bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of MEG‐based studies in Parkinson's disease: The motor system and beyond
Authors: Boon Lennard I. , Geraedts Victor J. , Hillebrand Arjan , Tannemaat Martijn R. , Contarino Maria Fiorella , Stam Cornelis J. , Berendse Henk W.
Published: March 2019

Parkinson's disease (PD) is accompanied by functional changes throughout the brain, including changes in the electromagnetic activity recorded with magnetoencephalography (MEG). An integrated overview of these changes, its relationship with clinical symptoms, and the influence of treatment is currently missing. Therefore, we systematically reviewed the MEG studies that have examined oscillatory activity and functional connectivity in the PD‐affected brain. The available articles could be separated into motor network‐focused and whole‐brain focused studies. Motor network studies revealed PD‐related changes in beta band (13–30 Hz) neurophysiological activity within and between several of its components, although it remains elusive to what extent these changes underlie clinical motor symptoms. In whole‐brain studies PD‐related oscillatory slowing and decrease in functional connectivity correlated with cognitive decline and less strongly with other markers of disease progression. Both approaches offer a different perspective on PD‐specific disease mechanisms and could therefore complement each other. Combining the merits of both approaches will improve the setup and interpretation of future studies, which is essential for a better understanding of the disease process itself and the pathophysiological mechanisms underlying specific PD symptoms, as well as for the potential to use MEG in clinical care.
Usefulness of narrow band imaging with magnifying endoscopy for the differential diagnosis of cancerous and noncancerous laryngeal lesions
Authors: Hosono Hiroshi , Katada Chikatoshi , Okamoto Tabito , Ichinoe Masaaki , Sakamoto Yasutoshi , Matsuba Hiroki , Kano Koichi , Ishido Kenji , Tanabe Satoshi , Koizumi Wasaburo , Yamashita Taku
Published: March 2019

Background

We evaluated the accuracy of endoscopic findings observed by narrow band imaging (NBI) combined with magnifying gastrointestinal endoscopy (GIE) for the differential diagnosis of cancerous and noncancerous laryngeal lesions.

Methods

A total of 166 vocal cord lesions for which good images were obtained on NBI with magnifying GIE were evaluated with respect to the following 6 variables: macroscopic type, tumor location, color, white coat, keratinization, and abnormal microvessels.

Results

Multivariate analysis showed that white coat (odds ratio [OR], 2.95, P = 0.05), keratosis (OR, 3.14, P = 0.02) and abnormal microvessels (OR, 31.1, P < 0.0001) were significantly related to laryngeal cancer. In the diagnosis of laryngeal cancer, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of abnormal microvessels were 84.4%, 88.6%, 91%, 80.5%, and 86.1%, respectively.

Conclusion

The abnormal microvessels on NBI combined with magnifying GIE are useful for the differential diagnosis of laryngeal lesions.
Variability patterns of the annual frequency and timing of low streamflow days across the United States and their linkage to regional and large‐scale climate
Authors: Pournasiri Poshtiri Maryam , Pal Indrani , Lall Upmanu , Naveau Philippe , Towler Erin
Published: March 2019

Low‐flow events can cause significant impacts to river ecosystems and water‐use sectors; as such, it is important to understand their variability and drivers. In this study, we characterise the variability and timing of annual total frequency of low‐streamflow days across a range of headwater streams within the continental United States. To quantify this, we use a metric that counts the annual number of low‐flow days below a given threshold, defined as the cumulative dry days occurrence (CDO). First, we identify three large clusters of stream gauge locations using a Partitioning Around Medoids (PAM) clustering algorithm. In terms of timing, results reveal that for most clusters, the majority of low‐streamflow days occur from the middle of summer until early fall, although several locations in Central and Western United States also experience low‐flow days in cold seasons. Further, we aim to identify the regional climate and larger scale drivers for these low‐streamflow days. Regionally, we find that precipitation deficits largely associate with low‐streamflow days in the Western United States, whereas within the Central and Eastern U.S. clusters, high temperature indicators are also linked to low‐streamflow days. In terms of larger scale, we examine sea surface temperature (SST) anomalies, finding that extreme dry years exhibit a high degree of co‐occurrence with different patterns of warmer SST anomalies across the Pacific and Northern Atlantic Oceans. The linkages identified with regional climate and SSTs offer promise towards regional prediction of changing conditions of low‐streamflow events.
FGF2 induces breast cancer growth through ligand‐independent activation and recruitment of ERα and PRBΔ4 isoform to MYC regulatory sequences
Authors: Giulianelli Sebastián , Riggio Marina , Guillardoy Tomas , Pérez Piñero Cecilia , Gorostiaga María A. , Sequeira Gonzalo , Pataccini Gabriela , Abascal María F. , Toledo María F. , Jacobsen Britta M. , Guerreiro Ana C. , Barros António , Novaro Virginia , Monteiro Fátima L. , Amado Francisco , Gass Hugo , Abba Martin , Helguero Luisa A. , Lanari Claudia
Published: March 2019

