bluuebunny/crossref_metadata_2025_split huggingface dataset:
Test–retest reliability of the Arabic translation of the Lower Extremity Functional Status of the Orthotics and Prosthetics Users' Survey
Authors: Alhowimel Ahmed , Alodaibi Faris , Al-Nowaisri Khalid , Alotaibi Mazyad , Ghazal Haitham 
Published: December 2021

Background:
The number of amputations secondary to diverse factors in Arabic countries is expected to rise in the coming years. Therefore, there is a need for high-quality service that can be monitored by the use of standardized patient-reported outcome measures of amputee patients' functional status. This study aimed to translate the Lower Extremity Functional status Orthotics and Prosthetics Users' Survey (OPUS-LEFS) to Arabic and test its reliability in a sample of Arabic-speaking people with amputation.

Methods:
Standard forward and backward translation, followed by an examination by a team of experts, and then preliminary testing were conducted on the final translation. The OPUS-LEFS was cross-culturally validated, and its test–retest reliability was examined in patients with lower extremity amputations (N = 67).

Results:
No issues were observed concerning the patients' understanding or the meaning of the items on the Arabic translation of the OPUS-LEFS. The intraclass correlation coefficient was 0.99 (95% confidence interval [CI]: 0.985 to 0.995), and the mean difference was −0.278 (95% CI: −5.83 to 5.28), indicating excellent test–retest reliability.

Conclusions:
The study's results suggest that the Arabic translation of the OPUS-LEFS is a reliable tool that can be recommended for future use as an outcome measure for patients from Arabic-speaking nations with little knowledge of the English language.
Sentimental Tweets Classification of Symptomatic COVID-19
Authors: Tharun P 
Published: December 2021

ABSTRACTThe approach I described is straightforward, related to COVID-19 SARS based tweets and the symptoms, that people tweet about. Also, social media mining for health application reports was shared in many different tasks of 2021. The motto at the back of this observe is to analyses tweets of COVID-19 based symptoms. By performing BERT model and text classification with XLNET with which uses to classify text and purpose of the texts (i.e.) tweets. So that I can get a deep understanding of the texts. When developing the system, I used two models the XLNet and DistilBERT for the text sorting task, but the outcome was XLNET out-performs the given approach to the best accuracy achieved. Now I discover a whole lot vital for as it should be categorizing tweets as encompassing self-said COVID-19 indications. Whether or not a tweets associated with COVID-19 is a non-public report or an information point out to the virus. Which gives test accuracy to an F1 score of 96%.
Complete remission in a patient with widely metastatic HER2-amplified pancreatic adenocarcinoma following multimodal therapy informed by tumor sequencing and organoid profiling
Authors: King Daniel A , Smith Amber R , Pineda Gino , Nakano Michitaka , Michelini Flavia , Goedegebuure S. Peter , Thyparambil Sheeno , Liao Wei-Li , McCormick Aaron , Ju Jihang , Cioffi Michele , Zhang Xiuli , Hundal Jasreet , Griffith Malachi , Grandori Carla , Pollastro Maddy , Rosati Rachele , Margossian Astrid , Chatterjee Payel , Ainge Trevor , Flory Marta , Ocampo Paolo , Chen Lee-may , Poultsides George A , Baron Ari D , Chang Daniel T , Herman Joseph M , Gillanders William E , Park Haeseong , Hoos William A , Nichols Mike , Fisher George A , Kuo Calvin J 
Published: December 2021

AbstractHere, we demonstrate a complete clinical response achieved in a patient with HER2+ metastatic pancreatic ductal adenocarcinoma to a coordinated barrage of anti-HER2, personalized vaccine and checkpoint inhibition immunotherapy, radiation, and chemotherapy. Comprehensive organoid profiling with drug sensitivity screening and drug testing suggested a vulnerability to anti-HER2 directed therapy, facilitating personalized treatment selection for our patient, which contributed to her clinical benefit. Immune response monitoring following personalized vaccine, radiation and checkpoint inhibition showed a sustained increase in neoantigen specific T cell response.
Amyloid-PET of the white matter: relationship to free water, fiber integrity, and cognition in patients with dementia and small vessel disease
Authors: Ottoy Julie , Ozzoude Miracle , Zukotynski Katherine , Kang Min Su , Adamo Sabrina , Scott Christopher , Ramirez Joel , Swardfager Walter , Lam Benjamin , Bhan Aparna , Mojiri Parisa , Kiss Alex , Strother Stephen , Bocti Christian , Borrie Michael , Chertkow Howard , Frayne Richard , Hsiung Robin , Laforce Robert , Noseworthy Michael D. , Prato Frank S. , Sahlas Demetrios J. , Smith Eric E. , Kuo Phillip H. , Chad Jordan A. , Pasternak Ofer , Sossi Vesna , Thiel Alexander , Soucy Jean-Paul , Tardif Jean-Claude , Black Sandra E. , Goubran Maged ,   the Medical Imaging Trials Network of Canada (MITNEC) and Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: December 2021

