bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of temperature on the mechanical performance of plywood used in membrane-type LNG carrier insulation systems
Authors: Cha Seung-Joo , Kim Jeong-Dae , Kim Seul-Kee , Kim Jeong-Hyeon , Oh Hoon-Kyu , Kim Yong-Tai , Park Seong-Bo , Lee Jae-Myung
Published: April 2020

In this study, the mechanical performance of melamine–urea–formaldehyde (MUF) resin plywood composed of an orthotropic material, which is used as a structural material in liquefied natural gas (LNG) cargo containment systems (CCSs), is evaluated. With a decrease in temperature, the plywood changes from ductile to brittle under compressive loads; thus, it may fail to distribute the compressive loads caused by sloshing impact as well as lose its stiffness, which helps maintain the shape of the structure. However, only a few studies investigated the mechanical characteristics of MUF resin plywood under compressive loads caused by sloshing impact as well as the crack propagation and change in material features with decreasing temperatures. Therefore, the present study investigated the mechanical performance of MUF plywoods of different thicknesses under different temperatures and grain orientation parameters. The results indicate the mechanical properties of MUF plywood for compression with decreasing temperatures. Furthermore, based on thermomechanical analysis, this study shows that the critical temperature at which the plywood material tends to transition from ductile to brittle behavior is − 110 °C. This finding will help in the design of MUF plywood-based LNG CCSs considering its low-temperature brittleness.
PathME: pathway based multi-modal sparse autoencoders for clustering of patient-level multi-omics data
Authors: Lemsara Amina , Ouadfel Salima , Fröhlich Holger
Published: April 2020

Background

Recent years have witnessed an increasing interest in multi-omics data, because these data allow for better understanding complex diseases such as cancer on a molecular system level. In addition, multi-omics data increase the chance to robustly identify molecular patient sub-groups and hence open the door towards a better personalized treatment of diseases. Several methods have been proposed for unsupervised clustering of multi-omics data. However, a number of challenges remain, such as the magnitude of features and the large difference in dimensionality across different omics data sources.

Results

We propose a multi-modal sparse denoising autoencoder framework coupled with sparse non-negative matrix factorization to robustly cluster patients based on multi-omics data. The proposed model specifically leverages pathway information to effectively reduce the dimensionality of omics data into a pathway and patient specific score profile. In consequence, our method allows us to understand, which pathway is a feature of which particular patient cluster. Moreover, recently proposed machine learning techniques allow us to disentangle the specific impact of each individual omics feature on a pathway score. We applied our method to cluster patients in several cancer datasets using gene expression, miRNA expression, DNA methylation and CNVs, demonstrating the possibility to obtain biologically plausible disease subtypes characterized by specific molecular features. Comparison against several competing methods showed a competitive clustering performance. In addition, post-hoc analysis of somatic mutations and clinical data provided supporting evidence and interpretation of the identified clusters.

Conclusions

Our suggested multi-modal sparse denoising autoencoder approach allows for an effective and interpretable integration of multi-omics data on pathway level while addressing the high dimensional character of omics data. Patient specific pathway score profiles derived from our model allow for a robust identification of disease subgroups.
Assessing breed integrity of Göttingen Minipigs
Authors: Reimer Christian , Ha Ngoc-Thuy , Sharifi Ahmad Reza , Geibel Johannes , Mikkelsen Lars Friis , Schlather Martin , Weigend Steffen , Simianer Henner
Published: April 2020

Background

Göttingen Minipigs (GMP) is the smallest commercially available minipig breed under a controlled breeding scheme and is globally bred in five isolated colonies. The genetic isolation harbors the risk of stratification which might compromise the identity of the breed and its usability as an animal model for biomedical and human disease. We conducted whole genome re-sequencing of two DNA-pools per colony to assess genomic differentiation within and between colonies. We added publicly available samples from 13 various pig breeds and discovered overall about 32 M loci, ~ 16 M. thereof variable in GMPs. Individual samples were virtually pooled breed-wise. FSTbetween virtual and DNA pools, a phylogenetic tree, principal component analysis (PCA) and evaluation of functional SNP classes were conducted. An F-test was performed to reveal significantly differentiated allele frequencies between colonies. Variation within a colony was quantified as expected heterozygosity.

Results

Phylogeny and PCA showed that the GMP is easily discriminable from all other breads, but that there is also differentiation between the GMP colonies. Dependent on the contrast between GMP colonies, 4 to 8% of all loci had significantly different allele frequencies. Functional annotation revealed that functionally non-neutral loci are less prone to differentiation. Annotation of highly differentiated loci revealed a couple of deleterious mutations in genes with putative effects in the GMPs .

Conclusion

Differentiation and annotation results suggest that the underlying mechanisms are rather drift events than directed selection and limited to neutral genome regions. Animal exchange seems not yet necessary. The Relliehausen colony appears to be the genetically most unique GMP sub-population and could be a valuable resource if animal exchange is required to maintain uniformity of the GMP.
Integrated likelihood for phylogenomics under a no-common-mechanism model
Authors: Tidwell Hunter , Nakhleh Luay
Published: April 2020

Background

Multi-locus species phylogeny inference is based on models of sequence evolution on gene trees as well as models of gene tree evolution within the branches of species phylogenies. Almost all statistical methods for this inference task assume a common mechanism across all loci as captured by a single value of each branch length of the species phylogeny.

