bluuebunny/crossref_metadata_2025 huggingface dataset:
Handwriting in children with Attention Deficient Hyperactive Disorder: role of graphology
Authors: Cohen Rony , Cohen-Kroitoru Batia , Halevy Ayelet , Aharoni Sharon , Aizenberg Irena , Shuper Avinoam
Published: December 2019

Background

Handwriting difficulties are common in children with attention deficient hyperactive disorder (ADHD). The aim of our study was to find distinctive characteristics of handwriting in children with ADHD by using graphology to analyze physical characteristics and patterns, and to evaluate whether graphological analysis is an effective ADHD diagnostic tool for clinicians.

Method

The cohort included 49 children aged 13–18 years attending a tertiary neurology and epilepsy center in 2016–2017; 22 had a previous DSM-IV/V diagnosis of ADHD. The children were asked to write a 10–12-line story in Hebrew on a blank sheet of paper with a blue pen over a 20-min period. The samples were analyzed by a licensed graphologist blinded to the clinical details of the children against a predetermined handwriting profile of individuals with ADHD. Each ADHD characteristic identified in each sample was accorded 1 point, up to a total of 15 points. Patients with a graphology score of 9–15 were considered to have ADHD.

Results

There were 21 boys (43%) and 28 girls (57%) in the cohort; 15 boys (71.4%) and 7 girls (25%) had a DSM-IV/V diagnosis of ADHD. The mean graphology score was significantly higher in the children who had a DSM-IV/V diagnosis of ADHD than in the children who did not (9.61 + 3.49 vs. 5.79 + 4.01,p = 0.002, respectfully).Using a score of 9 as the cutoff, in the girls, graphology had a specificity of 80% (95% CI 59.2–92.8) and a of sensitivity 71.4% for predicting ADHD.Corresponding values in the boys were 75.0 and 76.2%.

Conclusion

The handwriting of children with ADHD has specific characteristics. Graphology may serve as a clinically useful tool in the diagnosis of ADHD.
RETRACTED ARTICLE: Therapeutic effect of nanoliposomal PCSK9 vaccine in a mouse model of atherosclerosis
Authors: Momtazi-Borojeni Amir Abbas , Jaafari Mahmoud Reza , Badiee Ali , Banach Maciej , Sahebkar Amirhossein
Published: December 2019

Background

Proprotein convertase subtilisin/kexin 9 (PCSK9) is an important regulator of low-density lipoprotein receptor (LDLR) and plasma levels of LDL cholesterol (LDL-C). PCSK9 inhibition is an efficient therapeutic approach for the treatment of dyslipidemia. We tested the therapeutic effect of a PCSK9 vaccine on dyslipidemia and atherosclerosis.

Methods

Lipid film hydration method was used to prepare negatively charged nanoliposomes as a vaccine delivery system. An immunogenic peptide called immunogenic fused PCSK9-tetanus (IFPT) was incorporated on the surface of nanoliposomes using DSPE-PEG-maleimide lipid (L-IFPT) and adsorbed to Alhydrogel® (L-IFPTA+). The prepared vaccine formulation (L-IFPTA+) and empty liposomes (negative control) were inoculated four times with bi-weekly intervals in C57BL/6 mice on the background of a severe atherogenic diet and poloxamer 407 (thrice weekly) injection. Antibody titers were evaluated 2 weeks after each vaccination and at the end of the study in vaccinated mice. Effects of anti-PCSK9 vaccination on plasma concentrations of PCSK9 and its interaction with LDLR were determined using ELISA. To evaluate the inflammatory response, interferon-gamma (IFN-γ)- and interleukin (IL)-10-producing splenic cells were assayed using ELISpot analysis.

Results

L-IFPTA+ vaccine induced a high IgG antibody response against PCSK9 peptide in the vaccinated hypercholesterolemic mice. L-IFPTA+-induced antibodies specifically targeted PCSK9 and decreased its plasma consecration by up to 58.5% (− 164.7 ± 9.6 ng/mL, p = 0.0001) compared with the control. PCSK9-LDLR binding assay showed that generated antibodies could inhibit PCSK9-LDLR interaction. The L-IFPTA+ vaccine reduced total cholesterol, LDL-C, and VLDL-C by up to 44.7%, 51.7%, and 19.2%, respectively, after the fourth vaccination booster, compared with the control group at week 8. Long-term studies of vaccinated hypercholesterolemic mice revealed that the L-IFPTA+ vaccine was able to induce a long-lasting humoral immune response against PCSK9 peptide, which was paralleled by a significant decrease of LDL-C by up to 42% over 16 weeks post-prime immunization compared to control. Splenocytes isolated from the vaccinated group showed increased IL-10-producing cells and decreased IFN-γ-producing cells when compared with control and naive mice, suggesting the immune safety of the vaccine.

Conclusions

L-IFPTA+ vaccine could generate long-lasting, functional, and safe PCSK9-specific antibodies in C57BL/6 mice with severe atherosclerosis, which was accompanied by long-term therapeutic effect against hypercholesterolemia and atherosclerosis.
1,25-(OH)2D3/Vitamin D receptor alleviates systemic lupus erythematosus by downregulating Skp2 and upregulating p27
Authors: Liu Dan , Fang Yu-Xuan , Wu Xia , Tan Wei , Zhou Wei , Zhang Yu , Liu Yan-Qing , Li Guo-Qing
Published: December 2019

Background

Recent evidence has suggested that the 1,25(OH)2D3/Vitamin D receptor (VDR) acts to suppress the immune response associated with systemic lupus erythematosus (SLE), a serious multisystem autoimmune disease. Hence, the aim of the current study was to investigate the mechanism by which 1,25-(OH)2D3/VDR influences SLE through regulating the Skp2/p27 signaling pathway.

