bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipoatrophy Associated With Maxillary Bone Graft for the Purpose of Dental Implants and Correction by Fat Grafting: A Case Report
Authors: Sadeghi Shayan , Saleh Eli , Danino Michel Alain
Published: December 2019

Lipoatrophy could be a manifestation of a metabolic disorder, pharmacological therapy, or as the result of an immune reaction in adipose tissue. Localized lipoatrophy after a dental intervention is a finding rarely described in scientific literature of head and neck pathology. A 56-year-old woman reported experiencing tissue loss on the right cheek. A maxillary bone graft for the purpose of dental implants had been performed 10 months prior to the first signs. Medical imaging showed no signs of any lytic bone lesions. A fat graft harvested from the abdomen was used to fill the deficit. For a clinician, lipoatrophy even if extremely rare should be considered among the inflammatory complications after a dento-alveolar bone graft. Especially because of its rarity, any coincidental systemic disorder should be excluded during the assessment of the condition.
Optimization of Cutting Parameters for Trade-off Among Carbon Emissions, Surface Roughness, and Processing Time
Authors: Jiang Zhipeng , Gao Dong , Lu Yong , Liu Xianli
Published: December 2019

As the manufacturing industry is facing increasingly serious environmental problems, because of which carbon tax policies are being implemented, choosing the optimum cutting parameters during the machining process is crucial for automobile panel dies in order to achieve synergistic minimization of the environment impact, product quality, and processing efficiency. This paper presents a processing task-based evaluation method to optimize the cutting parameters, considering the trade-off among carbon emissions, surface roughness, and processing time. Three objective models and their relationships with the cutting parameters were obtained through input–output, response surface, and theoretical analyses, respectively. Examples of cylindrical turning were applied to achieve a central composite design (CCD), and relative validation experiments were applied to evaluate the proposed method. The experiments were conducted on the CAK50135di lathe cutting of AISI 1045 steel, and NSGA-II was used to obtain the Pareto fronts of the three objectives. Based on the TOPSIS method, the Pareto solution set was ranked to find the optimal solution to evaluate and select the optimal cutting parameters. An S/N ratio analysis and contour plots were applied to analyze the influence of each decision variable on the optimization objective. Finally, the changing rules of a single factor for each objective were analyzed. The results demonstrate that the proposed method is effective in finding the trade-off among the three objectives and obtaining reasonable application ranges of the cutting parameters from Pareto fronts.
Refining the concept of GFAP toxicity in Alexander disease
Authors: Messing Albee
Published: December 2019

Background

Alexander disease is caused by dominantly acting mutations in glial fibrillary acidic protein (GFAP), the major intermediate filament of astrocytes in the central nervous system.

Main body

In addition to the sequence variants that represent the origin of disease, GFAP accumulation also takes place, together leading to a gain-of-function that has sometimes been referred to as “GFAP toxicity.” Whether the nature of GFAP toxicity in patients, who have mixtures of both mutant and normal protein, is the same as that produced by simple GFAP excess, is not yet clear.

Conclusion

The implications of these questions for the design of effective treatments are discussed.
A diffusion-weighted imaging tract-based spatial statistics study of autism spectrum disorder in preschool-aged children
Authors: Andrews Derek Sayre , Lee Joshua K. , Solomon Marjorie , Rogers Sally J. , Amaral David G. , Nordahl Christine Wu
Published: December 2019

Background

The core symptoms of autism spectrum disorder (ASD) are widely theorized to result from altered brain connectivity. Diffusion-weighted magnetic resonance imaging (DWI) has been a versatile method for investigating underlying microstructural properties of white matter (WM) in ASD. Despite phenotypic and etiological heterogeneity, DWI studies in majority male samples of older children, adolescents, and adults with ASD have largely reported findings of decreased fractional anisotropy (FA) across several commissural, projection, and association fiber tracts. However, studies in preschool-aged children (i.e., < 30–40 months) suggest individuals with ASD have increased measures of WM FA earlier in development.

Methods

We analyzed 127 individuals with ASD (85♂, 42♀) and 54 typically developing (TD) controls (42♂, 26♀), aged 25.1–49.6 months. Voxel-wise effects of ASD diagnosis, sex, age, and their interaction on DWI measures of FA, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were investigated using tract-based spatial statistics (TBSS) while controlling mean absolute and relative motion.

Results

Compared to TD controls, males and females with ASD had significantly increased measures of FA in eight clusters (threshold-free cluster enhancement p < 0.05) that incorporated several WM tracts including regions of the genu, body, and splenium of the corpus callosum, inferior frontal-occipital fasciculi, inferior and superior longitudinal fasciculi, middle and superior cerebellar peduncles, and corticospinal tract. A diagnosis by sex interaction was observed in measures of AD across six significant clusters incorporating areas of the body, genu, and splenium of the corpus collosum. In these tracts, females with ASD showed increased AD compared to TD females, while males with ASD showed decreased AD compared to TD males.

Conclusions

The current findings support growing evidence that preschool-aged children with ASD have atypical measures of WM microstructure that appear to differ in directionality from alterations observed in older individuals with the condition. To our knowledge, this study represents the largest sample of preschool-aged females with ASD to be evaluated using DWI. Microstructural differences associated with ASD largely overlapped between sexes. However, differential relationships of AD measures indicate that sex likely modulates ASD neuroanatomical phenotypes. Further longitudinal study is needed to confirm and quantify the developmental relationship of WM structure in ASD.
White matter as a monitoring biomarker for neurodevelopmental disorder intervention studies
Authors: Swanson Meghan R. , Hazlett Heather C.
Published: December 2019

Background

Early intervention is a valuable tool to support the development of toddlers with neurodevelopmental disorders. With recent research advances in early identification that allow for pre-symptomatic detection of autism in infancy, scientists are looking forward to intervention during infancy. These advances may be supported by the identification of biologically based treatment and outcome measures that are sensitive and dimensional.

