bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frozen sections and complete resection in oral cancer surgery
Authors: Tirelli Giancarlo , Hinni Michael L. , Fernández‐Fernández Mario M. , Bussani Rossana , Gatto Annalisa , Bonini Pierluigi , Giudici Fabiola , Boscolo Nata Francesca 
Published: April 2019

AbstractObjectivesAlthough the reliability of frozen sections for the intraoperative assessment of complete tumour excision has been established, the best location for collection and the impact of the type of sampling are still debated. We retrospectively investigated the reliability of frozen sections when collected from the surgical bed as tissue strips representative of the whole superficial margin and as a bowl of tissue underlying the resection site for deep margin, and the possibility of relying on frozen section negativity to consider resections complete.Materials and MethodsFrozen section reliability was calculated by comparing histology before and after formalin embedding and then categorised by sampling type, in 182 patients undergoing transoral resection of oral cancer.ResultsComparing frozen and permanent histology, sensitivity, specificity and accuracy were 69%, 98% and 96%, respectively; categorisation by sampling type failed to produce statistically significant differences. Based on frozen section negativity after formalin embedding, complete resections were obtained in 91.7% of patients with multiple‐strip and bowl frozen sections.ConclusionFrozen sections collected as tissue strips and bowl are as reliable as point sampling in the intraoperative guidance of surgical resections. They effectively provide for margin enlargement, thereby increasing the surgeon's confidence that negative margins are clear.
Roles of microRNA‐22 in Suppressing Proliferation and Promoting Sensitivity of Osteosarcoma Cells via Metadherin‐mediated Autophagy
Authors: Wang Peng , Zhao Zhen‐qun , Guo Shi‐bing , Yang Tie‐yi , Chang Zhi‐qiang , Li Dai‐he , Zhao Wei , Wang Yu‐xin , Sun Chao , Wang Yong , Feng Wei 
Published: April 2019

ObjectiveTo analyze the effect of microRNA‐22 on autophagy and proliferation and to investigate the underlying molecular mechanism of osteosarcoma cell chemotherapy sensitivity.MethodsMG‐63 cells were divided into four groups, including a control group, a negative control (NC) group, a cisplatin group, and a cisplatin + miR‐22 group. Proliferation of MG‐63 cells that had been treated with cisplatin and transfected with miR‐22 mimics was determined using MTT assay and colony formation assay. We assessed the degree of autophagy using flow cytometry through cellular staining of the autophagy lysosomal marker monodansylcadaverine (MDC). The effect of microRNA‐22 on autophagy was observed along with the expression levels of Beclin1, LC3, metadherin (MTDH) and ATG5 by western blot and quantitative reverse transcription polymerase chain reaction (qRT‐PCR). Luciferase reporter assay revealed the targeted binding site between miR‐22 and the 3′‐untranslated region (3′‐UTR) of MTDH mRNA. Western blot and qRT‐PCR were used to explore the level of MTDH in the control group, the NC group, the cisplatin group, and the miR‐22 group for 6, 12, and 24 h.ResultsIn the in vitro study, the MTT results indicated that the MG‐63 cells with overexpression of miR‐22 exhibited a significant decline in the proliferation capacity compared with the control group (0.513 ± 0.001, P < 0.0005). Similar to the MTT results, MG‐63 cells that were transfected with miR‐22 mimic (101.0 ± 10.58) formed fewer colonies compared with the cisplatin group (129.7 ± 4.163). MDC staining revealed that miR‐22‐overexpressing osteosarcoma (OS) cells treated with cisplatin showed a significant decrease in the expression of autophagy (7.747 ± 0.117, P < 0.0001). Our data revealed that miR‐22 could regulate not only autophagy but also proliferation in the chemosensitivity of osteosarcoma cells. We found that miR‐22 sensitized osteosarcoma cells to cisplatin treatment by regulating autophagy‐related genes. In addition, Luciferase Reporter Assay revealed that miR‐22 negatively regulated autophagy through direct targeting of MTDH. We performed western blot analysis to detect the MTDH expression level. The results revealed that the overexpression of miR‐22 obviously decreased the expression of MTDH (1.081 ± 0.023, P < 0.001).ConclusionInhibition of miR‐22 ameliorated the anticancer drug‐induced cell proliferation decrease in osteosarcoma cells. MTDH was identified as the miR‐22 target in OS cells and MTDH‐triggered autophagy played a key function in the miR‐22‐associated chemotherapy sensitivity.
Incidence of Low‐energy Upper Extremity Fractures and the Risk Factors in Chinese People 50 years or Older
Authors: Zhang Xiao‐juan , Zhu Yan‐bin , Liu Song , Chen Wei , Liu Bo , Zhang Fei , Lv Hong‐zhi , Ji Chen‐ni , Zhang Xiao‐lin , Zhang Ying‐ze 
Published: April 2019

