bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agyrotropic Electron Distributions in the Terrestrial Foreshock Transients
Authors: Gao C.‐H. , Tang B.‐B. , Guo X.‐C. , Li W. Y. , Khotyaintsev Y. V. , Graham D. B. , Turner D. L. , Yang Z. W. , Wang C. 
Published: February 2023

AbstractAgyrotropic electron distributions are frequently taken as an indicator of electron diffusion regions of magnetic reconnection. However, they have also been found at electron‐scale boundaries of the non‐reconnecting magnetopause and are generated by the electron finite gyroradius effect. Here, we present magnetospheric multiscale observations of agyrotropic electron distributions in the foreshock region. These distributions are generated by the electron finite gyroradius effect after magnetic curvature scattering at a thin electron‐scale boundary. Meanwhile, the signatures of magnetic reconnection are absent at this boundary. The test‐particle simulation is adopted to verify the generation of the agyrotropic electron distributions by assuming one‐dimensional magnetic geometry. These observations suggest that agyrotropic electron distributions can be more widely formed at electron‐scale boundaries in space plasma environment.
TRICE‐2 Rocket Observations in the Low‐Altitude Cusp: Boundaries and Comparisons With Models
Authors: Petrinec S. M. , Kletzing C. A. , Bounds S. R. , Fuselier S. A. , Trattner K. J. , Sawyer R. P. 
Published: February 2023

AbstractThe launch of the Twin Rockets to Investigate Cusp Electrodynamics‐2 (TRICE‐2) took place on the morning of 08 December 2018. The two rockets of this campaign each sampled the low‐altitude Northern Hemisphere cusp region at approximately the apex of each rocket's trajectory (1,042 and 757 km for the High flyer and Low flyer, respectively). Ion and electron electrostatic analyzers (ESAs) on board each rocket measured in situ particle populations throughout the flights. Energy‐flux spectrograms of ions and electrons from each ESA clearly show the passage of each rocket through the cusp region. This work examines the locations of these entrance/exit points in relation to cusp models as provided in and compiled from the published literature, along with a discussion of model variables that have been optimized to best fit the cusp region boundary sampling locations by TRICE‐2. The results of this study set the stage for understanding the upcoming NASA Small Explorer Tandem Reconnection and Cusp Electrodynamics Reconnaissance Satellites orbital plane intersections with (i.e., “trajectory cuts” through) the cusp region.
Clinical and biological markers predictive of treatment response associated with metastatic pancreatic adenocarcinoma
Authors: Dayimu Alimu , Di Lisio Lorena , Anand Shubha , Roca-Carreras Isart , Qian Wendi , Al-Mohammad Abdulrahman , Basu Bristi , Valle Juan W. , Jodrell Duncan , Demiris Nikos , Corrie Pippa 
Published: February 2023

Abstract
Background
Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) offers limited benefits, but survival outcomes vary. Reliable predictive response biomarkers to guide patient management are lacking.

Methods
Patient performance status, tumour burden (determined by the presence or absence of liver metastases), plasma protein biomarkers (CA19-9, albumin, C-reactive protein and neutrophils) and circulating tumour DNA (ctDNA) were assessed in 146 patients with metastatic PDAC prior to starting either concomitant or sequential nab-paclitaxel + gemcitabine chemotherapy in the SIEGE randomised prospective clinical trial, as well as during the first 8 weeks of treatment. Correlations were made with objective response, death within 1 year and overall survival (OS).

Results
Initial poor patient performance status, presence of liver metastases and detectable mutKRAS ctDNA all correlated with worse OS after adjusting for the different biomarkers of interest. Objective response at 8 weeks also correlated with OS (P = 0.026). Plasma biomarkers measured during treatment and prior to the first response assessment identified ≥10% decrease in albumin at 4 weeks predicted for worse OS (HR 4.75, 95% CI 1.43–16.94, P = 0.012), while any association of longitudinal evaluation of mutKRAS ctDNA with OS was unclear (β = 0.024, P = 0.057).

Conclusions
Readily measurable patient variables can aid the prediction of outcomes from combination chemotherapy used to treat metastatic PDAC. The role of mutKRAS ctDNA as a tool to guide treatment warrants further exploration.

