bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-Associated Seroprevalence of Coronavirus Antibodies: Population-Based Serosurveys in 2013 and 2020, British Columbia, Canada
Authors: Tanunliong Guadalein , Liu Aaron C. , Kaweski Samantha , Irvine Mike , Reyes Romina C. , Purych Dale , Krajden Mel , Morshed Muhammad , Sekirov Inna , Gantt Soren , Skowronski Danuta M. , Jassem Agatha N. 
Published: March 2022

BackgroundOlder adults have been disproportionately affected during the SARS-CoV-2 pandemic, including higher risk of severe disease and long-COVID. Prior exposure to endemic human coronaviruses (HCoV) may modulate the response to SARS-CoV-2 infection and contribute to age-related observations. We hypothesized that cross-reactive antibodies to SARS-CoV-2 are associated with antibodies to HCoV and that both increase with age.MethodsTo assess SARS-CoV-2 unexposed individuals, we drew upon archived anonymized residual sero-surveys conducted in British Columbia (BC), Canada, including before SARS-CoV-2 emergence (May, 2013) and before widespread community circulation in BC (May, 2020). Fifty sera, sex-balanced per ten-year age band, were sought among individuals ≤10 to ≥80 years old, supplemented as indicated by sera from March and September 2020. Sera were tested on the Meso Scale Diagnostics (MSD) electrochemiluminescent multiplex immunoassay to quantify IgG antibody against the Spike proteins of HCoV, including alpha (HCoV-229E, HCoV-NL63) and beta (HCoV-HKU1, HCoV-OC43) viruses, and the 2003 epidemic beta coronavirus, SARS-CoV-1. Cross-reactive antibodies to Spike, Nucleocapsid, and the Receptor Binding Domain (RBD) of SARS-CoV-2 were similarly measured, with SARS-CoV-2 sero-positivity overall defined by positivity on ≥2 targets.ResultsSamples included 407 sera from 2013, of which 17 were children ≤10 years. The 2020 samples included 488 sera, of which 88 were children ≤10 years. Anti-Spike antibodies to all four endemic HCoV were acquired by 10 years of age. There were 20/407 (5%) sera in 2013 and 8/488 (2%) in 2020 that were considered sero-positive for SARS-CoV-2 based on MSD testing. Of note, antibody to the single SARS-CoV-2 RBD target was detected in 329/407 (81%) of 2013 sera and 91/488 (19%) of 2020 sera. Among the SARS-CoV-2 overall sero-negative population, age was correlated with anti-HCoV antibody levels and these, notably 229E and HKU1, were correlated with cross-reactive anti-SARS-CoV-2 RBD titres. SARS-CoV-2 overall sero-positive individuals showed higher titres to HCoV more generally.ConclusionMost people have an HCoV priming exposure by 10 years of age and IgG levels are stable thereafter. Anti-HCoV antibodies can cross-react with SARS-CoV-2 epitopes. These immunological interactions warrant further investigation with respect to their implications for COVID-19 clinical outcomes.
Emergence of Lyme Disease on the French Riviera, a Retrospective Survey
Authors: Sevestre Jacques , Benichou Antoine , Rio Vanessa , Delaunay Pascal , Gonfrier Géraldine , Martaresche Cécile , Carlo Virginie , Nakam Sarah , Mondain Véronique , Carles Michel , Jeandel Pierre Yves , Durant Jacques 
Published: March 2022

BackgroundThe French Riviera has been declared free of Lyme Borreliosis (LB) for years. Many patients are referred for presumed LB, sometimes with atypical clinical signs and/or doubtful serology, calling the diagnosis into question.MethodsPatients were assessed for LB diagnosis, depending on clinical presentation, laboratory findings, and further examination by other medical professionals.ResultsAmong 255 patients, 45 (18%) were classified as confirmed LB cases [including 28 ongoing LB (10%) and 17 past LB (8%)], and for 210 (82%) a Lyme borreliosis diagnosis was ruled out. Among ongoing LB, 56% had been exposed to or bitten by ticks, exclusively in rural locations of the Alpes-Maritimes. As a result of the diagnostic procedure, 132 (52%) patients had been treated. An alternative diagnosis was established for 134 (52%) patients, covering a wide range of conditions, including mainly psychological (28%) and neurological conditions (25%) or inflammatory and systemic diseases (22%).ConclusionsOur results strongly suggest the endemicity of LB in the Alpes-Maritimes region. Confirmed LB accounted for 18% of patients while 52% were diagnosed with other conditions.
NeuralDock: Rapid and Conformation-Agnostic Docking of Small Molecules
Authors: Sha Congzhou M. , Wang Jian , Dokholyan Nikolay V. 
Published: March 2022

