts on conserved forests and protected areas all over the world. Recent research has shown that megadisturbance impacts (after the events of hurricanes and prolonged drought) may be detected in subtropical forest cover using changes in spectral indices derived from satellite imagery. The objective of this study is to assess the impact of megadisturbance on forest types of the Alejandro de Humboldt National Park, Republic of Cuba in the 2001–2017 time-period. The Global Forest Cover Change (GFCC, available on the Global Forest Watch website) product was validated and indicated the prominence of megadisturbance for year 2016 (85% of the total disturbed area), largely associated with the Hurricane Matthew event. A robust estimator of the disturbed forest area, based on GFCC-stratified sampled verification sites, suggests that 11,110 ± 1,771 hectares of forest (~ 16% of the Park’s total area) was affected by megadisturbance between 2001 and 2017. In 2017, about 1276 hectares of forests were impacted, presumably related to a long-lasting effect of megadisturbance due to Hurricane Matthew and prolonged droughts in previous years. Four types of tropical rainforests (especially lowland rainforest and submountainous sclerophyllous rainforest on serpentinite), that cover 43% of the National Park, accounted for about 85% of the impacts by megadisturbance. The Easternmost portion of these forests should be prioritized for conservation monitoring and possibly for forest restoration strategies. This study contributes to establishing methodological guidelines for rapid environmental assessment of remote, tropical protected areas facing the impacts of extreme meteorological events and climate change.
Counting generations in birth and death processes with competing Erlang and exponential waiting times
Authors: Belluccini Giulia , López-García Martín , Lythe Grant , Molina-París Carmen
Published: July 2022

Lymphocyte populations, stimulated in vitro or in vivo, grow as cells divide. Stochastic models are appropriate because some cells undergo multiple rounds of division, some die, and others of the same type in the same conditions do not divide at all. If individual cells behave independently, then each cell can be imagined as sampling from a probability density of times to division and death. The exponential density is the most mathematically and computationally convenient choice. It has the advantage of satisfying the memoryless property, consistent with a Markov process, but it overestimates the probability of short division times. With the aim of preserving the advantages of a Markovian framework while improving the representation of experimentally-observed division times, we consider a multi-stage model of cellular division and death. We use Erlang-distributed (or, more generally, phase-type distributed) times to division, and exponentially distributed times to death. We classify cells into generations, using the rule that the daughters of cells in generation n are in generation $$n+1$$

n
+
1

. In some circumstances, our representation is equivalent to established models of lymphocyte dynamics. We find the growth rate of the cell population by calculating the proportions of cells by stage and generation. The exponent describing the late-time cell population growth, and the criterion for extinction of the population, differs from what would be expected if N steps with rate $$\lambda$$
λ
were equivalent to a single step of rate $$\lambda /N$$

λ
/
N

. We link with a published experimental dataset, where cell counts were reported after T cells were transferred to lymphopenic mice, using Approximate Bayesian Computation. In the comparison, the death rate is assumed to be proportional to the generation and the Erlang time to division for generation 0 is allowed to differ from that of subsequent generations. The multi-stage representation is preferred to a simple exponential in posterior distributions, and the mean time to first division is estimated to be longer than the mean time to subsequent divisions.
Object based classification of a riparian environment using ultra-high resolution imagery, hierarchical landcover structures, and image texture
Authors: Kutz Kain , Cook Zachary , Linderman Marc
Published: July 2022

