bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of baseline clinical status and surgical strategy on early good to excellent result in spinal lumbar arthrodesis: a machine learning approach
Authors: Langella Francesco , Ventriglia Luca , Compagnone Domenico , Barletta Paolo , Huber David , Mangili Francesca , Licandro Ginevra , Galbusera Fabio , Cina Andrea , Bassani Tito , Lamartina Claudio , Scaramuzzo Laura , Bassani Roberto , Brayda-Bruno Marco , Villafañe Jorge Hugo , Berjano Pedro , Azzimonti Laura 
Published: September 2021

AbstractAimsTo create, using a machine learning (ML) approach, a preoperative model from baseline demographic and health-related quality of life scores (HRQOL) to predict a good to excellent early clinical outcome.Patients and MethodsA single spine surgery center retrospective review of prospectively collected data from January 2016 to December 2020 from the institutional registry (SpineREG) was performed. The inclusion criteria were age ≥ 18 years, both sexes, lumbar arthrodesis procedure, a complete follow up assessment (ODI, SF-36 and COMI back) and the capability to read and understand the Italian language. A delta of improvement of the ODI higher than 12.7/100 was considered a “good early outcome”. A combined target model of ODI (Δ ≥ 12.7/100), SF-36 PCS (Δ ≥ 6/100) and COMI back (Δ ≥ 2.2/10) was considered an “excellent early outcome”. The performance of the ML models was evaluated in terms of sensitivity, i.e., True Positive Rate (TPR), specificity, i.e., True Negative Rate (TNR), accuracy and area under the receiver operating characteristic curve (AUC ROC).ResultsA total of 1243 patients were included in this study. The model for predicting ODI at 6 months follow up showed a good balance between sensitivity (74.3%) and specificity (79.4%), while providing a good accuracy (75.8%) with ROC AUC = 0.842. The combined target model showed a sensitivity of 74.2% and specificity of 71.8%, with an accuracy of 72.8%, and a ROC AUC = 0.808.ConclusionThe results of our study suggest that a machine learning approach showed high performance in predicting early good to excellent clinical results.
Modeling SARS-CoV-2 RNA Degradation in Small and Large Sewersheds
Authors: McCall Camille , Fang Zheng N. , Li Dongfeng , Czubai Andrew J. , Juan Andrew , LaTurner Zachary , Ensor Katherine , Hopkins Loren , Bedient Phil , Stadler Lauren B. 
Published: September 2021

AbstractWastewater-based epidemiology has been at the forefront of the COVID-19 pandemic, yet little is known about losses of SARS-CoV-2 in sewer networks. Here, we used advanced sewershed modeling software to simulate SARS-CoV-2 RNA loss in sewersheds across Houston, TX under various temperatures and decay rates. Moreover, a novel metric, population times travel time (PT), was proposed to identify localities with a greater likelihood of undetected COVID-19 outbreaks and to aid in the placement of upstream samplers. Findings suggest that travel time has a greater influence on viral loss across the sewershed as compared to temperature. SARS-CoV-2 viral loss at median travel times was approximately two times greater in 20°C wastewater between the small sewershed, Chocolate Bayou, and the larger sewershed, 69th Street. Lastly, placement of upstream samplers according to the PT metric can provide a more representative snapshot of disease incidence in large sewersheds. This study helps to elucidate discrepancies between SARS-CoV-2 viral load in wastewater and clinical incidence of COVID-19. Incorporating travel time and SARS-CoV-2 decay can improve wastewater surveillance efforts.
Impact of COVID-19 on the quality of life (QoL) of patients living with Sickle Cell Disorder (SCD) in Lagos, Nigeria
Authors: Akinsete Annette , Ottun Michael , Adelabu Hammed , Ajuwon Larry , Veeneman Jorden 
Published: September 2021