Methods

Initially, the levels of 1,25(OH)2D3, VDR, Skp2, and p27 were measured in collected renal tissues and peripheral blood. Meanwhile, the levels of inflammatory factors, biochemical indicators (BUN, Cr, anti-nRNP IgG, anti-dsDNA IgG) and urinary protein levels were assayed in in VDRinsert and VDR-knockout mice in response to 1,25(OH)2D3 supplement. In addition, the distribution of splenic immune cells was observed in these mice.

Results

Among the SLE patients, the levels of 1,25(OH)2D3, VDR and p27 were reduced, while the levels of Skp2 were elevated. In addition, the levels of anti-nRNP IgG and anti-dsDNA IgG were increased, suggesting induction of inflammatory responses. Notably, 1,25(OH)2D3/VDR mice had lower concentrations of BUN and Cr, urinary protein levels, precipitation intensity of the immune complex and complement, as well as the levels of anti-nRNP IgG and anti-dsDNA IgG in SLE mice. Additionally, 1,25(OH)2D3 or VDR reduced the degree of the inflammatory response while acting to regulate the distribution of splenic immune cells.

Conclusion

This study indicated that 1,25-(OH)2D3/VDR facilitated the recovery of SLE by downregulating Skp2 and upregulating p27 expression, suggesting the potential of 1,25-(OH)2D3/VDR as a promising target for SLE treatment.
Identification of emerging viral genomes in transcriptomic datasets of alfalfa (Medicago sativa L.)
Authors: Jiang Peng , Shao Jonathan , Nemchinov Lev G.
Published: December 2019

Background

Publicly available transcriptomic datasets have become a valuable tool for the discovery of new pathogens, particularly viruses. In this study, several coding-complete viral genomes previously not found or experimentally confirmed in alfalfa were identified in the plant datasets retrieved from the NCBI Sequence Read Archive.

Methods

Publicly available Medicago spp. transcriptomic datasets were retrieved from the NCBI SRA database. The raw reads were first mapped to the reference genomes of Medicago sativa and Medigago truncatula followed by the alignment of the unmapped reads to the NCBI viral genome database and de novo assembly using the SPAdes tool. When possible, assemblies were experimentally confirmed using 5′/3′ RACE and RT-PCRs.

Results

Twenty three different viruses were identified in the analyzed datasets, of which several represented emerging viruses not reported in alfalfa prior to this study. Among them were two strains of cnidium vein yellowing virus, lychnis mottle virus and Cactus virus X, for which coding-complete genomic sequences were obtained by a de novo assembly.

Conclusions

The results improve our knowledge of the diversity and host range of viruses infecting alfalfa, provide essential tools for their diagnostics and characterization and demonstrate the utility of transcriptomic datasets for the discovery of new pathogens.
Pathological changes of liver one year later in CHB patients with negative HBV DNA
Authors: Shanshan Wu , Xinfang Du , Shuihong Yu , Kecong Lai , Jinjin Qi , Zhi Chen , Feng Chen
Published: December 2019

Background

In this study, we aim to determine the hepatic pathological changes in HBV DNA-negative chronic Hepatitis B (CHB) patients after 12-month antiviral therapy.

Methods

Blood routine indicators including platelet count (PLT) and white blood cell (WBC) were determined. The coagulation function was evaluated by determining the prothrombin time (PT) and prothrombin time activity (PTA), together with the HBV DNA quantification and alpha fetoprotein (AFP). The virology data included hepatitis B surface antigen (HBsAg)/antibodies against hepatitis B surface antigen (anti-HBs), hepatitis B e antigen (HBeAg)/antibodies against hepatitis B e antigen (anti-HBe) and antibodies against hepatitis B core antigen (anti-HBc) were tested. Pathological assay was performed to the liver puncture tissues. Based on the HBV DNA data in the 12-month follow-up of the cases that received anti-viral therapy during this time, the experimental group was divided into group A (HBV DNA negative at the baseline level, HBV DNA negative after 12 months, N = 79) and group B (HBV DNA negative at the baseline level, HBV DNA turning to be positive after 12 months, N = 13). Statistical analysis was performed on the each test index of the two groups.

Results

The inflammation grade of group A showed significant improvement after 12-month treatment (P < 0.05). The pathological inflammation grade of group B was increased after one year, and the liver function indices and the PTA (P < 0.05) levels were all increased. Pathological results indicated that the proportion of disease progression in group A was decreased after 12-month follow-up while that proportion was increased in group B. Significant differences were noticed in AFP levels between the patients with progression in group A and those with progression in group B.

Conclusion

Negative HBV DNA does not mean a controlled hepatitis B. Hepatitis B patients transferred to HBV DNA positivity during the anti-viral therapy are easily to show disease progression, and then special attention should be paid to the HBV DNA monitoring. Meanwhile, close monitoring to the changes of liver function, PTA and AFP levels may help to detect changes on the disease in a timely manner.
Expression of progenitor cell/immature neuron markers does not present definitive evidence for adult neurogenesis
Authors: Hagihara Hideo , Murano Tomoyuki , Ohira Koji , Miwa Miki , Nakamura Katsuki , Miyakawa Tsuyoshi
Published: December 2019

