bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric validation techniques applied to the IND-VFQ-33 visual function questionnaire: the Hyderabad ocular morbidity in the elderly study (HOMES)
Authors: Mitchell William , Marmamula Srinivas , Zebardast Nazlee , Ng Weiwen , Locascio Joseph J. , Kumbam Thirupathi , Brahmanandam Satya , Barrenkala Navya Rekha
Published: February 2021

Background

Over 2 billion people suffer from vision impairment or blindness globally, and access to validated visual measurement tools in imperative in accurately describing and managing the burden of eye disease. The present study applies contemporary psychometric validation techniques to the widely used 33-item Indian Visual Function Questionnaire (IND-VFQ-33).

Methods

We first estimated the polychoric correlation between each pair of items. Next, an unrotated and oblique Promax rotated factor analysis, item response theory (IRT, using a graded response model (GRM)), and differential item functioning (DIF) testing were applied to the IND-VFQ-33. We subsequently propose a validated IND-VFQ-33 questionnaire after psychometric testing, data reduction, and adjustment.

Results

Exploratory unrotated factor analysis identified two factors; one with a particularly high eigenvalue (18.1) and a second with a lower eigenvalue still above our threshold (1.1). A subsequent oblique Promax factor rotation was undertaken for a 2-factor solution, revealing two moderately correlated factors (+ 0.68) with clinically discrete item loadings onto either Factor 1 (21 items; collectively labelled “daily activities”) or Factor 2 (5 items; collectively labelled “bright lights”). IRT confirmed high item discrimination for all remaining items with good separation between difficulty thresholds. We found significant DIF on depression for six items in Factor 1 (all uniform DIF, except item 21 (non-uniform DIF) with no substantive difference in beta thresholds for any item and no substantive difference in expected individual or sum score, by depression at baseline. For Factor 2, only one item demonstrated significant uniform DIF on gender, similarly without major differences in beta thresholds or expected total score between gender at baseline. Consequently, no further item recalibration or reduction was undertaken after IRT and DIF analysis.

Conclusion

Applying IRT and DIF validation techniques to the IND-VFQ-33 identified 2 discrete factors with 26 uniquely-loading items, clinically representative of difficulty performing daily activities and experiencing difficulty due to bright lights/glare respectively. The proposed modified scale may be useful in evaluating symptomatic disease progression or response to treatment in an Indian population.
Household physical activity is positively associated with gray matter volume in older adults
Authors: Koblinsky Noah D. , Meusel Liesel-Ann C. , Greenwood Carol E. , Anderson Nicole D.
Published: February 2021

Background

Total physical activity is positively associated with brain volume and cognition in older adults. While we have ample evidence that recreational physical activity influences brain health, the contributions of other daily activities are less understood. In particular, the associations between household physical activity and brain health in older adults is underexplored. The purpose of this study was to identify associations between household physical activity, brain volume, and cognition in a sample of cognitively unimpaired older adults.

Methods

We report data from 66 cognitively unimpaired older adults (71 ± 4 years) who participated in a health evaluation, cognitive assessment, and structural brain imaging. Physical activity was assessed using the Phone-FITT questionnaire and separated into household and recreational physical activity. We quantified whole brain volume, gray matter volume, and white matter volume, and assessed cognitive performance in four domains: memory, working memory/attention, processing speed, and executive function. Associations between physical activity, brain volume, and cognition were investigated in an omnibus approach using two multivariate analysis of variance (MANOVA) models. The first model assessed the associations between physical activity and brain volume adjusting for age, sex, Framingham Risk score (FRS) and intracranial volume. The second model assessed the associations between physical activity and overall cognitive performance adjusting for age, sex, FRS and education. Post hoc regression analyses were conducted to investigate significant MANOVA results. We also conducted further regression analyses to investigate associations with hippocampal and frontal lobe volume.

Results

Household, but not recreational, physical activity was positively associated with brain volume measurements (F = 3.07, p = .035), specifically gray matter volume (t = 2.51, p = .015). Further exploratory analyses identified that household physical activity was associated with hippocampal (p = .015) and frontal lobe (p = .010) volume. No significant relationships were observed between household or recreational physical activity and cognition.