Results

In this paper, we pursue a “no common mechanism" (NCM) model, where every gene tree evolves according to its own parameters of the species phylogeny. Based on this model, we derive an analytically integrated likelihood of both species trees and networks given the gene trees of multiple loci under an NCM model. We demonstrate the performance of inference under this integrated likelihood on both simulated and biological data.

Conclusions

The model presented here will afford opportunities for exploring connections among various criteria for estimating species phylogenies from multiple, independent loci. Furthermore, further development of this model could potentially result in more efficient methods for searching the space of species phylogenies by focusing solely on the topology of the phylogeny.
Getting insight into the pan-genome structure with PangTree
Authors: Dziadkiewicz Paulina , Dojer Norbert
Published: April 2020

Background

The term pan-genome was proposed to denominate collections of genomic sequences jointly analyzed or used as a reference. The constant growth of genomic data intensifies development of data structures and algorithms to investigate pan-genomes efficiently.

Results

This work focuses on providing a tool for discovering and visualizing the relationships between the sequences constituting a pan-genome. A new structure to represent such relationships – called affinity tree – is proposed. Each node of this tree has assigned a subset of genomes, as well as their homogeneity level and averaged consensus sequence. Moreover, subsets assigned to sibling nodes form a partition of the genomes assigned to their parent.

Conclusions

Functionality of affinity tree is demonstrated on simulated data and on the Ebola virus pan-genome. Furthermore, two software packages are provided: PangTreeBuild constructs affinity tree, while PangTreeVis presents its result.
Transcriptomic analysis of sea cucumber (Holothuria leucospilota) coelomocytes revealed the echinoderm cytokine response during immune challenge
Authors: Wu Xiaofen , Chen Ting , Huo Da , Yu Zonghe , Ruan Yao , Cheng Chuhang , Jiang Xiao , Ren Chunhua
Published: April 2020

Background

The sea cucumberHolothuria leucospilotabelongs to echinoderm, which is evolutionally the most primitive group of deuterostomes. Sea cucumber has a cavity between its digestive tract and the body wall that is filled with fluid and suspended coelomic cells similar to blood cells. The humoral immune response of the sea cucumber is based on the secretion of various immune factors from coelomocytes into the coelomic cavity. The aim of this study is to lay out a foundation for the immune mechanisms in echinoderms and their origins in chordates by using RNA-seq.

Results

Sea cucumber primary coelomocytes were isolated from healthyH. leucospilotaand incubated with lipopolysaccharide (LPS, 10 μg/ml), polyinosinic-polycytidylic acid [Poly (I:C), 10 μg/ml] and heat-inactivedVibrio harveyi(107cell/ml) for 24 h, respectively. After high-throughput mRNA sequencing on an Illumina HiSeq2500, a de novo transcriptome was assembled and the Unigenes were annotated. Thirteen differentially expressed genes (DEGs) were selected randomly from our data and subsequently verified by using RT-qPCR. The results of RT-qPCR were consistent with those of the RNA-seq (R2 = 0.61). The top 10 significantly enriched signaling pathways and immune-related pathways of the common and unique DEGs were screened from the transcriptome data. Twenty-one cytokine candidate DEGs were identified, which belong to 4 cytokine families, namely, BCL/CLL, EPRF1, IL-17 and TSP/TPO. Gene expression in response to LPS dose-increased treatment (0, 10, 20 and 50 μg/ml) showed that IL-17 family cytokines were significantly upregulated after 10 μg/ml LPS challenge for 24 h.

Conclusion

A de novo transcriptome was sequenced and assembled to generate the gene expression profiling across the sea cucumber coelomocytes treated with LPS, Poly (I:C) andV. harveyi. The cytokine genes identified in DEGs could be classified into 4 cytokine families, in which the expression of IL-17 family cytokines was most significantly induced after 10 μg/ml LPS challenge for 24 h. Our findings have laid the foundation not only for the research of molecular mechanisms related to the immune response in echinoderms but also for their origins in chordates, particularly in higher vertebrates.
Genome-wide analysis of the citrus B3 superfamily and their association with somatic embryogenesis
Authors: Liu Zheng , Ge Xiao-Xia , Wu Xiao-Meng , Xu Qiang , Atkinson Ross G. , Guo Wen-Wu
Published: April 2020

Background

In citrus, genetic improvement via biotechnology is hindered by the obstacle of in vitro regeneration via somatic embryogenesis (SE). Although a few B3 transcription factors are reported to regulate embryogenesis, little is known about the B3 superfamily in citrus, and which members might be involved in SE.

Results

Genome-wide sequence analysis identified 72 (CsB3) and 69 (CgB3) putative B3 superfamily members in the genomes of sweet orange (Citrus sinensis, polyembryonic) and pummelo (C. grandis, monoembryonic), respectively. Genome duplication analysis indicated that segmental and tandem duplication events contributed to the expansion of the B3 superfamily in citrus, and that the B3 superfamily evolved under the effect of purifying selection. Phylogenetic relationships were well supported by conserved gene structure and motifs outside the B3 domain, which allowed possible functions to be inferred by comparison with homologous genes from Arabidopsis. Expression analysis identified 23 B3 superfamily members that were expressed during SE in citrus and 17 that may play functional roles at late SE stages. Eight B3 genes were identified that were specific to the genome of polyembryonic sweet orange compared to monoembryonic pummelo. Of these eight B3 genes, CsARF19 was found to be specifically expressed at higher levels in embryogenic callus (EC), implying its possible involvement in EC initiation.

