bluuebunny/crossref_metadata_2025 huggingface dataset:
Single cell RNA sequencing uncovers cellular developmental sequences and novel potential intercellular communications in embryonic kidney
Authors: Matsui Isao , Matsumoto Ayumi , Inoue Kazunori , Katsuma Yusuke , Yasuda Seiichi , Shimada Karin , Sakaguchi Yusuke , Mizui Masayuki , Kaimori Jun-ya , Takabatake Yoshitsugu , Isaka Yoshitaka
Published: January 2021

Kidney development requires the coordinated growth and differentiation of multiple cells. Despite recent single cell profiles in nephrogenesis research, tools for data analysis are rapidly developing, and offer an opportunity to gain additional insight into kidney development. In this study, single-cell RNA sequencing data obtained from embryonic mouse kidney were re-analyzed. Manifold learning based on partition-based graph-abstraction coordinated cells, reflecting their expected lineage relationships. Consequently, the coordination in combination with ForceAtlas2 enabled the inference of parietal epithelial cells of Bowman’s capsule and the inference of cells involved in the developmental process from the S-shaped body to each nephron segment. RNA velocity suggested developmental sequences of proximal tubules and podocytes. In combination with a Markov chain algorithm, RNA velocity suggested the self-renewal processes of nephron progenitors. NicheNet analyses suggested that not only cells belonging to ureteric bud and stroma, but also endothelial cells, macrophages, and pericytes may contribute to the differentiation of cells from nephron progenitors. Organ culture of embryonic mouse kidney demonstrated that nerve growth factor, one of the nephrogenesis-related factors inferred by NicheNet, contributed to mitochondrial biogenesis in developing distal tubules. These approaches suggested previously unrecognized aspects of the underlying mechanisms for kidney development.
Acute systemic loss of Mad2 leads to intestinal atrophy in adult mice
Authors: Schukken Klaske M. , Zhu Yinan , Bakker Petra L. , Koster Mirjam H. , Harkema Liesbeth , Youssef Sameh A. , de Bruin Alain , Foijer Floris
Published: January 2021

Chromosomal instability (CIN) is a hallmark of cancer, leading to aneuploid cells. To study the role that CIN plays in tumor evolution, several mouse models have been engineered over the last 2 decades. These models have unequivocally shown that systemic high-grade CIN is embryonic lethal. We and others have previously shown that embryonic lethality can be circumvented by provoking CIN in a tissue-specific fashion. In this study, we provoke systemic high-grade CIN in adult mice as an alternative to circumvent embryonic lethality. For this, we disrupt the spindle assembly checkpoint (SAC) by alleviating Mad2 or truncating Mps1, both essential genes for SAC functioning, with or without p53 inactivation. We find that disruption of the SAC leads to rapid villous atrophy, atypia and apoptosis of the epithelia of the jejunum and ileum, substantial weight loss, and death within 2–3 weeks after the start of the CIN insult. Despite this severe intestinal phenotype, most other tissues are unaffected, except for minor abnormalities in spleen, presumably due to the lower proliferation rate in these tissues. We conclude that high-grade CIN in vivo in adult mice is most toxic to the high cell turnover intestinal epithelia.
The effects of anticholinergic medications on cognition in children: a systematic review and meta-analysis
Authors: Ghezzi Erica , Chan Michelle , Kalisch Ellett Lisa M. , Ross Tyler J. , Richardson Kathryn , Ho Jun Ni , Copley Dayna , Steele Claire , Keage Hannah A. D.
Published: January 2021

Cognitive side effects of anticholinergic medications in older adults are well documented. Whether these poor cognitive outcomes are observed in children has not been systematically investigated. We aimed to conduct a systematic review and meta-analysis on the associations between anticholinergic medication use and cognitive performance in children. Systematic review was conducted using Medline, PsychInfo, and Embase, identifying studies testing cognitive performance relative to the presence versus absence of anticholinergic medication(s) in children. We assessed effects overall, as well as relative to drug class, potency (low and high), cognitive domain, and duration of administration. The systematic search identified 46 articles suitable for meta-analysis. For the most part, random effects meta-analyses did not identify statistically significant associations between anticholinergic exposure and cognitive performance in children; the one exception was a small effect of anticholinergic anti-depressants being associated with better cognitive function (Hedges’ g = 0.24, 95% CI 0.06–0.42, p = 0.01). Anticholinergic medications do not appear to be associated with poor cognitive outcomes in children, as they do in older adults. The discrepancy in findings with older adults may be due to shorter durations of exposure in children, differences in study design (predominantly experimental studies in children rather than predominantly epidemiological in older adults), biological ageing (e.g. blood brain barrier integrity), along with less residual confounding due to minimal polypharmacy and comorbidity in children.
Factors associated with measles resurgence in the United States in the post-elimination era
Authors: Dimala Christian Akem , Kadia Benjamin Momo , Nji Miriam Aiwokeh Mbong , Bechem Ndemazie Nkafu
Published: January 2021

