bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embryonic keratin19+ progenitors generate multiple functionally distinct progeny to maintain epithelial diversity in the adult thymus medulla
Authors: Lucas Beth , White Andrea J. , Klein Fabian , Veiga-Villauriz Clara , Handel Adam , Bacon Andrea , Cosway Emilie J. , James Kieran D. , Parnell Sonia M. , Ohigashi Izumi , Takahama Yousuke , Jenkinson William E. , Hollander Georg A. , Lu Wei-Yu , Anderson Graham 
Published: April 2023

AbstractThe thymus medulla is a key site for immunoregulation and tolerance, and its functional specialisation is achieved through the complexity of medullary thymic epithelial cells (mTEC). While the importance of the medulla for thymus function is clear, the production and maintenance of mTEC diversity remains poorly understood. Here, using ontogenetic and inducible fate-mapping approaches, we identify mTEC-restricted progenitors as a cytokeratin19+ (K19+) TEC subset that emerges in the embryonic thymus. Importantly, labelling of a single cohort of K19+ TEC during embryogenesis sustains the production of multiple mTEC subsets into adulthood, including CCL21+ mTEClo, Aire+ mTEChi and thymic tuft cells. We show K19+ progenitors arise prior to the acquisition of multiple mTEC-defining features including RANK and CCL21 and are generated independently of the key mTEC regulator, Relb. In conclusion, we identify and define a multipotent mTEC progenitor that emerges during embryogenesis to support mTEC diversity into adult life.
Seismic magnitude clustering is prevalent in field and laboratory catalogs
Authors: Xiong Q. , Brudzinski M. R. , Gossett D. , Lin Q. , Hampton J. C. 
Published: April 2023

AbstractClustering of earthquake magnitudes is still actively debated, compared to well-established spatial and temporal clustering. Magnitude clustering is not currently implemented in earthquake forecasting but would be important if larger magnitude events are more likely to be followed by similar sized events. Here we show statistically significant magnitude clustering present in many different field and laboratory catalogs at a wide range of spatial scales (mm to 1000 km). It is universal in field catalogs across fault types and tectonic/induced settings, while laboratory results are unaffected by loading protocol or rock types and show temporal stability. The absence of clustering can be imposed by a global tensile stress, although clustering still occurs when isolating to triggered event pairs or spatial patches where shear stress dominates. Magnitude clustering is most prominent at short time and distance scales and modeling indicates >20% repeating magnitudes in some cases, implying it can help to narrow physical mechanisms for seismogenesis.
Widespread global disparities between modelled and observed mid-depth ocean currents
Authors: Su Fenzhen , Fan Rong , Yan Fengqin , Meadows Michael , Lyne Vincent , Hu Po , Song Xiangzhou , Zhang Tianyu , Liu Zenghong , Zhou Chenghu , Pei Tao , Yang Xiaomei , Du Yunyan , Wei Zexun , Wang Fan , Qi Yiquan , Chai Fei 
Published: April 2023

AbstractThe mid-depth ocean circulation is critically linked to actual changes in the long-term global climate system. However, in the past few decades, predictions based on ocean circulation models highlight the lack of data, knowledge, and long-term implications in climate change assessment. Here, using 842,421 observations produced by Argo floats from 2001-2020, and Lagrangian simulations, we show that only 3.8% of the mid-depth oceans, including part of the equatorial Pacific Ocean and the Antarctic Circumpolar Current, can be regarded as accurately modelled, while other regions exhibit significant underestimations in mean current velocity. Knowledge of ocean circulation is generally more complete in the low-latitude oceans but is especially poor in high latitude regions. Accordingly, we propose improvements in forecasting, model representation of stochasticity, and enhancement of observations of ocean currents. The study demonstrates that knowledge and model representations of global circulation are substantially compromised by inaccuracies of significant magnitude and direction, with important implications for modelled predictions of currents, temperature, carbon dioxide sequestration, and sea-level rise trends.
Stretchable array electromyography sensor with graph neural network for static and dynamic gestures recognition system
Authors: Lee Hyeyun , Lee Soyoung , Kim Jaeseong , Jung Heesoo , Yoon Kyung Jae , Gandla Srinivas , Park Hogun , Kim Sunkook 
Published: April 2023

