bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrothermal Friction Experiments on Simulated Basaltic Fault Gouge and Implications for Megathrust Earthquakes
Authors: Okuda Hanaya , Niemeijer André R. , Takahashi Miki , Yamaguchi Asuka , Spiers Christopher J.
Published: December 2022

Nucleation of earthquake slip at the plate boundary fault (décollement) in subduction zones has been widely linked to the frictional properties of subducting sedimentary facies. However, recent seismological and geological observations suggest that the décollement develops in the subducting oceanic crust in the depth range of the seismogenic zone, at least in some cases. To understand the frictional properties of oceanic crustal material and their influence on seismogenesis, we performed hydrothermal friction experiments on simulated fault gouges of altered basalt, at temperatures of 100–550°C. The friction coefficient (μ) lies around 0.6 at most temperature conditions but a low μ down to 0.3 was observed at the highest temperature and lowest velocity condition. The velocity dependence of μ, (a−b), changes with increasing temperature from positive to negative at ∼100°C and from negative to positive at ∼450°C. Compared to gouges derived from sedimentary facies, the altered basalt gouge showed potentially unstable velocity weakening over a wider temperature range. Microstructural observations and microphysical interpretation infer that competition between dilatant granular flow and viscous compaction through pressure‐solution creep of albite contributed to the observed transition in (a−b). Alteration of oceanic crust during subduction produces fine grains of albite and chlorite through interactions with interstitial water, leading to reduction in its frictional strength and an increase in its seismogenic potential. Therefore, shear deformation possibly localizes within the altered oceanic crust leading to a larger potential for the nucleation of a megathrust earthquake in the depth range of the seismogenic zone.
Intradecadal Fluctuations and Three‐Dimensional Crustal Kinematic Deformation of the Tianshan and Pamir Derived From Multi‐Geodetic Imaging
Authors: Pan Yuanjin , Jiang Weiping , Ding Hao , Shum C. K. , Jiao Jiashuang , Li Jiangtao
Published: December 2022

The uplift of the Tianshan and Pamir Mountains/Areas are caused by active intracontinental tectonic movements. The dynamic mechanism is controversial and has aroused great interest among scholars. In this study, we investigate the present three‐dimensional (3‐D) crustal deformation in the Tianshan and Pamir areas from multi‐geodetic observations from 2002 to 2021. The continuous water deficit throughout Tianshan and Pamir locates mainly in glacier‐covered areas, at a total rate of −0.8 cm w.e./yr, inducing spatial surface uplifting at rates of ∼0.2–0.5 mm/yr. These Global Positioning System (GPS)‐derived velocities in the vertical deformation of the Tianshan and Pamir were corrected based on surface elastic loading models and the Gravity Recovery and Climate Experiment Follow‐On (GRACE/GFO)‐inferred hydrological loading deformation, and interpolated using the GPS imaging method for a higher 3‐D crustal deformation spatial resolution. In conclusion, surface hydrology is one of the driven factors affecting the regional vertical velocity field observed by GPS. The kinematic crustal shortening and vertical tectonic uplift are integrated within different blocks, which illustrate the contemporary dynamics throughout the Tianshan and Pamir. The relevant spatial characteristics between the 3‐D crustal deformation and dynamic tomography along the Tianshan indicate that the relatively weaker lithosphere beneath the central Tianshan is subject to strong compression, which induces the present‐day crustal uplift.
The Malolotsha Klippe: Large‐Scale Subhorizontal Tectonics Along the Southern Margin of the Archean Barberton Greenstone Belt, Eswatini
Authors: Heubeck Christoph , Thomsen Tonny B. , Heredia Benjamin D. , Zeh Armin , Balling Philipp
Published: December 2022

Whether Archean tectonics were horizontally or vertically dominated is controversially discussed because arguments bear on the kinematics and thermal state of the Archean mantle and constrain the mode of formation of the earliest continental crust. Highly deformed strata of Archean greenstone belts figure prominently in this debate because they record long periods of time and multiple deformation phases. Among the best‐preserved greenstone belts counts the Barberton Greenstone Belt (BGB) of southern Africa. Geological mapping of part of the southern BGB in Eswatini (Swaziland), combined with U‐Pb zircon dating, shows that the region preserves a tightly re‐folded imbricate thrust stack in which metavolcanic and ‐volcaniclastic strata of the Onverwacht Group, deposited at 3.34–3.29 Ga, have been thrust on top of ca. 3.22 Ga siliciclastic strata of the Moodies Group. The structurally highest element, the Malolotsha Syncline, forms a tectonic klippe of substantial size and is >1,450 m thick. Forward modeling of a balanced cross section indicates that this thrust stack was part of a northwestward‐verging orogen along the southern margin of the BGB and records a minimum horizontal displacement of 33 km perpendicular to its present‐day faulted, ductily strained and multiply metamorphosed margin. Because conglomerate clasts indicate a significantly higher degree of prolate strain which extends further into the BGB than at its northern margin, late‐stage tectonic architecture of the BGB may be highly asymmetrical. Our study documents that the BGB, and perhaps other Archean greenstone belts, preserves a complex array of both vertically‐ and horizontally‐dominated deformation styles that have interfered with each other at small regional and short temporal scales.
Intrapore Geometry and Flow Rate Controls on the Transition of Non‐Fickian to Fickian Dispersion
Authors: Bradley Jacob , Singh Kuldeep , Wang Lichun
Published: December 2022

