bluuebunny/crossref_metadata_2025 huggingface dataset:
Vinculin presents unfavorable prediction in ovarian cancer and prevents proliferation and migration of ovarian cancer cells
Authors: Wang Fei , Fang Meixia , Kong Min , Wang Changhe , Xu Yuting
Published: May 2020

The influences of Vinculin on many cancers were blurry, including ovarian cancer. Thus, we concentrated on the efficient role of Vinculin in ovarian cancer and explored the potential mechanism(s). Expression of Vinculin in ovarian cancer tissues and cell lines was investigated by real‐time polymerase chain reaction, immunohistochemistry, and Western blot. The Kaplan–Meier manner with the logrank was performed to assess overall survival. We further evaluated the relations between Vinculin expression and clinicopathological features of ovarian cancer. Moreover, Vinculin was overexpressed or silenced by respectively transfection with pcDNA‐Vinculin or small interfering (si‐Vinculin) into human ovarian cancer cell line Caov3 or human ovarian epithelial cell line (HOEpiC). Thereafter, cell viability, cell apoptosis, and migration were checked by 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide, flow cytometer, and scratch assay, respectively. Likewise, the apoptosis‐ and migration‐related proteins were distinguished by Western blot. Compared to the nontumor tissues or HOEpiC cells, Vinculin was significantly lower expressed in the ovarian cancer tissues and cells. Furthermore, we found out that Vinculin was primarily distributed at the cell membrane and cytoplasm. Moreover, Vinculin was negatively associated with International Federation of Gynecology and Obstetrics stage, grade, and distant metastasis. Overexpression of Vinculin dramatically weakened cell viability and migration and stimulated apoptosis. Conversely, suppression of Vinculin showed opposite results. Vinculin presents unfavorable prediction in ovarian cancer and inhibits ovarian cancer proliferation and migration.
Use of telephone intake for family history taking at a cancer genetics service in Asia
Authors: Chin Xin Wei , Ang Zoe L. T. , Tan Ryan Y. C. , Courtney Eliza , Shaw Tarryn , Chen Yanni , Li Shao‐Tzu , Ngeow Joanne Yuen Yie
Published: May 2020

Family history taking is a fundamental part of genetic counseling, and however, it is also a time‐consuming process. To cope with the increasing demands at the Cancer Genetics Service in Singapore, alternative methods to collect patients’ family history were implemented to reduce the duration of the initial consultation and increase the clinic's capacity. Two interventions were performed in this study, where a family history questionnaire and telephone intakes (telephone calls to collect patient family history) were implemented prior to a cancer genetics consultation. The primary outcome of this study is the duration of the initial consultation in relation to both interventions while the secondary outcome is the clinic attendance rate before and after implementing the telephone intake. The impact of interventions was evaluated with a Plan‐Do‐Study‐Act (PDSA) methodology. The use of a family history questionnaire could not be evaluated due to poor patient response while the telephone intake was found to be feasible among the local population. Two improvements were observed after the implementation of telephone intake: (a) a significant reduction in the duration of the initial consultation from 60 to 45 min (p = .001) and (b) a significant increase of 29.7% in clinic attendance (p = .01). This study demonstrates that collecting family history information ahead of genetic counseling via telephone intake is a useful measure in improving clinic capacity, which potentially resulting in optimization of clinical resources.
Survival prediction model for non‐small cell lung cancer based on somatic mutations
Authors: Zhang Weiran , Lin Xuefeng , Li Xin , Wang Meng , Sun Wei , Han Xingpeng , Sun Daqiang
Published: May 2020

Background

The 5‐year survival rate of non‐small cell lung cancer (NSCLC) is only 15%. Screening some combined gene mutations could predict the survival of NSCLC patients and also provide new ideas for the diagnosis and treatment of NSCLC. The present study aimed to identify signature mutations for survival prediction of NSCLC.

Methods

Clinical and gene mutation information for 949 NSCLC patients was downloaded from TCGA. High frequency mutation and common mutation genes were analyzed based on 1000 cancer related genes. The LASSO‐COX model was used to screen gene mutation points and analyze their survival, and then a survival prediction model was established. Fifty NSCLC patients were collected and 1000 targeted genes were enriched by targeted next generation sequencing. The results were used to verify the combination of common mutation genes and the function of the survival model, and then to clarify their clinical significance.

Results

Ten variables were screened out after LASSO‐COX analysis, including age, tumor stage, EGFR c.[2,573 T>G], PIK3CA c.[1624G>A], TP53 c.[375G>T], TP53 c.[527G>T], TP53 c.[733G>T], TP53 c.[734G>T], TP53 c.[743G>T], NFE2L2 c.[100C>G]. Except for TP53 c.[743G>T] and NFE2L2 c.[100C>G], the residual six hot spot mutations of EGFR, PIK3CA and TP53 could be regarded as a signature mutations for forecasting the survival time of NSCLC.

Conclusions

The combination of six hot spot mutations of EGFR, PIK3CA and TP53 is expected to be used for predicting the survival time of NSCLC.
Chitinase 3‐like 1 polymorphisms and risk of chronic obstructive pulmonary disease and asthma in a Chinese population
Authors: Yu Tao , Niu Wenquan , Niu Hongtao , Duan Ruirui , Dong Fen , Yang Ting
Published: May 2020

Background

Chitinase 3‐like 1 (CHI3L1) plays an important role in airway inflammation and tissue remodeling; however, its pathogenic role in lung diseases remains unclear. In the present study, we investigated whether CHI3L1 polymorphisms are associated with the risk of chronic obstructive pulmonary disease (COPD) and asthma in a Chinese population.

