bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNFα inhibitors reduce bone loss in rheumatoid arthritis independent of clinical response by reducing osteoclast precursors and IL-20
Authors: Al-Bogami Mohammed , Bystrom Jonas , Clanchy Felix , Taher Taher E , Mangat Pamela , Williams Richard O , Jawad Ali S , Mageed Rizgar A 
Published: August 2020

Abstract

Objectives
About half of RA patients treated with TNFα inhibitors either do not respond or lose their initial therapeutic response over time. The clinical response is measured by reduction in DAS28, which primarily reflects inflammation. However, other effects of TNFα inhibitors, such as impact on bone erosion, are not assessed by DAS28. We aimed to examine the effect of TNFα inhibitors on bone density, bone biomarkers and cytokine production in responder and non-responder patients and assessed mechanisms of action.

Methods
BMD in the lumbar spine and femur neck of 117 RA patients was measured by DEXA scan. Bone turnover biomarkers CTX, osteoprotegerin (OPG), osteocalcin and RANKL were measured by ELISA. Levels of 16 cytokines in plasma and in tissue culture supernatants of ex vivo T cells were measured by multiplex assays and ELISA. The effect of treatment with TNFα inhibitors on blood mononuclear cell (MNC) differentiation to osteoclast precursors (OCP) was measured flow cytometry and microscopy.

Results
TNFα inhibitors improved lumbar spine BMD but had modest effects on blood bone biomarkers, irrespective of patients’ clinical response. Blood OCP numbers and the ability of monocytes to differentiate to OCP in vitro declined after treatment. Treatment also reduced RANK expression and IL-20 production. BMD improvement correlated with reduced levels of IL-20 in responder patients.

Conclusion
This study reveals that TNFα inhibitors reduce lumbar spine bone loss in RA patients irrespective of changes in DAS28. The reduction in bone loss is associated with reduction in IL-20 levels in responder patients.
Is obesity related to enhanced neural reactivity to visual food cues? A review and meta-analysis
Authors: Morys Filip , García-García Isabel , Dagher Alain 
Published: August 2020

AbstractTheoretical work suggests that obesity is related to enhanced incentive salience of food cues. However, evidence from both behavioral and neuroimaging studies on the topic is mixed. In this work, we review the literature on cue reactivity in obesity and perform a preregistered meta-analysis of studies investigating effects of obesity on brain responses to passive food pictures viewing. Further, we examine whether age influences brain responses to food cues in obesity. In the meta-analysis, we included 13 studies of children and adults that investigated group differences (obese vs lean) in responses to food vs non-food pictures viewing. While we found no significant differences in the overall meta-analysis, we show that age significantly influences brain response differences to food cues in the left insula and the left fusiform gyrus. In the left insula, obese vs lean brain differences in response to food cues decreased with age, while in the left fusiform gyrus the pattern was opposite. Our results suggest that there is little evidence for obesity-related differences in responses to food cues and that such differences might be mediated by additional factors that are often not considered.
Tools of the trade: estimating time-varying connectivity patterns from fMRI data
Authors: Iraji Armin , Faghiri Ashkan , Lewis Noah , Fu Zening , Rachakonda Srinivas , Calhoun Vince D 
Published: August 2020

AbstractGiven the dynamic nature of the brain, there has always been a motivation to move beyond ‘static’ functional connectivity, which characterizes functional interactions over an extended period of time. Progress in data acquisition and advances in analytical neuroimaging methods now allow us to assess the whole brain’s dynamic functional connectivity (dFC) and its network-based analog, dynamic functional network connectivity at the macroscale (mm) using fMRI. This has resulted in the rapid growth of analytical approaches, some of which are very complex, requiring technical expertise that could daunt researchers and neuroscientists. Meanwhile, making real progress toward understanding the association between brain dynamism and brain disorders can only be achieved through research conducted by domain experts, such as neuroscientists and psychiatrists. This article aims to provide a gentle introduction to the application of dFC. We first explain what dFC is and the circumstances under which it can be used. Next, we review two major categories of analytical approaches to capture dFC. We discuss caveats and considerations in dFC analysis. Finally, we walk readers through an openly accessible toolbox to capture dFC properties and briefly review some of the dynamic metrics calculated using this toolbox.
Diethylhexyl phthalate induces teratogenic effects through oxidative stress response in a chick embryo model
Authors: Song Ge , Wang Rui , Cui Yi , Hao Chan Juan , Xia Hong-Fei , Ma Xu 
Published: August 2020

