bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncogenic enhancers drive esophageal squamous cell carcinogenesis and metastasis
Authors: Ye Bo , Fan Dandan , Xiong Weiwei , Li Min , Yuan Jian , Jiang Qi , Zhao Yuting , Lin Jianxiang , Liu Jie , Lv Yilv , Wang Xiongjun , Li Zhigang , Su Jianzhong , Qiao Yunbo 
Published: July 2021

AbstractThe role of cis-elements and their aberrations remains unclear in esophageal squamous cell carcinoma (ESCC, further abbreviated EC). Here we survey 28 H3K27ac-marked active enhancer profiles and 50 transcriptomes in primary EC, metastatic lymph node cancer (LNC), and adjacent normal (Nor) esophageal tissues. Thousands of gained or lost enhancers and hundreds of altered putative super-enhancers are identified in EC and LNC samples respectively relative to Nor, with a large number of common gained or lost enhancers. Moreover, these differential enhancers contribute to the transcriptomic aberrations in ECs and LNCs. We also reveal putative driver onco-transcription factors, depletion of which diminishes cell proliferation and migration. The administration of chemical inhibitors to suppress the predicted targets of gained super-enhances reveals HSP90AA1 and PDE4B as potential therapeutic targets for ESCC. Thus, our epigenomic profiling reveals a compendium of reprogrammed cis-regulatory elements during ESCC carcinogenesis and metastasis for uncovering promising targets for cancer treatment.
Hearing difficulty is linked to Alzheimer’s disease by common genetic vulnerability, not shared genetic architecture
Authors: Abidin Fatin N. Zainul , Wells Helena R. R. , Altmann Andre , Dawson Sally J. 
Published: July 2021

AbstractAge-related hearing loss was recently established as the largest modifiable risk factor for Alzheimer’s disease (AD), however, the reasons for this link remain unclear. We investigate shared underlying genetic associations using results from recent large genome-wide association studies (GWAS) on adult hearing difficulty and AD. Genetic correlation and Mendelian randomization (MR) analysis do not support a genetic correlation between the disorders, but suggest a direct causal link from AD genetic risk to hearing difficulty, driven by APOE. Systematic MR analyses on the effect of other traits revealed shared effects of glutamine, gamma-glutamylglutamine, and citrate levels on reduced risk of both hearing difficulty and AD. In addition, pathway analysis on GWAS risk variants suggests shared function in neuronal signalling pathways as well as etiology of diabetes and cardiovascular disease. However, after multiple testing corrections, neither analysis led to statistically significant associations. Altogether, our genetic-driven analysis suggests hearing difficulty and AD are linked by a shared vulnerability in molecular pathways rather than by a shared genetic architecture.
Altered oral and gut microbiota and its association with SARS-CoV-2 viral load in COVID-19 patients during hospitalization
Authors: Wu Yongjian , Cheng Xiaomin , Jiang Guanmin , Tang Huishu , Ming Siqi , Tang Lantian , Lu Jiahai , Guo Cheng , Shan Hong , Huang Xi 
Published: July 2021

AbstractThe human oral and gut commensal microbes play vital roles in the development and maintenance of immune homeostasis, while its association with susceptibility and severity of SARS-CoV-2 infection is barely understood. In this study, we investigated the dynamics of the oral and intestinal flora before and after the clearance of SARS-CoV-2 in 53 COVID-19 patients, and then examined their microbiome alterations in comparison to 76 healthy individuals. A total of 140 throat swab samples and 81 fecal samples from these COVID-19 patients during hospitalization, and 44 throat swab samples and 32 fecal samples from sex and age-matched healthy individuals were collected and then subjected to 16S rRNA sequencing and viral load inspection. We found that SARS-CoV-2 infection was associated with alterations of the microbiome community in patients as indicated by both alpha and beta diversity indexes. Several bacterial taxa were identified related to SARS-CoV-2 infection, wherein elevated Granulicatella and Rothia mucilaginosa were found in both oral and gut microbiome. The SARS-CoV-2 viral load in those samples was also calculated to identify potential dynamics between COVID-19 and the microbiome. These findings provide a meaningful baseline for microbes in the digestive tract of COVID-19 patients and will shed light on new dimensions for disease pathophysiology, potential microbial biomarkers, and treatment strategies for COVID-19.
Restructured single parabolic band model for quick analysis in thermoelectricity
Authors: Zhu Jianbo , Zhang Xuemei , Guo Muchun , Li Jingyu , Hu Jinsuo , Cai Songting , Cai Wei , Zhang Yongsheng , Sui Jiehe 
Published: July 2021