It is agreed upon that adult hippocampal neurogenesis (AHN) occurs in the dentate gyrus (DG) in rodents. However, the existence of AHN in humans, particularly in elderly individuals, remains to be determined. Recently, several studies reported that neural progenitor cells, neuroblasts, and immature neurons were detected in the hippocampus of elderly humans, based on the expressions of putative markers for these cells, claiming that this provides evidence of the persistence of AHN in humans. Herein, we briefly overview the phenomenon that we call “dematuration,” in which mature neurons dedifferentiate to a pseudo-immature status and re-express the molecular markers of neural progenitor cells and immature neurons. Various conditions can easily induce dematuration, such as inflammation and hyper-excitation of neurons, and therefore, the markers for neural progenitor cells and immature neurons may not necessarily serve as markers for AHN. Thus, the aforementioned studies have not presented definitive evidence for the persistence of hippocampal neurogenesis throughout adult life in humans, and we would like to emphasize that those markers should be used cautiously when presented as evidence for AHN. Increasing AHN has been considered as a therapeutic target for Alzheimer’s disease (AD); however, given that immature neuronal markers can be re-expressed in mature adult neurons, independent of AHN, in various disease conditions including AD, strategies to increase the expression of these markers in the DG may be ineffective or may worsen the symptoms of such diseases.
Valorization of waste forest biomass toward the production of cello-oligosaccharides with potential prebiotic activity by utilizing customized enzyme cocktails
Authors: Karnaouri Anthi , Matsakas Leonidas , Krikigianni Eleni , Rova Ulrika , Christakopoulos Paul
Published: December 2019

Background

Production of value-added materials from lignocellulosic biomass residues is an emerging sector that has attracted much attention as it offers numerous benefits from an environmental and economical point of view. Non-digestible oligosaccharides represent a group of carbohydrates that are resistant to gastrointestinal digestion, and therefore, they are considered as potential prebiotic candidates. Such oligosaccharides can derive from the biomass cellulose fraction through a controlled enzymatic hydrolysis that eliminates the yield of monomers.

Results

In the present study, hydrolysis of organosolv-pretreated forest residues (birch and spruce) was tested in the presence of four cellulases (EG5, CBH7, CBH6, EG7) and one accessory enzyme (LPMO). The optimal enzyme combinations were comprised of 20% EG5, 43% CBH7, 22% TtLPMO, 10% PaCbh6a and 5% EG7 in the case of birch and 35% EG5, 45% CBH7, 10% TtLPMO, 10% PaCbh6a and 5% EG7 in the case of spruce, leading to 22.3% and 19.1 wt% cellulose conversion into cellobiose, respectively. Enzymatic hydrolysis was applied on scale-up reactions, and the produced oligosaccharides (consisted of > 90% cellobiose) were recovered and separated from glucose through nanofiltration at optimized temperature (50 °C) and pressure (10 bar) conditions, yielding a final product with cellobiose-to-glucose ratio of 21.1 (birch) and 20.2 (spruce). Cellobiose-rich hydrolysates were tested as fermentative substrates for different lactic acid bacteria. It was shown that they can efficiently stimulate the growth of two Lactobacilli strains.

Conclusions

Controlled enzymatic hydrolysis with processive cellulases, combined with product recovery and purification, as well as enzyme recycling can potentially support the sustainable production of food-grade oligosaccharides from forest biomass.
Schistosoma haematobium infection morbidity, praziquantel effectiveness and reinfection rate among children and young adults in Gabon
Authors: Dejon-Agobé Jean Claude , Edoa Jean Ronald , Honkpehedji Yabo Josiane , Zinsou Jeannot Fréjus , Adégbitè Bayodé Roméo , Ngwese Mirabeau Mbong , Mangaboula Ance , Lell Bertrand , Woldearegai Tamirat Gebru , Grobusch Martin Peter , Mordmüller Benjamin , Adegnika Ayôla Akim
Published: December 2019

Background

Sub-Saharan Africa carries most of the global burden of schistosomiasis. To optimize disease control and reduce morbidity, precise data are needed for control measures adapted to the local epidemiological situation. The objective of this study is to provide baseline information on schistosomiasis dynamics, including praziquantel (PZQ) treatment outcome in children and young adults living in the vicinity of Lambaréné, Gabon.

Methods

Eligible volunteers were included into a prospective longitudinal study. Urine filtration technique was used to detect eggs in urine for schistosomiasis diagnosis. Subjects were treated with 60 mg of PZQ once per month for three consecutive months, and the outcome was assessed by cure rate (CR) and egg reduction rate (ERR).

Results

A total of 328 volunteers were enrolled in the study with a mean (± SD) age of 12.2 ± 4.7 years-old. The female-to-male ratio was 0.99. Out of 258 participants in total, 45% had schistosomiasis during the survey and 43% presented with heavy infections. The incidences of haematuria and schistosomiasis were 0.11 and 0.17 person-years, respectively. After the first and third dose of PZQ, overall ERR of 93% and 95% were found, respectively; while the CR were 78% and 88%, respectively. Both ERR (100 vs 88%) and CR (90 vs 68%) were higher among females than males after the first dose. The CR increased for both groups after the third dose to 95% and 80%, respectively. After the first PZQ dose, ERR was higher for heavy compared to light infections (94 vs 89%), while the CR was higher for light than for heavy infections (87 vs 59%). After the third PZQ dose, ERR increased only for light infections to 99%, while CR increased to 98% and 75% for light and for heavy infections, respectively. The reinfection rate assessed at a mean of 44.6 weeks post-treatment was 25%.

Conclusions

The prevalence of schistosomiasis is moderate in communities living in the vicinity of Lambaréné, where a subpopulation with a high risk of reinfection bears most of the burden of the disease. To improve schistosomiasis control in this scenario, we suggest education of these high-risk groups to seek themselves a one-year PZQ treatment.