Progression to hormone‐independent growth leading to endocrine therapy resistance occurs in a high proportion of patients with estrogen receptor alpha (ERα) and progesterone receptors (PR) positive breast cancer. We and others have previously shown that estrogen‐ and progestin‐induced tumor growth requires ERα and PR interaction at their target genes. Here, we show that fibroblast growth factor 2 (FGF2)‐induces cell proliferation and tumor growth through hormone‐independent ERα and PR activation and their interaction at the MYC enhancer and proximal promoter. MYC inhibitors, antiestrogens or antiprogestins reverted FGF2‐induced effects. LC–MS/MS identified 700 canonical proteins recruited to MYC regulatory sequences after FGF2 stimulation, 397 of which required active ERα (ERα‐dependent). We identified ERα‐dependent proteins regulating transcription that, after FGF2 treatment, were recruited to the enhancer as well as proteins involved in transcription initiation that were recruited to the proximal promoter. Also, among the ERα‐dependent and independent proteins detected at both sites, PR isoforms A and B as well as the novel protein product PRBΔ4 were found. PRBΔ4 lacks the hormone‐binding domain and was able to induce reporter gene expression from estrogen‐regulated elements and to increase cell proliferation when cells were stimulated with FGF2 but not by progestins. Analysis of the Cancer Genome Atlas data set revealed that PRBΔ4 expression is associated with worse overall survival in luminal breast cancer patients. This discovery provides a new mechanism by which growth factor signaling can engage nonclassical hormone receptor isoforms such as PRBΔ4, which interacts with growth‐factor activated ERα and PR to stimulate MYC gene expression and hence progression to endocrine resistance.
Repeated oral dose toxicity study of nickel oxide nanoparticles in Wistar rats: a histological and biochemical perspective
Authors: Dumala Naresh , Mangalampalli Bhanuramya , Kalyan Kamal Sarika Srinivas , Grover Paramjit
Published: March 2019

Despite the increasing use of nickel oxide (NiO) nanoparticles (NPs), limited information is available on their toxicological effects. Health consequences of 28 days repeated oral exposure to NiO NPs have not been explored thoroughly. Hence, toxicity investigations were performed after 28‐day daily exposure in albino Wistar rats with NiO NPs following Organization for Economic Co‐operation and Development test guideline 407. Histopathology, biochemical indices including oxidative stress and biodistribution patterns were evaluated to decipher the toxicological impact of NiO NPs. NiO NP characterization by transmission electron microscopy showed an average size of 12.9 (±3.4) nm. Histological studies depicted a prominent impact on the vital organs of the rats. A dose‐dependent rise in both aminotransferase enzyme values was recorded in the homogenates of liver and kidney tissues. A significant decrease in superoxide dismutase activity and increase in catalase activity was noted. Further, a dose‐dependent decrease in reduced glutathione content was recorded in rats, which suggested generation of reactive oxygen species and oxidative stress. Increase in the malondialdehyde levels was observed with an increase in the dose substantiating the antioxidant enzyme activity profiles. Biodistribution studies indicated maximum accumulation of Ni content in liver followed by kidney. Excretion of Ni was predominantly through feces and a little through renal clearance. Our study indicated that NiO NPs adversely alter the biochemical profile of the rats and cause histological damage. Further investigations are warranted to address the mechanism by which physiological path these NiO NPs exhibit their toxic nature in in vivo.
The clinical significance of HOXA9 promoter hypermethylation in head and neck squamous cell carcinoma
Authors: Zhou Chongchang , Li Jinyun , Li Qun , Liu Huigao , Ye Dong , Wu Zhenhua , Shen Zhisen , Deng Hongxia
Published: March 2019

Background

The purpose of the current study was to assess the association between HOXA9 (homeobox A9) promoter methylation and head and neck squamous cell carcinoma (HNSCC) and its diagnostic value.

Methods

Quantitative methylation‐specific PCR (qMSP) was applied to measure HOXA9 promoter methylation levels in 145 paired HNSCC and corresponding normal tissue samples. Data from the Cancer Genome Atlas (TCGA) database (n = 578; 528 HNSCC and 50 normal) were also analyzed.

Results

Significantly higher levels of HOXA9 promoter methylation were detected in HNSCC, compared with normal, tissues (our cohort: P = 1.06E‐35; TCGA cohort: P = 3.06E‐39). Moreover, HOXA9 methylation was significantly increased in patients with advanced tumor (T) stage, lymph node metastasis, and advanced clinical stage. Areas under the receiver characteristic curves (AUCs) based on our cohort and TCGA data were 0.930 and 0.967, respectively.

Conclusion

In summary, our study reveals that HOXA9 promoter hypermethylation contributes to the risk of HNSCC and its progression and metastasis. Additionally, HOXA9 hypermethylation is a potential biomarker for the early diagnosis and screening of patients with HNSCC.
Exploring genetic counselors’ perceptions of usefulness and intentions to use refined risk models in clinical care based on the Technology Acceptance Model (TAM)
Authors: Heinlen Christopher , Hovick Shelly R. , Brock Guy N. , Klamer Brett G. , Toland Amanda Ewart , Senter Leigha
Published: March 2019

Pathogenic germline mutations in the BRCA1 or BRCA2 genes are associated with an elevated lifetime risk for breast (50%–85% risk) and ovarian cancer (20%–40% risk). Genome‐wide association studies have identified over 100 genetic variants associated with modified breast and/or ovarian cancer risk in BRCA1 and BRCA2 carriers. Risk models generated based on these variants have shown that these genetic modifiers strongly influence absolute risk of developing breast or ovarian cancer in BRCA mutation carriers. There is a lack of understanding, however, about the clinical applicability and utility of these risk models. To investigate this gap, we collected survey data from 274 cancer genetic counselors (GCs) through the National Society of Genetic Counselors Cancer Special Interest Group. Questions assessed perceptions of usefulness and intentions of genetic counselors to use these refined risk models in clinical care based on the Technology Acceptance Model (TAM). We found that GCs’ reactions to the estimates were largely positive, though they thought the possibility of changing management based on results was unlikely. Additionally, we found that more experienced GCs were more likely to consider refined risk estimates in clinic. Support also was provided for core predictions within the TAM, whereby the perceived usefulness (indirect effect est. = 0.08, 95% CI: [0.04, 0.13]) and perceived ease of use (indirect effect est. = 0.078, 95% CI: [0.04, 0.13]) of refined risk estimates were indirectly associated with intentions to use via attitudes.
Patients' reactions and follow‐up testing decisions related to Tay‐Sachs (HEXA) variants of uncertain significance results
Authors: Yip Tiffany , Grinzaid Karen A. , Bellcross Cecelia , Moore Reneé H. , Page Patricia Z. , Hardy Melanie W.
Published: March 2019