Hydraulic heterogeneity leads to non‐Fickian transport characteristics, which cannot be entirely accounted for by the continuum‐scale advection‐dispersion equation. In this pore‐scale computational study, we investigate the combined effects of flow rate (i.e., Peclet number, Pe) and first‐order hydraulic heterogeneity, that is, resulting from intrapore geometry exclusively, on the transition from non‐Fickian to Fickian dispersion. A set of intrapore geometries is designed and quantified by a dimensionless pore geometry factor (β), which accounts for a broad range of pore shapes likely found in nature. Navier‐Stokes and Advection‐Diffusion equations are solved numerically to study the transport phenomenon using velocity variance, residence time distribution, and coefficients of hydrodynamic dispersion and dispersivity. We determine the length scale (i.e., the linear distance in flow direction) for each pore shape and Pe when non‐Fickian features transition to the Fickian transport regime by incrementally extending the length, that is, the linear array of pores. We show how velocity distribution and variance (σ2) depend on β, and directly control the transition to Fickian dispersion. Pores with a larger β, that is, complex pore shapes with constricted pore‐body or with “slit‐type” attributes, result in a substantial non‐Fickian characteristics. The magnitude of non‐Fickian characteristics gets amplified with an increase in Pe requiring a significantly longer length scale, that is, up to 1 m or a linear array of 500 pores to transition to the Fickian transport regime. We find the hydrodynamic dispersion coefficient (Dh) exponentially depends on the pore shape factor β, with its exponent dependent on flow rate or Pe. We determine constitutive relations to quantify how σ2, β, and Pe, contribute to the degree of non‐Fickian characteristics, the length scale needed for the transition to Fickian transport regime, asymptotic Dh, and the length‐scale dependence of longitudinal dispersivity.
Insights into divalent cation regulation and G13-coupling of orphan receptor GPR35
Authors: Duan Jia , Liu Qiufeng , Yuan Qingning , Ji Yujie , Zhu Shengnan , Tan Yangxia , He Xinheng , Xu Youwei , Shi Jingjing , Cheng Xi , Jiang Hualiang , Eric Xu H. , Jiang Yi
Published: December 2022

Endogenous ions play important roles in the function and pharmacology of G protein-coupled receptors (GPCRs) with limited atomic evidence. In addition, compared with G protein subtypes Gs, Gi/o, and Gq/11, insufficient structural evidence is accessible to understand the coupling mechanism of G12/13 protein by GPCRs. Orphan receptor GPR35, which is predominantly expressed in the gastrointestinal tract and is closely related to inflammatory bowel diseases (IBDs), stands out as a prototypical receptor for investigating ionic modulation and G13 coupling. Here we report a cryo-electron microscopy structure of G13-coupled GPR35 bound to an anti-allergic drug, lodoxamide. This structure reveals a novel divalent cation coordination site and a unique ionic regulatory mode of GPR35 and also presents a highly positively charged binding pocket and the complementary electrostatic ligand recognition mode, which explain the promiscuity of acidic ligand binding by GPR35. Structural comparison of the GPR35–G13 complex with other G protein subtypes-coupled GPCRs reveals a notable movement of the C-terminus of α5 helix of the Gα13 subunit towards the receptor core and the least outward displacement of the cytoplasmic end of GPR35 TM6. A featured ‘methionine pocket’ contributes to the G13 coupling by GPR35. Together, our findings provide a structural basis for divalent cation modulation, ligand recognition, and subsequent G13 protein coupling of GPR35 and offer a new opportunity for designing GPR35-targeted drugs for the treatment of IBDs.
Lacrimal gland biopsies—results from a tertiary centre in the UK
Authors: Awotesu Segun , Obi Ebube , Awad Mary , Mudhar Hardeep , Burns Joyce , De Silva Ian , Sampath Raghavan
Published: December 2022

Purpose

To report the histopathological results of lacrimal gland biopsies over a 21-year period in a tertiary referral centre in the United Kingdom. To the best of our knowledge, this represents the largest series to be published in the United Kingdom.

Methods

A retrospective observational review was carried out for patients who underwent lacrimal gland biopsies in a tertiary referral centre at the University Hospitals of Leicester, United Kingdom between the years of 2000 and 2021.

Results

Lacrimal gland biopsies were performed on 248 patients during the specified 21-year period. They comprised 157 (63.3%) females and 91 (36.7%) males. The mean age at presentation was 50.8 years (range 15–94 years). The majority of patients were Caucasian (69.4%, n = 172) followed by Asians (25.0%, n = 62), African/Afro-Caribbean (4.8%, n = 12) and other ethnicities (0.8%, n = 2). The most common histopathological diagnosis was chronic inflammation dacryoadenitis (69.0%, n = 171) followed by lymphomas (15.3%, n = 38).