Conclusion

Time spent engaging in household physical activity was positively associated with brain volume, specifically gray matter volume, in older adults. Highlighting the benefits associated with household chores may motivate older adults to be more active by providing a more attainable, low risk form of physical activity.
Consistent use of lipid lowering therapy in HIV infection is associated with low mortality
Authors: Drechsler Henning , Ayers Colby , Cutrell James , Arasaratnam Reuben , Bedimo Roger
Published: February 2021

Abstract

Background

In people living with HIV (PLWH), statins may be disproportionately effective but remain underutilized. A large prospective trial in patients with low to moderate cardiovascular (ASCVD) risk will reveal whether they should be considered in all PLWH. But its effect size may not apply to real-world PLWH with higher ASCVD and mortality risk. Also, the clinical role of non-statin lipid-lowering therapy (LLT) and LLT adherence in this population is unknown.

Methods

Comparative multi-level marginal structural model for all-cause mortality examining four time-updated exposure levels to LLT, antihypertensives, and aspirin in a virtual cohort of older PLWH. Incident coronary, cerebrovascular, and overall ASCVD events, serious infections, and new cancer diagnoses served as explanatory outcomes.

Results

In 23,276 HIV-infected US-veterans who were followed for a median of 5.2 years after virologic suppression overall mortality was 33/1000 patient years: > 3 times higher than in the US population. Use of antihypertensives or aspirin was associated with increased mortality. Past LLT use (> 1 year ago) had no effect on mortality. LLT exposure in the past year was associated with a reduced hazard ratio (HR) of death: 0.59, 95% confidence interval (CI) 0.51–0.69,p < 0.0001 for statin containing LLT and 0.71 (CI: 0.54–0.93),p = 0.03 for statin-free LLT. For consistent LLT use (> 11/12 past months) the HR of death was 0.48 (CI: 0.35–0.66) for statin-only LLT, 0.34 (CI: 0.23–0.52) for combination LLT, and 0.27 (CI: 0.15–0.48) for statin-free LLT (p < 0.0001 for all). The ASCVD risk in these patients was reduced in similar fashion. Use of statin containing LLT was also associated with reduced infection and cancer risk. Multiple contrasting subgroup analyses yielded comparable results. Confounding is unlikely to be a major contributor to our findings.

Conclusions

In PLWH, ongoing LLT use may lead to substantially lower mortality, but consistent long-term adherence may be required to reduce ASCVD risk. Consistent non-statin LLT may be highly effective and should be studied prospectively.
Knowledge, attitudes, and practices (KAP) toward COVID-19: a cross-sectional study in South Korea
Authors: Lee Minjung , Kang Bee-Ah , You Myoungsoon
Published: February 2021

Background

The public must routinely practice precautionary behaviors to control the spread of COVID-19, as no vaccines and antiviral treatments are currently available. This paper examines the public’s knowledge, attitudes, and practices (KAP) related to COVID-19 and their relationships and identified the pandemic’s vulnerable populations to provide recommendations for behavioral interventions and policies.

Methods

Data collection took place over 3 days (June 26–29) via an online survey 5 months after the Korea Centers for Disease Control and Prevention (KCDC) confirmed the first COVID case in South Korea; 970 subjects were included in the statistical data analysis.

Results

Knowledge directly affected both attitudes (e.g., perceived risk and efficacy belief) and practices (e.g., personal hygiene practices and social distancing). Among the influencing factors of COVID-19 preventive behaviors, efficacy belief was the most influential and significant practice factor. It mediated the relationship between knowledge and all three preventive behaviors (wearing facial masks, practicing hand hygiene, and avoiding crowded places). The level of knowledge varied by sociodemographic characteristics. Females (β = 0.06,p <  0.05) and individuals with higher levels of education (β = 0.06,p <  0.05) demonstrated higher levels of knowledge.

Conclusion

To increase precautionary behaviors among the public, health officials and policymakers must promote knowledge and efficacy belief. Future interventions and policies should also be developed in a ‘person-centered’ approach, targeting vulnerable subgroups, embracing them, and closing the gap of KAP toward COVID-19.
Palliative treatment of endometrial cancer: what is the role of anastrozole in elderly women?
Authors: Gardella Barbara , Dominoni Mattia , Bogliolo Stefano , Cassani Chiara , Carletti Giulia Vittoria , De Silvestri Annalisa , Spinillo Arsenio
Published: February 2021

Background

Type I endometrial cancer is the most common gynaecological tumour in developed countries and its incidence is increasing also because of population aging. The aim of this work is to test the feasibility and safety of anastrozole as palliative treatment of endometrial cancer in elderly women ineligible for standard surgical treatment.

Methods

Patients with histological diagnosis of type I endometrial cancer not suitable for surgical treatment were enrolled in this pilot study. Anastrozole was administered 1 mg daily orally after performing an accurate clinical and radiological staging. Validated questionnaire and self-reported outcomes were used to evaluate quality of life and compliance during the study period.