Trial registration clinicaltrials.gov Identifier NCT 02769103. Registered 11 May 2016, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT02769013
The mitochondrial transcriptome of the anglerfish Lophius piscatorius
Authors: Dubin Arseny , Jørgensen Tor Erik , Jakt Lars Martin , Johansen Steinar Daae
Published: December 2019

Objective

Analyze key features of the anglerfish Lophius piscatorius mitochondrial transcriptome based on high-throughput total RNA sequencing.

Results

We determined the complete mitochondrial DNA and corresponding transcriptome sequences of L. piscatorius. Key features include highly abundant mitochondrial ribosomal RNAs (10–100 times that of mRNAs), and that cytochrome oxidase mRNAs appeared > 5 times more abundant than both NADH dehydrogenase and ATPase mRNAs. Unusual for a vertebrate mitochondrial mRNA, the polyadenylated COI mRNA was found to harbor a 75 nucleotide 3′ untranslated region. The mitochondrial genome expressed several non-canonical genes, including the long noncoding RNAs lncCR-H, lncCR-L and lncCOI. Whereas lncCR-H and lncCR-L mapped to opposite strands in a non-overlapping organization within the control region, lncCOI appeared novel among vertebrates. We found lncCOI to be a highly abundant mitochondrial RNA in antisense to the COI mRNA. Finally, we present the coding potential of a humanin-like peptide within the large subunit ribosomal RNA.
Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia
Authors: van Tilburg Cornelis M. , Milde Till , Witt Ruth , Ecker Jonas , Hielscher Thomas , Seitz Angelika , Schenk Jens-Peter , Buhl Juliane L. , Riehl Dennis , Frühwald Michael C. , Pekrun Arnulf , Rossig Claudia , Wieland Regina , Flotho Christian , Kordes Uwe , Gruhn Bernd , Simon Thorsten , Linderkamp Christin , Sahm Felix , Taylor Lenka , Freitag Angelika , Burhenne Jürgen , Foerster Kathrin I. , Meid Andreas D. , Pfister Stefan M. , Karapanagiotou-Schenkel Irini , Witt Olaf
Published: December 2019

Background

Until today, adult and pediatric clinical trials investigating single-agent or combinatorial HDAC inhibitors including vorinostat in solid tumors have largely failed to demonstrate efficacy. These results may in part be explained by data from preclinical models showing significant activity only at higher concentrations compared to those achieved with current dosing regimens. In the current pediatric trial, we applied an intra-patient dose escalation design.

The purpose of this trial was to determine a safe dose recommendation (SDR) of single-agent vorinostat for intra-patient dose escalation, pharmacokinetic analyses (PK), and activity evaluation in children (3–18 years) with relapsed or therapy-refractory malignancies.

Results

A phase I intra-patient dose (de)escalation was performed until individual maximum tolerated dose (MTD). The starting dose was 180 mg/m2/day with weekly dose escalations of 50 mg/m2 until DLT/maximum dose. After MTD determination, patients seamlessly continued in phase II with disease assessments every 3 months. PK and plasma cytokine profiles were determined. Fifty of 52 patients received treatment. n = 27/50 (54%) completed the intra-patient (de)escalation and entered phase II. An SDR of 130 mg/m2/day was determined (maximum, 580 mg/m2/day). n = 46/50 (92%) patients experienced treatment-related AEs which were mostly reversible and included thrombocytopenia, fatigue, nausea, diarrhea, anemia, and vomiting. n = 6/50 (12%) had treatment-related SAEs. No treatment-related deaths occurred. Higher dose levels resulted in higher Cmax. Five patients achieved prolonged disease control (> 12 months) and showed a higher Cmax (> 270 ng/mL) and MTDs. Best overall response (combining PR and SD, no CR observed) rate in phase II was 6/27 (22%) with a median PFS and OS of 5.3 and 22.4 months. Low levels of baseline cytokine expression were significantly correlated with favorable outcome.

Conclusion

An SDR of 130 mg/m2/day for individual dose escalation was determined. Higher drug exposure was associated with responses and long-term disease stabilization with manageable toxicity. Patients with low expression of plasma cytokine levels at baseline were able to tolerate higher doses of vorinostat and benefited from treatment. Baseline cytokine profile is a promising potential predictive biomarker.

Trial registration

ClinicalTrials.gov, NCT01422499. Registered 24 August 2011,
Location recommendation privacy protection method based on location sensitivity division
Authors: Yin Chunyong , Ju Xiaokang , Yin Zhichao , Wang Jin
Published: December 2019

Location-based recommendation services can provide users with convenient services, but this requires monitoring and collecting a large amount of location information. In order to prevent location information from being leaked after monitoring and collection, location privacy must be effectively protected. Therefore, this paper proposes a privacy protection method based on location sensitivity for location recommendation. This method uses location trajectories and check-in frequencies to set a threshold so as to classify location sensitivity levels. The corresponding privacy budget is then assigned based on the sensitivity to add Laplace noise that satisfies the differential privacy. Experimental results show that this method can effectively protect the user’s location privacy and reduce the impact of differential privacy noise on service quality.
Benefits and harms of medical cannabis: a scoping review of systematic reviews
Authors: Pratt Misty , Stevens Adrienne , Thuku Micere , Butler Claire , Skidmore Becky , Wieland L. Susan , Clemons Mark , Kanji Salmaan , Hutton Brian
Published: December 2019

Background

There has been increased interest in the role of cannabis for treating medical conditions. The availability of different cannabis-based products can make the side effects of exposure unpredictable. We sought to conduct a scoping review of systematic reviews assessing benefits and harms of cannabis-based medicines for any condition.