Land cover mapping is an important part of resource management, planning, and economic predictions. Improvements in remote sensing, machine learning, image processing, and object based image analysis (OBIA) has made the process of identifying land cover types increasingly faster and reliable but these advances have not been able to utilize all of the information encompassed within ultra-high (sub-meter) resolution imagery. There have been few known attempts to try and maximize this detailed information in high resolution imagery using advanced textural components. Hierarchical land classes are also rarely used as an attribute within the machine learning step of object-based image analysis. In this study we try to circumnavigate the inherent problems associated with high resolution imagery by combining well researched data transformations that aid the OBIA process with a seldom used texture transformation in Geographic Object Based Image Analyses (GEOBIA/OBIA) known as the Gabor Transform and the hierarchal organization of landscapes. We will observe the difference made in segmentation and classification accuracy of a random forest classifier when we fuse a Gabor transformed image to a Normalized Difference Vegetation Index (NDVI), high resolution multi-spectral imagery (RGB and NIR) and Light Detection and Ranging (LiDAR) derived canopy height model (CHM) within a riparian area in Southeast Iowa, United States. Additionally, we will observe the effects on classification accuracy when adding multi-scale land cover data to objects. Both, the addition of hierarchical information and Gabor textural information, could aid the GEOBIA process in delineating and classifying the same objects that human experts would delineate within this riparian landscape.
Motivations underlying self-infliction of pain during thinking for pleasure
Authors: Eder Andreas B. , Maas Franzisca , Schubmann Alexander , Krishna Anand , Erle Thorsten M.
Published: July 2022

Previous research suggested that people prefer to administer unpleasant electric shocks to themselves rather than being left alone with their thoughts because engagement in thinking is an unpleasant activity. The present research examined this negative reinforcement hypothesis by giving participants a choice of distracting themselves with the generation of electric shock causing no to intense pain. Four experiments (N = 254) replicated the result that a large proportion of participants opted to administer painful shocks to themselves during the thinking period. However, they administered strong electric shocks to themselves even when an innocuous response option generating no or a mild shock was available. Furthermore, participants inflicted pain to themselves when they were assisted in the generation of pleasant thoughts during the waiting period, with no difference between pleasant versus unpleasant thought conditions. Overall, these results question that the primary motivation for the self-administration of painful shocks is avoidance of thinking. Instead, it seems that the self-infliction of pain was attractive for many participants, because they were curious about the shocks, their intensities, and the effects they would have on them.
Laser cluster interaction in ambient magnetic fields for accelerating electrons in two stages without external injection
Authors: Swain Kalyani , Mahalik Sagar Sekhar , Kundu Mrityunjay
Published: July 2022

In the few-cycle pulse regime of laser-cluster interaction (intensity $$>10^{16}\,\text{ W/cm}^{2}$$

>

10
16

W/cm
2

, wavelength $$> 780$$

>
780

 nm), laser absorption is mostly collisionless and may happen via anharmonic resonance (AHR) process in the overdense (cluster) plasma potential. Many experiments, theory and simulation show average absorbed energy per cluster-electron ($${\mathcal {E}_A}$$

E
A

) close to the electron’s ponderomotive energy ($$U_\mathrm {p}$$

U
p

) in the collisionless regime. In this work, by simple rigid sphere model (RSM) and detailed particle-in-cell (PIC) simulation, we show enhanced $${\mathcal {E}_A}\approx$$

E
A

≈

30–70$$U_\mathrm {p}$$

U
p

—a 15–30 fold increase—with an external (crossed) magnetic field near the electron-cyclotron resonance (ECR). Due to relativistic mass increase, electrons quickly deviate from the standard (non-relativistic) ECR, but time-dependent relativistic-ECR (RECR) happens which also contributes to enhanced $${\mathcal {E}_A}$$

E
A

. Here laser is coupled to electrons in two stages, i.e, AHR and ECR/RECR. To probe further we retrieve the phase-difference $$\Delta \psi$$

Δ
ψ

between the driving electric field and corresponding velocity component for each electron (in PIC and RSM). We find absorption by electron via AHR happens in a very short interval $$\Delta \tau$$

Δ
τ

for less than half a laser period where $$\Delta \psi$$

Δ
ψ

remains close to $$\pi$$
π
(necessary condition for maximum laser absorption) and then $$\Delta \psi$$

Δ
ψ

drops to its initial $$\pi /2$$

π
/
2

(meaning no absorption) after such short-lived AHR. On the contrary, auxiliary magnetic field near the ECR modifies AHR scenario inside the cluster and also helps maintaining the required phase $$\Delta \psi \approx \pi$$

Δ
ψ
≈
π

for the liberated cluster-electron accompanied by frequency matching for ECR/RECR for a prolonged $$\Delta \tau$$