AbstractThe single parabolic band (SPB) model has been widely used to preliminarily elucidate inherent transport behaviors of thermoelectric (TE) materials, such as their band structure and electronic thermal conductivity, etc. However, in the SPB calculation, it is necessary to determine some intermediate variables, such as Fermi level or the complex Fermi-Dirac integrals. In this work, we establish a direct carrier-concentration-dependent restructured SPB model, which eliminates Fermi-Dirac integrals and Fermi level calculation and emerges stronger visibility and usability in experiments. We have verified the reliability of such restructured model with 490 groups of experimental data from state-of-the-art TE materials and the relative error is less than 2%. Moreover, carrier effective mass, intrinsic carrier mobility and optimal carrier concentration of these materials are systematically investigated. We believe that our work can provide more convenience and accuracy for thermoelectric data analysis as well as instructive understanding on future optimization design.
The complexity of mental health care for people with COPD: a qualitative study of clinicians’ perspectives
Authors: Wang Juliet , Willis Karen , Barson Elizabeth , Smallwood Natasha 
Published: July 2021

AbstractAnxiety and depression are common mental health illnesses in people with chronic obstructive pulmonary disease (COPD). However, patients often decline formal mental health care with barriers identified at the patient, health provider and health system levels. Currently clinicians’ perspectives on this issue are not well understood. A qualitative study using semi-structured interviews was undertaken to explore clinician perceived barriers and facilitators to acceptance of psychological care amongst people with COPD. Twenty-four Australian respiratory health professionals participated. Interview transcripts were analysed thematically. An overarching theme of ‘complexity’ was identified, which was evident across five domains: (1) physical and mental health illnesses; (2) psychosocial circumstances; (3) community views and stigma; (4) educational needs and knowledge gaps; (5) navigating the health system. Targeted patient education around psychological interventions and integration of mental health clinicians within multidisciplinary outpatient respiratory services are needed to address the current challenges.
Links between fecal microbiota and the response to vaccination against influenza A virus in pigs
Authors: Borey Marion , Blanc Fany , Lemonnier Gaëtan , Leplat Jean-Jacques , Jardet Deborah , Rossignol Marie-Noëlle , Ravon Laure , Billon Yvon , Bernard Maria , Estellé Jordi , Rogel-Gaillard Claire 
Published: July 2021

AbstractThis study describes the associations between fecal microbiota and vaccine response variability in pigs, using 98 piglets vaccinated against the influenza A virus at 28 days of age (D28) with a booster at D49. Immune response to the vaccine is measured at D49, D56, D63, and D146 by serum levels of IAV-specific IgG and assays of hemagglutination inhibition (HAI). Analysis of the pre-vaccination microbiota characterized by 16S rRNA gene sequencing of fecal DNA reveals a higher vaccine response in piglets with a richer microbiota, and shows that 23 operational taxonomic units (OTUs) are differentially abundant between high and low IAV-specific IgG producers at D63. A stronger immune response is linked with OTUs assigned to the genus Prevotella and family Muribaculaceae, and a weaker response is linked with OTUs assigned to the genera Helicobacter and Escherichia-Shigella. A set of 81 OTUs accurately predicts IAV-specific IgG and HAI titer levels at all time points, highlighting early and late associations between pre-vaccination fecal microbiota composition and immune response to the vaccine.
A single dose of replication-competent VSV-vectored vaccine expressing SARS-CoV-2 S1 protects against virus replication in a hamster model of severe COVID-19
Authors: Malherbe Delphine C. , Kurup Drishya , Wirblich Christoph , Ronk Adam J. , Mire Chad , Kuzmina Natalia , Shaik Noor , Periasamy Sivakumar , Hyde Matthew A. , Williams Julie M. , Shi Pei-Yong , Schnell Matthias J. , Bukreyev Alexander 
Published: July 2021

