bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration
Authors: Roy Akanksha , Tolone Arianna , Hilhorst Riet , Groten John , Tomar Tushar , Paquet-Durand François
Published: March 2022

Inherited retinal diseases (IRDs) are a group of neurodegenerative disorders that lead to photoreceptor cell death and eventually blindness. IRDs are characterised by a high genetic heterogeneity, making it imperative to design mutation-independent therapies. Mutations in a number of IRD disease genes have been associated with a rise of cyclic 3’,5’-guanosine monophosphate (cGMP) levels in photoreceptors. Accordingly, the cGMP-dependent protein kinase (PKG) has emerged as a new potential target for the mutation-independent treatment of IRDs. However, the substrates of PKG and the downstream degenerative pathways triggered by its activity have yet to be determined. Here, we performed kinome activity profiling of different murine organotypic retinal explant cultures (diseased rd1 and wild-type controls) using multiplex peptide microarrays to identify proteins whose phosphorylation was significantly altered by PKG activity. In addition, we tested the downstream effect of a known PKG inhibitor CN03 in these organotypic retina cultures. Among the PKG substrates were potassium channels belonging to the Kv1 family (KCNA3, KCNA6), cyclic AMP-responsive element-binding protein 1 (CREB1), DNA topoisomerase 2-α (TOP2A), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (F263), and the glutamate ionotropic receptor kainate 2 (GRIK2). The retinal expression of these PKG targets was further confirmed by immunofluorescence and could be assigned to various neuronal cell types, including photoreceptors, horizontal cells, and ganglion cells. Taken together, this study confirmed the key role of PKG in photoreceptor cell death and identified new downstream targets of cGMP/PKG signalling that will improve the understanding of the degenerative mechanisms underlying IRDs.
Changes to gut amino acid transporters and microbiome associated with increased E/I ratio in Chd8+/− mouse model of ASD-like behavior
Authors: Yu You , Zhang Bing , Ji Peifeng , Zuo Zhenqiang , Huang Yongxi , Wang Ning , Liu Chang , Liu Shuang-Jiang , Zhao Fangqing
Published: March 2022

Autism spectrum disorder (ASD), a group of neurodevelopmental disorders characterized by social communication deficits and stereotyped behaviors, may be associated with changes to the gut microbiota. However, how gut commensal bacteria modulate brain function in ASD remains unclear. Here, we used chromodomain helicase DNA-binding protein 8 (CHD8) haploinsufficient mice as a model of ASD to elucidate the pathways through which the host and gut microbiota interact with each other. We found that increased levels of amino acid transporters in the intestines of the mouse model of ASD contribute to the high level of serum glutamine and the increased excitation/inhibition (E/I) ratio in the brain. In addition, elevated α-defensin levels in the haploinsufficient mice resulted in dysregulation of the gut microbiota characterized by a reduced abundance of Bacteroides. Furthermore, supplementation with Bacteroides uniformis improved the ASD-like behaviors and restored the E/I ratio in the brain by decreasing intestinal amino acid transport and the serum glutamine levels. Our study demonstrates associations between changes in the gut microbiota and amino acid transporters, and ASD-like behavioral and electrophysiology phenotypes, in a mouse model.
Causal networks of phytoplankton diversity and biomass are modulated by environmental context
Authors: Chang Chun-Wei , Miki Takeshi , Ye Hao , Souissi Sami , Adrian Rita , Anneville Orlane , Agasild Helen , Ban Syuhei , Be’eri-Shlevin Yaron , Chiang Yin-Ru , Feuchtmayr Heidrun , Gal Gideon , Ichise Satoshi , Kagami Maiko , Kumagai Michio , Liu Xin , Matsuzaki Shin-Ichiro S. , Manca Marina M. , Nõges Peeter , Piscia Roberta , Rogora Michela , Shiah Fuh-Kwo , Thackeray Stephen J. , Widdicombe Claire E. , Wu Jiunn-Tzong , Zohary Tamar , Hsieh Chih-hao
Published: March 2022

Untangling causal links and feedbacks among biodiversity, ecosystem functioning, and environmental factors is challenging due to their complex and context-dependent interactions (e.g., a nutrient-dependent relationship between diversity and biomass). Consequently, studies that only consider separable, unidirectional effects can produce divergent conclusions and equivocal ecological implications. To address this complexity, we use empirical dynamic modeling to assemble causal networks for 19 natural aquatic ecosystems (N24◦~N58◦) and quantified strengths of feedbacks among phytoplankton diversity, phytoplankton biomass, and environmental factors. Through a cross-system comparison, we identify macroecological patterns; in more diverse, oligotrophic ecosystems, biodiversity effects are more important than environmental effects (nutrients and temperature) as drivers of biomass. Furthermore, feedback strengths vary with productivity. In warm, productive systems, strong nitrate-mediated feedbacks usually prevail, whereas there are strong, phosphate-mediated feedbacks in cold, less productive systems. Our findings, based on recovered feedbacks, highlight the importance of a network view in future ecosystem management.
Anisotropic fluid with phototunable dielectric permittivity
Authors: Nishikawa Hiroya , Sano Koki , Araoka Fumito
Published: March 2022