Δ
τ

(which covers 50–60% of the laser pulse through pulse maxima) even after AHR—leading to jump in $${\mathcal {E}_A}\approx$$

E
A

≈

30–70$$U_\mathrm {p}$$

U
p

. We note that to realize the second stage of enhanced energy coupling via ECR/RECR, the first stage via AHR is necessary.
Pathogenicity of missense variants affecting the collagen IV α5 carboxy non-collagenous domain in X-linked Alport syndrome
Authors: Gibson Joel T. , Sadeghi-Alavijeh Omid , Gale Daniel P. , Rothe Hansjörg ,   Genomics England Research Consortium, Sadeghi-Alavijeh Omid , Gale Daniel P. , Savige Judy , Ambrose J. C. , Arumugam P. , Baple E. L. , Bleda M. , Boardman-Pretty F. , Boissiere J. M. , Boustred C. R. , Brittain H. , Caulfield M. J. , Chan G. C. , Craig C. E. H. , Daugherty L. C. , de Burca A. , Devereau A. , Elgar G. , Foulger R. E. , Fowler T. , Furió-Tarí P. , Giess A. , Hackett J. M. , Halai D. , Hamblin A. , Henderson S. , Holman J. E. , Hubbard T. J. P. , Ibáñez K. , Jackson R. , Jones L. J. , Kasperaviciute D. , Kayikci M. , Kousathanas A. , Lahnstein L. , Lawson K. , Leigh S. E. A. , Leong I. U. S. , Lopez F. J. , Maleady-Crowe F. , Mason J. , McDonagh E. M. , Moutsianas L. , Mueller M. , Murugaesu N. , Need A. C. , Odhams C. A. , Orioli A. , Patch C. , Perez-Gil D. , Pereira M. B. , Polychronopoulos D. , Pullinger J. , Rahim T. , Rendon A. , Riesgo-Ferreiro P. , Rogers T. , Ryten M. , Savage K. , Sawant K. , Scott R. H. , Siddiq A. , Sieghart A. , Smedley D. , Smith K. R. , Smith S. C. , Sosinsky A. , Spooner W. , Stevens H. E. , Stuckey A. , Sultana R. , Tanguy M. , Thomas E. R. A. , Thompson S. R. , Tregidgo C. , Tucci A. , Walsh E. , Watters S. A. , Welland M. J. , Williams E. , Witkowska K. , Wood S. M. , Zarowiecki M. , Savige Judy
Published: July 2022

X-linked Alport syndrome is a genetic kidney disease caused by pathogenic COL4A5 variants, but little is known of the consequences of missense variants affecting the NC1 domain of the corresponding collagen IV α5 chain. This study examined these variants in a normal (gnomAD) and other databases (LOVD, Clin Var and 100,000 Genomes Project) to determine their pathogenicity and clinical significance. Males with Cys substitutions in the collagen IV α5 NC1 domain reported in LOVD (n = 25) were examined for typical Alport features, including age at kidney failure. All NC1 variants in LOVD (n = 86) were then assessed for structural damage using an online computational tool, Missense3D. Variants in the ClinVar, gnomAD and 100,000 Genomes Project databases were also examined for structural effects. Predicted damage associated with NC1 substitutions was then correlated with the level of conservation of the affected residues. Cys substitutions in males were associated with the typical features of X-linked Alport syndrome, with a median age at kidney failure of 31 years. NC1 substitutions predicted to cause structural damage were overrepresented in LOVD (p < 0.001), and those affecting Cys residues or ‘buried’ Gly residues were more common than expected (both p < 0.001). Most NC1 substitutions in gnomAD (88%) were predicted to be structurally-neutral. Substitutions affecting conserved residues resulted in more structural damage than those affecting non-conserved residues (p < 0.001). Many pathogenic missense variants affecting the collagen IV α5 NC1 domain have their effect through molecular structural damage and 3D modelling is a useful tool in their assessment.
Role of copper and alumina for heat transfer in hybrid nanofluid by using Fourier sine transform
Authors: Souayeh Basma , Abro Kashif Ali , Siyal Ambreen , Hdhiri Najib , Hammami Faycal , Al-Shaeli Muayad , Alnaim Nisrin , Raju S. Suresh Kumar , Alam Mir Waqas , Alsheddi Tarfa
Published: July 2022