ABSTRACTThe study aimed to assess the impact of the COVID-19 pandemic on Quality of Life (QoL) in persons living with Sickle Cell Disorder (SCD) in Lagos, Nigeria and to determine how they coped during the pandemic, particularly during the period of total lockdown with the additional “SHIELDING” measures to which they had to adhere. Data was collected using a standardized protocol PedsQL, Sickle Cell Disease Module version.3.0 designed for youth within the ages of (13-18) years, (19-35) years and their parents/Guardian if underage. The survey captured data on patients’ pain impact, hurts, management, treatments, communication with their caregivers and their Guardian’s perception. The survey was performed online, or Face-to-Face/telephone interview if online was not possible. Contacts of patients and parents were obtained from the database of Sickle Cell Foundation Nigeria. A total of 105 (80 patients and 25 parents) participants responded to the survey. The age distribution of respondents was highest at 56 % in the age bracket of 13 - 18 years old. Pain crisis were very common amongst patients. The survey revealed that the type of treatment or care received at these times determined whether or not the patients visited the hospital when they had pain crises. In addition, as patients’ reports an increase in ill-treatment they experienced in the hands of health care givers, so did the fear of accessing treatment during the COVID pandemic. It was observed that the frequency of pain crises experienced by SCD patients was proportional to the patient’s quality of life (the higher the frequency of pains, the worse the QoL). As a follow-up, a more detailed study would be required, as this study was limited in the capturing of the demographics, sex and number of participants; Considering the number of persons living with SCD that visit the Sickle Cell Foundation Nigeria, (about 3,000 patients), the number of responses in this study was low (105). It is believed that a higher number of responses would have given more information about the Sickle Cell burden and the QoL of persons living with SCD in Lagos during the COVID-19 pandemic. Lagos was the epicentre of the COVID-19 pandemic in Nigeria.
Long-term Impact of Prior Secondhand Tobacco Smoke Exposure on Respiratory Health
Authors: del Valle Fernando Diaz , Zakrajsek Jonathan K. , Min Sung-Joon , Koff Patricia B. , Bell Harold W. , Kincaid Keegan A. , Frank Daniel N. , Ramakrishnan Vijay , Ghosh Moumita , Vandivier R. William 
Published: September 2021

ABSTRACTRationaleOngoing secondhand tobacco smoke (SHS) exposure is associated with worsened respiratory health, but little is known about the long-term impact decades after exposure ended.ObjectiveDetermine the long-term consequences of SHS exposure on respiratory health.MethodsPopulation-based, cohort study in subjects ≥50 years old who had >1 year versus ≤1 year of airline occupational SHS-exposure.Measurements and Main ResultsRespiratory health was the primary outcome measured by the St. George’s Respiratory Questionnaire (SGRQ). Key secondary outcomes included respiratory symptoms measured by COPD Assessment Test (CAT) and pre-bronchodilator lung function. The study enrolled 183 SHS-exposed and 59 unexposed subjects. SHS-exposed subjects were exposed to airline SHS for 16.1±9.3 years, which ended 27.5±9.4 years prior to enrollment. Prior SHS-exposure was associated with worse respiratory health based on a 6.7-unit increase in SGRQ (95% CI=[2.7, 10.7]; p=0.001) and 3-unit increase in CAT (95% CI=1.4, 4.6]; p<0.001) versus unexposed subjects, but was not associated with airflow obstruction defined by FEV1:FVC<0.7. Clinically-significant respiratory symptoms (CAT≥10) in SHS-exposed never smokers with preserved lung function (FEV1:FVC ≥0.7 and FVC ≥lower limit of normal) were associated with decreased respiratory and non-respiratory quality-of-life, reduced lung function that remained within the normal range, increased comorbidities and inhaled bronchodilator use, higher plasma CRP and SAA-1 and fewer sinonasal basal stem/progenitor cells versus asymptomatic (CAT<10) SHS-exposed subjects.ConclusionSHS is associated with a phenotype of impaired respiratory health almost 3 decades after exposure ended, consistent with a symptomatic form of COPD with preserved lung function recently described in smokers.
A Two-tiered Functional Screen Identifies Herpesviral Transcriptional Modifiers and their Essential Domains
Authors: Morgens David W , Nandakumar Divya , Didychuk Allison L , Yang Kevin J , Glaunsinger Britt 
Published: September 2021