Methods

We detected seven single nucleotide polymorphisms in CHI3L1 among 361 patients and 527 age‐ and sex‐matched control subjects. We analysed genotype and allele distributions using Stata software (StataCorp,CollegeStation,TX,USA). We used haplotype disease analysis and haplotype phenotype analysis to assess the relationship between seven polymorphisms and the risk of COPD and asthma.

Results

The results showed significant differences between controls and patients with COPD/asthma in the genotype distributions of the polymorphism rs4950928. Additionally, significant differences were observed in the genotype and allele distributions of rs10399805 and rs10399931 between COPD patients and controls. Moreover, the frequencies of haplotype G‐G‐T‐G‐T‐C‐G, G‐G‐T‐G‐T‐C‐C and G‐A‐T‐G‐T‐C‐G (alleles of rs12141494, rs7542294, rs880633, rs10399805, rs10399931, rs946261 and rs4950928, respectively) were significantly higher in patients with COPD. Consideration of the haplotypes of these seven single nucleotide polymorphisms in CHI3L1 in asthma patients revealed a significant association with homocysteine levels (p < 0.001).

Conclusions

Our findings suggest that the CHI3L1 polymorphisms rs4950928, rs10399805 and rs10399931 can be used as genetic markers for predicting COPD and asthma risk in the Chinese population.
Long non‐coding RNA LINC00675 is associated with bladder cancer metastasis and patient survival
Authors: Liu Xing , Ke Jingwei , Gu Li , Tang Hai , Luo Xiaoqin
Published: May 2020

Background

Muscle‐invasive bladder cancer (MIBC), a bladder cancer that spreads into the detrusor muscle of the bladder, leads to a poor outcome. Long noncoding RNA LINC00675 has been reported to play import roles in several cancer types, although its biological function and underlying mechanism in MIBC remain largely unclear.

Methods

Eighty‐nine patients with MIBC were enrolled in the present study. RNA expression was measured using a quantitative reverse transcription‐polymerase chain reaction. Protein expression was detected using western blotting. Transwell assays were performed to analyze the abilities of bladder cancer cells to migrate and invade. An RNA microarray was carried out to analyze LINC00675‐regulated mRNAs in bladder cancer cells.

Results

We found that LINC00675 expression was decreased in MIBC tissues compared to matched normal tissues, and was correlated with lymph node‐metastatic MIBC. MIBC patients with low expression of LINC00675 had worse survival rates than those with high expression. Functional investigation showed that ectopic expression of LINC00675 inhibited bladder cancer cell migration, invasion and proliferation, whereas LINC00675 knockdown presented an opposite effect. Mechanistically, we found that LINC00675 inhibited β‐catenin and its downstream gene expression.

Conclusions

The findings of the present study suggest that LINC00675 regulates β‐catenin expression, and is associated with bladder cancer metastasis and patient survival.
LINC00641 hinders the progression of cervical cancer by targeting miR‐378a‐3p/CPEB3
Authors: Zhang Yan , Yu Rong , Li Lei
Published: May 2020

Background

LINC00641 was found to act in anti‐tumor manner in several types of cancers. Nonetheless, the detailed functions of LINC00641 have not been determined in cervical cancer (CC).

Methods

The expression of LINC00641, miR‐378a‐3p and CPEB3 was examined using a quantitative reverse transcriptase‐polymerase chain reaction. The relationships between LINC00641 and its downstream mechanism were illustrated by RNA pull‐down and luciferase reporter experiments.

Results

LINC00641 was found to be under‐expressed in CC cell lines. By overexpressing LINC00641, cell proliferative, migratory and invasive abilities, as well as epithelial mesenchymal transition (EMT) characteristics, were inhibited, whereas the rate of apoptosis was increased. Next, a starBase search (http://starbase.sysu.edu.cn) was applied to select microRNAs that had binding sequences with LINC00641. By up‐regulating LINC00641 expression, miR‐378a‐3p expression displayed the strongest decline. Moreover, miR‐378a‐3p was found to be up‐regulated in CC cell lines. In addition, LINC00641 hindered the progression of CC by decreasing miR‐378a‐3p expression. CPEB3 was discovered as a downstream target of miR‐378a‐3p and was under‐expressed in CC cells. Furthermore, knockdown of CPEB3 could counter the influence of an overexpression of LINC00641 with respect to CC progression.

Conclusions

LINC00641 suppressed the progression of CC by targeting miR‐378a‐3p/CPEB3, suggesting that LINC00641 may have positive therapeutic impact for treatment for CC.
Hepatocellular carcinoma with a non‐smooth tumor margin on hepatobiliary‐phase gadoxetic acid disodium‐enhanced magnetic resonance imaging. Is sectionectomy the suitable treatment?
Authors: Romanzi Andrea , Ariizumi Shunichi , Kotera Yoshihito , Omori Akiko , Yamashita Shingo , Katagiri Satoshi , Egawa Hiroto , Yamamoto Masakazu
Published: May 2020

Background/Purpose

Anatomical sectionectomy or larger resection is known to be effective in patients with hepatocellular carcinoma (HCC) with microvascular invasion. A non‐smooth tumor margin on hepatobiliary‐phase gadoxetic acid disodium‐enhanced magnetic resonance imaging (EOB‐MRI) can predict microvascular invasion of HCC. We evaluated the usefulness of EOB‐MRI for operative planning.

Methods

We evaluated 224 patients with single HCC who underwent hepatectomy between 2010 and 2013. The tumor margin was determined preoperatively. The hepatic resection was determined based on tumor location, liver function, 3D CT simulation and functional liver reserve. To control for confounding variable distributions, propensity score match was applied to compare the outcomes. Multivariate analysis was conducted to identify independent predictors of 5‐year recurrence‐free survival (RFS) and overall survival (OS).