Conclusions

This study provides a genome-wide analysis of the citrus B3 superfamily, including its genome organization, evolutionary features and expression profiles, and identifies specific family members that may be associated with SE.
The role of C-afferents in mediating neurogenic vasodilatation in plantar skin after acute sciatic nerve injury in rats
Authors: Zhang Tao , Niu Jiahui , Wang Yaxian , Yan Junying , Hu Wen , Mi Daguo
Published: April 2020

Background

Vasomotor regulation of dermal blood vessels, which are critical in the function of the skin in thermoregulatory control, involves both neural and non-neural mechanisms. Whereas the role of sympathetic nerves in regulating vasomotor activities is comprehensively studied and well recognized, that of sensory nerves is underappreciated. Studies in rodents have shown that severance of the sciatic nerve leads to vasodilatation in the foot, but whether sympathetic or sensory nerve fibers or both are responsible for the neurogenic vasodilatation remains unknown.

Results

In adult Sprague–Dawley rats, vasodilatation after transection of the sciatic nerve gradually diminished to normal within 3–4 days. The neurotmesis-induced neurogenic vasodilatation was not detectable when the sciatic nerve was chronically deafferentated by selective resection of the dorsal root ganglia (DRGs) that supply the nerve. Specific activation of C-afferents by intra-neural injection of capsaicin resulted in neurogenic vasodilatation to a magnitude comparable to that by neurotmesis, and transection of the sciatic nerve pre-injected with capsaicin did not induce further vasodilatation.

Conclusions

Our results collectively indicate that vasodilatation after traumatic nerve injury in rats is predominantly mediated by C-fiber afferents.
Circulating metabolite profiles to predict response to cardiac resynchronization therapy
Authors: Gong Xue , Sun Zhonghan , Huang Zheyong , Zhou Qian , Yu Ziqing , Chen Xueying , Shao Wenqi , Zheng Yan , Liang Yixiu , Qin Shengmei , Su Yangang , Ge Junbo
Published: April 2020

Background

Heart failure is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT) with approximately one-third of non-response rate. Thus far, there is no specific biomarker to predict the response to CRT in patients with heart failure. In this study, we assessed the role of the blood metabolomic profile in predicting the response to CRT.

Methods

A total of 105 dilated cardiomyopathy patients with severe heart failure who received CRT were included in our two-stage study. Baseline blood samples were collected prior to CRT implantation. The response to CRT was defined according to echocardiographic criteria. Metabolomic profiling of serum samples was carried out using ultrahigh performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

Results

Seventeen metabolites showed significant differences in their levels between responders and non-responders, and these metabolites were primarily involved in six pathways, including linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, citrate cycle, tryptophan metabolism, and sphingolipid metabolism. A combination of isoleucine, tryptophan, and linoleic acid was identified as an ideal metabolite panel to distinguish responders from non-responders in the discovery set (n = 51 with an AUC of 0.981), and it was confirmed in the validation set (n = 54 with an AUC of 0.929).

Conclusions

Mass spectrometry based serum metabolomics approach provided larger coverage of metabolome which can help distinguish CRT responders from non-responders. A combination of isoleucine, tryptophan, and linoleic acid may associate with significant prognostic values for CRT.
Correction to: Sex differences in 10-year ischemic cardiovascular disease risk prediction in Chinese patients with prediabetes and type 2 diabetes
Authors: Yang Lihong , Fish Anne F. , Zhu Yuanyuan , Yuan Xiaodan , Li Jianing , Wang Xiaoyun , Yuan Li , Jia Zhumin , Liu Chao , Xu Chenyun , Lou Qingqing
Published: April 2020

After the publication of the original article [1], we were notified that one of the corresponding author’s name and her related institution were wrongly spelled.
Narrow-band imaging and high-definition white-light endoscopy in patients with serrated lesions not fulfilling criteria for serrated polyposis syndrome: a randomized controlled trial with tandem colonoscopy
Authors: Riu Pons Fausto , Andreu Montserrat , Naranjo Dolores , Álvarez-González Marco Antonio , Seoane Agustín , Dedeu Josep Maria , Barranco Luis , Bessa Xavier
Published: April 2020

Background

It is unknown whether narrow-band imaging (NBI) could be more effective than high-definition white-light endoscopy (HD-WLE) in detecting serrated lesions in patients with prior serrated lesions > 5 mm not completely fulfilling serrated polyposis syndrome (SPS) criteria.

Methods

We conducted a randomized, cross-over trial in consecutive patients with prior detection of at least one serrated polyp ≥10 mm or ≥ 3 serrated polyps larger than 5 mm, both proximal to the sigmoid colon. Five experienced endoscopists performed same-day tandem colonoscopies, with the order being randomized 1:1 to NBI—HD-WLE or HD-WLE—NBI. All tandem colonoscopies were performed by the same endoscopist.