Dielectric permittivity, a measure of polarisability, is a fundamental parameter that dominates various physical phenomena and properties of materials. However, it remains a challenge to control the dielectric permittivity of materials reversibly over a large range. Herein, we report an anisotropic fluid with photoresponsive dielectric permittivity (200 < ε < 18,000) consisting of a fluorinated liquid-crystalline molecule (96 wt%) and an azobenzene-tethered phototrigger (4 wt%). The reversible trans-cis isomerisation of the phototrigger under blue and green light irradiation causes a switch between two liquid-crystalline phases that exhibit different dielectric permittivities, with a rapid response time (<30 s) and excellent reversibility (~100 cycles). This anisotropic fluid can be used as a flexible photovariable capacitor that, for example, allows the reversible modulation of the sound frequency over a wide range (100 < f < 8500 Hz) in a remote manner using blue and green wavelengths.
Optical sensors for operando stress monitoring in lithium-based batteries containing solid-state or liquid electrolytes
Authors: Albero Blanquer Laura , Marchini Florencia , Seitz Jan Roman , Daher Nour , Bétermier Fanny , Huang Jiaqiang , Gervillié Charlotte , Tarascon Jean-Marie
Published: March 2022

The study of chemo-mechanical stress taking place in the electrodes of a battery during cycling is of paramount importance to extend the lifetime of the device. This aspect is particularly relevant for all-solid-state batteries where the stress can be transmitted across the device due to the stiff nature of the solid electrolyte. However, stress monitoring generally relies on sensors located outside of the battery, therefore providing information only at device level and failing to detect local changes. Here, we report a method to investigate the chemo-mechanical stress occurring at both positive and negative electrodes and at the electrode/electrolyte interface during battery operation. To such effect, optical fiber Bragg grating sensors were embedded inside coin and Swagelok cells containing either liquid or solid-state electrolyte. The optical signal was monitored during battery cycling, further translated into stress and correlated with the voltage profile. This work proposes an operando technique for stress monitoring with potential use in cell diagnosis and battery design.
Surface-ligand-induced crystallographic disorder–order transition in oriented attachment for the tuneable assembly of mesocrystals
Authors: Park Bum Chul , Ko Min Jun , Kim Young Kwang , Kim Gyu Won , Kim Myeong Soo , Koo Thomas Myeongseok , Fu Hong En , Kim Young Keun
Published: March 2022

In the crystallisation of nanomaterials, an assembly-based mechanism termed ‘oriented attachment’ (OA) has recently been recognised as an alternative mechanism of crystal growth that cannot be explained by the classical theory. However, attachment alignment during OA is not currently tuneable because its mechanism is poorly understood. Here, we identify the crystallographic disorder-order transitions in the OA of magnetite (Fe3O4) mesocrystals depending on the types of organic surface ligands on the building blocks, which produce different grain structures. We find that alignment variations induced by different surface ligands are guided by surface energy anisotropy reduction and surface deformation. Further, we determine the effects of alignment-dependent magnetic interactions between building blocks on the global magnetic properties of mesocrystals and their chains. These results revisit the driving force of OA and provide an approach for chemically controlling the crystallographic order in colloidal nanocrystalline materials directly related to grain engineering.
Socioeconomic disparities and household crowding in association with the fecal microbiome of school-age children
Authors: Lapidot Yelena , Reshef Leah , Maya Mayan , Cohen Dani , Gophna Uri , Muhsen Khitam
Published: March 2022

The development of the gut microbiome occurs mainly during the first years of life; however, little is known on the role of environmental and socioeconomic exposures, particularly within the household, in shaping the microbial ecology through childhood. We characterized differences in the gut microbiome of school-age healthy children, in association with socioeconomic disparities and household crowding. Stool samples were analyzed from 176 Israeli Arab children aged six to nine years from three villages of different socioeconomic status (SES). Sociodemographic data were collected through interviews with the mothers. We used 16 S rRNA gene sequencing to characterize the gut microbiome, including an inferred analysis of metabolic pathways. Differential analysis was performed using the analysis of the composition of microbiomes (ANCOM), with adjustment for covariates. An analysis of inferred metagenome functions was performed implementing PICRUSt2. Gut microbiome composition differed across the villages, with the largest difference attributed to socioeconomic disparities, with household crowding index being a significant explanatory variable. Living in a low SES village and high household crowding were associated with increased bacterial richness and compositional differences, including an over-representation of Prevotella copri and depleted Bifidobacterium. Secondary bile acid synthesis, d-glutamine and d-glutamate metabolism and Biotin metabolism were decreased in the lower SES village. In summary, residential SES is a strong determinant of the gut microbiome in healthy school-age children, mediated by household crowding and characterized by increased bacterial richness and substantial taxonomic and metabolic differences. Further research is necessary to explore possible implications of SES-related microbiome differences on children’s health and development.
Thermal property and failure behaviors of Gd doped LaZrCeO coatings with feathery microstructure
Authors: Shen Zaoyu , Liu Guanxi , He Limin , Mu Rende , Dai Jianwei
Published: March 2022

LaZrCeO coatings are promising candidates to substitute Y2O3-stabilized ZrO2 in advanced gas turbine engines. In this study, Gd doped LaZrCeO coatings were deposited by electron beam physical vapor deposition. This study focuses on the phase, microstructure, thermal property, and thermal durability of (La1-xGdx)2(Zr0.7Ce0.3)2O7 coatings. The as-deposited coatings show relatively good thermal shock life and thermal cycling life. The broken regions are observed on the interface of thermal barrier coatings. The failure behaviors are relevant with crack evolution and thermally grown oxide growth. This study might guide the investigation of advanced coatings under high temperature.
Aberrant dopamine transporter and functional connectivity patterns in LRRK2 and GBA mutation carriers
Authors: Droby Amgad , Artzi Moran , Lerman Hedva , Hutchison R. Matthew , Bashat Dafna Ben , Omer Nurit , Gurevich Tanya , Orr-Urtreger Avi , Cohen Batsheva , Cedarbaum Jesse M. , Sapir Einat Even , Giladi Nir , Mirelman Anat , Thaler Avner
Published: March 2022

