bluuebunny/crossref_metadata_2025 huggingface dataset:
Tofacitinib Blocks Entheseal Lymphocyte Activation and modulates MSC adipogenesis but does not directly affect chondro- and osteogenesis
Authors: Russell Tobias , Rowe Hannah , Bridgewood Charlie , Cuthbert Richard , Watad Abdulla , Newton Darren , Jones Elena , McGonagle Dennis
Published: September 2021

Entheseal spinal inflammation and new bone formation with progressive ankylosis may occur in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). This study evaluated whether JAK inhibition with tofacitinib modulated the key disease associated cytokines, TNF and IL-17A and whether tofacitinib also modulated bone marrow stromal cell-derived mesenchymal stem cells (MSCs) function including osteogenesis, since post inflammation new bone formation occurs in these conditions. Methods: Conventional entheseal derived αβ CD4+ and CD8+ T-cells were in-vestigated following anti-CD3/CD28 bead stimulation to determine IL-17A and TNF levels in Tofacitinib treated (1000nM) peri-entheseal bone (PEB) and peripheral blood mononuclear cells (PBMC) following ELISA. Bone marrow stromal cell-derived mesenchymal stem cells (MSCs) colony forming unit (CFU-F) and multilineage potential was evaluated using tofacitinib (dosag-es ranging between 100, 500, 1000 and 10000nM). Results: Induced IL-17A and TNF cytokine production from both entheseal CD4+ T-cells and CD8+ T-cells were effectively inhibited by to-facitinib. Tofacitinib treatment did not impact on CFU-F potential or in vitro chondro- and oste-ogenesis. However, tofacitinib stimulation increased MSC adipogenic potential with greater Oil Red O stained area. Conclusion: Inducible IL-17A and TNF production by healthy human enthe-seal CD4+ and CD8+ T-cells was robustly inhibited in vitro by tofacitinib. However, tofacitinib did not impact on MSC osteogenesis but stimulated in vitro MSC adipogenesis, the rele-vance of which needs further evaluation given the adipocytes are associated with new bone formation in SpA.
A New Double-Stranded RNA Mycovirus in Cryphonectria naterciae is Able to Cross the Species Barrier and is Deleterious to a New Host
Authors: Cornejo Carolina , Hisano Sakae , Bragança Helena , Suzuki Nobuhiro , Rigling Daniel
Published: September 2021

Cryphonectria is a fungal genus associated with economically significant disease of trees. Herein we characterized a novel double-stranded RNA virus from the fungal species Cryphonectria naterciae, a species unexplored as a virus host. De novo assembly of RNA-seq data and Sanger sequencing of RACE (rapid amplification of cDNA ends) clones gave the complete, non-segmented genome (10,164 bp) of the virus termed Cryphonectria naterciae fusagravirus (CnFGV1) that was phylogenetically placed within the previously proposed viral family Fusagraviridae. Of 31 field-collected strains of C. naterciae, 40% tested CnFGV1-positive. Co-cultivation resulted in within-species transmission of CnFGV1 to virus-free strains of C. naterciae. Comparison of the mycelium phenotype and the growth rate of CnFGV1-infected and virus-free isogenic strains revealed frequent sectoring and growth reduction in C. naterciae. Co-culturing also led to cross-species transmission of CnFGV1 to Cryphonectria carpinicola and Cryphonectria radicalis, but not to Cryphonectria parasitica. The virus-infected C. naterciae and the experimentally infected Cryphonectria spp. readily transmitted CnFGV1 through asexual spores to the next generation. CnFGV1 strongly reduced conidiation and in some cases vegetative growth of C. carpinicola, which is involved in the European hornbeam disease. This study is the first report of a fusagravirus in the family Cryphonectriaceae and lays the groundwork for assessing a hypovirulence effect of CnFGV1 against the hornbeam decline in Europe.
Computational Insights into the Binding Mechanism of OxyS sRNA with Chaperone Protein Hfq
Authors: Li Mengxin , Cong Yalong , Qi Yifei , Zhang John Z.H.
Published: September 2021

Under the oxidative stress condition, the small RNA (sRNA) Oxys that acts as essential post-transcriptional regulators of gene expression is produced and plays a regulatory function with the assistance of the RNA chaperone Hfq protein. Interestingly, experimental studies found that the N48A mutation of Hfq protein could enhance the binding affinity with OxyS while resulting in defection of gene regulation. But, how the Hfq protein interacts with sRNA Oxys and the origin of the stronger affinity of N48A mutation are both unclear. In this paper, molecular dynamics (MD) simulations were performed on the complex structure of Hfq and OxyS to explore their binding mechanism. The molecular mechanics generalized Born surface area (MM/GBSA) and interaction entropy (IE) method were combined to calculate the binding free energy between Hfq and OxyS sRNA, and the computational result is in excellent correlation with the experimental result. Per-residue decomposition of the binding free energy revealed that the enhanced binding ability of the N48A mutation mainly comes from the increased van der Waals interactions (vdW). This research explores the binding mechanism between Oxys and chaperone protein Hfq, and revealed the origin of the strong binding affinity of N48A mutation. The results provided important insights on the mechanism of gene expression regulation affected by protein mutations.
A Comparative Analysis of the New Mexico Organic and Conventional Producer: Implications for Occupational Safety and Health Research and Practice
Authors: Parshall Carolyn A , Soto Mas Francisco , Qeadan Fares
Published: September 2021

