bluuebunny/crossref_metadata_2025 huggingface dataset:
Particle swarm optimization‐based liver disorder ultrasound image classification using multi‐level and multi‐domain features
Authors: Krishnamurthy Raghesh Krishnan , Radhakrishnan Sudhakar , Kattuva Mohaideen Abdul Kadhar
Published: November 2020

Liver ultrasound is a cost‐effective, non‐invasive, and sufficient technique to diagnose most of the liver disorders. The recent advancements in research in image processing have led to the development of image‐based liver disorder classification systems. In spite of being popular in the diagnostic imaging of liver, ultrasound images, owing to their poor quality, render the conventional and state of the art segmentation and feature extraction techniques incapable, to accurately classify a large mixed group of liver disorders; due to the similarities and differences in appearances among the different and same disorders, respectively. Classification of liver disorders using ultrasound images poses various challenges at each phase, from segmentation to classification. There is a need for better segmentation, powerful features, and optimal classification parameter combinations to obtain decent classification accuracy, when a large sub‐set of liver disorders is considered. In this work, the region of interest is extracted using iso‐contour technique. Feature extraction is performed using multi‐level fractal features and multi‐domain wavelet‐texture features for better discrimination capability. Then, an optimization problem is formulated, for minimizing the five fold cross validation error to classify 10 types of disorders, both focal and diffused, by selecting the best features, suitable classifier, and its parameters using the particle swarm optimization technique for obtaining better classification. An overall accuracy of 91% is obtained using the proposed features in addition to 50% reduction in multi‐level fractal feature set which justifies the efficacy of the proposed technique.
Recent progress in contact, mobility, and encapsulation engineering of InSe and GaSe
Authors: Arora Himani , Erbe Artur
Published: November 2020

The field of two‐dimensional (2D) materials has stimulated considerable interest in the scientific community. Owing to quantum confinement in one direction, intriguing properties have been reported in 2D materials that cannot be observed in their bulk form. The advent of semiconducting 2D materials with a broad range of electronic properties has provided fascinating opportunities to design and configure next‐generation electronics. One such emerging class is the family of III‐VI monochalcogenides, the two prominent members of which are indium selenide (InSe) and gallium selenide (GaSe). In contrast to transition metal dichalcogenides, their high intrinsic mobility and the availability of a direct bandgap at small thicknesses have attracted researchers to investigate the underlying physical phenomena as well as their technological applications. However, the sensitivity of InSe and GaSe to environmental influences has limited their exploitation in functional devices. The lack of methods for their scalable synthesis further hinders the realization of their devices. This review article outlines recent advancements in the synthesis and understanding of the charge transport properties of InSe and GaSe for their integration into technological applications. A detailed summary of the improvements in the device structure by optimizing extrinsic factors such as bottom substrates, metal contacts, and device fabrication schemes is provided. Furthermore, various encapsulation techniques that have been proven effective in preventing the degradation of InSe and GaSe layers under ambient conditions are thoroughly discussed. Finally, this article presents an outlook on future research ventures with respect to ongoing developments and practical viability of these materials.

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Antimicrobial activity of amphiphilic nanomicelles loaded with curcumin against Pseudomonas aeruginosa alone and activated by blue laser light
Authors: Rupel Katia , Zupin Luisa , Brich Silvia , Mardirossian Mario , Ottaviani Giulia , Gobbo Margherita , Di Lenarda Roberto , Pricl Sabrina , Crovella Sergio , Zacchigna Serena , Biasotto Matteo
Published: November 2020

The aim of this work was to assess the antimicrobial efficacy on Pseudomonas aeruginosa of nanomicelles loaded with curcumin (CUR) alone and activated by blue laser light in an antimicrobial photodynamic therapy (APDT) approach. First, free CUR in liquid suspension and loaded in three amphiphilic nanomicelles (CUR‐DAPMA, CUR‐SPD and CUR‐SPM) were tested both on bacteria and keratinocytes. While free CUR exerted limited efficacy showing moderate cytotoxicity, a strong inhibition of bacterial growth was obtained using all three nanosystems without toxicity on eukaryotic cells. CUR‐SPM emerged as the most effective, and was therefore employed in APDT experiments. Among the three sublethal blue laser (λ 445 nm) protocols tested, the ones characterized by a fluence of 18 and 30 J/cm2 further decreased the antimicrobial concentration to 50 nM. The combination of blue laser APDT with CUR‐SPM nanomicelles results in an effective synergistic activity that represents a promising novel therapeutic approach on resistant species.
cMET promotes metastasis and epithelial‐mesenchymal transition in colorectal carcinoma by repressing RKIP
Authors: Wang Siyun , Ma Haiqing , Yan Yan , Chen Yu , Fu Sirui , Wang Junjiang , Wang Ying , Chen Hao , Liu Jianhua
Published: November 2020

