bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide gene-environment interactions in neuroticism: an exploratory study across 25 environments
Authors: Werme Josefin , van der Sluis Sophie , Posthuma Danielle , de Leeuw Christiaan A. 
Published: March 2021

AbstractGene-environment interactions (GxE) are often suggested to play an important role in the aetiology of psychiatric phenotypes, yet so far, only a handful of genome-wide environment interaction studies (GWEIS) of psychiatric phenotypes have been conducted. Representing the most comprehensive effort of its kind to date, we used data from the UK Biobank to perform a series of GWEIS for neuroticism across 25 broadly conceptualised environmental risk factors (trauma, social support, drug use, physical health). We investigated interactions on the level of SNPs, genes, and gene-sets, and computed interaction-based polygenic risk scores (PRS) to predict neuroticism in an independent sample subset (N = 10,000). We found that the predictive ability of the interaction-based PRSs did not significantly improve beyond that of a traditional PRS based on SNP main effects from GWAS, but detected one variant and two gene-sets showing significant interaction signal after correction for the number of analysed environments. This study illustrates the possibilities and limitations of a comprehensive GWEIS in currently available sample sizes.
The release of toxic oligomers from α-synuclein fibrils induces dysfunction in neuronal cells
Authors: Cascella Roberta , Chen Serene W. , Bigi Alessandra , Camino José D. , Xu Catherine K. , Dobson Christopher M. , Chiti Fabrizio , Cremades Nunilo , Cecchi Cristina 
Published: March 2021

AbstractThe self-assembly of α-synuclein (αS) into intraneuronal inclusion bodies is a key characteristic of Parkinson’s disease. To define the nature of the species giving rise to neuronal damage, we have investigated the mechanism of action of the main αS populations that have been observed to form progressively during fibril growth. The αS fibrils release soluble prefibrillar oligomeric species with cross-β structure and solvent-exposed hydrophobic clusters. αS prefibrillar oligomers are efficient in crossing and permeabilize neuronal membranes, causing cellular insults. Short fibrils are more neurotoxic than long fibrils due to the higher proportion of fibrillar ends, resulting in a rapid release of oligomers. The kinetics of released αS oligomers match the observed kinetics of toxicity in cellular systems. In addition to previous evidence that αS fibrils can spread in different brain areas, our in vitro results reveal that αS fibrils can also release oligomeric species responsible for an immediate dysfunction of the neurons in the vicinity of these species.
Learned spectral decoloring enables photoacoustic oximetry
Authors: Gröhl Janek , Kirchner Thomas , Adler Tim J. , Hacker Lina , Holzwarth Niklas , Hernández-Aguilera Adrián , Herrera Mildred A. , Santos Edgar , Bohndiek Sarah E. , Maier-Hein Lena 
Published: March 2021

AbstractThe ability of photoacoustic imaging to measure functional tissue properties, such as blood oxygenation sO$$_2$$

2

, enables a wide variety of possible applications. sO$$_2$$

2

can be computed from the ratio of oxyhemoglobin HbO$$_2$$

2

and deoxyhemoglobin Hb, which can be distuinguished by multispectral photoacoustic imaging due to their distinct wavelength-dependent absorption. However, current methods for estimating sO$$_2$$

2

yield inaccurate results in realistic settings, due to the unknown and wavelength-dependent influence of the light fluence on the signal. In this work, we propose learned spectral decoloring to enable blood oxygenation measurements to be inferred from multispectral photoacoustic imaging. The method computes sO$$_2$$

2

pixel-wise, directly from initial pressure spectra $$S_{\text {p}_0}(\lambda , \mathbf {x})$$

S

p
0

(
λ
,
x
)

, which represent initial pressure values at a fixed spatial location $$\mathbf {x}$$
x
over all recorded wavelengths $$\lambda$$
λ
. The method is compared to linear unmixing approaches, as well as pO$$_2$$

2

and blood gas analysis reference measurements. Experimental results suggest that the proposed method is able to obtain sO$$_2$$

2

estimates from multispectral photoacoustic measurements in silico, in vitro, and in vivo.
Clinical outcomes of endoscopic resection of preoperatively diagnosed non-circumferential T1a-muscularis mucosae or T1b-submucosa 1 esophageal squamous cell carcinoma
Authors: Namikawa Ken , Yoshio Toshiyuki , Yoshimizu Shoichi , Ishiyama Akiyoshi , Tsuchida Tomohiro , Tokai Yoshitaka , Horiuchi Yusuke , Hirasawa Toshiaki , Fujisaki Junko 
Published: March 2021