Virtual screening is a cost- and time-effective alternative to traditional high-throughput screening in the drug discovery process. Both virtual screening approaches, structure-based molecular docking and ligand-based cheminformatics, suffer from computational cost, low accuracy, and/or reliance on prior knowledge of a ligand that binds to a given target. Here, we propose a neural network framework, NeuralDock, which accelerates the process of high-quality computational docking by a factor of 106, and does not require prior knowledge of a ligand that binds to a given target. By approximating both protein-small molecule conformational sampling and energy-based scoring, NeuralDock accurately predicts the binding energy, and affinity of a protein-small molecule pair, based on protein pocket 3D structure and small molecule topology. We use NeuralDock and 25 GPUs to dock 937 million molecules from the ZINC database against superoxide dismutase-1 in 21 h, which we validate with physical docking using MedusaDock. Due to its speed and accuracy, NeuralDock may be useful in brute-force virtual screening of massive chemical libraries and training of generative drug models.
Subthalamic Beta Activity in Parkinson's Disease May Be Linked to Dorsal Striatum Gray Matter Volume and Prefrontal Cortical Thickness: A Pilot Study
Authors: Sanmartino Florencia , Cruz-Gómez Álvaro J. , Rashid-López Raúl , Lozano-Soto Elena , López-Sosa Fernando , Zuazo Amaya , Riqué-Dormido Jesús , Espinosa-Rosso Raúl , González-Rosa Javier J. 
Published: March 2022

BackgroundExcessive oscillations at beta frequencies (13–35 Hz) in the subthalamic nucleus (STN) represent a pathophysiological hallmark of Parkinson's disease (PD), which correlates well with parkinsonian symptoms and is reduced in response to standard disease treatments. However, the association of disease-specific regional gray matter (GM) atrophy or cortical thickness (CT) with the presence of STN beta oscillatory activity has been poorly investigated but is of relevance given the potential of these variables for extracting information about PD pathophysiology. This exploratory study investigated the involvement of regional GM volume and CT in the basal ganglia-cortical network and its potential association with the presence of STN beta oscillatory activity in PD.MethodsWe acquired preoperative GM densities on T1-weighted magnetic resonance imaging scans and we carried out regional estimation of GM volume and CT. LFP activities from the STN were recorded post-operatively in 7 cognitively preserved PD patients off dopaminergic medication undergoing deep-brain stimulation surgery. Oscillatory beta power was determined by power spectral density of 4-min resting state STN LFP activity. Spearman partial correlations and regression analysis were used to screen the presence of STN beta power for their relationship with GM volume and CT measurements.ResultsAfter controlling for the effects of age, educational level, and disease duration, and after correcting for multiple testing, enhanced STN beta power showed significant and negative correlations between, first, volume of the right putamen and left caudate nucleus, and second, smaller CT in frontal regions involving the left rostral middle frontal gyrus (MFG) and left medial orbitofrontal gyrus. A lower volume in the right putamen and a lower CT in the left MFG demonstrated the strongest associations with increased STN beta power.ConclusionsThese tentative results seem to suggest that STN LFP beta frequencies may be mainly linked to different but ongoing parallel neurodegenerative processes, on the one hand, to GM volume reduction in dorsal striatum, and on the other hand, to CT reduction of prefrontal-“associative” regions. These findings could further delineate the brain structural interactions underpinning the exaggerated STN beta activity commonly observed in PD patients.
Thoracic Excursion Is a Biomarker for Evaluating Respiratory Function in Amyotrophic Lateral Sclerosis
Authors: Iguchi Naohiko , Mano Tomoo , Iwasa Naoki , Ozaki Maki , Yamada Nanami , Kikutsuji Naoya , Kido Akira , Sugie Kazuma 
Published: March 2022