Increasing evidence indicates that c‐mesenchymal‐epithelial transition factor (cMET) plays an important role in the malignant progression of colorectal cancer (CRC). However, the underlying mechanism is not fully understood. As a metastasis suppressor, raf kinase inhibitory protein (RKIP) loss has been reported in many cancer types. In this study, the expression levels of cMET and RKIP in CRC tissues and cell lines were determined, and their crosstalk and potential biological effects were explored in vitro and in vivo. Our results showed that cMET was inversely correlated with RKIP. Both cMET upregulation and RKIP downregulation indicated poor clinical outcomes. Moreover, the MAPK/ERK signaling pathway was implicated in the regulation of cMET and RKIP. Overexpression of cMET promoted tumor cell epithelial‐mesenchymal transition, invasion, migration, and chemoresistance, whereas the effects could be efficiently inhibited by increased RKIP. Notably, small hairpin RNA‐mediated cMET knockdown dramatically suppressed cell proliferation, although no RKIP‐induced influence on cell growth was observed in CRC. Altogether, cMET overexpression may contribute to tumor progression by inhibiting the antioncogene RKIP, providing preclinical justification for targeting RKIP to treat cMET‐induced metastasis of CRC.
Professional regulation for Australasian genetic counselors
Authors: Hoskins Cass , Gaff Clara , McEwen Alison , Macciocca Ivan , Pearn Amy , Shalhoub Carolyn , Salvemini Hayley , Berkman Jennifer , Riley Kate E. , Williams Rachel , Milward Michael , Young Mary‐Anne
Published: November 2020

As a result of the ongoing global expansion of genetic counseling, the need to formalize a system of professional regulation for genetic counselors was identified in Australasia. In June 2017, under the auspices of the Human Genetics Society of Australasia (HGSA), a working party was convened. The purpose of the working party was to provide strategic leadership for the profession of Australasian genetic counselors with a goal to formalize a national regulatory framework for genetic counselors across both Australian and New Zealand jurisdictions. This was ultimately achieved in Australia through full membership with the National Alliance of Self‐Regulating Health Professions (NASRHP) while the profession of genetic counseling in New Zealand is utilizing this framework to establish their regulation pathway. Regulation has a number of implications for genetic counselors, their employers, and the wider community, with the primary purpose of regulation being protection of the public from harm. This paper details the process of formalizing self‐regulation for genetic counselors in Australasia, by defining professional regulation; outlining the purpose of regulation and the status of regulation for genetic counselors in Australasia and internationally, as well as health professionals more broadly; exploring the challenges of establishing regulation in Australasia; and the next steps for regulation in Australasia. Through detailing this process, the intention is to provide a framework to support genetic counseling colleagues internationally as well as other health professions in Australasia to explore and achieve regulation through their respective jurisdiction.
Down‐regulation of lncRNA HCG11 promotes cell proliferation of oral squamous cell carcinoma through sponging miR‐455‐5p
Authors: Wu Jingjing , Li Yong , Liu Jian , Xu Yanzhi
Published: November 2020

Background

As a type of head and neck squamous cell carcinoma (HNSCC), oral squamous cell carcinoma (OSCC) has a high incidence and low survival rate. Frequent deletion of protein tyrosine phosphatase receptor type sigma (PTPRS) has been found in HNSCC. Long non‐coding RNA (lncRNA) HCG11 and miR‐455‐5p have been reported to be involved in several cancers, in which miR‐455‐5p was found to be up‐regulated in the OSCC. However, the role of HCG11 in OSCC development is still unclear.

Methods

Several co‐transfection systems were established to explore the regulation of HCG11 on OSCC cells. Cell proliferation was evaluated by the MTT assay, flow cytometry of cell cycle distribution, immunofluorescence of Ki67 and western blotting. A dual luciferase reporter assay was performed to verify the binding effects of miR‐455‐5p on HCG11 and PTPRS. The role of HCG11 knockdown in OSCC cell growth was also confirmed by nude mouse tumorigenicity assay in vivo.

Results

Knockdown of HCG11 increased OSCC cell proliferation, as indicated by enhanced cell vitalities over time, increased G1/S transition and Ki67 levels. Furthermore, lncRNA HCG11 was shown to negatively regulate miR‐455‐5p and miR‐455‐5p targeted PTPRS directly to affect its downstream indicators, which can further modulate OSCC cell proliferation and growth. The results obtained in vivo confirmed that HCG11 knockdown promoted OSCC cell growth.

Conclusions

The lncRNA HCG11/miR‐R‐455‐5p axis can be considered as an upstream signalling circuit of PTPRS with respect to regulating its activity and downstream pathways to further influence the progression of OSCC. This finding may provide a novel RNA‐based therapeutic target for OSCC treatment.
Quantitative Evaluations of Geometrical Distortion Corrections in Cortical Surface‐Based Analysis of High‐Resolution Functional MRI Data at 7T
Authors: Yamamoto Tetsuya , Fukunaga Masaki , Sugawara Sho K. , Hamano Yuki H. , Sadato Norihiro
Published: November 2020

Background

Although 7T functional MRI (fMRI) provides better signal‐to‐noise ratio and higher spatial resolution than 3T fMRI, geometric distortions become more challenging because fMRI is more susceptible to distortions than structural MRI. Accurate alignment of 7T fMRI to structural MRI data is critical for precise cortical surface‐based analysis.

Purpose

To quantify the effectiveness of distortion corrections of 7T fMRI data.

Study Type

Prospective.

Subjects

Fifteen healthy individuals aged 19–26 years (mean: 21.9 years).

Field Strength/Sequence

Multiband gradient‐echo echo‐planar imaging sequence at 7T; 3D T1/T2‐weighted sequences (magnetization prepared rapid acquisition with gradient echo [MPRAGE] and sampling perfection with application optimized contrast using different flip angle evolution [SPACE]) at 3T.