Results

We included 41 patients. Baseline characteristics were similar in the two cohorts: NBI—HD-WLE (n = 21) and HD-WLE—NBI (n = 20). No differences were observed in the serrated lesion detection rate of NBI versus HD-WLE: 47.4% versus 51.9% (OR 0.84, 95% CI: 0.37–1.91) for the first and second withdrawal, respectively. Equally, no differences were found in the polyp miss rate of NBI versus HD-WLE: 21.3% versus 26.1% (OR 0.77, 95% CI: 0.43–1.38). Follow-up colonoscopy in nine patients (22%) allowed them to be reclassified as having SPS.

Conclusions

In patients with previous serrated lesions, the serrated lesion detection rate was similar with NBI and HD-WLE. A shorter surveillance colonoscopy interval increases the detection of missed serrated polyps and could change the diagnosis of SPS in approximately one in every five patients.

Trial registration

ClinicalTrials.gov NCT02406547, registered on April 2, 2015.
Correction to: Short-term outcome associated with disease severity and electrolyte abnormalities among critically ill children with acute kidney injury
Authors: Safdar Osama Y. , Alhasan Khalid A. , Shalaby Mohamed A. , Khathlan Norah , Al Rezgan Suleman A. , Albanna Amr S. , Kari Jameela A.
Published: April 2020

Following publication of the original article [1]
Standardized regression-based clinical change score cutoffs for normal pressure hydrocephalus
Authors: Davis Alexander , Yasar Sevil , Emerman Iris , Gulyani Seema , Khingelova Kristina , Rao Aruna , Manthripragada Lacie , Luciano Mark , Moghekar Abhay
Published: April 2020

Background

Presently, for patients presenting with suspected Normal Pressure Hydrocephalus (NPH) who undergo temporary drainage of cerebrospinal fluid (CSF) there is no defined model to differentiate chance improvement form clinical significance change at the individual patient level. To address this lack of information we computed standard regression based clinical change models for the 10 Meter Walk Test, Timed Up & Go, Dual Timed Up & Go, 6-Minute Walk Test, Mini-Balance Evaluation Systems Test, Montreal Cognitive Assessment, and Symbol Digit Modalities using data from patients with suspected NPH that underwent temporary drainage of CSF. These clinically significant change modes can classify clinically significant improvement following temporary drainage of CSF at the individual patient level. This allows for physicians to differentiate a clinically significant improvement in symptoms from chance improvement.

Methods

Data was collected from 323 patients, over the age of 60, with suspected NPH that underwent temporary drainage of CSF with corresponding gait and cognitive testing. McSweeney Standardized Regression Based Clinical Change Models were computed for standard gait and cognitive measures: Timed Up & Go, Dual Timed Up & Go, 10 Meter Walk Test, MiniBESTest, 6-Minute Walk Test, Montreal Cognitive Assessment, and Symbol Digit Modalities Test. To assess the discriminate validity of the measures we used correlations, Chi2, and regression analyses.

Results

The clinical change models explained 69–91.8% of the variability in post-drain performance (p <  0.001). As patient scores became more impaired, the percent change required for improvement to be clinically significant increased for all measures. We found that the measures were not discriminate, the Timed Up & Go was highly related to the 10 Meter Walk Test (r = 0.85, R2 = 0.769–0.738, p <  0.001), MiniBESTest (r = − 0.67, R2 = 0.589–0.734, p <  0.001), and 6 Minute Walk Test (r = − 0.77, R2 = 0.71–0.734, p <  0.001).

Conclusion

Standardized Regression Based Clinically Significant Change Models allow for physicians to use an evidence-based approach to differentiate clinically significant change from chance improvement at the individual patient level. The Timed Up & Go was shown to be predictive of detailed measures of gait velocity, balance, and endurance.
A randomized controlled trial of daily weighing in pregnancy to control gestational weight gain
Authors: Arthur Christopher , Di Corleto Ellen , Ballard Emma , Kothari Alka
Published: April 2020

Background

Excessive gestational weight gain is a modifiable risk factor for the development of obstetric and neonatal complications, and can have a lifelong impact on the health of both mother and offspring. The purpose of this study was to assess whether in addition to standardized medical advice regarding weight gain in pregnancy (including adherence to the Institute of Medicine (IOM) guidelines) (IOM (Institute of Medicine) and NRC (National Research Council, Weight Gain During Pregnancy: Re-examining the guidelines, 2009)), the addition of daily weighing would provide a low cost and simple intervention to reduce excessive weight gain in pregnancy by maintaining weight gain within the target range.

Methods

Women presenting for antenatal care to a secondary level hospital were randomised to routine care or daily weight monitoring. Both groups received nutrition and exercise advice.

Results

Three hundred and ninety-six women were randomised to either the daily weight monitoring group or control group with complete data available for 326 women. The percentage weight gain above target (86.9% (SD 52.3) v 92.7% (SD 50.8) p = 0.31) and change in weight per week during the study period (0.59 kg (SD 0.30) v 0.63 kg (SD 0.31) p = 0.22) were lesser in those undergoing daily weighing compared to routine management, however these did not reach statistical significance.

Conclusion

Daily weight monitoring as a stand-alone intervention has potential to reduce excessive gestational weight gain. It may have a role as a part of a larger intervention involving dietary and exercise modifications.