AbstractWhite matter (WM) injury is frequently observed along with dementia. Positron emission tomography with amyloid-ligands (Aβ-PET) recently gained interest for detecting WM injury. Yet, little is understood about the origin of the altered Aβ-PET signal in WM regions. Here, we investigated the relative contributions of diffusion MRI-based microstructural alterations, including free water and tissue-specific properties, to Aβ-PET in WM and to cognition. We included a unique cohort of 115 participants covering the spectrum of low-to-severe white matter hyperintensity (WMH) burden and cognitively normal to dementia. We applied a bi-tensor diffusion-MRI model that differentiates between (i) the extracellular WM compartment (represented via free water), and (ii) the fiber-specific compartment (via free water-adjusted fractional anisotropy [FA]). We observed that, in regions of WMH, a decrease in Aβ-PET related most closely to higher free water and higher WMH volume. In contrast, in normal-appearing WM, an increase in Aβ-PET related more closely to higher cortical Aβ (together with lower free water-adjusted FA). In relation to cognitive impairment, we observed a closer relationship with higher free water than with either free water-adjusted FA or WM PET. Our findings support free water and Aβ-PET as markers of WM abnormalities in patients with mixed dementia, and contribute to a better understanding of processes giving rise to the WM PET signal.
Variable loss of antibody potency against SARS-CoV-2 B.1.1.529 (Omicron)
Authors: Sheward Daniel J. , Kim Changil , Ehling Roy A. , Pankow Alec , Dopico Xaquin Castro , Martin Darren , Reddy Sai , Dillner Joakim , Karlsson Hedestam Gunilla B. , Albert Jan , Murrell Ben 
Published: December 2021

AbstractThe recently-emerged SARS-CoV-2 B.1.1.529 variant (Omicron) is spreading rapidly in many countries, with a spike that is highly diverged from the pandemic founder, raising fears that it may evade neutralizing antibody responses. We cloned the Omicron spike from a diagnostic sample which allowed us to rapidly establish an Omicron pseudotyped virus neutralization assay, sharing initial neutralization results only 13 days after the variant was first reported to the WHO, 8 days after receiving the sample.Here we show that Omicron is substantially resistant to neutralization by several monoclonal antibodies that form part of clinical cocktails. Further, we find neutralizing antibody responses in pooled reference sera sampled shortly after infection or vaccination are substantially less potent against Omicron, with neutralizing antibody titers reduced by up to 45 fold compared to those for the pandemic founder. Similarly, in a cohort of convalescent sera prior to vaccination, neutralization of Omicron was low to undetectable. However, in recent samples from two cohorts from Stockholm, Sweden, antibody responses capable of cross-neutralizing Omicron were prevalent. Sera from infected-then-vaccinated healthcare workers exhibited robust cross-neutralization of Omicron, with an average potency reduction of only 5-fold relative to the pandemic founder variant, and some donors showing no loss at all. A similar pattern was observed in randomly sampled recent blood donors, with an average 7-fold loss of potency. Both cohorts showed substantial between-donor heterogeneity in their ability to neutralize Omicron. Together, these data highlight the extensive but incomplete evasion of neutralizing antibody responses by the Omicron variant, and suggest that increasing the magnitude of neutralizing antibody responses by boosting with unmodified vaccines may suffice to raise titers to levels that are protective.
Rare risk variants associate with epigenetic dysregulation in migraine
Authors: Techlo Tanya Ramdal , Chalmer Mona Ameri , Møller Peter L. , Kogelman Lisette J. A. , Olofsson Isa A. ,   DBDS Genomic Consortium, Banasik Karina , Nyegaard Mette , Olesen Jes , Hansen Thomas Folkmann 
Published: December 2021