Methods

A protocol was followed throughout the conduct of this scoping review. A protocol-guided scoping review conduct. Searches of bibliographic databases (e.g., MEDLINE®, Embase, PsycINFO, the Cochrane Library) and gray literature were performed. Two people selected and charted data from systematic reviews. Categorizations emerged during data synthesis. The reporting of results from systematic reviews was performed at a high level appropriate for a scoping review.

Results

After screening 1975 citations, 72 systematic reviews were included. The reviews covered many conditions, the most common being pain management. Several reviews focused on management of pain as a symptom of conditions such as multiple sclerosis (MS), injury, and cancer. After pain, the most common symptoms treated were spasticity in MS, movement disturbances, nausea/vomiting, and mental health symptoms. An assessment of review findings lends to the understanding that, although in a small number of reviews results showed a benefit for reducing pain, the analysis approach and reporting in other reviews was sub-optimal, making it difficult to know how consistent findings are when considering pain in general. Adverse effects were reported in most reviews comparing cannabis with placebo (49/59, 83%) and in 20/24 (83%) of the reviews comparing cannabis to active drugs. Minor adverse effects (e.g., drowsiness, dizziness) were common and reported in over half of the reviews. Serious harms were not as common, but were reported in 21/59 (36%) reviews that reported on adverse effects. Overall, safety data was generally reported study-by-study, with few reviews synthesizing data. Only one review was rated as high quality, while the remaining were rated of moderate (n= 36) or low/critically low (n= 35) quality.

Conclusions

Results from the included reviews were mixed, with most reporting an inability to draw conclusions due to inconsistent findings and a lack of rigorous evidence. Mild harms were frequently reported, and it is possible the harms of cannabis-based medicines may outweigh benefits.

Systematic review registration

The protocol for this scoping review was posted in the Open Access (https://ruor.uottawa.ca/handle/10393/37247).
Understanding freehand gestures: a study of freehand gestural interaction for immersive VR shopping applications
Authors: Wu Huiyue , Luo Weizhou , Pan Neng , Nan Shenghuan , Deng Yanyi , Fu Shengqian , Yang Liuqingqing
Published: December 2019

Unlike retail stores, in which the user is forced to be physically present and active during restricted opening hours, online shops may be more convenient, functional and efficient. However, traditional online shops often have a narrow bandwidth for product visualizations and interactive techniques and lack a compelling shopping context. In this paper, we report a study on eliciting user-defined gestures for shopping tasks in an immersive VR (virtual reality) environment. We made a methodological contribution by providing a varied practice for producing more usable freehand gestures than traditional elicitation studies. Using our method, we developed a gesture taxonomy and generated a user-defined gesture set. To validate the usability of the derived gesture set, we conducted a comparative study and answered questions related to the performance, error count, user preference and effort required from end-users to use freehand gestures compared with traditional immersive VR interaction techniques, such as the virtual handle controller and ray-casting techniques. Experimental results show that the freehand-gesture-based interaction technique was rated to be the best in terms of task load, user experience, and presence without the loss of performance (i.e., speed and error count). Based on our findings, we also developed several design guidelines for gestural interaction.
Proteome changes of porcine follicular fluid during follicle development
Authors: Paes Victor M. , Liao Shengfa F. , Figueiredo Jose R. , Willard Scott T. , Ryan Peter L. , Feugang Jean M.
Published: December 2019

Background

Ovarian follicular fluid influences follicle and oocyte growth, but the fluctuation of its protein content during folliculogenesis has not been comprehensively analyzed. Here we used a shotgun approach and bioinformatics analyses to investigate and compare the proteomes of porcine follicular fluid (pFF) obtained from small (< 4 mm), medium (4–6 mm) and large (> 6–12 mm) follicles.

Results

Follicular fluid samples containing highest estrogen levels were selected as non-atretic from small (SNA: 26.1 ± 15 ng/mL), medium (MNA: 162 ± 54 ng/mL), and large (LNA: 290 ± 37 ng/mL) follicles for proteomic analyses. We detected 1627, 1699, and 1756 proteins in SNA, MNA, and LNA samples, respectively. Nearly 60–63% of total proteins were specific to each sample, 11–13% were shared in pairwise comparisons, and 247 proteins were shared among all samples. Functional categorization indicated comparable gene ontology (GO) terms distribution per cellular component, molecular function, and biological process categories across samples; however, the ranking of highly significantly enriched GO terms per category revealed differences between samples. The patterns of protein-to-protein interactions varied throughout follicle development, and proteins such as serine protease inhibitor, clade E (SERPINE); plasminogen activator, urokinase (PLAU); and plasminogen activator, urokinase receptor (PLAUR) appeared stage-specific to SNA, MNA, and LNA, respectively. The “complement and coagulation cascades” was the common major pathway. Besides, properdin and fibulin-1 were abundant proteins that appeared absent in LNA samples.

Conclusion

This study provides extensive and functional analyses of the pFF proteome changes during folliculogenesis and offers the potential for novel biomarker discovery in pFF for oocyte quality assessment.
Human genetics and genomics research in Ecuador: historical survey, current state, and future directions
Authors: Zambrano-Mila Marlon S. , Agathos Spiros N. , Reichardt Juergen K. V.
Published: December 2019

Background

In South America, the history of human genetics is extensive and its beginnings go back to the onset of the twentieth century. In Ecuador, the historical record of human genetics and genomics research is limited. In this context, our work analyzes the current status and historical panorama of these fields, based on bibliographic searches in Scopus, Google Scholar, PubMed, and Web of Science.

