bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early maternal care restores LINE-1 methylation and enhances neurodevelopment in preterm infants
Authors: Fontana Camilla , Marasca Federica , Provitera Livia , Mancinelli Sara , Pesenti Nicola , Sinha Shruti , Passera Sofia , Abrignani Sergio , Mosca Fabio , Lodato Simona , Bodega Beatrice , Fumagalli Monica 
Published: February 2021

Abstract
Background
Preterm birth affects almost 9–11% of newborns and is one of the leading causes of childhood neurodevelopmental disabilities; the underlying molecular networks are poorly defined. In neurons, retrotransposons LINE-1 (L1) are an active source of genomic mosaicism that is deregulated in several neurological disorders; early life experience has been shown to regulate L1 activity in mice.

Methods
Very preterm infants were randomized to receive standard care or early intervention. L1 methylation was measured at birth and at hospital discharge. At 12 and 36 months, infants’ neurodevelopment was evaluated with the Griffiths Scales. L1 methylation and CNVs were measured in mouse brain areas at embryonic and postnatal stages.

Results
Here we report that L1 promoter is hypomethylated in preterm infants at birth and that an early intervention program, based on enhanced maternal care and positive multisensory stimulation, restores L1 methylation levels comparable to healthy newborns and ameliorates neurodevelopment in childhood. We further show that L1 activity is fine-tuned in the perinatal mouse brain, suggesting a sensitive and vulnerable window for the L1 epigenetic setting.

Conclusions
Our results open the field on the inspection of L1 activity as a novel molecular and predictive approach to infants’ prematurity-related neurodevelopmental outcomes.

Trial registration
ClinicalTrial.gov (NCT02983513). Registered on 6 December 2016, retrospectively registered.
Genome-wide genetic links between amyotrophic lateral sclerosis and autoimmune diseases
Authors: Li Chun Yu , Yang Tian Mi , Ou Ru Wei , Wei Qian Qian , Shang Hui Fang 
Published: February 2021

AbstractBackgroundEpidemiological and clinical studies have suggested comorbidity between amyotrophic lateral sclerosis (ALS) and autoimmune disorders. However, little is known about their shared genetic architecture.MethodsTo examine the relation between ALS and 10 autoimmune diseases, including asthma, celiac disease (CeD), Crohn’s disease (CD), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and ulcerative colitis (UC), and identify shared risk loci, we first estimated the genetic correlation using summary statistics from genome-wide association studies, and then analyzed the genetic enrichment leveraging the conditional false discovery rate statistical method.ResultsWe identified a significant positive genetic correlation between ALS and CeD, MS, RA, and SLE, as well as a significant negative genetic correlation between ALS and IBD, UC, and CD. Robust genetic enrichment was observed between ALS and CeD and MS, and moderate enrichment was found between ALS and UC and T1D. Thirteen shared genetic loci were identified, among which five were suggestively significant in another ALS GWAS, namely rs3828599 (GPX3), rs3849943 (C9orf72), rs7154847 (G2E3), rs6571361 (SCFD1), and rs9903355 (GGNBP2). By integratingcis-expression quantitative trait loci analyses in Braineac and GTEx, we further identifiedGGNBP2,ATXN3, andSLC9A8as novel ALS risk genes. Functional enrichment analysis indicated that the shared risk genes were involved in four pathways including membrane trafficking, vesicle-mediated transport, ER to Golgi anterograde transport, and transport to the Golgi and subsequent modification.ConclusionsOur findings demonstrate a specific genetic correlation between ALS and autoimmune diseases and identify shared risk loci, including three novel ALS risk genes. These results provide a better understanding for the pleiotropy of ALS and have implications for future therapeutic trials.
Immunoglobulin G1 subclass responses can be used to detect specific allergy to the house dust mites Dermatophagoides farinae and Dermatophagoides pteronyssinus in atopic dogs
Authors: Khantavee N. , Chanthick C. , Tungtrongchitr A. , Techakriengkrai N. , Suradhat S. , Sookrung N. , Roytrakul S. , Prapasarakul N. 
Published: February 2021