Research indicates that farmers’ demographic characteristics and production practices have safety and health implications. However, current systems do not identify organic farmers independently from conventional farmers, and literature on how organic and conventional farmers compare is very limited. We conducted a secondary analysis of 2012 Census of Agriculture data to compare organic and non-organic farms and principal operators (POs) in New Mexico (NM). Organic farms were smaller in size, and POs of farms with organic sales were significantly younger (55.8±9.5 vs. 60.5±5.5 years) and less experienced (19.5±6.8 vs. 25.2±6.8 years). Significant differences were also found in POs ethnicity, race, and primary occupation. More farms with organic sales had a female PO compared to farms with non-organic sales (27% vs. 19%). Other significant differences related to work arrangements, household income, living conditions, and access to Internet. National surveys and regional studies may not accurately typify and describe the local organic producer, which is essential in order to advance policy, develop health interventions, and properly address occupational safety and risk among organic farmers. This study makes a unique contribution to understanding the importance of surveillance and collecting place-based data that are specific to the organic producer.
Shannon (Information) Measures of Symmetry for 1D and 2D Shapes and Patterns
Authors: Bormashenko Edward , Legchenkova Irina , Frenkel Mark , Shvalb Nir , Shoval Shraga
Published: September 2021

Informational (Shannon) measures of symmetry are introduced and analyzed for the patterns built of 1D and 2D shapes. The informational measure of symmetry Hsym (G) characterizes the an averaged uncertainty in the presence of symmetry elements from the group G in a given pattern; whereas the Shannon-like measure of symmetry Ωsym (G) quantifies averaged uncertainty of appearance of shapes possessing in total n elements of symmetry belonging to group G in a given pattern. Hsym(G1)=Ωsym(G1)=0 for the patterns built of irregular, non-symmetric shapes. Both of informational measures of symmetry are intensive parameters of the pattern and do not depend on the number of shapes, their size and area of the pattern. They are also insensitive to the long-range order inherent for the pattern. Informational measures of symmetry of fractal patterns are addressed. The mixed patterns including curves and shapes are considered. Time evolution of the Shannon measures of symmetry is treated. The close-packed and dispersed 2D patterns are analyzed.
A Parallel Tracking of Salivary and Gut Microbiota Profiles Can Reveal Maturation and Interplay of Early Life Microbial Communities in Healthy Infants
Authors: Reddel Sofia , Pascucci Giuseppe Rubens , Foligno Silvia , Del Chierico Federica , Vernocchi Pamela , Marzullo Alessandra , Pattumelli Maria Grazia , Palma Paolo , Salvatori Guglielmo , Putignani Lorenza
Published: September 2021

The onset and progression of the salivary and gut microbiota, the transmission and the impact of the salivary microbiota on the development of early fecal microbial communities was herein explored. We characterized the microbiota of 82 faecal and 80 salivary samples, collected from 82 healty newborns at birth, 7, 15, 30, 90 and 180 days of life, by 16S rRNA targeted-metagenomics approach. Correlation heat-maps and co-occurrence networks were used to investigate microbial taxa relationship in saliva, gut and between the two ecosystems. In saliva microbiota, Streptococcus and Staphylococcus appeared as early commensals, dominating this ecosystem through the time, while Fusobacterium, Prevotella, Porphyromonas, Granulicatella and Veillonella were late colonizers. anaerobes as Enterobacteriace, Staphylococcus and Streptococcus, were gut microbiota pioneers, followed by the anaerobic Bifidobacterium, Veillonella, Eggerthella and Bacteroides. Streptococcus, Staphylococcus and Veillonella were shared by gut and saliva ecosystems (core microbiota). Early saliva and gut microbiota seem to evolve independently driven by local adaptation strategies, with the only exception for the oral Streptococcus and Veillonella genera, involved in gut microbiota development as seeding species. A more comprehensive knowledge of how oral microbiota may impact pathophysiological conditions of gut microbiota may open new avenues on the design of postbiotics.
Provably Safe Artificial General Intelligence via Interactive Proofs
Authors: Carlson Kristen
Published: September 2021

Methods are currently lacking to prove artificial general intelligence (AGI) safety. An AGI ‘hard takeoff’ is possible, in which first generation AGI1 rapidly triggers a succession of more powerful AGIn that differ dramatically in their computational capabilities (AGIn≪AGIn+1). No proof exists that AGI will benefit humans or of a sound value-alignment method. Numerous paths toward human extinction or subjugation have been identified. We suggest that probabilistic proof methods are the fundamental paradigm for proving safety and value-alignment between disparately powerful autonomous agents. Interactive proof systems (IPS) describe mathematical communication protocols wherein a Verifier queries a computationally more powerful Prover and reduces the probability of the Prover deceiving the Verifier to any specified low probability (e.g., 2-100). IPS procedures can test AGI behavior control systems that incorporate hard-coded ethics or value-learning methods. Mapping the axioms and transformation rules of a behavior control system to a finite set of prime numbers allows validation of ‘safe’ behavior via IPS number-theoretic methods. Many other representations are needed for proving various AGI properties. Multi-prover IPS, program-checking IPS, and probabilistically checkable proofs further extend the paradigm. In toto, IPS provides a way to reduce AGIn↔AGIn+1 interaction hazards to an acceptably low level.
Target-AID-Mediated Multiplex Base Editing in Porcine Fibroblasts
Authors: Yum Soo-Young , Jang Goo , Koo Okjae
Published: September 2021