Results

Of 113 patients with a non‐smooth tumor margin, 40 patients (35%) showed microscopic portal invasion. The 5‐year RFS and OS rates were significantly higher after sectionectomy or larger hepatectomy (hemihepatectomy) than after segmentectomy or smaller hepatectomy (non‐anatomical resection). Of 111 patients with a smooth tumor margin, eight patients (7%) showed microscopic portal invasion. The 5‐year RFS and OS rates did not differ significantly between patients who underwent sectionectomy and those who underwent segmentectomy.

Conclusions

Our preliminary results appear to recommend that HCC with a non‐smooth margin on HB‐phase images is treated with anatomical sectionectomy or larger hepatectomy.
Reaction of tris(hydroxymethyl)phosphine and cinnamaldehyde in methanol
Authors: Moiseev Dmitry V. , Malysheva Yulia B. , Gushchin Aleksey V. , James Brian R.
Published: May 2020

Reaction of tris(hydroxymethyl)phosphine with excess cinnamaldehyde in CH3OH or CD3OD, followed using NMR, proceeds via several phosphorus‐containing intermediates, multiple transformations of organic parts, and with the solvent H/D isotope effect on products. In both solvents, one CH2OH group of tris(hydroxymethyl)phosphine is readily replaced by the cinnamaldehyde moiety to give the primary product, a 1,3‐oxaphosphorinane derivative. Slower replacement of the second CH2OH group leads to a mixture of aliphatic and heterocyclic phosphine intermediates in a ratio of ~4:1 in CH3OH and ~1:1 in CD3OD; both intermediates contain alcohol and aldehyde groups and convert rapidly into intra‐ and intermolecular hemiacetals. The hemiacetals of the aliphatic phosphine rearrange further into an unsymmetrical trialkylphosphine oxide, whereas the hemiacetals of the heterocyclic phosphine react with the third mole of cinnamaldehyde to replace the third CH2OH group of tris(hydroxymethyl)phosphine. All intermediates and products are formed as mixtures of stereoisomers.
Synthesis, anti‐platelet aggregation activity evaluation and structure–activity relationships of a series of novel purine derivatives
Authors: Li Shunlai , Zhou Cheng , Yu Mingwu , He Qiwen , Du Hongguang
Published: May 2020

This article described how further extensive variation of the substituents on the purine scaffold of adenosine triphosphate (ATP), and the human anti‐platelet aggregation activities were modified in order to find exploitation of the structure–activity relationships (SAR). A series of novel designed 6‐alkylamino‐2‐alkylthio‐9‐hydroxyalkyl(carbalkoxy) purine derivatives were synthesized via a modification procedure, and the human anti‐platelet aggregation activities were evaluated. The SAR of these compounds were analyzed in detail, and the results of the structural requirements of the substituents to improve potency may provide a basis for the development of potent P2Y12 antagonists.
Clinical characteristics and outcomes of cancer patients with COVID‐19
Authors: Yang Fan , Shi Shaobo , Zhu Jiling , Shi Jinzhi , Dai Kai , Chen Xiaobei
Published: May 2020

This retrospective study aimed to analysis clinical characteristics and outcomes of cancer patients with novel coronavirus disease‐19 (COVID‐19). Medical records, laboratory results and radiologic findings of 52 cancer patients with COVID‐19 were collected, clinical characteristics and outcomes were summarized. A total of 52 cancer patients with COVID‐19 were included. Median age of 52 cancer patients with COVID‐19 was 63 years (34‐98). Thirty‐three (63.5%) patients were mild and 19 (36.5%) were severe/critical. Lung cancer was the most frequent cancer type (10, 19.2%). The common symptoms were as follows: fever (25%), dry cough (17.3%), chest distress (11.5%), and fatigue (9.6%). There were 33 (63.5%) patients had comorbidities, the most common symptom was hypertension (17, 51.5%). Twenty‐six (78.8%) patients developed pneumonia on admission. Lymphocytes (0.6 × 109/L) decreased in both mild and severe/critical patients. Median levels of D‐dimer, C‐reactive protein, procalcitonin, and lactate dehydrogenase were 2.8 mg/L, 70.5 mg/L, 0.3 ng/mL, and 318 U/L, respectively, which increased significantly in severe/critical patients compared with the mild patients. Interleukin‐6 (12.6  pg/mL) increased in both mild and severe/critical patients, there was a significant difference between them. Complications were observed in 29 (55.8%) patients, such as liver injury (19, 36.5%), acute respiratory distress syndrome (9, 17.3%), sepsis (8, 15.4%), myocardial injury (8, 15.4%), renal insufficiency (4, 7.7%), and multiple organ dysfunction syndrome (3, 5.8%). Eleven (21.2%) patients with cancer died. The infection rate of severe acute respiratory syndrome coronavirus 2 in patients with cancer was higher than the general population, cancer patients with COVID‐19 showed deteriorating conditions and poor outcomes.
Hepatic involvement in COVID‐19 patients: Pathology, pathogenesis, and clinical implications
Authors: Li Yueying , Xiao Shu‐Yuan
Published: May 2020

During the clinical course of coronavirus disease 2019 (COVID‐19), it has been observed that hepatic injury occurs in a significant proportion of patients, particularly in those with severe or critical illness. Mild increase in sinusoidal lymphocytic infiltration, sinusoidal dilatation, steatosis and multifocal hepatic necrosis are the pathologic changes reported. Direct viral‐induced cellular injuries and potential hepatotoxicity from therapeutic drugs are two likely underlying mechanisms. In addition, the pre‐existing chronic liver disease exacerbated during COVID‐19, and COVID‐19‐related hyperinflammatory reactions may contribute to liver injury as well. Further studies of additional autopsy cases will help clarifying these possibilities.
Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside‐Wuhan patients, China
Authors: Qiu Chengfeng , Deng Ziwei , Xiao Qian , Shu Yuanlu , Deng Ye , Wang Hongqiang , Liao Xin , Liu Huiwen , Zhou Dinghui , Zhao Xiang , Zhou Jianliang , Wang Jin , Shi Zhihua , Long Da
Published: May 2020

