bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractTo 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

AbstractThe 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

AbstractImpaired 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

AbstractThe 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

AbstractAsgard 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

AbstractSingle-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

AbstractIn 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

AbstractAsthma 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

AbstractTranscutaneous 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

AbstractAlthough 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

AbstractAvian 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.