AbstractBackgroundIn dogs with atopic dermatitis, intradermal testing (IDT) or allergen specific IgE serological testing are routinely employed to identify causative allergens. These allergens can then be used for allergen-specific immunotherapy and allergy management. The clinical relevance of this testing is affected by the source of allergen, and other biomarkers that are more related to specific allergens still need to be identified. The aim of this study was to investigate levels of specific IgE, total IgG, and IgG1 and IgG2 subclasses against the local house dust mites (HDM)Dermatophagoides farinae(DF) andD. pteronyssinus(DP) as biomarkers by using in-house ELISAs in healthy (n = 33) and atopic dogs (AD) (n = 44) that were either positive or negative by IDT to HDM.ResultsBeing over 3 years of age was a risk factor for AD (Odds Ratio (OD) = 4.10, 95% Confidence interval (CI) 1.57–10.75,p = 0.0049), but there was no relation to IDT outcomes (OR = 0.9091, 95% CI 0.22–3.74,p = 1.00). High levels of all antibody isotypes (IgE, IgG, IgG1 and IgG2) against HDM were found in aged healthy dogs (> 3 years old). In AD, HDM-IgE and IgG1 levels were higher in dogs that were IDT positive to HDM than in IDT negative animals. Levels of IgE and IgG1 could be used to distinguish the specific allergens, whereas total IgG and IgG2 levels were not different between IDT-positive and IDT-negative AD. By the receiver operating characteristic curve at a false-positive rate = 0.10, both IgE and IgG1 showed better sensitivity than IgG and IgG2. Similar to IgE, serum IgG1 concentration was also relevant to IDT outcomes.ConclusionsOur in-house ELISAs coated with local HDM were useful for evaluating antibody levels, and we propose use of the HDM-specific IgG1 subclass as a biomarker to detect HDM specific allergens in AD, potentially together with an IgE based platform.
Development and validation of a prognostic COVID-19 severity assessment (COSA) score and machine learning models for patient triage at a tertiary hospital
Authors: Schöning Verena , Liakoni Evangelia , Baumgartner Christine , Exadaktylos Aristomenis K. , Hautz Wolf E. , Atkinson Andrew , Hammann Felix 
Published: February 2021

Abstract
Background
Clinical risk scores and machine learning models based on routine laboratory values could assist in automated early identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients at risk for severe clinical outcomes. They can guide patient triage, inform allocation of health care resources, and contribute to the improvement of clinical outcomes.

Methods
In- and out-patients tested positive for SARS-CoV-2 at the Insel Hospital Group Bern, Switzerland, between February 1st and August 31st (‘first wave’, n = 198) and September 1st through November 16th 2020 (‘second wave’, n = 459) were used as training and prospective validation cohort, respectively. A clinical risk stratification score and machine learning (ML) models were developed using demographic data, medical history, and laboratory values taken up to 3 days before, or 1 day after, positive testing to predict severe outcomes of hospitalization (a composite endpoint of admission to intensive care, or death from any cause). Test accuracy was assessed using the area under the receiver operating characteristic curve (AUROC).

Results
Sex, C-reactive protein, sodium, hemoglobin, glomerular filtration rate, glucose, and leucocytes around the time of first positive testing (− 3 to + 1 days) were the most predictive parameters. AUROC of the risk stratification score on training data (AUROC = 0.94, positive predictive value (PPV) = 0.97, negative predictive value (NPV) = 0.80) were comparable to the prospective validation cohort (AUROC = 0.85, PPV = 0.91, NPV = 0.81). The most successful ML algorithm with respect to AUROC was support vector machines (median = 0.96, interquartile range = 0.85–0.99, PPV = 0.90, NPV = 0.58).