Cases of coronavirus disease 2019 (COVID‐19) emigrating from Wuhan escalated the risk of spreading the disease in other cities. This report focused on outside‐Wuhan patients to assess the transmission and clinical characteristics of this illness. Contact investigation was conducted on each patient who was admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from 22 January to 23 February 2020. Cases were confirmed by the polymerase chain reaction test. Demographic, clinical, and outcomes were collected and analyzed. Of the 104 patients, 48 (46.15%) were cases who immigrated from Wuhan; 93 (89.42%) had a definite contact history with infection. Family clusters were the major body of patients. Transmission along the chain of three “generations” was observed. Five asymptomatic infected cases were found and two of them infected their relatives. Mean age was 43 (range, 8‐84) years, and 49 (47.12%) were male. The median incubation period was 6 (range, 1‐32) days, which of 8 patients ranged from 18 to 32 days, 96 (92.31%) were discharged, and 1 (0.96%) died. The average hospital stay was 10 (range, 8‐14) days. Family but not community transmission became the main body of infections in the two centers, suggesting the timely control measures after the Wuhan shutdown worked well. Asymptomatic transmission demonstrated here warned us that it may lead to the widespread of COVID‐19. A 14‐day quarantine may need to be prolonged.
Patient characteristics, procedure details including catheter devices, and complications of catheter ablation for ventricular tachycardia: a nationwide observational study
Authors: Kitamura Takeshi , Nakajima Mikio , Kawamura Iwanari , Ohbe Hiroyuki , Sasabuchi Yusuke , Matsui Hiroki , Fushimi Kiyohide , Fukamizu Seiji , Yasunaga Hideo
Published: May 2020

Background

Nationwide data are insufficient with respect to the characteristics of patients undergoing ventricular tachycardia (VT) ablation, complications of VT ablation, and procedure details including catheter devices used during VT ablation. The present study was performed to describe the patient characteristics, procedure details including catheter devices, and in‐hospital complications of catheter ablation for VT using a national inpatient database.

Methods

We used the Diagnosis Procedure Combination database, a national Japanese inpatient database, to identify patients who underwent VT ablation from July 2010 to March 2017. We examined patients’ age, gender, baseline diseases, comorbid conditions, admission status, catheter devices and drugs used, and in‐hospital complications of VT ablation.

Results

We identified 10 641 patients (median age, 61 years) who underwent VT ablation. The most frequently observed background heart disease among patients with structural heart disease was ischemic cardiomyopathy. An irrigated ablation catheter was used in 73% of patients, a force‐sensing ablation catheter was used in 22%, and intracardiac echocardiography was used in 25%. The frequency of using these procedures continuously increased over time. Overall, the prevalence of in‐hospital complications was 3.5% (cardiac tamponade, 0.8%; stroke, 0.6%; critical bleeding, 1.9%; mechanical circulatory support, 0.9%; and in‐hospital death, 0.8%).

Conclusions

The results of this study show the clinical features of VT ablation in a real‐world clinical setting. The use of irrigated catheters, force‐sensing catheters, and intracardiac echocardiography increased over time. The prevalence of in‐hospital complications was 3.5%.
Image‐based design and 3D‐metal printing of a rat hip implant for use in a clinically representative model of joint replacement
Authors: Paish Adam D. M. , Nikolov Hristo N. , Welch Ian D. , El‐Warrak Alexander O. , Teeter Matthew G. , Naudie Douglas D. R. , Holdsworth David W.
Published: May 2020

The aim of this study was to obtain micro‐computed tomography derived measurements of the rat proximal femur, to create parameterized rat hip implants that could be surgically installed in a clinically representative small animal model of joint replacement. The proximal femoral anatomy of N = 25 rats (male, Sprague‐Dawley, 390‐605 g) was quantified. Key measurements were used to parameterize computer‐aided design models of monoblock rat femoral implants. Linear regression analysis was used to determine if rat hip dimensions could be predicted from animal weight. A correlation analysis was used to determine how implants could be scaled to create a range of sizes. Additive manufacturing (3D printing) was used to create implants in medical‐grade metal alloys. Linear regressions comparing rat weight to femoral head diameter and neck‐head axis length revealed a significant nonzero slope (P < .05). Pearson's correlation analysis revealed five significant correlations between key measurements in the rat femur (P < .05). Implants were installed into both cadaveric and live animals; iterative design modifications were made to prototypes based on these surgical findings. Animals were able to tolerate the installation of implants and were observed ambulating on their affected limbs postoperatively. Clinical significance: We have developed a preclinical rat hip hemiarthroplasty model using image‐based and iterative design techniques to create 3D‐metal printed implants in medical‐grade metal alloys. Our findings support further development of this model for use as a low‐cost translational test platform for preclinical orthopaedic research into areas such as osseointegration, metal‐on‐cartilage wear, and periprosthetic joint infection.
Predicting Axillary Lymph Node Metastasis in Patients With Breast Invasive Ductal Carcinoma With Negative Axillary Ultrasound Results Using Conventional Ultrasound and Contrast‐Enhanced Ultrasound
Authors: Zhu An‐Qi , Li Xiao‐Long , An Li‐Wei , Guo Le‐Hang , Fu Hui‐Jun , Sun Li‐Ping , Xu Hui‐Xiong
Published: May 2020

Objectives

The purpose of this study was to establish a scoring system for predicting axillary lymph node metastasis (ALNM) in patients with breast invasive ductal carcinoma with negative axillary ultrasound (US) results.

