bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternations of interhemispheric functional connectivity in children with strabismus and amblyopia: a resting-state fMRI study
Authors: Peng Jiaxin , Yao Fan , Li Qiuyu , Ge Qianmin , Shi Wenqing , Su Ting , Tang Liying , Pan Yicong , Liang Rongbin , Zhang Lijuan , Shao Yi 
Published: July 2021

AbstractPrevious neuroimaging studies demonstrated that patients with strabismus or amblyopia can show significant functional and anatomical changes in the brain, but alterations of interhemispheric functional connectivity (FC) have not been well studied in this population. The current study analyzed whole-brain changes of interhemispheric FC in children with strabismus and amblyopia (CSA) using voxel-mirrored homotopic connectivity (VMHC).A total of 24 CSA (16 males and 8 females) and 24 normal controls (NCs) consisting of 16 and 8 age-, sex, and education-matched males and females, respectively, underwent functional magnetic resonance imaging (fMRI) scans in the resting state. According to Gaussian random field theory, changes in the resting state FC (rsFC) between hemispheres were evaluated using the VMHC method. The relationships between mean VMHC values in multiple brain regions and behavioral performance were evaluated by Pearson correlation analysis. In contrast to NCs, the CSA group showed significantly decreased VMHC values in the bilateral cerebellum, bilateral frontal superior orbital (frontal sup orb), bilateral temporal inferior(temporal inf),and bilateral frontal superior(frontal sup). CSA have abnormal interhemispheric FC in many brain regions, which may reflect dysfunction of eye movements and visual fusion. These findings might provide insight into the underlying pathogenetic mechanisms of CSA.
Development of a local empirical model of ionospheric total electron content (TEC) and its application for studying solar-ionospheric effects
Authors: Davoudifar Pantea , Tabari Keihanak Rowshan , Shafigh Amir Abbas Eslami , Ajabshirizadeh Ali , Bagheri Zahra , Akbarian Tork Abad Fakhredin , Shayan Milad 
Published: July 2021

AbstractRegular and irregular variations in total electron content (TEC) are one of the most significant observables in ionospheric studies. During the solar cycle 24, the variability of ionosphere is studied using global positioning system derived TEC at a mid-latitude station, Tehran (35.70N, 51.33E). Based on solar radio flux and seasonal and local time-dependent features of TEC values, a semi-empirical model is developed to represent its monthly/hourly mean values. Observed values of TEC and the results of our semi-empirical model then are compared with estimated values of a standard plasmasphere–ionosphere model. The outcome of this model is an expected mean TEC value considering the monthly/hourly regular effects of solar origin. Thus, it is possible to use it for monitoring irregular effects induced by solar events. As a result, the connection of TEC variations with solar activities are studied for the case of coronal mass ejections accompanying extreme solar flares. TEC response to solar flares of class X is well reproduced by this model. Our resulting values show that the most powerful flares (i.e. class X) induce a variation of more than 20 percent in daily TEC extent.
Viability of acellular biologic graft for nipple-areolar complex reconstruction in a non-human primate model
Authors: Caronna Vincent C. , Rosenberg Allison F. , Graham David M. , Heim William M. , Grasperge Brooke F. , Sullivan Scott K. , Chaffin Abigail E. , Bunnell Bruce A. , Pashos Nicholas C. 
Published: July 2021

AbstractMany of the > 3.5 million breast cancer survivors in the US have undergone breast reconstruction following mastectomy. Patients report that nipple-areolar complex (NAC) reconstruction is psychologically important, yet current reconstruction techniques commonly result in inadequate shape, symmetry, and nipple projection. Our team has developed an allogeneic acellular graft for NAC reconstruction (dcl-NAC) designed to be easy to engraft, lasting, and aesthetically pleasing. Here, dcl-NAC safety and host-mediated re-cellularization was assessed in a 6-week study in rhesus macaque non-human primates (NHPs). Human-derived dcl-NACs (n = 30) were engrafted on the dorsum of two adult male NHPs with each animal’s own nipples as controls (n = 4). Weight, complete blood counts, and metabolites were collected weekly. Grafts were removed at weeks 1, 3, or 6 post-engraftment for histology. The primary analysis evaluated health, re-epithelialization, and re-vascularization. Secondary analysis evaluated re-innervation. Weight, complete blood counts, and metabolites remained mostly within normal ranges. A new epidermal layer was observed to completely cover the dcl-NAC surface at week 6 (13–100% coverage, median 93.3%) with new vasculature comparable to controls at week 3 (p = 0.10). Nerves were identified in 75% of dcl-NACs (n = 9/12) at week 6. These data suggest that dcl-NAC is safe and supports host-mediated re-cellularization.
Dietary salt exacerbates intestinal fibrosis in chronic TNBS colitis via fibroblasts activation
Authors: Amamou Asma , Rouland Matthieu , Yaker Linda , Goichon Alexis , Guérin Charlène , Aziz Moutaz , Savoye Guillaume , Marion-Letellier Rachel 
Published: July 2021

