bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond Prior and Volatility: The Distinct Iterative Updating Account of ASD
Authors: Shi Zhuanghua , Allenmark Fredrik , Theisinger Laura A. , Pistorius Rasmus L. , Glasauer Stefan , Müller Hermann J. , Falter-Wagner Christine M. 
Published: January 2022

AbstractThe nature of predictive-processing differences between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals is widely debated. Some studies suggest impairments in predictive processing in ASD, while others report intact processes, albeit with atypical learning dynamics. Here, we assessed duration reproduction tasks in high- and low-volatility settings to examine the updating dynamics of prior beliefs and sensory estimates. Employing a two-state Bayesian model, we differentiated how individuals with ASD and TD controls update their priors and perceptual estimates, and how these updates affect long-term prediction and behavior. Our findings indicate that individuals with ASD use prior knowledge and sensory input similarly to TD controls in perceptual estimates. However, they place a greater weight on sensory inputs specifically for iteratively updating their priors. This distinct approach to prior updating led to slower adaptation across trials; individuals with ASD relied less on their priors in perceptual estimates during the first half of sessions but achieved comparable integration weights as TD controls by the end of the session. By differentiating these aspects, our study highlights the importance of considering inter-trial updating dynamics to reconcile diverse findings of predictive processing in ASD. In consequence to the current findings, we suggest the distinct iterative updating account of predictive processing in ASD.Significance StatementResearch on predictive processing in Autism Spectrum Disorder (ASD) remains controversial. The current study employed a two-state Bayesian model in varied volatility settings to explore inter-trial updating dynamics in ASD compared to typically developing (TD) peers. We found that individuals with ASD, while utilizing prior knowledge similarly to TD controls, place a disproportionate emphasis on sensory inputs when updating their priors. This unique pattern of slower adaptation during iterative updating leads to significant behavioral differences in the first half of trials between the two groups, but comparable levels by the end of the session. These findings not only highlight the importance of considering different timescales and dynamic updating processes in ASD, but also suggest that the predictive processing framework in ASD involves unique prior updating mechanisms that is likely associated with increased sensory reliance.
Nasally-delivered interferon-λ protects mice against upper and lower respiratory tract infection of SARS-CoV-2 variants including Omicron
Authors: Chong Zhenlu , Karl Courtney E. , Halfmann Peter J. , Kawaoka Yoshihiro , Winkler Emma S. , Yu Jinsheng , Diamond Michael S. 
Published: January 2022

SUMMARYAlthough vaccines and monoclonal antibody countermeasures have reduced the morbidity and mortality associated with SARS-CoV-2 infection, variants with constellations of mutations in the spike gene threaten their efficacy. Accordingly, antiviral interventions that are resistant to further virus evolution are needed. The host-derived cytokine IFN-λ has been proposed as a possible treatment based on correlative studies in human COVID-19 patients. Here, we show IFN-λ protects against SARS-CoV-2 B.1.351 (Beta) and B.1.1.529 (Omicron)variants in three strains of conventional and human ACE2 transgenic mice. Prophylaxis or therapy with nasally-delivered IFN-λ2 limited infection of historical or variant (B.1.351 and B.1.1.529) SARS-CoV-2 strains in the upper and lower respiratory tracts without causing excessive inflammation. In the lung, IFN-λ was produced preferentially in epithelial cells and acted on radio-resistant cells to protect against of SARS-CoV-2 infection. Thus, inhaled IFN-λ may have promise as a treatment for evolving SARS-CoV-2 variants that develop resistance to antibody-based countermeasures.
Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons
Authors: Chaguza Chrispin , Coppi Andreas , Earnest Rebecca , Ferguson David , Kerantzas Nicholas , Warner Frederick , Young H. Patrick , Breban Mallery I. , Billig Kendall , Koch Robert Tobias , Pham Kien , Kalinich Chaney C. , Ott Isabel M. , Fauver Joseph R. , Hahn Anne M. , Tikhonova Irina R. , Castaldi Christopher , De Kumar Bony , Pettker Christian M. , Warren Joshua L. , Weinberger Daniel M. , Landry Marie L. , Peaper David R. , Schulz Wade , Vogels Chantal B.F. , Grubaugh Nathan D. 
Published: January 2022

AbstractThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continues to shape the coronavirus disease 2019 (Covid-19) pandemic. The detection and rapid spread of the SARS-CoV-2 ‘ Omicron’ variant (lineage B.1.1.529) in Botswana and South Africa became a global concern because it contained 15 mutations in the spike protein immunogenic receptor binding domain and was less neutralized by sera derived from vaccinees compared to the previously dominant Delta variant. To investigate if Omicron is more likely than Delta to cause infections in vaccinated persons, we analyzed 37,877 nasal swab PCR tests conducted from 12-26 December 2021 and calculated the test positivity rates for each variant by vaccination status. We found that the positivity rate among unvaccinated persons was higher for Delta (5.2%) than Omicron (4.5%). We found similar results in persons who received a single vaccine dose. Conversely, our results show that Omicron had higher positivity rates than Delta among those who received two doses within five months (Omicron = 4.7% vs. Delta = 2.6%), two doses more than five months ago (4.2% vs. 2.9%), and three vaccine doses (2.2% vs. 0.9%). Our estimates of Omicron positivity rates in persons receiving one or two vaccine doses were not significantly lower than unvaccinated persons but were 49.7% lower after three doses. In comparison, the reduction in Delta positivity rates from unvaccinated to 2 vaccine doses was 45.6-49.6% and to 3 vaccine doses was 83.2%. Despite the higher positivity rates for Omicron in vaccinated persons, we still found that 91.2% of the Omicron infections in our study occurred in persons who were eligible for 1 or more vaccine doses at the time of PCR testing. In conclusion, escape from vaccine-induced immunity likely contributed to the rapid rise in Omicron infections.
Evaluate the risk in conventional IVF frozen human blastocysts undergoing PGT using a new quantification method for parental contamination testing (qPCT)
Authors: Dong Yunqiao , Liu Dun , Zou Yangyun , Wan Cheng , Chen Chuangqi , Dong Mei , Huang Yuqiang , Huang Cuiyu , Weng Huinan , Zhu Xiulan , Wang Fang , Jiao Shujing , Liu Na , Lu Sijia , Zhang Xiqian , Liu Fenghua 
Published: January 2022

AbstractObjectiveTo establish a method to assess risks associated with preimplantation genetic testing (PGT) in embryos simultaneously with adhered sperm and cumulus cells.DesignA prospective pilot study.SettingUniversity teaching hospital.Patient(s)120 frozen blastocysts that could be biopsied from 34 patients who had experienced repeated implantation failure or abortion due to chromosomal abnormalities after embryos transfer in prior routine IVF cycles.Intervention(s)Chromosome screening and parental DNA contamination testing was performed in the surplus frozen IVF blastocysts from 34 patients.Main Outcome Measure(s)Parental DNA contamination rate and euploidy rate in biopsied blastocysts.Result(s)A new quantification method for parental contamination testing (qPCT) in single-cell whole-genome amplification (WGA) products based on allelic ratio analysis was established and validated in an artificial model by comparing 22 results obtained before and after adding different numbers of sperm and cumulus cells to biopsied TE cells. The results of the prospective clinical study of qPCT-PGT-A showed that the maternal contamination rate was 0.83% (1/120) and the risk of paternal contamination was negligible. The euploidy rate in these blastocysts was 47.50% (57/120), and 21 frozen embryo transfer (FET) cycles resulted in ten ongoing clinical pregnancies and four healthy births.Conclusion(s)The evidence we provide in the study shows a low risk of PGT in embryos simultaneously with adhered sperm and cumulus cells. The qPCT assay can be used to detect the risk of potential contamination and ensure the accuracy of PGT results, thereby improving the clinical outcome of IVF.CapsuleDuring PGT for human frozen conventional IVF embryos, paternal source pollution is negligible, while maternal pollution can not be ignored. qPCT method can effectively detect the parent DNA contamination in WGA products of biopsied TE cells.
Identification of age-associated transcriptomic changes linked to immunotherapy response in primary melanoma
Authors: Zowalaty Ahmed Ezat El 
Published: January 2022