ObjectiveTo investigate the incidence of low‐energy upper extremity fractures and identify the associated risk factors in Chinese people aged 50 years or older.MethodsThis study was a part of the Chinese National Fracture Survey, which was performed between January and May 2015 and aimed to investigate the epidemiology of traumatic fractures in China in 2014. The China National Fracture Study (CNFS) was registered with the Chinese Clinical Trial Registry (number ChiCTR‐EPR‐15005878). A stratified multistage cluster randomized sampling method was used to recruit subjects and the survey was conducted through a questionnaire. The relevant results have been published elsewhere. In the current study, 154 099 Chinese men and women aged 50 years or older were included for data collection and analysis. Low‐energy fractures were defined as fractures that were caused by simple falls from standing height. Individuals who had low‐energy upper extremity fractures were included in the case group and the remainder were included in the control group. Univariate and multivariate logistics regression analysis models were constructed to investigate the independent risk factors, after adjustment for confounding variables.ResultsIn total, 184 patients sustained low‐energy upper extremity fractures in 2014, indicating that the overall incidence was 119.4/100 000 persons, with 57.4 and 180.9/100 000 person‐years in men and women. Approximately 80% of fractures occurred at home and on the common road (other than high way). In men, alcohol consumption (OR, 2.12; 95%CI, 1.11–4.06), residence at ≥2nd floor without an elevator (OR, 2.86; 95%CI, 1.16–7.06), sleep duration<7 h/day (OR, 2.77; 95%CI, 1.42–5.37), and history of past fractures (OR, 3.10; 95%CI, 1.21–7.93) were identified as significant risk factors. In women, obesity (BMI ≥ 28.0) (OR, 1.86; 95%CI, 1.31–2.66), living in the central region in China (OR, 1.53; 95%CI, 1.01–2.31), living at a higher latitude (40°–49.9°N) (OR, 1.79; 95%CI, 1.02–3.14), alcohol consumption (OR, 2.40; 95%CI, 1.58–3.63), more births (OR, 1.45; 95%CI, 1.15–1.83), sleep duration <7 h/day (OR, 2.21; 95%CI, 1.53–3.20), and history of past fracture (OR, 2.70; 95%CI, 1.52–4.80) were identified as significant risk factors.ConclusionBased on these results, health policies that focus on decreasing alcohol consumption and encouraging individuals to improve their quality and duration of sleep should be implemented in China. The significance of moving to a ground floor or to a building equipped with an elevator for men, and maintaining a healthy body weight for women should be emphasized to prevent upper extremity fractures.
Quality of life benefits from arrhythmia ablation: A longitudinal study using the C‐CAP questionnaire and EQ5D
Authors: Evans James M. , Withers Kathleen L. , Lencioni Mauro , Carolan‐Rees Grace , Wood Kathryn A. , Patrick Hannah , Griffith Michael 
Published: April 2019