ObjectiveTo evaluate the usefulness of thoracic excursion as a biomarker in patients with amyotrophic lateral sclerosis (ALS).MethodsWe measured the forced the vital capacity (FVC), thoracic excursion, baseline-to-peak diaphragmatic compound muscle action potential (DCMAP) amplitude, diaphragm thickness at full inspiration (DTfi), Medical Research Council (MRC) sum score for muscle strength, and arterial partial pressures of oxygen and carbon dioxide and administered the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) and modified Medical Research Council (mMRC) Dyspnea Scale. The test–retest reliability of thoracic excursion was determined.Results and ConclusionsThirty-four patients with ALS and 26 age- and sex-matched healthy participants were enrolled. Thoracic excursion measurement had excellent test–retest reliability (intraclass coefficient: 0.974). Thoracic excursion was more strongly correlated with FVC (r = 0.678, p &lt; 0.001) than DCMAP amplitude (r = 0.501, p = 0.003) and DTfi (r = 0.597, p &lt; 0.001). It was also correlated with ALSFRS-R score (r = 0.610, p &lt; 0.001), MRC sum score (r = 0.470, p = 0.005), and mMRC Dyspnea Scale score (r = −0.446, p = 0.008) and was the most sensitive parameter for assessing dyspnea and FVC. Thoracic excursion decreased as FVC declined in the early and late stages, there were no differences in DCMAP amplitude and DTfi between the early and late stages, and ALSFRS-R score and MRC sum score decreased only in the late stage. Thoracic excursion was well correlated with respiratory function and is useful for predicting respiratory and general dysfunction in patients with ALS regardless of stage.
Paclitaxel Chemotherapy Elicits Widespread Brain Anisotropy Changes in a Comprehensive Mouse Model of Breast Cancer Survivorship: Evidence From In Vivo Diffusion Weighted Imaging
Authors: Otto Lauren D. , Russart Kathryn L. G. , Kulkarni Praveen , McTigue Dana M. , Ferris Craig F. , Pyter Leah M. 
Published: March 2022

Breast cancer is one of the most common diseases in the United States with 1 in 8 women developing the disease in her lifetime. Women who develop breast cancer are often post-menopausal and undergo a complex sequence of treatments including surgery, chemotherapy, and aromatase inhibitor therapy. Both independently and through potential interactions, these factors and treatments are associated with behavioral comorbidities reported in patients (e.g., fatigue), although the underlying neurobiological mechanisms are poorly understood. Currently, brain imaging is the most feasible way to assess neurobiology in patients. Indeed, breast cancer patients display alterations in white matter connections and chemotherapy is associated with decreased white and gray matter in the corpus callosum and cortex as well as decreased hippocampal volume. However, imaging in breast cancer rodent models is lacking, impeding translation of the mechanistic neurobiological findings made possible through modeling. Furthermore, current rodent models of breast cancer often lack the complexity of typical multimodal breast cancer treatments, thereby limiting translational value. The present study aimed to develop a comprehensive model of post-menopausal breast cancer survival using immunocompetent ovariectomized mice, including an orthotopic syngeneic tumor, surgical tumor removal, chemotherapy, and aromatase inhibitor therapy. Using this model, we systematically investigated the cumulative effects of chemotherapy and hormone replacement therapy on neurostructure and behavior using diffusion weighted imaging, open field test, and spontaneous alternation test. Our previous findings, in a simplified chemotherapy-only model, indicate that this regimen of chemotherapy causes circulating and central inflammation concurrent with reduced locomotor activity. The current study, in the more comprehensive model, has recapitulated the peripheral inflammation coincident with reduced locomotor activity as well as demonstrated that chemotherapy also drives widespread changes in brain anisotropy. Validating the clinical relevance of this comprehensive rodent breast cancer model will allow for additional neurobiological investigations of the interactions among various cancer components associated with behavioral comorbidities, as well as the relationship between these mechanisms and neurostructural imaging changes that can be measured in cancer patients.
Development and External Validation of a Novel Model for Predicting Postsurgical Recurrence and Overall Survival After Cytoreductive R0 Resection of Epithelial Ovarian Cancer
Authors: Li Qiaqia , Deng Yinghong , Wei Wei , Yang Fan , Lin An , Yao Desheng , Zhu Xiaofeng , Li Jundong 
Published: March 2022