AbstractWith advances in artificial intelligence (AI)-based algorithms, gesture recognition accuracy from sEMG signals has continued to increase. Spatiotemporal multichannel-sEMG signals substantially increase the quantity and reliability of the data for any type of study. Here, we report an array of bipolar stretchable sEMG electrodes with a self-attention-based graph neural network to recognize gestures with high accuracy. The array is designed to spatially cover the skeletal muscles to acquire the regional sampling data of EMG activity from 18 different gestures. The system can differentiate individual static and dynamic gestures with ~97% accuracy when training a single trial per gesture. Moreover, a sticky patchwork of holes adhered to an array sensor enables skin-like attributes such as stretchability and water vapor permeability and aids in delivering stable EMG signals. In addition, the recognition accuracy (~95%) remained unchanged even after long-term testing for over 72 h and being reused more than 10 times.
OpcA and PorB are novel bactericidal antigens of the 4CMenB vaccine in mice and humans
Authors: Viviani Viola , Fantoni Adele , Tomei Sara , Marchi Sara , Luzzi Enrico , Bodini Margherita , Muzzi Alessandro , Giuliani Marzia M. , Maione Domenico , Derrick Jeremy P. , Delany Isabel , Pizza Mariagrazia , Biolchi Alessia , Bartolini Erika 
Published: April 2023

AbstractThe ability ofNeisseria meningitidisOuter Membrane Vesicles (OMV) to induce protective responses in humans is well established and mainly attributed to Porin A (PorA). However, the contribution of additional protein antigens to protection remains to be elucidated. In this study we dissected the immunogenicity of antigens originating from the OMV component of the 4CMenB vaccine in mice and humans. We collected functional data on a panel of strains for which bactericidal responses to 4CMenB in infants was attributable to the OMV component and evaluated the role of 30 OMV-specific protein antigens in cross-coverage. By using tailor-made protein microarrays, the immunosignature of OMV antigens was determined. Three of these proteins, OpcA, NspA, and PorB, triggered mouse antibodies that were bactericidal against severalN. meningitidisstrains. Finally, by genetic deletion and/or serum depletion studies, we demonstrated the ability of OpcA and PorB to induce functional immune responses in infant sera after vaccination. In conclusion, while confirming the role of PorA in eliciting protective immunity, we identified two OMV antigens playing a key role in protection of infants vaccinated with the 4CMenB vaccine against differentN. meningitidisserogroup B strains.
Dynamic synchronization between hippocampal representations and stepping
Authors: Joshi Abhilasha , Denovellis Eric L. , Mankili Abhijith , Meneksedag Yagiz , Davidson Thomas J. , Gillespie Anna K. , Guidera Jennifer A. , Roumis Demetris , Frank Loren M. 
Published: April 2023

AbstractThe hippocampus is a mammalian brain structure that expresses spatial representations1 and is crucial for navigation2,3. Navigation, in turn, intricately depends on locomotion; however, current accounts suggest a dissociation between hippocampal spatial representations and the details of locomotor processes. Specifically, the hippocampus is thought to represent mainly higher-order cognitive and locomotor variables such as position, speed and direction of movement4–7, whereas the limb movements that propel the animal can be computed and represented primarily in subcortical circuits, including the spinal cord, brainstem and cerebellum8–11. Whether hippocampal representations are actually decoupled from the detailed structure of locomotor processes remains unknown. To address this question, here we simultaneously monitored hippocampal spatial representations and ongoing limb movements underlying locomotion at fast timescales. We found that the forelimb stepping cycle in freely behaving rats is rhythmic and peaks at around 8 Hz during movement, matching the approximately 8 Hz modulation of hippocampal activity and spatial representations during locomotion12. We also discovered precisely timed coordination between the time at which the forelimbs touch the ground (‘plant’ times of the stepping cycle) and the hippocampal representation of space. Notably, plant times coincide with hippocampal representations that are closest to the actual position of the nose of the rat, whereas between these plant times, the hippocampal representation progresses towards possible future locations. This synchronization was specifically detectable when rats approached spatial decisions. Together, our results reveal a profound and dynamic coordination on a timescale of tens of milliseconds between central cognitive representations and peripheral motor processes. This coordination engages and disengages rapidly in association with cognitive demands and is well suited to support rapid information exchange between cognitive and sensory–motor circuits.
Extrachromosomal DNA in the cancerous transformation of Barrett’s oesophagus
Authors: Luebeck Jens , Ng Alvin Wei Tian , Galipeau Patricia C. , Li Xiaohong , Sanchez Carissa A. , Katz-Summercorn Annalise C. , Kim Hoon , Jammula Sriganesh , He Yudou , Lippman Scott M. , Verhaak Roel G. W. , Maley Carlo C. , Alexandrov Ludmil B. , Reid Brian J. , Fitzgerald Rebecca C. , Paulson Thomas G. , Chang Howard Y. , Wu Sihan , Bafna Vineet , Mischel Paul S. 
Published: April 2023

