bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does SARS-CoV-2 affect neurodegenerative disorders? TLR2, a potential receptor for SARS-CoV-2 in the CNS
Authors: Szabo Marcell P. , Iba Michiyo , Nath Avindra , Masliah Eliezer , Kim Changyoun 
Published: April 2022

AbstractThe coronavirus (COVID-19) pandemic, caused by severe acute respiratory system coronavirus 2 (SARS-CoV-2), has created significant challenges for scientists seeking to understand the pathogenic mechanisms of SARS-CoV-2 infection and to identify the best therapies for infected patients. Although ACE2 is a known receptor for the virus and has been shown to mediate viral entry into the lungs, accumulating reports highlight the presence of neurological symptoms resulting from infection. As ACE2 expression is low in the central nervous system (CNS), these neurological symptoms are unlikely to be caused by ACE2-virus binding. In this review, we will discuss a proposed interaction between SARS-CoV-2 and Toll-like receptor 2 (TLR2) in the CNS. TLR2 is an innate immune receptor that recognizes exogenous microbial components but has also been shown to interact with multiple viral components, including the envelope (E) protein of SARS-CoV-2. In addition, TLR2 plays an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Based on these observations, we hypothesize that TLR2 may play a critical role in the response to SARS-CoV-2 infiltration in the CNS, thereby resulting in the induction or acceleration of AD and PD pathologies in patients.
Assessment of child psychological attributes using strength and difficulties questionnaire for prediction of child behavior at first dental visit: a cross-sectional study
Authors: Anwar Sandra Moussa , Mahmoud Sara Ahmed , Aly Mariam Mohsen 
Published: April 2022

Abstract
Introduction
Predicting child behavior before the first dental visit is considered an effective approach that enables the dentist to guide child behavior during the dental treatment.

Aim
The present study aimed to detect psychological attributes of children seeking dental treatment for the first time using the strength and difficulties questionnaire (SDQ), evaluate actual child behavior during the dental treatment using Frankl Behavior Rating Scale, and test the association between these attributes and child behavior.

Material and method
The study was conducted on 128 children aged between 4 and 7 years attending the outpatient Pediatric Dentistry clinic for the first time. Parents were asked to answer the SDQ, then a simple restorative treatment under local anesthesia was performed for children to evaluate their behavior using Frankl Behavior Rating Scale.

Results
About 19.5% of the study sample were categorized as psychologically abnormal, where emotional and conduct problems were the most prevalent psychological attributes by a percentage of 22.7% and 20% respectively. A strong correlation was detected between the total difficulty score and child behavior.

Conclusions
Psychological problems are common among children aged from 4 to 7 years and they also affect their dental behavior.
Elevated FAM84B promotes cell proliferation via interacting with NPM1 in esophageal squamous cell carcinoma
Authors: Wang Fang , Cheng Caixia , Wang Xinhui , Chen Fei , Li Hongyi , Zhou Yan , Wang Yanqiang , Hu Xiaoling , Kong Pengzhou , Zhang Ling , Cheng Xiaolong , Cui Yongping 
Published: April 2022

AbstractFamily with sequence similarity 84, member B (FAM84B) is a significant copy number amplification gene in the 8q24.21 locus identified by our previous WGS study in esophageal squamous cell carcinoma (ESCC). However, its clinical relevance and potential mechanisms have been elusive. Here, we performed the association analyses between FAM84BAmp and clinicopathological features using 507 ESCC samples. The results indicated that, compared with the FAM84Bnon-Amp patients, the FAM84BAmp patients showed a more aggressive and a worse prognosis. A significant correlation was discovered between the expression level of FAM84B and FAM84BAmp in the ESCC cohort. Furthermore, we found that the forced expression change of FAM84B can influence ESCC cell proliferation and cell-cycle status, which is probably mediated by NPM1. A direct interaction between FAM84B and the C-terminal (189–294aa) of NPM1 was identified, which increased the NPM1 nuclear expression. Over-expression of NPM1 could inhibit the CDKN2A protein expression, which might affect the ESCC cell cycle. Our results indicate FAM84B CNA may be a potential diagnostic and therapeutic biomarker in ESCC, meanwhile, reveal a novel mechanism of FAM84B that promotes tumorigenesis via interacting with NPM1 and suppressing CDKN2A.
Targeting NOX4 disrupts the resistance of papillary thyroid carcinoma to chemotherapeutic drugs and lenvatinib
Authors: Tang Ping , Sheng Jianfeng , Peng Xiujuan , Zhang Renfei , Xu Tao , Hu Jun , Kang Yuexi , Wu Baiyi , Dang Hao 
Published: April 2022

