bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between insulin resistance and left ventricular hypertrophy in asymptomatic Black sub-Saharan African hypertensive patients: A case-control study
Authors: PHANZU Bernard KIANU , Aliocha Nkodila Natuhoyila , Eleuthère Kintoki Vita , Jean-René M’Buyamba Kabangu , Benjamin Longo-Mbenza
Published: October 2020

Background: Conflicting information exists regarding the association between insulin resistance (IR) and left ventricular hypertrophy (LVH).

Here, we described the associations between parameters of obesity, fasting insulinaemia, homeostasis model assessment of insulin resistance (HOMA-IR) and LVH in Black patients with essential hypertension.

Methods: A case-control study was conducted at the Centre Médical de Kinshasa (CMK), the Democratic Republic of the Congo, between January and December 2019. Cases and controls were hypertensive patients with and without LVH, respectively. The relationships between obesity indices, physical inactivity, parameters of glucose metabolism and lipid disorders and LVH were assessed using linear and logistic regression analyses in simple and univariate exploratory analyses, respectively. When differences were observed between LVH and the independent variables, the effect of potential confounders was studied by adjustment in multiple linear regression and conditional logistic regression in multivariate analysis. The coefficients of determination (R2), the adjusted ORs and their 95% CIs were calculated to determine the association between LVH and the independent variables.

Results: Eighty-eight cases (52 men) were compared to 132 controls (81 men). Nineteen percent (19%) of left ventricular mass (LVM) variation was predicted by age; 31.3%, by the duration of hypertension; 44.4%, by body mass index (BMI); 42.5%, by waist circumference (WC); 20%, by glycaemia; 44.8%, by insulinaemia; and 43.7%, by HOMA-IR. In multiple linear regression analysis, duration of hypertension, BMI, insulinaemia and HOMA-IR explained 68.3% of the variability in the increase in LVM. In the logistic model, obesity multiplied the risk of LVH by 3 (aOR: 2.8, 95% CI (1.06-7.4), p = 0.038) and IR by 8 (aOR: 8.4, 95: (3.7-15.7), p <0.001).

Conclusions: Obesity and IR appear to be the main predictors of LVH in Black sub-Saharan African hypertensive patients. The comprehensive management of cardiovascular risk factors should be emphasized with particular attention to obesity and IR. A prospective Black sub-Saharan population-based study with serial imaging remains essential to better understand subclinical LV deterioration over time and to confirm the role of IR in Black sub-Saharan individuals with hypertension.
Just Say “No”: Can Dentists Refuse Care on the Basis of Finances? A Survey Using an Ethical Vignette in an Iranian Dental School
Authors: Kazemian Ali , Fayyazi Mahsa , Shafiee Shahrzad
Published: October 2020

Background: Decision making when patients ask a dentist for fee reduction is a real ethical dilemma at dental settings. The aim of this study was to evaluate how dental students and tutors think about their position for, or against fee reduction at dental offices. Method: It was a questionnaire-based survey, which examined the ethical attitudes of students and tutors of an Iranian Dental School. The questionnaire included a vignette about an ethical dilemma at a dental office. Different ethical approaches, i.e. duty-based, virtue-oriented and consequentialist arguments, for or against fee reduction at dental office were suggested. Respondents were asked to rank those ethical options. Data was entered and analyzed in SPSS 16.0.Result: 121 dental students and thirty-six faculty members (dental specialists) participated in this study. It revealed that a majority of dental students and tutors (68%) are in favor of charging patients less, when facing an imagined request at dental office, using either virtue-oriented (54%) or consequentialist (14%) argument for fee reduction. The difference between rankings of four options was statistically significant, while no statistically significant difference exists neither between male and female respondents, nor students and tutors. Conclusion: This case study provides a basis for fruitful discussions in ethics courses for dental students. Our study suggests that financial issues should be considered as a part of ethical training within the dental student's curriculum.
In Utero and Peripubertal Metals Exposure in Relation to Reproductive Hormones and Sexual Maturation and Progression among Boys in Mexico City
Authors: Ashrap Pahriya , Meeker John D. , Sánchez Brisa N. , Basu Niladri , Tamayo-Ortiz Marcela , Solano-González Maritsa ,   Adriana Mercado-García4, Téllez-Rojo Martha M. , Peterson Karen E. , Watkins Deborah
Published: October 2020