Clinical trial registration
ISRCTN71070888; ClinialTrials.gov (NCT03529175).
The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures
Authors: Fusée Leila , Salomao Norman , Ponnuswamy Anand , Wang Lixiao , López Ignacio , Chen Sa , Gu Xiaolian , Polyzoidis Stavros , Vadivel Gnanasundram Sivakumar , Fahraeus Robin 
Published: February 2023

AbstractCellular stress conditions activate p53-dependent pathways to counteract the inflicted damage. To achieve the required functional diversity, p53 is subjected to numerous post-translational modifications and the expression of isoforms. Little is yet known how p53 has evolved to respond to different stress pathways. The p53 isoform p53/47 (p47 or ΔNp53) is linked to aging and neural degeneration and is expressed in human cells via an alternative cap-independent translation initiation from the 2nd in-frame AUG at codon 40 (+118) during endoplasmic reticulum (ER) stress. Despite an AUG codon in the same location, the mouse p53 mRNA does not express the corresponding isoform in either human or mouse-derived cells. High-throughput in-cell RNA structure probing shows that p47 expression is attributed to PERK kinase-dependent structural alterations in the human p53 mRNA, independently of eIF2α. These structural changes do not take place in murine p53 mRNA. Surprisingly, PERK response elements required for the p47 expression are located downstream of the 2nd AUG. The data show that the human p53 mRNA has evolved to respond to PERK-mediated regulation of mRNA structures in order to control p47 expression. The findings highlight how p53 mRNA co-evolved with the function of the encoded protein to specify p53-activities under different cellular conditions.
Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer
Authors: Tintelnot Joseph , Xu Yang , Lesker Till R. , Schönlein Martin , Konczalla Leonie , Giannou Anastasios D. , Pelczar Penelope , Kylies Dominik , Puelles Victor G. , Bielecka Agata A. , Peschka Manuela , Cortesi Filippo , Riecken Kristoffer , Jung Maximilian , Amend Lena , Bröring Tobias S. , Trajkovic-Arsic Marija , Siveke Jens T. , Renné Thomas , Zhang Danmei , Boeck Stefan , Strowig Till , Uzunoglu Faik G. , Güngör Cenap , Stein Alexander , Izbicki Jakob R. , Bokemeyer Carsten , Sinn Marianne , Kimmelman Alec C. , Huber Samuel , Gagliani Nicola 
Published: February 2023

AbstractPancreatic ductal adenocarcinoma (PDAC) is expected to be the second most deadly cancer by 2040, owing to the high incidence of metastatic disease and limited responses to treatment1,2. Less than half of all patients respond to the primary treatment for PDAC, chemotherapy3,4, and genetic alterations alone cannot explain this5. Diet is an environmental factor that can influence the response to therapies, but its role in PDAC is unclear. Here, using shotgun metagenomic sequencing and metabolomic screening, we show that the microbiota-derived tryptophan metabolite indole-3-acetic acid (3-IAA) is enriched in patients who respond to treatment. Faecal microbiota transplantation, short-term dietary manipulation of tryptophan and oral 3-IAA administration increase the efficacy of chemotherapy in humanized gnotobiotic mouse models of PDAC. Using a combination of loss- and gain-of-function experiments, we show that the efficacy of 3-IAA and chemotherapy is licensed by neutrophil-derived myeloperoxidase. Myeloperoxidase oxidizes 3-IAA, which in combination with chemotherapy induces a downregulation of the reactive oxygen species (ROS)-degrading enzymes glutathione peroxidase 3 and glutathione peroxidase 7. All of this results in the accumulation of ROS and the downregulation of autophagy in cancer cells, which compromises their metabolic fitness and, ultimately, their proliferation. In humans, we observed a significant correlation between the levels of 3-IAA and the efficacy of therapy in two independent PDAC cohorts. In summary, we identify a microbiota-derived metabolite that has clinical implications in the treatment of PDAC, and provide a motivation for considering nutritional interventions during the treatment of patients with cancer.
Essential elements of radical pair magnetosensitivity in Drosophila
Authors: Bradlaugh Adam A. , Fedele Giorgio , Munro Anna L. , Hansen Celia Napier , Hares John M. , Patel Sanjai , Kyriacou Charalambos P. , Jones Alex R. , Rosato Ezio , Baines Richard A. 
Published: February 2023