AbstractOncogene amplification on extrachromosomal DNA (ecDNA) drives the evolution of tumours and their resistance to treatment, and is associated with poor outcomes for patients with cancer1–6. At present, it is unclear whether ecDNA is a later manifestation of genomic instability, or whether it can be an early event in the transition from dysplasia to cancer. Here, to better understand the development of ecDNA, we analysed whole-genome sequencing (WGS) data from patients with oesophageal adenocarcinoma (EAC) or Barrett’s oesophagus. These data included 206 biopsies in Barrett’s oesophagus surveillance and EAC cohorts from Cambridge University. We also analysed WGS and histology data from biopsies that were collected across multiple regions at 2 time points from 80 patients in a case–control study at the Fred Hutchinson Cancer Center. In the Cambridge cohorts, the frequency of ecDNA increased between Barrett’s-oesophagus-associated early-stage (24%) and late-stage (43%) EAC, suggesting that ecDNA is formed during cancer progression. In the cohort from the Fred Hutchinson Cancer Center, 33% of patients who developed EAC had at least one oesophageal biopsy with ecDNA before or at the diagnosis of EAC. In biopsies that were collected before cancer diagnosis, higher levels of ecDNA were present in samples from patients who later developed EAC than in samples from those who did not. We found that ecDNAs contained diverse collections of oncogenes and immunomodulatory genes. Furthermore, ecDNAs showed increases in copy number and structural complexity at more advanced stages of disease. Our findings show that ecDNA can develop early in the transition from high-grade dysplasia to cancer, and that ecDNAs progressively form and evolve under positive selection.
MicroRNA-142-3p promotes renal cell carcinoma progression by targeting RhoBTB3 to regulate HIF-1 signaling and GGT/GSH pathways
Authors: Zhang Yijing , Ma Sha , Zhang Jun , Lou Lu , Liu Wanqi , Gao Chao , Miao Long , Sun Fanghao , Chen Wei , Cao Xiliang , Wei Jin 
Published: April 2023

AbstractMicroRNAs play a critical regulatory role in different cancers, but their functions in renal cell carcinoma (RCC) have not been elucidated. Reportedly, miR-142-3p is involved in the tumorigenesis and the development of RCC in vitro and is clinically correlated with the poor prognosis of RCC patients. However, the molecular target of miR-142-3p and the underlying mechanism are unclear. In this study, we found that miR-142-3p was upregulated in RCC tumor tissues and downregulated in exosomes compared to normal tissues. The expression of miR-142-3p was inversely associated with the survival of patients with kidney renal clear cell carcinoma (KIRC). RhoBTB3 was reduced in RCC, and miR-142-3p plays an inverse function with RhoBTB3 in KIRC. The direct interaction between RhoBTB3 and miR-142-3p was demonstrated by a dual luciferase reporter assay. miR-142-3p promoted metastasis in the xenograft model, and the suppression of miR-142-3p upregulated RhoBTB3 protein expression and inhibited the mRNAs and proteins of HIF1A, VEGFA, and GGT1. Also, the miR-142-3p overexpression upregulated the mRNA of HIF1A, VEGFA, and GGT1. In conclusion, miR-142-3p functions as an oncogene in RCC, especially in KIRC, by targeting RhoBTB3 to regulate HIF-1 signaling and GGT/GSH pathways, which needs further exploration.
Facial emotion recognition in patients with depression compared to healthy controls when using human avatars
Authors: Monferrer Marta , García Arturo S. , Ricarte Jorge J. , Montes María J. , Fernández-Caballero Antonio , Fernández-Sotos Patricia 
Published: April 2023