Conclusion
With a small set of easily obtainable parameters, both the clinical risk stratification score and the ML models were predictive for severe outcomes at our tertiary hospital center, and performed well in prospective validation.
Immediate impact of extremity manipulation on dual task performance: a randomized, crossover clinical trial
Authors: Malaya Christopher A. , Haworth Joshua , Pohlman Katherine A. , Smith Dean L. 
Published: February 2021

Abstract
Background
Previous research demonstrated that manipulation of the extremities was associated with changes in multisegmental postural sway as well as improvement in a lower extremity balancing task. We were interested if these effects would extend to an upper extremity task. Our aim in this study was to investigate whether extremity manipulation could influence dual task performance where the explicit suprapostural task was balancing a water filled tube in the frontal plane.

Methods
Participants were healthy volunteers (aged 21–32 years). Upper- or lower-extremity manipulations were delivered in a participant and assessor blinded, randomized crossover, clinical trial. Postural (center of pressure) and suprapostural (tube motion) measurements in the frontal plane were made pre-post manipulation under eyes open and eyes closed conditions using a BTrackS™ force plate and a Shimmer inertial measurement unit, respectively. Pathlength, range, root mean square and sample entropy were calculated to describe each signal during the dual task performance.

Results
There was no main effect of manipulation or vision for the suprapostural task (tube motion). However, follow-up to interaction effects indicates that roll pathlength, range and root means square of tube motion all decreased (improvement) following lower extremity manipulation with eyes open. Regarding the postural task, there was a main effect of manipulation on mediolateral center of pressure such that pathlength reduced with both upper and lower extremity manipulation with larger decreases in pathlength values following upper extremity manipulation.

Conclusion
Our findings show that manipulation of the extremities enhanced stability (e.g. tube stabilization and standing balance) on performance of a dual task. This furthers the argument that site-specific manipulations influence context specific motor behavior/coordination. However, as this study focused only on the immediate effects of extremity manipulation, caution is urged in generalizing these results to longer time frames until more work has been done examining the length of time these effects last.

Trial registration
Clinicaltrials.gov, NCT03877367, Registered 15 March 2019. Data collection took place July 2019.
Incidence and locations of preoperative deep venous thrombosis (DVT) of lower extremity following tibial plateau fractures: a prospective cohort study
Authors: Zhu Yanbin , Chen Wei , Li Junyong , Zhao Kuo , Zhang Junzhe , Meng Hongyu , Zhang Yingze , Zhang Qi 
Published: February 2021

Abstract
Background
There is still lack of data on deep vein thrombosis (DVT) following bone trauma. This study aimed to determine the epidemiologic characteristics of deep venous thrombosis (DVT) of lower extremities following tibial plateau fractures.

Methods
Retrospective analysis of prospectively collected data on patients presenting with tibial plateau fractures between October 2014 and December 2018 was conducted. Duplex ultrasonography (DUS) was routinely used to screen for preoperative DVT of bilateral lower extremities. Data on demographics, comorbidities, injury-related data, and laboratory biomarkers at admission were collected. Univariate analyses and multivariate logistic regression analyses were used to identify the independent risk factors associated with DVT.

Results
A total of 1179 patients were included, among whom 192 (16.3%) had a preoperative DVT, with incidence rate of 1.0% for proximal and 15.3% for distal DVT. The average interval between fracture occurrence and diagnosis of DVT was 3.5 days (median, 2 days), ranging from 0 to 19 days. DVT involved the injured extremity in 166 (86.4%) patients, both the injured and uninjured extremities in 14 patients (7.3%) and only the uninjured extremity in 12 patients (6.3%). Six risk factors were identified to be associated with DVT, including gender (male vs female), hypertension, open fracture, alkaline phosphatase > 100 u/L, sodium concentration < 135 mmol/L, and D-dimer > 0.5 mg/L.