Background: Endocrine disrupting chemicals (EDCs) such as metals have been reported to alter circulating reproductive hormone concentrations and pubertal development in animals. However, the relationship has rarely been investigated among humans, with the exception of heavy metals, such as Pb and Cd. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone concentrations and sexual maturation and progression among boys from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts.Methods: Our analysis included 118 pregnant women and their male children from the ELEMENT study. Essential and non-essential metals were measured in urine collected from the mothers during the third trimester of pregnancy and their male children at 8-14 years. Reproductive hormone concentrations [serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG)] were measured in blood samples from the children at 8-14 years. We also assessed Tanner stages for sexual maturation (genital, pubic hair development, and testicular volume), at two time points (8–14, 10-18 years). We used linear regression to independently examine urinary metal concentrations in relation to each peripubertal reproductive hormones adjusting for child age and BMI. Generalized estimation equations (GEEs) were used to evaluate the association of in utero and peripubertal metal exposures with sexual maturation and progression during follow-up based on Tanner staging and testicular volume.Results: In utero and prepubertal concentrations of some urinary metals were associated with increased concentrations of peripubertal reproductive hormones, especially non-essential metal(loid)s As and Cd (in utero), and Ba (peripubertal) as well as essential metal Mo (in utero) in association with testosterone. More advanced pubic hair developmental stage and higher testicular volume at the early teen visit was observed for boys with higher non-essential metal concentrations, including in utero Al and peripubertal Ba, and essential metal Zn concentration (peripubertal). These metals were also associated with slower pubertal progression between the two visits.Conclusion: These findings suggest that male reproductive development may be associated with both essential and non-essential metal exposure during in utero and peripubertal windows.
Eye movement biomarkers allow for the definition of phenotypes in Gaucher Disease
Authors: Donald Aimee , Tan Chong Yew , Chakrapani Anupam , Hughes Derralyn , Sharma Reena , Cole Duncan , Bardins Stanislav , Gorges Martin , Jones Simon Allan , Schneider Erich
Published: October 2020

Background

Neurological forms of Gaucher disease, the inherited disorder of β-Glucosylceramidase caused by bi-allelic variants in GBA1, is a progressive disorder which lacks a disease-modifying therapy. Systemic manifestations of disease are effectively treated with Enzyme Replacement Therapy (ERT), however, molecules which cross the blood-brain barrier are still under investigation. Clinical trials of such therapeutics require robust, reproducible clinical endpoints to demonstrate efficacy and clear phenotypic definitions to identify suitable patients for inclusion in trials.

The single consistent clinical feature in all patients with neuronopathic disease is the presence of a supranuclear saccadic gaze palsy, in the presence of Gaucher disease this finding serves as diagnostic of ‘type 3’ Gaucher disease.

Methods

We undertook a study to evaluate saccadic eye movements in Gaucher patients and to assess the role of the EyeSeeCam in measuring saccades. The EyeSeeCam is a video oculography device which was used to run a protocol of saccade measures. We studied 39 patients with non-neurological Gaucher disease (type 1), 21 patients with type 3 (neurological) disease and a series of 35 healthy controls. Mean saccade parameters were compared across disease subgroups.

Results

We confirmed the saccadic abnormality in patients with type 3 Gaucher disease and identified an unexpected subgroup of patients with type 1 Gaucher disease who demonstrated significant saccade parameter abnormalities. These patients also showed subtle neurological findings and shared a GBA1 variant.

Conclusions

This striking novel finding of a potentially attenuated type 3 Gaucher phenotype associated with a specific GBA1 variant and detectable saccadic abnormality prompts review of current disease classification. Further, this finding highlights the broad spectrum of neuronopathic Gaucher phenotypes relevant when designing inclusion criteria for clinical trials.
LncRNA LEF1-AS1 promotes metastasis of prostatic carcinoma via the Wnt/β-catenin pathway
Authors: Li Weiyuan , Yang Ganggang , Yang Dengke , Li Dong , Sun Qian
Published: October 2020

Background: Long noncoding RNAs (lncRNAs) are important functional regulators of many biological processes of cancers. However, the mechanisms by which lncRNAs modulate androgen-independent prostate cancer (AIPC) development remain largely unknown.Methods: Next-generation sequencing technology and RT-qPCR were used to assess LEF1-AS1 expression level in AIPC tissues and adjacent normal tissues. Functional in vitro experiments, including colony formation, EDU and transwell assays were performed to assess the role of LEF1-AS1 in AIPC. Xenograft assays were conducted to assess the effect of LEF1-AS1 on cell proliferation in vivo. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) assays were performed to elucidate the regulatory network of LEF1-AS1.Results: The next-generation sequencing results showed that LEF1-AS1 is significantly overexpressed in AIPC. Furthermore, our RT-qPCR assay data showed that LEF1-AS1 is overexpressed in AIPC tissues. Functional experiments showed that LEF1-AS1 promotes the proliferation, migration, invasion and angiogenic ability of AIPC cells in vitro and tumour growth in vivo by recruiting the transcription factor C-myb to the promoter of FZD2, inducing its transcription. Furthermore, LEF1-AS1 was shown to function as a competing endogenous RNA (ceRNA) that sponges miR-328 to activate CD44.Conclusion: In summary, the results of our present study revealed that LEF1-AS1 acts as a tumour promoter in the progression of AIPC. Furthermore, the results revealed that LEF1-AS1 functions as a ceRNA and regulates Wnt/β-catenin pathway activity via FZD2 and CD44. Our results provide new insights into the mechanism that links the function of LEF1-AS1 with AIPC and suggests that LEF1-AS1 may serve as a novel potential target for the improvement of AIPC therapy.
The prognostic role of plasma fibrinogen in adult secondary hemophagocytic lymphohistiocytosis
Authors: Yin Guangli , Man Changfeng , Huang Jiayu , Liao Shengen , Gao Xin , Tian Tian , Duan Limin , Xu Ji , Qiu Hon'gxia
Published: October 2020