Non-manifesting carriers (NMCs) of Parkinson’s disease (PD)-related mutations such as LRRK2 and GBA are at an increased risk for developing PD. Dopamine transporter (DaT)-spectral positron emission computed tomography is widely used for capturing functional nigrostriatal dopaminergic activity. However, it does not reflect other ongoing neuronal processes; especially in the prodromal stages of the disease. Resting-state fMRI (rs-fMRI) has been proposed as a mode for assessing functional alterations associated with PD, but its relation to dopaminergic deficiency remains unclear. We aimed to study the association between presynaptic striatal dopamine uptake and functional connectivity (FC) patterns among healthy first-degree relatives of PD patients with mutations in LRRK2 and GBA genes. N = 85 healthy first-degree subjects were enrolled and genotyped. All participants underwent DaT and rs-fMRI scans, as well as a comprehensive clinical assessment battery. Between-group differences in FC within striatal regions were investigated and compared with striatal binding ratios (SBR). N = 26 GBA-NMCs, N = 25 LRRK2-NMCs, and N = 34 age-matched nonmanifesting noncarriers (NM-NCs) were included in each study group based on genetic status. While genetically-defined groups were similar across clinical measures, LRRK2-NMCs demonstrated lower SBR in the right putamen compared with NM-NCs, and higher right putamen FC compared to GBA-NMCs. In this group, higher striatal FC was associated with increased risk for PD. The observed differential SBR and FC patterns among LRRK2-NMCs and GBA-NMCs indicate that DaTscan and FC assessments might offer a more sensitive prediction of the risk for PD in the pre-clinical stages of the disease.
Global correlation and local information flows in controllable non-Markovian open quantum dynamics
Authors: Chen Xin-Yu , Zhang Na-Na , He Wan-Ting , Kong Xiang-Yu , Tao Ming-Jie , Deng Fu-Guo , Ai Qing , Long Gui-Lu
Published: March 2022

In a fully-controllable experiment platform for studying non-Markovian open quantum dynamics, we show that the non-Markovianity could be investigated from the global and local aspects. By mixing random unitary dynamics, we demonstrate non-Markovian and Markovian open quantum dynamics. From the global point of view, by tuning the base frequency we demonstrate the transition from the Markovianity to the non-Markovianity as measured by the quantum mutual information (QMI). In a Markovian open quantum process, the QMI decays monotonically, while it may rise temporarily in a non-Markovian process. However, under some circumstances, it is not sufficient to globally investigate the non-Markovianity of the open quantum dynamics. As an essential supplement, we further utilize the quantum Fisher information (QFI) flow to locally characterize the non-Markovianity in different channels. We demonstrate that the QMI in combination with the QFI flow are capable of measuring the non-Markovianity for a multi-channel open quantum dynamics.
Thermal transport investigation and shear drag at solid–liquid interface of modified permeable radiative-SRID subject to Darcy–Forchheimer fluid flow composed by γ-nanomaterial
Authors: Adnan  , Ashraf Waqas , Khan Ilyas , Andualem M.
Published: March 2022

The modern world moves towards the art of nanotechnology which is impossible without the analysis of thermal performance and thermophysical featuring of nanofluids. Therefore, a case study for Darcy–Forchheimer Flow (DFF) (γ-Al2O3/H2O)nf over a permeable Stretching Rotating Inclined Disk (SRID) under the impacts of thermal radiation and viscus dissipation is organized. The nanofluid is synthesized by novel γ-aluminum nanomaterial and pure water. Then, the problem is formulated properly via similarity equations by inducing empirical correlations of (γ-Al2O3/H2O)nf with their thermophysical attributes. A numerical algorithm is successfully implemented for mathematical analysis and furnished the results for DFF of (γ-Al2O3/H2O)nf. It is inspected that the Fr opposes the motion and the fluid moves promptly by increasing the strength of stretching parameter. The temperature of (γ-Al2O3/H2O)nf enhances due to higher dissipation and fraction factor favors the thermophysical attributes of (γ-Al2O3/H2O)nf. Therefore, the nanofluid has high thermal performance rate and would be better for industrial and engineering purposes.
Early neuroimaging and delayed neurological sequelae in carbon monoxide poisoning: a systematic review and meta-analysis
Authors: Ahn Chiwon , Oh Jaehoon , Kim Chan Woong , Lee Heekyung , Lim Tae Ho , Kang Hyunggoo
Published: March 2022

We aimed to assess the evidence regarding the usefulness of brain imaging as a diagnostic tool for delayed neurological sequelae (DNS) in patients with acute carbon monoxide poisoning (COP). Observational studies that included adult patients with COP and DNS were retrieved from Embase, MEDLINE, and Cochrane Library databases in December 2020 and pooled using a random-effects model. Seventeen studies were systematically reviewed. Eight and seven studies on magnetic resonance imaging (MRI) and computed tomography (CT), respectively, underwent meta-analysis. The pooled sensitivity and specificity of MRI for diagnosis of DNS were 70.9% (95% confidence interval [CI] 64.8–76.3%, I2 = 0%) and 84.2% (95% CI 80.1–87.6%, I2 = 63%), respectively. The pooled sensitivity and specificity of CT were 72.9% (95% CI 62.5–81.3%, I2 = 8%) and 78.2% (95% CI 74.4–87.1%, I2 = 91%), respectively. The areas under the curve for MRI and CT were 0.81 (standard error, 0.08; Q* = 0.74) and 0.80 (standard error, 0.05, Q* = 0.74), respectively. The results indicate that detecting abnormal brain lesions using MRI or CT may assist in diagnosing DNS in acute COP patients.
Investigating the effects of statins on ischemic heart disease allowing for effects on body mass index: a Mendelian randomization study
Authors: Li Shun , Schooling C. M.
Published: March 2022