Results

Our results determined that the oldest paper in human genetics coauthored by an Ecuadorian institution originates from the Central University of Ecuador in 1978. From a historical standpoint, the number of articles has increased since the 1990s. This growth has intensified and it is reflected in 137 manuscripts recorded from 2010 to 2019. Areas such as human population genetics, phylogeography, and forensic sciences are the core of genetics and genomics-associated research in Ecuador. Important advances have been made in the understanding of the bases of cancer, some genetic diseases, and congenital disorders. Fields such as pharmacogenetics and pharmacogenomics have begun to be explored during the last years.

Conclusions

This work paints a comprehensive picture and provides additional insights into the future panorama of human genetic and genomic research in Ecuador as an example of an emerging, resource-limited country with interesting phylogeographic characteristics and public health implications.
Investigating RNA expression profiles altered by nicotinamide mononucleotide therapy in a chronic model of alcoholic liver disease
Authors: Assiri Mohammed A. , Ali Hadi R. , Marentette John O. , Yun Youngho , Liu Juan , Hirschey Matthew D. , Saba Laura M. , Harris Peter S. , Fritz Kristofer S.
Published: December 2019

Background

Chronic alcohol consumption is a significant cause of liver disease worldwide. Several biochemical mechanisms have been linked to the initiation and progression of alcoholic liver disease (ALD) such as oxidative stress, inflammation, and metabolic dysregulation, including the disruption of NAD+/NADH. Indeed, an ethanol-mediated reduction in hepatic NAD+ levels is thought to be one factor underlying ethanol-induced steatosis, oxidative stress, steatohepatitis, insulin resistance, and inhibition of gluconeogenesis. Therefore, we applied a NAD+ boosting supplement to investigate alterations in the pathogenesis of early-stage ALD.

Methods

To examine the impact of NAD+ therapy on the early stages of ALD, we utilized nicotinamide mononucleotide (NMN) at 500 mg/kg intraperitoneal injection every other day, for the duration of a Lieber-DeCarli 6-week chronic ethanol model in mice. Numerous strategies were employed to characterize the effect of NMN therapy, including the integration of RNA-seq, immunoblotting, and metabolomics analysis.

Results

Our findings reveal that NMN therapy increased hepatic NAD+ levels, prevented an ethanol-induced increase in plasma ALT and AST, and changed the expression of 25% of the genes that were modulated by ethanol metabolism. These genes were associated with a number of pathways including the MAPK pathway. Interestingly, our analysis revealed that NMN treatment normalized Erk1/2 signaling and prevented an induction of Atf3 overexpression.

Conclusions

These findings reveal previously unreported mechanisms by which NMN supplementation alters hepatic gene expression and protein pathways to impact ethanol hepatotoxicity in an early-stage murine model of ALD. Overall, our data suggest further research is needed to fully characterize treatment paradigms and biochemical implications of NAD+-based interventions.
The role of temperature as a driver of metabolic flexibility in the Red-billed Leiothrix (Leiothrix lutea)
Authors: Cui Danqi , Wang Na , Ge Jingru , Xu Jiaying , Zheng Weihong , Liu Jinsong
Published: December 2019

Background

The thermoregulatory ability of animals is strongly influenced by the temperature of their environment. Acclimation to cold requires a range of physiological and morphological adjustments. In this study, we tested the hypothesis that a small passerine, the Red-billed Leiothrix (Leiothrix lutea), can maintain homeothermy in cold conditions by adjusting the physiology and biochemistry of its tissue and organs and return to its former physiological and biochemical state when moved to a warm temperature.

Methods

Phenotypic variation in thermogenic activity of the Red-billed Leiothrixs (Leiothrix lutea) was investigated under warm (35 °C), normal (25 °C) or cold (15 °C) ambient temperature conditions. Oxygen consumption was measured using an open-circuit respirometry system. Mitochondrial state-4 respiration and cytochrome-c oxidase (COX) activity in liver, kidney heart and pectoral muscle were measured with a Clark electrode.

Results

Birds acclimated to an ambient temperature of 15 °C for 4 weeks significantly increased their basal metabolic rate (BMR) compared to a control group kept at 25 °C. Birds acclimated to 35 °C decreased their BMR, gross energy intake (GEI) and digestible energy intake (DEI). Furthermore, birds acclimated to 15 °C increased state-4 respiration in their pectoral muscles and cytochrome-c oxidase (COX) activity in their liver and pectoral muscle, compared to the 25 °C control group. Birds acclimated to 35 °C also displayed lower state-4 respiration and COX activity in the liver, heart and pectoral muscles, compared to those kept at 25 °C. There was a positive correlation between BMR and state-4 respiration, and between BMR and COX activity, in all of the above organs except the liver and heart.

Conclusions

Our study illustrates that the morphological, physiological, and enzymatic changes are associated with temperature acclimation in the Red-billed Leiothrix, and supports the notion that the primary means by which small birds meet the energetic challenges of cold conditions is through metabolic adjustments.
Noise reduction using a Bayesian penalized-likelihood reconstruction algorithm on a time-of-flight PET-CT scanner
Authors: Caribé Paulo R. R. V. , Koole M. , D’Asseler Yves , Van Den Broeck B. , Vandenberghe S.
Published: December 2019

Purpose

Q.Clear is a block sequential regularized expectation maximization (BSREM) penalized-likelihood reconstruction algorithm for PET. It tries to improve image quality by controlling noise amplification during image reconstruction. In this study, the noise properties of this BSREM were compared to the ordered-subset expectation maximization (OSEM) algorithm for both phantom and patient data acquired on a state-of-the-art PET/CT.