Conclusion

Our study shows that chronic inflammation accounts for the majority of histopathological diagnosis followed by lymphoproliferative disorders.
On-skin and tele-haptic application of mechanically decoupled taxel array on dynamically moving and soft surfaces
Authors: Kwon Se Young , Park Gyeongsuk , Jin Hanbit , Gu Changyeon , Oh Seung Jin , Sim Joo Yong , Youm Wooseup , Kim Taek-Soo , Kim Hye Jin , Park Steve
Published: December 2022

To accurately probe the tactile information on soft skin, it is critical for the pressure sensing array to be free of noise and inter-taxel crosstalk, irrespective of the measurement condition. However, on dynamically moving and soft surfaces, which are common conditions for on-skin and robotic applications, obtaining precise measurement without compromising the sensing performance is a significant challenge due to mechanical coupling between the sensors and with the moving surface. In this work, multi-level architectural design of micro-pyramids and trapezoid-shaped mechanical barrier array was implemented to enable accurate spatiotemporal tactile sensing on soft surfaces under dynamic deformations. Trade-off relationship between limit of detection and bending insensitivity was discovered, which was overcome by employing micropores in barrier structures. Finally, in-situ pressure mapping on dynamically moving soft surfaces without signal distortion is demonstrated while human skin and/or soft robots are performing complicated tasks such as reading Braille and handling the artificial organs.
Diffusion along perivascular spaces as marker for impairment of glymphatic system in Parkinson’s disease
Authors: Shen Ting , Yue Yumei , Ba Fang , He Tinging , Tang Xiaocui , Hu Xingyue , Pu Jiali , Huang Cong , Lv Wen , Zhang Baorong , Lai Hsin-Yi
Published: December 2022

The brain glymphatic system is involved in the clearance of misfolding α-synuclein, the impaired glymphatic system may contribute to the progression of Parkinson’s disease (PD). We aimed to analyze the diffusion tensor image along the perivascular space (DTI-ALPS) and perivascular space (PVS) burden to reveal the relationship between the glymphatic system and PD. A cross-sectional study using a 7 T MRI of 76 PD patients and 48 controls was performed to evaluate the brain’s glymphatic system. The DTI-ALPS and PVS burden in basal ganglia were calculated. Correlation analyses were conducted between DTI-ALPS, PVS burden and clinical features. We detected lower DTI-ALPS in the PD subgroup relative to controls, and the differences were more pronounced in patients with Hoehn & Yahr stage greater than two. The decreased DTI-ALPS was only evident in the left hemisphere in patients in the early stage but involved both hemispheres in more advanced PD patients. Decreased DTI-ALPS were also correlated with longer disease duration, higher Unified Parkinson’s Disease Rating Scale motor score (UPDRS III) and UPDRS total scores, as well as higher levodopa equivalent daily dose. Moreover, the decreased DTI-ALPS correlated with increased PVS burden, and both indexes correlated with PD disease severity. This study demonstrated decreased DTI-ALPS in PD, which might initiate from the left hemisphere and progressively involve right hemisphere with the disease progression. Decreased DTI-ALPS index correlated with increased PVS burden, indicating that both metrics could provide supporting evidence of an impaired glymphatic system. MRI evaluation of the PVS burden and diffusion along PVS are potential imaging biomarkers for PD for disease progression.
Sphingolipid subtypes differentially control proinsulin processing and systemic glucose homeostasis
Authors: Griess Kerstin , Rieck Michael , Müller Nadine , Karsai Gergely , Hartwig Sonja , Pelligra Angela , Hardt Robert , Schlegel Caroline , Kuboth Jennifer , Uhlemeyer Celina , Trenkamp Sandra , Jeruschke Kay , Weiss Jürgen , Peifer-Weiss Leon , Xu Weiwei , Cames Sandra , Yi Xiaoyan , Cnop Miriam , Beller Mathias , Stark Holger , Kondadi Arun Kumar , Reichert Andreas S. , Markgraf Daniel , Wammers Marianne , Häussinger Dieter , Kuss Oliver , Lehr Stefan , Eizirik Decio , Lickert Heiko , Lammert Eckhard , Roden Michael , Winter Dominic , Al-Hasani Hadi , Höglinger Doris , Hornemann Thorsten , Brüning Jens C. , Belgardt Bengt-Frederik
Published: December 2022

Impaired proinsulin-to-insulin processing in pancreatic β-cells is a key defective step in both type 1 diabetes and type 2 diabetes (T2D) (refs. 1,2), but the mechanisms involved remain to be defined. Altered metabolism of sphingolipids (SLs) has been linked to development of obesity, type 1 diabetes and T2D (refs. 3–8); nonetheless, the role of specific SL species in β-cell function and demise is unclear. Here we define the lipid signature of T2D-associated β-cell failure, including an imbalance of specific very-long-chain SLs and long-chain SLs. β-cell-specific ablation of CerS2, the enzyme necessary for generation of very-long-chain SLs, selectively reduces insulin content, impairs insulin secretion and disturbs systemic glucose tolerance in multiple complementary models. In contrast, ablation of long-chain-SL-synthesizing enzymes has no effect on insulin content. By quantitatively defining the SL–protein interactome, we reveal that CerS2 ablation affects SL binding to several endoplasmic reticulum–Golgi transport proteins, including Tmed2, which we define as an endogenous regulator of the essential proinsulin processing enzyme Pcsk1. Our study uncovers roles for specific SL subtypes and SL-binding proteins in β-cell function and T2D-associated β-cell failure.
The molecular evolution of spermatogenesis across mammals
Authors: Murat Florent , Mbengue Noe , Winge Sofia Boeg , Trefzer Timo , Leushkin Evgeny , Sepp Mari , Cardoso-Moreira Margarida , Schmidt Julia , Schneider Celine , Mößinger Katharina , Brüning Thoomke , Lamanna Francesco , Belles Meritxell Riera , Conrad Christian , Kondova Ivanela , Bontrop Ronald , Behr Rüdiger , Khaitovich Philipp , Pääbo Svante , Marques-Bonet Tomas , Grützner Frank , Almstrup Kristian , Schierup Mikkel Heide , Kaessmann Henrik
Published: December 2022