AbstractThe development of effective countermeasures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent responsible for the COVID-19 pandemic, is a priority. We designed and produced ConVac, a replication-competent vesicular stomatitis virus (VSV) vaccine vector that expresses the S1 subunit of SARS-CoV-2 spike protein. We used golden Syrian hamsters as animal models of severe COVID-19 to test the efficacy of the ConVac vaccine. A single vaccine dose elicited high levels of SARS-CoV-2 specific binding and neutralizing antibodies; following intranasal challenge with SARS-CoV-2, animals were protected from weight loss and viral replication in the lungs. No enhanced pathology was observed in vaccinated animals upon challenge, but some inflammation was still detected. The data indicate rapid control of SARS-CoV-2 replication by the S1-based VSV-vectored SARS-CoV-2 ConVac vaccine.
A multi-site, year-round turbulence microstructure atlas for the deep perialpine Lake Garda
Authors: Piccolroaz Sebastiano , Fernández-Castro Bieito , Toffolon Marco , Dijkstra Henk A. 
Published: July 2021

AbstractA multi-site, year-round dataset comprising a total of 606 high-resolution turbulence microstructure profiles of shear and temperature gradient in the upper 100 m depth is made available for Lake Garda (Italy). Concurrent meteorological data were measured from the fieldwork boat at the location of the turbulence measurements. During the fieldwork campaign (March 2017-June 2018), four different sites were sampled on a monthly basis, following a standardized protocol in terms of time-of-day and locations of the measurements. Additional monitoring activity included a 24-h campaign and sampling at other sites. Turbulence quantities were estimated, quality-checked, and merged with water quality and meteorological data to produce a unique turbulence atlas for a lake. The dataset is open to a wide range of possible applications, including research on the variability of turbulent mixing across seasons and sites (demersal vs pelagic zones) and driven by different factors (lake-valley breezes vs buoyancy-driven convection), validation of hydrodynamic lake models, as well as technical studies on the use of shear and temperature microstructure sensors.
Chronic musculoskeletal pain, catastrophizing, and physical function in adult women were improved after 3-month aerobic-resistance circuit training
Authors: Sato Seira , Ukimoto Sho , Kanamoto Takashi , Sasaki Nao , Hashimoto Takao , Saito Hikaru , Hida Eisuke , Sato Tomoharu , Mae Tatsuo , Nakata Ken 
Published: July 2021

AbstractAlthough exercise is beneficial for chronic musculoskeletal pain (CMP), the optimal type and amount of exercise are unclear. This study aimed to determine the impact of circuit training that combines aerobic and resistance exercises on adult women with CMP. A total of 139 women with CMP underwent circuit training for 3 months and were asked to complete the following questionnaires at baseline and 3 months later: Numeric Rating Scale (NRS), Pain Catastrophizing Scale (PCS), Roland-Morris Disability Questionnaire (RDQ), Shoulder36, and Knee injury and Osteoarthritis Outcome Score (KOOS). Significant improvements were observed in NRS, PCS, RDQ, and KOOS activities of daily living (ADL) scores after the intervention relative to baseline (p < 0.0001, p = 0.0013, 0.0004, and 0.0295, respectively), whereas shoulder function did not improve. When considering the impact of exercise frequency, NRS scores improved regardless of exercise frequency. Furthermore, PCS, RDQ, and KOOS scores improved in participants who exercised at least twice a week (24 sessions over the course of 3 months). In conclusion, CMP, pain catastrophizing, and physical function in adult female fitness club participants with CMP of NRS 4 or higher improved after 3 months of aerobic-resistance circuit training.
Analysis of variant-pairing tendencies in lenticular martensite microstructures based on rank-1 connection
Authors: Shinohara Yuri , Akabane Satomu , Inamura Tomonari 
Published: July 2021

AbstractHerein, variant-pairing tendencies of lenticular martensite in an Fe–30Ni–0.3C (wt%) alloy are analyzed based on rank-1 connection at martensite/martensite junction planes (JPs) to facilitate the understanding of martensite microstructure. The degree of incompatibility (θ) at the JPs successfully explained their observed frequency; in the actual microstructure, variant pairs with a smallθform preferentially. The experimentally obtained JPs were consistent with theoretical ones. To the best of our knowledge, this is the first study to confirm the validity of variant-pair crystallography in steel based on rank-1 connection, both theoretically and experimentally. Diamond, composite-spear, and composite-kink clusters are considered. The cumulativeθat the JPs can suppress diamond cluster formation because it exceeds theθof a single variant pair, and the diamond cluster is not observed experimentally. However,θat the JPs cancel out in composite-spear (CS) and composite-kink (CK) clusters, but CK clusters are rarely observed experimentally, while a few CS clusters are observed. This demonstrates the analytical limitations of 2D approaches used to evaluate the frequency of variant pairs and clusters. These two variant clusters have a narrow window of 2D observation because the orientation relationships between JPs and intersection lines between two habit planes affect the areas of JPs.
Tyrosine and Tryptophan vibrational bands as markers of kidney injury: a renocardiac syndrome induced by renal ischemia and reperfusion study
Authors: Nepomuceno Gabrielle , Junho Carolina Victoria Cruz , Carneiro-Ramos Marcela Sorelli , da Silva Martinho Herculano 
Published: July 2021