Background In adult patients with secondary hemophagocytic lymphohistiocytosis (sHLH), no valid immune biomarker has been available for predicting the prognosis of untreated sHLH patients. Methods: Circulating plasma levels of fibrinogen (FIB) were measured at diagnosis in 293 cases of adult sHLH. We categorized FIB levels into tertiles. Multivariable Cox proportional hazards models were used to evaluate the relationship between FIB and survival. Restricted cubic spline models and two-piecewise Cox proportional hazards models were used to address the nonlinear association between FIB and mortality. Results: During a median follow-up of 52 (interquartile ranges, 18-221) days, 208 deaths occurred, with 137 deaths in malignancy-associated hemophagocytic lymphohistiocytosis (MHLH) and 71 deaths in non-malignancy-associated hemophagocytic lymphohistiocytosis (non-MHLH). After multivariable adjustment, compared with the highest tertile of FIB, the hazard ratios (HRs) with 95% confidence intervals (CIs) of survival for tertile 2 and tertile 1 were 1.06 (0.90-1.24) and 0.84 (0.71-0.98), respectively. The restricted cubic spline curve displayed a nonlinear and inverse relationship between FIB and mortality. Furthermore, the threshold effect analysis demonstrated that the inflection point for the curve was at an FIB level of 1.76 g/L. The HRs (95% CIs) for survival were 0.68 (0.55-0.83) and 1.08 (0.96-1.21) on the left and right side of the inflection point, respectively. Conclusions: These results suggest that plasma fibrinogen is nonlinearly and inversely associated with the risk of mortality in adult secondary hemophagocytic lymphohistiocytosis.
Dissecting the Roles of Kalirin-7/PSD-95/GluN2B Interactions in Different Forms of Synaptic Plasticity
Authors: Yeh Mason L. , Yasko Jessica R , Levine Eric S. , Eipper Betty A. , Mains Richard
Published: October 2020

Background: Kalirin-7 (Kal7) is a multidomain scaffold and guanine nucleotide exchange factor localized to the postsynaptic density, where Kal7 is crucial for synaptic plasticity. Kal7 knockout mice exhibit marked suppression of long-term potentiation and long-term depression in hippocampus, cerebral cortex and spinal cord, with depressed surface expression of GluN2B receptor subunits and dramatically blunted perception of pain. Kal7 knockout animals show exaggerated locomotor responses to psychostimulants and self-administer cocaine more enthusiastically than wildtype mice. Results: To explore the underlying cellular and molecular mechanisms which are deranged by loss of Kal7, we infused candidate intracellular interfering peptides to acutely challenge the synaptic function(s) of Kal7 with potential protein binding partners, to determine if plasticity deficits in Kal7-/- mice are the product of developmental processes since conception, or could be produced on a much shorter time scale. We demonstrated that these small intracellular peptides disrupted normal long-term potentiation and long-term depression, strongly suggesting that maintenance of established interactions of Kal7 with PSD-95 and/or GluN2B is crucial to synaptic plasticity. Conclusions: Blockade of the Kal7-GluN2B interaction was most effective at blocking long-term potentiation, but had no effect on long-term depression. Biochemical approaches indicated that Kal7 interacted with PSD-95 at multiple sites within Kal7.
Gender differences in externalizing and internalizing problems in Singaporean children and adolescents with attention-deficit/ hyperactivity disorder
Authors: Lau Tsz Wing Ivy , Lim Choon Guan , Acharryya Sanchalika , Lim-Ashworth Nikki , Tan Yi Ren , Fung Daniel
Published: October 2020

Background: Studies on gender differences in attention-deficit/ hyperactivity disorder (ADHD) comorbidities in the Asian populations have been limited and previous studies have shown inconclusive findings. Singapore is a city-state country in Southeast Asia with a population of 5.7 million. This study examined gender differences in internalizing and externalizing problems in Singaporean children and adolescents with ADHD. The plausible social factors underlying the gender differences were discussed.Methods: A total of 773 participants (aged 6 to 18, 88% males) newly diagnosed with ADHD were recruited from the largest public child and adolescent psychiatric center in Singapore. Their internalizing and externalizing problems were assessed using the Child Behavioral Checklist and Teacher’s Report Form by parents and teachers respectively. Demographics and relevant social factors were collected using parent questionnaires.Results: Females with ADHD were reported to have less delinquent and aggressive behavior but more depressive symptoms than their male counterparts, similar to findings in the Western literature. Older age, lower socioeconomic status and parental use of physical punishment were associated with higher internalizing and externalizing problems after controlling for other factors.Conclusions: Gender differences in ADHD comorbidities do exist in the Asian clinical population. The lack of externalizing symptoms in females with ADHD has made timely referral and diagnosis challenging. More research is needed in understanding the gender differences in ADHD and the biopsychosocial mechanism underlying the differences in order to improve the detection of ADHD in females.
Investigation of the piroplasm diversity circulating in wildlife and cattle of the greater Kafue ecosystem, Zambia
Authors: Squarre David , Nakamura Yukiko , Hayashida Kyoko , Kawai Naoko , Chambaro Herman , Namangala Boniface , Sugimoto Chihiro , Yamagishi Junya
Published: October 2020