AbstractAdvanced differentiated thyroid cancer cells are subjected to extreme nutritional starvation which contributes to develop resistance to treatments; however, the underlying mechanism remains unclear. Cells were subjected to serum deprivation by culture in medium containing 0.5% fetal bovine serum. A CCK8 assay, cell death Detection ELISAPLUS kit, and PI staining were conducted to determine cell viability, cell apoptosis, and cell cycle, respectively. NADPH oxidase 4 (NOX4) knockdown–stable cell lines were generated by lentivirus-mediated shRNA knockdown in BCPAP cells and TPC-1 cells. Etoposide and doxorubicin, two chemotherapeutic drugs, as well as lenvatinib were utilized to determine the effect of NOX4 on drug resistance. Lenvatinib-resistant BCPAP cells (LRBCs) were established to confirm this effect. The underlining mechanisms of NOX4 under starvation were explored using western blot. Finally, GLX351322, an inhibitor targeting NOX4, was used to inhibit NOX4-derived ROS in vitro and detect its effect on drug resistance of tumor cells in vivo. NOX4 is overexpressed under serum deprivation in BCPAP or TPC-1 cells. NOX4 knockdown impairs cell viability, increases cell apoptosis, extends G1 phase during cell cycle and modulates the level of energy-associated metabolites in starved cells. When the starved cells or LRBCs are treated with chemotherapeutic drugs or Lenvatinib, NOX4 knockdown inhibits cell viability and aggravates cell apoptosis depending on NOX4-derived ROS production. Mechanistically, starvation activates TGFβ1/SMAD3 signal, which mediates NOX4 upregulation. The upregulated NOX4 then triggers ERKs and PI3K/AKT pathway to influence cell apoptosis. GLX351322, a NOX4-derived ROS inhibitor, has an inhibitory effect on cell growth in vitro and the growth of BCPAP-derived even LRBCs-derived xenografts in vivo. These findings highlight NOX4 and NOX4-derived ROS as a potential therapeutic target in resistance to PTC.
Ubiquitin ligase STUB1 destabilizes IFNγ-receptor complex to suppress tumor IFNγ signaling
Authors: Apriamashvili Georgi , Vredevoogd David W. , Krijgsman Oscar , Bleijerveld Onno B. , Ligtenberg Maarten A. , de Bruijn Beaunelle , Boshuizen Julia , Traets Joleen J. H. , D’Empaire Altimari Daniela , van Vliet Alex , Lin Chun-Pu , Visser Nils L. , Londino James D. , Sanchez-Hodge Rebekah , Oswalt Leah E. , Altinok Selin , Schisler Jonathan C. , Altelaar Maarten , Peeper Daniel S. 
Published: April 2022