There have been growing concerns of a potential re-establishment of measles transmission in the United States (US) in the years to come. This study aims to explore potential factors underlying the resurgence of measles in the US by objectively assessing the associations between annual incidence rates (AIR), case importation, vaccination status and disease outbreaks. Data on measles transmission between January 1st, 2001 and December 31st, 2019 were obtained from the national centres for disease control and prevention (CDC) surveillance databases and other published reports. Changes in incidence rates over time were assessed by binomial regression models. Of the 3874 cases of measles in the US over the study period, 3506 (90.5%, 95% CI: 89.5–91.4) occurred in US residents. The AIR per million population in US residents over this period was 0.60 (95% CI: 0.59–0.61), with an overall significant increase over time (p = 0.011). The median percentage of imported and vaccinated cases were 36% [17.9–46.6] and 15% [12.1–23.2] respectively. There was a significant decrease in the percentage of imported cases (p < 0.001) but not of vaccinated cases (p = 0.159) over time. There was a moderate and weak negative correlation between the AIR and the percentage of imported and vaccinated cases respectively (r = –0.59 and r = –0.27 respectively). On multiple linear regression there was a significant linear association between the AIR and the number of outbreaks (p = 0.003) but not with the percentage of imported cases (p = 0.436) and vaccinated cases (p = 0.692), R2 = 0.73. Strong negative and positive correlations were seen between the number of outbreaks and the percentage of imported cases (r = –0.61) and the of number states affected (r = 0.88) respectively. Despite the overall reduction in the percentage of imported cases of measles over the past two decades, pockets of internal transmission of the disease following importation via increasing number of outbreaks in unvaccinated subpopulations, reinforced by vaccine hesitancy, account for the sustained increase in measles incidence rates in the US. Controlling indigenous transmission through efficient vaccination coverage in at-risk subpopulations and among international US travellers, improved disease surveillance and rapid outbreak containment are essential in curbing the measles resurgence.
Analysis of human mitochondrial genome co-occurrence networks of Asian population at varying altitudes
Authors: Verma Rahul K. , Kalyakulina Alena , Giuliani Cristina , Shinde Pramod , Kachhvah Ajay Deep , Ivanchenko Mikhail , Jalan Sarika
Published: January 2021

Networks have been established as an extremely powerful framework to understand and predict the behavior of many large-scale complex systems. We studied network motifs, the basic structural elements of networks, to describe the possible role of co-occurrence of genomic variations behind high altitude adaptation in the Asian human population. Mitochondrial DNA (mtDNA) variations have been acclaimed as one of the key players in understanding the biological mechanisms behind adaptation to extreme conditions. To explore the cumulative effects of variations in the mitochondrial genome with the variation in the altitude, we investigated human mt-DNA sequences from the NCBI database at different altitudes under the co-occurrence motifs framework. Analysis of the co-occurrence motifs using similarity clustering revealed a clear distinction between lower and higher altitude regions. In addition, the previously known high altitude markers 3394 and 7697 (which are definitive sites of haplogroup M9a1a1c1b) were found to co-occur within their own gene complexes indicating the impact of intra-genic constraint on co-evolution of nucleotides. Furthermore, an ancestral ‘RSRS50’ variant 10,398 was found to co-occur only at higher altitudes supporting the fact that a separate route of colonization at these altitudes might have taken place. Overall, our analysis revealed the presence of co-occurrence interactions specific to high altitude at a whole mitochondrial genome level. This study, combined with the classical haplogroups analysis is useful in understanding the role of co-occurrence of mitochondrial variations in high altitude adaptation.
Substrate induced electronic phase transitions of CrI$$_{3}$$ based van der Waals heterostructures
Authors: Chakraborty Shamik , Ravikumar Abhilash
Published: January 2021

We perform first principle density functional theory calculations to predict the substrate induced electronic phase transitions of CrI$$_{3}$$

3

based 2-D heterostructures. We adsorb graphene and MoS$$_{2}$$

2

on novel 2-D ferromagnetic semiconductor—CrI$$_{3}$$

3

and investigate the electronic and magnetic properties of these heterostructures with and without spin orbit coupling (SOC). We find that when strained MoS$$_{2}$$

2

is adsorbed on CrI$$_{3}$$

3

, the spin dependent band gap which is a characteristic of CrI$$_{3}$$

3

, ceases to remain. The bandgap of the heterostructure reduces drastically ($$\sim$$
∼
70%) and the heterostructure shows an indirect, spin-independent bandgap of $$\sim$$
∼
0.5 eV. The heterostructure remains magnetic (with and without SOC) with the magnetic moment localized primarily on CrI$$_{3}$$

3

. Adsorption of graphene on CrI$$_{3}$$

3

induces an electronic phase transition of the subsequent heterostructure to a ferromagnetic metal in both the spin configurations with magnetic moment localized on CrI$$_{3}$$

3

. The SOC induced interaction opens a bandgap of $$\sim$$
∼
30 meV in the Dirac cone of graphene, which allows us to visualize Chern insulating states without reducing van der Waals gap.
Hypoxia-induced amniotic fluid stem cell secretome augments cardiomyocyte proliferation and enhances cardioprotective effects under hypoxic-ischemic conditions
Authors: Kukumberg Marek , Phermthai Tatsanee , Wichitwiengrat Suparat , Wang Xiaoyuan , Arjunan Subramanian , Chong Suet Yen , Fong Chui-Yee , Wang Jiong-Wei , Rufaihah Abdul Jalil , Mattar Citra Nurfarah Zaini
Published: January 2021