Despite effective lipid reduction and corresponding benefits for cardiovascular disease prevention and treatment, statins have pleiotropic effects potentially increasing the risk of ischemic heart disease (IHD), particularly by increasing body mass index (BMI). We assessed whether the effects of genetically mimicked statins on IHD were strengthened by adjusting for BMI in men and women. We also assessed if increasing BMI was specific to statins in comparison to other major lipid-lowering treatments in current use, i.e., proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe. Using univariable and multivariable Mendelian randomization (MR) we found genetically mimicked effects of statins increased BMI (0.33, 95% confidence interval (CI) 0.28 to 0.38), but genetically mimicked PCSK9 inhibitors and ezetimibe did not. Genetically mimicked effects of statins on IHD reduction in both sexes (odds ratio (OR) 0.55 per unit decrease in effect size of low-density lipoprotein cholesterol (LDL-c), 95% confidence interval (CI) 0.40 to 0.76), was largely similar after adjusting for BMI, in both men (OR 0.48, 95% CI 0.38 to 0.61) and women (OR 0.66, 95% CI 0.53 to 0.82). Compared with variations in PCSK9 and NPC1L1, only variation in HMGCR was associated with higher BMI. The effects on IHD of mimicking statins were similar after adjusting for BMI in both men and women. The BMI increase due to statins does not seem to be a concern as regards the protective effects of statins on IHD, however other factors driving BMI and the protective effects of statins could be.
A spatiotemporal data mining study to identify high-risk neighborhoods for out-of-hospital cardiac arrest (OHCA) incidents
Authors: Wong Paulina Pui-yun , Low Chien-Tat , Cai Wenhui , Leung Kelvin Tak-yiu , Lai Poh-Chin
Published: March 2022

Out-of-hospital cardiac arrest (OHCA) is a worldwide health problem. The aim of the study is to utilize the territorial-wide OHCA data of Hong Kong in 2012–2015 to examine its spatiotemporal pattern and high-risk neighborhoods. Three techniques for spatiotemporal data mining (SaTScan’s spatial scan statistic, Local Moran’s I, and Getis Ord Gi*) were used to extract high-risk neighborhoods of OHCA occurrence and identify local clusters/hotspots. By capitalizing on the strengths of these methods, the results were then triangulated to reveal “truly” high-risk OHCA clusters. The final clusters for all ages and the elderly 65+ groups exhibited relatively similar patterns. All ages groups were mainly distributed in the urbanized neighborhoods throughout Kowloon. More diverse distribution primarily in less accessible areas was observed among the elderly group. All outcomes were further converted into an index for easy interpretation by the general public. Noticing the spatial mismatches between hospitals and ambulance depots (representing supplies) and high-risk neighborhoods (representing demands), this setback should be addressed along with public education and strategic ambulance deployment plan to shorten response time and improve OHCA survival rate. This study offers policymakers and EMS providers essential spatial evidence to assist with emergency healthcare planning and informed decision-making.
Impact of hip abductor and adductor strength on dynamic balance and ankle biomechanics in young elite female basketball players
Authors: Domínguez-Navarro Fernando , Benitez-Martínez Josep Carles , Ricart-Luna Borja , Cotolí-Suárez Pedro , Blasco-Igual Jose María , Casaña-Granell Jose
Published: March 2022

This study aimed to evaluate, in an isolated and relative manner, hip abductor (ABD) and adductor (AD) strength and to study the extent to which these factors are related to balance and ankle dorsiflexion mobility in young elite female basketball players. Sixty trainee-level elite female basketball players (13–18 years old), who voluntarily agreed to participate in the study, were divided into three subgroups based on competition age divisions (U14, U16, U18). Isometric hip ABD and AD strength in each leg was evaluated using the ForceFrame Strength Testing System, also calculating the strength ratio and imbalance between legs. Y Balance Test (YBT) and ankle dorsiflexion mobility were also assessed. ANOVA was used for between-group differences analysis. Likewise, the impact of hip strength on balance and ankle mobility was analyzed using Pearson's correlation coefficient. A linear regression model for dependent variables was created with all variables that exhibited significant correlations. A between-group comparison analysis for the three competition age subgroups (U14, U16, U18) revealed non-significant differences (p > 0.005) for the hip strength variables except for hip ABD strength. The correlation study showed low-moderate effect sizes for hip ABD (in both the contralateral and homolateral limb) and AD strength (only the homolateral limb) with YBT and ankle dorsiflexion. However, when performing a regression model, only right hip ABD significantly predicted right limb YBT scores (β = 0.592, p = 0.048). The present study indicated that, although both hip ABD and AD strength correlate with balance and ankle mobility with low-moderate effect sizes, only hip ABD strength was found to significantly predict YBT scores. Therefore, the potential role of hip ABD strength in particular, but also hip AD strength, for monitoring and enhancing balance and ankle mobility outcomes, should be taken into consideration when designing and implementing preventive strategies for lower-limb injuries.
miR-96-5p targets PTEN to mediate sunitinib resistance in clear cell renal cell carcinoma
Authors: Park Sang Eun , Kim Wonju , Hong Ji-Ye , Kang Dayeon , Park Seulki , Suh Jungyo , You Dalsan , Park Yun-Yong , Suh Nayoung , Hwang Jung Jin , Kim Choung-Soo
Published: March 2022

