bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of International Classification of Diseases Codes for Identifying Acute Optic Neuritis
Authors: Muro-Fuentes Elena A. , Villarreal Navarro Sylvia E. , Moss Heather E. 
Published: January 2023

Background:
The accuracy of International Classification of Diseases (ICD) codes for identifying cases of acute optic neuritis (aON) is not known. A prior study reported 61% accuracy for ICD code plus MRI consistent with aON within 2 months. This study determined accuracy for ICD code plus MRI within 2 months regardless of results.

Methods:
Retrospective chart review was conducted using a medical record research repository of a tertiary care institution from 1998 to 2019. Subjects with ICD-9/10 codes for ON and an MRI brain and/or orbits within 2 months of earliest (initial) ICD code were included. MRI was classified as positive or negative for aON based on report noting gadolinium-contrast enhancement. Clinical diagnosis at the time of initial code was classified as aON, prior ON, considered ON, alternative diagnosis, or unknown based on review of physician authored clinical notes within 7 days of the initial code. Accuracy of ICD code for aON, acute or prior ON, and acute, prior, or considered ON were calculated for all subjects and stratified based on MRI result.

Results:
Two hundred fifty-one subjects had MRI results within 2 months of their initial ON ICD code (49 positive MRI [previously reported]; 202 negative MRI). Among those with negative MRI, 32 (16%) had aON, 40 (20%) had prior ON, 19 (9%) considered ON as a diagnosis, 92 (46%) had other confirmed diagnoses, and 19 (9%) had unknown diagnosis at time of code. Considering all subjects, accuracy for ICD code was 25% for acute ON, 41% for acute or prior ON, and 48% for acute, prior, or considered ON. Positive MRI, increased number of ON ICD codes, a code given by an ophthalmologist or neurologist within 2 months, and the presence of a neurology encounter within 2 months were associated with an increased accuracy for clinical aON diagnosis.

Conclusions:
In the setting of an MRI within 2 months, ICD codes for ON have low accuracy for acute ON and only slightly better accuracy for acute or prior ON. Accuracy is higher for cases with a positive MRI than those with a negative MRI, suggesting positive MRI in conjunction with ICD codes may help more accurately identify cases. Reliance on ICD and Current Procedural Terminology codes alone to identify aON cases may introduce substantial misclassification bias in claims-based research.
Are Non-lactose fermenting Escherichia coli important diarrhoeal pathogens in children and adults?
Authors: Sharma Bhawna , Modgil Vinay , Mahindroo Jaspreet , Kumar Ajay , Kaur Varpreet , Narayan Chandradeo , Verma Ritu , Mohan Balvinder , Taneja Neelam 
Published: January 2023

Introduction: Diarrheagenic Escherichia coli (DEC) are responsible for about 30–40% of acute diarrhoea episodes in developing countries. Up to 10% of isolates of E. coli from stool specimens have been reported to be non-lactose fermenting (NLF E. coli). There is scarcity of literature available regarding the pathogenicity of NLF E. coli causing infectious diarrhoea. Aim: We aimed to elucidate the importance of NLF E. coli in causing diarrhoea in both adults as well as children by detecting various DEC pathotypes among NLF E. coli in stool samples from gastroenteritis cases. Material and Methods: A total of 376 non-lactose fermenting (NLF) E. coli isolates isolated from 3110 stool samples of diarrhoea/ gastroenteritis patients were included in the study. Upto 3 non-lactose fermenting colonies which did not confirm as V.cholerae, Aeromonas spp., Salmonella spp., Shigella spp., but were identified as E.coli on MALDI-TOF were selected from each MacConkey agar plate and streaked onto fresh, sterilized nutrient agar and biochemical reactions were put up. Multiplex PCR was put up for EAEC, EPEC, ETEC, EHEC pathotypes and PCR for ipaH gene was put up for EIEC. Antibiotic sensitivity testing was performed with the disc diffusion method. Results: Using multiplex PCR and ipaH PCR, a total of 63 pathotypes of DEC were obtained, EAEC being the most predominant (n= 31) followed by EIEC (n=22), EPEC (n=8) and ETEC (n=2). To further differentiate EIEC from Shigella, additional biochemicals were performed which include acetate utilization, mucate and salicin fermentation, and esculin hydrolysis. Antimicrobial susceptibility testing (AST) showed that maximum resistance was seen against ciprofloxacin (82.5%) followed by ampicillin (77.8%) and cotrimoxazole (68.2%) and minimum resistance was seen against ertapenem (4.8%). Conclusion: In our study two pathotypes (EAEC, EIEC) were predominant among NLF E. coli and these were important etiological agents not only in children but also in adults. Our study also sheds light on epidemiology of EIEC which is one of the most neglected DEC pathotype as hardly any microbiological laboratory process NLF E. coli for EIEC.
Second monovalent SARS-CoV-2 mRNA booster restores Omicron-specific neutralizing activity in both nursing home residents and health care workers
Authors: Nugent Clare , Abul Yasin , White Elizabeth , Shehadeh Fadi , Kaczynski Matthew , Felix Lewis Oscar , Ganesan Narchonai , Oyebanji Oladayo A. , Vishnepolskiy Igor , Didion Elise M. , Paxitzis Alexandra , Sheehan Maegan L. , Mylonakis Eleftherios , Wilson Brigid M. , Balazs Alejandro B. , Chan Philip A. , King Christopher L. , Pfeifer Walther M. , Dickerson Evan , Canaday David H. , Gravenstein Stefan 
Published: January 2023