Conclusion
These epidemiologic data are conducive to the individualized assessment, risk stratification, and development of targeted prevention programs.
Complications of dual growing rod with all-pedicle screw instrumentation in the treatment of early-onset scoliosis
Authors: Zarei Mohammad , Tavakoli Mehdi , Ghadimi Ehsan , Moharrami Alireza , Nili Ali , Vafaei Ali , Tamehri Zadeh Seyed Saeed , Baghdadi Soroush 
Published: February 2021

AbstractBackgroundTreatment of early-onset scoliosis (EOS) is still a challenge to patients, families, and surgeons. Previous studies have indicated that EOS patients are at high risk for complications following growth-friendly surgery. This study was performed to evaluate the results and complications of all-pedicle screw dual growing rod instrumentation in the treatment of EOS.MethodsIn an IRB-approved retrospective study, we searched the electronic medical records of our institution for all patients who underwent posterior spinal instrumentation for scoliosis between March 2014 and March 2017. Patients under the age of 10 at the time of surgery who were treated with a growth-friendly technique were then selected. Patients with incomplete records and less than 2 years of follow-up were excluded. Charts, operative notes, clinic visits, and radiographs were extracted. Radiographs were reviewed, and the main curve Cobb angle, thoracic kyphosis, pelvic tilt, pelvic incidence, sacral slope, and proximal junctional angles were measured. We specifically looked for any intra-operative or post-operative complications. Statistical analysis was performed to determine the risk factors of complications.ResultsA total of 42 patients with a mean age of 4.8 ± 2.1 years (range, 1.5–8 years) were included in the final analysis. Patients were followed for a median of 34 months (range, 24–55). The major curve was corrected from a mean of 42.9° ± 10.7° to 28.8° ± 9.6° at the latest follow-up. Proximal junctional angles and thoracic kyphosis increased significantly during the follow-up period (bothPvalues < 0.001). A total of 7 complications (17%) were observed. Four patients (10%) developed superficial surgical site infections, all of which resolved with antibiotics and one round of surgical debridement. Three cases (7%) of proximal junctional kyphosis (PJK) were encountered during the study period, none of which required revision surgery. Pre-operative thoracic kyphosis was the only significant risk factor for the development of PJK.ConclusionsOur findings suggest that in settings without access to magnetically controlled growing rods, dual growing rods with all-pedicle screw instrumentation is still a viable treatment strategy with comparable results and complications. The most common complications are infection and PJK, with the latter being associated with a larger pre-operative thoracic kyphosis.
Molecular mechanics and dynamic simulations of well-known Kabuki syndrome-associated KDM6A variants reveal putative mechanisms of dysfunction
Authors: Chi Young-In , Stodola Timothy J. , De Assuncao Thiago M. , Leverence Elise N. , Tripathi Swarnendu , Dsouza Nikita R. , Mathison Angela J. , Basel Donald G. , Volkman Brian F. , Smith Brian C. , Lomberk Gwen , Zimmermann Michael T. , Urrutia Raul 
Published: February 2021

Abstract
Background
Kabuki syndrome is a genetic disorder that affects several body systems and presents with variations in symptoms and severity. The syndrome is named for a common phenotype of faces resembling stage makeup used in a Japanese traditional theatrical art named kabuki. The most frequent cause of this syndrome is mutations in the H3K4 family of histone methyltransferases while a smaller percentage results from genetic alterations affecting the histone demethylase, KDM6A. Because of the rare presentation of the latter form of the disease, little is known about how missense changes in the KDM6A protein sequence impact protein function.

Results
In this study, we use molecular mechanic and molecular dynamic simulations to enhance the annotation and mechanistic interpretation of the potential impact of eleven KDM6A missense variants found in Kabuki syndrome patients. These variants (N910S, D980V, S1025G, C1153R, C1153Y, P1195L, L1200F, Q1212R, Q1248R, R1255W, and R1351Q) are predicted to be pathogenic, likely pathogenic or of uncertain significance by sequence-based analysis. Here, we demonstrate, for the first time, that although Kabuki syndrome missense variants are found outside the functionally critical regions, they could affect overall function by significantly disrupting global and local conformation (C1153R, C1153Y, P1195L, L1200F, Q1212R, Q1248R, R1255W and R1351Q), chemical environment (C1153R, C1153Y, P1195L, L1200F, Q1212R, Q1248R, R1255W and R1351Q), and/or molecular dynamics of the catalytic domain (all variants). In addition, our approaches predict that many mutations, in particular C1153R, could allosterically disrupt the key enzymatic interactions of KDM6A.