Results

Eight patients with a mean age of 85 (range 80–88 years) were enrolled. All patients had endometrial cancer confined to the uterus, and none progression of disease was observed during the study period. A partial response to the therapy was reported in seven patients, while one patient had stable disease. Tumour symptoms improvement such as pain, vaginal bleeding and vaginal discomfort was reported. The endometrial thickness after twelve months has showed a reduction of 9.25 ± 4.77 mm. The average follow-up time was 18.25 months. Four women died for non oncological reasons, none death related to endometrial cancer was reported. Evaluation of symptoms showed a significant reduction of appetite loss and insomnia, while a significant increase of global health status and fatigue was reported.

Conclusions

Our preliminary data suggested that the palliative use of anastrozole may be a suitable therapy for the proper management of early stages endometrial cancer in elderly women not suitable for surgical treatment with good compliance and tolerance.

Trial registration

2013000840. Date of registration: 21/09/2013. URL: trials.sanmatteo.loc.
Cost burden and net monetary benefit loss of neonatal hypoglycaemia
Authors: Glasgow Matthew J. , Edlin Richard , Harding Jane E.
Published: February 2021

Background

Neonatal hypoglycaemia is a common but treatable metabolic disorder that affects newborn infants and which, if not identified and treated adequately, may result in neurological sequelae that persist for the lifetime of the patient. The long-term financial and quality-of-life burden of neonatal hypoglycaemia has not been previously examined.

Methods

We assessed the postnatal hospital and long-term costs associated with neonatal hypoglycaemia over 80 year and 18 year time horizons, using a health-system perspective and assessing impact on quality of life using quality-adjusted life year (QALYs). A decision analytic model was used to represent key outcomes in the presence and absence of neonatal hypoglycaemia.

Results

The chance of developing one of the outcomes of neonatal hypoglycaemia in our model (cerebral palsy, learning disabilities, seizures, vision disorders) was 24.03% in subjects who experienced neonatal hypoglycaemia and 3.56% in those who do did not.

Over an 80 year time horizon a subject who experienced neonatal hypoglycaemia had a combined hospital and post-discharge cost of NZ$72,000 due to the outcomes modelled, which is NZ$66,000 greater than a subject without neonatal hypoglycaemia. The net monetary benefit lost due to neonatal hypoglycaemia, using a value per QALY of NZ$43,000, is NZ$180,000 over an 80 year time horizon.

Conclusions

Even under the most conservative of estimates, neonatal hypoglycaemia contributes a significant financial burden to the health system both during childhood and over a lifetime. The combination of direct costs and loss of quality of life due to neonatal hypoglycaemia means that this condition warrants further research to focus on prevention and effective treatment.
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

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

Background

Epidemiological and clinical studies have suggested comorbidity between amyotrophic lateral sclerosis (ALS) and autoimmune disorders. However, little is known about their shared genetic architecture.

Methods

To 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.

Results

We 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.

Conclusions

Our 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

Background

In 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.

Results

Being 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.

Conclusions

Our 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

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

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

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

Background

Treatment 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.

Methods

In 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.

Results

A 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.

Conclusions

Our 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

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

Background

Sensory 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.

Methods

Behavioral 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.

Results

ASD 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.

Limitations

Sensory 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.

Conclusions

Touch 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

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.
Integrity at end of life in the intensive care unit: a qualitative study of nurses’ views
Authors: Palmryd Lena , Rejnö Åsa , Godskesen Tove E.
Published: February 2021

Background

Integrity is a core value for delivering ethical health care. However, there is a lack of precision in defining what integrity is and how nurses understand it. In the setting of nurses caring for critically ill and dying patients in intensive care units (ICUs), integrity has not received much attention. Therefore, the aim of this study was to explore how nurses perceive and maintain the integrity of patients during end-of-life care in the ICU setting.

Methods

This study had a qualitative descriptive design. Data were collected using individual semi-structured interviews with 16 intensive care nurses working at ICUs in four Swedish hospitals. The data were analysed by applying qualitative content analysis.

Results

Five overall categories were explored: seeing the unique individual; sensitive to patient vulnerability; observant of patients’ physical and mental sphere; perceptive of patients’ religion and culture; and being respectful during patient encounters. Many nurses found it difficult to define integrity and to explain what respecting integrity entails in the daily care of dying patients. They often used notions associated with respect and patient-centred attitudes, such as listening and being sensitive or by trying to describe good care. Integrity was nonetheless seen as a central value for their clinical work and a precondition for ethical nursing practice. Some nurses were concerned about patient integrity, which is at risk of being “wiped out” due to the patient’s illness/injury, unfamiliarity with the ICU environment and utter dependence on others for care. Protecting patients from harm and reducing patient vulnerability were also seen as important and a way to maintain the integrity of patients.