AbstractThe cytokine IFNγ differentially impacts on tumors upon immune checkpoint blockade (ICB). Despite our understanding of downstream signaling events, less is known about regulation of its receptor (IFNγ-R1). With an unbiased genome-wide CRISPR/Cas9 screen for critical regulators of IFNγ-R1 cell surface abundance, we identify STUB1 as an E3 ubiquitin ligase for IFNγ-R1 in complex with its signal-relaying kinase JAK1. STUB1 mediates ubiquitination-dependent proteasomal degradation of IFNγ-R1/JAK1 complex through IFNγ-R1K285and JAK1K249. Conversely, STUB1 inactivation amplifies IFNγ signaling, sensitizing tumor cells to cytotoxic T cells in vitro. This is corroborated by an anticorrelation betweenSTUB1expression and IFNγ response in ICB-treated patients. Consistent with the context-dependent effects of IFNγ in vivo, anti-PD-1 response is increased in heterogenous tumors comprising both wildtype and STUB1-deficient cells, but not full STUB1 knockout tumors. These results uncover STUB1 as a critical regulator of IFNγ-R1, and highlight the context-dependency of STUB1-regulated IFNγ signaling for ICB outcome.
Emergence and phenotypic characterization of the global SARS-CoV-2 C.1.2 lineage
Authors: Scheepers Cathrine , Everatt Josie , Amoako Daniel G. , Tegally Houriiyah , Wibmer Constantinos Kurt , Mnguni Anele , Ismail Arshad , Mahlangu Boitshoko , Lambson Bronwen E. , Martin Darren P. , Wilkinson Eduan , San James Emmanuel , Giandhari Jennifer , Manamela Nelia , Ntuli Noxolo , Kgagudi Prudence , Cele Sandile , Richardson Simone I. , Pillay Sureshnee , Mohale Thabo , Ramphal Upasana , Naidoo Yeshnee , Khumalo Zamantungwa T. , Kwatra Gaurav , Gray Glenda , Bekker Linda-Gail , Madhi Shabir A. , Baillie Vicky , Van Voorhis Wesley C. , Treurnicht Florette K. , Venter Marietjie , Mlisana Koleka , Wolter Nicole , Sigal Alex , Williamson Carolyn , Hsiao Nei-yuan , Msomi Nokukhanya , Maponga Tongai , Preiser Wolfgang , Makatini Zinhle , Lessells Richard , Moore Penny L. , de Oliveira Tulio , von Gottberg Anne , Bhiman Jinal N. 
Published: April 2022

AbstractGlobal genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The initial C.1.2 detection is associated with a high substitution rate, and includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 variants of concern or variants of interest. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta show high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2.
Inter-species Metabolic Interactions in an In-vitro Minimal Human Gut Microbiome of Core Bacteria
Authors: Shetty Sudarshan A. , Kuipers Ben , Atashgahi Siavash , Aalvink Steven , Smidt Hauke , de Vos Willem M. 
Published: April 2022

AbstractKnowledge of the functional roles and interspecies interactions are crucial for improving our understanding of the human intestinal microbiome in health and disease. However, the complexity of the human intestinal microbiome and technical challenges in investigating it pose major challenges. In this proof-of-concept study, we rationally designed, assembled and experimentally tested a synthetic Diet-based Minimal Microbiome (Db-MM) consisting of ten core intestinal bacterial species that together are capable of efficiently converting dietary fibres into short chain fatty acids (SCFAs). Despite their genomic potential for metabolic competition, all ten bacteria coexisted during growth on a mixture of dietary fibres, including pectin, inulin, xylan, cellobiose and starch. By integrated analyses of metabolite production, community composition and metatranscriptomics-based gene expression data, we identified interspecies metabolic interactions leading to production of key SCFAs such as butyrate and propionate. While public goods, such as sugars liberated from colonic fibres, are harvested by non-degraders, some species thrive by cross-feeding on energetically challenging substrates, including the butyrogenic conversion of acetate and lactate. Using a reductionist approach in an in-vitro system combined with functional measurements, our study provides key insights into the complex interspecies metabolic interactions between core intestinal bacterial species.
Genetic evidence supports the development of SLC26A9 targeting therapies for the treatment of lung disease
Authors: Gong Jiafen , He Gengming , Wang Cheng , Bartlett Claire , Panjwani Naim , Mastromatteo Scott , Lin Fan , Keenan Katherine , Avolio Julie , Halevy Anat , Shaw Michelle , Esmaeili Mohsen , Côté-Maurais Guillaume , Adam Damien , Bégin Stéphanie , Bjornson Candice , Chilvers Mark , Reisman Joe , Price April , Parkins Michael , van Wylick Richard , Berthiaume Yves , Bilodeau Lara , Mateos-Corral Dimas , Hughes Daniel , Smith Mary J. , Morrison Nancy , Brusky Janna , Tullis Elizabeth , Stephenson Anne L. , Quon Bradley S. , Wilcox Pearce , Leung Winnie M. , Solomon Melinda , Sun Lei , Brochiero Emmanuelle , Moraes Theo J. , Gonska Tanja , Ratjen Felix , Rommens Johanna M. , Strug Lisa J. 
Published: April 2022