Abstract
Diethylhexyl phthalate (DEHP) is known as a persistent environmental pollutant. However, the possible effects of DEHP on human neural tube defects (NTDs) remain elusive. We set out to investigate the exposure of DEHP in human and explore the association of DEHP and NTDs. The level of DEHP in maternal urine was measured and analyzed by GC-MS. To further validate the results in human NTDs, chick embryos were used as animal models. Viability, reactive oxygen species (ROS) level, oxidative stress indicators and apoptosis were detected in DEHP-treated chick embryos. Our research revealed that the detection ratio of positive DEHP and its metabolites in maternal urine were observed dramatically higher in NTDs population than that in normal controls (P &lt; 0.01, P &lt; 0.05, respectively). Moreover, DEHP treatment (10−6 M) led to developmental toxicity in chick embryos via accelerating oxidative stress response and cell apoptosis, and changing the level of oxidative stress-related indicators. Moreover, high dose choline (100 μg/μl) could partially restrain the toxicity effects induced by DEHP. Our data collectively imply that the incidence of NTDs may closely associate with DEHP exposure, which disturbs the development of neural tubes by enhancing oxidative stress.
COVID-19 and its Implications for Research on Work Ability
Authors: Truxillo Donald M , Cadiz David M , Brady Grant M 
Published: August 2020

Abstract
Research into work ability is increasing in the aging workforce literature. We argue that the COVID-19 pandemic has uncovered a number of possible gaps in our understanding of the work ability concept itself, its antecedents, and outcomes. We offer future research directions to further examine the theoretical underpinnings of work ability, moderators that may enhance its effects, and ways to broaden work ability conceptually to better capture the experiences of older workers.
Menopausal transition experiences and management strategies of Chinese immigrant women: a scoping review
Authors: Zou Ping , Shao Jing , Luo Yan , Huang Yanjin , Zhang Hui , Sidani Souraya 
Published: August 2020

Abstract

Importance and Objective:
Chinese immigrants are among some of the fastest growing groups in many Western countries, and experience challenges such as language barriers, education gaps, and gender discrimination, which highlights the need for special attention and consideration in Western health care. The purpose of this scoping review is to summarize existing research on the menopausal experiences of Chinese immigrant women (CIW).

Methods:
This scoping review was written in accordance with PRISMA guidelines. MEDLINE, PsycINFO, CINAHL, AgeLine, ERIC, ProQuest, Nursing and Allied Health Database, PsycARTICLES, Sociology Database, and Education Research Complete were utilized for the literature search. Articles were included if they examined CIW experiencing menopausal transition. A total of 18 studies were included for review.

Discussion and Conclusion:
Findings suggested that CIW experienced a variety of physical symptoms, including muscle and joint pain, urogenital symptoms, vasomotor symptoms, weight gain, decreased physical strength, vision changes, and skin changes. Muscle and joint pain were particularly prevalent and emphasized. CIW also experienced psycho-behavioral symptoms including emotional changes, depression, memory loss, and sexual dysfunction. However, they had a decreased concern regarding symptoms of sexual dysfunction and decreased libido when compared with women from Western cultures. CIW interpreted menopause as a natural aging process involving the next step in life. Cultural expectations of stoicism and silence may cause immigrant women to be less vocal about their menopause experiences and result in feelings of loneliness. Acculturation may be both a facilitator and a barrier to a healthy menopausal transition. CIW were resistant to Western Medicine management such as hormone therapy but were willing to incorporate traditional medicine into their health care. They believed that a healthy mentality was important and used various psychocognitive strategies to maintain a good quality of life. Healthcare providers, researchers, and policymakers need to consider the unique characteristics of CIW's menopausal transition in research, intervention innovation, and practice.
Clinical Characteristics and Severity of COVID-19 Disease in Patients from Boston Area Hospitals
Authors: Dashti Hesam , Bates David W. , Roche Elise , Fiskio Julie , Mora Samia , Demler Olga V. 
Published: August 2020