Secretome derived from human amniotic fluid stem cells (AFSC-S) is rich in soluble bioactive factors (SBF) and offers untapped therapeutic potential for regenerative medicine while avoiding putative cell-related complications. Characterization and optimal generation of AFSC-S remains challenging. We hypothesized that modulation of oxygen conditions during AFSC-S generation enriches SBF and confers enhanced regenerative and cardioprotective effects on cardiovascular cells. We collected secretome at 6-hourly intervals up to 30 h following incubation of AFSC in normoxic (21%O2, nAFSC-S) and hypoxic (1%O2, hAFSC-S) conditions. Proliferation of human adult cardiomyocytes (hCM) and umbilical cord endothelial cells (HUVEC) incubated with nAFSC-S or hAFSC-S were examined following culture in normoxia or hypoxia. Lower AFSC counts and richer protein content in AFSC-S were observed in hypoxia. Characterization of AFSC-S by multiplex immunoassay showed higher concentrations of pro-angiogenic and anti-inflammatory SBF. hCM demonstrated highest proliferation with 30h-hAFSC-S in hypoxic culture. The cardioprotective potential of concentrated 30h-hAFSC-S treatment was demonstrated in a myocardial ischemia–reperfusion injury mouse model by infarct size and cell apoptosis reduction and cell proliferation increase when compared to saline treatment controls. Thus, we project that hypoxic-generated AFSC-S, with higher pro-angiogenic and anti-inflammatory SBF, can be harnessed and refined for tailored regenerative applications in ischemic cardiovascular disease.
Particle size-related limitations of persistent phosphors based on the doped Y3Al2Ga3O12 system
Authors: Boiko Vitalii , Dai Zhengfa , Markowska Marta , Leonelli Cristina , Mortalò Cecilia , Armetta Francesco , Ursi Federica , Nasillo Giorgio , Saladino Maria Luisa , Hreniak Dariusz
Published: January 2021

Co-doped Ce3+, Cr3+and Pr3+yttrium–aluminium–gallium garnet powders of various sizes were obtained by co-precipitation method. The microstructure and morphology were investigated by XRPD, TEM and gas porosimetry. The luminescence properties were studied by excitation and emission spectra, quantum yield and decay times. Thermoluminescence measurements were performed to evaluate the activation energy, traps redistribution and frequency factor. Limitation in the energy transfer between dopant ions in the small particles, traps depth and surface defects were considered and investigated as responsible for the quenching of persistent luminescence. The phosphors annealed at 1100 °C show the optimal persistent luminescence and nano-particle size.
Ion tracks in silicon formed by much lower energy deposition than the track formation threshold
Authors: Amekura H. , Toulemonde M. , Narumi K. , Li R. , Chiba A. , Hirano Y. , Yamada K. , Yamamoto S. , Ishikawa N. , Okubo N. , Saitoh Y.
Published: January 2021

Damaged regions of cylindrical shapes called ion tracks, typically in nano-meters wide and tens micro-meters long, are formed along the ion trajectories in many insulators, when high energy ions in the electronic stopping regime are injected. In most cases, the ion tracks were assumed as consequences of dense electronic energy deposition from the high energy ions, except some cases where the synergy effect with the nuclear energy deposition plays an important role. In crystalline Si (c-Si), no tracks have been observed with any monomer ions up to GeV. Tracks are formed in c-Si under 40 MeV fullerene (C60) cluster ion irradiation, which provides much higher energy deposition than monomer ions. The track diameter decreases with decreasing the ion energy until they disappear at an extrapolated value of ~ 17 MeV. However, here we report the track formation of 10 nm in diameter under C60 ion irradiation of 6 MeV, i.e., much lower than the extrapolated threshold. The diameters of 10 nm were comparable to those under 40 MeV C60 irradiation. Furthermore, the tracks formed by 6 MeV C60 irradiation consisted of damaged crystalline, while those formed by 40 MeV C60 irradiation were amorphous. The track formation was observed down to 1 MeV and probably lower with decreasing the track diameters. The track lengths were much shorter than those expected from the drop of Se below the threshold. These track formations at such low energies cannot be explained by the conventional purely electronic energy deposition mechanism, indicating another origin, e.g., the synergy effect between the electronic and nuclear energy depositions, or dual transitions of transient melting and boiling.
Advanced characterization of biomineralization at plaque layer and inside rice roots amended with iron- and silica-enhanced biochar
Authors: Chen Guanhong , Taherymoosavi Sarasadat , Cheong Soshan , Yin Yao , Akter Rabeya , Marjo Christopher E. , Rich Anne M. , Mitchell David R. G. , Fan Xiaorong , Chew Jinkiat , Pan Genxing , Li Lianqing , Bian Rongjun , Horvat Joseph , Mohammed Mohanad , Munroe Paul , Joseph Stephen
Published: January 2021