Conclusions

The study results show that even though integrity is a fundamental ethical concept and a core value in nursing, ethical codes and guidelines are not always helpful in clinical situations in the end-of-life care of ICU patients. Hence, opportunities must regularly be made available for ICU nurses to reflect on and discuss ethical issues in terms of their decision-making and behaviour.
Polar poly(n-butyl acrylate)-g-polyacrylonitrile elastomer with high temperature elasticity and healability as flexible electronic substrate
Authors: Zheng Yuzhu , Xu Deli , Tian Shiyou , Li Manli , Wang Wenwen , Liu Ke
Published: February 2021

In this work, graft copolymer poly (n-butyl acrylate)-g-polyacrylonitrile with poly (n-butyl acrylate) as backbones and polyacrylonitrile as side chains (PnBA-g-PAN) was synthesized by macromonomer method and emulsion polymerization. The macromonomer was synthesized by atom transfer radical polymerization and end-group modification. The chemical structures and thermal properties of macromonomer and graft copolymer were investigated by FTIR, GPC, NMR and TGA, etc. The mechanical properties of graft copolymer elastomer was also measured by uniaxial tensile test. Rheological properties at different temperature and mechanical property demonstrated that graft copolymer elastomer possessed elasticity until 180 oC because of cyclization of cyano groups. Ag nanowires@PnBA-g-PAN composite elastomer was developed, and the resulted material exhibited autonomic healing property on account of segments’ flexibility and dynamic interaction between Ag nanowires (AgNWs) and cyano groups. This is a general method for generation of elastomer with high temperature elasticity and fast self-healing. The composite elastomer has potential application in flexible electronic conductor.
Design of optimal hybrid power system to provide reliable supply to rural areas of Ethiopia using MATLAB and Homer
Authors: Nebey Abraham Hizkiel
Published: February 2021

Integrating different energy resources, like solar PV, wind, and hydro is used to ensure reliable power to the rural community loads. Hybrid power system offers sufficient power supply for the rural villages by providing alternative supply for intermittent nature of renewable energy resource. Hence, intermittency of renewable energy resources is a challenge to electrify the rural community in a sustainable manner with the above sources. Thus, efficient resources management is a reasonable choice for intermittent renewable energy resources. The majority of rural villages in Ethiopia are suffering from lack of electricity. This causes deforestation, travel for long distance to fetch water, and no good social services, like clinic and schools, sufficiently. Therefore, the objective of this study was to maximize reliability of power supply by renewable energy sources. Data on wind speed and solar radiation are obtained from the NASA surface meteorological agency. While hydro data are obtained from physical measurements. Different configuration options are considered by Homer software to find the optimal configuration of hybrid system. The optimal configuration system is selected and hybrid components are sized. The optimal hybrid system consists of solar PV, wind, and hydro to supply a community load with a share of 13%, 52%, and 35% respectively. The fuzzy logic controller is designed to manage the intermittent nature of energies. Hence, the demand and energy sources are unpredictable; intelligent control system is important to manage the system accordingly. The control system is designed in MATALAB software. The result obtained from resource combination shows demand and supply are balanced. From the Twelve probabilistic combinations of demand and energy sources, one of the combinations shows that when 7.5 kW is demanded, the power generated/output from hybrid system is 10 kW which is greater than demand. To satisfy 7.5 kW demand control system takes 4.25 kW, 2.75 kW, and 1.08 kW share from wind, hydro, and solar sources respectively. The fuzzy logic control system is designed, to monitor the resource availability and load demand. This controller was managing the demand and the available resources according to the rule.
Infection dynamics and persistence of hepatitis E virus on pig farms – a review
Authors: Meester M. , Tobias T. J. , Bouwknegt M. , Kusters N. E. , Stegeman J. A. , van der Poel W. H. M.
Published: February 2021

Background

Hepatitis E virus (HEV) genotype 3 and 4 is a zoonosis that causes hepatitis in humans. Humans can become infected by consumption of pork or contact with pigs. Pigs are the main reservoir of the virus worldwide and the virus is present on most pig farms.