PurposeTreatment of epithelial ovarian cancer is evolving towards personalization and precision, which require patient-specific estimates of overall survival (OS) and progression-free survival (PFS).Patients and MethodsMedical records of 1173 patients who underwent debulking surgery in our center were comprehensively reviewed and randomly allocated into a derivation cohort of 879 patients and an internal validation cohort of 294 patients. Five hundred and seventy-seven patients from the other three cancer centers served as the external validation cohort. A novel nomogram model for PFS and OS was constructed based on independent predictors identified by multivariable Cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell’s concordance index (C-index) and calibration curve.ResultsThe C-index values were 0.82 (95% CI: 0.76–0.88) and 0.84 (95% CI: 0.78–0.90) for the PFS and OS models, respectively, substantially higher than those obtained with the FIGO staging system and most nomograms reported for use in epithelial ovarian cancer. The nomogram score could clearly classify the patients into subgroups with different risks of recurrence or postoperative mortality. The online versions of our nomograms are available at https://eocnomogram.shinyapps.io/eocpfs/ and https://eocnomogram.shinyapps.io/eocos/.ConclusionA externally validated nomogram predicting OS and PFS in patients after R0 reduction surgery was established using a propensity score matching model. This nomogram may be useful in estimating individual recurrence risk and guiding personalized surveillance programs for patients after surgery, and it could potentially aid clinical decision-making or stratification for clinical trials.
Gender Specificity and Local Socioeconomic Influence on Association of GHR fl/d3 Polymorphism With Growth and Metabolism in Children and Adolescents
Authors: Chen Xiaotian , Liu Chunlan , Yang Song , Yang Yaming , Chen Yanchun , Zhao Xianghai , Zhu Weiguang , Zhao Qihui , Ni Chuan , Huang Xiangyuan , Yan Weili , Shen Chong , Gu Harvest F. 
Published: March 2022

ObjectiveGrowth hormone receptor (GHR) mediates most GH biological actions. This study is aimed to evaluate whether GHR fl/d3 polymorphism contributes to the inter-individual variability of growth and metabolism in healthy children and adolescents.MethodsA total of 4,730 students aged 6-16 years from Yixing and Suqian City in China were included in this cross-sectional study. Height and body mass index (BMI) were transformed into the form of z-score corresponding to age and gender. Logistic regression was used to evaluate the associations of GHR fl/d3 polymorphism with height, BMI, metabolic traits, and hypertension by estimating the odds ratios (ORs) and 95% confidence intervals (CIs).ResultsGHR d3 allele was inversely associated with overweight, total cholesterol (TC) and triglyceride (TG) levels (OR [95% CI] for overweight: 0.754 [0.593-0.959], P = 0.021; OR [95% CI] for TC: 0.744 [0.614-0.902], P = 0.003; OR [95% CI] for TG: 0.812 [0.654-0.998], P = 0.047). GHR d3 allele was associated with decreased odds of pre-hypertension in boys (OR [95% CI]: 0.791 [0.645-0.971], P = 0.025), but associated with increased odds of pre-hypertension and hypertension in girls (ORs [95% CIs]: 1.379 [1.106-1.719], P = 0.004; OR [95% CI]: 1.240 [1.013-1.519], P = 0.037). Interaction of GHR fl/d3 polymorphism with gender contributed to increased odds of pre-hypertension and hypertension (interactive ORs [95% CIs]: 1.735 [1.214-2.481], P = 0.003; OR [95% CI]: 1.509 [1.092-2.086], P = 0.013). Stratification analysis showed that the correlation tendencies of GHR fl/d3 polymorphism and BMI with age were different between two cities with discrepant economic development levels.ConclusionGHR fl/d3 polymorphism is associated with growth, metabolism, and hypertension in children and adolescents with the gender specificity, and the genetic effect of GHR fl/d3 may be modified by the local socioeconomic levels.
Prediction of Retinopathy of Prematurity Using the WINROP (Weight, IGF-1, Neonatal Retinopathy of Prematurity) Algorithm in a South African Population
Authors: Kesting Samantha Jane , Nakwa Firdose Lambey 
Published: March 2022

AimThis study aimed to assess the efficacy of the WINROP (Weight, IGF-1, Neonatal Retinopathy of Prematurity) screening algorithm in a South African population.MethodsA retrospective record review included infants born between 1 January 2013 and 1 December 2014 who underwent ROP (retinopathy of prematurity) screening. Outcomes of ophthalmology examinations were compared to alarms triggered on WINROP after gestational age, date of birth, and weekly weights were entered. Sensitivity, specificity, positive predictive, and negative predictive values and mean time of alarm were calculated.ResultsRates of ROP were 5.9% for all stages of ROP and 2.3% for severe ROP in the 220 infants included. Mean gestation age was 29.1 ± 1.3 weeks and mean birth weight 1,115.5 ± 201 g. WINROP triggered high-risk alarms in 70.5% of infants at a mean of 30.7 weeks of gestational age. Sensitivity for severe ROP was 100 and 76.9% for all stages of ROP. Specificity was low for both severe ROP and all stages of ROP at 30.2 and 30.0%, respectively.ConclusionRates of ROP are low in this population. The high number of alarms with a low negative predictive value would reduce the number of screens by 29.5%. Alarms were triggered before scheduled screening, possibly helpful in planning discharges and follow-up visits.
Impact of Adolescent Intermittent Ethanol Exposure on Social Investigation, Social Preference, and Neuronal Activation in cFos-LacZ Male and Female Rats
Authors: Towner Trevor T. , Applegate Devon T. , Varlinskaya Elena I. , Werner David F. 
Published: March 2022