Assessment

fMRI data at 7T were registered to cortical surfaces reconstructed from 3T structural data acquired in the same subjects. Distortions induced by B0 inhomogeneity and gradient nonlinearity (B0 and gradient distortions) were evaluated as cortical fallout (misregistration of noncortical areas) and displacement (misregistration along gray matter).

Statistical Tests

Repeated measures analyses of variance with post‐hoc t‐tests with Bonferroni correction.

Results

The accuracy of fully corrected fMRI images based on the intensity distribution was 89.2%. Without any corrections, 9.7% of vertices in the whole surfaces were fallout and the average displacement was 0.96 mm for the rest of the vertices. B0 and gradient distortion corrections significantly reduced the fallout (to 2.1% and 8.7%) and displacement (to 0.29 mm and 0.86 mm). These corrections were effective even around regions with moderate distortions (the somatosensory and visual cortices for B0 distortion, and the anterior frontal, inferior temporal, and posterior occipital cortices for gradient distortion).

Data Conclusion

B0 distortion correction is crucial for surface‐based analysis of fine‐resolution fMRI at 7T. Gradient distortion correction should be considered when regions of interest include regions distant from the isocenter of scanners.

Evidence Level

1

Technical Efficacy Stage

1
SARS‐CoV‐2 and inflammatory responses: From mechanisms to the potential therapeutic use of intravenous immunoglobulin
Authors: Mascolo Silvia , Carleo Maria A. , Contieri Marcella , Izzo Sara , Perna Angelica , De Luca Antonio , Esposito Vincenzo
Published: November 2020

A novel coronavirus (SARS‐CoV‐2) is responsible for a severe acute respiratory syndrome called coronavirus disease 2019 (COVID‐19). It is originated in Wuhan, China, in December 2019. Due to its extreme transmissibility with droplets and human contacts, in a few months, it has become a pandemic. Nowadays, no effective therapy is available, and the scientific community is moving to find a therapeutic choice to fight this silent enemy. Studies are ongoing on several therapeutic options, including antiviral agents, immunomodulant drugs, and immunotherapy. Due to viral features, including the ability to start an inflammatory response that seems to be the fulcrum of COVID‐19 pathogenic action, immunotherapy could represent a promising alternative waiting for the vaccine. High‐dose intravenous immunoglobulin (IVIg), already used in other infectious diseases, could represent an effective help. The aim of this narrative review is to reassemble the clinical experiences on the use of IVIg in COVID‐19 and the rationale of its use.
Utility of procalcitonin as an early diagnostic marker of bacteremia in individuals with periodontitis Stage II and III
Authors: Mohan Ranjitha , Srirangarajan  , Rao Ravi J. , Prabhu Srikumar , Rudresh Vinaya
Published: November 2020

Background

The aim of the present study is to assess the ability of procalcitonin (PCT) to differentiate between periodontal health and Stage II and III periodontitis. We further assessed, if PCT can reflect early bacteremia induced by non‐surgical periodontal treatment (NSPT).

Methods

Sixty‐four systemically healthy individuals were divided into Group I, periodontally healthy, and Group II, Stage II and III periodontitis. NSPT was done for both the groups. Standardized serum and salivary samples were obtained and analyzed for PCT levels using highly sensitive double antibody sandwich enzyme‐linked immunosorbent assay at baseline and 2 weeks. In addition, the serum levels of PCT were recorded at immediate and 1‐hour post‐NSPT.

Results

Mean PCT levels (saliva = 0.03 ng/mL and serum = 0.05 ng/mL) in periodontally healthy group were considerably lower than that in the periodontitis group (saliva = 0.22 ng/mL and serum = 1.85 ng/mL) with significant intergroup comparison at P < 0.001. Post NSPT the mean serum PCT values increased from 1.854 ng/mL to 1.871 ng/mL at the immediate interval and remained at 0.879 ng/mL after 2 weeks at P < 0.001. Spearman correlation showed highly significant positive correlation between serum and salivary PCT values to clinical attachment level (CAL) at P < 0.001 and rho = 0.78 and 0.75, respectively. Linear regression model showed serum PCT to be a significant predictor for CAL.

Conclusion

Screening for serum PCT levels in patients with periodontitis could act not only as a guide to assess the bacterial load and use of antibiotics but also as a predictor for CAL loss in patients with periodontitis.
Impact of resection margin on outcomes in high‐grade soft tissue sarcomas of the extremity—A USSC analysis
Authors: Chouliaras Konstantinos , Patel Nathan , Senehi Rebecca , Ethun Cecilia G. , Poultsides George , Grignol Valerie , Gamblin Thomas Clark , Roggin Kevin K. , Fields Ryan C. , D'Agostino Ralph , Levine Edward A. , Cardona Kenneth , Votanopoulos Konstantinos
Published: November 2020

Background

The optimal margin of resection for high‐grade extremity sarcomas and its impact on survival has long been questioned in the setting of adjuvant radiotherapy. The objective of this study was to investigate the impact of resection status on recurrence and survival.

Methods

All patients with primary, nonmetastatic, high‐grade extremity sarcomas that underwent surgical resection from January 2000 to April 2016 in the U.S. Sarcoma Collaborative (USSC) were retrospectively reviewed. Recurrence patterns, recurrence‐free survival (RFS), and overall survival (OS) were examined in multivariate analyses (MVA).