Multiplex genome editing may induce genotoxicity and chromosomal rearrangements due to double-strand DNA breaks at multiple loci simultaneously induced by programmable nucleases, including CRISPR/Cas9. However, recently developed base-editing systems can directly substitute target sequences without double-strand breaks. Thus, the base-editing system is expected to be a safer method for multiplex genome-editing platforms for livestock. Target-AID is a base editing system composed of PmCDA1, a cytidine deaminase from sea lampreys, fused to Cas9 nickase. It can be used to substitute cytosine for thymine in 3-5 base editing windows, 18 bases upstream of the protospacer-adjacent motif site. In the current study, we demonstrated Target-AID-mediated base editing in porcine cells for the first time. We targeted multiple loci in the porcine genome using the Target-AID system and successfully induced target-specific base substitutions with up to 63.15% efficiency. This system can be used for the further production of various genome-engineered pigs.
Black Holes as Markers of Dimensionality
Authors: Łukaszyk Szymon
Published: September 2021

Black hole temperature as a function of its Planck length diameter multiple is derived from black hole surface gravity and Hawking temperature. It is conjectured that this multiple corresponds to dimensionality of the graph of nature with d = 1/2pi describing primordial Big Bang singularity. A black hole interacts with the environment and observable black holes have uniquely defined Delaunay triangulations with a natural number of spherical triangles having Planck areas (bits), where a Planck triangle is active and has gravitational potential of -c^2 if all its vertices have black hole gravitational potential of -c^2/2 and is inactive otherwise. Temporary distribution of active triangles on an event horizon tends to maximize Shannon entropy. Black hole blackbody radiation, informational capacity fluctuations, and quantum statistics are discussed. On the basis of the latter, wavelength bounds for BE, MB, and FD statistics are derived as a function of a diameter. A similarity of the logistic function and black hole FD statistics leads to the BE logistic function and map. This outlines the program for research of other nature phenomena that emit perfect blackbody radiation, such as neutron stars and white dwarfs.
On the Inverse Fourier Transform of the Planck-Einstein law
Authors: Jamali Alireza
Published: September 2021

After proposing a natural metric for the space in which particles spin which implements the principle of maximum frequency, E=hf is generalised and its inverse Fourier transform is calculated.
PERAN WARGA DALAM REVITALISASI SISKAMLING DI TENGAH PANDEMI COVID-19 SEBAGAI UPAYA MENJAGA KEAMANAN LINGKUNGAN
Authors: Khoirunisa Nida
Published: September 2021

Sejak terjadi pandemi covid-19 tindak kejahatan di masyarakat terus meningkat. Desa Kerep ditunjuk oleh Kapolres Kediri kota untuk menjalankan Program Kampung Tangguh. Dalam penerapan program Kampung Tangguh tersebut Desa Kerep memperkuat keamanan lingkungan dengan revitalisasi program siskamling yang sempat berheti lama. Tujuan penelitian ini adalah menganalisis peran warga Desa Kerep RT 04 RW 03 dalam revitalisasi program Siskamling menggunakan teori Tindakan Sosial Max Weber. Adapun metode yang digunakan dalam penelitian ini adalah metode deskriptif kualitatif. Hasil penelitian menunjukkan bahwa peran warga Desa Kerep dalam revitalisasi siskamling di tengah pandemi covid-19 antaralain ikut serta dalam musyawarah pendirian pos keamanan lingkungan, kerja bakti pendirian pos keamanan lingkungan, serta ronda malam.
PENGUATAN JEJARING KOMUNITAS MELALUI TINDAKAN KOLABORATIF
Authors: Mahendro Anggoro Yudo Mahendro
Published: September 2021

This research is directed to strengthen the network among the drivers of the Climate Village program in ten RWs in DKI Jakarta. Using collaboration action research, this research uses focus group discussion techniques which are conducted twice in each community. During the FGD twice there was an increase in community network marked by the creation of an organizational structure and work program that had not been made so far. These two outcomes are certainly important for building relationships that are more equal to elements of the local government and also the private sector which tends to impose programs on the community.
Translating Al-Fuzai’s ‘An Increase in Worry’
Authors: Dohal Gassim H.
Published: September 2021

In 'An Increase in Worry’, Khalil I. Al-Fuzai presents and tackles a social problem; violating a wife’s rights as seen by the local society. By translating and introducing this story to the English readers, I will introduce the Arabian author of this story. Also, using translation is used here as a device of communicating with those who have no access to the original text.
Rapidly Destructive Hip Disease Following Intra-Articular Corticosteroid Injection of the Hip
Authors: Okike Kanu , King Ryan K. , Merchant Jason C. , Toney Eugene A. , Lee Gregory Y. , Yoon Hyo-Chun
Published: September 2021

Background:

While recent reports have suggested that hip corticosteroid injections can hasten joint degeneration, there are few published data on the topic. The purpose of the present study was to evaluate for an association between corticosteroid injection and rapidly destructive hip disease (RDHD) and to determine the rate of, and risk factors for, occurrence.

Methods:

This study was conducted in 2 parts. First, to assess for a potential association between hip corticosteroid injection and RDHD, a case-control analysis was performed. Patients who developed RDHD between 2013 and 2016 served as cases, whereas those who underwent total hip arthroplasty for diagnoses other than RDHD during the same period served as controls, and the exposure of interest was prior intra-articular hip corticosteroid injection. Second, in a retrospective cohort analysis, we analyzed all patients who received a fluoroscopically guided intra-articular hip corticosteroid injection at our institution from 2013 to 2016. The rate of post-injection RDHD was determined, and logistic regression was used to identify risk factors for occurrence.