A multiple receptor tyrosine kinase inhibitor, sunitinib, is a first-line therapy for clear cell renal cell carcinoma (CCRCC). Unfortunately, it has the major challenges of low initial response rate and resistance after about one year of treatment. Here we evaluated a microRNA (miRNA) and its target responsible for sunitinib resistance. Using miRNA profiling, we identified miR-96-5p upregulation in tumors from sunitinib-resistant CCRCC patients. By bioinformatic analysis, PTEN was selected as a potential target of miR-96-5p, which showed low levels in tumors from sunitinib-resistant CCRCC patients. Furthermore, PTEN and miR-96-5p levels were negatively correlated in a large The Cancer Genome Atlas kidney renal clear cell carcinoma cohort and high miR-96 and low PTEN represented poor prognosis in this cohort. Additionally, four-week sunitinib treatment increased miR-96-5p and decreased PTEN only in tumors from a sunitinib-resistant patient-derived xenograft model. We found a novel miR-96-5p binding site in the PTEN 3′ UTR and confirmed direct repression by luciferase reporter assay. Furthermore, we demonstrated that repression of PTEN by miR-96-5p increased cell proliferation and migration in sunitinib-treated cell lines. These results highlight the direct suppression of PTEN by miR-96-5p and that high miR-96-5p and low PTEN are partially responsible for sunitinib resistance and poor prognosis in CCRCC.
Virtual simulation of the biomechanics of the abdominal wall with different stoma locations
Authors: Tuset Lluís , López-Cano Manuel , Fortuny Gerard , López Josep M. , Herrero Joan , Puigjaner Dolors
Published: March 2022

An ostomy is a surgical procedure by which an artificial opening in the abdominal wall, known as a stoma, is created. We assess the effects of stoma location on the abdominal wall mechanics. We perform three-dimensional finite element simulations on an anatomy model which was generated on the basis of medical images. Our simulation methodology is entirely based on open source software. We consider seventeen different locations for the stoma incision (trephine) and we simulate the mechanical response of the abdominal wall when an intraabdominal pressure as high as 20 kPa is applied. We focus on factors related to the risk of parastomal hernia development such as the deformation experienced by the abdominal wall, the stress levels supported by its tissues and the corresponding level of trephine enlargement. No significant dependence was found between stoma location and the levels of abdominal wall deformations or stress supported by tissues, except for the case with a stoma located on the linea alba. Trephine perimeter and area respectively increased by as much as $$44\%$$

44
%

and $$85\%$$

85
%

. The level of trephine deformation depends on stoma location with considerably higher trephine enlargements found in stomas laterally located with respect to the rectus abdominis muscle.
Machine learning for technical skill assessment in surgery: a systematic review
Authors: Lam Kyle , Chen Junhong , Wang Zeyu , Iqbal Fahad M. , Darzi Ara , Lo Benny , Purkayastha Sanjay , Kinross James M.
Published: March 2022

Accurate and objective performance assessment is essential for both trainees and certified surgeons. However, existing methods can be time consuming, labor intensive, and subject to bias. Machine learning (ML) has the potential to provide rapid, automated, and reproducible feedback without the need for expert reviewers. We aimed to systematically review the literature and determine the ML techniques used for technical surgical skill assessment and identify challenges and barriers in the field. A systematic literature search, in accordance with the PRISMA statement, was performed to identify studies detailing the use of ML for technical skill assessment in surgery. Of the 1896 studies that were retrieved, 66 studies were included. The most common ML methods used were Hidden Markov Models (HMM, 14/66), Support Vector Machines (SVM, 17/66), and Artificial Neural Networks (ANN, 17/66). 40/66 studies used kinematic data, 19/66 used video or image data, and 7/66 used both. Studies assessed the performance of benchtop tasks (48/66), simulator tasks (10/66), and real-life surgery (8/66). Accuracy rates of over 80% were achieved, although tasks and participants varied between studies. Barriers to progress in the field included a focus on basic tasks, lack of standardization between studies, and lack of datasets. ML has the potential to produce accurate and objective surgical skill assessment through the use of methods including HMM, SVM, and ANN. Future ML-based assessment tools should move beyond the assessment of basic tasks and towards real-life surgery and provide interpretable feedback with clinical value for the surgeon.

PROSPERO: CRD42020226071
Cytoskeletal dynamics regulates stromal invasion behavior of distinct liver cancer subtypes
Authors: Nguyen Ryan Y. , Xiao Hugh , Gong Xiangyu , Arroyo Alfredo , Cabral Aidan T. , Fischer Tom T. , Flores Kaitlin M. , Zhang Xuchen , Robert Marie E. , Ehrlich Barbara E. , Mak Michael
Published: March 2022

Drug treatment against liver cancer has limited efficacy due to heterogeneous response among liver cancer subtypes. In addition, the functional biophysical phenotypes which arise from this heterogeneity and contribute to aggressive invasive behavior remain poorly understood. This study interrogated how heterogeneity in liver cancer subtypes contributes to differences in invasive phenotypes and drug response. Utilizing histological analysis, quantitative 2D invasion metrics, reconstituted 3D hydrogels, and bioinformatics, our study linked cytoskeletal dynamics to differential invasion profiles and drug resistance in liver cancer subtypes. We investigated cytoskeletal regulation in 2D and 3D culture environments using two liver cancer cell lines, SNU-475 and HepG2, chosen for their distinct cytoskeletal features and invasion profiles. For SNU-475 cells, a model for aggressive liver cancer, many cytoskeletal inhibitors abrogated 2D migration but only some suppressed 3D migration. For HepG2 cells, cytoskeletal inhibition did not significantly affect 3D migration but did affect proliferative capabilities and spheroid core growth. This study highlights cytoskeleton driven phenotypic variation, their consequences and coexistence within the same tumor, as well as efficacy of targeting biophysical phenotypes that may be masked in traditional screens against tumor growth.
PDGF regulates guanylate cyclase expression and cGMP signaling in vascular smooth muscle
Authors: Hildebrand Staffan , Ibrahim Mohamed , Schlitzer Andreas , Maegdefessel Lars , Röll Wilhelm , Pfeifer Alexander
Published: March 2022