Main body of abstract

The purpose of this review is to evaluate white matter neurodevelopment as a monitoring biomarker for early treatment of neurodevelopmental disorders. Fragile X syndrome (FXS) and autism spectrum disorder (ASD) as used as exemplars. White matter has unique neurobiology, including a prolonged period of dynamic development. This developmental pattern may make white matter especially responsive to treatment. White matter develops aberrantly in children with ASD and FXS. Histologic studies in rodents have provided targets for FXS pharmacological intervention. However, pharmaceutical clinical trials in humans failed to garner positive clinical results. In this article, we argue that the use of neurobiological monitoring biomarkers may overcome some of these limitations, as they are objective, not susceptible to placebo effects, and are dimensional in nature.

Short conclusion

As the field moves towards earlier detection and early intervention for neurodevelopmental disorders, we encourage scientists to consider the advantages of using neurobiological features as monitoring biomarkers.
Identification of genetic loci and candidate genes related to soybean flowering through genome wide association study
Authors: Li Minmin , Liu Ying , Tao Yahan , Xu Chongjing , Li Xin , Zhang Xiaoming , Han Yingpeng , Yang Xue , Sun Jingzhe , Li Wenbin , Li Dongmei , Zhao Xue , Zhao Lin
Published: December 2019

Background

As a photoperiod-sensitive and self-pollinated species, the growth periods traits play important roles in the adaptability and yield of soybean. To examine the genetic architecture of soybean growth periods, we performed a genome-wide association study (GWAS) using a panel of 278 soybean accessions and 34,710 single nucleotide polymorphisms (SNPs) with minor allele frequencies (MAF) higher than 0.04 detected by the specific-locus amplified fragment sequencing (SLAF-seq) with a 6.14-fold average sequencing depth. GWAS was conducted by a compressed mixed linear model (CMLM) involving in both relative kinship and population structure.

Results

GWAS revealed that 37 significant SNP peaks associated with soybean flowering time or other growth periods related traits including full bloom, beginning pod, full pod, beginning seed, and full seed in two or more environments at -log10(P) > 3.75 or -log10(P) > 4.44 were distributed on 14 chromosomes, including chromosome 1, 2, 3, 5, 6, 9, 11, 12, 13, 14, 15, 17, 18, 19. Fourteen SNPs were novel loci and 23 SNPs were located within known QTLs or 75 kb near the known SNPs. Five candidate genes (Glyma.05G101800, Glyma.11G140100, Glyma.11G142900, Glyma.19G099700, Glyma.19G100900) in a 90 kb genomic region of each side of four significant SNPs (Gm5_27111367, Gm11_10629613, Gm11_10950924, Gm19_34768458) based on the average LD decay were homologs of Arabidopsis flowering time genes of AT5G48385.1, AT3G46510.1, AT5G59780.3, AT1G28050.1, and AT3G26790.1. These genes encoding FRI (FRIGIDA), PUB13 (plant U-box 13), MYB59, CONSTANS, and FUS3 proteins respectively might play important roles in controlling soybean growth periods.

Conclusions

This study identified putative SNP markers associated with soybean growth period traits, which could be used for the marker-assisted selection of soybean growth period traits. Furthermore, the possible candidate genes involved in the control of soybean flowering time were predicted.
Genetic deletion of Sphk2 confers protection against Pseudomonas aeruginosa mediated differential expression of genes related to virulent infection and inflammation in mouse lung
Authors: Ebenezer David L. , Fu Panfeng , Krishnan Yashaswin , Maienschein-Cline Mark , Hu Hong , Jung Segun , Madduri Ravi , Arbieva Zarema , Harijith Anantha , Natarajan Viswanathan
Published: December 2019

Background

Pseudomonas aeruginosa(PA) is an opportunistic Gram-negative bacterium that causes serious life threatening and nosocomial infections including pneumonia.PAhas the ability to alter host genome to facilitate its invasion, thus increasing the virulence of the organism. Sphingosine-1- phosphate (S1P), a bioactive lipid, is known to play a key role in facilitating infection. Sphingosine kinases (SPHK) 1&2 phosphorylate sphingosine to generate S1P in mammalian cells. We reported earlier thatSphk2−/−mice offered significant protection against lung inflammation, compared to wild type (WT) animals. Therefore, we profiled the differential expression of genes between the protected group ofSphk2−/−and the wild type controls to better understand the underlying protective mechanisms related to theSphk2deletion in lung inflammatory injury. Whole transcriptome shotgun sequencing (RNA-Seq) was performed on mouse lung tissue using NextSeq 500 sequencing system.

Results

Two-way analysis of variance (ANOVA) analysis was performed and differentially expressed genes followingPAinfection were identified using whole transcriptome ofSphk2−/−mice and their WT counterparts. Pathway (PW) enrichment analyses of the RNA seq data identified several signaling pathways that are likely to play a crucial role in pneumonia caused byPAsuch as those involved in: 1. Immune response toPAinfection and NF-κB signal transduction; 2. PKC signal transduction; 3. Impact on epigenetic regulation; 4. Epithelial sodium channel pathway; 5. Mucin expression; and 6. Bacterial infection related pathways.