Methods

The NEMA IQ phantom and a whole-body patient study were acquired on a GE DMI 3-rings system in list mode and different datasets with varying noise levels were generated. Phantom data was evaluated using four different contrast ratios. These were reconstructed using BSREM with different β-factors of 300–3000 and with a clinical setting used for OSEM including point spread function (PSF) and time-of-flight (TOF) information. Contrast recovery (CR), background noise levels (coefficient of variation, COV), and contrast-to-noise ratio (CNR) were used to determine the performance in the phantom data. Findings based on the phantom data were compared with clinical data. For the patient study, the SUV ratio, metabolic active tumor volumes (MATVs), and the signal-to-noise ratio (SNR) were evaluated using the liver as the background region.

Results

Based on the phantom data for the same count statistics, BSREM resulted in higher CR and CNR and lower COV than OSEM. The CR of OSEM matches to the CR of BSREM with β = 750 at high count statistics for 8:1. A similar trend was observed for the ratios 6:1 and 4:1. A dependence on sphere size, counting statistics, and contrast ratio was confirmed by the CNR of the ratio 2:1. BSREM with β = 750 for 2.5 and 1.0 min acquisition has comparable COV to the 10 and 5.0 min acquisitions using OSEM. This resulted in a noise reduction by a factor of 2–4 when using BSREM instead of OSEM. For the patient data, a similar trend was observed, and SNR was reduced by at least a factor of 2 while preserving contrast.

Conclusion

The BSREM reconstruction algorithm allowed a noise reduction without a loss of contrast by a factor of 2–4 compared to OSEM reconstructions for all data evaluated. This reduction can be used to lower the injected dose or shorten the acquisition time.
Primary peritoneal carcinoma with late-phase pulmonary metastases: a case report
Authors: Ozeki Naoki , Hakiri Shuhei , Tateyama Hisashi , Yokoi Kohei , Chen-Yoshikawa Toyofumi
Published: December 2019

Background

Primary peritoneal carcinoma (PPC) is a very rare and aggressive type of malignancy with a poor prognosis.

Case presentation

A 66-year-old woman was referred to our hospital with two pulmonary nodules that developed after PPC resection and postoperative adjuvant chemotherapy administered 5 years earlier. Computed tomography revealed a 1.3-cm-sized nodule in the left lung with a small airspace in the posterior basal segment and a 0.9-cm-sized solid nodule in the apico-posterior segment that grew slightly within a 2-month period. 18F-Fluorodeoxyglucose-positron emission tomography of these lesions revealed respective maximum standardized uptake values of 7.11 and 2.46. Her serum cancer antigen-125 level remained within the normal range, despite elevation before the first surgery. The posterior basal segment and superior division were subjected to anatomical segmentectomy. An intraoperative frozen section examination could not distinguish metastatic PPC from primary lung cancer. Immunopathologically, the two nodules were identified as metastatic PPC.

Conclusions

Our findings suggest that PPC patients may develop late-phase thoracic recurrence that is difficult to diagnose clinically after initial treatment in a potentially resectable setting.
Prevalence of considering revision rhinoplasty in Saudi patients and its associated factors
Authors: Alsubeeh Najlaa Abdulrahman , AlSaqr Mayar Abdulsalam , Alkarzae Mohammed , Aldosari Badi
Published: December 2019

Background

Primary rhinoplasty outcomes may not meet individual expectations. Consequently, reoperation may be advocated to improve results. This study examines the prevalence of individuals considering revision rhinoplasty, while identifying the main cosmetic and functional complaints and factors associated.

Methodology

This is a cross-sectional study conducted in Saudi Arabia using a self-reported online questionnaire distributed through social media channels. The sample included 1370 participants who were all Saudi nationals over the age of 16 who had undergone primary rhinoplasty at least 1 year prior.

Results

The prevalence of individuals considering revision rhinoplasty was 44.7%. The primary reason for considering it was the desire for further esthetic improvement in an already acceptable result (50.16%). The most common cosmetic complaints subjectively reported were poorly defined nasal tip (32.35%). The most prevalent nasal function symptom was nasal obstruction (56.9%). Significant factors associated with considering revision rhinoplasty included the physician not understanding the patient’s complaints, short consultation time, low monthly income, inadequate information about the expected results, not using computer imaging to predict outcomes, lack of rapport with the surgeon, and inadequate information about the risks and complications.

Conclusions

A thorough understanding of patient concerns and expectations, as well as thoughtful consideration of risk factors, may help surgeons achieve more successful outcomes and potentially reduce the incidence of revision rhinoplasties.

Level of evidence

III
Changes in retinal and choriocapillaris density in diabetic patients receiving anti-vascular endothelial growth factor treatment using optical coherence tomography angiography
Authors: Conti Felipe F. , Song Weilin , Rodrigues Eduardo B. , Singh Rishi P.
Published: December 2019

Background

Optical coherence tomography angiography (OCTA) enables detailed, non-invasive assessment of ocular vasculature. This study uses OCTA imaging to evaluate choriocapillaris and retinal capillary perfusion density (CPD) changes in diabetic retinopathy following anti-vascular endothelial growth factor (VEGF) treatment.

Methods

Records of 38 eyes at a single institution were reviewed, grouped as non-diabetic controls (19 eyes), diabetes mellitus patients with diabetic retinopathy (DR, 19 eyes) and macular edema (DME). DR eyes were imaged at baseline, 6-months and 12-months after anti-VEGF treatment. Quantitative analyses assessed CPD of the choriocapillaris and retinal plexus.