The convection, thermal conductivity, and heat transfer of hybrid nanofluid through nanoparticles has become integral part of several natural and industrial processes. In this manuscript, a new fractionalized model based on hybrid nanofluid is proposed and investigated by employing singular verses and non-singular kernels. The mathematical modeling of hybrid nanofluid is handled via modern fractional definitions of differentiations. The combined Laplace and Fourier Sine transforms have been configurated on the governing equations of hybrid nanofluid. The analytical expression of the governing temperature and velocity equations of hybrid nanofluid have been solved via special functions. For the sake of thermal performance, dimensional analysis of governing equations and suitable boundary conditions based on Mittage-Leffler function have been invoked for the first time in literature. The comparative analysis of heat transfer from hybrid nanofluid has been observed through Caputo-Fabrizio and Atangana-Baleanu differential operators. Finally, our results suggest that volume fraction has the decelerated and accelerated trends of temperature distribution and inclined and declined profile of heat transfer is observed copper and alumina nanoparticles.
Machine learning predicts clinically significant health related quality of life improvement after sensorimotor rehabilitation interventions in chronic stroke
Authors: Liao Wan-Wen , Hsieh Yu-Wei , Lee Tsong-Hai , Chen Chia-ling , Wu Ching-yi
Published: July 2022

Health related quality of life (HRQOL) reflects individuals perceived of wellness in health domains and is often deteriorated after stroke. Precise prediction of HRQOL changes after rehabilitation interventions is critical for optimizing stroke rehabilitation efficiency and efficacy. Machine learning (ML) has become a promising outcome prediction approach because of its high accuracy and easiness to use. Incorporating ML models into rehabilitation practice may facilitate efficient and accurate clinical decision making. Therefore, this study aimed to determine if ML algorithms could accurately predict clinically significant HRQOL improvements after stroke sensorimotor rehabilitation interventions and identify important predictors. Five ML algorithms including the random forest (RF), k-nearest neighbors (KNN), artificial neural network, support vector machine and logistic regression were used. Datasets from 132 people with chronic stroke were included. The Stroke Impact Scale was used for assessing multi-dimensional and global self-perceived HRQOL. Potential predictors included personal characteristics and baseline cognitive/motor/sensory/functional/HRQOL attributes. Data were divided into training and test sets. Tenfold cross-validation procedure with the training data set was used for developing models. The test set was used for determining model performance. Results revealed that RF was effective at predicting multidimensional HRQOL (accuracy: 85%; area under the receiver operating characteristic curve, AUC-ROC: 0.86) and global perceived recovery (accuracy: 80%; AUC-ROC: 0.75), and KNN was effective at predicting global perceived recovery (accuracy: 82.5%; AUC-ROC: 0.76). Age/gender, baseline HRQOL, wrist/hand muscle function, arm movement efficiency and sensory function were identified as crucial predictors. Our study indicated that RF and KNN outperformed the other three models on predicting HRQOL recovery after sensorimotor rehabilitation in stroke patients and could be considered for future clinical application.
Development and implementation of patient-level prediction models of end-stage renal disease for type 2 diabetes patients using fast healthcare interoperability resources
Authors: Wang San , Han Jieun , Jung Se Young , Oh Tae Jung , Yao Sen , Lim Sanghee , Hwang Hee , Lee Ho-Young , Lee Haeun
Published: July 2022