AbstractMelanoma is a lethal form of skin cancers that develops due to constitutive activation of MAPK signaling pathway driven by BRAF and NRAS mutations. Immunotherapeutic agents such as anti-PD-1 (pembrolizumab and nivolumab) and anti-CTLA-4 (ipilimumab) have revolutionized melanoma treatment, however drug resistance is rapidly acquired. Several studies reported the increase in melanoma rates in older patients. Thus, the impact of ageing on transcriptional profiles of melanoma and response to immunotherapy is essential to understand. In this study, bioinformatic analysis of RNA seq data of old and young melanoma patients receiving immunotherapy identified significant upregulation of extracellular matrix and cellular adhesion genes in young cohorts while genes involved in cell proliferation, inflammation, non-canonical Wnt signaling and tyrosine kinase receptor ROR2 were significantly upregulated in the old cohort. Several Treg signature genes as well as transcription factors that are associated with dysfunctional T cell tumor infiltration, were differentially expressed. Differential expression of several genes involved in oxidative phosphorylation, glycolysis and glutamine metabolism has been observed as well. Taken together, this study provides novel findings on the impact of ageing on transcriptional changes during melanoma and novel therapeutic targets for future studies.
Muscle and Adipose Tissue Segmentations at the C3 Vertebral Level for Sarcopenia-Related Clinical Decision-Making in Patients with Head and Neck Cancer
Authors: Wahid Kareem A. , Olson Brennan , Jain Rishab , Grossberg Aaron J. , El-Habashy Dina , Dede Cem , Salama Vivian , Abobakr Moamen , Mohamed Abdallah S.R. , He Renjie , Jaskari Joel , Sahlsten Jaakko , Kaski Kimmo , Fuller Clifton D. , Naser Mohamed A. 
Published: January 2022

AbstractThe accurate determination of sarcopenia is critical for disease management in patients with head and neck cancer (HNC). Quantitative determination of sarcopenia is currently dependent on manually-generated segmentations of skeletal muscle derived from computed tomography (CT) cross-sectional imaging. This has prompted the increasing utilization of machine learning models for automated sarcopenia determination. However, extant datasets of head and neck CT imaging currently do not provide the necessary manually-generated skeletal muscle segmentations at the C3 vertebral level needed for building these models. In this data descriptor, we detail the annotation of a large set of head and neck CT images for use in automated sarcopenia-related clinical decision making and body composition analysis. A set of 394 HNC patients were selected from The Cancer Imaging Archive, and their skeletal muscle and adipose tissue was manually segmented at the C3 vertebral level using sliceOmatic in .tag format. Subsequently, using publicly disseminated Python scripts, we generated corresponding segmentations files in Neuroimaging Informatics Technology Initiative format. In addition to segmentation data, additional clinical demographic data germane to body composition analysis have been retrospectively collected for these patients from the University of Texas MD Anderson Cancer Center databases. These data are a valuable resource for studying sarcopenia and body composition analysis in patients with HNC.
Detection of SARS-CoV-2 in Different Human Biofluids Using the Loop-Mediated Isothermal Amplification Assay: A Prospective Diagnostic Study in Fortaleza, Brazil
Authors: Clementino Marco , Cavalcante Karene Ferreira , Feitosa Viana Vania Angelica , Silva Dayara de Oliveira , Damasceno Caroline Rebouças , de Souza Jessica Fernandes , Gondim Rafhaella Nogueira Della Guardia , Jorge Daniel Macedo de Melo , Magalhães Lyvia Maria Vasconcelos Carneiro , de Arruda Érico Antônio Gomes , Neto Roberto da Justa Pires , Medeiros Melissa Soares , dos Santos Armênio Aguiar , Magalhães Pedro Jorge Caldas , Perdigão Mello Liana , Arruda Eurico , Moreira Lima Aldo Ângelo , Havt Alexandre 
Published: January 2022