AbstractIn Japan, preoperatively diagnosed T1a-muscularis mucosae or T1b-submucosa 1 (MM/SM1) esophageal squamous cell carcinoma (ESCC) is a relative indication for endoscopic resection (ER). We evaluated long-term outcomes in patients after ER for non-circumferential ESCC with a preoperative diagnosis of MM/SM1 invasion. We retrospectively reviewed 66 patients with a preoperative diagnosis of non-circumferential MM/SM1 ESCC endoscopically resected between 2010 and 2015. Patients were divided into low- (adequate follow-up) and high-risk (requiring additional treatment) groups for lymph node metastasis according to risk factors (submucosal invasion, lymphovascular invasion, or droplet infiltration) and long-term outcomes were analyzed. Pathological invasion to T1a-lamina propria mucosa, MM/SM1, and T1b-SM2 was seen in 22, 38, and 6 lesions, respectively. Overall, 71.2% patients were classified into the “adequate follow-up” group. Of these, only one patient had a lymph node recurrence, which was successfully treated by additional therapy. The remaining 28.8% patients were classified into the “requiring additional treatment” group, where no recurrences were observed after additional treatments. After a median follow-up of 58.6 months, no deaths happened due to ESCC. The 3- and 5-year overall survival rates were 93.6% and 88.7%, respectively. ER is a valid initial treatment for non-circumferential ESCC with preoperatively diagnosed MM/SM1 invasion.
Optical signatures of radiofrequency ablation in biological tissues
Authors: Lanka Pranav , Francis Kalloor Joseph , Kruit Hindrik , Farina Andrea , Cubeddu Rinaldo , Sekar Sanathana Konugolu Venkata , Manohar Srirang , Pifferi Antonio 
Published: March 2021

AbstractAccurate monitoring of treatment is crucial in minimally-invasive radiofrequency ablation in oncology and cardiovascular disease. We investigated alterations in optical properties of ex-vivo bovine tissues of the liver, heart, muscle, and brain, undergoing the treatment. Time-domain diffuse optical spectroscopy was used, which enabled us to disentangle and quantify absorption and reduced scattering spectra. In addition to the well-known global (1) decrease in absorption, and (2) increase in reduced scattering, we uncovered new features based on sensitive detection of spectral changes. These absorption spectrum features are: (3) emergence of a peak around 840 nm, (4) redshift of the 760 nm deoxyhemoglobin peak, and (5) blueshift of the 970 nm water peak. Treatment temperatures above 100 °C led to (6) increased absorption at shorter wavelengths, and (7) further decrease in reduced scattering. This optical behavior provides new insights into tissue response to thermal treatment and sets the stage for optical monitoring of radiofrequency ablation.
Metabolomics analysis of follicular fluid coupled with oocyte aspiration reveals importance of glucocorticoids in primate periovulatory follicle competency
Authors: Ravisankar Sweta , Hanna Carol B. , Brooks Kelsey E. , Murphy Melinda J. , Redmayne Nash , Ryu Junghyun , Kinchen Jason M. , Chavez Shawn L. , Hennebold Jon D. 
Published: March 2021

AbstractGonadotropin administration during infertility treatment stimulates the growth and development of multiple ovarian follicles, yielding heterogeneous oocytes with variable capacity for fertilization, cleavage, and blastocyst formation. To determine how the intrafollicular environment affects oocyte competency, 74 individual rhesus macaque follicles were aspirated and the corresponding oocytes classified as failed to cleave, cleaved but arrested prior to blastulation, or those that formed blastocysts following in vitro fertilization. Metabolomics analysis of the follicular fluid (FF) identified 60 unique metabolites that were significantly different between embryo classifications, of which a notable increase in the intrafollicular ratio of cortisol to cortisone was observed in the blastocyst group. Immunolocalization of the glucocorticoid receptor (GR, NR3C1) revealed translocation from the cytoplasm to nucleus with oocyte maturation in vitro and, correlation to intrafollicular expression of the 11-hydroxy steroid dehydrogenases that interconvert these glucocorticoids was detected upon an ovulatory stimulus in vivo. While NR3C1 knockdown in oocytes had no effect on their maturation or fertilization, expansion of the associated cumulus granulosa cells was inhibited. Our findings indicate an important role for NR3C1 in the regulation of follicular processes via paracrine signaling. Further studies are required to define the means through which the FF cortisol:cortisone ratio determines oocyte competency.
Multi-frequency impedance sensing for detection and sizing of DNA fragments
Authors: Sui Jianye , Gandotra Neeru , Xie Pengfei , Lin Zhongtian , Scharfe Curt , Javanmard Mehdi 
Published: March 2021