Main body

Though HEV is present on most farms, the proportion of infected pigs at slaughter and thus the level of exposure to consumers differs between farms and countries. Understanding the cause of that difference is necessary to install effective measures to lower HEV in pigs at slaughter. Here, HEV studies are reviewed that include infection dynamics of HEV in pigs and on farms, risk factors for HEV farm prevalence, and that describe mechanisms and sources that could generate persistence on farms. Most pigs become infected after maternal immunity has waned, at the end of the nursing or beginning of the fattening phase. Risk factors increasing the likelihood of a high farm prevalence or proportion of actively infected slaughter pigs comprise of factors such as farm demographics, internal and external biosecurity and immunomodulating coinfections. On-farm persistence of HEV is plausible, because of a high transmission rate and a constant influx of susceptible pigs. Environmental sources of HEV that enhance persistence are contaminated manure storages, water and fomites.

Conclusion

As HEV is persistently present on most pig farms, current risk mitigation should focus on lowering transmission within farms, especially between farm compartments. Yet, one should be aware of the paradox of increasing the proportion of actively infected pigs at slaughter by reducing transmission insufficiently. Vaccination of pigs may aid HEV control in the future.
Correction to: Establishing a common metric for patient-reported outcomes in cancer patients: linking patient reported outcomes measurement information system (PROMIS), numerical rating scale, and patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE)
Authors: Lee Minji K. , Schalet Benjamin D. , Cella David , Yost Kathleen J. , Dueck Amylou C. , Novotny Paul J. , Sloan Jeff A.
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
Clinical differentiation of psychogenic non-epileptic seizure: a practical diagnostic approach
Authors: Widyadharma I. Putu Eka , Soejitno Andreas , Samatra D. P. G. Purwa , Sinardja Anna M. G.
Published: February 2021

Background

Psychogenic non-epileptic seizure (PNES) has long been the counterpart of epileptic seizure (ES). Despite ample of evidence differentiating the two, PNES mistakenly diagnosed as ES was still common, resulting in unnecessary exposure to long-term antiepileptic medications and reduced patient’s and caregiver’s quality of life, not to mention the burgeoning financial costs.

Objectives

In this review, we aimed to elucidate various differences between PNES and epileptic seizure with respect to baseline characteristics, seizure semiology, EEG pattern, and other key hallmark features.

Methods

An unstructured search was carried out in PubMed, MEDLINE, and EMBASE using keywords pertinent to PNES and ES differentiation. Relevant information was subsequently summarized herein.

Results

PNES differs significantly with ES in terms of baseline characteristics, prodromal symptoms, seizure semiology, presence of pseudosleep, and other hallmark features (for instance provoking seizure with suggestion). The combined approach, if applied appropriately, can yield high diagnostic yield.

Conclusions

PNES can be clearly differentiated from ES via careful adherence to a set of valid clinical cues. The summarized clinical hallmarks is highly useful to prevent unnecessary ES diagnosis and treatment with AEDs.
Quantitative 3-tesla multiparametric MRI in differentiation between renal cell carcinoma subtypes
Authors: Elsorougy Ali , Farg Hashim , Bayoumi Dalia , El-Ghar Mohamed Abou , Shady Magda
Published: February 2021

Background

MRI provides several distinct quantitative parameters that may better differentiate renal cell carcinoma (RCC) subtypes. The purpose of the study is to evaluate the diagnostic accuracy of apparent diffusion coefficient (ADC), chemical shift signal intensity index (SII), and contrast enhancement in differentiation between different subtypes of renal cell carcinoma.

Results

There were 63 RCC as regard surgical histopathological analysis: 43 clear cell (ccRCC), 12 papillary (pRCC), and 8 chromophobe (cbRCC). The mean ADC ratio for ccRCC (0.75 ± 0.13) was significantly higher than that of pRCC (0.46 ± 0.12, P < 0.001) and cbRCC (0.41 ± 0.15, P < 0.001). The mean ADC value for ccRCC (1.56 ± 0.27 × 10−3 mm2/s) was significantly higher than that of pRCC (0.96 ± 0.25 × 10−3 mm2/s, P < 0.001) and cbRCC (0.89 ± 0.29 × 10−3 mm2/s, P < 0.001). The mean SII of pRCC (1.49 ± 0.04) was significantly higher than that of ccRCC (0.93 ± 0.01, P < 0.001) and cbRCC (1.01 ± 0.16, P < 0.001). The ccRCC absolute corticomedullary enhancement (196.7 ± 81.6) was significantly greater than that of cbRCC (177.8 ± 77.7, P < 0.001) and pRCC (164.3 ± 84.6, P < 0.001).

Conclusion

Our study demonstrated that multiparametric MRI is able to afford some quantitative features such as ADC ratio, SII, and absolute corticomedullary enhancement which can be used to accurately distinguish different subtypes of renal cell carcinoma.