Results

A cohort of 959 patients was identified with a median follow‐up of 34.7 months from diagnosis. R0 resection was achieved in 86.7% (831) while R1 resection in 13.3% (128). Locoregional recurrence for R0 and R1 groups occurred in 9.1% (76) versus 14.8% (19; p = .05) while distant recurrence occurred in 24.7% (205) versus 26.6% (34; p = .65), respectively. Median RFS was 171.2 versus 48.5 (p = .01) while median OS was 149.8 versus 71.5 months (p = .02) for the R0 versus R1 group, respectively. On MVA, female gender (hazard ratio [HR] = 0.69, p = .007) and adjuvant radiotherapy (0.7, p = .04) were associated with improved OS, whereas older age (HR = 1.03, p < .001) and tumor size (HR = 1.01, p < .001) were associated with worse OS. R0 resection status was associated with improved locoregional RFS (HR = 0.56, p = .03) but not with distant RFS (HR = 0.84, p = .4) or OS (HR = 0.7, p = .052).

Conclusions

In high‐grade extremity sarcomas, tumor size and gender are predictive of OS while R0 resection status is associated with improved locoregional recurrence rate without a significant impact on distant RFS or OS.
Preparation of multiwall carbon nanotube/urea‐formaldehyde nanocomposite as a new sorbent in solid‐phase extraction and its combination with deep eutectic solvent‐based dispersive liquid–liquid microextraction for extraction of antibiotic residues in honey
Authors: Shahi Mohsen , Javadi Afshin , Afshar Mogaddam Mohammad Reza , Mirzaei Hamid , Nemati Mahboob
Published: November 2020

A solid‐phase extraction method combined with deep eutectic solvent‐based dispersive liquid–liquid microextraction has been developed for the extraction of three antibiotics in honey samples prior to their determination by ion mobility spectrometry. In this method, first, a multiwall carbon nanotube/urea‐formaldehyde nanocomposite was synthesized using co‐precipitation polymerization method and then it was used as a sorbent for the analytes extraction from the samples. After that the adsorbed analytes were eluted from the sorbent using a water‐miscible organic solvent. The collected elution solvent was mixed with tetrabutylammonium chloride:butanol deep eutectic solvent and the mixture was applied in the following microextraction method. The method provided low limits of detection and quantification in the ranges of 0.32–0.86 and 1.1–2.9 ng/g, respectively. The method had a proper repeatability expressed as relative standard deviation less than or equal to 9.1%. The validated method was successfully performed on different honey samples obtained from different producers.
A novel online preparative high‐performance liquid chromatography system with the multiple trap columns‐valve switch technique for the rapid and efficient isolation of main flavonoids from Epimedium koreanum Nakai
Authors: Zhuang Linwu , Ding Yan , Ma Fenglian , li Jinliu , M Safian Murad , Xiao Wei , Wang Zhenzhong , Zhu Jingbo
Published: November 2020

In this work, a new online preparative high‐performance liquid chromatography was developed for the fast and efficient separation of complex chemical mixtures from natural products. This system integrates two chromatographic systems into an online automatic separation system using the technique of multiple trap columns with valve switching. The sample was first separated into 18 subfractions in the online preparative high‐performance liquid chromatography, and the sample eluents were then diluted and captured online on 18 trap columns by the multiple trap columns technique, respectively. Each subfraction retained on the trap column was transferred online to the separation column for the second separation. Finally, the target compounds were purified by appropriate separation conditions and multiple heart‐cutting strategies. Importantly, the system was successfully used to separate 18 high‐purity flavonoids from the crude extract of Epimedium koreanum Nakai online in one step. The entire separation time was approximately 20 h, and the structures were characterized by the high‐performance liquid chromatography quadrupole time‐of‐flight tandem mass spectrometry and nuclear magnetic resonance. This online preparative high‐performance liquid chromatography system represents an efficient and rapid separation system that has the potential for a wide array of applications in the separation of complex chemical components from natural products.
Reliability and Validity of a German Standardized Diagnostic Interview Module for ICD‐11 Adjustment Disorder
Authors: Perkonigg Axel , Strehle Jens , Beesdo‐Baum Katja , Lorenz Louisa , Hoyer Jana , Venz John , Maercker Andreas
Published: November 2020

The ICD‐11 includes a new definition of adjustment disorder (AjD). The present study aimed to examine interrater reliability, internal consistency, and construct validity of a new diagnostic interview module to assess ICD‐11 AjD. Data from two studies that used a standardized diagnostic interview assessment (i.e., DIA‐X/M‐CIDI and updated DIA‐X‐5) were used. For interrater reliability, agreement indicators (i.e., κ) were calculated using data from the DIA‐X‐5 test–retest study (N = 60). To examine internal consistency and construct validity, Cronbach's alpha values and the Kuder–Richardson correlation coefficient were computed along with confirmatory factor and latent class analyses (LCA), using data from the Zurich Adjustment Disorder Study (N = 330). Interrater reliability analyses found an adjusted kappa of 0.807 for the ICD‐11 AjD diagnosis. Few items from the impairment criterion of the diagnostic algorithm performed poorly. The internal consistency was acceptable, Cronbach's αs = .43–.80; the lower‐bound estimate resulted from the two‐item preoccupation symptom pattern. However, both items were significantly associated, OR = 3.14, 95% CI [1.97, 4.99]. Regarding LCA results, a two‐class model was favored. We found that 94.3% of all ICD‐11 AjD cases belonged to Class 2, OR = 23.69, 95% CI [7.15, 79.54], which was associated with subjectively rated distress, OR = 2.18, 95% CI [1.57, 3.02], and the external measure of the Brief Symptom Inventory global severity index, OR = 2.18, 95% CI [1.57, 3.02]. Overall, the new AjD interview module provided a reliable, valid assessment of the ICD‐11 diagnosis; confirmation by other studies is needed.
Balloon Eustachian Tuboplasty in Pediatric Patients: Is it Safe?
Authors: Howard Anthony , Babu Seilesh , Haupert Michael , Thottam Prasad John
Published: November 2020

Objectives/Hypothesis

The objective of this study is to demonstrate that balloon eustachian tuboplasty (BET) is safe and had limited complications in the pediatric patient population.