Our genomic data suggests a potential role for SPHK2 inPA-induced pneumonia through elevated expression of inflammatory genes in lung tissue. Further, validation by RT-PCR on 10 differentially expressed genes showed 100% concordance in terms of vectoral changes as well as significant fold change.

Conclusion

UsingSphk2−/−mice and differential gene expression analysis, we have shown here that S1P/SPHK2 signaling could play a key role in promotingPApneumonia. The identified genes promote inflammation and suppress others that naturally inhibit inflammation and host defense. Thus, targeting SPHK2/S1P signaling inPA-induced lung inflammation could serve as a potential therapy to combatPA-induced pneumonia.
Interactions between Yersinia pestis V-antigen (LcrV) and human Toll-like receptor 2 (TLR2) in a modelled protein complex and potential mechanistic insights
Authors: Wei Tiandi , Gong Jing , Qu Guojing , Wang Mingyu , Xu Hai
Published: December 2019

Background

Yersinia pestis, the etiological pathogen of plague, is capable of repressing the immune response of white blood cells to evade phagocytosis. The V-antigen (LcrV) was found to be involved in this process by binding to human Toll-like Receptor 2 (TLR2). The detailed mechanism behind this LcrV and TLR2 mediated immune response repression, however, is yet to be fully elucidated due to the lack of structural information.

Results

In this work, with protein structure modelling, we were able to construct a structure model of the heterotetramer of Y. pestis LcrV and human TLR2. Molecular dynamics simulation suggests the stability of this structure in aquatic environment. The LcrV model has a dumbbell-like structure with two globule domains (G1 at N-terminus and G2 away from membrane) connected with a coiled-coil linker (CCL) domain. The two horseshoe-shape TLR2 subunits form a V-shape structure, are not in direct contact with each other, and are held together by the LcrV homodimer. In this structure model, both the G1 and CCL domains are involved in the formation of LcrV homodimer, while all three domains are involved in LcrV-TLR2 binding. A mechanistic model was proposed based on this heterotetrameric structure model: The LcrV homodimer separates the TLR2 subunits to inhibit the dimerization of TLR2 and subsequent signal transfer for immune response; while LcrV could also inhibit the formation of heterodimers of TLR2 with other TLRs, and leads to immune response repression.

Conclusions

A heterotetrameric structure of Y. pestis LcrV and human TLR2 was modelled in this work. Analysis of this modelled structure showed its stability in aquatic environments and the role of LcrV domains and residues in protein-protein interaction. A mechanistic model for the role of LcrV in Y. pestis pathogenesis is raised based on this heterotetrameric structure model. This work provides a hypothesis of LcrV function, with which further experimental validation may elucidate the role of LcrV in human immune response repression.
Haplotype block analysis of an Argentinean hexaploid wheat collection and GWAS for yield components and adaptation
Authors: Luján Basile Silvana Marisol , Ramírez Ignacio Abel , Crescente Juan Manuel , Conde Maria Belén , Demichelis Melina , Abbate Pablo , Rogers William John , Pontaroli Ana Clara , Helguera Marcelo , Vanzetti Leonardo Sebastián
Published: December 2019

Background

Increasing wheat (Triticum aestivum L.) production is required to feed a growing human population. In order to accomplish this task a deeper understanding of the genetic structure of cultivated wheats and the detection of genomic regions significantly associated with the regulation of important agronomic traits are necessary steps. To better understand the genetic basis and relationships of adaptation and yield related traits, we used a collection of 102 Argentinean hexaploid wheat cultivars genotyped with the 35k SNPs array, grown from two to six years in three different locations. Based on SNPs data and gene-related molecular markers, we performed a haplotype block characterization of the germplasm and a genome-wide association study (GWAS).

Results

The genetic structure of the collection revealed four subpopulations, reflecting the origin of the germplasm used by the main breeding programs in Argentina. The haplotype block characterization showed 1268 blocks of different sizes spread along the genome, including highly conserved regions like the 1BS chromosome arm where the 1BL/1RS wheat/rye translocation is located. Based on GWAS we identified ninety-seven chromosome regions associated with heading date, plant height, thousand grain weight, grain number per spike and fruiting efficiency at harvest (FEh). In particular FEh stands out as a promising trait to raise yield potential in Argentinean wheats; we detected fifteen haplotypes/markers associated with increased FEh values, eleven of which showed significant effects in all three evaluated locations. In the case of adaptation, the Ppd-D1 gene is consolidated as the main determinant of the life cycle of Argentinean wheat cultivars.

Conclusion

This work reveals the genetic structure of the Argentinean hexaploid wheat germplasm using a wide set of molecular markers anchored to the Ref Seq v1.0. Additionally GWAS detects chromosomal regions (haplotypes) associated with important yield and adaptation components that will allow improvement of these traits through marker-assisted selection.
Anatomy and RNA-Seq reveal important gene pathways regulating sex differentiation in a functionally Androdioecious tree, Tapiscia sinensis
Authors: Xin Gui-Liang , Liu Jia-Qian , Liu Jia , Ren Xiao-Long , Du Xiao-Min , Liu Wen-Zhe
Published: December 2019

Background

Gametogenesis is a key step in the production of ovules or pollen in higher plants. The sex-determination aspects of gametogenesis have been well characterized in the model plantArabidopsis. However, little is known about this process in androdioecious plants.Tapiscia sinensisOliv. is a functionally androdioecious tree, with both male and hermaphroditic individuals. Hermaphroditic flowers (HFs) are female-fertile flowers that can produce functional pollen and set fruits. However, compared with male flowers (MFs), the pollen viability and number of pollen grains per flower are markedly reduced in HFs. MFs are female-sterile flowers that fail to set fruit and that eventually drop.