Trial registration

The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry. (ACTRN12613001165774, 23/10/ 2013).
Psychosocial and environmental determinants of child cognitive development in rural south africa and tanzania: findings from the mal-ed cohort
Authors: Drago Fabrizio , Scharf Rebecca J. , Maphula Angelina , Nyathi Emanuel , Mahopo Tjale C. , Svensen Erling , Mduma Estomih , Bessong Pascal , Rogawski McQuade Elizabeth T.
Published: April 2020

Background

Approximately 66% of children under the age of 5 in Sub-Saharan African countries do not reach their full cognitive potential, the highest percentage in the world. Because the majority of studies investigating child cognitive development have been conducted in high-income countries (HICs), there is limited knowledge regarding the determinants of child development in low- and middle-income countries (LMICs).

Methods

This analysis includes 401 mother-child dyads from the South Africa and Tanzania sites of the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal birth cohort study. We investigated the effect of psychosocial and environmental determinants on child cognitive development measured by the Wechsler Preschool Primary Scales of Intelligence (WPPSI) at 5 years of age using multivariable linear regression.

Results

Socioeconomic status was most strongly associated with child cognitive development (WPSSI Score Difference (SD):14.27, 95% CI:1.96, 26.59). Modest associations between the organization of the home environment and its opportunities for cognitive stimulation and child cognitive development were also found (SD: 3.08, 95% CI: 0.65, 5.52 and SD: 3.18, 95% CI: 0.59, 5.76, respectively).

Conclusion

This study shows a stronger association with child cognitive development at 5 years of age for socioeconomic status compared to more proximal measures of psychosocial and environmental determinants. A better understanding of the role of these factors is needed to inform interventions aiming to alleviate the burden of compromised cognitive development for children in LMICs.
Addressing quadruple aims through primary care and public health collaboration: ten Canadian case studies
Authors: Valaitis Ruta K. , Wong Sabrina T. , MacDonald Marjorie , Martin-Misener Ruth , O’Mara Linda , Meagher-Stewart Donna , Isaacs Sandy , Murray Nancy , Baumann Andrea , Burge Fred , Green Michael , Kaczorowski Janusz , Savage Rachel
Published: April 2020

Background

Health systems in Canada and elsewhere are at a crossroads of reform in response to rising economic and societal pressures. The Quadruple Aim advocates for: improving patient experience, reducing cost, advancing population health and improving the provider experience. It is at the forefront of Canadian reform debates aimed to improve a complex and often-fragmented health care system. Concurrently, collaboration between primary care and public health has been the focus of current research, looking for integrated community-based primary health care models that best suit the health needs of communities and address health equity. This study aimed to explore the nature of Canadian primary care - public health collaborations, their aims, motivations, activities, collaboration barriers and enablers, and perceived outcomes.

Methods

Ten case studies were conducted in three provinces (Nova Scotia, Ontario, and British Columbia) to elucidate experiences of primary care and public health collaboration in different settings, contexts, populations and forms. Data sources included a survey using the Partnership Self-Assessment Tool, focus groups, and document analysis. This provided an opportunity to explore how primary care and public health collaboration could serve in transforming community-based primary health care with the potential to address the Quadruple Aims.

Results

Aims of collaborations included: provider capacity building, regional vaccine/immunization management, community-based health promotion programming, and, outreach to increase access to care. Common precipitators were having a shared vision and/or community concern. Barriers and enablers differed among cases. Perceived barriers included ineffective communication processes, inadequate time for collaboration, geographic challenges, lack of resources, and varying organizational goals and mandates. Enablers included clear goals, trusting and inclusive relationships, role clarity, strong leadership, strong coordination and communication, and optimal use of resources. Cases achieved outcomes addressing the Q-Aims such as improving access to services, addressing population health through outreach to at-risk populations, reducing costs through efficiencies, and improving provider experience through capacity building.

Conclusions

Primary care and public health collaborations can strengthen community-based primary health care while addressing the Quadruple Aims with an emphasis on reducing health inequities but requires attention to collaboration barriers and enablers.
A combination of kissing molars, maxillary bilateral supernumerary teeth and macrodontia: a rare case report
Authors: Lao An , Bi Siyuan , Cheng Haoran , Lai Tiehan , Huang Shengbin , Zhao Shufan
Published: April 2020

Background

Supernumerary teeth (ST) is defined as an additional number of teeth compared to the normal dental formula. The prevalence rate of ST varies from 0.5 to 3.8% in the permanent dentition. When ST located distal to the third molar is acclaimed as distomolar. Moreover, kissing molar is an extremely scarce condition of distomolars, pointed in the opposite direction in a single follicular space. Meanwhile, macrodontia is also a rare shape anomaly characterized by a large crown and tapering root.

Case presentation

A 22-year-old Chinese man presented a combination of kissing molars, maxillary bilateral supernumerary teeth and macrodontia. Radiographically, two maxillary bilateral distomolars located at the buccal side of adjacent third molars. One mandibular distomolar with the adjacent third molar was contacted by occlusal surfaces while roots were pointed oppositely, which could be diagnosed as KM. Furthermore, the left mandibular third molar can be inferred to be a macrodontia, characterized by a large crown and tapering root. After a thorough investigation, we excluded the possibilities of systemic diseases and genetic inheritance. However, the etiology of this rare combination deserves to be further explored.