AbstractWe examined whether the second monovalent SARS-CoV-2 mRNA booster increased antibody levels and their neutralizing activity to Omicron variants in nursing home residents (NH) residents and healthcare workers (HCW). We sampled 367 NH residents and 60 HCW after primary mRNA vaccination, first and second boosters, for antibody response and pseudovirus neutralization assay against SARS-CoV-2 wild-type (WT) (Wuhan-Hu-1) strain and Omicron BA1 variant. Antibody levels and neutralizing activity progressively increased with each booster but subsequently waned over weeks. NH residents, both those without and with prior infection, had a robust geometric mean fold rise (GMFR) of 10.2 (95% CI 5.1, 20.3) and 6.5 (95% CI 4.5, 9.3) respectively in Omicron-BA.1 subvariant specific neutralizing antibody levels following the second booster vaccination (p<0.001). These results support the ongoing efforts to ensure that both NH residents and HCW are up to date on recommended SARS-CoV-2 vaccine booster doses.
Scoring epidemiological forecasts on transformed scales
Authors: Bosse Nikos I. , Abbott Sam , Cori Anne , van Leeuwen Edwin , Bracher Johannes , Funk Sebastian 
Published: January 2023

AbstractForecast evaluation is essential for the development of predictive epidemic models and can inform their use for public health decision-making. Common scores to evaluate epidemiological forecasts are the Continuous Ranked Probability Score (CRPS) and the Weighted Interval Score (WIS), which can be seen as measures of the absolute distance between the forecast distribution and the observation. However, applying these scores directly to predicted and observed incidence counts may not be the most appropriate due to the exponential nature of epidemic processes and the varying magnitudes of observed values across space and time. In this paper, we argue that transforming counts before applying scores such as the CRPS or WIS can effectively mitigate these difficulties and yield epidemiologically meaningful and easily interpretable results. Using the CRPS on log-transformed values as an example, we list three attractive properties: Firstly, it can be interpreted as a probabilistic version of a relative error. Secondly, it reflects how well models predicted the time-varying epidemic growth rate. And lastly, using arguments on variance-stabilizing transformations, it can be shown that under the assumption of a quadratic mean-variance relationship, the logarithmic transformation leads to expected CRPS values which are independent of the order of magnitude of the predicted quantity. Applying a transformation of log(x + 1) to data and forecasts from the European COVID-19 Forecast Hub, we find that it changes model rankings regardless of stratification by forecast date, location or target types. Situations in which models missed the beginning of upward swings are more strongly emphasised while failing to predict a downturn following a peak is less severely penalised when scoring transformed forecasts as opposed to untransformed ones. We conclude that appropriate transformations, of which the natural logarithm is only one particularly attractive option, should be considered when assessing the performance of different models in the context of infectious disease incidence.
PolyAMiner-Bulk: A Machine Learning Based Bioinformatics Algorithm to Infer and Decode Alternative Polyadenylation Dynamics from bulk RNA-seq data
Authors: Jonnakuti Venkata Soumith , Wagner Eric J. , Maletić-Savatić Mirjana , Liu Zhandong , Yalamanchili Hari Krishna 
Published: January 2023