Results

Compared with HF, a notable cause of MF female sterility inT. sinensisis when the early gynoecium meristem is disrupted. During the early stage of HF development (stage 6), the ring meristem begins to form as a ridge around the center of the flower. At this stage, the internal fourth-whorl organ is stem-like rather than carpelloid in MF.

A total of 52,945 unigenes were identified as transcribed in MF and HF. A number of differentially expressed genes (DEGs) and metabolic pathways were detected as involved in the development of the gynoecium, especially the ovule, carpel and style. At the early gynoecium development stage, DEGs were shown to function in the metabolic pathways regulating ethylene biosynthesis and signal transduction (upstream regulator), auxin, cytokinin transport and signalling, and sex determination (or flower meristem identity).

Conclusions

Pathways for the female sterility model were initially proposed to shed light on the molecular mechanisms of gynoecium development at early stages inT. sinensis.
Protective mechanisms of melatonin against selenium toxicity in Brassica napus: insights into physiological traits, thiol biosynthesis and antioxidant machinery
Authors: Ulhassan Zaid , Huang Qian , Gill Rafaqat Ali , Ali Skhawat , Mwamba Theodore Mulembo , Ali Basharat , Hina Faiza , Zhou Weijun
Published: December 2019

Background

The ubiquitous signaling molecule melatonin (N-acetyl-5-methoxytryptamine) (MT) plays vital roles in plant development and stress tolerance. Selenium (Se) may be phytotoxic at high concentrations. Interactions between MT and Se (IV) stress in higher plants are poorly understood. The aim of this study was to evaluate the defensive roles of exogenous MT (0 μM, 50 μM, and 100 μM) against Se (IV) (0 μM, 50 μM, 100 μM, and 200 μM) stress based on the physiological and biochemical properties, thiol biosynthesis, and antioxidant system of Brassica napus plants subjected to these treatments.

Results

Se (IV) stress inhibited B. napus growth and biomass accumulation, reduced pigment content, and lowered net photosynthetic rate (Pn) and PSII photochemical efficiency (Fv/Fm) in a dose-dependent manner. All of the aforementioned responses were effectively alleviated by exogenous MT treatment. Exogenous MT mitigated oxidative damage and lipid peroxidation and protected the plasma membranes from Se toxicity by reducing Se-induced reactive oxygen species (ROS) accumulation. MT also alleviated osmotic stress by restoring foliar water and sugar levels. Relative to standalone Se treatment, the combination of MT and Se upregulated the ROS-detoxifying enzymes SOD, APX, GR, and CAT, increased proline, free amino acids, and the thiol components GSH, GSSG, GSH/GSSG, NPTs, PCs, and cys and upregulated the metabolic enzymes γ-ECS, GST, and PCS. Therefore, MT application attenuates Se-induce oxidative damage in plants. MT promotes the accumulation of chelating agents in the roots, detoxifies Se there, and impedes its further translocation to the leaves.

Conclusions

Exogenous MT improves the physiological traits, antioxidant system, and thiol ligand biosynthesis in B. napus subjected to Se stress primarily by enhancing Se detoxification and sequestration especially at the root level. Our results reveal better understanding of Se-phytotoxicity and Se-stress alleviation by the adequate supply of MT. The mechanisms of MT-induced plant tolerance to Se stress have potential implications in developing novel strategies for safe crop production in Se-rich soils.

Graphical abstract
The plant defensin gene AtPDF2.1 mediates ammonium metabolism by regulating glutamine synthetase activity in Arabidopsis thaliana
Authors: Yao Junyue , Luo Jin-Song , Xiao Yan , Zhang Zhenhua
Published: December 2019

Background

In plants, ammonium metabolism is particularly important for converting absorbed nitrogen into amino acids. However, the molecular mechanism underlying this conversion remains largely unknown.

Results

Using wild type Arabidopsis thaliana (Col-0) and AtPDF2.1 mutants (pdf2.1–1 and pdf2.1–2), we found that the small cysteine-rich peptide AtPDF2.1, a plant defensin, is involved in regulating ammonium metabolism in the shoot. Ammonium significantly induced the expression of AtPDF2.1 in the shoot and root, particularly in root xylem vascular bundles, as demonstrated by histochemical analysis. Subcellular localization analysis revealed that AtPDF2.1 was localized to the cell wall. Ammonium concentration was higher in the shoot of mutants than in the shoot of Col-0, but no differences were found for total nitrogen content, root ammonium concentration, and the expression of the ammonium transporter gene AtAMT2.1. The activity of glutamine synthetase was significantly decreased in mutants, and the glutamine synthetase family genes GLN1.3 and GLN1.5 were significantly downregulated in mutants compared to Col-0. The activity of nitrate reductase showed no difference between mutants and Col-0.

Conclusions

Overall, these data suggest that AtPDF2.1 affects ammonium metabolism by regulating the expression of GLN1.3 and GLN1.5 through a yet unidentified mechanism.
Differences in the photosynthetic and physiological responses of Leymus chinensis to different levels of grazing intensity
Authors: Liu Min , Gong Jirui , Yang Bo , Ding Yong , Zhang Zihe , Wang Biao , Zhu Chenchen , Hou Xiangyang
Published: December 2019

Background

Grazing is an important land use in northern China. In general, different grazing intensities had a different impact on the morphological and physiological traits of plants, and especially their photosynthetic capacity. We investigated the responses of Leymus chinensis to light, medium, and heavy grazing intensities in comparison with a grazing exclusion control.