AbstractMany animals use Earth’s magnetic field (also known as the geomagnetic field) for navigation1. The favoured mechanism for magnetosensitivity involves a blue-light-activated electron-transfer reaction between flavin adenine dinucleotide (FAD) and a chain of tryptophan residues within the photoreceptor protein CRYPTOCHROME (CRY). The spin-state of the resultant radical pair, and therefore the concentration of CRY in its active state, is influenced by the geomagnetic field2. However, the canonical CRY-centric radical-pair mechanism does not explain many physiological and behavioural observations2–8. Here, using electrophysiology and behavioural analyses, we assay magnetic-field responses at the single-neuron and organismal levels. We show that the 52 C-terminal amino acid residues of Drosophila melanogaster CRY, lacking the canonical FAD-binding domain and tryptophan chain, are sufficient to facilitate magnetoreception. We also show that increasing intracellular FAD potentiates both blue-light-induced and magnetic-field-dependent effects on the activity mediated by the C terminus. High levels of FAD alone are sufficient to cause blue-light neuronal sensitivity and, notably, the potentiation of this response in the co-presence of a magnetic field. These results reveal the essential components of a primary magnetoreceptor in flies, providing strong evidence that non-canonical (that is, non-CRY-dependent) radical pairs can elicit magnetic-field responses in cells.
Four ways blue foods can help achieve food system ambitions across nations
Authors: Crona Beatrice I. , Wassénius Emmy , Jonell Malin , Koehn J. Zachary , Short Rebecca , Tigchelaar Michelle , Daw Tim M. , Golden Christopher D. , Gephart Jessica A. , Allison Edward H. , Bush Simon R. , Cao Ling , Cheung William W. L. , DeClerck Fabrice , Fanzo Jessica , Gelcich Stefan , Kishore Avinash , Halpern Benjamin S. , Hicks Christina C. , Leape James P. , Little David C. , Micheli Fiorenza , Naylor Rosamond L. , Phillips Michael , Selig Elizabeth R. , Springmann Marco , Sumaila U. Rashid , Troell Max , Thilsted Shakuntala H. , Wabnitz Colette C. C. 
Published: February 2023

AbstractBlue foods, sourced in aquatic environments, are important for the economies, livelihoods, nutritional security and cultures of people in many nations. They are often nutrient rich1, generate lower emissions and impacts on land and water than many terrestrial meats2, and contribute to the health3, wellbeing and livelihoods of many rural communities4. The Blue Food Assessment recently evaluated nutritional, environmental, economic and justice dimensions of blue foods globally. Here we integrate these findings and translate them into four policy objectives to help realize the contributions that blue foods can make to national food systems around the world: ensuring supplies of critical nutrients, providing healthy alternatives to terrestrial meat, reducing dietary environmental footprints and safeguarding blue food contributions to nutrition, just economies and livelihoods under a changing climate. To account for how context-specific environmental, socio-economic and cultural aspects affect this contribution, we assess the relevance of each policy objective for individual countries, and examine associated co-benefits and trade-offs at national and international scales. We find that in many African and South American nations, facilitating consumption of culturally relevant blue food, especially among nutritionally vulnerable population segments, could address vitamin B12and omega-3 deficiencies. Meanwhile, in many global North nations, cardiovascular disease rates and large greenhouse gas footprints from ruminant meat intake could be lowered through moderate consumption of seafood with low environmental impact. The analytical framework we provide also identifies countries with high future risk, for whom climate adaptation of blue food systems will be particularly important. Overall the framework helps decision makers to assess the blue food policy objectives most relevant to their geographies, and to compare and contrast the benefits and trade-offs associated with pursuing these objectives.
RCS reduction using grounded multi-height multi-dielectrics metasurfaces
Authors: Heidari Maryam , Sedighy Seyed Hassan , Amirhosseini Mohamad Khalaj 
Published: February 2023

AbstractIn this paper, the PO method with the array theory are used to formulate the RCS of a grounded multi-height dielectric surface which can be employed in the design and optimization of a metasurface consisting of dielectric tiles with different heights and permittivities. The proposed closed form relations can be used instead of full wave simulation to design an optimized dielectric grounded metasurface, properly. Finally, three different RCS reducer metasurfaces are designed and optimized with three different dielectric tiles by using the proposed analytical relations. The results prove that the proposed ground dielectric metasurface achieve more than 10 dB RCS reduction at 4.4–16.3 GHz (114.9%) frequency range. This result proves the accuracy and effectiveness of the proposed analytical method which can be used in the RCS reducer metasurfaces design.
GRIM-19 in asthenozoospermia regulates GC-2 spd cell proliferation, apoptosis and migration
Authors: Li Fei , Niu Aiqin , Zhao Kangjun , Feng Jianbing , Chen Ying 
Published: February 2023