AbstractElectronic biosensors for DNA detection typically utilize immobilized oligonucleotide probes on a signal transducer, which outputs an electronic signal when target molecules bind to probes. However, limitation in probe selectivity and variable levels of non-target material in complex biological samples can lead to nonspecific binding and reduced sensitivity. Here we introduce the integration of 2.8 μm paramagnetic beads with DNA fragments. We apply a custom-made microfluidic chip to detect DNA molecules bound to beads by measuring Impedance Peak Response (IPR) at multiple frequencies. Technical and analytical performance was evaluated using beads containing purified Polymerase Chain Reaction (PCR) products of different lengths (157, 300, 613 bp) with DNA concentration ranging from 0.039 amol to 7.8 fmol. Multi-frequency IPR correlated positively with DNA amounts and was used to calculate a DNA quantification score. The minimum DNA amount of a 300 bp fragment coupled on beads that could be robustly detected was 0.0039 fmol (1.54 fg or 4750 copies/bead). Additionally, our approach allowed distinguishing beads with similar molar concentration DNA fragments of different lengths. Using this impedance sensor, purified PCR products could be analyzed within ten minutes to determine DNA fragment length and quantity based on comparison to a known DNA standard.
Raman spectroscopy and artificial intelligence to predict the Bayesian probability of breast cancer
Authors: Kothari Ragini , Jones Veronica , Mena Dominique , Bermúdez Reyes Viviana , Shon Youkang , Smith Jennifer P. , Schmolze Daniel , Cha Philip D. , Lai Lily , Fong Yuman , Storrie-Lombardi Michael C. 
Published: March 2021

AbstractThis study addresses the core issue facing a surgical team during breast cancer surgery: quantitative prediction of tumor likelihood including estimates of prediction error. We have previously reported that a molecular probe, Laser Raman spectroscopy (LRS), can distinguish healthy and tumor tissue. We now report that combining LRS with two machine learning algorithms, unsupervised k-means and stochastic nonlinear neural networks (NN), provides rapid, quantitative, probabilistic tumor assessment with real-time error analysis. NNs were first trained on Raman spectra using human expert histopathology diagnostics as gold standard (74 spectra, 5 patients). K-means predictions using spectral data when compared to histopathology produced clustering models with 93.2–94.6% accuracy, 89.8–91.8% sensitivity, and 100% specificity. NNs trained on k-means predictions generated probabilities of correctness for the autonomous classification. Finally, the autonomous system characterized an extended dataset (203 spectra, 8 patients). Our results show that an increase in DNA|RNA signal intensity in the fingerprint region (600–1800 cm−1) and global loss of high wavenumber signal (2800–3200 cm−1) are particularly sensitive LRS warning signs of tumor. The stochastic nature of NNs made it possible to rapidly generate multiple models of target tissue classification and calculate the inherent error in the probabilistic estimates for each target.
Intra-arterial transplantation of stem cells in large animals as a minimally-invasive strategy for the treatment of disseminated neurodegeneration
Authors: Malysz-Cymborska Izabela , Golubczyk Dominika , Kalkowski Lukasz , Kwiatkowska Joanna , Zawadzki Michal , Głodek Joanna , Holak Piotr , Sanford Joanna , Milewska Kamila , Adamiak Zbigniew , Walczak Piotr , Janowski Miroslaw 
Published: March 2021