Results:

In the case-control analysis, hip corticosteroid injection was associated with the development of RDHD (adjusted odds ratio, 8.56 [95% confidence interval, 3.29 to 22.3], p < 0.0001). There was evidence of a dose-response curve, with the risk of RDHD increasing with injection dosage as well as with the number of injections received. In the retrospective cohort analysis, the rate of post-injection RDHD was 5.4% (37 of 688). Cases of post-injection RDHD were diagnosed at an average of 5.1 months following injection and were characterized by rapidly progressive joint-space narrowing, osteolysis, and collapse of the femoral head.

Conclusions:

This study documents an association between hip corticosteroid injection and RDHD. While the risk of RDHD following a single low-dose (≤40 mg) triamcinolone injection is low, the risk is higher following high-dose (≥80 mg) injection and multiple injections. These findings provide information that can be used to counsel patients about the risks associated with this common procedure. In addition, caution should be taken with intra-articular hip injections utilizing ≥80 mg of corticosteroid and multiple injections.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Extra-wide-angle parabolic equations in motionless and moving media
Authors: Ostashev Vladimir , Muhlestein Michael , Wilson D.
Published: September 2021

Wide-angle parabolic equations (WAPEs) play an important role in physics. They are derived by an expansion of a square-root pseudo-differential operator in one-way wave equations, and then solved by finite-difference techniques. In the present paper, a different approach is suggested. The starting point is an extra-wide-angle parabolic equation (EWAPE) valid for small variations of the refractive index of a medium. This equation is written in an integral form, solved by a perturbation technique, and transformed to the spectral domain. The resulting split-step spectral algorithm for the EWAPE accounts for the propagation angles up to 90° with respect to the nominal direction. This EWAPE is also generalized to large variations in the refractive index. It is shown that WAPEs known in the literature are particular cases of the two EWAPEs. This provides an alternative derivation of the WAPEs, enables a better understanding of the underlying physics and ranges of their applicability, and opens an opportunity for innovative algorithms. Sound propagation in both motionless and moving media is considered. The split-step spectral algorithm is particularly useful in the latter case since complicated partial derivatives of the sound pressure and medium velocity reduce to wave vectors (essentially, propagation angles) in the spectral domain.
Quantifying Late Pennsylvanian Multivariate Morphological Change in the Fusulinid GenusTriticitesfrom the Central and Southwestern United States
Authors: Sims Eileah R. , Belanger Christina L.
Published: September 2021

Fusulinid Foraminifera are important for biostratigraphic correlation of strata in the Upper Paleozoic of the central and southwestern United States due to their high abundance and diversity in shallow marine carbonates. These correlations rely on consistent species-level identifications as well as geographically consistent morphological variation within species. However, many taxonomically important characters are described qualitatively, which can lead to conflicting identifications among taxonomists and cause biostratigraphic disagreements. Quantitative morphometric comparisons among species can increase the consistency of identifications among workers and capture temporal and geographic morphological gradients. Here, we used 14 linear measurements to describe the morphology of 18 biostratigraphically important species within the genus Triticites. Canonical variates analysis (CVA) showed that whereas specimens of a given species occupy similar areas of morphospace, species overlap considerably and, thus, these linear measurements poorly differentiate among species. However, species morphology covaried with geological age and multivariate analyses focused on age differences reveal an increase in the size of the initial chamber (proloculus) and a relative decrease in test expansion along the long axes over time. These morphological changes are consistent with an adaptation to shallow water conditions following the fall in relative sea-level across the Virgilian-Newwellian/Bursumian transition. Given the consistency of the morphological shift among North American basins, these morphological changes may be more useful for the recognition of the Virgilian-Newwellian/Bursumian transition than species-level biozones because they do not depend on consistent species identification.
Effects of long-term warming on microbial nutrient limitation of soil aggregates on the Qinghai-Tibet Plateau
Authors: Chen Wenjing , Zhou Huakun , Qiao Leilei , Li Yuanze , Wu Yang , Zhai Jiaying , Liu Guobin , Xue Sha
Published: September 2021