AbstractAsthenozoospermia (AZS) is a severe form of male infertility with no clear pathogenesis, despite numerous research efforts, there is no consensus on this. This study was to investigate the expression of gene-associated with retinoid-interferon-induced mortality 19 (GRIM-19) in the sperm of patients with asthenozoospermia and the regulation of GC-2 spd cell proliferation, apoptosis and migration. We analyzed the sperm samples from 82 asthenozoospermia and normal patients were collected in the First People's Hospital of Shangqiu and the First Affiliated Hospital of Zhengzhou University. Immunofluorescence, western blots and RT-qPCR analyses were used to verify the expressions of GRIM-19. MTT assays were used to assess cell proliferations, flow cytometry was performed to assess cell apoptosis, wound‑healing was performed to measure cell migration. Immunofluorescence showed that GRIM-19 is predominantly expressed in the sperm mid-piece, the mRNA expressions of GRIM-19 in sperms of the asthenozoospermia group were significantly low, relative to the normal group (OR 0.266; 95% CI = 0.081–0.868; P = 0.028). The protein expressions of GRIM-19 in sperms of the asthenozoospermia group were significantly lower than that of the normal group as well (GRIM-19/GAPDH: 0.827 ± 0.063 vs 0.458 ± 0.033; P < 0.001). GRIM-19 overexpression promotes GC-2 spd cell proliferation and migration and reduces apoptosis, while GRIM-19-silenced reduces GC-2 spd cell proliferation and migration and increased apoptosis. GRIM-19 is closely related to the occurrence of asthenozoospermia and promotes GC-2 spd cell proliferation and migration and reduces apoptosis.
A multiplexed, paired-pooled droplet digital PCR assay for detection of SARS-CoV-2 in saliva
Authors: Wagner Kaitlyn , Fox Phil , Gordon Elizabeth , Hahn Westen , Olsen Kenzie , Markham Alex , Buglewicz Dylan , Selemenakis Platon , Lessard Avery , Goldstein Daniella , Threatt Alissa , Davis Luke , Miller-Dawson Jake , Stockett Halie , Sanders Hailey , Rugh Kristin , Turner Houston , Remias Michelle , Williams Maggie , Chavez Jorge , Galindo Gabriel , Cialek Charlotte , Koch Amanda , Fout Alex , Fosdick Bailey , Broeckling Bettina , Zabel Mark D. 
Published: February 2023

AbstractIn response to the SARS-CoV-2 pandemic, we developed a multiplexed, paired-pool droplet digital PCR (MP4) screening assay. Key features of our assay are the use of minimally processed saliva, 8-sample paired pools, and reverse-transcription droplet digital PCR (RT-ddPCR) targeting the SARS-CoV-2 nucleocapsid gene. The limit of detection was determined to be 2 and 12 copies per µl for individual and pooled samples, respectively. Using the MP4 assay, we routinely processed over 1,000 samples a day with a 24-h turnaround time and over the course of 17 months, screened over 250,000 saliva samples. Modeling studies showed that the efficiency of 8-sample pools was reduced with increased viral prevalence and that this could be mitigated by using 4-sample pools. We also present a strategy for, and modeling data supporting, the creation of a third paired pool as an additional strategy to employ under high viral prevalence.
Targeting DNA repair pathways with B02 and Nocodazole small molecules to improve CRIS-PITCh mediated cassette integration in CHO-K1 cells
Authors: Rahmani Behnaz , Kheirandish Mohammad Hassan , Ghanbari Samaneh , Raz Abbasali , Shamsi Fahimeh , Davami Fatemeh 
Published: February 2023