The nitric oxide-cGMP (NO-cGMP) pathway is of outstanding importance for vascular homeostasis and has multiple beneficial effects in vascular disease. Neointimal hyperplasia after vascular injury is caused by increased proliferation and migration of vascular smooth muscle cells (VSMCs). However, the role of NO-cGMP signaling in human VSMCs in this process is still not fully understood. Here, we investigate the interaction between platelet derived growth factor (PDGF)-signaling, one of the major contributors to neointimal hyperplasia, and the cGMP pathway in vascular smooth muscle, focusing on NO-sensitive soluble guanylyl cyclase (sGC). We show that PDGF reduces sGC expression by activating PI3K and Rac1, which in turn alters Notch ligand signaling. These data are corroborated by gene expression analysis in human atheromas, as well as immunohistological analysis of diseased and injured arteries. Collectively, our data identify the crosstalk between PDGF and NO/sGC signaling pathway in human VSMCs as a potential target to tackle neointimal hyperplasia.
The burden of rare protein-truncating genetic variants on human lifespan
Authors: Liu Jimmy Z. , Chen Chia-Yen , Tsai Ellen A. , Whelan Christopher D. , Sexton David , John Sally , Runz Heiko
Published: March 2022

Genetic predisposition has been shown to contribute substantially to the age at which we die. Genome-wide association studies (GWASs) have linked more than 20 loci to phenotypes related to human lifespan1. However, little is known about how lifespan is impacted by gene loss of function. Through whole-exome sequencing of 352,338 UK Biobank participants of European ancestry, we assessed the relevance of protein-truncating variant (PTV) gene burden on individual and parental survival. We identified four exome-wide significant (P < 4.2 × 10−7) human lifespan genes, BRCA1, BRCA2, ATM and TET2. Gene and gene-set, PTV-burden, phenome-wide association studies support known roles of these genes in cancer to impact lifespan at the population level. The TET2 PTV burden was associated with a lifespan through somatic mutation events presumably due to clonal hematopoiesis. The overlap between PTV burden and common variant-based lifespan GWASs was modest, underscoring the value of exome sequencing in well-powered biobank cohorts to complement GWASs for identifying genes underlying complex traits.
Risk assessment of COVID-19 epidemic resurgence in relation to SARS-CoV-2 variants and vaccination passes
Authors: Krueger Tyll , Gogolewski Krzysztof , Bodych Marcin , Gambin Anna , Giordano Giulia , Cuschieri Sarah , Czypionka Thomas , Perc Matjaz , Petelos Elena , Rosińska Magdalena , Szczurek Ewa
Published: March 2022

The introduction of COVID-19 vaccination passes (VPs) by many countries coincided with the Delta variant fast becoming dominant across Europe. A thorough assessment of their impact on epidemic dynamics is still lacking. Here, we propose the VAP-SIRS model that considers possibly lower restrictions for the VP holders than for the rest of the population, imperfect vaccination effectiveness against infection, rates of (re-)vaccination and waning immunity, fraction of never-vaccinated, and the increased transmissibility of the Delta variant. Some predicted epidemic scenarios for realistic parameter values yield new COVID-19 infection waves within two years, and high daily case numbers in the endemic state, even without introducing VPs and granting more freedom to their holders. Still, suitable adaptive policies can avoid unfavorable outcomes. While VP holders could initially be allowed more freedom, the lack of full vaccine effectiveness and increased transmissibility will require accelerated (re-)vaccination, wide-spread immunity surveillance, and/or minimal long-term common restrictions.
Composition analysis of ceramic raw materials using laser-induced breakdown spectroscopy and autoencoder neural network
Authors: Lv Zunji , Yu Hongxia , Sun Lanxiang , Zhang Peng
Published: March 2022

We proposed a spectral data feature extraction method that combines the linear regression and sparse and under-complete autoencoder. LR + SUAC can effectively extract the important information in the secondary features.
Gold nanobipyramids doped with Au/Pd alloyed nanoclusters for high efficiency ethanol electrooxidation
Authors: Hanqi Baihe , Xu Juan , Zhu Xingzhong , Kan Caixia
Published: March 2022

AuBPs@AuxPd1−x nanocatalysts were synthesized as a promising electrocatalyst for ethanol fuel cells.
The first exploration of coordination chemistry using a methyl substituted o-vanillin based ligand: an example starting with Dy4/Zn2Dy2 systems displaying slow relaxation of magnetization
Authors: Panja Anangamohan , Jagličić Zvonko , Herchel Radovan , Brandão Paula , Pramanik Kuheli , Jana Narayan Ch.
Published: March 2022

Two butterfly-shaped Dy4 and Zn2Dy2 complexes displaying slow relaxation of magnetization have been synthesized from a new methyl substituted o-vanillin based ligand, enlarging the scope for finding better SMMs.
Controlling the charge carrier dynamics by modulating the orientation diversity of perovskites
Authors: Cha Wonhee , Cha Won-Young , Noh Insub , Seki Shu , Ohkita Hideo , Kim Dongho
Published: March 2022

Photo-induced charge carrier dynamics over a wide time domain from sub-nanoseconds to microseconds, via time-correlated single photon counting and flash photolysis time-resolved microwave conductivity measurements.
Electroanalytical overview: screen-printed electrochemical sensing platforms for the detection of vital cardiac, cancer and inflammatory biomarkers
Authors: Crapnell Robert D. , Garcia-Miranda Ferrari Alejandro , Dempsey Nina C. , Banks Craig E.
Published: March 2022