JScreen is a national public health initiative based out of Emory University that provides reproductive carrier screening through an online portal and follow‐up genetic counseling services. In 2014, JScreen began reporting to patients variants of uncertain significance (VUSs) in the gene that causes Tay‐Sachs disease (HEXA). Genetic counseling was provided to discuss the VUS and patients were offered hexosaminidase A (HEXA) blood enzyme testing to assist with VUS reclassification. To identify patient reactions and factors influencing their follow‐up testing decisions after receiving these results, we conducted a retrospective quantitative study by administering online surveys to 62 patients with HEXA VUSs. Participants who pursued enzyme testing and those who did not both experienced low levels of distress when receiving the VUS results. Perceptions of HEXA carrier status after genetic counseling, decisional conflict levels, plans to have children in the near future, time available to pursue enzyme testing, and eligibility for research were significant factors influencing decision‐making to pursue or not pursue enzyme testing. Genetic counseling played an important role in helping patients understand the VUS and follow‐up testing options. When discussing VUSs with patients, it would be beneficial for genetic counselors to focus on the patient's perception of the VUS, anxiety related to the uncertainty of their results, and follow‐up options, when available.
Gene therapy prevents hepatic tumor initiation in murine glycogen storage disease type Ia at the tumor‐developing stage
Authors: Cho Jun‐Ho , Lee Young Mok , Starost Matthew F. , Mansfield Brian C. , Chou Janice Y.
Published: March 2019

Hepatocellular adenoma/carcinoma (HCA/HCC) is a long‐term complication of glycogen storage disease type‐Ia (GSD‐Ia), which is caused by a deficiency in glucose‐6‐phosphatase‐α (G6Pase‐α or G6PC), a key enzyme in gluconeogenesis. Currently, there is no therapy to address HCA/HCC in GSD‐Ia. We have previously shown that a recombinant adeno‐associated virus (rAAV) vector‐mediated G6PC gene transfer to 2‐week‐old G6pc−/− mice prevents HCA development. However, it remains unclear whether G6PC gene transfer at the tumor developing stage of GSD‐Ia can prevent tumor initiation or abrogate the pre‐existing tumors. Using liver‐specific G6pc‐knockout (L‐G6pc−/−) mice that develop HCA/HCC, we now show that treating the mice at the tumor‐developing stage with rAAV‐G6PC restores hepatic G6Pase‐α expression, normalizes glucose homeostasis, and prevents de novo HCA/HCC development. The rAAV‐G6PC treatment also normalizes defective hepatic autophagy and corrects metabolic abnormalities in the nontumor liver tissues of both tumor‐free and tumor‐bearing mice. However, gene therapy cannot restore G6Pase‐α expression in the HCA/HCC lesions and fails to abrogate any pre‐existing tumors. We show that the expression of 11 β‐hydroxysteroid dehydrogenase type‐1 that mediates local glucocorticoid activation is downregulated in HCA/HCC lesions, leading to impairment in glucocorticoid signaling critical for gluconeogenesis activation. This suggests that local glucocorticoid action downregulation in the HCA/HCC lesions may suppress gene therapy mediated G6Pase‐α restoration. Collectively, our data show that rAAV‐mediated gene therapy can prevent de novo HCA/HCC development in L‐G6pc−/− mice at the tumor developing stage, but it cannot reduce any pre‐existing tumor burden.
Automatic image processing pipeline for tracking longitudinal vessel changes in magnetic resonance angiography
Authors: Hsu Chih‐Yang , Li Yimei , Han Yuanyuan , Elijovich Lucas , Sabin Noah D. , Abuelem Tarek , Torabi Radmehr , Faught Austin , Hua Chia‐Ho , Klimo Paul , Merchant Thomas E. , Lucas John T.
Published: March 2019

Background

Cerebral vessel diameter changes objectively and automatically derived from longitudinal magnetic resonance angiography (MRA) facilitate quantification of vessel changes and further modeling.

Purpose

To characterize longitudinal changes in intracranial vessel diameter using time‐of‐flight (TOF) MRA.

Study Type

Retrospective longitudinal study.

Subject Population

IN all, 112 pediatric patients, aged 9.96 ± 4.59 years, with craniopharyngioma from 2006–2011 scanned annually.

Field Strength/Sequence

1.5T and 3T TOF MRA.

Statistical Tests

Chi‐square and Wilcoxon–Mann–Whitney tests.

Assessment

Manual measurements using interventional angiography was established as a reference standard for diameter measurements. Constant and linear quantile regression with absolute difference, percentage difference, and relative difference was used for outlier detection.