AbstractCRISPR-mediated integration could be used to develop the recombinant CHO (rCHO) cells by knock-in into the hotspot loci. However, low HDR efficiency besides the complex donor design is the main barrier for achieving so. The recently introduced MMEJ-mediated CRISPR system (CRIS-PITCh) uses a donor with short homology arms, being linearized in the cells via two sgRNAs. In this paper, a new approach to improve CRIS-PITCh knock-in efficiency by employing small molecules was investigated. Two small molecules, B02, a Rad51 inhibitor, and Nocodazole, a G2/M cell cycle synchronizer, were used to target the S100A hotspot site using a bxb1 recombinase comprised landing pad in CHO-K1 cells. Following transfection, the CHO-K1 cells were treated with the optimum concentration of one or combination of small molecules, being determined by the cell viability or flow cytometric cell cycle assay. Stable cell lines were generated and the single-cell clones were achieved by the clonal selection procedure. The finding showed that B02 improved the PITCh-mediated integration approximately twofold. In the case of Nocodazole treatment, the improvement was even more significant, up to 2.4-fold. However, the combinatorial effects of both molecules were not substantial. Moreover, according to the copy number and out-out PCR analyses, 5 and 6 of 20 clonal cells exhibited mono-allelic integration in Nocodazole and B02 groups, respectively. The results of the present study as the first attempt to enhance the CHO platform generation by exploiting two small molecules in the CRIS-PITCh system could be used in future researches to establish rCHO clones.
Exploring soil bacterial diversity in different micro-vegetational habitats of Dachigam National Park in North-western Himalaya
Authors: Mushtaq Hina , Ganai Bashir Ahmad , Jehangir Arshid 
Published: February 2023

AbstractDachigam National Park (DNP), in Zabarwan mountains of north-western Himalaya constitutes a region of high biodiversity with greater endemism. DNP is known for its unique micro-climate together with distinct vegetational zones providing home to variety of threatened and endemic plant, animal, and bird species. However, studies on soil microbial diversity in fragile ecosystems of north-western Himalaya in general and DNP in particular are lacking. This was thus a maiden attempt to study variations in soil bacterial diversity of DNP with respect to changing soil physico-chemical properties, vegetation, and altitude. Soil parameters depicted significant variations among different sites with highest values for temperature, OC, OM and TN being 22.2 ± 0.75 °C, 6.53 ± 0.32%, 11.25 ± 0.54%, 0.545 ± 0.04% from site-2 (low altitudinal grassland site) in summer and lowest of 5.1 ± 0.65 °C, 1.24 ± 0.26%, 2.14 ± 0.45% and 0.132 ± 0.04% at site-9 (high altitudinal mixed pine site) in winter. Bacterial CFU showed significant correlations with soil physico-chemical attributes. This study led to the isolation and identification of 92 morphologically varied bacteria with the highest (15) from site-2 and lowest (04) from site-9 which post BLAST analysis (via 16S rRNA analysis) depicted presence of only 57 distinct bacterial species under taxonomic phylum, Firmicutes and Proteobacteria. Nine species were widely spread (i.e., isolated from > 3 sites), however, most bacteria (37) were restricted to a particular site. Diversity indices ranged between 1.380 to 2.631 (Shannon–Weiner’s index); 0.747 to 0.923 (Simpson’s index) with highest values for site-2 and lowest for site-9. Index of similarity was highest (47.1%) between riverine sites (site-3 and site-4) whereas two mixed pine sites (site-9 and site-10) showed no similarity.
Identification of Parkinson’s disease-associated chromatin regulators
Authors: Xing Hailong , Wang Shanshan , Li Ke 
Published: February 2023

AbstractParkinson’s disease (PD) is a common neurological disorder that causes quiescent tremors, motor delays, depression, and sleep disturbances. Existing treatments can only improve symptoms, not stop progression or cure the disease, but effective treatments can significantly improve patients’ quality of life. There is growing evidence that chromatin regulatory proteins (CRs) are involved in a variety of biological processes, including inflammation, apoptosis, autophagy, and proliferation. But the relationship of chromatin regulators in Parkinson’s disease has not been studied. Therefore, we aim to investigate the role of CRs in the pathogenesis of Parkinson’s disease. We collected 870 chromatin regulatory factors from previous studies and downloaded data on patients with PD from the GEO database. 64 differentially expressed genes were screened, the interaction network was constructed and the key genes with the top 20 scores were calculated. Then we discussed its correlation with the immune function of PD. Finally, we screened potential drugs and miRNAs. Five genes related to the immune function of PD, BANF1, PCGF5, WDR5, RYBP and BRD2, were obtained by using the absolute value of correlation greater than 0.4. And the disease prediction model showed good predictive efficiency. We also screened 10 related drugs and 12 related miRNAs, which provided a reference for the treatment of PD. BANF1, PCGF5, WDR5, RYBP and BRD2 are related to the immune process of Parkinson’s disease and can predict the occurrence of Parkinson’s disease, which is expected to become a new target for the diagnosis and treatment of Parkinson’s disease.