Methods

In this retrospective study, 156 breast invasive ductal carcinoma lesions from 156 women were retrospectively enrolled. The features of conventional US and contrast‐enhanced ultrasound (CEUS) qualitative enhancement patterns and quantitative enhancement parameters were analyzed. Subsequently, a scoring system was created by a multivariate logistic regression analysis.

Results

The results found that 60 patients (38%) showed ALNM. A scoring system was defined as risk score = 1.75 × (if lesion size ≥20 mm) + 1.93 × (if uncircumscribed margin shown on conventional US) + 1.77 × (if coarse or twisting penetrating vessels shown on CEUS). When the risk scores were less than 1.75, 1.75 to 1.93, 1.94 to 3.70, and 3.70 or higher, the risk rates of ALNM were 0% (0 of 9), 10.7% (5 of 46), 29.2% (14 of 48) and 77.4% (41 of 53), respectively. In comparison with conventional US alone, the scoring system using the combination of conventional US and CEUS showed better discrimination ability in terms of the area under the curve (0.830 versus 0.777; P = .037).

Conclusions

A scoring system based on conventional US and CEUS may improve the prediction of ALNM.
Laryngotracheal Mucosal Surface Expression of Candidate Biomarkers in Idiopathic Subglottic Stenosis
Authors: Liu Melissa M. , Motz Kevin M. , Murphy Michael K. , Yin Linda X. , Ding Dacheng , Gelbard Alexander , Hillel Alexander T.
Published: May 2020

Objectives

Idiopathic subglottic stenosis (iSGS) is an inflammatory process leading to fibrosis and narrowing of the laryngotracheal airway. There is variability in patient response to surgical intervention, but the mechanisms underlying this variability are unknown. In this pilot study, we measure expression of candidate targets at the mucosal surface of the subglottis in iSGS patients. We aim to identify putative biomarkers for iSGS that provide insights into the molecular basis of disease progression, yield a gene signature for the disease, and/or predict a response to therapy.

Study Design

In vitro comparative study of human cells.

Methods

Levels of candidate transcripts and proteins were measured in healthy and stenotic laryngotracheal tissue specimens taken from the mucosal surface in 16 iSGS patients undergoing endoscopic balloon dilation. Pre‐ and post‐operative pulmonary function test and patient reported voice and breathing outcomes were also assessed. Unsupervised clustering was used to define patient subgroups based on expression profile.

Results

Pulmonary function and voice and breathing outcome metrics demonstrated significant post‐operative improvement. Transcript levels of αSMA, CCL2, COL1A1, COL3A1, FN1, IFNG, and TGFB1 and protein levels of CCL2, IFNG, and IL‐6 were significantly upregulated in stenotic as compared to healthy tissues. Marked heterogeneity was observed in the patterns of expression of candidate markers across individuals and tissue types. Patient subgroups defined by expression profile did not show a statistically significant difference in dilation interval.

Conclusion

Pro‐inflammatory and pro‐fibrotic pathways are significantly upregulated along the mucosal surface of stenotic laryngotracheal tissues, and CCL2 and IFNG merit further investigation as potential iSGS biomarkers.

Level of Evidence

4 Laryngoscope, 131:342–349, 2021
Which Anesthesia Regimen Is Best to Reduce Pulmonary Complications After Head and Neck Surgery?
Authors: Zhou Dan , Zhu Xi , Wang Likuan , Yang Xudong , Liu Yun , Zhang Xiang
Published: May 2020

Objectives/Hypothesis

The differences between intravenous and inhalation anesthesia in clinical postoperative pulmonary complications (PPCs) have been studied in cardiac and lung resection surgery. Clinical evidence for the effects of these two anesthetics on PPCs in other types of surgery is still missing. We aimed to assess the impact of sevoflurane and propofol on the incidence of PPCs in patients undergoing surgery for head and neck cancer.

Study Design

Double‐blind, randomized, controlled trial.

Methods

We assigned 220 adults at intermediate‐to‐high risk of PPCs scheduled for head and neck cancer surgery with radial forearm or fibular flap reconstruction to either propofol or sevoflurane as a general anesthetic. The occurrence of pulmonary complications according to the Clavien‐Dindo score was defined as the primary (within 7 days after surgery) outcome.

Results

The PPC incidence during 7 days after surgery was 32.4% and 18.2% in the propofol and sevoflurane groups, respectively (P = .027). The corresponding incidence of PPCs in patients who underwent tracheotomy at the end of surgery in the two groups was 44.8% and 24.5%, respectively (P = .030). In addition, the Clavien‐Dindo classification showed significant differences between groups in minor complications (grades I and II) but not in major complications (grades III–V).

Conclusions

Compared with intravenous anesthesia, the administration of sevoflurane reduces the incidence of minor PPCs (grades I and II) in moderate‐ and high‐risk patients who have undergone tracheotomy after head and neck cancer surgery with radial forearm or fibular flap reconstruction.

Level of Evidence

2 Laryngoscope, 131:E108–E115, 2021
The GRIA3 c.2477G > A Variant Causes an Exaggerated Startle Reflex, Chorea, and Multifocal Myoclonus
Authors: Piard Juliette , Béreau Matthieu , XiangWei Wenshu , Wirth Thomas , Amsallem Daniel , Buisson Lauren , Richard Philippe , Liu Nana , Xu Yuchen , Myers Scott J. , Traynelis Stephen F. , Chelly Jameleddine , Anheim Mathieu , Raynaud Martine , Maldergem Lionel Van , Yuan Hongjie
Published: May 2020

Background

Hemizygous mutations in GRIA3 encoding the GluA3 subunit of the amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor are known to be associated with neurodevelopmental disorders, including intellectual disability, hypotonia, an autism spectrum disorder, sleep disturbances, and epilepsy in males.