Results

Major vessels surrounding the circle of Willis were successfully segmented except for posterior communicating arteries, mostly due to disease‐related hypoplasia. Diameter measurements were calculated at 1‐mm segments with a median computed vessel diameter of 1.25 mm. Diameter distortion due to registration was within 0.04 mm for 99% of vessel segments. Outlier detection using quantile regression detected less than 4.34% as being outliers. Outliers were more frequent in smaller vessels and proximity to bifurcations (P < 0.001).

Data Conclusion

Using the proposed method, objective changes in vessel diameter can be acquired noninvasively from routine longitudinal imaging. High‐throughput analyses of imaging‐derived vascular trees combined with clinical and treatment parameters will allow rigorous modeling of vessel diameter changes.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:1063–1074.
Design of 199 to 238 GHz broadband subharmonic mixer combining two‐stage reduced matching technology with Global Design Method
Authors: Cui Jianhang , Zhang Yong , Liu Xiaoyu , Li Yukun , Wu Chengkai
Published: March 2019

Terahertz technology is widely used in communications, radar, electronic countermeasures, precision guidance, and biomedical applications. In this paper, a 199 to 238 GHz broadband subharmonic mixer combining two‐stage reduced matching technology with Global Design Method is designed, fabricated, measured, and analysed successfully. Compared with traditional single‐stage reduced matching technology and Subdivision Design Method, the two‐stage reduced matching technology is applied for terahertz mixer's Radio Frequency (RF) waveguide and Local Frequency (LO) waveguide, while the LO/Intermediate Frequency (IF) Low‐Pass Filter of terahertz mixers is not necessary to design separately. The core of Global Design Method is that the whole mixer circuit, including LO/RF waveguide, is divided into basic transmission units, which match and filter circuit simultaneously with more optimization variables. When LO driven power is 3.1 mW, LO frequency is 108, 112 GHz. The measured single‐sideband (SSB) conversion loss ranges from 7.84 to 12.4 dB with RF frequency 199 to 238 GHz. The measured double‐sideband (DSB) noise temperature varies between 580 and 1059 K with LO driven power 2 to 5 mW. The multi‐stage reduced matching technology and Global Design Method is general, effective, accurate, can reduce circuit size, simplify circuit structure, broaden frequency band, and can be applied for terahertz harmonically mixers.
Feasibility of late gadolinium enhancement magnetic resonance imaging to detect ablation lesion gaps in patients undergoing cryoballoon ablation of paroxysmal atrial fibrillation
Authors: Mishima Tsuyoshi , Miyamoto Koji , Morita Yoshiaki , Kamakura Tsukasa , Nakajima Kenzaburo , Yamagata Kenichiro , Wada Mitsuru , Ishibashi Kouhei , Inoue Yuko , Nagase Satoshi , Noda Takashi , Aiba Takeshi , Izumi Chisato , Noguchi Teruo , Yasuda Satoshi , Kusano Kengo
Published: March 2019

Background

Although late gadolinium enhancement magnetic resonance imaging (LGE‐MRI) allows the identification of lesions and gaps after a cryothermal balloon (CB) ablation of paroxysmal atrial fibrillation (PAF), the accuracy has not yet been well established.

Methods

The subjects consisted of 10 consecutive patients who underwent a second ablation procedure among our cohort of 80 patients who underwent LGE‐MRI after the CB ablation of PAF. LGE‐MRI scar regions were compared with electroanatomical mapping during the second procedure. In the analysis, the unilateral pulmonary vein (PV) antrum was divided into 7 regions.

Results

The gap characterization analysis was performed in 140 regions around 40 PVs in total. There were 16 LGE‐MRI gaps around 11 PVs (mean 1.6 ± 1.4 gaps/patient) in 7 patients and 14 electrical gaps around 10 PVs in 8 patients (mean 1.4 ± 1.1 gaps/patient). The locations of 13 electrical gaps were well matched to that on the LGE‐MRI, whereas the remaining 1 electrical gap had not been predicted on the LGE‐MRI. Compared to the electrical gaps in the second procedure, the sensitivity and specificity of the LGE‐MRI gaps were 93% (13 LGE‐MRI gaps of 14 electrical gaps) and 98% (123 LGE‐MRI scars out of 126 electrical scars), respectively.

Conclusion

LGE‐MRI can accurately localize the lesion gaps after CB ablation of PAF.
Meteorology and summer net radiation of an Arctic alpine glacier: Svenbreen, Svalbard
Authors: Małecki Jakub
Published: March 2019

Arctic glaciers have been, and are predicted to remain, an important sea‐level rise contributor over the 20th and 21st centuries. However, multi‐annual observations of their basic meteorological characteristics, which drive melt processes, are very sparse, contributing to uncertainties in sea‐level rise projections. This paper presents a methodology to process and analyse 6 years (September 2011–September 2017) of glacier meteorology data collected by an automatic weather station on the ablation zone of a small valley glacier in Svalbard (~79°N). The study focuses on the microclimate of the study glacier and its differences with that of large glaciers in the region, namely slightly increased summer air temperature with steep near‐surface lapse rates, frequently superadiabatic, reduced wind speed and incoming shortwave radiation flux. These differences are likely related to the adjacent complex relief and non‐ice‐covered surfaces within the basin of the study glacier and, as such, pose a challenge for accurate simulation of alpine glacier microclimates in regional melt assessments in the Arctic. The processing routine applied in this paper might serve as a reference for future similar studies.
Gene polymorphism of DNA repair gene X‐ray repair cross complementing group 1 and xeroderma pigmentosum group D and environment interaction in non‐small‐cell lung cancer for Chinese nonsmoking female patients
Authors: Wang Lei , Wang Le‐Le , Shang Di , Yin Sheng‐Jie , Sun Li‐Li , Wang Xiao‐Ying , Ji Hong‐Bo
Published: March 2019