AbstractAimsTo investigate long‐term efficacy of cardiac ablation for symptomatic arrhythmia by gathering generic and arrhythmia‐related quality of life data using patient‐reported outcome measures before and after ablation.MethodsConsecutive patients undergoing cardiac ablation procedures at three sites in the United Kingdom were enrolled (n = 561). Data were collected at baseline, at 8–16 weeks, and 12 months after the ablation with responses from 390 patients received at all three time points. Nonparametric tests were used to identify any changes in patient outcomes due to nonnormal data.ResultsThere were significant improvements in symptom severity, impact on life scores, EQ‐5D‐5L indices, and visual analogue score (VAS) scores at pre‐ versus 3 months and at preablation versus 1 year. Impact on life score showed additional improvement at 1 year versus 3 months, while improvements in symptom severity, EQ‐5D‐5L indices, and VAS scores continued to be maintained between 3 months and 1 year.ConclusionCardiac ablation provides patients with arrhythmias relief from symptoms, and results in an improvement in quality of life. Improvements observed at 3 months are maintained at 1 year follow‐up.
Dental root abnormalities in four children with PHACE syndrome
Authors: Youssef Molly J. , Siegel Dawn H. , Chiu Yvonne E. , Drolet Beth A. , Hodgson Brian D. 
Published: April 2019

AbstractPHACE(S) syndrome is a condition characterized by posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities, sternal cleft, and supraumbilical raphe. We present four children with PHACE(S) syndrome who have absence of or severe malformation of the roots of their permanent first molars (PFMs). Root abnormalities in the children's molars were bilateral and not restricted to the segments affected by cutaneous hemangioma. The reason for root abnormalities is unknown, but given the rarity of these findings in healthy children, it is likely an additional dental manifestation of PHACE syndrome. The absence of functional roots in the PFMs can result in significant consequences. Therefore, we recommend a panoramic dental radiograph during transitional dentition for children with PHACE syndrome to screen for dental root abnormalities.
Investigation of Different Prototropic Forms of Biologically Active Flavin Lumichrome in the Presence of Liposome
Authors: Bapli Aloke , Gautam Rajesh Kumar , Jana Rabindranath , Seth Debabrata 
Published: April 2019

AbstractHerein, we reported the photophysical behavior of lumichrome (LC), one of the biologically active flavin molecules, in the presence of small unilamellar vesicle of anionic lipid 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine (DMPC). With the help of different spectroscopic techniques, we have proposed that anionic DMPC liposome interacts with the cationic form LC in ground state and in excited state and modulate the spectral properties of LC. Photophysical study reveals that different prototropic forms of LC are present in DMPC liposome medium. In the presence of DMPC liposome, fluorescence emission properties of LC vary with change in excitation and emission wavelengths. This indicates switch over between different structural forms of LC. From fluorescence lifetime measurements and fluorescence lifetime imaging (FLIM) study, it was revealed that emission decay profile of LC was fitted biexponentially in the presence of liposome. It suggests that in the presence of liposome, more than one form of LC is present. We have constructed the time‐resolved area‐normalized emission spectra (TRANES) of LC in the liposome and found one isoemissive point. This confirmed that two emissive species of LC are present in liposome. FLIM study and FE‐SEM study give an idea about the structural feature of the complex between LC and liposome.
Nocturnal hypoxaemia is associated with adverse outcomes in interstitial lung disease
Authors: Troy Lauren K. , Young Iven H. , Lau Edmund M.T. , Wong Keith K.H. , Yee Brendon J. , Torzillo Paul J. , Corte Tamera J. 
Published: April 2019