AbstractWe summarize key demographic, clinical, and medical characteristics of patients with respect to the severity of COVID-19 disease using Electronic Health Records Data of 4,140 SARS-CoV-2 positive subjects from several large Boston Area Hospitals. We found that prior use of antihypertensive medications as well as lipid lowering and other cardiovascular drugs (such as direct oral anticoagulants and antiplatelets) all track with increased severity of COVID-19 and should be further investigated with appropriate adjustment for confounders such as age and frailty. The three most common prior comorbidities are hyperlipidemia, hypertension, and prior pneumonia, all associated with increased severity.
Membrane Orientation and Oligomerization of the Melanocortin Receptor Accessory Protein 2
Authors: Chen Valerie , Bruno Antonio E. , Britt Laura L. , Hernandez Ciria C. , Gimenez Luis E. , Peisley Alys , Cone Roger D. , Millhauser Glenn L. 
Published: August 2020

ABSTRACTThe melanocortin receptor accessory protein 2 (MRAP2) plays a pivotal role in the regulation of several G-protein coupled receptors (GPCR) that are essential for energy balance and food intake. MRAP2 loss-of-function results in obesity in mammals. MRAP2 and its homolog MRAP1 have an unusual membrane topology and are the only known eukaryotic proteins that thread into the membrane in both orientations. In this study, we demonstrate that the conserved polybasic motif that dictates the membrane topology and dimerization of MRAP1 does not control the membrane orientation and dimerization of MRAP2. We also show that MRAP2 dimerizes through its transmembrane domain and can form higher order oligomers that arrange MRAP2 monomers in a parallel orientation. Investigating the molecular details of MRAP2 structure is essential for understanding the mechanism by which it regulates GPCRs and will aid in elucidating the pathways involved in metabolic dysfunction.
chTOG is a conserved mitotic error correction factor
Authors: Herman Jacob A. , Miller Matthew P. , Biggins Sue 
Published: August 2020

AbstractAccurate chromosome segregation requires kinetochores on duplicated chromatids to biorient by attaching to dynamic microtubules from opposite spindle poles, which exerts forces to bring kinetochores under tension. However, kinetochores initially bind to MTs indiscriminately, resulting in errors that must be corrected. While the Aurora B protein kinase destabilizes low-tension attachments by phosphorylating kinetochores, low-tension attachments are intrinsically less stable than those under higher tensionin vitroindependent of Aurora activity. Intrinsic tensionsensitive behavior requires the microtubule regulator Stu2 (budding yeast Dis1/XMAP215 ortholog), which we demonstrate here is likely a conserved function for the TOG protein family. The human TOG protein, chTOG, localizes to kinetochores independent of microtubules by interacting with Hec1. We identify a chTOG mutant that regulates microtubule dynamics but accumulates erroneous kinetochore-microtubule attachments that Aurora B fails to destabilize. Thus, TOG proteins confer a unique, intrinsic error correction activity to kinetochores that ensures accurate chromosome segregation.
Time-series transcriptomics from cold, oxic subseafloor crustal fluids reveals a motile, mixotrophic microbial community
Authors: Seyler L.M. , Trembath-Reichert E. , Tully B.J. , Huber J.A. 
Published: August 2020

AbstractThe rock-hosted oceanic crustal aquifer is one of the largest habitable volumes on Earth, and it harbors a reservoir of microbial life that influences global-scale biogeochemical cycles. Here, we use time series metagenomic and metatranscriptomic data from a low-temperature, ridge flank environment that is representative of the majority of global hydrothermal fluid circulation in the ocean to reconstruct microbial metabolic potential, transcript abundance, and community dynamics. The data suggest that the microbial community in this subseafloor habitat is motile, chiefly heterotrophic or mixotrophic, and capable of using alternative electron acceptors such as nitrate and thiosulfate, in addition to oxygen. Anaerobic processes are most abundant in subseafloor horizons deepest in the aquifer, furthest from connectivity with the deep ocean, and there was little overlap in the active microbial populations between sampling horizons. Together, our results indicate the microbial community in the North Pond aquifer plays an important role in the oxidation of organic carbon within the crust, and is also metabolically flexible, with the ability to switch from autotrophy to heterotrophy, as well as function under low oxygen conditions. This work highlights the heterogeneity of microbial life in the subseafloor aquifer and provides new insights into biogeochemical cycling in ocean crust.
Nasal commensal,Staphylococcus epidermidisshapes the mucosal environment to prevent influenza virus invasion through Serpine1 induction
Authors: Jo Ara , Won Jina , Chil Chan Hee , Choi Jae Young , Lee Kang-Mu , Yoon Sang Sun , Kim Hyun Jik 
Published: August 2020