The testis produces gametes through spermatogenesis and evolves rapidly at both the morphological and molecular level in mammals1–6, probably owing to the evolutionary pressure on males to be reproductively successful7. However, the molecular evolution of individual spermatogenic cell types across mammals remains largely uncharacterized. Here we report evolutionary analyses of single-nucleus transcriptome data for testes from 11 species that cover the three main mammalian lineages (eutherians, marsupials and monotremes) and birds (the evolutionary outgroup), and include seven primates. We find that the rapid evolution of the testis was driven by accelerated fixation rates of gene expression changes, amino acid substitutions and new genes in late spermatogenic stages, probably facilitated by reduced pleiotropic constraints, haploid selection and transcriptionally permissive chromatin. We identify temporal expression changes of individual genes across species and conserved expression programs controlling ancestral spermatogenic processes. Genes predominantly expressed in spermatogonia (germ cells fuelling spermatogenesis) and Sertoli (somatic support) cells accumulated on X chromosomes during evolution, presumably owing to male-beneficial selective forces. Further work identified transcriptomal differences between X- and Y-bearing spermatids and uncovered that meiotic sex-chromosome inactivation (MSCI) also occurs in monotremes and hence is common to mammalian sex-chromosome systems. Thus, the mechanism of meiotic silencing of unsynapsed chromatin, which underlies MSCI, is an ancestral mammalian feature. Our study illuminates the molecular evolution of spermatogenesis and associated selective forces, and provides a resource for investigating the biology of the testis across mammals.
Actin cytoskeleton and complex cell architecture in an Asgard archaeon
Authors: Rodrigues-Oliveira Thiago , Wollweber Florian , Ponce-Toledo Rafael I. , Xu Jingwei , Rittmann Simon K.-M. R. , Klingl Andreas , Pilhofer Martin , Schleper Christa
Published: December 2022

Asgard archaea are considered to be the closest known relatives of eukaryotes. Their genomes contain hundreds of eukaryotic signature proteins (ESPs), which inspired hypotheses on the evolution of the eukaryotic cell1–3. A role of ESPs in the formation of an elaborate cytoskeleton and complex cellular structures has been postulated4–6, but never visualized. Here we describe a highly enriched culture of ‘CandidatusLokiarchaeum ossiferum’, a member of the Asgard phylum, which thrives anaerobically at 20 °C on organic carbon sources. It divides every 7–14 days, reaches cell densities of up to 5 × 107cells per ml and has a significantly larger genome compared with the single previously cultivated Asgard strain7. ESPs represent 5% of its protein-coding genes, including four actin homologues. We imaged the enrichment culture using cryo-electron tomography, identifying ‘Ca. L. ossiferum’ cells on the basis of characteristic expansion segments of their ribosomes. Cells exhibited coccoid cell bodies and a network of branched protrusions with frequent constrictions. The cell envelope consists of a single membrane and complex surface structures. A long-range cytoskeleton extends throughout the cell bodies, protrusions and constrictions. The twisted double-stranded architecture of the filaments is consistent with F-actin. Immunostaining indicates that the filaments comprise Lokiactin—one of the most highly conserved ESPs in Asgard archaea. We propose that a complex actin-based cytoskeleton predated the emergence of the first eukaryotes and was a crucial feature in the evolution of the Asgard phylum by scaffolding elaborate cellular structures.
A spatially resolved atlas of the human lung characterizes a gland-associated immune niche
Authors: Madissoon Elo , Oliver Amanda J. , Kleshchevnikov Vitalii , Wilbrey-Clark Anna , Polanski Krzysztof , Richoz Nathan , Ribeiro Orsi Ana , Mamanova Lira , Bolt Liam , Elmentaite Rasa , Pett J. Patrick , Huang Ni , Xu Chuan , He Peng , Dabrowska Monika , Pritchard Sophie , Tuck Liz , Prigmore Elena , Perera Shani , Knights Andrew , Oszlanczi Agnes , Hunter Adam , Vieira Sara F. , Patel Minal , Lindeboom Rik G. H. , Campos Lia S. , Matsuo Kazuhiko , Nakayama Takashi , Yoshida Masahiro , Worlock Kaylee B. , Nikolić Marko Z. , Georgakopoulos Nikitas , Mahbubani Krishnaa T. , Saeb-Parsy Kourosh , Bayraktar Omer Ali , Clatworthy Menna R. , Stegle Oliver , Kumasaka Natsuhiko , Teichmann Sarah A. , Meyer Kerstin B.
Published: December 2022

Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable atlungcellatlas.org). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal and nerve bundle micro-environments. We identify and implicate peribronchial fibroblasts in lung disease. Importantly, we discover and validate a survival niche for IgA plasma cells in the airway submucosal glands (SMG). We show that gland epithelial cells recruit B cells and IgA plasma cells, and promote longevity and antibody secretion locally through expression of CCL28, APRIL and IL-6. This new ‘gland-associated immune niche’ has implications for respiratory health.
ETV3 and ETV6 enable monocyte differentiation into dendritic cells by repressing macrophage fate commitment
Authors: Villar Javiera , Cros Adeline , De Juan Alba , Alaoui Lamine , Bonte Pierre-Emmanuel , Lau Colleen M. , Tiniakou Ioanna , Reizis Boris , Segura Elodie
Published: December 2022