ABSTRACTBackground and objectiveSleep‐disordered breathing (SDB) has been reported as highly prevalent in idiopathic pulmonary fibrosis (IPF) and other interstitial lung disease (ILD) populations. Nocturnal oxygen desaturation (NOD), or the total sleep time spent with SpoO2 < 90% (TST < 90), can occur both with and without associated apnoeas, and is common in ILD. This study aimed to characterize abnormal SDB and extent of TST < 90 in ILD patients and evaluate relationships between TST < 90 and markers of disease severity, development of pulmonary hypertension (PH) and mortality.MethodsConsecutive, newly referred ILD patients attending a specialist clinic underwent polysomnography (PSG). Serial lung function tests, echocardiography and other clinical variables were recorded. Predictors of PH and mortality were evaluated using logistic regression and Cox proportional hazards regression analyses.ResultsA total of 92 ILD patients (including 44 with IPF) underwent PSG. At least mild obstructive sleep apnoea (OSA) was observed in 65.2%, with rapid eye movement (REM)‐related events occurring frequently. At least 10% TST < 90 (designated ‘significant NOD’) was present in 35.9% of patients, and was associated with PH at baseline echocardiography. Multiple indices of hypoxaemia during sleep, including significant NOD, predicted the development of new or worsening PH. TST < 90 predicted overall and progression‐free survival.ConclusionNocturnal oxygen saturation is associated with poorer prognosis in ILD patients and may contribute towards the pathogenesis of pulmonary vascular disease.
Inventory Routing Problem with Carbon Emission Consideration
Authors: Aziz Nur Arina Bazilah , Jing Yee Choong 
Published: April 2019

Inventory Routing Problem (IRP) has been continuously developed and improved due to pressure from global warming issue particularly related to greenhouse gases (GHGs) emission. The burning of fossil fuel for transportations such as cars, trucks, ships, trains, and planes primarily emits GHGs. Carbon dioxide (CO2) from burning of fossil fuel to power transportation and industrial process is the largest contributor to global GHGs emission. Therefore, the focus of this study is on solving a multi-period inventory routing problem (MIRP) involving carbon emission consideration based on carbon cap and offset policy. Hybrid genetic algorithm (HGA) based on allocation first and routing second is used to compute a solution for the MIRP in this study. The objective of this study is to solve the proposed MIRP model with HGA then validate the effectiveness of the proposed HGA on data of different sizes. Upon validation, the proposed MIRP model and HGA is applied on real-world data. The HGA is found to be able to solve small size and large size instances effectively by providing near optimal solution in relatively short CPU execution time.
Effect of self-reported home smoking restriction on smoking initiation among adolescents in Taiwan: a prospective cohort study
Authors: Luh Dih-Ling , Chen Hsiu-Hsi , Yen Amy Ming-Fang , Wang Ting-Ting , Chiu Sherry Yueh-Hsia , Fann Ching-Yuan , Chen Sam Li-Sheng 
Published: April 2019

ObjectiveThe aims of this study were to investigate the influence of home smoking restriction (HSR) and the modified effect of parental smoking on smoking initiation among adolescents.DesignProspective Cohort Study.SettingJunior high school in Keelung City, Taiwan.ParticipantsThis study collected and evaluated primary data from the Adolescent Smoking and Other Health-Related Behaviour Survey conducted in Keelung City, which aimed to investigate smoking and health-related behaviours in junior high school students (2008–2009). Data on students free of smoking in 2008 and following them until 2009 (n=901) to ascertain whether they had started smoking were analysed with logistic regression mode to examine the proposed postulates.Main outcome measureThe outcome variable was smoking initiation, which was defined as smoking status (yes/no) in the 2009 follow-up questionnaire. The main independent variable was HSR obtained from an adolescent self-reported questionnaire. Information on parental smoking was measured by adolescents self-reporting the smoking behaviour of their father and mother.ResultsThe rate of HSR was 29.79% among 7th grade adolescents. The effect of HSR on smoking initiation in adolescents was statistically significantly modified by paternal smoking (p=0.04) but not by maternal smoking (p=0.54). The effect of HSR on smoking initiation was small for fathers with the habit of smoking (OR=0.89, 95% CI (0.42 to 1.88)), but the corresponding effect size was 3.2-fold (OR=2.84, 95% CI 1.19 to 6.81) for fathers without the habit of smoking.ConclusionsPaternal smoking behaviour may play an interactive role with HSR in preventing smoking initiation among Taiwanese adolescents.
Ultra-sensitive EGFRT790M Detection as an Independent Prognostic Marker for Lung Cancer Patients Harboring EGFRdel19 Mutations and Treated with First-generation TKIs
Authors: Vendrell Julie A. , Mazieres Julien , Senal Romain , Rouquette Isabelle , Quantin Xavier , Pujol Jean-Louis , Roch Benoit , Bouidioua Abdelali , Godreuil Sylvain , Coyaud Etienne , Brousset Pierre , Solassol Jérôme 
Published: April 2019