ABSTRACTMigraine has a heritability of up to 65%. Genome-wide association studies (GWAS) on migraine have identified 123 risk loci, explaining only 10.6% of migraine heritability. Thus, there is a considerable genetic component not identified with GWAS. Further, the causality of the identified risk loci remains inconclusive. Rare variants contribute to the risk of migraine but GWAS are often underpowered to detect these. Whole genome sequencing is reliable for analyzing rare variants but is not frequently used in large-scale. We assessed if rare variants in the migraine risk loci associated with migraine. We used a large cohort of whole genome sequenced migraine patients (1,040 individuals from 155 families). The findings were replicated in an independent case-control cohort (2,027 migraine patients, 1,650 controls). We found rare variants (minor allele frequency<0.1%) associated with migraine in a Polycomb Response Element in theASTN2locus. The association was independent of the GWAS lead risk variant in the locus. The findings place rare variants as risk factors for migraine. We propose a biological mechanism by which epigenetic regulation by Polycomb Response Elements plays a crucial role in migraine etiology.
Omicron mutations enhance infectivity and reduce antibody neutralization of SARS-CoV-2 virus-like particles
Authors: Syed Abdullah M. , Ciling Alison , Khalid Mir M. , Sreekumar Bharath , Chen Pei-Yi , Kumar G. Renuka , Silva Ines , Milbes Bilal , Kojima Noah , Hess Victoria , Shacreaw Maria , Lopez Lauren , Brobeck Matthew , Turner Fred , Spraggon Lee , Taha Taha Y. , Tabata Takako , Chen Irene P. , Ott Melanie , Doudna Jennifer A. 
Published: December 2021

AbstractThe Omicron SARS-CoV-2 virus contains extensive sequence changes relative to the earlier arising B.1, B.1.1 and Delta SARS-CoV-2 variants that have unknown effects on viral infectivity and response to existing vaccines. Using SARS-CoV-2 virus-like particles (SC2-VLPs), we examined mutations in all four structural proteins and found that Omicron showed 3-fold higher capsid assembly and cell entry relative to Delta, a property conferred by S and N protein mutations. Thirty-eight antisera samples from individuals vaccinated with Pfizer/BioNTech, Moderna, Johnson & Johnson vaccines and convalescent sera from unvaccinated COVID-19 survivors had 15-fold lower efficacy to prevent cell transduction by VLPs containing the Omicron mutations relative to the ancestral B.1 spike protein. A third dose of Pfizer vaccine elicited substantially higher neutralization titers against Omicron, resulting in detectable neutralizing antibodies in 8 out of 8 subjects compared to 1 out of 8 pre-boost. Furthermore, the monoclonal antibody therapeutics Casirivimab and Imdevimab had robust neutralization activity against B.1, B.1.1 or Delta VLPs but no detectable neutralization of Omicron VLPs. Our results suggest that Omicron is more efficient at assembly and cell entry compared to Delta, and the antibody response triggered by existing vaccines or previous infection, at least prior to boost, will have limited ability to neutralize Omicron. In addition, some currently available monoclonal antibodies will not be useful in treating Omicron-infected patients.One-Sentence SummaryOmicron SARS-CoV-2 virus-like particles have enhanced infectivity that is only weakly neutralized by vaccination without boost or prior infection, or antibody therapeutics.
A phosphorylation code regulates the multi-functional protein RETINOBLASTOMA-RELATED1 in Arabidopsis thaliana
Authors: Zamora-Zaragoza Jorge , Klap Katinka , Sánchez-Pérez Jaheli , Vielle-Calzada Jean-Philippe , Scheres Ben 
Published: December 2021