In inflamed tissues, monocytes differentiate into macrophages (mo-Macs) or dendritic cells (mo-DCs). In chronic nonresolving inflammation, mo-DCs are major drivers of pathogenic events. Manipulating monocyte differentiation would therefore be an attractive therapeutic strategy. However, how the balance of mo-DC versus mo-Mac fate commitment is regulated is not clear. In the present study, we show that the transcriptional repressors ETV3 and ETV6 control human monocyte differentiation into mo-DCs. ETV3 and ETV6 inhibit interferon (IFN)-stimulated genes; however, their action on monocyte differentiation is independent of IFN signaling. Instead, we find that ETV3 and ETV6 directly repress mo-Mac development by controlling MAFB expression. Mice deficient for Etv6 in monocytes have spontaneous expression of IFN-stimulated genes, confirming that Etv6 regulates IFN responses in vivo. Furthermore, these mice have impaired mo-DC differentiation during inflammation and reduced pathology in an experimental autoimmune encephalomyelitis model. These findings provide information about the molecular control of monocyte fate decision and identify ETV6 as a therapeutic target to redirect monocyte differentiation in inflammatory disorders.
A genome-wide association study implicates the pleiotropic effect of NMUR2 on asthma and COPD
Authors: Do Ah Ra , An Jin , Jo Jinyeon , Kim Woo Jin , Kang Hae Yeon , Lee Sanghun , Yoon Dankyu , Cho You Sook , Adcock Ian M. , Chung Kian Fan , Won Sungho , Kim Tae-Bum
Published: December 2022

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct diseases that are associated with chronic inflammation. They share common features in terms of their advanced stages and genetic factors. This study aimed to identify novel genes underlying both asthma and COPD using genome-wide association study (GWAS) to differentiate between the two diseases. We performed a GWAS of asthma and COPD in 7828 Koreans from three hospitals. In addition, we investigated genetic correlations. The UK Biobank dataset was used for the replication studies. We found that rs2961757, located near neuromedin U receptor 2 (NMUR2) on chromosome 5, was genome-wide significant ($${\upbeta }_{\mathrm{Asthma}-\mathrm{COPD}}$$

β

Asthma
-
COPD

= 0.44, P-valueAsthma-COPD = 3.41 × 10−8), and significant results were replicated with the UK Biobank data ($${\upbeta }_{\mathrm{Asthma}-\mathrm{COPD}}$$

β

Asthma
-
COPD

= 0.04, P-valueAsthma-COPD = 0.0431). A positive genetic correlation was observed between asthma and COPD (39.8% in the Korean dataset and 49.8% in the UK Biobank dataset). In this study, 40–45% of the genetic effects were common to asthma and COPD. Moreover, NMUR2 increases the risk of asthma development and suppresses COPD development. This indicates that NMUR2 allows for better differentiation of both diseases, which can facilitate tailored medical therapy.
Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis
Authors: Kim Angela Yun , Marduy Anna , de Melo Paulo S. , Gianlorenco Anna Carolyna , Kim Chi Kyung , Choi Hyuk , Song Jae-Jun , Fregni Felipe
Published: December 2022

Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet been investigated. This systematic review and meta-analysis on taVNS aimed to (1) systematically analyze study characteristics and AE assessment, (2) characterize and analyze possible AEs and their incidence, (3) search for predictable risk factors, (4) analyze the severity of AE, and (5) suggest an evidence-based taVNS adverse events questionnaire for safety monitoring. The articles searched were published through April 7, 2022, in Medline, Embase, Web of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies that assessed 6322 subjects. From these, 55.37% of studies did not mention the presence or absence of any AEs; only 24.86% of the studies described that at least one adverse event occurred. In the 35 studies reporting the number of subjects with at least one adverse event, a meta-analytic approach to calculate the risk differences of developing an adverse event between active taVNS and controls was used. The meta-analytic overall adverse events incidence rate was calculated for the total number of adverse events reported on a 100,000 person-minutes-days scale. There were no differences in risk of developing an adverse event between active taVNS and controls. The incidence of AE, in general, was 12.84/100,000 person-minutes-days of stimulation, and the most frequently reported were ear pain, headache, and tingling. Almost half of the studies did not report the presence or absence of any AEs. We attribute this to the absence of AE in those studies. There was no causal relationship between taVNS and severe adverse events. This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical intervention.
Machine learning-assisted system using digital facial images to predict the clinical activity score in thyroid-associated orbitopathy
Authors: Moon Jae Hoon , Shin Kyubo , Lee Gyeong Min , Park Jaemin , Lee Min Joung , Choung Hokyung , Kim Namju
Published: December 2022