AbstractStem cell transplantation proved promising in animal models of neurological diseases; however, in conditions with disseminated pathology such as ALS, delivery of cells and their broad distribution is challenging. To address this problem, we explored intra-arterial (IA) delivery route, of stem cells. The goal of this study was to investigate the feasibility and safety of MRI-guided transplantation of glial restricted precursors (GRPs) and mesenchymal stem cells (MSCs) in dogs suffering from ALS-like disease, degenerative myelopathy (DM). Canine GRP transplantation in dogs resulted in rather poor retention in the brain, so MSCs were used in subsequent experiments. To evaluate the safety of MSC intraarterial transplantation, naïve pigs (n = 3) were used as a pre-treatment control before transplantation in dogs. Cells were labeled with iron oxide nanoparticles. For IA transplantation a 1.2-French microcatheter was advanced into the middle cerebral artery under roadmap guidance. Then, the cells were transplanted under real-time MRI with the acquisition of dynamic T2*-weighted images. The procedure in pigs has proven to be safe and histopathology has demonstrated the successful and predictable placement of transplanted porcine MSCs. Transplantation of canine MSCs in DM dogs resulted in their accumulation in the brain. Interventional and follow-up MRI proved the procedure was feasible and safe. Analysis of gene expression after transplantation revealed a reduction of inflammatory factors, which may indicate a promising therapeutic strategy in the treatment of neurodegenerative diseases.
Effects of acute heat stress on protein expression and histone modification in the adrenal gland of male layer-type country chickens
Authors: Zheng Hao-Teng , Zhuang Zi-Xuan , Chen Chao-Jung , Liao Hsin-Yi , Chen Hung-Lin , Hsueh Huang-Chun , Chen Chih-Feng , Chen Shuen-Ei , Huang San-Yuan 
Published: March 2021

AbstractThe adrenal gland responds to heat stress by epinephrine and glucocorticoid release to alleviate the adverse effects. This study investigated the effect of acute heat stress on the protein profile and histone modification in the adrenal gland of layer-type country chickens. A total of 192 roosters were subject to acute heat stress and thereafter classified into a resistant or susceptible group according to body temperature change. The iTRAQ analysis identified 80 differentially expressed proteins, in which the resistant group had a higher level of somatostatin and hydroxy-δ-5-steroid dehydrogenase but a lower parathymosin expression in accordance with the change of serum glucocorticoid levels. Histone modification analysis identified 115 histone markers. The susceptible group had a higher level of tri-methylation of histone H3 lysine 27 (H3K27me3) and showed a positive crosstalk with K36me and K37me in the H3 tails. The differential changes of body temperature projected in physiological regulation at the hypothalamus–pituitary–adrenal axis suggest the genetic heterogeneity in basic metabolic rate and efficiency for heat dissipation to acclimate to thermal stress and maintain body temperature homeostasis. The alteration of adrenal H3K27me3 level was associated with the endocrine function of adrenal gland and may contribute to the thermotolerance of chickens.
Puerarin enhances intestinal function in piglets infected with porcine epidemic diarrhea virus
Authors: Wu Mengjun , Yi Dan , Zhang Qian , Wu Tao , Yu Kui , Peng Meng , Wang Lei , Zhao Di , Hou Yongqing , Wu Guoyao 
Published: March 2021

AbstractPuerarin has been reported to be an excellent antioxidant, anti-inflammatory and antimicrobial agent, but the potential effect of puerarin on porcine epidemic diarrhea virus (PEDV) is unclear. This study aimed to determine whether puerarin could alleviate intestinal injury in piglets infected with PEDV. A PEDV (Yunnan province strain) infection model was applied to 7-day-old piglets at 104.5 TCID50 (50% tissue culture infectious dose). Piglets were orally administered with puerarin at the dosage of 0.5 mg/kg body weight from day 5 to day 9. On day 9 of the trial, piglets were inoculated orally with PEDV. Three days later, jugular vein blood and intestinal samples were collected. Results showed puerarin reduced morbidity of piglets infected with PEDV. In addition, puerarin reduced the activities of aspartate aminotransferase and alkaline phosphatase, the ratio of serum aspartate aminotransferase to serum alanine aminotransferase, the number of white blood cells and neutrophils, and the plasma concentrations of interleukin-6, interleukin-8 and tumor necrosis factor-α, as well as protein abundances of heat shock protein-70 in PEDV-infected piglets. Moreover, puerarin increased D-xylose concentration but decreased intestinal fatty acid-binding protein concentration and diamine oxidase activity in the plasma of piglets infected with PEDV. Puerarin increased the activities of total superoxide dismutase, glutathione peroxidase and catalase, while decreasing the activities of myeloperoxidase and concentration of hydrogen peroxide in both the intestine and plasma of PEDV-infected piglets. Puerarin decreased mRNA levels of glutathione S-transferase omega 2 but increased the levels of nuclear factor erythroid 2-related factor 2. Furthermore, puerarin increased the abundance of total eubacteria (16S rRNA), Enterococcus genus, Lactobacillus genus and Enterobacteriaceae family in the intestine, but reduced the abundance of Clostridium coccoides in the caecum. These data indicate puerarin improved intestinal function in piglets infected by PEDV and may be a promising supplement for the prevention of PEDV infection.
Scarcity of scale-free topology is universal across biochemical networks
Authors: Smith Harrison B. , Kim Hyunju , Walker Sara I. 
Published: March 2021