Objective

To describe a new and consistent phenotype in 4 affected male patients associated with an undescribed deleterious variant in GRIA3.

Methods

We evaluated a large French family in which segregate a singular phenotype according to an apparent X‐linked mode of inheritance. Molecular analyses using next generation sequencing and in vitro functional studies using 2‐electrode voltage clamp recordings on Xenopus laevis oocytes and a β‐lactamase reporter assay in transfected human embryonic kidney (HEK293) cells were performed.

Results

In addition to mild intellectual disability and dysarthria, affected patients presented a tightly consistent early‐onset movement disorder combining an exaggerated startle reflex with generalized chorea and multifocal myoclonus. The unreported GRIA3 missense variant c.2477G > A; p.(Gly826Asp) affecting the fourth transmembrane domain of the protein was identified in index patients and their unaffected mothers. Functional studies revealed that variant receptors show decreased current response evoked by agonist (ie, kainic acid and glutamate) and reduced expression on the cell surface in favor of pathogenicity by a loss‐of‐function mechanism.

Conclusions

Taken together, our results suggest that apart from known GRIA3‐related disorders, an undescribed mutation‐specific singular movement disorder does exist. We thus advocate considering GRIA3 mutations in the differential diagnosis of hyperekplexia and generalized chorea with myoclonus. © 2020 International Parkinson and Movement Disorder Society
Mathematical modeling of the combustion process for a polydispersed fuel
Authors: Ivanov Alexander , Alexandrova Irina , Alexandrov Dmitri
Published: May 2020

In the present paper, we model a combustion process of a polydispersed fuel using the integro‐differential system of balance and kinetic equations supplemented by the boundary and initial conditions. Analytical solutions of this system are found in a parametric form. It is shown that the furnace temperature, oxidant concentration, and the particle‐size distribution function eventually approach the corresponding steady‐state solutions. As this takes place, the distribution function reduces with increasing the radii of burning particles.
Frequency increase of an InP‐based HBT using improved layout design and base‐collector undercut process
Authors: Lee Jongwon , Lee Kiwon
Published: May 2020

In this article, an improved layout design and a base‐collector undercut etching process have been proposed and demonstrated for a high‐speed InP/InGaAs heterojunction bipolar transistor (HBT). The fabricated HBT using proposed methods has a smaller parasitic base‐collector (B‐C) area, resulting in reduced B‐C capacitance (CBC), a reduction of 36% compared to that in the conventional HBT. A current gain cutoff frequency (fT) and a maximum oscillation frequency (fmax) of the proposed HBT have been increased from 110 to 131 GHz and from 112 to 131 GHz due to the reduced CBC. These results clearly show the effectiveness of the proposed technique for the HBTs.
Technical Note: Flattening filter free beam from Halcyon linac: Evaluation of the profile parameters for quality assurance
Authors: Fogliata A. , Cayez R. , Garcia R. , Khamphan C. , Reggiori G. , Scorsetti M. , Cozzi L.
Published: May 2020

Introduction

The use of flattening filter free (FFF) beams generated by standard linear accelerators is increasing in the clinical practice. The radiation intensity peaked toward the beam central axis is properly managed in the optimization process of treatment planning through intensity modulation. Specific FFF parameters for profile analysis, as unflatness and slope for FFF beams, based on the renormalization factor concept has been introduced for quality assurance purposes. Recently, Halcyon, an O‐ring based linear accelerator equipped with a 6 MV FFF beam only has been introduced by Varian.

Methods

Renormalization factors and related fit parameters according to Fogliata et al. [“Definition of parameters for quality assurance of FFF photon beams in radiation therapy,” Med. Phys. 39, 6455–6464 (2012)] have been evaluated for the 6 MV FFF beam generated by Halcyon units. The Halcyon representative beam data provided by Varian were used. Dose fall‐off at the field edges was matched with an unflattened beam generated by a 6 MV from a TrueBeam linac. Consistency of the results was evaluated against measurements on a clinical Halcyon unit, as well as a TrueBeam 6 MV FFF for comparison.

Results

The five parameters in the analytical equation for estimating the renormalization factor were determined with an R2 of 0.997. The comparison of the unflatness parameters between the Halcyon representative and hospital beam data was consistent within a range of 0.6%. Consistently with the computed parameters, the Halcyon profiles resulted in a less pronounced peak than TrueBeam.

Conclusion

Renormalization factors and related fit parameters from the 6 MV FFF beam generated by the Varian Halcyon unit are provided.
Retrospective rigid motion correction of three‐dimensional magnetic resonance fingerprinting of the human brain
Authors: Kurzawski Jan W. , Cencini Matteo , Peretti Luca , Gómez Pedro A. , Schulte Rolf F. , Donatelli Graziella , Cosottini Mirco , Cecchi Paolo , Costagli Mauro , Retico Alessandra , Tosetti Michela , Buonincontri Guido
Published: May 2020

Purpose

To obtain three‐dimensional (3D), quantitative and motion‐robust imaging with magnetic resonance fingerprinting (MRF).

Methods

Our acquisition is based on a 3D spiral projection k‐space scheme. We compared different orderings of trajectory interleaves in terms of rigid motion‐correction robustness. In all tested orderings, we considered the whole dataset as a sum of 56 segments of 7‐s duration, acquired sequentially with the same flip angle schedule. We performed a separate image reconstruction for each segment, producing whole‐brain navigators that were aligned to the first segment using normalized correlation. The estimated rigid motion was used to correct the k‐space data, and the aligned data were matched with the dictionary to obtain motion‐corrected maps.