Although the clinical activity score (CAS) is a validated scoring system for identifying disease activity of thyroid-associated orbitopathy (TAO), it may produce differing results depending on the evaluator, and an experienced ophthalmologist is required for accurate evaluation. In this study, we developed a machine learning (ML)-assisted system to mimic an expert’s CAS assessment using digital facial images and evaluated its accuracy for predicting the CAS and diagnosing active TAO (CAS ≥ 3). An ML-assisted system was designed to assess five CAS components related to inflammatory signs (redness of the eyelids, redness of the conjunctiva, swelling of the eyelids, inflammation of the caruncle and/or plica, and conjunctival edema) in patients’ facial images and to predict the CAS by considering two components of subjective symptoms (spontaneous retrobulbar pain and pain on gaze). To train and test the system, 3,060 cropped images from 1020 digital facial images of TAO patients were used. The reference CAS for each image was scored by three ophthalmologists, each with > 15 years of clinical experience. We repeated the experiments for 30 randomly split training and test sets at a ratio of 8:2. The sensitivity and specificity of the ML-assisted system for diagnosing active TAO were 72.7% and 83.2% in the test set constructed from the entire dataset. For the test set constructed from the dataset with consistent results for the three ophthalmologists, the sensitivity and specificity for diagnosing active TAO were 88.1% and 86.9%. In the test sets from the entire dataset and from the dataset with consistent results, 40.0% and 49.9% of the predicted CAS values were the same as the reference CAS, respectively. The system predicted the CAS within 1 point of the reference CAS in 84.6% and 89.0% of cases when tested using the entire dataset and in the dataset with consistent results, respectively. An ML-assisted system estimated the clinical activity of TAO and detect inflammatory active TAO with reasonable accuracy. The accuracy could be improved further by obtaining more data. This ML-assisted system can help evaluate the disease activity consistently as well as accurately and enable the early diagnosis and timely treatment of active TAO.
Integrating orientation mechanisms, adrenocortical activity, and endurance flight in vagrancy behaviour
Authors: Snell Katherine R. S. , Young Rebecca C. , Krause Jesse S. , Collinson J. Martin , Wingfield John C. , Thorup Kasper
Published: December 2022

Avian migratory processes are typically precisely oriented, yet vagrants are frequently recorded outside their normal range. Wind displaced vagrants often show corrective behaviour, and as an appropriate response is likely adaptive. We investigated the physiological response to vagrancy in passerines. Activation of the emergency life-history stage (ELHS), assessed by high baseline plasma corticosterone, is a potential mechanism to elicit compensatory behaviour in response to challenges resulting from navigational error, coupled with response to fuel load and flight. We compared circulating plasma corticosterone concentrations and body condition between three migratory groups in autumn: (1) wind displaced southwest (SW) vagrants and (2) long range southeast (SE) vagrants on the remote Faroe Islands, and (3) birds within the expected SW migratory route (controls) on the Falsterbo peninsula, Sweden. Vagrants were further grouped by those sampled immediately upon termination of over-water migratory flight and those already on the island. In all groups there was no indication of the activation of the ELHS in response to vagrancy. We found limited support for an increased rate of corticosterone elevation within our 3 min sample interval in a single species, but this was driven by an individual ELHS outlier. Fat scores were negatively correlated with circulating corticosterone; this relationship may suggest that ELHS activation depends upon an individual’s energetic states. Interestingly, in individuals caught at the completion of an obligate long-distance flight, we found some evidence of corticosterone suppression. Although limited, data did support the induction of negative feedback mechanisms that suppress corticosterone during endurance exercise, even when fuel loads are low.
Incidence rate and distinctive characteristics of first episode psychosis during the COVID-19 pandemic: a multicenter observational study
Authors: Casanovas Francesc , Trabsa Amira , Bergé Daniel , Sánchez-Gistau Vanessa , Moreno Irene , Sanchez Julia , Montalvo Itziar , Tost Meritxell , Labad Javier , Pérez-Solà Victor , Mané Anna
Published: December 2022

The COVID-19 pandemic has affected the mental health of people around the world. However, its impact on first-episode psychosis (FEP) remains unclear. The aim of this study was to determine the incidence rate (IR) and the clinical and sociodemographic characteristics of patients who developed FEP during the nine-month period following the COVID-19 outbreak in Spain and to compare these data to the corresponding period in the previous year. We included all patients (n = 220) treated for the first time during these two time periods at three FEP programs in Spain. The IR was 0.42/100,000 person-years during the pandemic vs. 0.54/100,000 in the prior year (p = 0.057). Compared to prior year, women accounted for a significantly higher proportion of FEP patients (46.3% vs. 28%; p = 0.005) during the COVID-19 period. This association was significant on the logistic regression analysis (odds ratio, female: 2.12 [confidence interval 1.17–3.82]; p = 0.014). These data reveal a non-significant trend towards a lower incidence of FEP during the pandemic period. Female sex was associated with a greater risk of developing FEP during the pandemic period, perhaps due to differences between males and females in the susceptibility and expression of psychosis. The findings of this study contribute to a better understanding of stress-related disorders.
Field study on the severity of photovoltaic potential induced degradation
Authors: Badran Ghadeer , Dhimish Mahmoud
Published: December 2022