This study aimed to develop a model to predict the 5-year risk of developing end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) using machine learning (ML). It also aimed to implement the developed algorithms into electronic medical records (EMR) system using Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR). The final dataset used for modeling included 19,159 patients. The medical data were engineered to generate various types of features that were input into the various ML classifiers. The classifier with the best performance was XGBoost, with an area under the receiver operator characteristics curve (AUROC) of 0.95 and area under the precision recall curve (AUPRC) of 0.79 using three-fold cross-validation, compared to other models such as logistic regression, random forest, and support vector machine (AUROC range, 0.929–0.943; AUPRC 0.765–0.792). Serum creatinine, serum albumin, the urine albumin-to-creatinine ratio, Charlson comorbidity index, estimated GFR, and medication days of insulin were features that were ranked high for the ESRD risk prediction. The algorithm was implemented in the EMR system using HL7 FHIR through an ML-dedicated server that preprocessed unstructured data and trained updated data.
In-vivo data-driven parcellation of Heschl’s gyrus using structural connectivity
Authors: Lee Hyebin , Byeon Kyoungseob , Park Bo-yong , Lee Sean H. , Park Hyunjin
Published: July 2022

The human auditory cortex around Heschl’s gyrus (HG) exhibits diverging patterns across individuals owing to the heterogeneity of its substructures. In this study, we investigated the subregions of the human auditory cortex using data-driven machine-learning techniques at the individual level and assessed their structural and functional profiles. We studied an openly accessible large dataset of the Human Connectome Project and identified the subregions of the HG in humans using data-driven clustering techniques with individually calculated imaging features of cortical folding and structural connectivity information obtained via diffusion magnetic resonance imaging tractography. We characterized the structural and functional profiles of each HG subregion according to the cortical morphology, microstructure, and functional connectivity at rest. We found three subregions. The first subregion (HG1) occupied the central portion of HG, the second subregion (HG2) occupied the medial-posterior-superior part of HG, and the third subregion (HG3) occupied the lateral-anterior-inferior part of HG. The HG3 exhibited strong structural and functional connectivity to the association and paralimbic areas, and the HG1 exhibited a higher myelin density and larger cortical thickness than other subregions. A functional gradient analysis revealed a gradual axis expanding from the HG2 to the HG3. Our findings clarify the individually varying structural and functional organization of human HG subregions and provide insights into the substructures of the human auditory cortex.
Guided-wave manipulation in SIW H-plane horn antenna by combining phase correction and holographic-based leakage
Authors: Araghi Ali , Khalily Mohsen , Yurduseven Okan , Xiao Pei , Tafazolli Rahim
Published: July 2022

A hybrid technique is proposed to manipulate the field distribution in a substrate integrated waveguide (SIW) H-plane horn to enhance its radiation characteristics. The technique comprises two cascaded steps to govern the guided waves in the structure. The first step is to correct the phase of fields and form a quasi-uniform distribution in the flare section so that the gain increases and side-lobe-level (SLL) decreases. This is obtained by loading the structure with a novel modulated metal-via lens. Field expansion on the radiating aperture of the SIW H-plane horn generates backward surface waves on both broad walls which increases the backlobe. In the second step, these backward surface waves are recycled and directed forward with the aid of holography theory. This is achieved by adding a couple of dielectric slabs with holographic-based patterns of metallic strips on both broad walls. With this step, the backlobe is reduced and the endfire gain is further increased. Using the proposed technique, the structure is designed and fabricated to operate at$$f=30$$f=30 GHz which simultaneously improves the measured values of gain to 11.65 dBi, H-plane SLL to$$-\,17.94$$-17.94 dB, and front-to-back ratio to 17.02 dB.
The iodide transporter Slc26a7 impacts thyroid function more strongly than Slc26a4 in mice
Authors: Yamaguchi Naoya , Suzuki Atsushi , Yoshida Aya , Tanaka Tatsushi , Aoyama Kohei , Oishi Hisashi , Hara Yuichiro , Ogi Tomoo , Amano Izuki , Kameo Satomi , Koibuchi Noriyuki , Shibata Yasuhiro , Ugawa Shinya , Mizuno Haruo , Saitoh Shinji
Published: July 2022