AbstractIntestinal fibrosis is a frequent complication in inflammatory bowel diseases (IBD). It is a challenge to identify environmental factors such as diet that may be driving this risk. Intestinal fibrosis result from accumulation of extracellular matrix (ECM) proteins secreted by myofibroblasts. Factors promoting intestinal fibrosis are unknown, but diet appears to be a critical component in its development. Consumption of salt above nutritional recommendations can exacerbate chronic inflammation. So far, high salt diet (HSD) have not been thoroughly investigated in the context of intestinal fibrosis associated to IBD. In the present study, we analyze the role of dietary salt in TNBS chronic colitis induced in rat, an intestinal fibrosis model, or in human colon fibroblast cells. Here, we have shown that high-salt diet exacerbates undernutrition and promoted ECM-associated proteins in fibroblasts. Taken together, our results suggested that dietary salt can activate intestinal fibroblasts, thereby contributing to exacerbation of intestinal fibrosis. Dietary salt may be considered as a putative environmental factor that drives intestinal fibrosis risk.
Psychedelic drug use and schizotypy in young adults
Authors: Lebedev Alexander V. , Acar K. , Garzón B. , Almeida R. , Råback J. , Åberg A. , Martinsson S. , Olsson A. , Louzolo A. , Pärnamets P. , Lövden M. , Atlas L. , Ingvar Martin , Petrovic P. 
Published: July 2021

AbstractDespite recently resurrected scientific interest in classical psychedelics, few studies have focused on potential harms associated with abuse of these substances. In particular, the link between psychedelic use and psychotic symptoms has been debated while no conclusive evidence has been presented. Here, we studied an adult population (n = 1032) with a special focus on young (18–35 years) and healthy individuals (n = 701) to evaluate the association of psychedelic drug use with schizotypy and evidence integration impairment typically observed in psychosis-spectrum disorders. Experimental behavioural testing was performed in a subsample of the subjects (n = 39). We observed higher schizotypy scores in psychedelic users in the total sample. However, the effect size was notably small and only marginally significant when considering young and healthy subjects (Cohen’s d = 0.13). Controlling for concomitant drug use, none of our analyses found significant associations between psychedelic use and schizotypal traits. Results from experimental testing showed that total exposure to psychedelics (frequency and temporal proximity of use) was associated with better evidence integration (Cohen’s d = 0.13) and a higher sensitivity of fear responses (Cohen’s d = 1.05) to the effects instructed knowledge in a reversal aversive learning task modelled computationally with skin conductance response and pupillometry. This effect was present even when controlling for demographics and concomitant drug use. On a group level, however, only difference in sensitivity of fear responses to instructed knowledge reached statistical significance. Taken together, our findings suggest that psychedelic drug use is only weakly associated with psychosis-like symptoms, which, in turn, is to a large extent explained by psychiatric comorbidities and use of other psychoactive substances. Our results also suggest that psychedelics may have an effect on flexibility of evidence integration and aversive learning processes, that may be linked to recently suggested therapeutic effects of psychedelic drugs in non-psychotic psychiatric populations.
Effects of high-intensity training on the quality of life of cancer patients and survivors: a systematic review with meta-analysis
Authors: Lavín-Pérez Ana Myriam , Collado-Mateo Daniel , Mayo Xián , Liguori Gary , Humphreys Liam , Copeland Robert James , Jiménez Alfonso 
Published: July 2021