Background and aims
Global warming has increasingly serious impacts on the structure and function of the Tibetan Plateau ecosystem. However, the mechanism by which warming affects the biogeochemical processes, and consequently the microbial nutrient limitation in soil aggregates, is not clear.
Methods
In the present study, we used open-top chamber experiments to simulate warming in an alpine meadow and an alpine shrubland on the Qinghai-Tibet Plateau, and we measured the C, N, and P-acquiring enzyme (β-1, 4-glucosidase, BG; leucine aminopeptidase, LAP; β-N-acetylglucosaminidase, NAG; alkali phosphatase, AP) activities and their stoichiometry to understand how warming affects microorganism-limiting mechanisms in soil aggregates.
Results
The results showed that long-term warming treatment significantly decreased soil organic carbon (SOC) and total nitrogen (TN) concentrations of large macroaggregates (LMGA) and small macroaggregates (SMGA) in alpine meadows, but significantly increased SOC concentration of LMGA in alpine shrubland. The SOC and TN concentrations of alpine meadows increased with the decrease of soil aggregate size and the concentrations in microaggregate (MIGA) were significantly higher than those LMGA. Soil enzyme activity increased with the decrease in aggregate size and was not significantly affected by warming treatment. Enzyme stoichiometry results demonstrated that soil microbes in alpine meadows and shrubland were limited by nutrient P relative to nitrogen; moreover, the long-term warming treatment aggravated the P limitation of soil microorganisms in the shrubland, and it had significant differences in LMGA and MIGA. At the same time, the long-term warming treatment had no significant effect on C limitation in the alpine shrubland and alpine meadows, but soil aggregate size affected the C limitation patterns of microorganisms and showed the greatest limitations in MIGA.
Conclusions
The microbial P limitation in shrubland is more sensitive to warming than that in meadow. Soil aggregates mediate the acquisition of C by microorganisms, and the C limitation in MIGA is the greatest. By providing a new perspective on this topic, our study increased our understanding of the effects of warming on microbial nutrient utilization and restriction patterns in soil aggregates.
A thermophilic Cas13 enzyme for sensitive and specific one-pot detection of SARS-CoV-2
Authors: Mahas Ahmed , Marsic Tin , Masson Mauricio , Wang Qiaochu , Aman Rashid , Zheng Cheng , Ali Zahir , Ghanem Bernard , Mahfouz MAGDY
Published: September 2021

Robust, sensitive, and specific diagnostic platforms for early pathogen detection are essential for the identification of infected patients and management of current and future pandemics. CRISPR-Cas systems have been repurposed for SARS-CoV-2 detection in two-pot assays. Two-pot assays require extra steps and are prone to cross-contamination; however, the temperature range of current Cas enzymes limits the development of one-pot assays Here, we characterized TccCas13a, a thermophilic Cas13a enzyme with cis and trans activities from 37–70°C, and HheCas13a, which had a limited range and lower activity. We harnessed TccCas13a in a one-pot SARS-CoV-2 assay with two layers of amplification and TccCas13a-mediated collateral degradation of a single-stranded RNA reporter. This assay showed 95% sensitivity and 100% specificity compared with RT-qPCR on clinical samples. We also developed a mobile phone application to facilitate data reading, collection, and sharing. Our OPTIMA-dx detection module exhibits key features for point-of-care SARS-CoV-2 screening and pathogen detection in general.
Integrative Clonal Evolution Analysis on SNV and CNV Levels in Multifocal Breast Cancer
Authors: Gao Yan , Wu Ning , Duan Qingke , Liu Hong , Xu Bo
Published: September 2021

Background:For multifocal or multicentric breast cancer with two or more separated malignant foci in ipsilateral breast, the origin of its multiple foci is still debatable: do they share a common origin or have they developed independently?Methods:By bulk exome sequencing combined with single cell whole genome sequencing using multiple annealing and looping-based amplification cycles (MALBAC), we obtained genomic information of two separated breast tumors and one metastatic lymph node in a multifocal breast cancer patient. We performed single nucleotide variation (SNV) and single cell copy number variation (CNV) analyses of the two breast tumors and lymph node. Results:On SNV level, we found common origin and single focus metastasis in this patient, concretely speaking that the two breast tumors were formed by the spread of one single tumor to another, instead of being developed independently. Furthermore, the lymph node was metastasized from one of the two tumors instead of co-metastasis by both of them. We also found that the SNV subclone architecture always kept stable between the two breast tumors as well as from the breast tumors to lymph node. On CNV level, in contrast, the frequency of CNV subclones changed dramatically from the breast tumors to lymph node. Among them, frequency of Clone 2 increased significantly, indicating metastatic advantages of it. By combining distinct clonal evolution patterns of SNVs and CNVs, we built an integrative evolutionary model for this patient. CNV subclones were determined at a relative early time and kept unchanged, and CNV Clone 2 with metastatic advantages was separated from the common ancestors during intramammary spread and metastasis. In the meantime, SNVs were accumulated gradually. Conclusions: In conclusion, we found distinct clonal evolution patterns on SNV and CNV levels in multifocal breast cancer and identified a CNV clone with metastatic advantages.
A genome-wide association study to identify candidate genes for metabolic disorders in offspring by in vitro fertilization
Authors: Liu Lihong , Ha Siyao , Li Zhiling , Li MingQing
Published: September 2021

In vitro fertilization (IVF) processes increase offspring's short-term and long-term health risks, but their mechanisms remain unclear. We conducted a bibliometric analysis to determine the landscape of IVF offspring health. Subsequently, a bioinformatics method was utilized to identify the co-genes properties and biological function mechanisms of IVF and type 2 diabetes mellitus (T2DM). Finally, we predicted compounds against key targets and performed multiple validations of the mechanisms underlying IVF offspring health risks. We identified 15 genes associated with T2DM, and their biological functions are primarily associated with lipid metabolism. We also identified the properties of co-genes, modified characteristics, confirmed a conserved motif, identified 3 SNPs sites, and determined the three core genes, APOA1, APOB, and APOE, which were mainly correlated with metabolic and cardiovascular diseases. In addition, we predicted drugs that may improve metabolic abnormalities in IVF offspring. The impact of aberrant lipid metabolism in offspring after IVF therapy warrants additional investigation, particularly in terms of long-term health consequences and possible mechanisms.
Categorization of Different Clamp Types Used For The Endurance Test of Human Grafts – A Systematic Review
Authors: Farago Denes , Kozma Blanka , Kiss Rita Maria
Published: September 2021