An association between genetic polymorphisms in encoding X‐ray repair cross complementing group 1 (XRCC1) and encoding xeroderma pigmentosum group D (XPD) and risks of non‐small‐cell lung cancer (NSCLC) in East Chinese Han population has been observed. Herein we hypothesized that genetic polymorphisms in these two DNA repair genes are likely to be important in the NSCLC in Chinese nonsmoking female patients. We recruited 327 nonsmoking female patients with NSCLC and 342 individuals with benign lung diseases or healthy controls. Genotype frequencies of XRCC1 T‐77C, Arg194Trp, Arg280His and Arg399Gln, Pro206Pro, and XPD Asp312Asn and Lys751Gln were calculated after Polymerase Chain Reaction amplification and sequencing. Generalized multifactor dimensionality reduction (GMDR) was used to detect the interactive effect of XRCC1 and XPD gene polymorphisms. The ratio of cooking oil mist exposure history and soot exposure history, and the gene frequencies of XRCC1 T‐77C TC + CC, XRCC1 AG + GG, XRCC1 399Gln/Gln, and XPD 751Gln/Gln were higher in female patients with NSCLC than those with benign lung diseases or healthy controls. The haplotypes of XRCC1 T‐Arg‐Arg‐Gln and XRCC1 C‐Arg‐Arg‐Arg were positively associated with the NSCLC occurrence in nonsmoking female patients. GMDR discovered that there was an interactive model of XRCC1 and XPD genes in multiple gene loci. Logistic regression analysis showed that XRCC1 T‐77C, XRCC1 Pro206Pro polymorphism, cooking oil mist and soot exposure history and tumor‐node‐metastasis (TNM) stage were related to NSCLC occurrence for nonsmoking female patients. Taken together, XRCC1 and XPD polymorphisms, cooking oil mist, and soot exposure history may be interactively correlated with NSCLC incidence for nonsmoking female patients.
Association of Rs13405728, Rs12478601, and Rs2479106 single nucleotide polymorphisms and in vitro fertilization and embryo transfer efficacy in patients with polycystic ovarian syndrome: A case control genome‐wide association study
Authors: Xia Jia‐Yu , Tian Wei , Yin Gui‐Hua , Yan Hua
Published: March 2019

Polycystic ovary syndrome (PCOS) is a common female endocrine disorder that has a detriment impact on female health. Herein, the study used a case‐control analysis to sought to explore the association of rs13405728, rs12478601, and rs2479106 single nucleotide polymorphisms (SNPs) with in vitro fertilization and embryo transfer (IVF‐ET) efficacy in treating PCOS. A total of 163 PCOS patients (52 cycles) were selected as the PCOS group and 171 patients with tubal factor infertility without PCOS (68 cycles) were selected as the control group. Polymerase chain reaction was used to amplify genome DNA and direct sequencing to detect SNPs. The LHCGR rs13405728, THADA rs12478601, and DENND1A rs2479106 genotypes were subsequently tested. Logistic regression analysis was conducted to analyze the risk factors influencing the occurrence of PCOS as well as those influencing the efficacy of IVF‐ET. rs13405728, rs12478601, and family history of DM were influencing factors for the occurrence of PCOS. The rate of abortion and number of oocytes retrieved of patients with the THADA rs12478601 CC genotype increased but the rate of clinical gestation decreased. Patients with AG + GG genotype of the DENND1A rs2479106 had increased number of oocytes retrieved, rate of abortion and incidence of gestational DM. rs13405728, rs12478601, serum E2 value as well as fertility rate were influencing factors for efficacy of IVF‐ET. It was suggested that the TT genotype of LHCGR rs13405728, CC genotype of THADA rs12478601 and AG + GG genotype of DENND1A rs2479106 had poor outcomes of IVF‐ET in treating PCOS.
HIV risk and the association with accessibility coverage to medical facilities and socioeconomic status among heroin users in Kaohsiung, Taiwan (2011‐2015): A GIS approach
Authors: Feng Ling‐Yi , Lan Yu‐Ching , Huang Joh‐Jong , Li Jih‐Heng
Published: March 2019

Illegal drug use has caused considerable health and social costs. Access to medical treatment has been one of the most cost‐effective interventions to reduce problematic drug use. Accessibility to treatment, which can be analyzed by the spatial approach such as geographic information system (GIS), has thus been utilized as a measure of the proportion of population that reaches appropriate health services. In this study, the association of accessibility coverage to medical facilities and socioeconomic status with human immunodeficiency virus (HIV) risk for heroin users was evaluated by GIS analysis in Kaohsiung, Taiwan. Data of 7890 heroin users were collected from 2011 to 2015 and categorized into five risk groups according to their income and distance to treatment settings. The results of this GIS‐based analysis show that the areas with over 50% accessibility coverage rate had less amounts of HIV cases with statistical significance. Inconvenient access to medical facilities could result in poor treatment outcomes such as higher HIV incidences. Therefore, in order to effectively reduce HIV incidences among the heroin users, the accessibility coverage and locations of medical treatment facilities should meet the needs of drug users. It is also advised that the formulation of policies associated with illegal drug use problems should be evidence‐based and geographical indicators could serve for this purpose from either prevention or intervention perspective.
Auricle shaping using 3D printing and autologous diced cartilage
Authors: Liao Junlin , Chen Yong , Chen Jia , He Bin , Qian Li , Xu Jiaqin , Wang Aijun , Li Qingfeng , Xie Hongju , Zhou Jianda
Published: March 2019

Objective

To reconstruct the auricle using a porous, hollow, three‐dimensional (3D)‐printed mold and autologous diced cartilage mixed with platelet‐rich plasma (PRP).