AbstractRenal injury caused by renal ischemia and reperfusion strongly influences heart morphology, electrophysiology, and redox unbalance. The so-called cardiorenal syndrome is an important class of dysfunction since heart and kidneys are responsible for hemodynamic stability and organ perfusion through a complex network. In the present work we investigate the vibrational spectral features probed by Fourier-Transform Raman (FT-Raman) spectroscopy due to physiological alterations induced by renal ischemic reperfusion aiming to detect molecular markers related to progression of acute to chronic kidney injury and mortality predictors as well. C57BL/6J mice were subjected to unilateral occlusion of the renal pedicle for 60 min and reperfusion for 5, 8, and 15 days. Biopsies of heart and kidney tissues were analyzed. Our findings indicated that cysteine/cystine, fatty acids, methyl groups of Collagen, α-form of proteins, Tyrosine, and Tryptophan were modulated during renal ischemia and reperfusion process. These changes are consistent with fibroblast growth factors and Collagen III contents changes. Interestingly, Tyrosine and Tryptophan, precursor molecules for the formation of uremic toxins such as indoxyl sulfate and p-cresyl sulfate were also modulated. They are markers of kidney injury and their increase is strongly correlated to cardiovascular mortality. Regarding this aspect, we notice that monitoring the Tyrosine and Tryptophan bands at 1558, 1616, and 1625 cm−1 is a viable and and advantageous way to predict fatality in cardiovascular diseases both “in vivo” or “in vitro”, using the real-time, multiplexing, and minimally invasive advantages of FT-Raman spectroscopy.
Human placental piwi-interacting RNA transcriptome is characterized by expression from the DLK1-DIO3 imprinted region
Authors: Martinez Victor D. , Sage Adam P. , Minatel Brenda C. , Marshall Erin A. , Price E. Magda , Becker-Santos Daiana D. , Robinson Wendy P. , Lam Wan L. 
Published: July 2021

AbstractThe placenta is vital to embryonic development and requires a finely-tuned pattern of gene expression, achieved in part by its unique epigenetic landscape. Piwi-interacting RNAs (piRNAs) are a class of small-non-coding RNA with established roles as epigenetic regulators of gene expression, largely via methylation of targeted DNA sequences. The expression of piRNAs have mainly been described in germ cells, but a fraction have been shown to retain expression in adult somatic tissues. To aid in understanding the contribution of these regulators in the placenta, we provide the first description of the piRNA transcriptome in human placentas. We find 297 piRNAs to be preferentially expressed in the human placenta, a subset of which are expressed at higher levels relative to testes samples. We also observed a large proportion of placental piRNAs to be expressed from a single locus, as distinct from canonical cluster locations associated with transposable element silencing. Finally, we find that 15 of the highest-expressed placental piRNAs maps to the DLK1-DIO3 locus, suggesting a link to placental biology. Our findings suggest that piRNAs could contribute to the molecular networks defining placental function in humans, and a biological impact of piRNA expression beyond germ cells.
Neutrophils are important for the development of pro-reparative macrophages after irreversible electroporation of the liver in mice
Authors: Lopez-Ichikawa Maya , Vu Ngan K. , Nijagal Amar , Rubinsky Boris , Chang Tammy T. 
Published: July 2021