Background: Piroplasms are vector-borne intracellular hemoprotozoan parasites that infect wildlife and livestock. Wildlife species are reservoir hosts to a diversity of piroplasms and play an important role in the circulation, maintenance and evolution of these parasites. The potential for likely spillover of both pathogenic and non-pathogenic piroplasm parasites from wildlife to livestock is underlined when common ecological niche is shared in the presence of a competent vector. Method: To investigate piroplasm diversity in wildlife and cattle population of the greater Kafue ecosystem, we utilized PCR to amplify the 18S rRNA V4 hyper-variable region and meta-barcoding strategy using illumina MiSeq sequencing platform and amplicon sequence variant (ASV) based bioinformatics pipeline to generate high resolution data which discriminate sequences down to a single nucleotide difference. Results: A parasite community of 45 ASVs corresponding to 23 species consisting of 4 genera of Babesia, Theileria, Hepatozoon and Colpodella, were identified in wildlife and cattle population from the study area. Theileria species were detected in buffalo, impala, hartebeest, sable antelope, sitatunga, wild dog and cattle. In contrast, Babesia species were only observed in cattle and wild dog. Our results demonstrate possible spillover of these hemoprotozoan parasites from wildlife, especially buffalo, to cattle population in the wildlife-livestock interface.Conclusion: We demonstrated that the deep amplicon sequencing of the 18S rRNA V4 hyper-variable region for wildlife was informative. Our results illustrated the diversity of piroplasma and the specificity of their hosts. They led us to speculate possible ecological cycle including transmission from wildlife to domestic animals in the greater Kafue ecosystem. Thus, this approach may contribute to the establishment of appropriate disease control strategies in wildlife-livestock interface areas.
Analyzing brain structural differences among undergraduates with different grades of self-esteem using multiple anatomical brain network
Authors: Peng Bo , Pang Gaofeng , Saxena Aditya , Liu Yan , Hu Baohua , Wang Suhong , Dai Yakang
Published: October 2020

Background: Self-esteem is the individual evaluation of oneself. People with high self-esteem grade have mental health and can bravely cope with the threats from the environment. With the development of neuroimaging techniques, researches on the cognitive neural mechanisms of self-esteem are increased. Existing methods based on brain morphometry and single-layer brain network cannot characterize the subtle structural differences related to self-esteem. Method: To solve this issue, we proposed multiple anatomical brain network framework based on multi-resolution ROI template to study the cognitive neuroscience mechanism of self-esteem. Multiple anatomical brain network consist of ROI features and hierarchal brain network features extracted from structural MRI. For each layer, we calculated the correlation relationship between pairs of ROIs. In order to solve the high-dimensional problem caused by the large amount of network features, hybrid feature selection methods are adopted to reduce the number of features while retaining discriminative information to the maximum extent. Multi-kernel SVM is employed to integrate the various types of features by appropriate weight coefficient.Result: The experimental results show that the proposed method can improve classification accuracy to 97.26% compared with single-layer brain network. Conclusions: The proposed method provides a new perspective for the analysis of brain structure differences of self-esteem, which also has potential guiding significance in other researches involved brain cognitive activity and brain disease diagnosis.
A primer in resilience status for German medical graduates - a necessary step in building an emotionally equipped healthcare workforce
Authors: Kiesewetter Jan , Huber Johanna
Published: October 2020

BackgroundResilience is a widely-used catchword in the last couple of years to describe the resistance to psychological strains of life, especially for the healthcare work force. The promises of resilience to burnout sound great and what we all would want: less health impairment despite stress, higher work satisfaction and last but not least higher work performance. However, little is known scientifically regarding the resilience status of the upcoming work-force. With our study we would like to investigate the resilience status of medical graduates from five medical schools within their first year after graduation. MethodsFor the identification of the resilience status we included the 5-point Likert 10-Item Connor-Davidson Resilience Scale, German Version in a graduate survey posted to 5 medical schools and over 1610 eligible participants of whom 610 (60% female) filled out at least parts of the survey. ResultsThe resilience status showed a mean resilience score of M = 37.1 (SD = 6.30). The score ranges from 3.22 (I am not easily discouraged by failure) to 4.26 (I am able to adapt to change). The item “I am able to handle unpleasant feeling” is interesting as one third of the participants did choose not to answer. Relationships to other constructs are presented in the article. ConclusionsThe study shows that the overall resilience status of medical graduates one year after their graduation is rather high, but subjectively they do not feel equivalently resilient for the different aspects they face in their job. Further research needs to see how trainings can provide medical students and professionals with the emotional coping skills that they lack in the moment.
Manufacturing and Banking Canine Adipose-Derived Mesenchymal Stem Cells for Veterinary Clinical Application
Authors: Luo Huina , Li Dongsheng , Chen Zhisheng , Wang Bingyun , Chen Shengfeng
Published: October 2020