AbstractCancer and associated medical treatments affect patients' health-related quality of life (HRQoL) by decreasing functional dimensions of physical, social, cognitive, and emotional well-being, while increasing short and late-term symptoms. Exercise, however, is demonstrated to be a useful therapy to improve cancer patients' and survivors’ HRQoL, yet the effectiveness of high-intensity training (HIT) exercise is uncertain. This systematic review and meta-analysis aimed to analyse the effects of HIT on HRQoL dimensions in cancer patients and survivors as well as evaluate the optimal prescription of HIT. The search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) and examined Web of Science and PubMed (Medline) databases. Data were analysed utilizing Review Manager Software. Twenty-two articles were included in the systematic review and 17 in the meta-analysis. Results showed HIT improved global quality of life, physical functioning, role functioning, social functioning, cognitive functioning, fatigue, pain, dyspnea, and insomnia, compared to an inactive control group, yet no differences were found between HIT and low to moderate-intensity exercise interventions. Particular improvements in HRQoL were observed during cancer treatment and with a training duration of more than eight weeks, a frequency of 2 days/week, and a volume of at least 120 min/week, including 15 min or more of HIT. Our findings whilst encouraging, highlight the infancy of the extant evidence base for the role of HIT in the HRQoL of cancer patients and survivors.
Daily steps and healthcare costs in Japanese communities
Authors: Okamoto Shohei , Kamimura Kazuki , Shiraishi Kenichi , Sumita Kazuto , Komamura Kohei , Tsukao Akiko , Chijiki Shoko , Kuno Shinya 
Published: July 2021

AbstractPhysical inactivity is a pandemic that requires intensive, usually costly efforts for risk reduction of related chronic diseases. Nevertheless, it is challenging to determine the effectiveness of physical activity in healthcare cost reduction based on existing literature. Therefore, this study aimed to investigate the impact of physical activity (daily steps) on healthcare costs utilising the data retrieved from a health promotion project (the e-wellness Project, held in three municipalities in Japan). Evaluating the effects of daily steps, measured by pedometers, on healthcare costs by a quasi-experimental approach among participants aged 40–75 years (about 4000 person-years of observation, between 2009 and 2013), we found that a one-step-increase in the annual average daily step reduced outpatient healthcare costs by 16.26 JPY (≒ 0.11 GBD) in the short run. Based on the assumption of a dynamic relationship between the health statuses in multiple years, the long-run effects of daily steps on healthcare costs were estimated at 28.24 JPY (≒ 0.20 GBD). We determined the health benefits of walking in a sample of middle-aged and older Japanese adults by our findings that an increase in step counts reduced healthcare costs.
Identification and physical characterization of a spontaneous mutation of the tobacco mosaic virus in the laboratory environment
Authors: Lumata Jenica L. , Ball Darby , Shahrivarkevishahi Arezoo , Luzuriaga Michael A. , Herbert Fabian C. , Brohlin Olivia , Lee Hamilton , Hagge Laurel M. , D’Arcy Sheena , Gassensmith Jeremiah J. 
Published: July 2021

AbstractVirus-like particles are an emerging class of nano-biotechnology with the Tobacco Mosaic Virus (TMV) having found a wide range of applications in imaging, drug delivery, and vaccine development. TMV is typically produced in planta, and, as an RNA virus, is highly susceptible to natural mutation that may impact its properties. Over the course of 2 years, from 2018 until 2020, our laboratory followed a spontaneous point mutation in the TMV coat protein—first observed as a 30 Da difference in electrospray ionization mass spectrometry (ESI–MS). The mutation would have been difficult to notice by electrophoretic mobility in agarose or SDS-PAGE and does not alter viral morphology as assessed by transmission electron microscopy. The mutation responsible for the 30 Da difference between the wild-type (wTMV) and mutant (mTMV) coat proteins was identified by a bottom-up proteomic approach as a change from glycine to serine at position 155 based on collision-induced dissociation data. Since residue 155 is located on the outer surface of the TMV rod, it is feasible that the mutation alters TMV surface chemistry. However, enzyme-linked immunosorbent assays found no difference in binding between mTMV and wTMV. Functionalization of a nearby residue, tyrosine 139, with diazonium salt, also appears unaffected. Overall, this study highlights the necessity of standard workflows to quality-control viral stocks. We suggest that ESI–MS is a straightforward and low-cost way to identify emerging mutants in coat proteins.
Manipulation of the Tyrosinase gene permits improved CRISPR/Cas editing and neural imaging in cichlid fish
Authors: Li Cheng-Yu , Steighner Joshua R. , Sweatt Garrett , Thiele Tod R. , Juntti Scott A. 
Published: July 2021