Conclusion

The combination of kissing molars, maxillary bilateral supernumerary teeth and macrodontia is very rare, especially presented in the patient with no syndromes. As there were no complications with these conditions, long-term observation has been recommended for the patient. In addition, the true etiology need a further exploration.
Influence of cervical preflaring and root canal preparation on the fracture resistance of endodontically treated teeth
Authors: da Silva Paula Barcellos , Duarte Simone Ferreti , Alcalde Murilo Priori , Duarte Marco Antonio Húngaro , Vivan Rodrigo Ricci , da Rosa Ricardo Abreu , Só Marcus Vinícius Reis , do Nascimento Angela Longo
Published: April 2020

Background

Evaluate the fracture resistance of endodontically treated teeth after cervical preflaring and root canal preparation and to assess the volume of the root canal and the amount of remaining root dentin before and after cervical preflaring.

Methods

Forty-four mandibular incisors were selected using micro-CT scanning and distributed into 4 groups (n = 11) according to the instrument used for cervical preflaring: control group - no cervical preflaring; Gates Glidden – burs size #2 and #3; WXN – 25.07 Navigator instrument; and Easy – 25.08 ProDesign S instrument. Coronal opening was performed, and the canals were prepared with Wave One Gold Primary and filled with an epoxy-resin based sealer and gutta-percha cones. Micro-CT scans were performed before and after root canal instrumentation. All images were reconstructed and assessed for the thickness of mesial and distal root dentin at 3 mm and 5 mm from the cement -enamel junction and for the volume of cervical portion of the canal after preparation. Fracture resistance test was performed applying compressive loads at a crosshead speed of 0.5 mm/min, applied on the palatal aspect of specimens at 135° along the long axis of the tooth. The data were analyzed using ANOVA and Tukey’s test (P = .05).

Results

Cervical preflaring and canal preparation reduced the dentin thickness (P < .05) and increased the canal volume (P < .05) in all groups at 3 mm an 5 mm. Cervical preflaring with Gates Gliden burs reduced the fracture resistance of endodontically treated teeth (P < .05).

Conclusions

All instruments reduced the dentin thickness and increased the canal volume in the cervical at 3 mm and 5 mm. Gates Glidden reduced fracture resistance of mandibular incisors submitted to cervical preflaring, whereas NiTi instruments did not.

Clinical relevance

Cervical preflaring assumes particular importance previously to the root canal preparation because it minimizes the occurrence of operative accidents, and permits more accurate determination of working length and the apical diameter.
Treatment seeking behavior and associated factors of suspected dengue fever among Shan people in eastern Shan special region IV, Myanmar: a cross-sectional study
Authors: Liu Hui , Xu Jian-Wei , Ai Zadan , Yu Yan , Yu Bian
Published: April 2020

Background

Dengue fever (DF) is a rapidly spreading mosquito-borne disease along the China-Myanmar border. Understanding treatment-seeking behaviors (TSBs) and associated factors of suspected DF patients in local communities helps to improve health services via promoting prompt treatment, improving patients’ prognosis, finding DF information and timely response to DF foci.

Methods

A combination of qualitative semi-structured in-depth interview (SDIs) included 18 key-informants, and quantitative household questionnaire survey (HHSs) involved 259 households was carried out to investigate TSBs and associated factors of suspected DF patients in the Eastern Shan Special Region IV (ESSR4), Myanmar.

Results

The key informants mentioned that most of their fellow villagers did not seek treatment in public health facilities first. The HHS questionnaires were distributed to household heads, and 241 of the 259 HHS respondents were valid after data auditing. Only 102 (43.2%) household heads reported that their family sought treatment for suspected DF at a public health facility immediately; 111 (46.1%) respondents said that they chose self-medication first. The adjusted odds ratio of multivariate logistic analysis (MLA) predicting household heads’ first seeking healthcare at a public hospital were 1.91 (95%CI: 1.03–3.53) for those who knew DF and 5.11 (95%CI: 2.08–12.58) for those who regarded DF as a deadly disease, indicating that families who knew DF and regarded DF as a deadly disease were more likely to seek treatment for suspected DF at a public health facility immediately.

Conclusion

The inappropriateness of treatment-seeking behaviors for suspected DF hinders the improvement of the patient prognosis and dengue control in ESSR4, Myanmar. People’s awareness of the potential seriousness of DF is a factor influencing appropriate healthcare-seeking behavior among Shan People.
Cardiopulmonary failure in children infected with Enterovirus A71
Authors: Hsia Shao-Hsuan , Lin Jainn-Jim , Chan Oi-Wa , Lin Tzou-Yien
Published: April 2020

Enterovirus A71 (EV-A71) is one of the causative pathogens of hand, foot, and mouth disease (HFMD), which may cause severe neurological and cardiopulmonary complications in children. In this review, we discuss the pathogenesis, clinical manifestations, management strategy, and clinical outcomes of cardiopulmonary failure (CPF) in patients with EV-A71 infection.