Study Design

Retrospective chart review.

Methods

This study analyzed the medical records of 43 consecutive encounters of patients under the age of 18 years old who underwent attempted BET. Charts of patients' postoperative appointments and appointments 30 days following the procedure were reviewed. Any complications that were reported by the surgeons' operative report or documented postoperatively were stratified by the Classification of Surgical Complications as outlined by the American College of Surgeons. Additional data points that were analyzed included concomitant surgical procedures, estimated blood loss, and demographic information.

Results

A cohort of 43 pediatric patient encounters were investigated. There was a total of two complications from BET (4.7%) and one aborted case. The complications included epistaxis controlled with oxymetazoline and pressure, and vertigo that was later attributed to vestibular migraines. One case was aborted due to inadequate exposure. The average age of patients evaluated was 12.4 ± 3.2 years old with a range of 6.6 to 17.7 years old.

Conclusions

In this retrospective cohort, BET was demonstrated to be a relatively safe intervention with an overall complication rate of 4.7% in patients as young as 6.6 years old with recurrent or chronic eustachian tube dysfunction and/or related issues.

Level of Evidence

4 Laryngoscope, 131:1657–1662, 2021
Environmental determinants impacting the spatial heterogeneity of karst ecosystem services in Southwest China
Authors: Gao Jiangbo , Zuo Liyuan , Liu Wanlu
Published: November 2020

Severe rocky desertification and considerable terrain relief in karst areas increase the difficulty of identifying determinants of ecosystem services (ESs), leading to relatively insufficient research on the quantitative attribution of karst ESs. This study investigates environmental determinants and their interactions affecting karst ESs in Southwest China and spatially variable correlations between environmental determinants and karst ESs in geomorphological regions using the geographical detector and geographical weighted regression methodologies. Results show that land use and vegetation coverage are the determinants of water yield and soil loss at the basin scale, with explanatory power of 67.2% and 32.3%, respectively; and the combination of elevation and vegetation coverage determines the spatial distribution of carbon sequestration. The determinants of ESs differed substantially among diverse geomorphological types due to differences in the inner characteristics of each. In addition to the dominant role of land use in each geomorphological type, the effects of vegetation coverage and precipitation on the water yield are significant in mountainous regions. The explanatory power of land use for soil loss decreases with increased terrain relief, while that of the vegetation coverage shows the opposite trend. For carbon sequestration, terrain factors play a more important role than land use at the basin scale, while land use is more influential in each geomorphological type. Furthermore, precipitation and vegetation coverage have the largest impact area on water yield and soil loss in each geomorphological type, respectively, and the impact area of each determinant of carbon sequestration shows obvious regional differences.
The biological role of metabolic reprogramming in pancreatic cancer
Authors: Suzuki Tatsunori , Otsuka Motoyuki , Seimiya Takahiro , Iwata Takuma , Kishikawa Takahiro , Koike Kazuhiko
Published: November 2020

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease and highly resistant to all forms of therapy. PDAC cells reprogram their metabolism extensively to promote their survival and growth. Reflecting the vital role of altered metabolism, experimental and clinical trials targeting the rewired metabolism are currently underway. In this review, we summarize the vital role of metabolic reprogramming in the development of PDAC and the future of novel therapeutic applications.
Genome‐Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients
Authors: Sarihan Elif Irem , Pérez‐Palma Eduardo , Niestroj Lisa‐Marie , Loesch Douglas , Inca‐Martinez Miguel , Horimoto Andrea R.V.R. , Cornejo‐Olivas Mario , Torres Luis , Mazzetti Pilar , Cosentino Carlos , Sarapura‐Castro Elison , Rivera‐Valdivia Andrea , Dieguez Elena , Raggio Victor , Lescano Andres , Tumas Vitor , Borges Vanderci , Ferraz Henrique B. , Rieder Carlos R. , Schumacher‐Schuh Artur F. , Santos‐Lobato Bruno L. , Velez‐Pardo Carlos , Jimenez‐Del‐Rio Marlene , Lopera Francisco , Moreno Sonia , Chana‐Cuevas Pedro , Fernandez William , Arboleda Gonzalo , Arboleda Humberto , Arboleda‐Bustos Carlos E. , Yearout Dora , Zabetian Cyrus P. , Thornton Timothy A. , O'Connor Timothy D. , Lal Dennis , Mata Ignacio F. ,   Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE‐PD)
Published: November 2020

Background

Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non‐European populations. In addition, the overall identification of copy number variants at a genome‐wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome‐wide burden of copy number variants in Latinos and its association with Parkinson's disease.

Methods

We used genome‐wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease.

Results

Genome‐wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69–10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10−7).