AbstractDirect tests of gene function have historically been performed in a limited number of model organisms. The CRISPR/Cas system is species-agnostic, offering the ability to manipulate genes in a range of models, enabling insights into evolution, development, and physiology. Astatotilapia burtoni, a cichlid fish from the rivers and shoreline around Lake Tanganyika, has been extensively studied in the laboratory to understand evolution and the neural control of behavior. Here we develop protocols for the creation of CRISPR-edited cichlids and create a broadly useful mutant line. By manipulating the Tyrosinase gene, which is necessary for eumelanin pigment production, we describe a fast and reliable approach to quantify and optimize gene editing efficiency. Tyrosinase mutants also remove a major obstruction to imaging, enabling visualization of subdermal structures and fluorophores in situ. These protocols will facilitate broad application of CRISPR/Cas9 to studies of cichlids as well as other non-traditional model aquatic species.
Adenosine deaminase modulates metabolic remodeling and orchestrates joint destruction in rheumatoid arthritis
Authors: Bhagavatham Sai Krishna Srimadh , Khanchandani Prakash , Kannan Vishnu , Potikuri Damodaram , Sridharan Divya , Pulukool Sujith Kumar , Naik Ashwin Ashok , Dandamudi Rajesh Babu , Divi Sai Mangala , Pargaonkar Ashish , Ray Rahul , Santha Saibharath Simha Reddy , Seshagiri Polani B. , Narasimhan K. , Gumdal Narsimulu , Sivaramakrishnan Venketesh 
Published: July 2021

AbstractRheumatoid Arthritis (RA) is a chronic autoimmune disease associated with inflammation and joint remodeling. Adenosine deaminase (ADA), a risk factor in RA, degrades adenosine, an anti-inflammatory molecule, resulting in an inflammatory bias. We present an integrative analysis of clinical data, cytokines, serum metabolomics in RA patients and mechanistic studies on ADA-mediated effects on in vitro cell culture models. ADA activity differentiated patients into low and high ADA sets. The levels of the cytokines TNFα, IFNγ, IL-10, TGFβ and sRANKL were elevated in RA and more pronounced in high ADA sets. Serum metabolomic analysis shows altered metabolic pathways in RA which were distinct between low and high ADA sets. Comparative analysis with previous studies shows similar pathways are modulated by DMARDs and biologics. Random forest analysis distinguished RA from control by methyl-histidine and hydroxyisocaproic acid, while hexose-phosphate and fructose-6-phosphate distinguished high ADA from low ADA. The deregulated metabolic pathways of High ADA datasets significantly overlapped with high ADA expressing PBMCs GEO transcriptomics dataset. ADA induced the death of chondrocytes, synoviocyte proliferation, both inflammation in macrophages and their differentiation into osteoclasts and impaired differentiation of mesenchymal stem cells to osteoblasts and mineralization. PBMCs expressing elevated ADA had increased expression of cytokines and P2 receptors compared to synovial macrophages which has low expression of ADA. Our data demonstrates increased cytokine levels and distinct metabolic signatures of RA based on the ADA activity, suggests an important role for ADA in the pathophysiology of RA joints and as a potential marker and therapeutic target in RA patients.
Preexisting heart failure with reduced ejection fraction attenuates renal fibrosis after ischemia reperfusion via sympathetic activation
Authors: Matsuura Ryo , Yamashita Tetsushi , Hayase Naoki , Hamasaki Yoshifumi , Noiri Eisei , Numata Genri , Takimoto Eiki , Nangaku Masaomi , Doi Kent 
Published: July 2021