ABSTRACTOur recent study presented evidence thatStaphylococcus epidermidis(S. epidermidis) was the most frequently encountered microbiome component in healthy human nasal mucus and thatS. epidermidiscould induce interferon (IFN)-dependent innate immunity to control acute viral lung infection. The serine protease inhibitor Serpine1 was identified to inhibit influenza A virus (IAV) spread by inhibiting glycoprotein cleavage, and the current study supports an additional mechanism of Serpine1 induction in the nasal mucosa, which can be regulated throughS. epidermidisand IFN signaling. The exposure ofin vivomice to humanS. epidermidisincreased IFN-λ secretion in nasal mucosa and prevented an increase in the burden of IAV in the lung.S. epidermidis-inoculated mice exhibited the significant induction of Serpine1in vivoin the nasal mucosa, and by targeting airway protease,S. epidermidis-inducedSerpine1 inhibited the intracellular invasion of IAV to the nasal epithelium and led to restriction of IAV spreading to the lung. Furthermore, IFN-λ secretion was involved in the regulation of Serpine1 inS. epidermidis-inoculated nasal epithelial cells andin vivonasal mucosa, and this was biologically relevant for the role of Serpine1 as an interferon-stimulated gene in the upper airway. Together, our findings reveal that human nasal commensalS. epidermidismanipulates the suppression of serine protease inin vivonasal mucosa through Serpine1 induction and protects the nasal mucosa from IAV invasion through IFN-λ signaling.IMPORTANCEPreviously, we proved that nasal microbiome could enhance IFN-related innate immune responses to protect the respiratory tract against influenza virus infection. The present study shows a great understanding of the intimate association of S. epidermidis-regulated IFN-lambda induction and serine protease inhibitor in nasal mucosa. Our data demonstrate that S. epidermidis-regulated Serpine1 suppresses the invasion of influenza virus through suppression of airway serine protease at the level of nasal mucosa and impedes IAV spread to the respiratory tract. Thus, human nasal commensalS. epidermidisrepresents a therapeutic potential for treating respiratory viral infections via the change of cellular environment in respiratory tract.
Mitotic activity shapes stage-specific histone modification profiles during Xenopus embryogenesis
Authors: Pokrovsky Daniil , Forné Ignasi , Straub Tobias , Imhof Axel , Rupp Ralph A.W. 
Published: August 2020

SummaryForming an embryo from a zygote poses an apparent conflict for epigenetic regulation. On one hand, the de novo induction of cell fate identities requires the establishment and subsequent maintenance of epigenetic information to harnish developmental gene expression. On the other hand, the embryo depends on cell proliferation, and every round of DNA replication dilutes preexisting histone modifications by incorporation of new unmodified histones into chromatin. Here we investigated the possible relationship between the propagation of epigenetic information and the developmental cell proliferation during Xenopus embryogenesis. We systemically inhibited cell proliferation during the G1/S-transition in gastrula embryos and followed their development until the tadpole stage. Comparing wild-type and cell cycle-arrested embryos, we show that the inhibition of cell proliferation is principally compatible with embryo survival and cellular differentiation. In parallel, we quantified by mass spectrometry the abundance of a large set of histone modification states, which reflects the developmental maturation of the embryonic epigenome. The arrested embryos developed abnormal stage-specific histone modification profiles, in which transcriptionally repressive histone marks were overrepresented. Embryos released from the cell cycle block during neurulation reverted back towards normality on morphological, molecular and epigenetic levels. These results indicate that replicational dilution of histone marks has a strong impact on developmental chromatin maturation. We propose that this influence is strong enough to control developmental decisions, specifically in cell populations that switch between resting and proliferating states such as stem cells.
Impact of COVID-19 Upon Changes in Emergency Room Visits with Chest Pain of Possible Cardiac Origin
Authors: Butt Adeel A. , Kartha Anand , Asaad Nidal , Azad Aftab M. , Bertollini Roberto , Abou-Samra Abdul-Badi 
Published: August 2020