BACKGROUND: Mesenchymal stem cells (MSCs) have generated a great amount of interest in recent years as a novel therapeutic application for improving the quality of pet life and helping them free from painful conditions and diseases. It has now become critical to address the challenges related to the safety and efficacy of MSCs expanded in vitro. In this study, we establish a standardized process for manufacture of canine adipose-derived MSCs (AD-MSCs), including tissue sourcing, cell isolation and culture, cryopreservation, thawing and expansion, quality control and testing, and evaluate the safety and efficacy of those cells for clinical applications. RESULTS: After expansion, the viability of AD-MSCs manufactured under our standardized process was above 90 %. Expression of surface markers and differentiation potential was consistent with ISCT standards. Sterility, mycoplasma, and endotoxin tests were consistently negative. No adverse events were noted in two cases treated with intravenously AD-MSCs. CONCLUSION: Herein we demonstrated the establishment of a feasible bioprocess for manufacturing and banking canine AD-MSCs for veterinary clinical use.
Gene expression profiling of orbital muscles in treatment-resistant ophthalmoplegic myasthenia gravis.
Authors: Europa Tarin A , Nel Melissa , Heckmann Jeannine M
Published: October 2020

Background: Unbiased in silico approaches applied to genome-wide data prioritized putative functional gene variants associating with treatment-resistant ophthalmoplegic myasthenia gravis (OP-MG). Although altered expression of genes harbouring these variants, or associated pathways, were shown in patient-derived transdifferentiated-myocyte models, gene expression in orbital-derived muscle was required to test the validity of the predictions. Methods: We sampled orbicularis oculi muscle (OOM) and one paralysed extraocular muscle (EOM) from six individuals with OP-MG during blepharoptosis and re-alignment surgeries, respectively. For controls, the OOMs were sampled from four individuals without myasthenia undergoing surgery for non-muscle causes of ptosis, and one non-paralysed EOM. Using a qPCR array, expression of 120 genes was compared between OP-MG and control OOMs, profiling putative “OP-MG” genes, genes in related biological pathways and genes reported to be dysregulated in MG cases or experimental MG models, and in EOMs of cases with strabismus. Normalization was performed with two stable reference genes. Differential gene expression was compared between OP-MG and control samples using the ΔΔCT method. Co-expression was analysed by pairwise correlation of gene transcripts to infer expression networks. Results: Overall, transcript levels were similar in OOMs and EOMs (p=0.72). In OOMs, significant downregulated expression of eight genes was observed in OP-MG cases compared with controls (>2-fold; p≤0.016), including TFAM, a mitochondrial transcription factor, and genes related to the following pathways: atrophy signalling; muscle regeneration and contraction; glycogen synthesis; and extracellular matrix remodelling. Several microRNAs, known to be highly expressed in EOMs, are predicted to regulate some of these genes. Co-expression analyses of gene-pairs suggested high interconnectedness of gene expression networks in OP-MG muscle, but not controls (r>0.96, p<0.01). Significant inverse directions of gene-pair correlations were noted in OP-MG vs controls OOM networks (r≥0.92, p<0.001) involving most OP-MG genes overlapping prominently with muscle atrophy/contractility and oxidative metabolism genes. Conclusions: The gene expression in orbital muscles derived from OP-MG individuals compared with normal controls, support the pathogenic hypothesis previously generated from whole genome sequence analyses. Repression of gene transcripts in OP-MG orbital muscle implicate tissue-specific regulatory mechanisms, which may inform future biomarker discovery approaches.
Thermally responsive poly(ethylene oxide)-based polyrotaxanes bearing hydrogen-bonding pillar [5] arene rings
Authors: Kato Kenichi , Onishi Katsuto , Maeda Koki , Yagyu Masafumi , Fa Shixin , Ichikawa Takahiro , Mizuno Motohiro , Kakuta Takahiro , Yamagishi Tada-aki , Ogoshi Tomoki
Published: October 2020

Poly(ethylene oxide)s (PEOs) are useful polymers with good water solubility, biological compatibility, and commercial availability. In this study, PEOs with various end groups were threaded into pillar[5]arene rings in a mixture of water and methanol to afford pseudopolyrotaxanes. Multiple hydrogen bonds between the pillar[5]arene rings and hydrophobic–hydrophilic interactions between the ethylene groups of the PEOs and the hydrophobic pillar[5]arenes are the driving forces to form the pseudopolyrotaxane structure. Corresponding polyrotaxanes were also constructed by capping COOH-terminated pseudopolyrotaxanes with bulky amines, in which multiple hydrogen bonds involving the pillar[5]arene OH groups were critically important to prevent de-threading. The number of threaded ring components could be rationally controlled in these materials, providing a simple and versatile method to tune the mechanical and thermal properties. Specifically, a polyrotaxane with a high-molecular-weight axle became elastic upon heating above the melting point of PEOs and exhibited temperature-dependent shape memory property, because of the topological confinement and cross-linking by hydrogen bonds.
Future river-flood damage increases under aggressive adaptations
Authors: Tanoue Masahiro , Taguchi Ryo , Alifu Haireti , Hirabayashi Yukiko
Published: October 2020