AbstractBiochemical reactions underlie the functioning of all life. Like many examples of biology or technology, the complex set of interactions among molecules within cells and ecosystems poses a challenge for quantification within simple mathematical objects. A large body of research has indicated many real-world biological and technological systems, including biochemistry, can be described by power-law relationships between the numbers of nodes and edges, often described as “scale-free”. Recently, new statistical analyses have revealed true scale-free networks are rare. We provide a first application of these methods to data sampled from across two distinct levels of biological organization: individuals and ecosystems. We analyze a large ensemble of biochemical networks including networks generated from data of 785 metagenomes and 1082 genomes (sampled from the three domains of life). The results confirm no more than a few biochemical networks are any more than super-weakly scale-free. Additionally, we test the distinguishability of individual and ecosystem-level biochemical networks and show there is no sharp transition in the structure of biochemical networks across these levels of organization moving from individuals to ecosystems. This result holds across different network projections. Our results indicate that while biochemical networks are not scale-free, they nonetheless exhibit common structure across different levels of organization, independent of the projection chosen, suggestive of shared organizing principles across all biochemical networks.
Synchrony and multimodality in the timing of Atlantic salmon smolt migration in two Norwegian fjords
Authors: Bjerck Helge B. , Urke Henning A. , Haugen Thrond O. , Alfredsen Jo Arve , Ulvund John Birger , Kristensen Torstein 
Published: March 2021

AbstractThe timing of the smolt migration of Atlantic salmon (Salmo salar) is a phenological trait increasingly important to the fitness of this species. Understanding when and how smolts migrate to the sea is crucial to understanding how salmon populations will be affected by both climate change and the elevated salmon lice concentrations produced by salmon farms. Here, acoustic telemetry was used to monitor the fjord migration of wild post-smolts from four rivers across two fjord systems in western Norway. Smolts began their migration throughout the month of May in all populations. Within-population, the timing of migration was multimodal with peaks in migration determined by the timing of spring floods. As a result, migrations were synchronized across populations with similar hydrology. There was little indication that the timing of migration had an impact on survival from the river mouth to the outer fjord. However, populations with longer fjord migrations experienced lower survival rates and had higher variance in fjord residency times. Explicit consideration of the multimodality inherent to the timing of smolt migration in these populations may help predict when smolts are in the fjord, as these modes seem predictable from available environmental data.
Single dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice
Authors: Jasperse Brittany , O’Connell Caitlin M. , Wang Yuxiang , Verardi Paulo H. 
Published: March 2021

AbstractZika virus (ZIKV), a flavivirus transmitted primarily by infected mosquitos, can cause neurological symptoms such as Guillian–Barré syndrome and microcephaly. We developed several vaccinia virus (VACV) vaccine candidates for ZIKV based on replication-inducible VACVs (vINDs) expressing ZIKV pre-membrane (prM) and envelope (E) proteins (vIND-ZIKVs). These vIND-ZIKVs contain elements of the tetracycline operon and replicate only in the presence of tetracyclines. The pool of vaccine candidates was narrowed to one vIND-ZIKV containing a novel mutation in the signal peptide of prM that led to higher expression and secretion of E and production of virus-like particles, which was then tested for safety, immunogenicity, and efficacy in mice. vIND-ZIKV grows to high titers in vitro in the presence of doxycycline (DOX) but is replication-defective in vivo in the absence of DOX, causing no weight loss in mice. C57BL/6 mice vaccinated once with vIND-ZIKV in the absence of DOX (as a replication-defective virus) developed robust levels of E-peptide-specific IFN-γ-secreting splenocytes and anti-E IgG titers, with modest levels of serum-neutralizing antibodies. Vaccinated mice treated with anti-IFNAR1 antibody were completely protected from ZIKV viremia post-challenge after a single dose of vIND-ZIKV. Furthermore, mice with prior immunity to VACV developed moderate anti-E IgG titers that increased after booster vaccination, and were protected from viremia only after two vaccinations with vIND-ZIKV.