Methods

Materialise Magics v20.03 was used to design a 3D, porous, hollow auricle mold. Ten molds were printed by selective laser sintering with polyamide. Cartilage grafts were harvested from one ear of a New Zealand rabbit, and PRP was prepared using 10 mL of auricular blood from the same animal. Ear cartilage was diced into 0.5‐ to 2.0‐mm pieces, weighed, mixed with PRP, and then placed inside the hollow mold. Composite grafts were then implanted into the backs of respective rabbits (n = 10) for 4 months. The shape and composition of the diced cartilage were assessed histologically, and biomechanical testing was used to determine stiffness.

Results

The 3D‐printed auricle molds were 0.6‐mm thick and showed connectivity between the internal and external surfaces, with round pores of 0.1 to 0.3 cm. After 4 months, the diced cartilage pieces had fused into an auricular shape with high fidelity to the anthropotomy. The weight of the diced cartilage was 5.157 ± 0.230 g (P > 0.05, compared with preoperative). Histological staining showed high chondrocyte viability and the production of collagen II, glycosaminoglycans, and other cartilaginous matrix components. In unrestricted compression tests, auricle stiffness was 0.158 ± 0.187 N/mm, similar to that in humans.

Conclusion

Auricle grafts were constructed successfully through packing a 3D‐printed, porous, hollow auricle mold with diced cartilage mixed with PRP. The auricle cartilage contained viable chondrocytes, appropriate extracellular matrix components, and good mechanical properties.

Levels of Evidence

NA. Laryngoscope, 129:2467–2474, 2019
Postoperative pain and analgesic requirements after septoplasty and rhinoplasty
Authors: Sclafani Anthony P. , Kim Matthew , Kjaer Klaus , Kacker Ashutosh , Tabaee Abtin
Published: March 2019

Objectives/Hypothesis

To assess and define the level of pain after rhinoplasty and septoplasty and to better define the strength and quantity of postoperative opioids needed.

Study Design

Prospective outcomes research.

Methods

Two groups of patients were enrolled. One group underwent septoplasty with/without turbinate reduction and the other group underwent functional and/or cosmetic rhinoplasty (with/without septoplasty). Patients completed a 15‐day log (daily, beginning on the day of surgery) to record the analgesics used and the daily maximal level of pain using a visual analog scale. Level of pain, number of days of moderate or severe pain, total number of opioid pills used, and total morphine milligram equivalents (MMEs) of opioid used were assessed.

Results

Pain after septoplasty and rhinoplasty was generally mild. Average pain was moderate through postoperative day (POD) 2 after rhinoplasty and only on POD 0 after septoplasty. There was no statistically significant difference between the two groups in terms of number of opioid tablets consumed or total MMEs used. Patients undergoing rhinoplasty consumed more acetaminophen than septoplasty‐only patients (7471 ± 1009 vs. 2781 ± 585, P = .0112). Ninety percent of patients would have received adequate analgesia with as few as 11 opioid tablets. All patients had excess opioid at the end of the study period.

Conclusions

Both septoplasty and rhinoplasty are associated with mostly mild pain, and postoperative opioid requirements are quite low. Surgeons can reliably reduce opioid prescription after septoplasty and rhinoplasty to as few as 11 tablets. Reducing opioid prescribing will not adversely affect the patient but will reduce the availability of opioids for misuse or diversion.

Level of Evidence

2c

Laryngoscope, 129:2020–2025, 2019
Quantitative proteomic analysis of dermal papilla from male androgenetic alopecia comparing before and after treatment with low‐level laser therapy
Authors: Panchaprateep Ratchathorn , Pisitkun Trairak , Kalpongnukul Nuttiya
Published: March 2019

Background

Currently, low‐level laser therapy (LLLT) has been approved as a new treatment for androgenetic alopecia (AGA). However, it has not been elucidated how LLLT promotes hair growth in vivo.

Objectives

To investigate the change in protein expression from dermal papilla (DP) tissues in male AGA patients after LLLT treatment using liquid chromatography tandem mass spectrometry (LC‐MS/MS) analysis.

Methods

This is an open‐label, prospective, single‐arm study obtained punch scalp biopsy specimens from patients with AGA before and after LLLT treatment. Each subject was self‐treated with helmet type of LLLT (655 nm, 5 mW) device at home for 25 minutes per treatment every other day for 24 weeks. LC‐MS/MS analysis based on the dimethyl labeling strategy for protein quantification was used to identify proteins expressed in DP tissues from AGA patients.

Results

Proteomic analysis revealed 11 statistically significant up‐regulated and 2 down‐regulated proteins in LLLT treated DP compared with baseline (P < 0.05). A bioinformatic analysis signifies that these proteins are involved in several biological processes such as regulation of cellular transcription, protein biosynthesis, cell energy, lipid homeostasis, extracellular matrix (ECM), ECM structural constituent, cell‐cell/cell‐matrix adhesion as well as angiogenesis. ATP‐binding cassette sub‐family G member, a transporter involved in cellular lipid homeostasis, was the most up‐regulated protein. Additionally, LLLT increased the main ECM proteins in DP which results in a bigger volume of DP and a clinical improvement of hair diameter in AGA patients.