ABSTRACTMore than half of human genes exercise alternative polyadenylation (APA) and generate mRNA transcripts with varying 3’ untranslated regions (UTR). However, current computational approaches for identifying cleavage and polyadenylation sites (C/PASs) and quantifying 3’UTR length changes from bulk RNA-seq data fail to unravel tissue- and disease-specific APA dynamics. Here, we developed a next-generation bioinformatics algorithm and application, PolyAMiner-Bulk, that utilizes an attention-based machine learning architecture and an improved vector projection-based engine to infer differential APA dynamics accurately. When applied to earlier studies, PolyAMiner-Bulk accurately identified more than twice the number of APA changes in an RBM17 knockdown bulk RNA-seq dataset compared to current generation tools. Moreover, on a separate dataset, PolyAMiner-Bulk revealed novel APA dynamics and pathways in scleroderma pathology and identified differential APA in a gene that was identified as being involved in scleroderma pathogenesis in an independent study. Lastly, we used PolyAMiner-Bulk to analyze the RNA-seq data of post-mortem prefrontal cortexes from the ROSMAP data consortium and unraveled novel APA dynamics in Alzheimer’s Disease. Our method, PolyAMiner-Bulk, creates a paradigm for future alternative polyadenylation analysis from bulk RNA-seq data.
A systematic comparison of VBM pipelines and their application to age prediction
Authors: Antonopoulos Georgios , More Shammi , Raimondo Federico , Eickhoff Simon B. , Hoffstaedter Felix , Patil Kaustubh R. 
Published: January 2023

AbstractVoxel-based morphometry (VBM) analysis is commonly used for localized quantification of gray matter volume (GMV). Several alternatives exist to implement a VBM pipeline. However, how these alternatives compare and their utility in applications, such as the estimation of aging effects, remain largely unclear. This leaves researchers wondering which VBM pipeline they should use for their project. In this study, we took a user-centric perspective and systematically compared five VBM pipelines, together with registration to either a general or a study-specific template, utilizing three large datasets (n>500 each). Considering the known effect of aging on GMV, we first compared the pipelines in their ability of individual-level age prediction and found markedly varied results. To examine whether these results arise from systematic differences between the pipelines, we classified them based on their GMVs, resulting in near-perfect accuracy. To gain deeper insights, we examined the impact of different VBM steps using the region-wise similarity between pipelines. The results revealed marked differences, largely driven by segmentation and registration steps. We observed large variability in subject-identification accuracies, highlighting the interpipeline differences in individual-level quantification of GMV. As a biologically meaningful criterion we correlated regional GMV with age. The results were in line with the age-prediction analysis, and two pipelines, CAT and the combination of fMRIPrep for tissue characterization with FSL for registration, reflected age information better.
Plasma membrane association and resistosome formation of plant helper immune receptors
Authors: Wang Zaiqing , Liu Xiaoxiao , Yu Jie , Yin Shuining , Cai Wenjuan , Kim Nak Hyun , Kasmi Farid El , Dangl Jeffery L. , Wan Li 
Published: January 2023

AbstractIntracellular plant immune receptors, termed NLRs, respond to pathogen effectors delivered into plant cells. Activation of NLRs typically confers immunity. Sensor NLRs, involved in effector recognition, are either TIR-NLRs (TNLs) or CC-NLRs (CNLs). Helper NLRs, required for sensor NLR signaling, include CCR-NLRs (RNLs) and a special class of CNLs known as NRCs. Activated TNLs produce small molecules that induce an association between the EDS1/SAG101 heterodimer and the NRG1s helper RNLs. Auto active NRG1s oligomerize and form calcium signaling channels largely localized at the plasma membrane (PM). The molecular mechanisms of helper NLR PM association and effector induced NRG1 oligomerization are not well characterized. We find that both RNLs and NRCs require positively charged residues in the second and fourth helices of their CCRor CC domain for phospholipid binding and PM association before and after activation, despite conformational changes that accompany activation. We demonstrate that effector activation of TNLs induces NRG1 oligomerization at the PM and that the cytoplasmic pool of EDS1/SAG101 is critical for cell death function. EDS1/SAG101 cannot be detected in the oligomerized NRG1 resistosome, suggesting that additional unknown triggers might be required to induce the dissociation of EDS1/SAG101 from the previously described NRG1/EDS1/SAG101 heterotrimer before subsequent NRG1 oligomerization, or that the conformational changes resulting from NRG1 oligomerization abrogate the interface for EDS1/SAG101 association. Our data provide new observations regarding dynamic PM association during helper NLR activation and underpin an updated model for effector induced NRG1 resistosome formation.
Aquaporins enriched in endothelial vacuole membrane regulate the diameters of microvasculature in hyperglycemia
Authors: Chen Changsheng , Qin Yinyin , Xu Yidan , Wang Xiaoning , Lei Wei , Shen Xiaozhong , Chen Lixun , Wang Linnong , Gong Jie , Wang Yongmin , Hu Shijun , Liu Dong 
Published: January 2023