AbstractWhile traditional methods for studying large DNA viruses allow the creation of individual mutants, CRISPR/Cas9 can be used to rapidly create thousands of mutant dsDNA viruses in parallel. Here, we used this approach to study the human oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV). We designed a sgRNA library containing all possible ~22,000 guides targeting the genome of KSHV – one cut site approximately every 8 base pairs – enabling the pooled screening of the entire genome. We used this tool to phenotype all possible Cas9-targeted viruses for transcription of KSHV late genes, which is required to produce structural components of the viral capsid. By performing targeted deep sequencing of the viral genome to distinguish between knock-out and in-frame alleles created by Cas9, we discovered a novel hit, ORF46 – and more specifically its DNA binding domain – is required for viral DNA replication. Our pooled Cas9 tiling screen followed by targeted deep viral sequencing represents a two-tiered screening paradigm that may be widely applicable to dsDNA viruses.
Quantification of neuron types in the rodent hippocampal formation by data mining and numerical optimization
Authors: Attili Sarojini M. , Moradi Keivan , Wheeler Diek W. , Ascoli Giorgio A. 
Published: September 2021

AbstractQuantifying the population sizes of distinct neuron types in different anatomical regions is an essential step towards establishing a brain cell census. Although estimates exist for the total neuronal populations in different species, the number and definition of each specific neuron type are still intensively investigated. Hippocampome.org is an open-source knowledge base with morphological, physiological, and molecular information for 122 neuron types in the rodent hippocampal formation. While such framework identifies all known neuron types in this system, their relative abundances remain largely unknown. This work quantitatively estimates the counts of all Hippocampome.org neuron types by literature mining and numerical optimization. We report the number of neurons in each type identified by main neurotransmitter (glutamate or GABA) and axonal-dendritic patterns throughout 26 subregions and layers of the dentate gyrus, Ammon’s horn, subiculum, and entorhinal cortex. We produce by sensitivity analysis reliable numerical ranges for each type and summarize the amounts across broad neuronal families defined by biomarkers expression and firing dynamics. Study of density distributions indicates that the number of dendritic-targeting interneurons, but not of other neuronal classes, is independent of anatomical volumes. All extracted values, experimental evidence, and related software code are released on Hippocampome.org.
The transposition rate has little influence on equilibrium copy numbers of the P-element
Authors: Kofler Robert , Nolte Viola , Schlötterer Christian 
Published: September 2021

AbstractThe invasion of transposable elements (TEs) in mammals and invertebrates, is likely stopped by piRNAs that emerge after insertion of the TE into a piRNA cluster (the trap model). It remains, however, still unclear which factors influence the dynamics of TE invasions. The activity of the TE (i.e. transposition rate) is one of the frequently discussed key factors. Here we take advantage of the temperature-dependent activity of the P-element, a widely studied eukaryotic TE, to test how TE activity affects the dynamics of a TE invasion. Taking advantage of the temperature-specific activity of the P-element, we monitored its invasion dynamics in experimentalDrosophila simulanspopulations at hot and cold culture conditions. Despite marked differences in transposition rates, the P-element reached very similar copy numbers at both temperatures. The reduction of the insertion rate upon approaching the copy number plateau was accompanied by the emergence of similar amounts of piRNAs against the P-element at both temperatures. Interestingly, the ping-pong cycle, which degrades TE transcripts, becomes only active after the copy number has reached the plateau. We show that the P-element abundance is an order of magnitude lower and fewer P-element insertions in piRNA clusters were observed than expected under the trap model. We conclude that the transposition rate has at the most only a minor influence on TE abundance, but other factors, such as paramutations or selection against TE insertions are shaping the TE composition of organism.
Integrated de novo Gene Prediction and Peptide Assembly of Metagenomic Sequencing Data
Authors: Thippabhotla Sirisha , Liu Ben , Yooseph Shibu , Yang Youngik , Zhang Jun , Zhong Cuncong 
Published: September 2021