AbstractThe RETINOBLASTOMA-RELATED (RBR) proteins play a central role coordinating cell division, cell differentiation and cell survival within an environmental and developmental context. These roles reflect RBR ability to engage in multiple protein-protein interactions (PPIs), which are regulated by multi-site phosphorylation. However the functional outcomes of RBR phosphorylation in multicellular organisms remain largely unexplored. Here we test the hypothesis that phosphorylation allows diversification of RBR functions in multicellular context. Using a representative collection of transgenic loss- and gain of function point mutations in RBR phosphosites, we analysed their complementation capacity in Arabidopsis thaliana root meristems. While the number of mutated residues often correlated to the phenotypic strength of RBR phosphovariants, phospho-sites contributed differentially to distinct phenotypes. For example, the pocket-domain has a greater influence on meristematic cell proliferation, whereas the C-terminal region associates to stem cell maintenance. We found combinatorial effects between the T406 phopspho-site with others in different protein domains. Moreover, a phospho-mimetic and a phospho-defective variant, both promoting cell death, indicate that RBR controls similar cell fate choices by distinct mechanisms. Thus, additivity and specificity of RBR phospho-sites fine tune RBR activity across its multiple roles. Interestingly, a mutation disrupting RBR interactions with the LXCXE motif suppresses dominant phospho-defective RBR phenotypes. By probing protein-protein interactions of RBR variants, we found that LXCXE-containing members of the DREAM complex constitute an important component of phosphorylation-regulated RBR function, but also that RBR participates in stress or environmental responses independently of its phosphorylation state. We conclude that developmental-related, but not stress- or environmental-related functions of RBR are defined and separable by a combinatorial phosphorylation code.
The impact of Piscirickettsia Salmonis infection on genome-wide DNA methylation profile in Atlantic Salmon
Authors: Mukiibi Robert , Peñaloza Carolina , Gutierrez Alejandro , Yáñez José M. , Houston Ross D. , Robledo Diego 
Published: December 2021

AbstractSalmon rickettsial septicaemia (SRS), caused by the intracellular bacteria Piscirickettsia Salmonis, generates significant mortalities to farmed Atlantic salmon, particularly in Chile. Due to its economic importance, a wealth of research has focussed on the biological mechanisms underlying pathogenicity of P. salmonis, the host response, and genetic variation in host resistance. DNA methylation is a fundamental epigenetic mechanism that influences almost every biological process via the regulation of gene expression and plays a key role in the response of an organism to stimuli. In the current study, the role of head kidney and liver DNA methylation in the response to P. salmonis infection was investigated in a commercial Atlantic salmon population. A total of 66 salmon were profiled using reduced representation bisulphite sequencing (RRBS), with head kidney and liver methylomes compared between infected animals (3 and 9 days post infection) and uninfected controls. These included groups of salmon with divergent (high or low) breeding values for resistance to P. salmonis infection, to examine the influence of genetic resistance. Head kidney and liver showed organ-specific global methylation patterns, but with similar distribution of methylation across gene features. Integration of methylation with RNA-Seq data revealed that methylation levels predominantly showed a negative correlation with gene expression, although positive correlations were also observed. Methylation within the first exon showed the strongest negative correlation with gene expression. A total of 911 and 813 differentially methylated CpG sites were identified between infected and control samples in the head kidney at 3 and 9 days respectively, whereas only 30 and 44 sites were differentially methylated in the liver. Differential methylation in the head kidney was associated with immunological processes such as actin cytoskeleton regulation, phagocytosis, endocytosis and pathogen associated pattern receptor signaling. We also identified 113 and 48 differentially methylated sites between resistant and susceptible fish in the head kidney and liver respectively. Our results contribute to the growing understanding of the role of methylation in regulation of gene expression and response to infectious diseases, and in particular reveal key immunological functions regulated by methylation in Atlantic salmon in response to P. salmonis.
Arsenal of Nanobodies for Broad-Spectrum Countermeasures against Current and Future SARS-CoV-2 Variants of Concerns
Authors: Rossotti M. A. , van Faassen H. , Tran A. , Sheff J. , Sandhu J. K. , Duque D. , Hewitt M. , Wen S. , Bavananthasivam R. , Beitari S. , Matte K. , Laroche G. , Giguère P. M. , Gervais C. , Stuible M. , Guimond J. , Perret S. , Hussack G. , Langlois M.-A. , Durocher Y. , Tanha J. 
Published: December 2021