Photovoltaic (PV) systems can be affected by different types of defects, faults, and mismatching conditions. A severe problem in PV systems has arisen in the last couple of years, known as potential-induced degradation (PID). During the early installation stage of the PV system, the PID may not be noticed because it appears over time (months or years). As time passes, it becomes more apparent since the output power may drop dramatically. We studied PV modules over the course of three years that were affected by PID. An electroluminescent and thermal imaging technique helped discover the PID. PID appeared in PV modules after being in different fields for 4–8 months, resulting in a 27–39% drop in power. An anti-PID box was fitted during the second year of the PV operation to recover the PID. Accordingly, it has stabilized the power degradation, but it could not restore the performance of the affected PID modules as compared with healthy/non-PID modules.
Anastellin impacts on the processing of extracellular matrix fibronectin and stimulates release of cytokines from coronary artery smooth muscle cells
Authors: He Jianfei , Steffen Jonas Hyld , Thulstrup Peter Waaben , Pedersen Jannik Nedergaard , Sauerland Max B. , Otzen Daniel E. , Hawkins Clare L. , Gourdon Pontus , Davies Michael J. , Hägglund Per
Published: December 2022

Anastellin, a recombinant protein fragment from the first type III module of fibronectin, mimics a partially unfolded intermediate implicated in the assembly of fibronectin fibrils. Anastellin influences the structure of fibronectin and initiates in vitro fibrillation, yielding “superfibronectin”, a polymer with enhanced cell-adhesive properties. This ability is absent in an anastellin double mutant, L37AY40A. Here we demonstrate that both wild-type and L37AY40A anastellin affect fibronectin processing within the extracellular matrix (ECM) of smooth muscle cells. Fibronectin fibrils are diminished in the ECM from cells treated with anastellin, but are partially rescued by supplementation with plasma fibronectin in cell media. Proteomic analyses reveal that anastellin also impacts on the processing of other ECM proteins, with increased collagen and decreased laminin detected in media from cells exposed to wild-type anastellin. Moreover, both anastellin forms stimulate release of inflammatory cytokines, including interleukin 6. At the molecular level, L37AY40A does not exhibit major perturbations of structural features relative to wild-type anastellin, though the mutant showed differences in heparin binding characteristics. These findings indicate that wild-type and L37AY40A anastellin share similar molecular features but elicit slightly different, but partially overlapping, responses in smooth muscle cells resulting in altered secretion of cytokines and proteins involved in ECM processing.
Analysis and design of terahertz reflectarrays based on graphene cell clusters
Authors: Hosseini Parinaz , Oraizi Homayoon
Published: December 2022

In this paper, the graphene cell-cluster is introduced, which is composed of an array of identical unit-cells placed in a geometrical configuration. Such graphene cell-clusters are then used for the realization of a reflectarray. To the best of our knowledge, identical unit-cells in a particular geometrical configuration have already been introduced, but the analytical formulas for this model have not been investigated so far. In this paper, the Fourier-optics and aperture field estimation methods are applied to investigate the effect of cell-cluster dimensions on the generation of specified far-field radiation patterns. Implementing cell-clusters in graphene reflectarrays and similar structures, and also applying the proposed formulas, lead to the simplicity of configuration and enhancing the design accuracy. First, the effect of cell-cluster dimensions on the reflectarray radiation pattern is investigated. Then, a reflectarray composed of graphene cell-clusters is designed. A new configuration of graphene unit-cell composed of two graphene layers is proposed, where a middle layer of metallic patch is inserted. In the common graphene unit-cells, the rate of amplitude variations is quite high and greatly depends on the variation of phase in the proposed unit-cell. However, the amplitude variation is quite smaller than the phase variations.
Poly(ADP-ribosyl)ating enzymes cooperate to coordinate development
Authors: Bordet Guillaume , Karpova Iaroslava , Tulin Alexei V.
Published: December 2022

The transcriptome is subject to rapid and massive changes during the transition between developmental stages. These changes require tight control to avoid the undesired reactivation of gene expression that is only important for previous developmental stages and, if unchecked during transition between developmental stages, could lead to anarchic proliferation and formation of malignant tumors. In this context, the involvement of chromatin factors is important since they can directly regulate the expression of multiple genes at the same time. Poly(ADP-ribose) enzymes, involved in several processes from DNA repair to transcription regulation, might play a role in this regulation. Here, we report that PARP-1 and PARG cooperate to temporally regulate the gene expression profile during the larval/pupa transition. PARP-1 and PARG are both essential in repressing the expression of genes coding for digestive enzymes and larval cuticle proteins, while PARG positively regulate the expression of defense response genes. These results suggest a cooperative coordination between PARP-1 and PARG that specifically maintains the integrity of expression profile between developmental stages.
Task-evoked pupillary responses track precision-weighted prediction errors and learning rate during interceptive visuomotor actions
Authors: Harris D. J. , Arthur T. , Vine S. J. , Liu J. , Abd Rahman H. R. , Han F. , Wilson M. R.
Published: December 2022

In this study, we examined the relationship between physiological encoding of surprise and the learning of anticipatory eye movements. Active inference portrays perception and action as interconnected inference processes, driven by the imperative to minimise the surprise of sensory observations. To examine this characterisation of oculomotor learning during a hand–eye coordination task, we tested whether anticipatory eye movements were updated in accordance with Bayesian principles and whether trial-by-trial learning rates tracked pupil dilation as a marker of ‘surprise’. Forty-four participants completed an interception task in immersive virtual reality that required them to hit bouncing balls that had either expected or unexpected bounce profiles. We recorded anticipatory eye movements known to index participants’ beliefs about likely ball bounce trajectories. By fitting a hierarchical Bayesian inference model to the trial-wise trajectories of these predictive eye movements, we were able to estimate each individual’s expectations about bounce trajectories, rates of belief updating, and precision-weighted prediction errors. We found that the task-evoked pupil response tracked prediction errors and learning rates but not beliefs about ball bounciness or environmental volatility. These findings are partially consistent with active inference accounts and shed light on how encoding of surprise may shape the control of action.
Bacterial infections epidemiology and factors associated with multidrug resistance in the northern region of Ghana
Authors: Gnimatin Jean-Pierre , Weyori Enoch Weikem , Agossou Shimea M. , Adokiya Martin Nyaaba
Published: December 2022