AbstractOver 400 variants in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) are CF-causing. CFTR modulators target variants to improve lung function, but marked variability in response exists and current therapies do not address all CF-causing variants highlighting unmet needs. Alternative epithelial ion channel/transporters such as SLC26A9 could compensate for CFTR dysfunction, providing therapeutic targets that may benefit all individuals with CF. We investigate the relationship between rs7512462, a marker ofSLC26A9activity, and lung function pre- and post-treatment with CFTR modulators in Canadian and US CF cohorts, in the general population, and in those with chronic obstructive pulmonary disease (COPD). Rs7512462 CC genotype is associated with greater lung function in CF individuals with minimal function variants (for which there are currently no approved therapies;p = 0.008); and for gating (p = 0.033) and p.Phe508del/ p.Phe508del (p = 0.006) genotypes upon treatment with CFTR modulators. In parallel, human nasal epithelia with CC and p.Phe508del/p.Phe508del after Ussing chamber analysis of a combination of approved and experimental modulator treatments show greater CFTR function (p = 0.0022). Beyond CF, rs7512462 is associated with peak expiratory flow in a meta-analysis of the UK Biobank and Spirometa Consortium (p = 2.74 × 10−44) and providesp = 0.0891 in an analysis of COPD case-control status in the UK Biobank defined by spirometry. These findings support SLC26A9 as a therapeutic target to improve lung function for all people with CF and in individuals with other obstructive lung diseases.
Magnetic chirality
Authors: Cheong Sang-Wook , Xu Xianghan 
Published: April 2022

AbstractChirality with all broken mirror symmetries matters ubiquitously from DNA functionality, vine climbing, to the piezoelectricity of quartz crystals. Magnetic chirality means chirality in spin-ordered states or (atomic-scale or mesoscopic) spin textures. Magnetic chirality does not change with time-reversal operation, and chirality prime ($${\mathcal{C}}^\prime$$

C

′

) means that time-reversal symmetry in addition to all mirror symmetries is broken with free spatial rotations. We will discuss a few examples of magnetic chirality and $${\mathcal{C}}^\prime$$

C

′

, and their emergent physical properties. Some of these exotic properties have been recently observed, and many of them need to be experimentally confirmed.
Orbital selective switching of ferromagnetism in an oxide quasi two-dimensional electron gas
Authors: Di Capua R. , Verma M. , Radovic M. , Strocov V. N. , Piamonteze C. , Guedes E. B. , Plumb N. C. , Chen Yu , D’Antuono M. , De Luca G. M. , Di Gennaro E. , Stornaiuolo D. , Preziosi D. , Jouault B. , Miletto Granozio F. , Sambri A. , Pentcheva R. , Ghiringhelli G. , Salluzzo M. 
Published: April 2022