Application of iron (Fe)- and silica (Si)-enhanced biochar compound fertilisers (BCF) stimulates rice yield by increasing plant uptake of mineral nutrients. With alterations of the nutrient status in roots, element homeostasis (e.g., Fe) in the biochar-treated rice root was related to the formation of biominerals on the plaque layer and in the cortex of roots. However, the in situ characteristics of formed biominerals at the micron and sub-micron scale remain unknown. In this study, rice seedlings (Oryza sativa L.) were grown in paddy soil treated with BCF and conventional fertilizer, respectively, for 30 days. The biochar-induced changes in nutrient accumulation in roots, and the elemental composition, distribution and speciation of the biomineral composites formed in the biochar-treated roots at the micron and sub-micron scale, were investigated by a range of techniques. Results of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) showed that biochar treatment significantly increased concentrations of nutrients (e.g., Fe, Si, and P) inside the root. Raman mapping and vibrating sample magnetometry identified biochar particles and magnetic Fe nanoparticles associated with the roots. With Fe plaque formation, higher concentrations of FeOx− and FeOxH− anions on the root surface than the interior were detected by time-of-flight secondary ionization mass spectrometry (ToF-SIMS). Analysis of data from scanning electron microscopy energy-dispersive spectroscopy (SEM-EDS), and from scanning transmission electron microscopy (STEM) coupled with EDS or energy electron loss spectroscopy (EELS), determined that Fe(III) oxide nanoparticles were accumulated in the crystalline fraction of the plaque and were co-localized with Si and P on the root surface. Iron-rich nanoparticles (Fe–Si nanocomposites with mixed oxidation states of Fe and ferritin) in the root cortex were identified by using aberration-corrected STEM and in situ EELS analysis, confirming the biomineralization and storage of Fe in the rice root. The findings from this study highlight that the deposition of Fe-rich nanocomposites occurs with contrasting chemical speciation in the Fe plaque and cortex of the rice root. This provides an improved understanding of the element homeostasis in rice with biochar-mineral fertilization.
Surgical Apgar score is strongly associated with postoperative ICU admission
Authors: Lin Ying-Chun , Chen Yi-Chun , Yang Chen-Hsien , Su Nuan-Yen
Published: January 2021

Immediate postoperative intensive care unit (ICU) admission can increase the survival rate in patients undergoing high-risk surgeries. Nevertheless, less than 15% of such patients are immediately admitted to the ICU due to no reliable criteria for admission. The surgical Apgar score (SAS) (0–10) can be used to predict postoperative complications, mortality rates, and ICU admission after high-risk intra-abdominal surgery. Our study was performed to determine the relationship between the SAS and postoperative ICU transfer after all surgeries. All patients undergoing operative anesthesia were retrospectively enrolled. Among 13,139 patients, 68.4% and < 9% of whom had a SASs of 7–10 and 0–4. Patients transferred to the ICU immediately after surgery was 7.8%. Age, sex, American Society of Anesthesiologists (ASA) class, emergency surgery, and the SAS were associated with ICU admission. The odds ratios for ICU admission in patients with SASs of 0–2, 3–4, and 5–6 were 5.2, 2.26, and 1.73, respectively (P < 0.001). In general, a higher ASA classification and a lower SAS were associated with higher rates of postoperative ICU admission after all surgeries. Although the SAS is calculated intraoperatively, it is a powerful tool for clinical decision-making regarding the immediate postoperative ICU transfer.
Activation of PKC supports the anticancer activity of tigilanol tiglate and related epoxytiglianes
Authors: Cullen Jason K. , Boyle Glen M. , Yap Pei-Yi , Elmlinger Stefan , Simmons Jacinta L. , Broit Natasa , Johns Jenny , Ferguson Blake , Maslovskaya Lidia A. , Savchenko Andrei I. , Mirzayans Paul Malek , Porzelle Achim , Bernhardt Paul V. , Gordon Victoria A. , Reddell Paul W. , Pagani Alberto , Appendino Giovanni , Parsons Peter G. , Williams Craig M.
Published: January 2021

The long-standing perception of Protein Kinase C (PKC) as a family of oncoproteins has increasingly been challenged by evidence that some PKC isoforms may act as tumor suppressors. To explore the hypothesis that activation, rather than inhibition, of these isoforms is critical for anticancer activity, we isolated and characterized a family of 16 novel phorboids closely-related to tigilanol tiglate (EBC-46), a PKC-activating epoxytigliane showing promising clinical safety and efficacy for intratumoral treatment of cancers. While alkyl branching features of the C12-ester influenced potency, the 6,7-epoxide structural motif and position was critical to PKC activation in vitro. A subset of the 6,7-epoxytiglianes were efficacious against established tumors in mice; which generally correlated with in vitro activation of PKC. Importantly, epoxytiglianes without evidence of PKC activation showed limited antitumor efficacy. Taken together, these findings provide a strong rationale to reassess the role of PKC isoforms in cancer, and suggest in some situations their activation can be a promising strategy for anticancer drug discovery.
Childhood maltreatment, prefrontal-paralimbic gray matter volume, and substance use in young adults and interactions with risk for bipolar disorder
Authors: Kirsch Dylan E. , Tretyak Valeria , Radpour Sepeadeh , Weber Wade A. , Nemeroff Charles B. , Fromme Kim , Strakowski Stephen M. , Lippard Elizabeth T. C.
Published: January 2021