AbstractIrreversible electroporation (IRE) is a non-thermal tissue ablative technology that has emerging applications in surgical oncology and regenerative surgery. To advance its therapeutic usefulness, it is important to understand the mechanisms through which IRE induces cell death and the role of the innate immune system in mediating subsequent regenerative repair. Through intravital imaging of the liver in mice, we show that IRE produces distinctive tissue injury features, including delayed yet robust recruitment of neutrophils, consistent with programmed necrosis. IRE treatment converts the monocyte/macrophage balance from pro-inflammatory to pro-reparative populations, and depletion of neutrophils inhibits this conversion. Reduced generation of pro-reparative Ly6CloF4/80hi macrophages correlates with lower numbers of SOX9+ hepatic progenitor cells in areas of macrophage clusters within the IRE injury zone. Our findings suggest that neutrophils play an important role in promoting the development of pro-reparative Ly6Clo monocytes/macrophages at the site of IRE injury, thus establishing conditions of regenerative repair.
A comparison of alternative selection methods for reporting spirometric parameters in healthy adults
Authors: Therkorn Jennifer H. , Toto Daniella R. , Falvo Michael J. 
Published: July 2021

AbstractAlternative methods have been proposed to report spirometry indices from test sessions (forced expiratory volume 1 s, FEV1; forced vital capacity, FVC). However, most use the American and European Societies’ standard (ATS/ERS) which stops sessions once a repeatability threshold is met which may not accurately represent intra-session variability. Our goal was to repeat trials beyond the repeatability threshold and evaluate alternative reporting methods. 130 adults performed spirometry across two visits. Spirometry indices were reported using the ATS/ERS standard and four alternatives. 78 participants (60%) had valid data for all methods and visits. Intra-session coefficients of variation were low (FEV1: 3.1–3.7%; FVC: 2.3–2.8%). Our four alternative methods yielded FEV1 and FVC values ≤ 0.08 L different from ATS/ERS standard, which is not clinically meaningful. Intraclass correlation coefficients were ≥ 0.97 indicating consistency across repeated measures. The smallest real differences ranged from FEV1: 0.20–0.27 L and FVC: 0.18–0.24 L indicating consistency and low measurement error. Overall, all methods for reporting FEV1 and FVC demonstrated similar measurement error, precision, and stability within- and between-visits. These results suggest that once ATS/ERS repeatability is achieved, which approach is used for reporting spirometric variables may be of low clinical significance in a healthy population.
Safety evaluation of a clinical focused ultrasound system for neuronavigation guided blood-brain barrier opening in non-human primates
Authors: Pouliopoulos Antonios N. , Kwon Nancy , Jensen Greg , Meaney Anna , Niimi Yusuke , Burgess Mark T. , Ji Robin , McLuckie Alicia J. , Munoz Fabian A. , Kamimura Hermes A. S. , Teich Andrew F. , Ferrera Vincent P. , Konofagou Elisa E. 
Published: July 2021

AbstractAn emerging approach with potential in improving the treatment of neurodegenerative diseases and brain tumors is the use of focused ultrasound (FUS) to bypass the blood–brain barrier (BBB) in a non-invasive and localized manner. A large body of pre-clinical work has paved the way for the gradual clinical implementation of FUS-induced BBB opening. Even though the safety profile of FUS treatments in rodents has been extensively studied, the histological and behavioral effects of clinically relevant BBB opening in large animals are relatively understudied. Here, we examine the histological and behavioral safety profile following localized BBB opening in non-human primates (NHPs), using a neuronavigation-guided clinical system prototype. We show that FUS treatment triggers a short-lived immune response within the targeted region without exacerbating the touch accuracy or reaction time in visual-motor cognitive tasks. Our experiments were designed using a multiple-case-study approach, in order to maximize the acquired data and support translation of the FUS system into human studies. Four NHPs underwent a single session of FUS-mediated BBB opening in the prefrontal cortex. Two NHPs were treated bilaterally at different pressures, sacrificed on day 2 and 18 post-FUS, respectively, and their brains were histologically processed. In separate experiments, two NHPs that were earlier trained in a behavioral task were exposed to FUS unilaterally, and their performance was tracked for at least 3 weeks after BBB opening. An increased microglia density around blood vessels was detected on day 2, but was resolved by day 18. We also detected signs of enhanced immature neuron presence within areas that underwent BBB opening, compared to regions with an intact BBB, confirming previous rodent studies. Logistic regression analysis showed that the NHP cognitive performance did not deteriorate following BBB opening. These preliminary results demonstrate that neuronavigation-guided FUS with a single-element transducer is a non-invasive method capable of reversibly opening the BBB, without substantial histological or behavioral impact in an animal model closely resembling humans. Future work should confirm the observations of this multiple-case-study work across animals, species and tasks.