AbstractMulti-orbital physics in quasi-two-dimensional electron gases (q2DEGs) triggers intriguing phenomena not observed in bulk materials, such as unconventional superconductivity and magnetism. Here, we investigate the mechanism of orbital selective switching of the spin-polarization in the oxide q2DEG formed at the (001) interface between the LaAlO3, EuTiO3 and SrTiO3 band insulators. By using density functional theory calculations, transport, magnetic and x-ray spectroscopy measurements, we find that the filling of titanium-bands with 3dxz/3dyz orbital character in the EuTiO3 layer and at the interface with SrTiO3 induces an antiferromagnetic to ferromagnetic switching of the exchange interaction between Eu-4f7 magnetic moments. The results explain the observation of the carrier density-dependent ferromagnetic correlations and anomalous Hall effect in this q2DEG, and demonstrate how combined theoretical and experimental approaches can lead to a deeper understanding of emerging electronic phases and serve as a guide for the materials design of advanced electronic applications.
Phage anti-CBASS and anti-Pycsar nucleases subvert bacterial immunity
Authors: Hobbs Samuel J. , Wein Tanita , Lu Allen , Morehouse Benjamin R. , Schnabel Julia , Leavitt Azita , Yirmiya Erez , Sorek Rotem , Kranzusch Philip J. 
Published: April 2022

AbstractThe cyclic oligonucleotide-based antiphage signalling system (CBASS) and the pyrimidine cyclase system for antiphage resistance (Pycsar) are antiphage defence systems in diverse bacteria that use cyclic nucleotide signals to induce cell death and prevent viral propagation1,2. Phages use several strategies to defeat host CRISPR and restriction-modification systems3–10, but no mechanisms are known to evade CBASS and Pycsar immunity. Here we show that phages encode anti-CBASS (Acb) and anti-Pycsar (Apyc) proteins that counteract defence by specifically degrading cyclic nucleotide signals that activate host immunity. Using a biochemical screen of 57 phages in Escherichia coli and Bacillus subtilis, we discover Acb1 from phage T4 and Apyc1 from phage SBSphiJ as founding members of distinct families of immune evasion proteins. Crystal structures of Acb1 in complex with 3′3′-cyclic GMP–AMP define a mechanism of metal-independent hydrolysis 3′ of adenosine bases, enabling broad recognition and degradation of cyclic dinucleotide and trinucleotide CBASS signals. Structures of Apyc1 reveal a metal-dependent cyclic NMP phosphodiesterase that uses relaxed specificity to target Pycsar cyclic pyrimidine mononucleotide signals. We show that Acb1 and Apyc1 block downstream effector activation and protect from CBASS and Pycsar defence in vivo. Active Acb1 and Apyc1 enzymes are conserved in phylogenetically diverse phages, demonstrating that cleavage of host cyclic nucleotide signals is a key strategy of immune evasion in phage biology.
Searching thousands of genomes to classify somatic and novel structural variants using STIX
Authors: Chowdhury Murad , Pedersen Brent S. , Sedlazeck Fritz J. , Quinlan Aaron R. , Layer Ryan M. 
Published: April 2022