ABSTRACTMetagenomics is the study of all genomic content presented in given microbial communities. Metagenomic functional analysis aims to quantify protein families and reconstruct metabolic pathways from the metagenome. It plays a central role in understanding the interaction between the microbial community and its host or environment. De novo functional analysis, which allows the discovery of novel protein families, remains challenging for high-complexity communities. There are currently three main approaches for recovering novel genes or proteins: de novo nucleotide assembly, gene calling, and peptide assembly. Unfortunately, their informational connection and dependency have been overlooked, and each has been formulated as an independent problem. In this work, we develop a sophisticated workflow called integrated Metagenomic Protein Predictor (iMPP), which leverages the informational dependencies for better de novo functional analysis. iMPP contains three novel modules: a hybrid assembly graph generation module, a graph-based gene calling module, and a peptide assembly-based refinement module. iMPP significantly improved the existing gene calling sensitivity on unassembled fragmented reads, achieving a 92% - 97% recall rate at a high precision level (>90%). iMPP further allowed for more sensitive and accurate peptide assembly, recovering more reference proteins and delivering more hypothetical protein sequences. The high performance of iMPP can provide a more comprehensive and unbiased view of the microbial communities under investigation. iMPP is freely available from https://github.com/Sirisha-t/iMPP.
Role of RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease
Authors: Awasthi Sanjay , Hindle Ashley , Sawant Neha A. , George Mathew , Vijayan Murali , Kshirsagar Sudhir , Morton Hallie , Bunquin Lloyd E. , Palade Philip T. , Lawrence J. Josh , Khan Hafiz , Bose Chhanda , Reddy P. Hemachandra , Singh Sharda P. 
Published: September 2021

AbstractThe purpose of our study is to understand the role of the Ralbp1 gene in oxidative stress (OS), mitochondrial dysfunction and cognition in Alzheimer’s disease (AD) pathogenesis. The Ralbp1 gene encodes the 76 kDa protein Rlip (aka RLIP76). Previous studies have revealed its role in OS-related cancer. However, Rlip is transcriptionally regulated by EP300, a CREB-binding protein that is important for synaptic plasticity in the brain. Rlip functions as a stress-responsive/protective transporter of glutathione conjugates (GS-E) and xenobiotic toxins. OS causes rapid cellular accumulation of Rlip and its translocation from a tubulin-bound complex to the plasma membrane, mitochondria and nucleus. Therefore, Rlip may play an important role in maintaining cognitive function in the face of OS-related injury. This study is aimed to determine whether Rlip deficiency in mice is associated with AD-like cognitive and mitochondrial dysfunction. Brain tissue obtained from cohorts of wildtype and Rlip+/- mice were analyzed for OS markers, expression of genes that regulate mitochondrial fission/fusion, and synaptic integrity. We also examined mitochondrial ultrastructure in mouse brains obtained from these mice and further analyzed the impact of Rlip deficiency on gene networks of AD, aging, inhibition of stress-activated gene expression, mitochondrial function, and CREB signaling. Our studies revealed a significant increase in the levels of OS markers and alterations in the expression of genes and proteins involved in mitochondrial biogenesis, dynamics and synapses in brain tissues of these mice. Furthermore, we compared the cognitive function of wildtype and Rlip+/- mice. Behavioral, basic motor and sensory function tests in Rlip+/- mice revealed cognitive decline, similar to AD. Gene network analysis indicated dysregulation of stress-activated gene expression, mitochondrial function, and CREB signaling genes in the Rlip+/- mouse liver. Our results suggest that the Rlip deficiency-associated increase in OS and mitochondrial dysfunction could contribute to the development of OS-related AD processes. Therefore, the restoration of Rlip activity and endogenous cytoprotective mechanisms by pharmacological interventions is a novel approach to protect against AD.
A preliminary study to evaluate white matter structural correlates of delayed visuospatial memory and one-week motor skill retention in nondemented older adults
Authors: VanGilder Jennapher Lingo , Bergamino Maurizio , Hooyman Andrew , Fitzhugh Megan , Rogalsky Corianne , Stewart Jill C. , Beeman Scott C. , Schaefer Sydney Y. 
Published: September 2021