AbstractThe negative, mood-congruent cognitive bias described in depression, as well as excessive rumination, have been found to interfere with emotional processing. This study focuses on the assessment of facial recognition of emotions in patients with depression through a new set of dynamic virtual faces (DVFs). The sample consisted of 54 stable patients compared to 54 healthy controls. The experiment consisted in an emotion recognition task using non-immersive virtual reality (VR) with DVFs of six basic emotions and neutral expression. Patients with depression showed a worst performance in facial affect recognition compared to healthy controls. Age of onset was negatively correlated with emotion recognition and no correlation was observed for duration of illness or number of lifetime hospitalizations. There was no correlation for the depression group between emotion recognition and degree of psychopathology, excessive rumination, degree of functioning, or quality of life. Hence, it is important to improve and validate VR tools for emotion recognition to achieve greater methodological homogeneity of studies and to be able to establish more conclusive results.
Outpatient clinic specific for end-stage renal disease improves patient survival rate after initiating dialysis
Authors: Fukuzaki Haruna , Nakata Junichiro , Nojiri Shuko , Shimizu Yuki , Shirotani Yuka , Maeda Takuya , Kano Toshiki , Mishiro Maiko , Nohara Nao , Io Hiroaki , Suzuki Yusuke 
Published: April 2023

AbstractThe importance of a shared decision-making (SDM) approach is widely recognized worldwide. In Japan, hospital accreditation involves the promotion of SDM for patients with end-stage renal disease (ESRD) when considering renal replacement therapy (RRT). This study aimed to clarify the effectiveness and long-term medical benefits of SDM in RRT. Patients with ESRD who underwent dialysis therapy were retrospectively divided into those who visited outpatient clinics specific for ESRD (ESRD clinic) supporting RRT selection with an SDM approach (visited group) and those who did not visit the ESRD clinic (non-visited group). Data of 250 patients (129 in the non-visited group and 121 in the visited group) were analyzed. Mortality was significantly higher in the non-visited group than in the visited group. Not seeing an ESRD specialist was associated with emergent initiation of dialysis and subsequent 1 year mortality. The number of patients who chose peritoneal dialysis as a modality of RRT was significantly larger in the visited group. These findings demonstrate the association between the ESRD clinic, 1 year survival in patients with ESRD after initiating dialysis, and the different RRT modalities. This specific approach in the ESRD clinic may improve the management of patients with ESRD.
Application of Mendelian randomization to explore the causal role of the human gut microbiome in colorectal cancer
Authors: Hatcher Charlie , Richenberg George , Waterson Samuel , Nguyen Long H. , Joshi Amit D. , Carreras-Torres Robert , Moreno Victor , Chan Andrew T. , Gunter Marc , Lin Yi , Qu Conghui , Song Mingyang , Casey Graham , Figueiredo Jane C. , Gruber Stephen B. , Hampe Jochen , Hampel Heather , Jenkins Mark A. , Keku Temitope O. , Peters Ulrike , Tangen Catherine M. , Wu Anna H. , Hughes David A. , Rühlemann Malte C. , Raes Jeroen , Timpson Nicholas J. , Wade Kaitlin H. 
Published: April 2023

AbstractThe role of the human gut microbiome in colorectal cancer (CRC) is unclear as most studies on the topic are unable to discern correlation from causation. We apply two-sample Mendelian randomization (MR) to estimate the causal relationship between the gut microbiome and CRC. We used summary-level data from independent genome-wide association studies to estimate the causal effect of 14 microbial traits (n = 3890 individuals) on overall CRC (55,168 cases, 65,160 controls) and site-specific CRC risk, conducting several sensitivity analyses to understand the nature of results. Initial MR analysis suggested that a higher abundance of Bifidobacterium and presence of an unclassified group of bacteria within the Bacteroidales order in the gut increased overall and site-specific CRC risk. However, sensitivity analyses suggested that instruments used to estimate relationships were likely complex and involved in many potential horizontal pleiotropic pathways, demonstrating that caution is needed when interpreting MR analyses with gut microbiome exposures. In assessing reverse causality, we did not find strong evidence that CRC causally affected these microbial traits. Whilst our study initially identified potential causal roles for two microbial traits in CRC, importantly, further exploration of these relationships highlighted that these were unlikely to reflect causality.
Association between soluble angiotensin-converting enzyme 2 in saliva and SARS-CoV-2 infection: a cross-sectional study
Authors: Bru Samuel , Brotons Pedro , Jordan Iolanda , Alsina Laia , Henares Desiree , Carballar Reyes , de Sevilla Mariona Fernandez , Barrabeig Irene , Fumado Victoria , Baro Bàrbara , Martínez-Láinez Joan Marc , Garcia-Garcia Juan J. , Bassat Quique , Balaguer Albert , Clotet Josep , Launes Cristian , Muñoz-Almagro Carmen 
Published: April 2023