Bacterial infections caused by multidrug resistant organisms are a major global threat. There is still a knowledge gap on this situation in the Northern Region of Ghana. This study determined the prevalence and resistance profile of bacterial infections. It also identified factors associated with multidrug resistance in the study area. This was a retrospective cross-sectional design and it analyzed data from the samples received at the Tamale Zonal Public Health Reference Laboratory from June 2018 to May 2022. The data were analyzed using the R software version 4.2.0. Univariate and multivariable binary logistic regression analyses were used to determine the factors associated with multidrug resistance. The samples included all specimen types possible. The specimens were collected for the purpose of clinical bacteriology diagnostics. Overall a total of 1222 isolates were obtained. The three (3) main bacteria responsible for infections were: Klebsiella spp. (27%), Moraxella spp. (22%), Escherichia spp. (16%). High resistance levels were found against the tested antibiotics and about 41.60% of the bacterial strains isolated were multidrug resistant. Hospitalization was associated with multidrug resistance in univariate (COR 1.96; 95% CI 1.43–2.71; P-value < 0.001) and multivariable analyses (AOR 1.78; 95% CI 1.28–2.49; P-value < 0.001). There is the need for further research on the molecular epidemiology of antibiotic resistance genes in the study area to effectively control the spread of multidrug resistant pathogens. In addition, efforts to build the capacity of health professionals on infection prevention and control as well as diagnostic and antimicrobial stewardship needs urgent attention.
Synergies of fuel cell system thermal management and cryogenic hydrogen exergy utilization
Authors: Lenger Magnus , Heinke Steffen , Tegethoff Wilhelm , Köhler Jürgen
Published: December 2022

Low-temperature polymer electrolyte fuel cell systems (FCSs) need to reject large amounts of low temperature heat. Often a mobile FCS’s cooling capacity limits the FCS power output. Cryogenic hydrogen is typically utilized as a direct heat sink using heat exchangers (HXs), even though HXs destroy most hydrogen exergy. This paper investigates synergies between FCS thermal management and cryogenic hydrogen exergy utilization in terms of their benchmark performance: the FCS coolant circuit supplies heat at coolant temperature level to a so named reversible cryogenic exergy utilization system (rCEUS) comprised of thermodynamically ideal heat engine processes. The rCEUS converts this heat partly to electrical energy (the value of which equals the hydrogen exergy) and rejects remaining heat to hydrogen to heat it to coolant temperature. The rCEUS output power is used to support the FCS, so the FCS rejects less heat and a significant fraction of this heat is utilized by the rCEUS. As a result, significantly less heat has to be transferred to ambient and the fuel demand decreases. In this paper, three hydrogen storage options are compared: liquid hydrogen, subcooled liquid hydrogen and cryo-compressed hydrogen. Different para- and orthohydrogen compositions are evaluated. For typical FCS operating points, rejected FCS heat to ambient is reducible by 40–67%. FCS power demand is reducible by 14–31%. FCS rejected heat to ambient reduction is 4.5–8 times larger than that of conventional HXs. Calculations are based on hydrogen’s lower heating value.
Sex and menopause impact 31P-Magnetic Resonance Spectroscopy brain mitochondrial function in association with 11C-PiB PET amyloid-beta load
Authors: Jett Steven , Dyke Jonathan P. , Andy Caroline , Schelbaum Eva , Jang Grace , Boneu Yepez Camila , Pahlajani Silky , Diaz Ivan , Diaz Brinton Roberta , Mosconi Lisa
Published: December 2022

Increasing evidence implicates sex and endocrine aging effects on brain bioenergetic aging in the greater lifetime risk of Alzheimer’s disease (AD) in women. We conducted 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) to assess the impact of sex and menopause on brain high-energy phosphates [adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi)] and membrane phospholipids [phosphomonoesters/phosphodiesters (PME/PDE)] in 216 midlife cognitively normal individuals at risk for AD, 80% female. Ninety-seven participants completed amyloid-beta (Aβ) 11C-PiB PET. Women exhibited higher ATP utilization than men in AD-vulnerable frontal, posterior cingulate, fusiform, medial and lateral temporal regions (p < 0.001). This profile was evident in frontal cortex at the pre-menopausal and peri-menopausal stage and extended to the other regions at the post-menopausal stage (p = 0.001). Results were significant after multi-variable adjustment for age, APOE-4 status, midlife health indicators, history of hysterectomy/oophorectomy, use of menopause hormonal therapy, and total intracranial volume. While associations between ATP/PCr and Aβ load were not significant, individuals with the highest Aβ load were post-menopausal and peri-menopausal women with ATP/PCr ratios in the higher end of the distribution. No differences in Pi/PCr, Pi/ATP or PME/PDE were detected. Outcomes are consistent with dynamic bioenergetic brain adaptations that are associated with female sex and endocrine aging.