AbstractSkill retention is important for motor rehabilitation outcomes. Recent work has demonstrated that delayed visuospatial memory performance may predict motor skill retention in older and neuropathological populations. White matter integrity between parietal and frontal cortices may explain variance in upper-extremity motor learning tasks and visuospatial processes. We performed a whole-brain analysis to determine the white matter correlates of delayed visuospatial memory and one-week motor skill retention in nondemented older adults. We hypothesized that better frontoparietal tract integrity would be positively related to better behavioral performance. Nineteen participants (age>58) completed diffusion-weighted imaging, then a clinical test of delayed visuospatial memory and 50 training trials of an upper-extremity motor task; participants were retested on the motor task one week later. Principal component analysis was used to create a composite score for each participant’s behavioral data, i.e. shared variance between delayed visuospatial memory and motor skill retention, which was then entered into a voxel-based regression analysis. Behavioral results demonstrated that participants learned and retained their skill level after a week of no practice, and their delayed visuospatial memory score was positively related to the extent of skill retention. Consistent with previous work, neuroimaging results indicated that regions within bilateral anterior thalamic radiations, corticospinal tracts, and superior longitudinal fasciculi were related to better delayed visuospatial memory and skill retention. Results of this study suggest that the simple act of testing for specific cognitive impairments prior to therapy may identify older adults who will receive little to no benefit from the motor rehabilitation regimen, and that these neural regions may be potential targets for therapeutic intervention.
Mosaic Evolution of Beta Barrel Porin Encoding Genes inEscherichia coli
Authors: Chen Xiongbin , Cai Xuxia , Chen Zewei , Wu Jinjin , Hao Gaofeng , Luo Quan , Zhu Guoqiang , Koester Wolfgang , White Aaron P , Cai Yi , Wang Yejun 
Published: September 2021

AbstractBacterial porins serve as the interface interacting with extracellular environment, and are often found under positive selection to fit in different environmental stresses. Local recombination has been identified in a handful of porin genes to facilitate the rapid adaptation of bacterial cells. It remains unknown whether it is a common evolutionary mechanism in gram-negative bacteria for all or a majority of the outer membrane proteins. In this research, we investigated the β-barrel porin encoding genes inEscherichia colithat were reported under positive Darwinia selection. BesidesfhuAthat was found with ingenic local recombination predominantly previously, we identified four other genes, i.e.,lamB, ompA, ompCandompF, all showing the similar mosaic evolution patterns as infhuA. Comparative analysis of the protein sequences disclosed a list of highly variable regions in each protein family, which are mostly located in the convex of extracellular loops and coinciding with the binding sites of various bacteriophages. For each of the porin family, mosaic recombination leads to various combinations of the HVRs with different sequence patterns, generating diverse protein groups. Structure modeling further indicated the conserved global topology for various groups of each porin family, but the extracellular surface varies a lot that is formed by individual or combinatorial HVRs. The conservation of global tertiary structure ensures the channel activity while the wide diversity of HVRs may assist bacteria avoiding the invasion of phages, antibiotics or immune surveillance factors. In summary, the study identified multiple bacterial porin genes with mosaic evolution, a likely general strategy, by which outer membrane proteins could facilitate the host bacteria to both maintain normal life processes and evade the attack of unflavored environmental factors rapidly.ImportanceMicroevolution studies can disclose more elaborate evolutionary mechanisms of genes, appearing especially important for genes with multifaceted function such as those encoding outer membrane proteins. However, in most cases, the gene is considered as a whole unit and the evolutionary patterns are disclosed. In this research, we reported that multiple bacterial porin proteins follow mosaic evolution, with local ingenic recombination combined with spontaneous mutations based positive Darwinia selection, and conservation for most of the other regions. It could represent a common mechanism for bacterial outer membrane proteins. The study also provides insights on development of new anti-bacterial agent or vaccines.