AbstractStructural variants are associated with cancers and developmental disorders, but challenges with estimating population frequency remain a barrier to prioritizing mutations over inherited variants. In particular, variability in variant calling heuristics and filtering limits the use of current structural variant catalogs. We present STIX, a method that, instead of relying on variant calls, indexes and searches the raw alignments from thousands of samples to enable more comprehensive allele frequency estimation.
Critical Assessment of Metagenome Interpretation: the second round of challenges
Authors: Meyer Fernando , Fritz Adrian , Deng Zhi-Luo , Koslicki David , Lesker Till Robin , Gurevich Alexey , Robertson Gary , Alser Mohammed , Antipov Dmitry , Beghini Francesco , Bertrand Denis , Brito Jaqueline J. , Brown C. Titus , Buchmann Jan , Buluç Aydin , Chen Bo , Chikhi Rayan , Clausen Philip T. L. C. , Cristian Alexandru , Dabrowski Piotr Wojciech , Darling Aaron E. , Egan Rob , Eskin Eleazar , Georganas Evangelos , Goltsman Eugene , Gray Melissa A. , Hansen Lars Hestbjerg , Hofmeyr Steven , Huang Pingqin , Irber Luiz , Jia Huijue , Jørgensen Tue Sparholt , Kieser Silas D. , Klemetsen Terje , Kola Axel , Kolmogorov Mikhail , Korobeynikov Anton , Kwan Jason , LaPierre Nathan , Lemaitre Claire , Li Chenhao , Limasset Antoine , Malcher-Miranda Fabio , Mangul Serghei , Marcelino Vanessa R. , Marchet Camille , Marijon Pierre , Meleshko Dmitry , Mende Daniel R. , Milanese Alessio , Nagarajan Niranjan , Nissen Jakob , Nurk Sergey , Oliker Leonid , Paoli Lucas , Peterlongo Pierre , Piro Vitor C. , Porter Jacob S. , Rasmussen Simon , Rees Evan R. , Reinert Knut , Renard Bernhard , Robertsen Espen Mikal , Rosen Gail L. , Ruscheweyh Hans-Joachim , Sarwal Varuni , Segata Nicola , Seiler Enrico , Shi Lizhen , Sun Fengzhu , Sunagawa Shinichi , Sørensen Søren Johannes , Thomas Ashleigh , Tong Chengxuan , Trajkovski Mirko , Tremblay Julien , Uritskiy Gherman , Vicedomini Riccardo , Wang Zhengyang , Wang Ziye , Wang Zhong , Warren Andrew , Willassen Nils Peder , Yelick Katherine , You Ronghui , Zeller Georg , Zhao Zhengqiao , Zhu Shanfeng , Zhu Jie , Garrido-Oter Ruben , Gastmeier Petra , Hacquard Stephane , Häußler Susanne , Khaledi Ariane , Maechler Friederike , Mesny Fantin , Radutoiu Simona , Schulze-Lefert Paul , Smit Nathiana , Strowig Till , Bremges Andreas , Sczyrba Alexander , McHardy Alice Carolyn 
Published: April 2022

AbstractEvaluating metagenomic software is key for optimizing metagenome interpretation and focus of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI). The CAMI II challenge engaged the community to assess methods on realistic and complex datasets with long- and short-read sequences, created computationally from around 1,700 new and known genomes, as well as 600 new plasmids and viruses. Here we analyze 5,002 results by 76 program versions. Substantial improvements were seen in assembly, some due to long-read data. Related strains still were challenging for assembly and genome recovery through binning, as was assembly quality for the latter. Profilers markedly matured, with taxon profilers and binners excelling at higher bacterial ranks, but underperforming for viruses and Archaea. Clinical pathogen detection results revealed a need to improve reproducibility. Runtime and memory usage analyses identified efficient programs, including top performers with other metrics. The results identify challenges and guide researchers in selecting methods for analyses.
Validation of a rapid, saliva-based, and ultra-sensitive SARS-CoV-2 screening system for pandemic-scale infection surveillance
Authors: Dewhurst Robert E. , Heinrich Tatjana , Watt Paul , Ostergaard Paul , Marimon Jose M. , Moreira Mariana , Houldsworth Philip E. , Rudrum Jack D. , Wood David , Kõks Sulev 
Published: April 2022

AbstractWithout any realistic prospect of comprehensive global vaccine coverage and lasting immunity, control of pandemics such as COVID-19 will require implementation of large-scale, rapid identification and isolation of infectious individuals to limit further transmission. Here, we describe an automated, high-throughput integrated screening platform, incorporating saliva-based loop-mediated isothermal amplification (LAMP) technology, that is designed for population-scale sensitive detection of infectious carriers of SARS-CoV-2 RNA. Central to this surveillance system is the “Sentinel” testing instrument, which is capable of reporting results within 25 min of saliva sample collection with a throughput of up to 3840 results per hour. It incorporates continuous flow loading of samples at random intervals to cost-effectively adjust for fluctuations in testing demand. Independent validation of our saliva-based RT-LAMP technology on an automated LAMP instrument coined the “Sentinel”, found 98.7% sensitivity, 97.6% specificity, and 98% accuracy against a RT-PCR comparator assay, confirming its suitability for surveillance screening. This Sentinel surveillance system offers a feasible and scalable approach to complement vaccination, to curb the spread of COVID-19 variants, and control future pandemics to save lives.