Results

With light grazing, L. chinensis showed decreased photosynthetic capacity. The low chlorophyll and carotenoid contents constrained light energy transformation and dissipation, and Rubisco activity was also low, restricting the carboxylation efficiency. In addition, the damaged photosynthetic apparatus accumulated reactive oxygen species (ROS). With medium grazing, more energy was used for thermal dissipation, with high carotene content and high non-photochemical quenching, whereas photosynthetic electron transport was lowest. Significantly decreased photosynthesis decreased leaf C contents. Plants decreased the risk caused by ROS through increased energy dissipation. With high grazing intensity, plants changed their strategy to improve survival through photosynthetic compensation. More energy was allocated to photosynthetic electron transport. Though heavy grazing damaged the chloroplast ultrastructure, adjustment of internal mechanisms increased compensatory photosynthesis, and an increased tiller number facilitated regrowth after grazing.

Conclusions

Overall, the plants adopted different strategies by adjusting their metabolism and growth in response to their changing environment.
Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation
Authors: Zhang Zhenxiao , Liu Mingyang , He Jianshuai , Zhang Xiaotian , Chen Yuehua , Li Hui
Published: December 2019

Background

Coronary heart disease (CHD) is the most common cause of mortality globally, yet mitochondrial genetic mutations associated with CHD development remain incompletely understood.

Methods

The subjects from three Chinese families with LHON underwent clinical, genetic, molecular, and biochemical evaluations. Biochemical characterizations included measuring the effects of the15910C > T mutation on tRNAThr levels, enzymatic activity of electron transport chain complexes, membrane permeability, and the mitochondria-mediated generation of both reactive oxygen species (ROS) and adenosine triphosphate (ATP).

Results

We characterize mitochondrial genetic mutations in a three-generation Chinese family exhibiting signs of maternally inherited CHD. Of the 24 different family members in this pedigree we assessed, CHD was detected in 6, with variable severity and age of first appearance. When we sequenced the mitochondrial genomes of these individuals, we found a tRNAThr 15910C > T mutation of the Eastern Asian haplogroup M7b’c. This mutation is predicted to destabilize the strongly conserved (24C-10G) base-pairing, thereby disrupting tRNAThr functionality. When we performed Northern blotting, we detected we observed a 37.5% reduction in tRNAThr levels at baseline in cybrid cell lines bearing the 15910C > T mutation. When we conducted western blot analysis, we detected a ~ 24.96% decrease in mitochondrial translation rates in these same cells.

Conclusions

In the present report, Together these findings suggest a possible link between this 15910C > T tRNAThr mutation and CHD, potentially offering new avenues for future disease intervention.
Self-reported data in environmental health studies: mail vs. web-based surveys
Authors: Cantuaria Manuella Lech , Blanes-Vidal Victoria
Published: December 2019

Background

Internet has been broadly employed as a facilitator for epidemiological surveys, as a way to provide a more economical and practical alternative to traditional survey modes. A current trend in survey research is to combine Web-based surveys with other survey modes by offering the participant the possibility of choosing his/her preferred response method (i.e. mixed-mode approach). However, studies have also demonstrated that the use of different survey modes may produce different responses to the same questions, posing potential challenges on the use of mixed-mode approaches.

Methods

In this paper, we have implemented a statistical comparison between mixed-mode survey responses collected via mail (i.e. paper) and Web methods obtained from a cross-sectional study in non-urban areas of Denmark. Responses provided by mail and Web participants were compared in terms of: 1) the impact of reminder letters in increasing response rates; 2) differences in socio-demographic characteristics between response groups; 3) changes on the likelihood of reporting health symptoms and negative attitudes towards environmental stressors. Comparisons were mainly performed by two sample t-test, Pearson’s Chi-squared test and multinomial logistic regression models.

Results

Among 3104 contacted households, 1066 residents decided to participate on the study. Out of those, 971 selected to respond via mail, whereas 275 preferred the Web method. The majority of socio-demographic characteristics between these two groups of respondents were shown to be statistically different. The use of mailed surveys increased the likelihood of reporting health symptoms and negative attitudes towards environmental stressors, even after controlling for demographic characteristics. Furthermore, the use of reminder letters had a higher positive impact in increasing responses of Web surveys when compared to mail surveys.

Conclusions

Our main findings suggest that the use of mail and Web surveys may produce different responses to the same questions posed to participants, but, at the same time, may reach different groups of respondents, given that the overall characteristics of both groups considerably differ. Therefore, the tradeoff between using mixed-mode survey as a way to increase response rate and obtaining undesirable measurement changes may be attentively considered in future survey studies.
Low serum estradiol levels are related to Mycobacterium avium complex lung disease: a cross-sectional study
Authors: Uwamino Yoshifumi , Nishimura Tomoyasu , Sato Yasunori , Tamizu Eiko , Asakura Takanori , Uno Shunsuke , Mori Masaaki , Fujiwara Hiroshi , Ishii Makoto , Kawabe Hiroshi , Murata Mitsuru , Hasegawa Naoki
Published: December 2019

Background

The risk factors for Mycobacterium avium complex lung disease (MAC-LD) are not well known. We hypothesized that low serum estradiol (E2) levels are related to MAC-LD as most patients with MAC-LD are postmenopausal women.