BackgroundThe use of tendon allografts for orthopedic repair has gained wide acceptance in recent years, most notably in anterior cruciate tendon reconstruction. Multiple studies support the use of tendon allografts and the benefits of its use are well accepted and understood. One of the important criteria of the use of tendon allografts is statistically similar histological and biomechanical properties to autographs. Five major scientific literature databases (Web of Science, Science Direct, Scopus, PloS ONE, Hindawi) and additional sources were used. ResultsThe objective of this systematic literature review is to investigate and categorize existing clamps used in the determination of the biomechanical properties (maximum load, maximum strength, modulus of elasticity, ultimate strain, stiffness) of tendons. Studies had to use an endurance test of tendons and clamps in detail. The database search and additional sources resulted in 274 records. 216 records eliminated during the screening for various reasons. The number of articles used in the final synthesis was 58. Search for publications dated between 1991 and Oct 31st, 2020. A variety of clamps for use during the endurance test of tendons were identified and categorized according to the temperature used during the measurement. The clamps are divided into three groups: room temperature, cooled or heated clamps.ConclusionsOn the basis of the systematic literature review, mechanical parameters determined by usage with cooled clamps proved to be more reliable than with those at room temperature and with heated clamps. The main advantage of the cooled clamps is that there is no limit to the type and length of the tendon. This study provides an overview of clamps and does not represent the modernity of any method.
Distribution of Sulfonamide Antibiotics and Resistance Genes and Their Correlation with Water Quality in Urban Rivers(Changchun City), China in Autumn and Winter
Authors: Zhao Ke , Li Chunming , Wang Qian , Lu Hai
Published: September 2021

With the extensive use of antibiotics, antibiotics contamination and antibiotic resistance genes (ARGs) in the water environment is becoming severe. In this study, the distribution characteristics of sulfonamide antibiotics and resistance genes in the urban section of the Yitong River in autumn and winter were studied. The correlation between them and water quality parameters was analyzed using liquid chromatography/mass spectrometry (LC/MS/MS) and polymerase chain reaction (PCR) fluorescence quantitative technology. The results showed that the concentration of seven sulfonamide antibiotics in surface water and sediment of the river was generally at the level of ng/L and ng/g; the total concentration range was 11.08-160.60ng/L and ND-85.68ng/g, respectively. The total concentrations of antibiotics were similar in autumn and winter, where SMX was the primary type of antibiotics. The results of Risk Quotients (RQs) showed that SMX and SDZ had moderate acute risk to the corresponding sensitive species in river water, SPD and SIZ had low acute risk, while the rest had no risk. The total bacterial abundance in surface water and sediment was in the range of 10 5 -10 6 and 10 8 -10 11 , respectively. The detection rates of three sulfonamide resistance genes were 100%; the relative abundance was in the range of 10 -3 -10 -1 , and sul1 was the primary resistance gene. The correlation analysis showed that most antibiotics were significantly related. The three resistance genes had a positive correlation, negative correlation, and non-correlation, and most antibiotics had a weak correlation with resistance genes. Nutrients had a more significant impact on antibiotics, and other water quality indicators had a more negligible effect on antibiotics and resistance genes.
Application of rapidly improving battery technology for direct electrification of intraregional container shipping
Authors: Kersey Jessica , Popovitch Natalie , Phadke Amol
Published: September 2021

International maritime shipping—powered by heavy fuel oil—contributes 2.5%, 12%, and 13% of global anthropogenic CO2, SO2, and NOx emissions, respectively. The direct electrification of vessels has been underexplored as a low-emission option despite its considerable efficiency advantage over electrofuels such as green hydrogen and ammonia. Previous studies of ship electrification have relied on outdated battery cost and energy density values and have incorrectly assumed mechanical space to be a fixed technical variable. We show that with near-future battery prices of $100 kWh-1 the electrification of intraregional trade routes of less than 1,000 km is economically feasible with minimal impact to ship carrying capacity. Projected declines in battery price to $50 kWh-1 could improve this range to 5,000 km. We describe a pathway for the battery electrification of containerships within this decade that electrifies over 40% of global containership traffic, reduces CO2 emissions by 40% for US-based vessels, and mitigates the health impacts of air pollution on coastal communities.
Analysis of BMP3 Variants In The Causality of Ocular Coloboma
Authors: Fox Sabrina , Widen Sonya A. , Asai-Coakwell Mika , Havrylov Serhiy , Benson Matthew , Prichard Lisa B. , Baddam Pranidhi , Graf Daniel , Lehmann Ordan J. , Waskiewicz Andrew J.
Published: September 2021

Coloboma, a congenital disorder characterized by gaps in ocular tissues, is caused when the choroid fissure fails to close during embryonic development. Several loci have been associated with coloboma, but these represent less than 40% of those that are involved with this disease. Here, we describe a novel coloboma-causing locus, BMP3. Whole exome sequencing and Sanger sequencing of patients with coloboma identified three variants in BMP3, two of which are predicted to be disease causing. Consistent with this, bmp3 mutant zebrafish have aberrant fissure closure. bmp3 is expressed in the ventral head mesenchyme and regulates phosphorylated Smad3 in a population of cells adjacent to the choroid fissure. Furthermore, mutations in bmp3 sensitize embryos to Smad3 inhibitor treatment resulting in open choroid fissures. Micro CT scans and Alcian blue staining of zebrafish demonstrate that mutations in bmp3 cause midface hypoplasia, suggesting that bmp3 regulates cranial neural crest cells. Consistent with this, we see active Smad3 in a population of periocular neural crest cells, and bmp3 mutant zebrafish have reduced neural crest cells in the choroid fissure. Taken together, this data suggests that Bmp3 controls Smad3 phosphorylation in neural crest cells to regulate early craniofacial and ocular development.
Feasibility of Laparoscopic Proximal Gastrectomy With Piggyback Jejunal Interposition Double-Tract Reconstruction for Proximal Gastric Cancer. A Propensity Score Matching Analysis
Authors: Li ZhiGuo , Dong JianHong , Huang QingXing , Guo Wei , Song YanYang , Zhang WanHong , Ma Jun , Wang Yi , Ma GuoLong , Wang ZhenHua , Ren YiPeng , Gao Fei , Li LinJie
Published: September 2021