Conclusion

We identified the proteome set of DP proteins of male patients with AGA treated with LLLT which implicates the role of LLLT in promoting hair growth and reversing of miniaturization process of AGA by enhancing DP cell function. Our results strongly support the benefit of LLLT in the treatment of AGA. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Pulsed‐dye laser as an adjuvant treatment for papulopustular eruptions from epidermal growth factor receptor inhibitors, a randomized blinded split‐faced controlled trial
Authors: Rerknimitr Pawinee , Suphankong Yada , Panchaprateep Ratchathorn , Kerr Stephen J. , Asawanonda Pravit
Published: March 2019

Objectives

To investigate the efficacy of pulsed‐dye laser (PDL) as an adjunctive treatment for facial papulopustular eruptions from EGFR inhibitors (EGFRi).

Methods

Fourteen patients with facial acneiform eruptions were recruited. Half side of the face was randomized to receive PDL treatment while the other side served as a control. The treatments were delivered every 2 weeks for 4 sessions. The patients were seen at baseline, weeks 2, 4, 6, 8, and 10. Erythema index (EI) measured by colorimeter, the papulopustular lesion count and physician global assessment (PGA) were obtained. Patients were allowed to use their standard treatments for their eruptions.

Results

Both arms had a significant decrease in EI from baseline at each subsequent visit. In the laser treated side, the mean (95%CI) EI decreased from 23.5 (22.24–24.76) at baseline to 16.3 (15.01–17.59) at week 10, while those of the sham were 23.49 (22.23–24.75) to 20.51 (19.22–21.8), respectively. The mean change was significantly lower in the PDL arm from week 4 onwards. The lesion counts in both groups also decreased significantly, but the mean difference between the arms was not different. PGA scores followed the same pattern as EI.

Conclusions

Adjunctive treatment with PDL was a safe and effective treatment. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
The Arg1038Gly missense variant in the NF1 gene causes a mild phenotype without neurofibromas
Authors: Trevisson Eva , Morbidoni Valeria , Forzan Monica , Daolio Cecilia , Fumini Valentina , Parrozzani Raffaele , Cassina Matteo , Midena Edoardo , Salviati Leonardo , Clementi Maurizio
Published: March 2019

Background

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by inactivating mutations of the NF1 gene. The wide allelic heterogeneity of this condition, with more than 3,000 pathogenic variants reported so far, is paralleled by its high clinical variability, which is observed even within the same family. The definition of genotype–phenotype correlations has been hampered by the complexity of the NF1 gene and, although a few exceptions have been recognized, the clinical course remains unpredictable in most patients.

Methods

Sequencing of NF1 in patients with cafè‐au‐lait spots identified the c.3112A>G variant. RNA analysis and a minigene assay were employed to investigate splicing.

Results

Here we report a novel genotype–phenotype correlation in NF1: the identification of the missense variant NM_000267.3:c.3112A>G p.(Arg1038Gly) in seven individuals from two unrelated families with a mild phenotype. All the patients manifest cafè‐au‐lait spots without neurofibromas or other NF1–associated complications, and Noonan syndrome features in most cases. The missense variant was not previously reported in available databases, segregates with the phenotype and involves a highly conserved residue. Both a minigene assay and patient's RNA analysis excluded an effect on splicing.

Conclusion

Our data support the correlation of the p.Arg1038Gly missense substitution with the cutaneous phenotype without neurofibromas or other complications. This finding may have relevant implications for patients and genetic counseling, but also to get insights into the function of neurofibromin.
PubChem and ChEMBL beyond Lipinski
Authors: Capecchi Alice , Awale Mahendra , Probst Daniel , Reymond Jean‐Louis
Published: March 2019

Seven million of the currently 94 million entries in the PubChem database break at least one of the four Lipinski constraints for oral bioavailability, 183,185 of which are also found in the ChEMBL database. These non‐Lipinski PubChem (NLP) and ChEMBL (NLC) subsets are interesting because they contain new modalities that can display biological properties not accessible to small molecule drugs. Unfortunately, the current search tools in PubChem and ChEMBL are designed for small molecules and are not well suited to explore these subsets, which therefore remain poorly appreciated. Herein we report MXFP (macromolecule extended atom‐pair fingerprint), a 217‐D fingerprint tailored to analyze large molecules in terms of molecular shape and pharmacophores. We implement MXFP in two web‐based applications, the first one to visualize NLP and NLC interactively using Faerun (http://faerun.gdb.tools/), the second one to perform MXFP nearest neighbor searches in NLP and NLC (http://similaritysearch.gdb.tools/). We show that these tools provide a meaningful insight into the diversity of large molecules in NLP and NLC. The interactive tools presented here are publicly available at http://gdb.unibe.ch and can be used freely to explore and better understand the diversity of non‐Lipinski molecules in PubChem and ChEMBL.
Use of kZ‐space for high through‐plane resolution in multislice MRI: Application to prostate
Authors: Kargar Soudabeh , Borisch Eric A. , Froemming Adam T. , Grimm Roger C. , Kawashima Akira , King Bernard F. , Stinson Eric G. , Riederer Stephen J.
Published: March 2019

Purpose

The goal of this work is to demonstrate 1 mm through‐plane resolution in multislice T2SE MRI using k‐space processing of overlapping slices and show applicability in prostate MRI.