Methods

This cross-sectional study compared patients with MAC-LD and healthy controls. Study subjects were postmenopausal women aged 65 years or younger. Serum testosterone, dehydroepiandrosterone sulfate (DHEA-S), and E2 levels were measured and categorized as high or low based on median levels. We performed multivariate analysis, receiver operating characteristic (ROC) curve analysis, and age- and body mass index (BMI)-matched subgroup analysis to evaluate the association between low serum E2 levels and MAC-LD.

Additionally, using blood samples obtained for other clinical studies, the levels of sex steroid hormones were compared between age- and BMI-matched MAC-LD and bronchiectasis female patients without non-tuberculosis mycobacterial infections (non-NTM BE).

Results

Forty-two patients with MAC-LD and 91 healthy controls were included. The median E2 (2.20 pg/mL vs. 15.0 pg/mL, p < 0.001), testosterone (0.230 ng/L vs. 0.250 ng/L, p = 0.005), and DHEA-S (82.5 μg/dL vs. 114.0 μg/dL, p < 0.001) levels were lower in the MAC-LD group than in the control group. Multivariate analysis revealed that low serum E2 (adjusted odds ratio = 34.62, 95% confidence interval = 6.02–199.14) was independently related to MAC-LD, whereas low DHEA-S and testosterone were not. ROC analysis illustrated a strong relationship between low serum E2 levels and MAC-LD (area under the curve = 0.947, 95% confidence interval = 0.899–0.995). Even the age- and BMI-matched subgroup analysis of 17 MAC-LD patients and 17 healthy controls showed lower serum E2 in MAC-LD patients than in healthy controls. Additionally, serum E2 levels of 20 MAC-LD patients were lower than plasma E2 levels of 11 matched non-NTM BE patients (1.79 pg/mL vs. 11.0 pg/mL, p < 0.001).

Conclusions

Low serum E2 levels were strongly related to MAC-LD in postmenopausal women.
The effects of repetitive transcranial magnetic stimulation in older adults with mild cognitive impairment: a protocol for a randomized, controlled three-arm trial
Authors: Taylor Joy L. , Hambro Benjamin C. , Strossman Nicole D. , Bhatt Priyanka , Hernandez Beatriz , Ashford J. Wesson , Cheng Jauhtai Joseph , Iv Michael , Adamson Maheen M. , Lazzeroni Laura C. , McNerney Margaret Windy
Published: December 2019

Background

Mild Cognitive Impairment (MCI) carries a high risk of progression to Alzheimer’s disease (AD) dementia. Previous clinical trials testing whether cholinesterase inhibitors can slow the rate of progression from MCI to AD dementia have yielded disappointing results. However, recent studies of the effects of repetitive transcranial magnetic stimulation (rTMS) in AD have demonstrated improvements in cognitive function. Because few rTMS trials have been conducted in MCI, we designed a trial to test the short-term efficacy of rTMS in MCI. Yet, in both MCI and AD, we know little about what site of stimulation would be ideal for improving cognitive function. Therefore, two cortical sites will be investigated in this trial: (1) the dorsolateral prefrontal cortex (DLPFC), which has been well studied for treatment of major depressive disorder; and (2) the lateral parietal cortex (LPC), a novel site with connectivity to AD-relevant limbic regions.

Methods/design

In this single-site trial, we plan to enroll 99 participants with single or multi-domain amnestic MCI. We will randomize participants to one of three groups: (1) Active DLPFC rTMS; (2) Active LPC rTMS; and (3) Sham rTMS (evenly split between DLPFC and LPC locations). After completing 20 bilateral rTMS treatment sessions, participants will be followed for 6 months to test short-term efficacy and track durability of effects. The primary efficacy measure is the California Verbal Learning Test-II (CVLT-II), assessed 1 week after intervention. Secondary analyses will examine effects of rTMS on other cognitive measures, symptoms of depression, and brain function with respect to the site of stimulation. Finally, selected biomarkers will be analyzed to explore predictors of response and mechanisms of action.

Discussion

The primary aim of this trial is to test the short-term efficacy of rTMS in MCI. Additionally, the project will provide information on the durability of cognitive effects and potentially distinct effects of stimulating DLPFC versus LPC regions. Future efforts would be directed toward better understanding therapeutic mechanisms and optimizing rTMS for treatment of MCI. Ultimately, if rTMS can be utilized to slow the rate of progression to AD dementia, this will be a significant advancement in the field.

Trial registration

Clinical Trials NCT03331796. Registered 6 November 2017, https://clinicaltrials.gov/ct2/show/NCT03331796. All items from the World Health Organization Trial Registration Data Set are listed in Appendix A.

Protocol version

This report is based on version 1, approved by the DSMB on 30 November, 2017 and amended on 14 August, 2018 and 19 September, 2019.
Case report on novel mutation in SPAST gene in Polish family with spastic paraplegia
Authors: Klimkowicz-Mrowiec Aleksandra , Dziubek Anna , Sado Malgorzata , Karpiński Marek , Gorzkowska Agnieszka
Published: December 2019

Background

Hereditary spastic paraplegia is a large group of degenerative, neurological disorders characterized by progressive lower limb spasticity and weakness. The disease was investigated precisely but still clinicians often make incorrect or late diagnosis. Our aim was to investigate the genetic background and clinical phenotype of spastic paraplegia in large Polish family.

Case presentation

A 37 years old woman presented with 4-year history of walking difficulties. On neurological examination, she had signs of upper motor lesion in lower extremities. She denied sphincter dysfunction and her cognition was normal. Her family history was positive for individuals with gait problems. The initial diagnosis was familial spastic paraplegia. Genetic testing identified a novel mutation in SPAST gene. All available family members were examined and had genetic testing. The same mutation in SPAST gene was identified in other affected family members. All patients caring the mutation presented with different phenotypes.