AbstractThis study aimed to investigate the association between saliva soluble angiotensin-converting enzyme 2 (sACE2) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adults. We selected a convenience sample of adults with post-acute SARS-CoV-2 infection and their household children living in quarantined family households of the metropolitan Barcelona region (Spain) during the spring 2020 pandemic national lockdown. Participants were tested for saliva sACE2 quantification by western blot and nasopharyngeal SARS-CoV-2 RT-PCR detection. A total of 161 saliva samples [82 (50.9%) from children; 79 (49.1%) from females] yielded valid western blot and RT-PCR results. Saliva sACE2 was detected in 79 (96.3%) children and 76 (96.2%) convalescent adults. Twenty (24.4%) children and 20 (25.3%) convalescent adults were positive for SARS-CoV-2 in nasopharynx by RT-PCR. SARS-CoV-2 RT-PCR-negative children had a significantly higher mean proportional level of saliva sACE2 (0.540 × 10–3%) than RT-PCR-positive children (0.192 × 10–3%, p < 0.001) and convalescent adults (0.173 × 10–3%, p < 0.001). In conclusion, children negative for nasopharyngeal SARS-CoV-2 RT-PCR appear to exhibit a higher concentration of saliva sACE2 than SARS-CoV-2 RT-PCR-positive children and convalescent adults. Release of adequate levels of sACE2 in saliva could play a protective role against SARS-CoV-2.
Factors hindering coverage of targeted mass treatment with primaquine in a malarious township of northern Myanmar in 2019–2020
Authors: Aung Pyae Linn , Soe Myat Thu , Soe Than Naing , Oo Thit Lwin , Win Kyawt Mon , Cui Liwang , Kyaw Myat Phone , Sattabongkot Jetsumon , Okanurak Kamolnetr , Parker Daniel M. 
Published: April 2023

AbstractTargeted mass primaquine treatment (TPT) might be an effective intervention to facilitate elimination of vivax malaria in Myanmar by 2030. In this study, we explored the factors hindering coverage of a TPT campaign conducted in a malarious township of northern Myanmar. From August 2019 to July 2020, a cross-sectional exploratory design including quantitative and qualitative data was conducted in five villages with high P. vivax prevalence following a TPT campaign. Among a targeted population of 2322; 1973 (85.0%) participated in the baseline mass blood survey (MBS) and only 52.0% of the total targeted population (1208, 91.9% of total eligible population) completed the TPT. G6PD deficiency was found among 13.5% of total MBS participants and those were excluded from TPT. Of 1315 eligible samples, farmers and gold miners, males, and those aged 15 to 45 years had higher percentages of non-participation in TPT. Qualitative findings showed that most of the non-participation groups were outside the villages during TPT because of time-sensitive agricultural and other occupational or education-related purposes. In addition to mitigating of some inclusion criteria (i.e. including young children or offering weekly PQ treatment to G6PD deficient individuals), strengthening community awareness and increasing engagement should be pursued to increase community participation.
Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injury
Authors: Jo Seongmoon , Baek Ahreum , Cho Yoonhee , Kim Sung Hoon , Baek Dawoon , Hwang Jihye , Cho Sung-Rae , Kim Hyun Jung 
Published: April 2023

AbstractPolydeoxyribonucleotide (PDRN) is an agonist that selectively stimulates adenosine A2A receptor (ADORA2A), which suppresses inflammatory responses. Ischemia/reperfusion (I/R) injury plays a major role in the pathogenesis of ischemic stroke by inducing neuroinflammation. Therefore, this study aimed to investigate the therapeutic effects of PDRN in an in vitro I/R injury model. The in vitro model was established with differentiated Neuro-2a cells under oxygen and glucose deprivation condition. The cells were treated with PDRN for 24 h under reoxygenation condition. As the results of RNA-seq transcriptome analysis, CSF1, IL-6, PTPN6, RAC2, and STAT1 were identified of its relation to the effect of PDRN on inflammatory responses in the model. To further investigate therapeutic effects of PDRN, RT-qPCR, western blotting, LDH assay, and TUNEL assay were performed. PDRN significantly reversed the expression of genes and proteins related to inflammatory responses. The elevated ADORA2A expression by PDRN treatment downregulated JAK/STAT pathway in the model. Furthermore, PDRN inhibited neuronal cell death in the model. Consequently, our results suggested that PDRN alleviated inflammatory responses through inhibition of JAK/STAT pathway by mediating ADORA2A expression and inhibited neuronal cell death in the model. These results provide significant insights into potential therapeutic approaches involving PDRN treatment for I/R injury.