Background

The clinical effect of laparoscopic proximal gastrectomy (LPG) with piggyback jejunal interposition double-tract reconstruction (PJIDTR) is not clear yet. The purpose of this study was to compare the efficacy of LPG with PJIDTR versus laparoscopic total gastrectomy (LTG) with Roux-en-Y reconstruction (overlap method) for proximal EGC using propensity score matching.
Methods

We retrospectively collected data from the patients with proximal EGC who were treated in Shanxi Cancer Hospital between January 2012 and December 2015. Propensity score was used to match LTG patients with LPG patients. The patient characteristics, clinical outcomes, nutritional indicators, reflux esophagitis incidence and overall survival were compared between the two groups.
Results

Of the 424 patients, 200 were excluded and 50 of the remaining patients received LPG with PJIDTR. Fifty matched LTG patients were screened. Comparison of intraoperative indicators, operative time, blood loss and number of retrieved lymphnodes between the two groups showed no statistical significance (P > 0.05). There was no statistically significant differences in first anal exhaust time, postoperative hospital stay, and early complications between the two groups (P > 0.05). The nutrition indexes at one year after surgery in the LPG group were significantly better than LTG group (P < 0.05). At one year, there were no differences in reflux symptoms (Visick score) or endoscopic esophagitis (Los Angeles Classification) between the two groups. No tumor recurrence was observed in either group. The 5-year overall survival rates of the two groups were 98% and 90%, respectively (p = 0.08).
Conclusion

The postoperative nutritional outcomes of LPG with PJIDTR were better than those of LTG. The incidence of reflux esophagitis, complications, and 5-year overall survival were similar between the two groups. LPG with PJIDTR may be suitable for proximal EGC.
Molecular and Cellular Reports A Pharmacological Study of the Action of Esculetin on Human Prostate Cancer Cells
Authors: Jan Chung-Ren , Wang Jue-Long , Liao Wei-Chuan , Lin Rong-An , Chang Shu-Han , Kuo Chun-Chi , Hao Lyh-Jyh , Chou Chiang-Ting
Published: September 2021

Esculetin is a derivative of coumarin, and is the dominant, vigorous component of the conventional Chinese medicine Cortex Fraxini. Recently, the molecular pathway study and clinical use of Cortex Fraxini and esculetin are becoming intensive. In vitro, esculetin has been shown to provoke apoptotic responses via mitochondrial routes and other cellular responses in diverse cell types. The action of esculetin on cytosolic Ca2+ concentration ([Ca2+]i) in prostate cells is unknown. [Ca2+]i were assayed by applying fura-2, a fluorescent Ca2+-sensitive probe. WST-1 was used to measure cell death. Esculetin at doses of 25–100 µM provoked [Ca2+]i raises. Removing external Ca2+ decreased the response by 15%. Esculetin (100 µM) provoked Mn2+ entry implying Ca2+ influx. Esculetin-provoked Ca2+ influx was suppressed by half by protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate, PMA) and inhibitor (GF109203X); and by three inhibitors of store-operated Ca2+ channels: nifedipine, econazole and SKF96365. In the absence of Ca2+, pretreatment with the endoplasmic reticulum (ER) Ca2+ pump suppressor thapsigargin completely suppressed esculetin-provoked [Ca2+]i raises. Suppression of phospholipase C (PLC) with U73122 eliminated esculetin-provoked [Ca2+]i raises. Esculetin at 20–70 µM caused death of cells, which was not prevented by incubation with the Ca2+ binder 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). In sum, in PC3 prostate cells, esculetin provoked [Ca2+]i raises by provoking PLC-associated Ca2+ discharge from ER and Ca2+ influx via PKC-sensitive store-operated Ca2+ influx. Additionally, esculetin provoked Ca2+-dissociated cell death.
Clinical Significance of Changes in the Subendocortical Volume of Wilson Disease
Authors: Xiao Xia , Zhou Xiangxue , Huang Zihuan , Liao Jian , Chu Jianping
Published: September 2021

Wilson disease (WD) is a rare neurogenetic disease with a variety of clinical manifestations. The disorder of copper metabolism can lead to cell necrosis, while nerve cell necrosis can reduce the volume of the corresponding parts. This study quantifies the degree of nerve cell injury by studying the subcortical volume changes in WD patients, and discusses the correlation between nerve cell injury in different parts and clinical manifestations. The results showed that compared with the healthy control group, the subcortical volume of WD decreased significantly, and the decrease in different parts was related to clinical symptoms. This study shows that we can quantify the degree of nerve cell injury by measuring the change of subcortical volume. Predict possible clinical symptoms.
Inhibition of FOXO1-Mediated Autophagy Promotes Paclitaxel-Induced Apoptosis in MDA-MB-231 Cell Lines
Authors: Xu Kaixiang , Zhu Wanyun , Xu Anyong , Xiong Zhe , Zhao Heng , Jiao Deling , Qing Yubo , Jamal Muhammad Ameen , Wei Hong-Jiang , Zhao Hong-Ye
Published: September 2021