Conclusions

We found that although overall genome‐wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early‐onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome‐wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population. © 2020 International Parkinson and Movement Disorder Society
Novel Protein Biomarkers of Monoamine Metabolism Defects Correlate with Disease Severity
Authors: Tristán‐Noguero Alba , Borràs Eva , Molero‐Luis Marta , Wassenberg Tessa , Peters Tessa , Verbeek Marcel M. , Willemsen Michel , Opladen Thomas , Jeltsch Kathrin , Pons Roser , Thony Beat , Horvath Gabriella , Yapici Zuhal , Friedman Jennifer , Hyland Keith , Agosta Guillermo E. , López‐Laso Eduardo , Artuch Rafael , Sabidó Eduard , García‐Cazorla Àngels
Published: November 2020

Background

Genetic defects of monoamine neurotransmitters are rare neurological diseases amenable to treatment with variable response. They are major causes of early parkinsonism and other spectrum of movement disorders including dopa‐responsive dystonia.

Objectives

The objective of this study was to conduct proteomic studies in cerebrospinal fluid (CSF) samples of patients with monoamine defects to detect biomarkers involved in pathophysiology, clinical phenotypes, and treatment response.

Methods

A total of 90 patients from diverse centers of the International Working Group on Neurotransmitter Related Disorders were included in the study (37 untreated before CSF collection, 48 treated and 5 unknown at the collection time). Clinical and molecular metadata were related to the protein abundances in the CSF.

Results

Concentrations of 4 proteins were significantly altered, detected by mass spectrometry, and confirmed by immunoassays. First, decreased levels of apolipoprotein D were found in severe cases of aromatic L‐amino acid decarboxylase deficiency. Second, low levels of apolipoprotein H were observed in patients with the severe phenotype of tyrosine hydroxylase deficiency, whereas increased concentrations of oligodendrocyte myelin glycoprotein were found in the same subset of patients with tyrosine hydroxylase deficiency. Third, decreased levels of collagen6A3 were observed in treated patients with tetrahydrobiopterin deficiency.

Conclusion

This study with the largest cohort of patients with monoamine defects studied so far reports the proteomic characterization of CSF and identifies 4 novel biomarkers that bring new insights into the consequences of early dopaminergic deprivation in the developing brain. They open new possibilities to understand their role in the pathophysiology of these disorders, and they may serve as potential predictors of disease severity and therapies. © 2020 International Parkinson and Movement Disorder Society
The enhancement of finite difference method for EM simulating the arbitrary fractures
Authors: Chen Fangzhou , Wu Dagang , Yu Mengping , Wang Hanming
Published: November 2020

The numerical technique—finite difference method (FDM) is one well‐known computational method requiring a delicate meshing algorithm used to optimize the simulation accuracy of complicated electromagnetic (EM) structures. The widely used Yee's staggered lattices discretize the EM field components and require the structured cubic meshing data. The structured mesh has intrinsic limitations on simulating irregular formations and objects. By applying a reliable numerical material‐mixing method to calculate the effective properties of mesh cells, the 2.5D FDM solver, with this numerical method implemented, can observe the inclined layers and the thin fracture in the formation without extra grids on interfaces. The tool responses from the practical complex formation with and without fracture showing up a distinguished difference in tool responses can be observed, verifying the validity of the proposed analysis strategies.
A low‐profile half‐mode substrate‐integrated waveguide antenna with frequency and radiation pattern reconfigurable characteristics
Authors: Zhou Jinzhi , Yang Ming
Published: November 2020

Based on half‐mode substrate‐integrated waveguide (HMSIW) cavity, a low‐profile antenna with frequency and radiation pattern reconfigurable characteristics is proposed in this article. A metal layer is printed on the bottom of the HMSIW cavity, which works as an extend ground plane. The resonance frequency, radiation gain and front‐to‐back ratio (FBR) of the HMSIW antenna are extremely sensitive to the dimension of the bottom layer, which consists of the original ground plane and the extended portion. Three PIN diodes are installed on the back of the antenna to change the length of the bottom metal layer. Attribute to the variable metal layer at the bottom of the antenna, two resonant modes with different radiation patterns are obtained. Meanwhile, an E‐shaped patch is also placed at the radiating edge of the HMSIW cavity to improve the impedance matching. In order to verify the reconfigurable features, a low‐profile HMSIW antenna is fabricated and tested. The measured results show that the designed antenna has two working states, which are basically agreement with the simulated results. Among them, the resonance bandwidth of state I is 4.99 to 5.05 GHz with a maximum gain of 3.6 dBi and an average efficiency of 78.6%. Similarly, the resonant bandwidth of state IІ is 5.14 to 5.19 GHz with a peak gain of 5.3 dBi and an average radiation efficiency of 87.4%. Moreover, the measured results of radiation pattern also exhibit the reconfigurable characteristics from quasi‐omnidirectional to directional in xoz plane.
Fully automatic quantification of fibroglandular tissue and background parenchymal enhancement with accurate implementation for axial and sagittal breast MRI protocols
Authors: Wei Dong , Jahani Nariman , Cohen Eric , Weinstein Susan , Hsieh Meng‐Kang , Pantalone Lauren , Kontos Despina
Published: November 2020

Purpose

To propose and evaluate a fully automated technique for quantification of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) in breast MRI.