Herein we review the use of electrochemical point-of-care SPE-based sensor technologies towards the detection of vital, established biomarkers related to cardiac injury, cancer diagnostics and acute inflammatory conditions.
Designed synthesis of a hierarchical MoSe2@WSe2 hybrid nanostructure as a bifunctional electrocatalyst for total water-splitting
Authors: Rai Rajeev Kumar , Sarkar Bidushi , Ram Ranit , Nanda Karuna Kar , Ravishankar N.
Published: March 2022

Reaction kinetics-controlled one-step wet-chemical synthesis of MoSe2@WSe2 hybrid nanostructure with enhanced electrocatalytic activity for total water-splitting reaction.
Electrostatic co-assembly of pillar[n]pyridiniums and calix[4]arene in aqueous media
Authors: Kravets Kateryna , Kravets Mykola , Butkiewicz Helena , Kosiorek Sandra , Sashuk Volodymyr , Danylyuk Oksana
Published: March 2022

Oppositely charged macrocyclic hosts pillar[n]pyridiniums and p-sulfonatocalix[4]arene co-assemble through encaging of the supercation units within/between the superanionic capsules.
Assessing the economic potential of large-scale carbonate-formation-free CO2 electrolysis
Authors: Jing Xuechen , Li Fengwang , Wang Yuhang
Published: March 2022

A techno-economic assessment unraveling the quantitative correlation between carbonate formation and the cost of CO2 electroreduction.
Carbon dot-based fluorescent antibody nanoprobes as brain tumour glioblastoma diagnostics
Authors: Ghirardello Mattia , Shyam Radhe , Liu Xia , Garcia-Millan Teodoro , Sittel Imke , Ramos-Soriano Javier , Kurian Kathreena M. , Galan M. Carmen
Published: March 2022

Carbon dot-labelled antibody for human brain tissue immunofluorescent staining.
Natural wood-derived free-standing films as efficient and stable separators for high-performance lithium ion batteries
Authors: Yang Yunlong , Li Ning , Lv Tian , Chen Zilin , Liu Yanan , Dong Keyi , Cao Shaokui , Chen Tao
Published: March 2022

A type of separator derived from natural wood films for lithium ion batteries with high performance and stability is demonstrated.
Hydroxyl-assisted selective epoxidation of perillyl alcohol with hydrogen peroxide by vanadium-substituted phosphotungstic acid hinged on imidazolyl activated carbon
Authors: He Huiting , Zheng Min , Liu Qiang , Liu Jian , Zhao Juan , Zhuang Yuting , Liu Xianxiang , Xu Qiong , Kirk Steven R. , Yin Dulin
Published: March 2022

Vanadium-substituted phosphotungstic acid hinged on imidazolyl activated carbon catalyzed efficiently and stably the selective epoxidation of perillyl alcohol with H2O2.
Syntheses of polylactides by means of tin catalysts
Authors: Kricheldorf Hans R. , Weidner Steffen M.
Published: March 2022

Reaction mechanisms and synthetic methods used for the preparation of homo- and copolylactides based on tin(ii) and tin(iv) catalysts are reviewed.
Direct C(sp3)–H difluoromethylation via radical–radical cross-coupling by visible-light photoredox catalysis
Authors: Xiong Wei , Qin Wen-Bing , Zhao Ya-Shi , Fu Kai-Zhong , Liu Guo-Kai
Published: March 2022

The first approach of photoredox catalyzed radical–radical cross-coupling difluoromethylation of C(sp3)−H bond was reported, featuring transition metal-free, good functional group tolerance, broad substrate scope and mild reaction conditions.
Chiral proline-substituted porous organic cages in asymmetric organocatalysis
Authors: Xu Ning , Su Kongzhao , El-Sayed El-Sayed M. , Ju Zhanfeng , Yuan Daqiang
Published: March 2022

Two calix[4]resorcinarene-based chiral POCs with different self-assembly forms were constructed. The difference in the spatial distribution of chiral organocatalytic sites leads to the two chiral POCs exhibiting distinct stereoselectivities.
Stronger together for in-cell translation: natural and unnatural base modified mRNA
Authors: Bornewasser Lisa , Domnick Christof , Kath-Schorr Stephanie
Published: March 2022

Introducing unnatural base modifications site-specifically into the 3′-UTR of an mRNA bearing natural base modifications allows efficient visualization in cells by click chemistry. An enhanced protein expression in cells is observed from this twofold modified mRNA.
Dynamic ionic behavior of gel-free diolefin rubber-based carboxylate ionomers preparedviaolefin metathesis
Authors: Wang Xiaotong , Liu Kai , Liu Yudong , Xie Tinghao , Hua Jing
Published: March 2022

Constructing dynamic ionic bonding interactions is acknowledged as an efficient strategy to improve the physical–mechanical characteristics of rubber materials, and to provide them with some novel features such as self-healing.
Electric field control by permittivity functionally graded and superficially non‐linear conductivity materials for DC‐GIS spacer
Authors: Du Boxue , Dong Jianan , Liang Hucheng
Published: March 2022