SLC26A4 is a known iodide transporter, and is localized at the apical membrane of thyrocytes. Previously, we reported that SLC26A7 is also involved in iodide transport and that Slc26a7 is a novel causative gene for congenital hypothyroidism. However, its detailed role in vivo remains to be elucidated. We generated mice that were deficient in Slc26a7 and Slc26a4 to delineate differences and associations in their roles in iodide transport. Slc26a7−/− mice showed goitrous congenital hypothyroidism and mild growth failure on a normal diet. Slc26a7−/− mice with a low iodine environment showed marked growth failure. In contrast, Slc26a4−/− mice showed no growth failure and hypothyroidism in the same low iodine environment. Double-deficient mice showed more severe growth failure than Slc26a7−/− mice. RNA-seq analysis revealed that the number of differentially expressed genes (DEGs) in Slc26a7−/− mice was significantly higher than that in Slc26a4−/− mice. These indicate that SLC26A7 is more strongly involved in iodide transport and the maintenance of thyroid function than SLC26A4.
Impact of lumbar spinal stenosis on metabolic syndrome incidence in community-dwelling adults in Aizu cohort study (LOHAS)
Authors: Ono Rei , Takegami Misa , Yamamoto Yosuke , Yamazaki Shin , Otani Koji , Sekiguchi Miho , Konno Shin-Ichi , Kikuchi Shin-Ichi , Fukuhara Shunichi
Published: July 2022

Metabolic syndrome and lumbar spinal stenosis (LSS) are common age-related diseases. However, the causal relationship between them remains unclear. This study aimed to identify the effects of LSS on metabolic syndrome incidence in community-dwelling adults. This prospective cohort study included participants of the Aizu cohort study (LOHAS) aged < 75 years as of 2008. Participants with metabolic syndrome at baseline were excluded. The primary outcome measure was metabolic syndrome incidence, and the main explanatory variable was the presence of LSS, as assessed by a self-reported questionnaire. A multivariate Cox proportional hazard regression model was used to estimate hazard ratios (HRs) for metabolic syndrome incidence during the 6-year follow-up period. Complete-case analyses were compared with the multiple imputation results. Among 1599 participants, 1390 complete cases were analyzed (mean [SD] age 62.3 [9.0] years; females, 734 [52.8%]). Among those participants, 525 (37.8%) developed metabolic syndrome during the follow-up of 3.89 [1.96] years. The presence of LSS was associated with developing metabolic syndrome (HR, 1.41; 95% confidence interval [CI] 1.02–1.95). Multiple imputation results showed similar trends of those having complete-case data (HR, 1.47; 95% CI 1.08–2.00). This finding suggests the importance of prevention and management of LSS in community settings.
Necroptosis-related lncRNA signatures determine prognosis in breast cancer patients
Authors: Zhang Yuan , Yue Qingfang , Cao Fei , Li YanQin , Wei Yifang
Published: July 2022

Necroptosis is a genetically regulated form of necrotic cell death that has emerged as an important pathway in cancers. Long non-coding RNAs (lncRNAs) are key regulators of breast cancer development. Nevertheless, few studies are reporting the effect of lncRNAs in necroptosis processes and the role of necroptosis-related lncRNAs (NRLs). The present study aimed to construct a prognostic model based on NRLs in breast cancer. NRLs were identified by combining expression profiling data from The Cancer Genome Atlas (TCGA) with necroptosis-related genes. The non-negative matrix factorization (NMF) clustering analysis was conducted to identify molecular subtypes of BC, and the clinical outcome and tumor-infiltrating immune cells (TIICs) in the different molecular subtypes were analyzed. Four molecular subtypes based on NRLs were identified, and these four molecular subtypes could predict clinical features, prognosis, and tumor-infiltrating immune cells (TIICs). A 4-NRLs signature and nomogram were established and validated its predictive capability of overall survival (OS) in breast cancer patients. Analyses of clinicopathological features, prognosis, TIICs, tumor microenvironment (TME), somatic mutations, and drug response revealed significant differences between the two risk groups. In addition, we found that low-risk patients exhibited higher levels of immune checkpoints and showed higher immunogenicity in immunophenoscore (IPS) analysis. In conclusion, we constructed a prognostic model based on the expression profile of NRLs, which may facilitate the assessment of patient prognosis, immunotherapeutic responses, and maybe a promising therapeutic target in clinical practice.