Methods

We propose a fully automated method, where after preprocessing, FGT is segmented in T1‐weighted, nonfat‐saturated MRI. Incorporating an anatomy‐driven prior probability for FGT and robust texture descriptors against intensity variations, our method effectively addresses major image processing challenges, including wide variations in breast anatomy and FGT appearance among individuals. Our framework then propagates this segmentation to dynamic contrast‐enhanced (DCE)‐MRI to quantify BPE within the segmented FGT regions. Axial and sagittal image data from 40 cancer‐unaffected women were used to evaluate our proposed method vs a manually annotated reference standard.

Results

High spatial correspondence was observed between the automatic and manual FGT segmentation (mean Dice similarity coefficient 81.14%). The FGT and BPE quantifications (denoted FGT% and BPE%) indicated high correlation (Pearson's r = 0.99 for both) between automatic and manual segmentations. Furthermore, the differences between the FGT% and BPE% quantified using automatic and manual segmentations were low (mean differences: −0.66 ± 2.91% for FGT% and −0.17 ± 1.03% for BPE%). When correlated with qualitative clinical BI‐RADS ratings, the correlation coefficient for FGT% was still high (Spearman's ρ = 0.92), whereas that for BPE was lower (ρ = 0.65). Our proposed approach also performed significantly better than a previously validated method for sagittal breast MRI.

Conclusions

Our method demonstrated accurate fully automated quantification of FGT and BPE in both sagittal and axial breast MRI. Our results also suggested the complexity of BPE assessment, demonstrating relatively low correlation between segmentation and clinical rating.
Association of genetic mutations and loss of ambulation in childhood‐onset dystrophinopathy
Authors: Haber Gregory , Conway Kristin M. , Paramsothy Pangaja , Roy Anindya , Rogers Hobart , Ling Xiang , Kozauer Nicholas , Street Natalie , Romitti Paul A. , Fox Deborah J. , Phan Han C. , Matthews Dennis , Ciafaloni Emma , Oleszek Joyce , James Katherine A. , Galindo Maureen , Whitehead Nedra , Johnson Nicholas , Butterfield Russell J. , Pandya Shree , Venkatesh Swamy , Bhattaram Venkatesh Atul
Published: November 2020

Background

Quantifying associations between genetic mutations and loss of ambulation (LoA) among males diagnosed with childhood‐onset dystrophinopathy is important for understanding variation in disease progression and may be useful in clinical trial design.

Methods

Genetic and clinical data from the Muscular Dystrophy Surveillance, Tracking, and Research Network for 358 males born and diagnosed from 1982 to 2011 were analyzed. LoA was defined as the age at which independent ambulation ceased. Genetic mutations were defined by overall type (deletion/duplication/point mutation) and among deletions, those amenable to exon‐skipping therapy (exons 8, 20, 44–46, 51–53) and another group. Cox proportional hazards regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

Mutation type did not predict time to LoA. Controlling for corticosteroids, Exons 8 (HR = 0.22; 95% CI = 0.08, 0.63) and 44 (HR = 0.30; 95% CI = 0.12, 0.78) were associated with delayed LoA compared to other exon deletions.

Conclusions

Delayed LoA in males with mutations amenable to exon‐skipping therapy is consistent with previous studies. These findings suggest that clinical trials including exon 8 and 44 skippable males should consider mutation information prior to randomization.
Responsiveness of two sexual function questionnaires: PISQ‐IR and FSFI in women with pelvic floor disorders
Authors: Grzybowska Magdalena Emilia , Wydra Dariusz
Published: November 2020

Aims

To assess responsiveness of sexual function questionnaires: Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA‐Revised (PISQ‐IR) and Female Sexual Function Index (FSFI) in women with pelvic floor disorders (PFD).

Methods

The study included 261 subjects who completed PISQ‐IR and FSFI at baseline and after treatment (median: 8 months). Standardized response mean (SRM) and effect size (ES) were calculated for sexually active (SA) and not‐SA (NSA) women. Patient Global Impression of Improvement (PGI‐I) was applied to assess treatment outcomes.

Results

A total of 184 women reported “very much better”/”much better” on the PGI‐I scale posttreatment and were enrolled for further study. After treatment, 21.7% of the NSA women resumed sexual activity, 13.9% of the initially SA‐abstained, and no change was reported for 152 (82.6%) subjects (87‐SA and 65‐NSA). Significant improvement in PISQ‐IR SA domains was observed, with mild responsiveness for Arousal/Orgasm (SRM = 0.34, ES = 0.29, p = .003) and good responsiveness for Condition Specific, Global Quality and Summary Score (SRM = 0.51, ES = 0.50; SRM = 0.54, ES = 0.47; SRM = 0.75, ES = 0.63, p < .001). The Condition Impact domain demonstrated excellent responsiveness (SRM = 1.13, ES = 1.17, p < .001). In NSA, PISQ‐IR had good responsiveness in Condition Impact (SRM = −0.76, ES = −0.59, p < .001), and mild in Condition Specific (SRM = −0.30, ES = −0.28, p < .03) domains. In FSFI, posttreatment sexual function in SA was improved in Desire, Arousal, Orgasm, Satisfaction, Pain domains and Total score, proving mild responsiveness (SRM, 0.24–0.48; p < .04). In NSA, FSFI proved nonresponsive.

Conclusion

PISQ‐IR and FSFI are responsive tools, useful to investigate the effects of treatment on sexual function in SA (both questionnaires) and NSA (only PISQ‐IR) women with PFD.
Suppression of Insulin Secretion in the Treatment of Obesity: A Systematic Review and Meta‐Analysis
Authors: Huang Zhengxiang , Wang Weihao , Huang Lili , Guo Lixin , Chen Chen
Published: November 2020

Objective

This proof‐of‐concept study aimed to evaluate the efficacy and safety of suppression of insulin secretion in the treatment of obesity.