Conclusion

This study presents a family with spastic paraplegia due to a novel mutation c.1390G›T(p.Glu464Term) in SPAST gene. Affected individuals showed a range of phenotypes that varied in their severity. This case report demonstrates, the signs of hereditary spastic paraplegia can be often misdiagnosed with other diseases. Therefore genetic testing should always be considered in patients with lower limb spasticity and positive family history in order to help to establish the correct diagnosis.
Effect of lymph node dissection on stage-specific survival in patients with upper urinary tract urothelial carcinoma treated with nephroureterectomy
Authors: Zhai Ting-Shuai , Jin Liang , Zhou Zhen , Liu Xiang , Liu Huan , Chen Wei , Lu Jing-Yi , Yao Xu-Dong , Feng Li-Ming , Ye Lin
Published: December 2019

Background

We aimed to estimate the stage-specific impact of lymph node dissection (LND) on survival for upper urinary tract urothelial carcinoma (UTUC) patients treated with nephroureterectomy (NU).

Methods

Overall, 7278 UTUC patients undergoing NU within the SEER database from 2004 to 2015 were identified. Kaplan-Meier plots illustrated overall survival (OS) and cancer-specific survival (CSS) rates according to LND status. Multivariable Cox regression analyses assessed the effect of LND on OS and CSS rates stratified by pathological tumor stage.

Results

LND was performed in 26.9% of patients, and in 18.6, 23.3, 31.2 and 45.9% for pT1, pT2, pT3 and pT4 patients, respectively (P <  0.001). In multivariable Cox regression analyses, LND was associated with a higher OS or CSS in UTUC patients with pT3 and pT4 disease (all P <  0.05), but failed to achieve independent predictor status in patients with pT1 and pT2 disease (all P > 0.05). LND with 1 to 3 regional lymph nodes removed was prone to a higher OS or CSS only in pT4 compared to no LND (both P <  0.01). LND with 4 or more regional lymph nodes removed predisposed to a higher OS or CSS in pT3 or pT4 (all P <  0.05).

Conclusions

The beneficial effect of LND especially LND with 4 or more regional lymph nodes removed on survival was evident in pT3/4 patients. LND can be considered for pT3 and pT4, for pT1/2 remains to be seen, both of which will be verified by further prospective studies.
Preoperative plasma fatty acid metabolites inform risk of prostate cancer progression and may be used for personalized patient stratification
Authors: Zoni Eugenio , Minoli Martina , Bovet Cédric , Wehrhan Anne , Piscuoglio Salvatore , Ng Charlotte K. Y. , Gray Peter C. , Spahn Martin , Thalmann George N. , Kruithof-de Julio Marianna
Published: December 2019

Background

Little is known about the relationship between the metabolite profile of plasma from pre-operative prostate cancer (PCa) patients and the risk of PCa progression. In this study we investigated the association between pre-operative plasma metabolites and risk of biochemical-, local- and metastatic-recurrence, with the aim of improving patient stratification.

Methods

We conducted a case-control study within a cohort of PCa patients recruited between 1996 and 2015. The age-matched primary cases (n = 33) were stratified in low risk, high risk without progression and high risk with progression as defined by the National Comprehensive Cancer Network. These samples were compared to metastatic (n = 9) and healthy controls (n = 10). The pre-operative plasma from primary cases and the plasma from metastatic patients and controls were assessed with untargeted metabolomics by LC-MS. The association between risk of progression and metabolite abundance was calculated using multivariate Cox proportional-hazard regression and the relationship between metabolites and outcome was calculated using median cut-off normalized values of metabolite abundance by Log-Rank test using the Kaplan Meier method.

Results

Medium-chain acylcarnitines (C6-C12) were positively associated with the risk of PSA progression (p = 0.036, median cut-off) while long-chain acylcarnitines (C14-C16) were inversely associated with local (p = 0.034) and bone progression (p = 0.0033). In primary cases, medium-chain acylcarnitines were positively associated with suberic acid, which also correlated with the risk of PSA progression (p = 0.032, Log-Rank test). In the metastatic samples, this effect was consistent for hexanoylcarnitine, L.octanoylcarnitine and decanoylcarnitine. Medium-chain acylcarnitines and suberic acid displayed the same inverse association with tryptophan, while indoleacetic acid, a breakdown product of tryptophan metabolism was strongly associated with PSA (p = 0.0081, Log-Rank test) and lymph node progression (p = 0.025, Log-Rank test). These data were consistent with the increased expression of indoleamine 2,3 dioxygenase (IDO1) in metastatic versus primary samples (p = 0.014). Finally, functional experiments revealed a synergistic effect of long chain fatty acids in combination with dihydrotestosterone administration on the transcription of androgen responsive genes.

Conclusions

This study strengthens the emerging link between fatty acid metabolism and PCa progression and suggests that measuring levels of medium- and long-chain acylcarnitines in pre-operative patient plasma may provide a basis for improving patient stratification.
Ramsay-Hunt syndrome and subsequent sensory neuropathy as potential immune-related adverse events of nivolumab: a case report
Authors: Sakoh Takashi , Kanzaki Mami , Miyamoto Atsushi , Mochizuki Sayaka , Kakumoto Toshiyuki , Sato Kenichiro , Uesaka Yoshikazu , Kishi Kazuma
Published: December 2019

Background

Nivolumab is an immune checkpoint inhibitor (ICI) and is used for the treatment of advanced non-small cell lung cancer (NSCLC). Several immune-mediated neurological adverse events associated with ICIs have been reported to date, such as Guillain-Barré syndrome. Nivolumab-associated neurological adverse events can vary, and their etiology remains unclear.