Results

A significant improvement on the motion‐affected maps after motion correction is evident with the suppression of motion artifacts. Correlation with the motionless baseline improved by 20% on average for both T1 and T2 estimations after motion correction. In addition, the average motion‐induced quantification bias of 70 ms for T1 and 18 ms for T2 values was reduced to 12 ms and 6 ms, respectively, improving the reliability of quantitative estimations.

Conclusion

We established a method that allows correcting 3D rigid motion on a 7‐s timescale during the reconstruction of MRF data using self‐navigators, improving the image quality and the quantification robustness.
Enduring impact of childhood adversity on lower urinary tract symptoms in adult women
Authors: Epperson C. Neill , Duffy Korrina A. , Johnson Rachel L. , Sammel Mary D. , Newman Diane K.
Published: May 2020

Aims

To determine whether childhood adversity is associated with self‐reported lower urinary tract symptoms (LUTS) among older adult women.

Methods

A convenience sample of women (≥55 years old) who presented to an academic urology practice or who had participated in a previous bladder health prevention study completed questionnaires including the LUTS Tool (on frequency and bother of LUTS), the Adverse Childhood Experiences (ACEs) Questionnaire, the Spielberger State‐Trait Anxiety Inventory, and the Center for Epidemiologic Studies Depression Scale.

Results

The average age (SD) of participants (N = 151) was 64.7 (6.9) years. The total number of ACEs predicted the total number of LUTS, β = .39 (95% confidence interval [CI] = 0.14, 0.64), P = .003, as well as LUTS frequency, β = .09 (95% CI = 0.04, 0.13), P < .001. ACEs predicted bother for nocturia, β = 0.12 (95% CI = 0.03, 0.22), P = .008. Negative affect symptoms did not mediate the relationship between the total number of ACEs and the total number of LUTS. Rather, ACEs predicted LUTS and negative affect symptoms through (at least partially) independent pathways. Analyses controlled for tobacco use, number of vaginal deliveries, hypertension, overactive bladder medication use, body mass index, income, and race because these variables were significantly associated with the total number of ACEs or total number of LUTS.

Conclusions

Childhood adversity has an enduring impact on risk for LUTS in adulthood even when controlling for potential confounds and this relationship cannot be explained by negative affect symptoms.
Exploring the characteristics, performance, and modification of Matrimid for development of thin‐film composite and thin‐film nanocomposite reverse osmosis membranes
Authors: Hosseini Seyed Saeid , Jalili Palandi Mousa Al‐Reza , Mokarinezhad Nikan
Published: May 2020

Reverse osmosis (RO) membrane technology is widely employed to address the demands for freshwater. In this study, fabrication and performance evaluation of customized RO membranes comprised of Matrimid and polyacrylonitrile (PAN) is carried out. While exploring adoption of slip coating procedure, the effects of various modification techniques including incorporation of TiO2 nanoparticles and polyethylene glycol (PEG) into the skin layer as well as cross‐linking were investigated. The individual and combined effects of parameters on membrane morphology, surface characteristics and performance were also examined. Despite the distinctive characteristics of involved materials, delamination‐free composite membranes were successfully formed with an intimate contact at the interface of two layers. The results also indicated that increasing concentration of Matrimid in dope solution led to increase in membrane thickness and consequently decline in water flux. In the best case, membrane prepared using 1 wt.% Matrimid in dope exhibited water flux of 0.98 LMH and NaCl rejection of 95.7%. Also, incorporation of 3 wt.% TiO2 nanoparticles offered membranes with improved water flux of 1.37 LMH and salt rejection of 95.8%. On the other hand, water flux and salt rejection in membranes containing 5 wt.% PEG were 1.18 LMH and 96.2%, respectively. The co‐presence of both nanoparticles and PEG provided more insights about the contributing factors in tuned membranes. Modification of skin layer by cross‐linking significantly improved salt rejection at the expense of water flux. The results are scientifically interpreted and compared to the values reported in literature.
Considerations for pharmacoepidemiological analyses in the SARS‐CoV‐2 pandemic
Authors: Pottegård Anton , Kurz Xavier , Moore Nicholas , Christiansen Christian F. , Klungel Olaf
Published: May 2020

The coronavirus disease 2019 (COVID‐19) pandemic has triggered several hypotheses regarding use of specific medicines and risk of infection as well as prognosis. Under these unique circumstances, rapid answers require quick engagement in data collection and analyses; however, appropriate design and conduct of pharmacoepidemiologic studies are needed to generate valid and reliable evidence. In this paper, endorsed by the International Society for Pharmacoepidemiology, we provide methodological considerations for the conduct of pharmacoepidemiological studies in relation to the pandemic across eight domains: (1) timeliness of evidence, including the need to prioritise some questions over others in the acute phase of the pandemic; (2) the need to align observational and interventional research on efficacy; (3) the specific challenges related to “real‐time epidemiology” during an ongoing pandemic; (4) what design to use to answer a specific question; (5) considerations on the definition of exposures; (6) what covariates to collect; (7) considerations on the definition of outcomes; and (8) the need for transparent reporting.
Long‐term pulmonary function testing in pediatric bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation
Authors: Walther Sophie , Rettinger Eva , Maurer Hannah Miriam , Pommerening Helena , Jarisch Andrea , Sörensen Jan , Schubert Ralf , Berres Martin , Bader Peter , Zielen Stefan , Jerkic Silvija Pera
Published: May 2020

Rationale

Bronchiolitis obliterans syndrome (BOS) is a severe, chronic inflammation of the airways leading to an obstruction of the bronchioles. So far, there are only a few studies looking at the long‐term development of pulmonary impairment in children with BOS.