Methods

A search of PubMed, Embase, and Cochrane databases was performed to identify randomized controlled trials (up to January 1, 2020) that used drugs that directly suppress insulin secretion (diazoxide or octreotide) in the treatment of obesity. The extracted data were analyzed using random‐effects meta‐analysis.

Results

A total of seven randomized controlled trials were included, with four using diazoxide and three using octreotide to suppress insulin secretion. Suppression of insulin secretion significantly reduced fasting insulin level (mean difference: −3.94 mIU/L; 95% CI: −7.40 to −0.47) but slightly increased fasting blood glucose level (mean difference: 0.48 mmol/L; 95% CI: 0.24 to 0.72). Following the suppression of insulin secretion, significant reductions in body weight (mean difference: −3.19 kg; 95% CI: −5.71 to −0.66), BMI (mean difference: −1.65 kg/m2; 95% CI: −2.41 to −0.90), and fat mass (mean difference: −5.92 kg; 95% CI: −8.28 to −3.56) were observed compared with placebo in the pooled data. No significant difference in fat‐free mass was observed (mean difference: 0.56 kg; 95% CI: −0.40 to 1.52).

Conclusions

Results suggest that suppression of insulin secretion may lead to reduced body weight and fat mass with slightly increased blood glucose in individuals with obesity.
Effect of Obesogenic Medication on Weight‐ and Fitness‐Change Outcomes: Evidence from the Look AHEAD Study
Authors: Moon Rena C. , Almuwaqqat Zakaria
Published: November 2020

Objective

This study evaluates whether obesogenic medications may decrease the effectiveness of lifestyle interventions. The authors of this study hypothesized that participants who took obesogenic medications would be less responsive to the intervention in the Look AHEAD trial.

Methods

In the trial, 5,145 participants with overweight or obesity, aged 45 to 76 years with type 2 diabetes, were randomly assigned to an intervention (vs. support and education). In this analysis, the association of exposure to obesogenic medications and successful weight loss (≥5% and ≥10% of total weight) and fitness gain (≥1 and ≥2 metabolic equivalents) was examined. For each outcome, multiple logistic regression models were fitted.

Results

Analytic sample sizes were 4,496 for weight‐change analyses and 4,051 for fitness‐change analyses. After adjusting for covariates, exposure to one or more obesogenic medications significantly decreased the odds of achieving ≥5% weight loss by 32% (odds ratio [OR] 0.68) and achieving ≥10% weight loss by 19% (OR 0.81). The association was dose‐dependent—participants using two or more medications were less likely to achieve weight loss than those using one medication. Obesogenic medication exposure was not associated with decreased odds of achieving fitness gain overall.

Conclusions

The results suggest that exposure to obesogenic medications could hinder successful weight loss in a lifestyle intervention for people with diabetes.
What Are the Water Sector's Greatest Operations Challenges?
Authors: Fox Christopher , Johnson Joseph , Novotny Thomas
Published: November 2020

As time and technology march forward, and we experience new challenges like the COVID‐19 pandemic, the world is in a constant state of change. This discussion highlights how operations challenges have changed in the past 20 years, where the water sector stands today, and what the future may hold.
Eliminate Taste‐and‐Odor Events With Cost‐Effective Algae Control
Authors: Buerkens Frances , Kilgore Tricia , Adams Hunter
Published: November 2020

Using a savvy approach focused on biological monitoring and management helps water utilities implement cost‐effective algae control.
Can a Water Treatment Plant Increase Its Filtration Rate to Boost Capacity?
Authors: Pilipovich Ashley
Published: November 2020

With its excess production capacity reduced to below 20 percent, a water service provider in Pennsylvania is conducting a study to determine whether adjusting filter rates could increase the design capacity of one of its main water treatment plants.
Food for thought: The underutilized potential of tropical tree‐sourced foods for 21st century sustainable food systems
Authors: Jansen Merel , Guariguata Manuel R. , Raneri Jessica E. , Ickowitz Amy , Chiriboga‐Arroyo Fidel , Quaedvlieg Julia , Kettle Chris J.
Published: November 2020

The global food system is causing large‐scale environmental degradation and is a major contributor to climate change. Its low diversity and failure to produce enough fruits and vegetables is contributing to a global health crisis.

The extraordinary diversity of tropical tree species is increasingly recognized to be vital to planetary health and especially important for supporting climate change mitigation. However, they are poorly integrated into food systems. Tropical tree diversity offers the potential for sustainable production of many foods, providing livelihood benefits and multiple ecosystem services including improved human nutrition.

First, we present an overview of these environmental, nutritional and livelihood benefits and show that tree‐sourced foods provide important contributions to critical fruit and micronutrient (vitamin A and C) intake in rural populations based on data from sites in seven countries.

Then, we discuss several risks and limitations that must be taken into account when scaling‐up tropical tree‐based food production, including the importance of production system diversity and risks associated with supply to the global markets.

We conclude by discussing several interventions addressing technical, financial, political and consumer behaviour barriers, with potential to increase the consumption and production of tropical tree‐sourced foods, to catalyse a transition towards more sustainable global food systems.

A free Plain Language Summary can be found within the Supporting Information of this article.