AbstractBackgroundIn patients with diabetic microvascular complications, decreased perfusion or vascular occlusion, caused by reduced vascular diameter, is a common characteristic that will lead to insufficient blood supply. However, the regulatory mechanism remains undetermined and the treatment approach is lacking.MethodsGene expression ofAquaporin 1(AQP1) was compared between diabetic and non-diabetic human retina samples. Confocal live imaging analysis of zebrafish was utilized to investigate the hyperglycemia-induced alterations in vascular morphology. Transcriptomic and single-cell RNA sequencing,in situhybridization, and quantitative PCR were used to analyze gene expressions. Gene knock-out zebrafish and stable transgenic lines were established for functional analysis. Human embryonic stem cells (H1 line), H1-derived endothelial cells (ECs), human umbilical vein endothelial cells (HUVECs), and human retinal microvascular endothelial cells (HRMECs) were used for functional analysis.ResultsFirstly, we found that the expression of humanAQP1was downregulated in diabetic human retina samples (49 healthy vs. 54 diabetic samples) and high-glucose-treated human retinal microvascular endothelial cells. Then, we observed the reduction of vascular diameter and compromised perfusion in high glucose-treated zebrafish embryos. Two aquaporins (aqp1a.1andaqp8a.1), highly enriched in ECs, were significantly down-regulated under hyperglycemic conditions.Aqp1a.1and/oraqp8a.1loss-of-function leaded to reduction in intersegmental vessel diameters, recapitulating the phenotype of the hyperglycemic zebrafish model.Overexpressingaqp1a.1/aqp8a.1in zebrafish ECs promoted the enlargement of microvascular diameters. Moreover, the reduced vessel diameters induced by high-glucose treatment was rescued by aquaporin overexpression. In addition, bothaqp1a.1andapq8a.1were localized in the intracellular vacuoles in cultured ECs as well as the ECs of sprouting ISVs, and loss of Aqps caused the reduction of those vacuoles, which was required for lumenization. Loss of AQP1 had no influence on EC differentiation from human stem cells but strongly inhibited the vascular tube formation of differentiated ECs.ConclusionsEC-enriched aquaporins regulate intracellular vacuole-mediated blood vessel diameter hyperglycemia. All of these suggest that EC-expressed aquaporins might be potential targets for gene therapy to cure diabetes-related vascular perfusion defects.
Age differences in spatial memory are mitigated during naturalistic navigation
Authors: Hill Paul F. , Bermudez Skyelynn , McAvan Andrew S. , Garren Joshua D. , Grilli Matthew D. , Barnes Carol A. , Ekstrom Arne D. 
Published: January 2023

AbstractSpatial navigation deficits in older adults are well documented. These findings are often based on experimental paradigms that require using a joystick or keyboard to navigate a virtual desktop environment. In the present study, we investigated whether age differences in spatial memory are attenuated when tested in a more naturalistic and ambulatory virtual environment. In Experiment 1, cognitively normal young and older adults navigated a virtual variant of the Morris Water Maze task in each of two virtual reality (VR) conditions: a desktop VR condition which required using a mouse and keyboard to navigate and an immersive and ambulatory VR condition which permitted unrestricted locomotion. In Experiment 2, we examined whether age- and VR-related differences in spatial performance were affected by the inclusion of additional spatial cues in an independent sample of young and older adults. In both experiments, older adults navigated to target locations less precisely than did younger individuals in the desktop condition, replicating numerous prior studies. These age differences were significantly attenuated, however, when tested in the fully immersive and ambulatory environment. These findings underscore the importance of developing naturalistic and ecologically valid measures of spatial memory and navigation, especially when performing cross-sectional studies of cognitive aging.
A Randomized Trial Comparing Omicron-Containing Boosters with the Original Covid-19 Vaccine mRNA-1273
Authors: Lee Ivan T. , Cosgrove Catherine A. , Moore Patrick , Bethune Claire , Nally Rhiannon , Bula Marcin , Kalra Philip A. , Clark Rebecca , Dargan Paul I. , Boffito Marta , Sheridan Ray , Moran Ed , Darton Thomas C. , Burns Fiona , Saralaya Dinesh , Duncan Christopher J. A. , Lillie Patrick , Ramos Alberto San Francisco , Galiza Eva , Heath Paul T. , Girard Bethany , Parker Christy , Rust Dondi , Mehta Shraddha , Windt Elizabeth de , Sutherland Andrea , Tomassini Joanne E. , Dutko Frank J. , Chalkias Spyros , Deng Weiping , Chen Xing , Tracy LaRee , Zhou Honghong , Miller Jacqueline M. , Das Rituparna 
Published: January 2023