Results

DR eyes showed decreased choriocapillaris whole-image CPD (62.6 ± 6.1 vs. 68.4 ± 5.1, p < 0.003), foveal CPD (61.2 ± 7.4 vs. 66.3 ± 9.8, p < 0.014), and parafoveal CPD (61.9 ± 6.6 vs. 68.2 ± 4.8, p < 0.002) at baseline. DR eyes also showed decreased retinal density, including whole-image CPD (46.9 ± 5.1 vs. 50.7 ± 5.6, p < 0.04), foveal CPD (27.6 ± 5.9 vs. 34.1 ± 6.1, p < 0.002), and parafoveal CPD (49.0 ± 5.6 vs. 53.1 ± 6.0, p < 0.011). Following 12 months of anti-VEGF treatment, no changes to retinal or choriocapillaris or CPD were observed. Retinal central subfield thickness decreased (397.1 ± 93.2 µm vs. 294.2 ± 71.5 µm, p < 0.005). Lastly, FAZ area (0.307 ± 0.133 mm2 vs. 0.184 ± 0.058 mm2, p = 0.008) and perimeter (2.415 ± 0.692 mm2 vs. 1.753 ± 0.408 mm2, p = 0.002) were increased in DR eyes at baseline. No changes to FAZ area or perimeter were seen with anti-VEGF treatment in DR eyes.

Conclusions

Compared to control, choriocapillaris and retinal CPD are reduced in DR, while FAZ area and perimeter are increased. No retinal capillary or choriocapillaris CPD changes were observed in DR eyes following anti-VEGF treatment.
Development of a novel PIG-A gene mutation assay based on a GPI-anchored fluorescent protein sensor
Authors: Tian Xu , Chen Youjun , Nakamura Jun
Published: December 2019

Background

Accumulation of somatic mutations caused by both endogenous and exogenous exposures is a high risk for human health, in particular, cancer. Efficient detection of somatic mutations is crucial for risk assessment of different types of exposures. Due to its requirement in the process of attaching glycosylphatidylinositol- (GPI-) anchored proteins to the cell surface, thePIG-Agene located on the X-chromosome is used in both in vivo and in vitro mutation assays. Loss-of-function mutations inPIG-Alead to the elimination of GPI-anchored proteins such that they can no longer be detected on the cell surface by antibodies. Historically, mutation assays based on thePIG-Agene rely on the staining of these cell-surface proteins by antibodies; however, as with any antibody-based assay, there are major limitations, especially in terms of variability and lack of specific antibodies.

Results

In the current study, we developed a modifiedPIG-Amutation assay that uses the expression of GPI-anchored fluorescent proteins (henceforth referred to as a GPI-sensor), whereby the presence of fluorescence on the cell membrane is dependent on the expression ofwild-type PIG-A. Using our modifiedPIG-Amutation assay, we have achieved complete separation ofwild typecells and spontaneously mutated cells, in which the presence ofPIG-Amutations has been confirmed via proaerolysin resistance and gene sequencing.

Conclusion

This study establishes a novelPIG-Amutation assay using GPI-anchored fluorescent protein expression that eliminates the need for antibody-based staining. This GPI-sensorPIG-Amutation assay should be widely applicable for accurate and efficient testing of genotoxicity for use in many mammalian and vertebrate cells.
Comparison of difficulty with activities of daily living in elderly adults undergoing hemodialysis and community-dwelling individuals: a cross-sectional study
Authors: Kutsuna Toshiki , Isobe Yusuke , Watanabe Takaaki , Matsunaga Yusuke , Kusaka Satomi , Kusumoto Yasuaki , Tsuchiya Junko , Umeda Masaru , Watanabe Hiroyuki , Shimizu Shinobu , Yoshida Atsushi , Matsunaga Atsuhiko
Published: December 2019

Background

Elderly adults undergoing hemodialysis (HD) have multiple comorbidities, physical frailty, and functional dependence with activities of daily living (ADL). ADL difficulty is an early predictor of ADL dependency in community-dwelling elderly adults. However, the characteristics of ADL difficulty in patients undergoing HD have not yet been reported. The present study aimed to examine the current status and characteristics of physical function and ADL difficulty in ambulatory elderly patients undergoing HD.

Methods

In all, 136 elderly outpatients undergoing HD and 40 community-dwelling controls participated in the present study. The characteristics, physical function (SARC-F score, grip strength, five-times sit-to-stand test time, usual gait speed, maximum gait speed, and short physical performance battery score), and scores from the ADL difficulty questionnaires [difficulty related to upper limb (U/L) and lower limb (L/L) functions] were compared between the HD and control groups. Multiple regression analysis was performed to examine whether the characteristics of physical function were able to discriminate ADL difficulty in the HD group.

Results

The HD group had a significantly greater SARC-F score, lower grip strength, longer five-times sit-to-stand test time, slower usual gait speed, slower maximum gait speed, lower short physical performance battery score, and lower U/L and L/L ADL difficulty scores compared to the control group (all P < 0.001). The distribution of U/L and L/L ADL difficulty scores showed a wider variation in the HD group than in the control group. The U/L ADL difficulty score was independently associated with the SARC-F score (β = −0.52, P < 0.001) and grip strength (β = 0.21, P = 0.02). The L/L ADL difficulty score was independently associated with the SARC-F score (β = −0.56, P < 0.001) and usual gait speed (β = 0.35, P < 0.001).

Conclusions

The elderly HD group had a poorer physical function and experienced stronger ADL difficulty than the control group. There was an association between ADL difficulty and sarcopenia or poor physical function among patients undergoing HD. These findings provide useful data for effective clinical management to prevent decline of ADL in ambulatory elderly patients undergoing HD.