AbstractBackgroundA decrease in Emergency Department (ED) visits for cardiac conditions has recently been reported from the US and Western Europe due to the COVID-19 pandemic. The data are still scant, and the correlation between cardiac symptoms and confirmed diagnoses are not available. There are no reports on changes in ED volumes at a national level, or from countries in the Asia-Middle Eastern region.MethodsWe report data from national referral centers for tertiary care and cardiac care centers in Qatar, which see >80% of cardiac emergencies in the country.ResultsWe analyzed 102,033 ED visits in the COVID-era (March-April 2020 and 2019) and determined the proportion presenting for cardiac symptoms and their confirmed diagnoses. We observed a 16-37% decline in ED volumes overall, with a 25-50% decline in patients presenting with cardiac symptoms in March-April 2020 compared with March-April 2019. Among those presenting with cardiac symptoms, we observed a 24-43% decline in cardiac diagnoses.ConclusionsA sharp decline in patients presenting with cardiac symptoms was observed in the COVID-era. A post-COVID surge in patients with these conditions may be anticipated and preparations should be made to address it.
SCV-2000bp: a primer panel for SARS-CoV-2 full-genome sequencing
Authors: Speranskaya AS , Kaptelova VV , Valdokhina AV , Bulanenko VP , Samoilov AE , Korneenko EV , Shipulina OY , Akimkin VG 
Published: August 2020

ABSTRACTHere we provide technical data for amplifying the complete genome of SARS-CoV-2 from clinical samples using only seventeen pairs of primers. We demonstrate that the СV2000bp primer panel successfully produces genomes when used with the residual total RNA extracts from positive clinical samples following diagnostic RT-PCRs (with Ct in the range from 13 to 20). The library preparation method reported here includes genome amplification of ~1750-2000 bp fragments followed by ultrasonic fragmentation combined with the introduction of Illumina compatible adapters. Using the SCV2000bp panel, 25 complete SARS-CoV-2 virus genome sequences were sequenced from clinical samples of COVID-19 patients from Moscow obtained in late March - early April.
Site-specific targeting of a light activated dCas9-KIllerRed fusion protein generates transient, localized regions of oxidative DNA damage
Authors: House Nealia C.M. , Layer Jacob V. , Price Brendan D. 
Published: August 2020

AbstractDNA repair requires reorganization of the local chromatin structure to facilitate access to and repair of the DNA. Studying DNA double-strand break (DSB) repair in specific chromatin domains has been aided by the use of sequence-specific endonucleases to generate targeted breaks. Here, we describe a new approach that combines KillerRed, a photosensitizer that generates reactive oxygen species (ROS) when exposed to light, and the genome-targeting properties of the CRISPR/Cas9 system. Fusing KillerRed to catalytically inactive Cas9 (dCas9) generates dCas9-KR, which can then be targeted to any desired genomic region with an appropriate guide RNA. Activation of dCas9-KR with green light generates a local increase in reactive oxygen species, resulting in “clustered” oxidative damage, including both DNA breaks and base damage. Activation of dCas9-KR rapidly (within minutes) increases both γH2AX and recruitment of the KU70/80 complex. Importantly, this damage is repaired within 10 minutes of termination of light exposure, indicating that the DNA damage generated by dCas9-KR is both rapid and transient. Further, repair is carried out exclusively through NHEJ, with no detectable contribution from HR-based mechanisms. Surprisingly, sequencing of repaired DNA damage regions did not reveal any increase in either mutations or INDELs in the targeted region, implying that NHEJ has high fidelity under the conditions of low level, limited damage. The dCas9-KR approach for creating targeted damage has significant advantages over the use of endonucleases, since the duration and intensity of DNA damage can be controlled in “real time” by controlling light exposure. In addition, unlike endonucleases that carry out multiple cut-repair cycles, dCas9-KR produces a single burst of damage, more closely resembling the type of damage experienced during acute exposure to reactive oxygen species or environmental toxins. dCas9-KR is a promising system to induce DNA damage and measure site-specific repair kinetics at clustered DNA lesions.