AbstractWe adopted the reverse transcriptase - loop mediated isothermal amplification (RT-LAMP) to detect SARS-Cov-2 in patient samples. Two primer sets for genes N and Orf1ab were designed to detect SARS-CoV-2, and one primer set was designed to detect the human gene Actin. We collected prospective 138 nasopharyngeal swabs, 70 oropharyngeal swabs, 69 saliva, and 68 mouth saline wash samples from patients suspected to have severe acute respiratory syndrome (SARS) caused by SARS-CoV-2 to test the RT-LAMP in comparison with the golden standard technique RT-qPCR. Accuracy of diagnosis using both primers, N5 and Orf9, was evaluated. Sensitivity and specificity for diagnosis was 96% (95% CI 87-99) and 85% (95% CI 76-91) in 138 samples, respectively. Accurate diagnosis results were obtained only in nasopharyngeal swab processed via extraction kit. Accurate and rapid diagnosis could aid COVID-19 pandemic management by identifying, isolating, and treating patients rapidly.HighlightsNew nucleic acid amplification test for the diagnosis of SARS-CoV-2 using the RT-LAMPN5 primer set showed mutations in strains of interest, such as the gamma strain (P.1) of SARS-CoV-2When evaluated in combination N5 and Orf9 primer sets maintained high sensitivity and specificity
RBDAct: Home screening of REM sleep behaviour disorder based on wrist actigraphy in Parkinson’s patients
Authors: Raschellà Flavio , Scafa Stefano , Puiatti Alessandro , Martin Moraud Eduardo , Ratti Pietro-Luca 
Published: January 2022

ABSTRACTBackgroundREM sleep behaviour disorder (RBD) is a disabling, often overlooked sleep disorder affecting up to 70% of patients with Parkinson’s disease. Identifying and treating RBD is critical to prevent severe sleep-related injuries, both to patients and bedpartners. Current diagnosis relies on nocturnal video-polysomnography, which is an expensive and cumbersome exam requiring specific clinical expertise.ObjectivesTo design, optimise, and validate a novel home-screening tool, termed RBDAct, that automatically identifies RBD in Parkinson’s patients based on wrist actigraphy only.MethodsTwenty-six Parkinson’s patients underwent two-week home wrist actigraphy worn on their more affected arm, followed by two non-consecutive in-lab evaluations. Patients were classified as RBD versus non-RBD based on dream enactment history and video-polysomnography. We characterised patients’ movement patterns during sleep using raw tri-axial accelerometer signals from wrist actigraphy. Machine learning classification algorithms were then trained to discriminate between patients with or without RBD using actigraphic features that described patients’ movements. Classification performance was quantified with respect to clinical diagnosis, separately for in-lab and at-home recordings.ResultsClassification performance from in-lab actigraphic data reached an accuracy of 92.9±8.16% (sensitivity 94.9±7.4%, specificity 92.7±13.8%). When tested on home recordings, accuracy rose to 100% over the two-week window. Features showed robustness across tests and conditions.ConclusionsRBDAct provides reliable predictions of RBD in Parkinson’s patients based on home wrist actigraphy only. These results open new perspectives for faster, cheaper and more regular screening of sleep disorders, both for routine clinical practice and for clinical trials.
Proteostasis is differentially modulated by inhibition of translation initiation or elongation
Authors: Clay Khalyd J. , Yang Yongzhi , Petrascheck Michael 
Published: January 2022

AbstractRecent work has revealed an increasingly important role for mRNA translation in maintaining proteostasis. Inhibiting translation protects from various proteostatic insults, including heat, expression of aggregation-prone proteins, or aging. However, multiple studies have come to differing conclusions about the mechanisms underlying the protective effects of translation inhibition. Here, we systematically lower translation either by pharmacologically inhibiting translation initiation or elongation and show that each step activates distinct protective responses in Caenorhabditis elegans. Targeting initiation triggers an HSF-1 dependent mechanism that protects from heat and age-associated protein misfolding but not from proteotoxicity caused by proteasome dysfunction. Conversely, targeting elongation triggers an HSF-1 independent mechanism that protects from heat and proteasome dysfunction but not from age-associated protein aggregation. Furthermore, while inhibiting translation initiation increases lifespan in wild-type worms, inhibiting translation elongation only extends lifespan when the animals exhibit preexisting proteotoxic stress—either as a result of aggregation-prone protein expression or hsf-1 deficiency. Together our findings suggest that organisms evolved complementary mechanisms that the mRNA translation machinery can trigger to restore proteostasis.
FiMO: Inferring the Temporal Order of Mutations on Clonal Phylogeny under Finite-sites Models
Authors: Agrawal Avesh Kumar , Zafar Hamim 
Published: January 2022