Case presentation

A 72-year-old man with NSCLC was treated with nivolumab as a second-line therapy. After 13 rounds of nivolumab therapy, he presented with Ramsay-Hunt syndrome (RHS) followed by acute ataxic sensory neuropathy. Antiviral therapy for Varicella-Zoster virus and prednisolone resulted in partial improvement of RHS, while almost no recovery was observed in the sensory neuropathy. However, the sensory ataxia significantly improved after intravenous immunoglobulin (IVIg) therapy, and interestingly, the facial palsy associated with RHS also improved. The neurological manifestations, nerve conduction study result, and imaging findings supported that dorsal root ganglia were the primary lesion site of acute ataxic sensory neuropathy.

Conclusions

Our case presented with the comorbidity of RHS and subsequent ataxic sensory neuropathy after nivolumab therapy to whom IVIg was effective. Our case suggested the wide variability of possible neurological symptoms, and the potential usefulness of IVIg to sensory ataxic neuropathy, seen in cancer patients with ICI treatment.
Neonatal body composition: crossectional study in healthy term singletons in Germany
Authors: Wiechers Cornelia , Kirchhof Sara , Balles Lena , Avelina Vanessa , Weber Romy , Maas Christoph , Pauluschke-Fröhlich Jan , Hallschmid Manfred , Preißl Hubert , Fritsche Andreas , Poets Christian F. , Franz Axel R.
Published: December 2019

Background

During pregnancy, a variety of factors can influence fetal growth and development. Intrauterine growth may impact on later life and health. Neonatal body composition may be a more sensitive marker for the intrauterine environment than established anthropometric parameters at birth.

Methods

To study neonatal body composition determined by air displacement plethysmography in healthy, term singletons as national reference data, and to establish factors impacting on neonatal body composition in this population. This prospective cross-sectional observational study included 271 healthy, full-term, singletons born between June 2014 and July 2015. Body composition was measured within 96 h of birth using air displacement plethysmography.

Results

Median (Q1, Q2) fat mass / total body mass (BF%) in German singletons was 10.8% (7.7–13.4) and fat free mass (FFM) 2843 g (2606–3099). Female infants had significantly increased BF% compared to male infants (11.2% (8.7–14.0) vs. 9.6% (7.2–12.1)). On multiple regression analysis, BF% and fat mass increased with female gender, maternal pre-pregnancy body mass index, non-smoking mother and parity, whereas FFM increased with male gender and increasing gestational age at birth. Gestational weight gain category, birth mode, and postnatal age at measurement were not associated with BF%, FFM or fat mass.

Conclusions

We generated BF% and FFM centiles for healthy, term, singletons born in Germany; these are similar to those found in other European countries. Infant body composition at birth was associated with modifiable (pre-pregnancy body mass index, smoking), and given factors (gender, gestational age at birth, parity).
Neonatal body composition by air displacement plethysmography in healthy term singletons: a systematic review
Authors: Wiechers Cornelia , Kirchhof Sara , Maas Christoph , Poets Christian F. , Franz Axel R.
Published: December 2019

Background

There is increasing evidence that intrauterine environment and, consequently, growth in utero have both immediate and far-reaching consequences for health. Neonatal body composition might be a more sensitive marker of intrauterine environment and neonatal adiposity than birth weight and could serve as a predictor for non-communicable diseases later in life.

Methods

To perform a systematic literature review on neonatal body composition determined by air displacement plethysmography in healthy infants. The systematic review was performed using the search terms “air displacement plethysmography”, “infant” and “newborn” in Pubmed. Data are displayed as mean (Standard deviation).

Results

Fourteen studies (including n = 6231 infants) using air displacement plethysmography fulfilled inclusion criteria for meta-analysis. In these, weighted mean body fat percentage was 10.0 (4.1) % and weighted mean fat free mass was 2883 (356) g in healthy term infants. Female infants had a higher body fat percentage (11.1 (4.1) % vs. 9.6 (4.0) %) and lower fat free mass (2827 (316) g vs. 2979 (344) g). In the Caucasian subpopulation (n = 2202 infants) mean body fat percentage was 10.8 (4.1), whereas data for reference values of other ethnic groups are still sparse.

Conclusions

Body composition varies depending on gender and ethnicity. These aggregated data may serve as reference for body composition in healthy, term, singletons at least for the Caucasian subpopulation.
Difficult differentiation of a somatic symptom disorder from anterior cutaneous nerve entrapment syndrome (ACNES): a case report
Authors: Yokoyama Narifumi , Shiraki Ryousuke , Watanabe Takashi , Shiinoki Makiko , Nin Michihiro , Shimizu Taro , Yasui-Furukori Norio , Shimoda Kazutaka
Published: December 2019

Background

Somatization is regarded as psychological or emotional distress in the form of physical symptoms that are otherwise medically unexplained.

Case presentation

We report a case of a patient with a somatic symptom disorder (SSD) and depression who was later diagnosed with anterior cutaneous nerve entrapment syndrome (ACNES) when Carnett’s test was positive and block anesthesia using trigger point injections dramatically improved the symptom of abdominal pain.

Conclusion

We concluded that the differentiation of SSDs, such as psychogenic pain, from ACNES is very difficult. Psychiatrists should be aware of this syndrome.