The risk of river flooding is expected to rise with climate change and socioeconomic development1-6, and therefore additional protection measures are required to reduce increased flood damage. Previous studies have investigated the effectiveness of adaptation measures to reduce flood risks7,8; however, there has been no evaluation of residual flood damage (RFD), which reflects the unavoidable increase in damage even under an aggressive adaptation strategy. Here, we evaluated RFD under several adaptation objectives. We found that China, India, Russia and countries in central Africa and Latin America can achieve a higher level of flood protection that will reduce RFD even under extreme scenarios. However, high RFD exceeding 0.1% of GDP remains, especially in eastern China, northern India, eastern Europe and central Africa. The high RFD are inevitable assuming the average construction period required for hard infrastructure (30 years), implying the need for immediate adaptation measures as well as soft adaptation.
Functional analysis of a monoclonal antibody reactive against anti-cluster A epitope obtained from a patient infected with HIV-1 CRF02_AG
Authors: Za Hasan Md , Kuwata Takeo , Takahama Shokichi , Yu Kaku , Biswas Shaswata , Matsumoto Kaho , Tamamura Hirokazu , Matsushita Shuzo
Published: October 2020

Background: Recent data suggest the importance of non-neutralizing antibodies (nnAbs) in the development of vaccines against HIV-1 because two types of nnAbs that recognize the coreceptor binding site (CoRBS) and inner domain cluster A mediate antibody-dependent cellular-cytotoxicity (ADCC) against HIV-1-infected cells. However, many studies have been conducted with nnAbs obtained from subtype B-infected individuals, with few studies in patients with non-subtype B infections. Results: We isolated a monoclonal antibody 1E5 from a CRF02_AG-infected individual and constructed two forms of antibody with constant regions of IgG1 or IgG3. The epitope of 1E5 belongs to cluster A, which consists of C1 and C2 of gp120, and 1E5 binds to 27 out of 35 strains (77%) across the subtypes. The 1E5 showed strong ADCC activity, especially in the form of IgG3 in the presence of small CD4-mimetic compounds (CD4mc) and anti-CoRBS antibody, but did not show any neutralizing activity even against the isolates with strong binding activities. The enhancement in the binding of A32, anti-cluster A antibody isolated from a patient with subtype B infection, was observed in the presence of 1E5 and the combination of both anti-cluster A antibodies enhanced ADCC activity. Conclusions: These results suggest that anti-cluster A antibodies that are induced in patients with different HIV-1 subtype infections have common functional modality and may have unexpected interactions. These data may have implications for vaccine development against HIV-1.
Universal scaling laws of keyhole stability and porosity in 3D printing of metals
Authors: Gan Zhengtao , Kafka Orion , Parab Niranjan , Zhao Cang , Fang Lichao , Heinonen Olle , Sun Tao , Liu Wing Kam
Published: October 2020

We leverage ultrahigh-speed synchrotron x-ray imaging and high-fidelity multiphysics modeling to identify strikingly simple yet universal scaling laws for keyhole stability and porosity in metal three-dimensional (3D) printing. The laws apply broadly and remain accurate for different materials, processing conditions, and printing machines. We define a new dimensionless number, the Keyhole number, to predict aspect ratio of a keyhole and the morphological transition from stable at low Keyhole number to chaotic at high Keyhole number. Furthermore, we discover inherent correlation between keyhole stability and porosity formation in metal 3D printing. By reducing the dimensions of the formulation of these challenging problems, the compact scaling laws will aid process optimization and defect elimination during metal 3D printing, and potentially lead to a quantitative predictive framework.
Differences in Assistive Technology Installed for People With Dementia Living at Home Who Have Wandering and Safety Risks
Authors: Curnow Eleanor , Rush Robert , Gorska Sylwia , Forsyth Kirsty
Published: October 2020

Background: Assistive Technology for people with dementia living at home is not meeting their care needs. Reasons for this may be due to limited understanding of variation in multiple characteristics of people with dementia including their safety and wandering risks, and how these affect their assistive technology requirements. To explore the possibility of grouping people with dementia according to data describing multiple person characteristics. Then to investigate the relationships between these groupings and installed Assistive Technology interventions.Methods: Partitioning Around Medoids cluster analysis was used to determine participant groupings based upon secondary data which described the person characteristics of 451 people with dementia with Assistive Technology needs. Relationships between installed Assistive Technology and participant groupings were then examined.Results: Two robust clustering solutions were identified within the person characteristics data. Relationships between the clustering solutions and installed Assistive Technology data indicate the utility of this method for exploring the impact of multiple characteristics on Assistive technology installations. Living situation and caregiver support influence installation of assistive technology more strongly than level of risk or cognitive impairment. People with dementia living alone received different AT from those living with others.Conclusions: Results suggest that caregiver support and the living situation of the person with dementia influence the type and frequency of installed Assistive Technology. Reasons for this include the needs of the caregiver themselves, the caregiver view of the participants’ needs, caregiver response to alerts, and the caregiver contribution to the assistive technology assessment and selection process. Selection processes should be refined to account for the needs and views of both caregivers and people with dementia. This will require additional assessor training, and the development of validated assessments for people with dementia who have additional impairments. Policies should support the development of services which provide a wider range of AT to facilitate interventions which are focused on the needs of the person with dementia.
Comprehensive genomic resources related to domestication and crop improvement traits in Lima bean
Authors: Garcia Tatiana , Duitama Jorge , Zullo Stephanie , Gil Juanita , Ariani Andrea , Dohle Sarah , Palkovic Antonia , Skeen Paola , Bermudez-Santana Clara , Debouck Daniel , Castillo Jaime Martinez , Gepts Paul , Chacón-Sánchez Maria
Published: October 2020