Childhood maltreatment is associated with adverse effects on the brain, and an increased risk for psychopathology, including mood and substance use disorders. Individuals vary on the degree to which they exhibit neurobiological and clinical differences following maltreatment. Individuals with bipolar disorder exhibit greater magnitude of maltreatment-related prefrontal-paralimbic gray matter volume (GMV) deficits compared to typically developing individuals. It is unclear if greater structural differences stem from greater neural vulnerability to maltreatment in bipolar disorder, or if they relate to presence of other clinical features associated with childhood maltreatment, e.g., elevated prevalence of comorbid substance use disorders. To investigate this, we compared young adults with a family history of bipolar disorder (n = 21), but who did not fulfill diagnostic criteria for bipolar disorder, with typically developing young adults without a family history of bipolar disorder (n = 26). Participants completed structural neuroimaging, clinical and family history interviews, and assessment of childhood maltreatment and recent alcohol and cannabis use patterns. We examined relations between childhood maltreatment and prefrontal-paralimbic GMV by modeling main effects of maltreatment and family history group by maltreatment interactions on prefrontal-paralimbic GMV. We also examined relations between maltreatment and associated GMV changes with recent alcohol and cannabis use. Childhood maltreatment correlated with lower ventral, rostral and dorsolateral prefrontal and insular cortical GMV across all participants regardless of the presence or absence of familial history of bipolar disorder. However, exploratory analyses did reveal greater maltreatment-related GMV differences in individuals with prodromal symptoms of depression. Lower insula GMV was associated with greater frequency of cannabis use across all participants and greater quantity of alcohol use only in those with familial risk for bipolar disorder. Results suggest familial risk for bipolar disorder, and presumably genetic risk, may relate to outcomes following childhood maltreatment and should be considered in prevention/early intervention strategies.
Low melting oxide glasses prepared at a melt temperature of 500 °C
Authors: Masai Hirokazu , Nishibe Toru , Yamamoto Satoshi , Niizuma Takaaki , Kitamura Naoyuki , Akai Tomoko , Ohkubo Takahiro , Yoshida Miki
Published: January 2021

Transparent low-melting inorganic glass is an attractive industrial material based on its high thermal and light resistance compared with conventional engineering plastics. If the melting temperature of inorganic glass could be decreased, the doping of guest materials or compression moulding on the glass surface would be easier. Although phosphate glass is considered as a potential candidate because of its transparency in the visible region and low-melting behaviour, water durability often becomes a problem for implementation. Here, we prepared inorganic low-melting phosphate glass at a temperature of 500 °C via a melting and quenching methodology. It was found that tin-doped phosphate glasses exhibited higher thermal and light resistance properties than polycarbonates. Colourless transparent oxide glasses without organic components are capable of bringing about new possibilities for the application of inorganic glasses.
Comparative analysis of chloroplast genomes indicated different origin for Indian tea (Camellia assamica cv TV1) as compared to Chinese tea
Authors: Rawal Hukam C. , Borchetia Sangeeta , Bera Biswajit , Soundararajan S. , Ilango R. Victor J. , Barooah Anoop Kumar , Sharma Tilak Raj , Singh Nagendra Kumar , Mondal Tapan Kumar
Published: January 2021

Based upon the morphological characteristics, tea is classified botanically into 2 main types i.e. Assam and China, which are morphologically very distinct. Further, they are so easily pollinated among themselves, that a third category, Cambod type is also described. Although the general consensus of origin of tea is India, Burma and China adjoining area, yet specific origin of China and Assam type tea are not yet clear. Thus, we made an attempt to understand the origin of Indian tea through the comparative analysis of different chloroplast (cp) genomes under the Camellia genus by performing evolutionary study and comparing simple sequence repeats (SSRs) and codon usage distribution patterns among them. The Cp genome based phylogenetic analysis indicated that Indian Tea, TV1 formed a different group from that of China tea, indicating that TV1 might have undergone different domestications and hence owe different origins. The simple sequence repeats (SSRs) analysis and codon usage distribution patterns also supported the clustering order in the cp genome based phylogenetic tree.
Simulating an ultra-broadband concept for Exawatt-class lasers
Authors: Li Zhaoyang , Kato Yoshiaki , Kawanaka Junji
Published: January 2021

The rapid development of the optical-cycle-level ultra-fast laser technologies may break through the bottleneck of the traditional ultra-intense laser [i.e., Petawatt (PW, 1015 W) laser currently] and enable the generation of even higher peak-power/intensity lasers. Herein, we simulate an ultra-broadband concept for the realization of an Exawatt-class (EW, 1018 W) high peak-power laser, where the wide-angle non-collinear optical parametric chirped-pulse amplification (WNOPCPA) is combined with the thin-plate post-compression. A frequency-chirped carrier-envelope-phase stable super-continuum laser is amplified to high-energy in WNOPCPA by pumping with two pump-beamlets and injected into the thin-plate post-compression to generate a sub-optical-cycle high-energy laser pulse. The numerical simulation shows this hybrid concept significantly enhances the gain bandwidth in the high-energy amplifier and the spectral broadening in the post-compression. By using this concept, a study of a prototype design of a 0.5 EW system is presented, and several key challenges are also examined.
Phenol-rich fulvic acid as a water additive enhances growth, reduces stress, and stimulates the immune system of fish in aquaculture
Authors: Lieke Thora , Steinberg Christian E. W. , Pan Bo , Perminova Irina V. , Meinelt Thomas , Knopf Klaus , Kloas Werner
Published: January 2021