Adolescence is a sensitive developmental period during which alcohol use is often initiated and consumed in high quantities, often at binge or even high-intensity drinking levels. Our lab has repeatedly found that adolescent intermittent ethanol (AIE) exposure in rats results in long-lasting social impairments, specifically in males, however our knowledge of the neuronal underpinnings to this sex-specific effect of AIE is limited. The present study was designed to test whether social anxiety-like alterations in AIE-exposed males would be accompanied by alterations of neuronal activation across brain regions associated with social behavior, with AIE females demonstrating no social impairments and alterations in neuronal activation. Adolescent male and female cFos-LacZ transgenic rats on a Sprague-Dawley background were exposed to ethanol (4 g/kg, 25% v/v) or water via intragastric gavage every other day during postnatal days (P) 25–45 for a total of 11 exposures (n = 13 per group). Social behavior of adult rats was assessed on P70 using a modified social interaction test, and neuronal activation in brain regions implicated in social responding was assessed via β-galactosidase (β-gal) expression. We found that AIE exposure in males resulted in a significantly lower social preference coefficient relative to water-exposed controls, with no effect evident in females. Exposure-specific relationships between social behavior and neuronal activation were identified, with AIE eliminating correlations found in water controls related to social interaction, and eliciting negative correlations mainly in limbic regions in a sex-specific manner. AIE exposure in the absence of social testing was also found to differentially affect neural activity in the orbitofrontal cortex and central amygdala in males and females. These data suggest that AIE produces sex-specific social impairments that are potentially driven by differential neuronal activation states in regions important for social behavior, including the medial prefrontal and orbitofrontal cortices, nucleus accumbens, lateral septum, and central amygdala. Future studies should be focused on identification of specific neuronal phenotypes activated by interaction with a social partner in AIE-exposed subjects and their control counterparts.
A Betulinic Acid Derivative, BA5, Induces G0/G1 Cell Arrest, Apoptosis Like-Death, and Morphological Alterations in Leishmania sp
Authors: Magalhães Tatiana Barbosa dos Santos , Silva Dahara Keyse Carvalho , Teixeira Jessica da Silva , De Lima Juliana Dizaira Teles , Barbosa-Filho José Maria , Moreira Diogo Rodrigo Magalhães , Guimarães Elisalva Teixeira , Soares Milena Botelho Pereira 
Published: March 2022

Leishmaniasis are endemic diseases caused by different species of intracellular parasites of the genus Leishmania. Due to the high toxicity and drug resistance of current antileishmanial drugs, it is necessary to identify new and more effective drugs. Previously, we investigated the immunomodulatory and anti-Trypanosoma cruzi action of BA5, a derivative of betulinic acid. In the present study, we investigated the in vitro activity of BA5 against different species of Leishmania and their action mechanism. BA5 exhibited low cytotoxicity against macrophages and inhibited the proliferation of promastigote forms of Leishmania amazonensis (IC50 = 4.5 ± 1.1 μM), Leishmania major (IC50 = 3.0 ± 0.8 μM), Leishmania braziliensis (IC50 = 0.9 ± 1.1 μM) and Leishmania infantum (IC50 = 0.15 ± 0.05 μM). Incubation with BA5 reduced the percentage of Leishmania amazonensis-infected macrophages and the number of intracellular parasites (IC50 = 4.1 ± 0.7 μM). To understand the mechanism of action underlying BA5 antileishmanial activity (incubation at IC50/2, IC50 or 2xIC50 values of the drug), we investigated ultrastructural changes by scanning electron microscopy and evaluated cell cycle, membrane mitochondrial potential, and cell death against promastigote forms of Leishmania amazonensis by flow cytometry. Promastigotes incubated with BA5 presented membrane blebbing, flagella damage, increased size, and body deformation. Flow cytometry analysis showed that parasite death is mainly caused by apoptosis-like death, arrested cell cycle in G0/G1 phase and did not alter the membrane mitochondrial potential of Leishmania amazonensis. Surprisingly, the combination of BA5 and amphotericin B, an assay used to determine the degree of drug interaction, revealed synergistic effects (CI = 0.15 ± 0.09) on promastigotes forms of Leishmania amazonensis. In conclusion, BA5 compound is an effective and selective antileishmanial agent.