Lima bean (Phaseolus lunatus L.) is one of the five domesticated Phaseolus bean crops, which are essential sources of dietary proteins for human consumption. Compared to common bean (P. vulgaris), it shows a wider range of ecological adaptations along its distribution range from Mexico to Argentina. These adaptations and its phenotypic plasticity make Lima bean a promising crop for improving food security under predicted scenarios of climate change in Latin America and elsewhere. Lima bean is also an excellent model to study convergent evolution of the adaptive domestication syndrome due to its dual domestication in Mesoamerica and the Andes. Combining long and short read sequencing technologies with a dense genetic map from a biparental population, we obtained the first chromosome-level genome assembly for Lima bean. Annotation of 28,326 gene models showed high diversity among 1,917 genes with conserved domains related to disease resistance. Structural comparison across 21,180 orthologs with common bean revealed high genome synteny and two large intrachromosomal rearrangements. Speciation between P. lunatus and P. vulgaris occurred about six million years ago according to nucleotide evolution between these orthologs. Population genomic analysis of GBS data for 482 wild and domesticated accessions from the Mesoamerican and Andean gene pools provided novel evidence on population structure at a finer geographical scale. Results show that wild Lima bean is organized into six clusters with mostly non-overlapping distributions and that Mesomerican landraces can be further subdivided into three subclusters. A new wild cluster of diversity was found in the Colombian Andes and a separate genetic cluster was observed for Mesoamerican landraces of the Peninsula of Yucatan in Mexico. This study also documents genome wide patterns of selection and haplotype introgression events among gene pools. Analysis of RNA-seq data obtained from wild and domesticated accessions at two different pod developmental stages revealed 4,275 differentially expressed genes, which could be related to pod dehiscence and seed development. We expect that the present resources serve as a solid basis to achieve a comprehensive view of the degree of convergent evolution of Phaseolus species under domestication and provide new tools and information for breeding for climate change resiliency of different domesticated species.
Extracellular Superoxide Dismutase (EC-SOD) Regulates Gene Methylation and Cardiac Fibrosis During Chronic Hypoxic Stress
Authors: Rajgarhia Ayan , Ayyasola Kameshwar , Zaghloul Nahla , Re Jorge M. Lopez Da , Miller Edmund J. , Ahmed Mohamed
Published: October 2020

Background: Chronic hypoxic stress induces epigenetic modifications mainly DNA methylation in cardiac fibroblasts, inactivating tumor suppressor genes (RASSF1A), and activating kinases (ERK1/2) leading to fibroblast proliferation and cardiac fibrosis. The Ras/ERK signaling pathway is an intracellular signal transduction critically involved in fibroblast proliferation. RASSF1A functions through its effect on downstream ERK1/2. The antioxidant enzyme, extracellular superoxide dismutase (EC-SOD), decreases oxidative stress from chronic hypoxia but it’s effects on these epigenetic changes has not been fully explored. Objectives: In-vitro model: Wild type C57B6 male mice (WT) and transgenic males with an extra copy of human hEC-SOD (TG) were housed in hypoxia (10% O2) for 21 days. Right ventricular tissue was studied for cardiac fibrosis markers using RT-PCR and Western Blot analyses. in-vitro model, downstream effects of RASSF-1 expression and methylation and its relation to ERK1/2, were studied using primary C57BL6 mouse cardiac fibroblast tissue culture.Results: There were significant increases in markers of cardiac fibrosis : Collagen 1, Alpha Smooth Muscle Actin (ASMA) and SNAIL, in the WT hypoxic animals as compared to the TG hypoxic group (p< 0.05). Expression of DNA methylation enzymes (DNMT 1,2) was significantly increased in the WT hypoxic mice as compared to the hypoxic TG mice (p<0.001). RASSF1A expression was significantly lower and ERK1/2 was significantly higher in hypoxia WT compared to the hypoxic TG group (p<0.05). Use of SiRNA to block RASSF1A gene expression in murine cardiac fibroblast tissue culture led to increased fibroblast proliferation (p<0.05). Methylation of RASSF1A promoter region was significantly reduced in the TG hypoxic group compared to the WT hypoxic group (0.59 vs 0.75 respectively). Conclusions: EC-SOD significantly attenuates RASSF1A gene methylation and can alleviate cardiac fibrosis induced by hypoxia.
Silencing Smad7 Potentiates BMP2-induced Chondrogenic Differentiation and Inhibits Endochondral Ossification in Human Synovial Derived Mesenchymal Stem Cells
Authors: xiao pengcheng , Zhu Zhenglin , Du Chengcheng , Zeng Yongsheng , Liao junyi , Cheng Qiang , Chen Hong , Zhao Chen , Huang Wei
Published: October 2020