AbstractAlthough chronic heart failure is clinically associated with acute kidney injury (AKI), the precise mechanism that connects kidney and heart remains unknown. Here, we elucidate the effect of pre-existing heart failure with reduced ejection fraction (HFrEF) on kidney via sympathetic activity, using the combining models of transverse aortic constriction (TAC) and unilateral renal ischemia reperfusion (IR). The evaluation of acute (24 h) and chronic (2 weeks) phases of renal injury following IR 8 weeks after TAC in C57BL/6 mice revealed that the development of renal fibrosis in chronic phase was significantly attenuated in TAC mice, but not in non-TAC mice, whereas no impact of pre-existing heart failure was observed in acute phase of renal IR. Expression of transforming growth factor-β, monocyte chemoattractant protein-1, and macrophage infiltration were significantly reduced in TAC mice. Lastly, to investigate the effect of sympathetic nerve activity, we performed renal sympathetic denervation two days prior to renal IR, which abrogated attenuation of renal fibrosis in TAC mice. Collectively, we demonstrate the protective effect of pre-existing HFrEF on long-term renal ischemic injury. Renal sympathetic nerve may contribute to this protection; however, further studies are needed to fully clarify the comprehensive mechanisms associated with attenuated renal fibrosis and pre-existing HFrEF.
Induction of cryptic pre-mRNA splice-switching by antisense oligonucleotides
Authors: Ham Kristin A. , Keegan Niall P. , McIntosh Craig S. , Aung-Htut May T. , Zaw Khine , Greer Kane , Fletcher Sue , Wilton Steve D. 
Published: July 2021

AbstractAntisense oligomers (AOs) are increasingly being used to modulate RNA splicing in live cells, both for research and for the development of therapeutics. While the most common intended effect of these AOs is to induce skipping of whole exons, rare examples are emerging of AOs that induce skipping of only part of an exon, through activation of an internal cryptic splice site. In this report, we examined seven AO-induced cryptic splice sites in six genes. Five of these cryptic splice sites were discovered through our own experiments, and two originated from other published reports. We modelled the predicted effects of AO binding on the secondary structure of each of the RNA targets, and how these alterations would in turn affect the accessibility of the RNA to splice factors. We observed that a common predicted effect of AO binding was disruption of the exon definition signal within the exon’s excluded segment.
Laboratory evolution of Mycobacterium on agar plates for analysis of resistance acquisition and drug sensitivity profiles
Authors: Maeda Tomoya , Kawada Masako , Sakata Natsue , Kotani Hazuki , Furusawa Chikara 
Published: July 2021

AbstractDrug-resistant tuberculosis (TB) is a growing public health problem. There is an urgent need for information regarding cross-resistance and collateral sensitivity relationships among drugs and the genetic determinants of anti-TB drug resistance for developing strategies to suppress the emergence of drug-resistant pathogens. To identify mutations that confer resistance to anti-TB drugs in Mycobacterium species, we performed the laboratory evolution of nonpathogenic Mycobacterium smegmatis, which is closely related to Mycobacterium tuberculosis, against ten anti-TB drugs. Next, we performed whole-genome sequencing and quantified the resistance profiles of each drug-resistant strain against 24 drugs. We identified the genes with novel meropenem (MP) and linezolid (LZD) resistance-conferring mutation, which also have orthologs, in M. tuberculosis H37Rv. Among the 240 possible drug combinations, we identified 24 pairs that confer cross-resistance and 18 pairs that confer collateral sensitivity. The acquisition of bedaquiline or linezolid resistance resulted in collateral sensitivity to several drugs, while the acquisition of MP resistance led to multidrug resistance. The MP-evolved strains showed cross-resistance to rifampicin and clarithromycin owing to the acquisition of a mutation in the intergenic region of the Rv2864c ortholog, which encodes a penicillin-binding protein, at an early stage. These results provide a new insight to tackle drug-resistant TB.
Signal envelope and speech intelligibility differentially impact auditory motion perception
Authors: Warnecke Michaela , Litovsky Ruth Y. 
Published: July 2021

AbstractOur acoustic environment contains a plethora of complex sounds that are often in motion. To gauge approaching danger and communicate effectively, listeners need to localize and identify sounds, which includes determining sound motion. This study addresses which acoustic cues impact listeners’ ability to determine sound motion. Signal envelope (ENV) cues are implicated in both sound motion tracking and stimulus intelligibility, suggesting that these processes could be competing for sound processing resources. We created auditory chimaera from speech and noise stimuli and varied the number of frequency bands, effectively manipulating speech intelligibility. Normal-hearing adults were presented with stationary or moving chimaeras and reported perceived sound motion and content. Results show that sensitivity to sound motion is not affected by speech intelligibility, but shows a clear difference for original noise and speech stimuli. Further, acoustic chimaera with speech-like ENVs which had intelligible content induced a strong bias in listeners to report sounds as stationary. Increasing stimulus intelligibility systematically increased that bias and removing intelligible content reduced it, suggesting that sound content may be prioritized over sound motion. These findings suggest that sound motion processing in the auditory system can be biased by acoustic parameters related to speech intelligibility.