Objective

The objective of this study was to investigate the incidence and long‐term outcome of BOS in children who underwent allogeneic hematopoietic stem cell transplantation (HSCT).

Methods

Medical charts of 526 children undergoing HSCT in Frankfurt/Main, Germany between 2000 and 2017 were analyzed retrospectively and as a result, 14 patients with BOS were identified. A total of 271 lung functions (spirometry and body plethysmography), 26 lung clearance indices (LCI), and 46 chest high‐resolution computed tomography (HRCT) of these 14 patients with BOS were evaluated.

Results

Fourteen patients suffered from BOS after HSCT (2.7%), whereby three distinctive patterns of lung function impairment were observed: three out of 14 patients showed a progressive lung function decline; two died and one received a lung transplant. In five out of 14 patients with BOS persisted with a severe obstructive and secondarily restrictive pattern in lung function (forced vital capacity [FVC] < 60%, forced expiratory volume in 1 second [FEV1] < 50%, and FEV1/FVC < 0.7) and increased LCI (11.67‐20.9), six out of 14 patients recovered completely after moderate lung function impairment and signs of BOS on HRCT. Long‐term FVC in absolute numbers was increased indicating that the children still have lung growth.

Conclusion

Our results showed that the incidence of BOS in children is low. BOS was associated with high mortality and may lead to persistent obstructive lung disease; although, lung growth continued to exist.
Association between dihydrotestosterone and long‐term risk for prostate cancer mortality: A prospective cohort study
Authors: Lundgren Per‐Olof , Kjellman Anders , Norming Ulf , Gustafsson Ove
Published: May 2020

Background

The androgen metabolism plays an important role in the progression of prostate cancer. Contradictory to what one might assume given the androgenic potency of dihydrotestosterone (DHT) there are indications that high DHT levels protect from prostate cancer. We want to determine whether there is a long‐term association between baseline levels of DHT and death from prostate cancer.

Method

During the years 1988 and 1989, 1782 men out of 2400 invited were screened for prostate cancer. The invited men were randomly selected from a background population of more than 27 000 men. Serum levels of DHT were analyzed for all 65 men diagnosed in the trial and 130 controls from the same cohort without any signs of prostate cancer. In this study we evaluate outcomes for the whole cohort (n = 195), the men without clinical signs of prostate cancer at beginning of follow up (n = 130) and men with screening detected cancer (n = 65).

The cohort was followed up after 30 years and data from the Swedish Cause of Death Registry and the Swedish Cancer Registry were extracted. Hazard ratios (HRs) were calculated using Cox regression models.

Result

High DHT levels were positively correlated to a lower risk for prostate cancer death in the entire cohort: HR = 0.44 (0.25‐0.77 95% confidence interval [CI]). The positive correlation remained significant for the subgroup analysis. HR for the men enrolled in the study without any clinical signs of prostate cancer was 0.25 (0.07‐0.88 95% CI) and for the men with a prostate cancer diagnosis at time of inclusion: HR = 0.50 (0.26‐0.94 95% CI).

Conclusion

DHT is negatively associated with long‐term prostate cancer death regardless of clinical presentation at time of inclusion.
Granulomatous lymphocytic interstitial lung disease: limiting immunosuppressive therapy—a single‐centre experience
Authors: Beaton Thomas J. , Gillis David , Morwood Karen , Bint Michael
Published: May 2020

Granulomatous lymphocytic interstitial lung disease (GLILD) is characterized by lymphocytic and granulomatous pulmonary infiltration occurring in common variable immunodeficiency (CVID). It is associated with increased mortality compared with CVID patients without GLILD. There are no treatment guidelines due to the low prevalence and the heterogeneity of the condition. A case review of three patients diagnosed with GLILD was performed from a single Australian centre. Patients met the European Society of Immunodeficiency criteria for CVID and a diagnosis of GLILD was confirmed by a multidisciplinary team. Patients were managed with immunoglobulin (Ig) replacement and immunosuppressive agents if required: the decision for immunosuppression was made on the basis of symptoms and declining pulmonary function. All patients clinically improved. One patient had immunosuppressive treatment ceased. GLILD responds to varying immunosuppressive regimes when IgG monotherapy fails. Immunosuppressive therapy can be discontinued following improvement, but patients require close observation. This series helps inform future GLILD treatment guidelines.
Pulmonary alveolar proteinosis after lung transplantation
Authors: Divithotawela Chandima , Apte Simon H. , Tan Maxine E. , De Silva Tharushi A. , Chambers Daniel C.
Published: May 2020

We report the case of a 69‐year‐old man five‐month post double lung transplant for idiopathic pulmonary fibrosis (IPF) who presented with progressive breathlessness, loss of lung function, and diffuse ground glass shadowing on the chest computed tomography. Transbronchial lung biopsy revealed foamy macrophages, hyperplasia of type II pneumocytes, and eosinophilic material in the alveolar space. Video thoracic lung biopsy was performed, and histology confirmed pulmonary alveolar proteinosis. Anti‐granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) antibodies were negative. Bilateral sequential whole lung lavage (WLL) was performed. Lavage fluid recovered during WLL was notably dark brown in colour and upon analysis was shown to contain heavily oxidized protein (lipofuscin), giant lipofuscin‐engorged macrophages, and a highly pro‐inflammatory gene expression profile. Following WLL, the patient's symptoms, lung function, and radiology appearance improved. His repeat bronchoalveolar lavage (BAL) fluid analysis showed reduced lipofuscin and normalized macrophage size and gene expression.