Background: Cartilage injuries pose formidable challenges for effective clinical management. Autologous stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage injuries. Bone morphogenetic protein 2 (BMP2) is a promising chondrogenic growth factors for transgene-enhanced cartilage tissue engineering. However the BMP2 is failed to maintain a stable chondrogenic phenotype as it also induces robust endochondral ossification. Recently, human synovial derived mesenchymal stem cells (hSMSCs) arouse interested through the poor differentiation potential into osteogenic lineage. Smad7, a protein to antagonizes TGF-β/BMP signaling pathway has been discovered significant in the endochondral ossification. In the present study ,we further explore the effect of downregulate Smad7 in BMP2-induced chondrogenic differentiation of hSMSCs. Methods: hSMSCs were isolated from synovium of human knee joint through adhesion growth. In vitro and in vivo chondrogenic differentiation models of hSMSCs were constructed . Transgenes of BMP2, silencing Smad7 and Smad7 were expressed by adenoviral vectors. The osteogenic differentiation was detected by alkaline phosphatase staining, alizarin red staining. The chondrogenic differentiation was detected by alcian blue staining. Gene expression was determined by reverse transcription and quantitative real-time PCR (RT-qPCR), Immunofluorescence and immunohistochemistry. The subcutaneous stem cell implantation model was established and evaluated by micro-CT , h＆e staining, alcian blue staining and immunohistochemistry assay.Results: Compared to other MSCs, hSMSCs performed less of capability to osteogenic differentiation. But the occurrence of endochondral ossification is still inevasible during BMP2 induced cartilage formation. We found that silencing Smad7 enhanced the BMP2-induced chondrogenic differentiation of hSMSCs in vitro. Also, it leading to much less of hypertrophic differentiation. The subcutaneous stem cells implantation assays demonstrated silencing Smad7 potentiates BMP2-induced cartilage formation and inhibits endochondral ossification. Conclusion: This study strongly suggests that application of hSMSCs , cell scaffolds and silencing Smad7 can potentiate BMP2-induced chondrogenic differentiation and inhibit endochondral ossification. Thus, inhibit the expression of Smad7 in BMP2-induced hSMSCs differentiation may be a new strategy for cartilage tissue engineering.
CT Metal Artifact Reduction based on Virtual Generated Artifacts Using Modified pix2pix
Authors: Kai Xie , Liugang Gao , Zhengda Lu , Chunying Li , Tao Lin , Jianfeng Sui , Hui Bi , Xinye Ni , Jianrong Dai
Published: October 2020

Background: Metal artifacts introduce challenges in image-guided diagnosis or accurate dose calculations. This study aims to reduce metal artifacts from the spinal brace by using virtual generated artifacts through convolutional neural networks and to compare the performance of this approach with two other methods, namely, linear interpolation metal artifact reduction (LIMAR) and normalized metal artifact reduction (NMAR) .Method: A total of 3,600-slice CT images of 60 vertebral metastases patients were selected. The spinal cord center was marked in each image, metal masks were added to two sides of the marker to generate artifact-insert CT images, and the CT values of the metal parts were copied to original CT images to obtain reference CT images. These images were divided into training (3,000 slices) and test (600) sets. The modified U-Net and pix2pix architecture was applied to understand the relationship between the reference and artifact-insert images. The mean absolute error (MAE), mean square error (MSE), peak signal-to-noise ratio (PSNR), and structural similarity (SSIM) were calculated between the reference CT images and the predicted CT through LIMAR, NMAR, U-Net, and pix2pix. The CT values of organs from different images were compared. Radiotherapy treatment plans for vertebral metastases were designed, and dose calculation was performed. The dose distribution in different types of images was also compared.Results: The MAE values between the reference images and those images generated by LIMAR, NMAR, U-Net, and pix2pix were 15.02, 16.16, 6.12, and 6.48 HU, respectively, and the corresponding PSNR values were 15.37, 152.70, 158.93, and 65.14 dB, respectively. Pix2pix restored more texture than U-Net according to the visual comparison. The average CT values in the artifact-insert images of the liver, spleen, and left and right kidneys were all significantly higher than those of the reference images (p<0.05). The average CT values of the organs in images processed by the four methods showed no significant differences from those of the organs in the reference images. The mean dose of planned target volume in the artifact-insert images was significantly lower than that in the reference CT images. The average γ passing rate (1%, 1 mm) of the artifact-insert images was significantly lower than that of the reference images (95.9±1.4% vs. 99.2±1.4%, p<0.05).Conclusions: U-Net and pix2pix deep learning networks can remarkably reduce metal artifacts and improve critical structure visualization compared with LIMAR and NMAR according to the simulation data of artifact-insert images in the spinal brace. Pix2pix can restore more texture with the help of a discriminator. Metal artifacts increase the dose calculation uncertainty in radiotherapy. The dose calculated through images obtained by U-Net and pix2pix was identical with that calculated through reference images.