AbstractDetermining the temporal order of somatic mutations that drives cancer progression is essential for understanding the intra-tumor heterogeneity (ITH) and designing personalized therapy. Recently emerged single-cell DNA sequencing (SCS) technologies provide high-resolution datasets suitable for elucidating the temporal order of mutation. However, this task is challenged by technical artifacts associated with single-cell sequencing. While computational methods have been developed to account for these errors, these methods rely on using infinite sites assumption which gets violated in human cancers due to deletion, loss of heterozygosity and parallel mutations. Here, we propose a novel method FiMO, which employs a Bayesian frameowrk for inferring the temporal order of somatic mutations from noisy SCS mutational profiles under tumor evolutionary models that account for mutation recurrence and losses. Using synthetic datasets generated under a wide variety of settings, we show that FiMO outperforms the state-of-the-art methods in inferring the temporal order of mutations. We also applied FiMO on two experimental colon cancer datasets for inferring the temporal order of somatic mutations and quantifying their posterior probability. FiMO is publicly available at https://github.com/aveshag/FiMO.
Genome-wide association analysis identifies ancestry-specific genetic variation associated with medication response in the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH)
Authors: Li Josephine H. , Brenner Laura N. , Kaur Varinderpal , Figueroa Katherine , Udler Miriam S. , Leong Aaron , Investigators MAGIC , Mercader Josep M. , Florez Jose C. 
Published: January 2022

ABSTRACTBackgroundCharacterization of genetic variation that influences response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes (T2D). SUGAR-MGH examined the acute response to two anti-diabetes medications in order to understand the functional relevance of known T2D- and glycaemic trait-associated genetic loci.Methods1,000 participants at risk for T2D from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping Array. Imputation was performed with the TOPMed reference panel. Multiple linear regression using an additive model tested for association between variants and primary endpoints of drug response. We evaluated the influence of 804 unique T2D and glycaemic trait-associated variants on SUGAR-MGH outcomes and performed colocalization analyses to identify shared genetic signals.FindingsFive genome-wide significant variants were associated with metformin or glipizide response. The strongest association was between an African ancestry-specific variant (minor allele frequency=0·026) at rs149403252 and lower fasting glucose following metformin, adjusted for baseline glucose (p=1·9×10−9), with a 0·94 mmol/L larger decrease in fasting glucose after metformin. We identified associations between T2D-associated variants and glycaemic response, including the T2D-protective C allele of rs703972 near ZMIZ1 and increased levels of active GLP-1 (p=1·6×10−5), supporting the role of alterations in incretin levels in T2D pathophysiology.InterpretationWe present a well phenotyped, densely genotyped, multi-ancestry resource to study gene-drug interactions, uncover novel variation associated with response to common anti-diabetes medications, and provide insight into mechanisms of action of T2D-related variation.FundingUS National Institutes of Health.
Over- and under-estimation of vaccine effectiveness
Authors: De-Leon Hilla , Aran Dvir 
Published: January 2022

ABSTRACTBackgroundThe effectiveness of SARS-CoV-2 vaccines has been a subject of debate, with varying results reported in different studies, ranging from 60-95% vaccine effectiveness (VE). This range is striking when comparing two studies conducted in Israel at the same time, as one study reported VE of 90-95%, while the other study reported only ~80%. We argue that this variability is due to inadequate accounting for indirect protection provided by vaccines, which can block further transmission of the virusMaterials and MethodsWe developed a novel analytic heterogenous infection model and extended our agent-based model of disease spread to allow for heterogenous interactions between vaccinated and unvaccinated across close-contacts and regions. We applied these models on real-world regional data from Israel from early 2021 to estimate VE using two common study designs: population-based and secondary infectionsResultsOur results show that the estimated VE of a vaccine with efficacy of 85% can range from 70-95% depending on the interactions between vaccinated and unvaccinated individuals. Since different study designs capture different levels of interactions, we suggest that this interference explains the variability across studies. Finally, we propose a methodology for more accurate estimation without knowledge of interactionsDiscussions and ConclusionsOur study highlights the importance of considering indirect protection when estimating vaccine effectiveness, explains how different study designs may report biased estimations, and propose a method to overcome this bias. We hope that our models will lead to more accurate understanding of the impact of vaccinations and inform public health policy.