Aquaculture has become imperative to cover the demands for dietary animal protein. Simultaneously, it has to overcome prejudices from excessive use of antibiotics and environmental impacts. Natural supplements are traditionally applied orally. In this study, we demonstrated another pathway: the gills. Humic substances are immunostimulants and a natural part of every aquatic ecosystem, making them ideal to be used as bath stimulants. Five and 50 mg C/L of a fulvic acid-rich humic substance was added for 28 days to the water of juvenile rainbow trout (Oncorhynchus mykiss). This fulvic acid is characterized by a high content of phenolic moieties with persistent free radicals and a high electron exchange capacity. The high concentration of the fulvic acid significantly increased growth and reduced the food conversion ratio and the response to a handling-stressor. Phagocytosis and potential killing activity of head kidney leukocytes were increased, as well as the total oxyradical scavenging capacity (TOSC) and lysozyme activity in the gills. In conclusion, immunostimulation via gills is possible with our fulvic acid, and the high phenolic content improved overall health and stress resistance of fish.
Thermoresponsive GenisteinNLC-dexamethasone-moxifloxacin multi drug delivery system in lens capsule bag to prevent complications after cataract surgery
Authors: Yan Tingyu , Ma Zhongxu , Liu Jingjing , Yin Na , Lei Shizhen , Zhang Xinxin , Li Xuedong , Zhang Yu , Kong Jun
Published: January 2021

Cataract surgery is the most common intraocular procedure. To decrease postsurgical inflammation, prevent infection and reduce the incidence of secondary cataract, we built a temperature-sensitive drug delivery system carrying dexamethasone, moxifloxacin and genistein nanostructured lipid carrier (GenNLC) modified by mPEG-PLA based on F127/F68 as hydrogel. Characterizations and release profiles of the drug delivery system were studied. In vitro functions were detected by CCK-8 test, immunofluorescence, wound-healing assay, real time-PCR and western blotting. The size of GenNLCs was 39.47 ± 0.69 nm in average with surface charges of − 4.32 ± 0.84 mV. The hydrogel gelation temperature and time were 32 °C, 20 s with a viscosity, hardness, adhesiveness and stringiness of 6.135 Pa.s, 54.0 g, 22.0 g, and 3.24 mm, respectively. Transmittance of the gel-release medium was above 90% (93.44 ± 0.33% to 100%) at range of 430 nm to 800 nm. Moxifloxacin released completely within 10 days. Fifty percent of dexamethasone released at a constant rate in the first week, and then released sustainably with a tapering down rate until day 30. Genistein released slowly but persistently with a cumulative release of 63% at day 40. The thermoresponsive hydrogel inhibited the proliferation, migration and epithelial-mesenchymal transition of SRA 01/04 cells, which were confirmed by testing CCK-8, wound-healing assay, western blot, real time-PCR (RT-PCR) and immunofluorescence. These results support this intracameral thermoresponsive in situ multi-drug delivery system with programmed release amounts and release profiles to cut down the need of eye drops for preventing inflammation or infection and to reduce posterior capsular opacification following cataract surgery.
In vitro antagonistic inhibitory effects of palm seed crude oils and their main constituent, lauric acid, with oxacillin in Staphylococcus aureus
Authors: Lalouckova Klara , Skrivanova Eva , Rondevaldova Johana , Frankova Adela , Soukup Josef , Kokoska Ladislav
Published: January 2021

Infections caused by Staphylococcus aureus are a serious global threat, and with the emergence of antibiotic resistance, even more difficult to treat. One of the possible complications in antistaphylococcal therapy represents negative interactions of antibiotics with food. In this study, the in vitro interaction between oxacillin and crude palm seed oil from Astrocaryum vulgare, Cocos nucifera, and Elaeis guineensis against nine strains of S. aureus was determined using the checkerboard method. Lauric acid was identified as a major constituent of all tested oils by gas chromatography. The results showed strong concentration dependent antagonistic interactions between palm oils and oxacillin with values of fractional inhibitory concentrations indices ranging from 4.02 to 8.56 at concentrations equal or higher than 1024 µg/mL of the tested oils. Similarly, lauric acid in combination with oxacillin produced antagonistic action with fractional inhibitory concentration indices ranging from 4.01 to 4.28 at 1024 µg/mL. These findings suggest that interference between oxacillin and palm oils and their constituents can negatively affect the treatment of staphylococcal infections in humans and other animals.
Exploring the taxonomical and functional profile of As Burgas hot spring focusing on thermostable β-galactosidases
Authors: DeCastro María-Eugenia , Doane Michael P. , Dinsdale Elizabeth Ann , Rodríguez-Belmonte Esther , González-Siso María-Isabel
Published: January 2021

In the present study we investigate the microbial community inhabiting As Burgas geothermal spring, located in Ourense (Galicia, Spain). The approximately 23 Gbp of Illumina sequences generated for each replicate revealed a complex microbial community dominated by Bacteria in which Proteobacteria and Aquificae were the two prevalent phyla. An association between the two most prevalent genera,ThermusandHydrogenobacter, was suggested by the relationship of their metabolism. The high relative abundance of sequences involved in the Calvin–Benson cycle and the reductive TCA cycle unveils the dominance of an autotrophic population. Important pathways from the nitrogen and sulfur cycle are potentially taking place in As Burgas hot spring. In the assembled reads, two complete ORFs matching GH2 beta-galactosidases were found. To assess their functional characterization, the two ORFs were cloned and overexpressed inE. coli. The pTsbg enzyme had activity towards o-Nitrophenyl-β-d-galactopyranoside (ONPG) and p-Nitrophenyl-β-d-fucopyranoside, with high thermal stability and showing maximal activity at 85 °C and pH 6, nevertheless the enzyme failed to hydrolyze lactose. The other enzyme, Tsbg, was unable to hydrolyze even ONPG or lactose. This finding highlights the challenge of finding novel active enzymes based only on their sequence.
Global wave number-4 pattern in the southern subtropical sea surface temperature
Authors: Senapati Balaji , Dash Mihir K. , Behera Swadhin K.
Published: January 2021