AbstractBackgroundOmicron-containing bivalent boosters are available worldwide. Results of a large, randomized, active-controlled study are presented.MethodsThis phase 3, randomized, observer-blind, active-controlled trial in the United Kingdom evaluated the immunogenicity and safety of 50-µg doses of omicron-BA.1-monovalent mRNA-1273.529 and bivalent mRNA-1273.214 booster vaccines compared with 50-µg mRNA-1273 administered as boosters in individuals ≥16 years. Participants had previously received 2 doses of any authorized/approved Covid-19 vaccine with or without an mRNA vaccine booster. Safety and immunogenicity were primary objectives; immunogenicity was assessed in all participants, with analysis conducted based on prior infection status. Incidence of Covid-19 post-boost was a secondary (mRNA-1273.214) or exploratory (mRNA-1273.529) objective.ResultsIn part 1 of the study, 719 participants received mRNA-1273.529 (n=362) or mRNA-1273 (n=357); in part 2, 2813 received mRNA-1273.214 (n=1418) or mRNA-1273 (n=1395). Median durations (months [interquartile range]) between the most recent Covid-19 vaccine and study boosters were similar in the mRNA-1273.529 (4.0 [3.6-4.7]) and mRNA-1273 (4.1 [3.5-4.7]) (part 1), and mRNA-1273.214 (5.5 [4.8-6.2] and mRNA-1273 (5.4 [4.8-6.2]) groups (part 2).Both mRNA-1273.529 and mRNA-1273.214 elicited superior neutralizing antibody responses against omicron BA.1 with geometric mean ratios (99% CIs) of 1.68 (1.45-1.95) and 1.53 (1.41-1.67) compared to mRNA-1273 at day 29 post-boost. Although the study was not powered to assess relative vaccine efficacy, the incidence rates/1000 person years (95% CI) of Covid-19 trended lower with mRNA-1273.529 (670.5 [528.3-839.3]) than mRNA-1273 (769.3 [615.4-950.1]) and mRNA-1273.214 (633.0 [538.1-739.7]) than mRNA-1273 (711.6 [607.5-828.5]).Sequence analysis in part 2 showed that this was driven by lower incidence of Covid-19 in the mRNA-1273.214 cohort with BA.2 and BA.4 sublineages but not BA.5 sublineages. All study boosters were well-tolerated.ConclusionThe bivalent omicron BA.1-containing booster elicited superior neutralizing antibody responses against omicron BA.1 with acceptable safety results consistent with the BA.1 monovalent vaccine. Incidence rates for Covid-19 were numerically lower in participants who received mRNA-1273.214 compared to the original booster vaccine mRNA-1273, driven by the BA.2 and BA.4 sublineages.
Single-cell transcriptomic landscape deciphers novel olfactory neuroblastoma subtypes and intratumoral heterogeneity
Authors: Yang Jingyi , Song Xiaole , Zhang Huankang , Liu Quan , Wei Ruoyan , Guo Luo , Yuan Cuncun , Xue Kai , Lai Yuting , Wang Li , Hu Li , Wang Huan , Zhang Chen , Zhang Qianqian , Gu Ye , Zhao Weidong , Yu Huapeng , Wang Jingjing , Liu Zhuofu , Li Han , Zheng Shixing , Liu Juan , Yang Lu , Li Wanpeng , Xu Rui , Chen Jiani , Zhou Yumin , Cheng Xiankui , Yu Yiqun , Wang Dehui , Sun Xicai , Yu Hongmeng 
Published: January 2023

SummaryOlfactory neuroblastoma (ONB) is an uncommon malignant tumor known to originate from the olfactory epithelial. The complex tumor ecosystem of this pathology remained unclear. Here, we explored the cellular components with ONB tumors based on scRNA profiles of 96,325 single-cells derived from 10 tumors and 1 olfactory mucosa sample. We discovered 11 major cell types, including 6 immune cell, 3 stromal cell subtypes and epithelial cluster in the tumor microenvironment (TME), and identified 5 common expression programs from malignant epithelial cells. We analyzed subclusters of TME and the interactions among different cell types in the TME. An innovative three-classification of ONB was established via scRNA analysis. Markers for categorizing tumor samples into new subtypes were elucidated. Different responses towards certain chemotherapy regimens could be inferred according to the molecular features of three tumor types. Relative abundance of immunosuppressive TAMs indicated the benefits of immunotherapies targeting myeloid cells.