This paper offers a simulation study on the application of a novel approach to control the electric field around a basin‐type spacer by combining permittivity functionally graded materials (ε‐FGM) and superficially non‐linear conductivity materials (SNCM), namely multi‐dimensional functional materials (MDFM). The permittivity distribution of the ε‐FGM spacer is designed by the iteration optimization algorithm, and the epoxy/SiC composites with 30 and 60 phr doping contents are assigned as the coating materials of two SNCM spacers, namely SNCM30 and SNCM60. The MDFM spacer combines ε‐FGM in its bulk and SNCM60 on its surface. The electric field regulation effect of each functional spacer is investigated under variable conditions, that is, DC steady state (DC‐steady), DC turn‐on state (DC‐on), DC polarity reversal (DC‐PR), and DC superimposed with switching impulse voltage (DC‐SI). Results show that the applicability of ε‐FGM and SNCM is limited to transient and stationary conditions, respectively. The MDFM spacer combines the advantages of ε‐FGM and SNCM for adaptively relaxing the electric field under all the above conditions. It is hoped that this research will be beneficial to the development and application of spacers for the direct current gas‐insulated switchgear (DC‐GIS).
Execution of synthetic Bayesian model average for solar energy forecasting
Authors: Abedinia Oveis , Bagheri Mehdi
Published: March 2022

Accurate photovoltaic (PV) forecasting is quite crucial in planning and in the regular operation of power system. Stochastic habit along with the high risks in PV signal uncertainty and a probabilistic forecasting model is required to address the numerical weather prediction (NWP) underdispersion. In this study, a new synthetic prediction process based on Bayesian model averaging (BMA) and Ensemble Learning is developed. The proposed model is initiated by the improved self‐organizing map (ISOM) clustering K‐fold cross‐validation for the training process. To provide desirable learning model for different input samples, three learners including long short‐term memory (LSTM) network, general regression neural network (GRNN), and non‐linear auto‐regressive eXogenous NN (NARXNN) are employed. The proposed BMA approach is combined with the output of the learners to obtain accurate and desirable outcomes. Different models are precisely compared with the obtained numerical results over real‐world engineering test site, that is, Arta‐Solar case study. The numerical analysis and recorded results validate the performance and superiority of the proposed model.
Data‐driven distributionally robust economic dispatch for park integrated energy systems with coordination of carbon capture and storage devices and combined heat and power plants
Authors: Wang Yuqi , Gao Song , Jia Wenhao , Ding Tao , Zhou Zhengyang , Wang Zekai
Published: March 2022

Park integrated energy system (PIES) can utilize multiple energy resources complementarily and promote comprehensive energy efficiency. However, the uncertainty of renewable energy generation poses significant challenges to the optimal operation of PIES. This paper proposes a data‐driven distributionally robust optimization (DDRO) model for the day‐ahead scheduling of PIESs with coordination of carbon capture and storage devices (CCS) and combined heat and power plants (CHP). First, a deterministic economic dispatch model of PIES was presented with the aim at minimizing the total operating costs of PIES and promoting the photovoltaic (PV) power accommodation. Then, a DDRO model was developed based on the historical data to yield the optimal solution in the worst PV output scenario, where the confidence set is established with comprehensive consideration of norm‐1 and norm‐inf constraints. Furthermore, an efficient solving framework was proposed for the DDRO based on the combination of the column‐and‐constraint generation (C&CG) algorithm and a duality‐free decomposition method. Finally, case studies are carried out to demonstrate the effectiveness of the proposed model.
The ISAQ Score Does Not Predict Adrenal Crisis in Patients with
Primary Adrenal Insufficiency
Authors: Quinkler Marcus , Kienitz Tina
Published: March 2022

Objective This study aimed to investigate the ability of the immune system
assessment questionnaire (ISAQ) to predict adrenal crisis (AC) and infectious
events in patients with primary adrenal insufficiency (PAI).

Design This was a prospective single-centre study over three years.

Methods Patients answered the ISAQ at baseline and were seen every
4–6 months in the endocrine outpatient clinic. At each visit previous
infectious periods which required an increase in daily glucocorticoid dosage and
AC were reported and documented. Seventy-five patients with PAI (53 women; 43
patients with autoimmune PAI, 20 patients with salt-wasting congenital adrenal
hyperplasia and 12 patients who underwent bilateral adrenalectomy) were
analysed. Due to the COVID-19 pandemic and consecutive lockdown measures, the
data were analysed separately for March 2018 to March 2020 (period 1), and March
2020 to March 2021 (period 2).

Results During period 1 the ISAQ score significantly correlated with the
number of reported infectious events (r=0.351; p<0.01), but not
during period 2 (r=0.059, p=0.613), in which the number of
infectious events per patient-year significantly decreased (1.1±0.1 vs
0.4±0.1; p<0.001). The frequency of AC decreased from 8.8 to 2.4
per 100 patient-years between the two study periods. The ISAQ score was not
different between patients with or without AC.

Conclusions The ISAQ score does not identify patients prone to ACs. The
COVID-19 pandemic and consecutive lockdown measures significantly diminished the
frequency of infectious events and ACs.
Die Behandlung von psychotischen Störungen im Neuen Testament
Authors: Juckel Georg , Pajonk Frank-G. , Mavrogiorgou Paraskevi
Published: March 2022

Die Behandlung von psychotischen Störungen wie der Schizophrenie stellt weiterhin eine große Herausforderung dar. Jesus „heilt“ nach den Darstellungen im Neuen Testament Menschen mit „Besessenheit“ mittels „Dämonenaustreibung“ vollständig im Sinne von Recovery. Obwohl in einer symbolischen Sprache niedergelegt, werden wichtige Wirkfaktoren hierfür deutlich, so z. B. starke und eindeutige Patientenführung, liebevolle und intensive Zuwendung, Gottesglauben und Gebet. Es wird vermutet, dass eine stärkere Berücksichtigung solcher religiös-geistlicher Praktiken bei der psychiatrisch-psychotherapeutischen Behandlung von Psychose-Kranken nicht nur diese Patienten günstig ansprechen, sondern auch das Repertoire unserer Möglichkeiten wirkungsvoll erweitern kann.