Methods

Multiple overlapped slices are acquired and Fourier transformed in the slice‐select direction. The slice profile is incorporated into a Tikhonov‐regularized reconstruction. Through‐plane resolution is tested in a resolution phantom. An anthropomorphic prostate phantom is used to study the SNR, and results are compared with theoretical prediction. The proposed method is tested in 16 patients indicated for clinical prostate MRI who gave written informed consent as overseen by our IRB. The “proposed” vs. “reference” multislice images are compared using multiple evaluation criteria for through‐plane resolution.

Results

The modulation transfer function (MTF) plots of the resolution phantom show good modulation at frequency 0.5 lp/mm, demonstrating 1 mm through‐plane resolution restoration. The SNR measurements experimentally match the theoretically predicted values. The radiological evaluation shows that the proposed method is superior to the reference method for five criteria of sharpness but inferior with respect to artifacts.

Conclusions

In conjunction with overlapped slices a k‐space‐based reconstruction approach can be used to improve through‐plane resolution in multislice T2SE MRI. 1 mm resolution is demonstrated from 3.2 mm thick slices. The in vivo results from prostate MRI show improved sharpness when compared to the standard multislice method.
Effects of Fishery-Related Fight Time and Air Exposure on Prespawn Survival and Reproductive Success of Adult Hatchery Steelhead
Authors: Whitney Don W. , Meyer Kevin A. , McCormick Joshua L. , Bowersox Brett J.
Published: March 2019

In recent years, increased scrutiny has been placed on the physiological effects of exhaustive exercise and air exposure on caught-and-released fish. Steelhead Oncorhynchus mykiss broodstock in the South Fork Clearwater River, Idaho, were collected by anglers during a winter fishery (water temperatures of 2–5°C); this enabled fight and air exposure times to be recorded to determine their influence on prespawn survival and progeny survival to the fry stage in the hatchery. The average fight time during angling was 164 s. Air exposure was measured when anglers landed fish and again during fish transport from the river to the hatchery vehicle; the longest interval of air exposure averaged 23 s during angling and 28 s during transport. Three-year average prespawn survival was 97.0% for 1,148 angler-caught fish, compared to 91.9% for 3,325 swim-in broodstock collected at the hatchery. The top mixed-effects logistic regression model estimated that the odds of progeny survival increased by 1.027 times with each additional day of the year until an adult fish spawned; this was likely a reflection of peak spawn time in the hatchery. Fight time and air exposure time did not influence progeny survival or prespawn mortality of adult steelhead captured by anglers.
Factors influencing the pace of food intake for nursing home residents with dementia: Resident characteristics, staff mealtime assistance and environmental stimulation
Authors: Liu Wen , Jao Ying‐Ling , Williams Kristine
Published: March 2019

Aim

To examine the association of resident characteristics, staff mealtime assistance and environmental stimulation with the pace of food intake.

Design

A secondary analysis of 36 baseline eating videos involving 19 nursing assistants and 15 residents with dementia in eight nursing homes from a communication intervention study.

Methods

The outcome variable was the pace of food intake (the number of bites and drinks per minute). The exploratory variables were resident characteristics (age, gender, dementia stage and eating performance), staff mealtime assistance (frequency of verbal, visual, partial and full physical assistance) and environmental stimulation. Multi‐level models were used to examine the association.

Results

A faster pace of food intake is associated with being male, better eating performance, staff provision of visual and physical assistance and better quality of environmental stimulation that involved interaction. The pace of food intake was not associated with resident age, staff verbal assistance or partial physical assistance.
Two grid finite element discretization method for semi‐linear hyperbolic integro‐differential equations
Authors: Chen Luoping , Chen Yanping , Huang Yunqing
Published: March 2019

In this paper, we will investigate a two grid finite element discretization method for the semi‐linear hyperbolic integro‐differential equations by piecewise continuous finite element method. In order to deal with the semi‐linearity of the model, we use the two grid technique and derive that once the coarse and fine mesh sizes H, h satisfy the relation h = H2 for the two‐step two grid discretization method, the two grid method achieves the same convergence accuracy as the ordinary finite element method. Both theoretical analysis and numerical experiments are given to verify the results.
Quantifying cultural ecosystem services: Disentangling the effects of management from landscape features
Authors: Tew Eleanor R. , Simmons Benno I. , Sutherland William J.
Published: March 2019

Cultural ecosystem services are undeniably important, yet are typically neglected in land management decisions due to a suite of intractable challenges: they are highly complex, localised, and inextricably associated with landscape features. However, to incorporate the ecosystem services framework into land management, decision‐makers need the tools to disentangle the effects of land use from other factors. This is a major challenge for ecosystem services research.

Forestry is a widespread land use that has considerable potential to deliver a broad range of ecosystem services, although this requires careful management planning. Additionally, modern production forestry is undergoing a period of rapid change in the face of a plethora of challenges, such as climate change and disease. To increase cultural ecosystem services delivery from forests, managers need tools to understand the implications of different management options.

In this paper, we directly test how land use affects cultural ecosystem services. We use a new approach that recognises the underlying complexity of cultural ecosystem services but produces easily interpretable results that are locally relevant and directly applicable to land management. By combining participatory geographic information systems (GIS) and a novel site matching technique, we relate cultural values explicitly to land management, while accounting for the influence of landscape features.

Applying this new method to a major UK forest site, we conducted a large survey to gather participatory GIS data points. We showed that land management significantly affected cultural ecosystem service values and were able to make a series of practical forest management recommendations. Notably, a greater diversity of tree species would improve cultural value, and open space is important within the forest landscape.

This approach is highly flexible and can be applied to any type of landscape. It allows cultural ecosystem services to be fully integrated into land management decisions to formulate the best management strategy to maximise ecosystem service delivery.

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