The pathogenesis of CPF involves both catecholamine-related cardiotoxicity following brainstem encephalitis and vasodilatory shock due to cytokine storm. Sympathetic hyperactivity, including tachycardia and hypertension, are the early clinical manifestations of cardiopulmonary involvement, which may progress to pulmonary edema/hemorrhage and/or CPF. The management strategy comprises multidisciplinary supportive treatment, including fluid management, positive pressure ventilation support, and use of milrinone, vasopressors, and inotropes. Some patients may require extracorporeal membrane oxygenation. Major neurological sequelae are almost inevitable once a child develops life-threatening illness. Long-term care of these children is an important medico-social issue.
Surveillance based estimation of burden of malaria in India, 2015–2016
Authors: Kumar Ashwani , Chaturvedi Himanshu K. , Mohanty Ajeet Kumar , Sharma Surya Kant , Malhotra Mantoshkumar S. , Pandey Arvind
Published: April 2020

Background

India has launched the malaria elimination initiative in February 2016. Studies suggest that estimates of malaria are useful to rationalize interventions and track their impact. Hence, a national study was launched to estimate burden of malaria in India in 2015.

Methods

For sampling, all 624 districts of India were grouped in three Annual Parasite Incidence (cases per thousand population) categories, < two (low); two-five (moderate) and > five (high) API. Using probability proportional to size (PPS) method, two districts from each stratum were selected covering randomly 200,000 persons per district. Active surveillance was strengthened with 40 trained workers per study district. Data on malaria cases and deaths was collated from all health care providers i.e. pathological laboratories, private practitioners and hospitals in private and public health sectors and was used for analysis and burden estimation.

Results

Out of 1215,114 population under surveillance, 198,612 (16.3%) tests were performed and 19,386 (9.7%) malaria cases were detected. The malaria cases estimated in India were 3875,078 (95% confidence interval 3792,018–3958,137) with API of 3.05 (2.99–3.12) including 2789,483 (2740,577–2838,389) Plasmodium falciparum with Annual Falciparum Incidence of 2.2 (2.16–2.24). Out of 8025 deaths investigated, 102 (1.27%) were attributed to malaria. The estimated deaths in India were 29,341 (23,354–35,327) including 19,067 (13,665–24,470) confirmed and 10,274 (7694–12,853) suspected deaths in 2015–2016.

Conclusions

Estimated malaria incidence was about four folds greater than one million reported by the national programme, but three folds lesser than thirteen million estimated by the World Health Organization (WHO). However, the estimated deaths were 93 folds more than average 313 deaths reported by the national malaria programme in 2015–2016. The 29,341 deaths were comparable with 24,000 deaths in 2015 and 22,786 deaths in 2016 estimated by the WHO for India. These malaria estimates can serve as a benchmark for tracking the success of malaria elimination campaign in India.
Merlin regulates signaling events at the nexus of development and cancer
Authors: Mota Mateus , Shevde Lalita A.
Published: April 2020

Background

In this review, we describe how the cytoskeletal protein Merlin, encoded by the Neurofibromin 2 (NF2) gene, orchestrates developmental signaling to ensure normal ontogeny, and we discuss how Merlin deficiency leads to aberrant activation of developmental pathways that enable tumor development and malignant progression.

Main body

Parallels between embryonic development and cancer have underscored the activation of developmental signaling pathways. Hippo, WNT/β-catenin, TGF-β, receptor tyrosine kinase (RTK), Notch, and Hedgehog pathways are key players in normal developmental biology. Unrestrained activity or loss of activity of these pathways causes adverse effects in developing tissues manifesting as developmental syndromes. Interestingly, these detrimental events also impact differentiated and functional tissues. By promoting cell proliferation, migration, and stem-cell like phenotypes, deregulated activity of these pathways promotes carcinogenesis and cancer progression. The NF2 gene product, Merlin, is a tumor suppressor classically known for its ability to induce contact-dependent growth inhibition. Merlin plays a role in different stages of an organism development, ranging from embryonic to mature states. While homozygous deletion of Nf2 in murine embryos causes embryonic lethality, Merlin loss in adult tissue is implicated in Neurofibromatosis type 2 disorder and cancer. These manifestations, cumulatively, are reminiscent of dysregulated developmental signaling.

Conclusion

Understanding the molecular and cellular repercussions of Merlin loss provides fundamental insights into the etiology of developmental disorders and cancer and has the potential, in the long term, to identify new therapeutic strategies.

Graphical abstract
The Great Debate at “Melanoma Bridge”, Naples, December 7th, 2019
Authors: Ascierto Paolo A. , Agarwala Sanjiv S. , Eggermont Alexander , Gershenwald Jeffrey E. , Grob Jean-Jacques , Hamid Omid , Michielin Olivier , Postow Michael , Puzanov Igor , Zarour Hassane M. , Caracò Corrado , Testori Alessandro
Published: April 2020

The Great Debate session at the 2019 Melanoma Bridge congress (December 5-7, Naples, Italy) featured counterpoint views from experts on five topical issues in melanoma. These were whether to choose local intratumoral treatment or systemic treatment, whether patients with stage IIIA melanoma require adjuvant therapy or not, whether treatment is better changed at disease progression or during stable disease, whether adoptive cell transfer (ACT) therapy is more appropriate used before or in combination with checkpoint inhibition therapy, and whether treatment can be stopped while the patient is still on response. As was the case for previous meetings, the debates were assigned by meeting Chairs. As such, positions taken by each of the melanoma experts during the debates may not have reflected their respective personal approach.
Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson’s disease brain
Authors: Rostami Jinar , Fotaki Grammatiki , Sirois Julien , Mzezewa Ropafadzo , Bergström Joakim , Essand Magnus , Healy Luke , Erlandsson Anna
Published: April 2020

Background

Many lines of evidence suggest that accumulation of aggregated alpha-synuclein (αSYN) in the Parkinson’s disease (PD) brain causes infiltration of T cells. However, in which ways the stationary brain cells interact with the T cells remain elusive. Here, we identify astrocytes as potential antigen-presenting cells capable of activating T cells in the PD brain. Astrocytes are a major component of the nervous system, and accumulating data indicate that astrocytes can play a central role during PD progression.