Conclusions
Our study demonstrates that the KDM6A Kabuki syndrome variants may impair histone demethylase function through various mechanisms that include altered protein integrity, local environment, molecular interactions and protein dynamics. Molecular dynamics simulations of the wild type and the variants are critical to gain a better understanding of molecular dysfunction. This type of comprehensive structure- and MD-based analyses should help develop improved impact scoring systems to interpret the damaging effects of variants in this protein and other related proteins as well as provide detailed mechanistic insight that is not currently predictable from sequence alone.
Touch and olfaction/taste differentiate children carrying a 16p11.2 deletion from children with ASD
Authors: Osório Joana Maria Almeida , Rodríguez-Herreros Borja , Romascano David , Junod Vincent , Habegger Aline , Pain Aurélie , Richetin Sonia , Yu Paola , Isidor Bertrand , Van Maldergem Lionel , Pons Linda , Manificat Sabine , Chabane Nadia , Jequier Gygax Marine , Maillard Anne Manuela 
Published: February 2021

AbstractBackgroundSensory processing atypicalities are frequent in Autism Spectrum Disorder (ASD) and neurodevelopmental disorders (NDD). Different domains of sensory processing appear to be differentially altered in these disorders. In this study, we explored the sensory profile of two clinical cohorts, in comparison with a sample of typically developing children.MethodsBehavioral responses to sensory stimuli were assessed using the Sensory Processing Measure (parent-report questionnaire). We included 121 ASD children, 17 carriers of the 16p11.2 deletion (Del 16p11.2) and 45 typically developing (TD) children. All participants were aged between 2 and 12 years. Additional measures included the Tactile Defensiveness and Discrimination Test-Revised, Wechsler Intelligence Scales and Autism Diagnostic Observation Schedule (ADOS-2). Statistical analyses included MANCOVA and regression analyses.ResultsASD children score significantly higher on all SPM subscales compared to TD. Del16p11.2 also scored higher than TD on all subscales except for tactile and olfactory/taste processing, in which they score similarly to TD. When assessing sensory modulation patterns (hyper-, hypo-responsiveness and seeking), ASD did not significantly differ from del16p11.2. Both groups had significantly higher scores across all patterns than the TD group. There was no significant association between the SPM Touch subscale and the TDDT-R.LimitationsSensory processing was assessed using a parent-report questionnaire. Even though it captures observable behavior, a questionnaire does not assess sensory processing in all its complexity. The sample size of the genetic cohort and the small subset of ASD children with TDDT-R data render some of our results exploratory. Divergence between SPM Touch and TDDT-R raises important questions about the nature of the process that is assessed.ConclusionsTouch and olfaction/taste seem to be particularly affected in ASD children compared to del16p11.2. These results indicate that parent report measures can provide a useful perspective on behavioral expression. Sensory phenotyping, when combined with neurobiological and psychophysical methods, might have the potential to provide a better understanding of the sensory processing in ASD and in other NDD.
Conservative management of primary malignant melanoma of the bladder: a case report
Authors: Rapisarda Sebastiano , Bada Maida , Polara Andrea , Crocetto Felice , Creta Massimiliano , Chiancone Francesco , Occhipinti Massimo , Bertoloni Rossella , Marciano Armando , Aresu Luca , Nazaraj Arjan , Grosso Sara , Grosso Gaetano 
Published: February 2021

Abstract
Background
Primary malignant melanoma (PMM) of the bladder represents a very rare clinic-pathologic entity. Given the rarity of the disease, the best treatment option is not well recognized.

Case presentation
We describe a case of neoplasm of the bladder in a 74 years-old Caucasian man presenting with massive hematuria. Based on clinical, instrumental and histological findings a diagnosis of PMM was made. The patient underwent trans urethral resection of bladder tumor plus intravesical Bacillus Calmette–Guérin.

Conclusions
To make a correct diagnosis, clinical history, endoscopic evaluation, histopathological examination and immunohistochemistry, are necessary. Multidisciplinary evaluation is required to discriminate primary from metastatic malignant melanoma.