Exploratory analysis using empirical orthogonal function revealed the presence of a stationary zonal wavenumber-4 (W4) pattern in the sea surface temperature (SST) anomaly in the southern subtropics (20°S–55°S). The signal over the Southern subtropics is seasonally phase-locked to the austral summer and persists up to mid-autumn. Thermodynamic coupling of atmosphere and the upper ocean helps in generating the W4 pattern, which later terminates due to the breaking of that coupled feedback. It is found that the presence of anomalous SST due to W4 mode in the surrounding of Australia affects the rainfall over the continent by modulating the local atmospheric circulation. During positive phase of W4 event, the presence of cold SST anomaly over the south-eastern and -western side of Australia creates an anomalous divergence circulation. This favours the moisture transport towards south-eastern Australia, resulting in more rainfall in February. The scenario reverses in case of a negative W4 event. There is also a difference of one month between the occurrence of positive and negative W4 peaks. This asymmetry seems to be responsible for the weak SST signal to the South of Australia. Correlation analysis suggests that the W4 pattern in SST is independent of other natural variabilities such as Southern Annular Mode, and Indian Ocean Dipole as well as a rather weak relationship with El Niño/Southern Oscillation.
Stimulatory, but not anxiogenic, doses of caffeine act centrally to activate interscapular brown adipose tissue thermogenesis in anesthetized male rats
Authors: Van Schaik L. , Kettle C. , Green R. , Sievers W. , Hale M. W. , Irving H. R. , Whelan D. R. , Rathner J. A.
Published: January 2021

The role of central orexin in the sympathetic control of interscapular brown adipose tissue (iBAT) thermogenesis has been established in rodents. Stimulatory doses of caffeine activate orexin positive neurons in the lateral hypothalamus, a region of the brain implicated in stimulating BAT thermogenesis. This study tests the hypothesis that central administration of caffeine is sufficient to activate BAT. Low doses of caffeine administered either systemically (intravenous [IV]; 10 mg/kg) and centrally (intracerebroventricular [ICV]; 5–10 μg) increases BAT thermogenesis, in anaesthetised (1.5 g/kg urethane, IV) free breathing male rats. Cardiovascular function was monitored via an indwelling intra-arterial cannula and exhibited no response to the caffeine. Core temperature did not significantly differ after administration of caffeine via either route of administration. Caffeine administered both IV and ICV increased neuronal activity, as measured by c-Fos-immunoreactivity within subregions of the hypothalamic area, previously implicated in regulating BAT thermogenesis. Significantly, there appears to be no neural anxiety response to the low dose of caffeine as indicated by no change in activity in the basolateral amygdala. Having measured the physiological correlate of thermogenesis (heat production) we have not measured indirect molecular correlates of BAT activation. Nevertheless, our results demonstrate that caffeine, at stimulatory doses, acting via the central nervous system can increase thermogenesis, without adverse cardio-dynamic impact.
Tumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen
Authors: Miebach Lea , Freund Eric , Horn Stefan , Niessner Felix , Sagwal Sanjeev Kumar , von Woedtke Thomas , Emmert Steffen , Weltmann Klaus-Dieter , Clemen Ramona , Schmidt Anke , Gerling Torsten , Bekeschus Sander
Published: January 2021

Recent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source (Vjet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the Vjet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not Vjet plasma-treated tumor cells by dendritic cells. Moreover, the Vjet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.
Glycemic indices predict outcomes after aneurysmal subarachnoid hemorrhage: a retrospective single center comparative analysis
Authors: McIntyre Matthew K. , Halabi Mohamed , Li Boyi , Long Andrew , Van Hoof Alexander , Afridi Adil , Gandhi Chirag , Schmidt Meic , Cole Chad , Santarelli Justin , Al-Mufti Fawaz , Bowers Christian A.
Published: January 2021

Although hyperglycemia is associated with worse outcomes after aneurysmal subarachnoid hemorrhage (aSAH), there is no consensus on the optimal glucose control metric, acceptable in-hospital glucose ranges, or suitable insulin regimens in this population. In this single-center retrospective cohort study of aSAH patients, admission glucose, and hospital glucose mean (MHG), minimum (MinG), maximum (MaxG), and variability were compared. Primary endpoints (mortality, complications, and vasospasm) were assessed using multivariate logistic regressions. Of the 217 patients included, complications occurred in 83 (38.2%), 124 (57.1%) had vasospasm, and 41 (18.9%) died. MHG was independently associated with (p < 0.001) mortality, MaxG (p = 0.017) with complications, and lower MinG (p = 0.015) with vasospasm. Patients with MHG ≥ 140 mg/dL had 10 × increased odds of death [odds ratio (OR) = 10.3; 95% CI 4.6–21.5; p < 0.0001] while those with MinG ≤ 90 mg/dL had nearly 2× increased odds of vasospasm (OR = 1.8; 95% CI 1.01–3.21; p = 0.0422). While inpatient insulin was associated with increased complications and provided no mortality benefit, among those with MHG ≥ 140 mg/dL insulin therapy resulted in lower mortality (OR = 0.3; 95% CI 0.1–0.9; p = 0.0358), but no increased complication risk. While elevated MHG and MaxG are highly associated with poorer outcomes after aSAH, lower MinG is associated with increased vasospasm risk. Future trials should consider initiating insulin therapy based on MHG rather than other hyperglycemia measures.
Feasibility of reduced-dose posttransplant cyclophosphamide and cotransplantation of peripheral blood stem cells and umbilical cord-derived mesenchymal stem cells for SAA
Authors: Zu Yingling , Zhou Jian , Fu Yuewen , Fang Baijun , Liu Xinjian , Zhang Yanli , Yu Fengkuan , Zuo Wenli , Zhou Hu , Gui Ruirui , Li Zhen , Liu Yanyan , Zhao Huifang , Zhang Chengjuan , Song Yongping
Published: January 2021

Posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis is an effective strategie for patients receiving matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and haploidentical HSCT (haplo-HSCT). We evaluated the effectiveness and safety of reduced-dose cyclophosphamide, 20 mg/kg for 13 patients in MSD-HSCT cohort and 25 mg/kg for 22 patients in haplo-HSCT cohort, on days + 3, + 4 combined with cotransplantation of peripheral blood stem cells (PBSCs) and human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for severe aplastic anemia (SAA). In MSD-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the MSD-control cohort (P < 0.05). The cumulative incidence of acute GVHD (aGVHD) at day + 100 (15.4%) was lower than that in the MSD-control cohort (P = 0.050). No patient developed chronic GVHD (cGVHD). The 1-year overall survival (OS) and event-free survival (EFS) rates were 100% and 92.3%. In haplo-PTCy cohort, the times to neutrophil and platelet engraftment were significantly shorter than those in the haplo-control cohort (P < 0.05). The cumulative incidences of aGVHD at day + 100 and 1-year cGVHD were 31.8% and 18.2%, and the 1-year OS and EFS rates were 81.8% and 66.9%. Reduced-dose PTCy and cotransplantation of PBSCs and UC-MSCs is an acceptable alternative to patients with SAA.
Neuromyelitis optica is an HLA associated disease different from Multiple Sclerosis: a systematic review with meta-analysis
Authors: Alvarenga Marcos Papais , do Carmo Luciana Ferreira , Vasconcelos Claudia Cristina Ferreira , Alvarenga Marina Papais , Alvarenga-Filho Helcio , de Melo Bento Cleonice Alves , Paiva Carmen Lucia Antão , Leyva-Fernández Laura , Fernández Óscar , Papais-Alvarenga Regina Maria
Published: January 2021

Neuromyelitis Optica and Multiple Sclerosis are idiopathic inflammatory demyelinating diseases of the central nervous system that currently are considered distinct autoimmune diseases, so differences in genetic susceptibility would be expected. This study aimed to investigate the HLA association with Neuromyelitis Optica by a systematic review with meta-analysis. The STROBE instrument guided research paper assessments. Thirteen papers published between 2009 and 2020 were eligible. 568 Neuromyelitis Optica patients, 41.4% Asians, 32.4% Latin Americans and 26.2% Europeans were analyzed. Only alleles of the DRB1 locus were genotyped in all studies. Neuromyelitis Optica patients have 2.46 more chances of having the DRB1*03 allelic group than controls. Ethnicity can influence genetic susceptibility. The main HLA association with Neuromyelitis Optica was the DRB1*03:01 allele in Western populations and with the DPB1*05:01 allele in Asia. Differences in the Multiple Sclerosis and Neuromyelitis Optica genetic susceptibility was confirmed in Afro descendants. The DRB1*03 allelic group associated with Neuromyelitis Optica has also been described in other systemic autoimmune diseases.
Impacts of sleep on the characteristics of dental biofilm
Authors: Sotozono Maki , Kuriki Nanako , Asahi Yoko , Noiri Yuichiro , Hayashi Mikako , Motooka Daisuke , Nakamura Shota , Machi Hiroyuki , Iida Tetsuya , Ebisu Shigeyuki
Published: January 2021

Dental biofilm present on the tooth surface is associated with oral diseases, such as dental caries and periodontal disease. Because bacterial numbers rapidly increase in saliva during sleep, oral care before sleeping is recommended for the prevention of chronic oral diseases. However, temporal circadian changes in the quantity and quality of dental biofilms are poorly understood. This study aimed to investigate the impacts of sleeping on dental biofilm amounts and compositions by using an in situ model. The use of this in situ model enabled us to investigate dental biofilm formed in the oral cavity and to perform a quantitative analysis. Subjects began wearing oral splints in the morning or before sleeping, and biofilm samples were collected at 8, 16, and 24 h after the subjects began wearing oral splints; these samples were then used in various experiments. No significant changes in the numbers of biofilm-forming bacteria were caused by sleep. However, the relative abundances of genera related to periodontitis (i.e., Fusobacterium and Prevotella) increased after awakening. In conclusion, the numbers of biofilm-forming bacteria were not affected by sleep, and the abundances of obligate anaerobes increased after sleep. This research may aid in defining efficacious preventive oral care.