Methods

To investigate the role of astrocytes in antigen presentation and T-cell activation in the PD brain, we analyzed post mortem brain tissue from PD patients and controls. Moreover, we studied the capacity of cultured human astrocytes and adult human microglia to act as professional antigen-presenting cells following exposure to preformed αSYN fibrils.

Results

Our analysis of post mortem brain tissue demonstrated that PD patients express high levels of MHC-II, which correlated with the load of pathological, phosphorylated αSYN. Interestingly, a very high proportion of the MHC-II co-localized with astrocytic markers. Importantly, we found both perivascular and infiltrated CD4+ T cells to be surrounded by MHC-II expressing astrocytes, confirming an astrocyte T cell cross-talk in the PD brain. Moreover, we showed that αSYN accumulation in cultured human astrocytes triggered surface expression of co-stimulatory molecules critical for T-cell activation, while cultured human microglia displayed very poor antigen presentation capacity. Notably, intercellular transfer of αSYN/MHC-II deposits occurred between astrocytes via tunneling nanotubes, indicating spreading of inflammation in addition to toxic protein aggregates.

Conclusions

In conclusion, our data from histology and cell culture studies suggest an important role for astrocytes in antigen presentation and T-cell activation in the PD brain, highlighting astrocytes as a promising therapeutic target in the context of chronic inflammation.
Isolated diaphragmatic metastasis from periosteal osteosarcoma of the humerus: a case report
Authors: Zhao Luo , Qin Yingzhi , Ma Dongjie , Wang Wenze , Li Shanqing , Liu Hongsheng
Published: April 2020

Background

Isolated diaphragmatic metastasis is rarely associated with periosteal osteosarcoma.

Case presentation

A 24-year-old female patient was found to have periosteal osteosarcoma of the right humerus 11 years ago. Computed tomography showed a mass in her left chest in 2018, and thoracotomy was performed to remove the tumour. The tumour showed the same characteristics as the original periosteal osteosarcoma. Genetic analysis of the tumour sample showed a TP53 point mutation and CCNE1 gene copy number variants.

Conclusions

We believe this is the first case report of haematogenous metastasis to the diaphragm of periosteal osteosarcoma, and an investigation of the genetic factors may help to unravel the underlying cause of periosteal osteosarcoma.
Strengthening mental health systems in Zambia
Authors: Munakampe Margarate Nzala
Published: April 2020

Background

Studies in mental health care for low resource settings indicate that providing services at primary care level would significantly improve provision and utilisation of mental health services. Challenges related to inadequate funding were noted as significant barriers to service provision, with the contribution of low knowledge of mental health conditions and stigma in the community. This study aimed to explore the barriers to the use of mental health services in Zambia, suggesting health systems thinking approaches to solving these challenges.

Methods

Primary data were collected through individual interviews from 12 participants; primary caregivers, health workers from public health institutions that treat mental health conditions and policymakers and implementers. The digitally recorded responses were transcribed and analysed using thematic analysis.

Results

Key barriers to care included inadequate funding, few human resources, poor infrastructure and stigma. Barriers to care at policy, facility and individual or community level could be alleviated by strengthening the mental health system. Engagement of community health workers and increasing efforts to sensitise the community about mental health would prove beneficial.

Conclusions

Strengthening the community health systems for mental health could improve access and increase utilisation of services.
Double Robertsonian translocations in an infertile patient with macrocytic anemia: a case report
Authors: Sasi Ramakrishnan , Senft Jamie , Spruill Michelle , Rej Soham , Perrotta Peter L.
Published: April 2020

Background

Constitutional heterologous double Robertsonian translocations (DRT) between chromosomes 13/14 and chromosomes 14/15 with 44 chromosomes are extremely rare. In this case report, we present the karyotype analysis of metaphases prepared from bone marrow, peripheral blood and cultured skin tissue cells. These showed only 44 chromosomes with DRT involving chromosomes 13, 14 and 15. To our knowledge this is the first reported case with DRT involving chromosomes 14 and 15.

Case presentation

The patient is an 81-year-old infertile male with a history of persistent macrocytic anemia (MA). The patient presented with fatigue, paleness of the skin, shortness of breath, lightheadedness and occasional dizziness. Work-up for common causes of macrocytic anemias in this case were excluded: folate/vitamin B12 deficiency, hypothyroidism, liver diseases, hemolysis, bleeding, alcoholism, exposure, HIV infection, chemotherapy or blood loss, drug-toxicity effect, or myelodysplasia. This individual with DRT had only six nucleolus organizer regions (NORs), instead of the usual ten, of which 50% of the 6 NORs were inactive (n = 3).

Conclusion

In this case, macrocytic anemia (MA) appeared to be due to reduction in active NORs in DRT. We postulate that the marked reduction in active NORs leads to reduction in active nucleoli formation, which may be limiting ribosomal RNA synthesis, contributing to MA. It is probable that reduction in NOR activity affected normal DNA synthesis and cellular functions.