ABSTRACTNanobodies offer several potential advantages over mAbs for the control of SARS-CoV-2. Their ability to access cryptic epitopes conserved across SARS-CoV-2 variants of concern (VoCs) and feasibility to engineer modular, multimeric designs, make these antibody fragments ideal candidates for developing broad-spectrum therapeutics against current and continually emerging SARS-CoV-2 VoCs. Here we describe a diverse collection of 37 anti-SARS-CoV-2 spike glycoprotein nanobodies extensively characterized as both monovalent and IgG Fc-fused bivalent modalities. The panel of nanobodies were shown to have high intrinsic affinity; high thermal, thermodynamic and aerosolization stability; broad subunit/domain specificity and cross-reactivity across many VoCs; wide-ranging epitopic and mechanistic diversity; high and broad in vitro neutralization potencies; and high neutralization efficacies in hamster models of SARS-CoV-2 infection, reducing viral burden by up to six orders of magnitude to below detectable levels. In vivo protection was demonstrated with anti-RBD and previously unreported anti-NTD and anti-S2 nanobodies. This collection of nanobodies provides a therapeutic toolbox from which various cocktails or multi-paratopic formats could be built to tackle current and future SARS-CoV-2 variants and SARS-related viruses. Furthermore, the high aerosol-ability of nanobodies provides the option for effective needle-free delivery through inhalation.
Molecular Dynamics Simulations of HLA-CW4-B2M-KIR2DL1 Protein and Homology Modeling of a Complex Associated with Psoriasis Disease (HLA-CW6-B2M-KIR2DS1)
Authors: Almatarneh Mansour H. , Alqaisi Ahmad M. , Ibrahim Enas K. , Kayed Ghada G. , Hollett Joshua W. 
Published: December 2021

AbstractMolecular dynamics (MD) simulation was used to study the interactions of two immune proteins of HLA-Cw4-β2m-KIR2DL1 complex with small peptide QYDDAVYKL (nine amino acids) in an aqueous solution. This study aims to gain a detailed information about the conformational changes and the dynamics of the complex. The right parameters and force field for performing the MD simulations that was needed to calibrate the complex structure were determined. The non-bonded interactions (Electrostatic and van der Waals contributions), H-bond formation, and salt bridges between the ligand HLA-Cw4 and the receptor KIR2DL1 were estimated using the obtained MD trajectories. The buried surface area due to binding was calculated to get insight into the causes of specificity of receptor to ligand and explains mutations experiment. The study concluded that β2-microglobulin, one part of the complex, is not directly interacting with the peptide at the groove; therefore, it could be neglected from simulation. Our results showed that β2-microglobulin does not have any significant effect on the dynamics of the 3D-structure of the complex. This project will help in understanding to optimize candidate drug design, a small peptide that disrupts the interaction, for the optimal biological effect.
Proteasome-dependent truncation of the negative heterochromatin regulator Epe1 mediates antifungal resistance
Authors: Yaseen Imtiyaz , White Sharon A. , Torres-Garcia Sito , Spanos Christos , Lafos Marcel , Gaberdiel Elisabeth , Yeboah Rebecca , Karoui Meriem El , Rappsilber Juri , Pidoux Alison L. , Allshire Robin C. 
Published: December 2021

AbstractEpe1 histone demethylase restricts H3K9-methylation-dependent heterochromatin, preventing it from spreading over, and silencing, gene-containing regions in fission yeast. External stress induces an adaptive response allowing heterochromatin island formation that confers resistance on surviving wild-type lineages. Here we investigate the mechanism by which Epe1 is regulated in response to stress. Exposure to caffeine or antifungals results in Epe1 ubiquitylation and proteasome-dependent removal of the N-terminal 150 residues from Epe1, generating truncated tEpe1 which accumulates in the cytoplasm. Constitutive tEpe1 expression increases H3K9 methylation over several chromosomal regions, reducing expression of underlying genes and enhancing resistance. Reciprocally, constitutive non- cleavable Epe1 expression decreases resistance. tEpe1-mediated resistance requires a functional JmjC demethylase domain. Moreover, caffeine-induced Epe1-to-tEpe1 cleavage is dependent on an intact cell-integrity MAP kinase stress signalling pathway, mutations in which alter resistance. Thus, environmental changes provoke a mechanism that curtails the function of this key epigenetic modifier, allowing heterochromatin to reprogram gene expression, thereby bestowing resistance to some cells within a population. H3K9me-heterochromatin components are conserved in human and crop plant fungal pathogens for which a limited number of antifungals exist. Our findings reveal how transient heterochromatin-dependent antifungal resistant epimutations develop and thus inform on how they might be countered.