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancers and often produces resistance to paclitaxel (PTX) therapy. Autophagy plays an important cytoprotective role in PTX-induced tumor cell death and targeting autophagy is promising to improve the efficacy of tumor chemotherapy in recent years. Here, we reported that PTX induced both apoptosis and autophagy of MDA-MB-231 cells, and inhibition of autophagy enable to promote apoptotic cell death. Furthermore, we found that FOXO1 enhanced PTX-induced autophagy by a transcriptional activation pattern in MDA-MB-231 cells, which was associated with its downstream target genes ATG5, VPS34, BECN1 and MAP1LC3B. The knockdown of FOXO1 attenuated the survival of MDA-MB-231 cells under the PTX treatment. These findings will be beneficial to improve the treatment efficacy of PTX and to develop the autophagic target therapy of TNBC.
Peroxisomal Proliferator-Activated Receptor β/δ Deficiency Induces Cognitive Alterations
Authors: Espinosa-Jimenez Triana , Busquets Oriol , Cano Amanda , Verdaguer Ester , Olloquequi Jordi , Auladell Carme , Folch Jaume , Wahli Walter , Vazquez-Carrera Manel , Camins Antoni , Ettcheto Miren
Published: September 2021

BackgroundPPARβ/δ, the most PPAR abundant isotype in the central nervous system is involved in the modulation of microglial homeostasis and metabolism. Several studies have demonstrated that people suffering from type 2 diabetes mellitus develop cognitive decline turning insulin resistance one of the best predictors of this disturbance. Although numerous investigations have studied the role of PPARb/d in metabolism, its role in neuronal and cognitive function has been underexplored. Therefore, the aim of the study is to determine the role of PPARb/d in the neuropathological pathways involved in the development of cognitive decline and as to whether a risk factor involved in cognitive loss such as obesity modulates neuropathological markers.6-month-old male PPARβ/δ-null (PPARβ/δ-/-) and wildtype (WT) littermates with the same genetic background (C57BL/6X129/SV) and exceptionally, C57BL/6 were used. After the weaning, animals were fed either with conventional chow (CT) or with a palmitic acid-enriched diet containing 45% of fat mainly from hydrogenated coconut oil (HFD). Thus, four groups were defined: WT CT, WT HFD, PPARβ/δ-/- CT and PPARβ/δ-/- HFD and several pathological mechanisms involved in cognitive decline were analyzed.ResultsOur results confirmed that C57BL/6X129/SV showed significantly increased levels of anxiety compared to C57BL/6. Therefore, to evaluate cognitive decline, behavioral tests were dismissed, and dendritic spine quantification and other biochemical biomarkers were performed.PPARβ/δ-/- mice exhibited a decrease in dendritic spine density and synaptic markers, suggesting an alteration in cognitive function and synaptic plasticity. Likewise, our study demonstrated that the lack of PPARβ/δ receptor enhances gliosis in the hippocampus, contributing to astrocyte and microglial activation and also induced an increase in neuroinflammatory biomarkers. Additionally, alterations in the hippocampal insulin receptor pathway were found. Interestingly, while some of the disturbances caused by the lack of PPARβ/δ were not affected by feeding the HFD, others were exacerbated or required the combination of both factors.ConclusionsTaken together, these findings suggest that the loss of PPARβ/δ-/- affects neuronal and synaptic structure, contributing to cognitive dysfunction and, they also present this receptor as a possible new target for the treatment of cognitive decline.
LncRNA-AK138945 Regulates Myocardial Ischemia-Reperfusion Injury Via the miR-1-GRP94 Signaling Pathway
Authors: Wang Yanying , Shao Yingchun , Huang Jian , Li Mengmeng , Yu Qi , Gong Manyu , Yang Xuewen , Qu Yunmeng , Liu Dongping , Wang Yaqi , Li Haodong , Jiao Lei , Zhang Ying
Published: September 2021

Myocardial ischemia-reperfusion injury (MIRI) is one of the main causes of high mortality of cardiovascular diseases (CVD). Long non-coding RNAs (lncRNAs), as a new type of gene expression regulators, play a key role in multiple processes of CVD. In this study, myocardial apoptosis was found to be increased in both MIRI heart and hydrogen peroxide (H2O2) treated myocardial cells. Meanwhile, the level of lncRNA-AK138945 was reduced. At the molecular level, knockdown of lncRNA-AK138945 increased the expression of pro-apoptosis proteins and decreased the expression of anti-apoptosis protein. Mechanically, miR-1a-3p was verified as the target of lncRNA-AK138945, which has been previously confirmed as a target regulator of endoplasmic reticulum stress-related protein GRP94. In addition, knockdown of lncRNA-AK138945 markedly inhibited the expression of GRP94, which further aggravated the apoptosis of cardiomyocytes. Notably, FOXO3 was identified as a transcriptional regulator of lncRNA-AK138945, and overexpression of FOXO3 could promote the expression of lncRNA-AK138945. In conclusion, lncRNA-AK138945 participated in the regulation of MIRI via the miR-1-GRP94 signaling pathway.