Abstract

Purpose:
The detection of preexisting EGFRT790M subclones and the assessment of their clinical significance in the pretreatment of patients with EGFRT790M non–small cell lung cancer (NSCLC) remain unclear.

Experimental Design:
A total of 179 tumor samples from patients treated or not with a first-generation tyrosine kinase inhibitor (TKI) was analyzed. The presence of ultra-low levels of preexisting EGFRT790M mutation was evaluated using ultra-sensitive droplet digital PCR (ddPCR) and the clinical implication of these mutations on first-generation TKI efficiency assessed.

Results:
With a ddPCR linear performance of 0.999 and an analytical sensitivity of approximately 0.001%, we observed a 66% (99/150) overall incidence of ultra-low EGFRT790M mutation. Among 82 patients harboring EGFRactivating mutations, the presence of a preexisting EGFRT790M mutation prior to any treatment was significantly associated with a longer progression-free survival (PFS; P = 0.009; log-rank test). Interestingly, longer PFS was linked to concomitant EGFRdel19 and ultra-low EGFRT790M mutations. Moreover, the presence of both EGFRdel19 and ultra-low EGFRT790M mutations was identified as the best fit for predicting the clinical outcome of patients treated with TKI compared with an ultra-low EGFRT790M mutation status or an activating mutation alone (P = 0.042 and P = 0.0071, respectively).

Conclusions:
We demonstrate that the detection of the ultra-low EGFRT790M mutation in TKI-naïve patients is not a rare event. We suggest that ddPCR should be used in clinical practice to distinguish patients who may respond to first- or third-generation TKIs.
Targeted Inhibition of the Dual Specificity Phosphatases DUSP1 and DUSP6 Suppress MPNST Growth via JNK
Authors: Ramkissoon Annmarie , Chaney Katherine E. , Milewski David , Williams Kyle B. , Williams Rory L. , Choi Kwangmin , Miller Adam , Kalin Tanya V. , Pressey Joseph G. , Szabo Sara , Azam Mohammad , Largaespada David A. , Ratner Nancy 
Published: April 2019

Abstract

Purpose:
In neurofibromatosis type 1 (NF1) and in highly aggressive malignant peripheral nerve sheath tumors (MPNSTs), constitutively active RAS-GTP and increased MAPK signaling are important in tumorigenesis. Dual specificity phosphatases (DUSPs) are negative regulators of MAPK signaling that dephosphorylate p38, JNK, and ERK in different settings. Although often acting as tumor suppressors, DUSPs may also act as oncogenes, helping tumor cells adapt to high levels of MAPK signaling. We hypothesized that inhibiting DUSPs might be selectively toxic to cells from NF1-driven tumors.

Experimental Design:
We examined DUSP gene and protein expression in neurofibroma and MPNSTs. We used small hairpin RNA (shRNA) to knock down DUSP1 and DUSP6 to evaluate cell growth, downstream MAPK signaling, and mechanisms of action. We evaluated the DUSP inhibitor, (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI), in MPNST cell lines and in cell-line and patient-derived MPNST xenografts.

Results:
DUSP1 and DUSP6 are expressed in NF1-deleted tumors. Knockdown of DUSP1 and DUSP6, alone or in combination, reduced MPNST cell growth and led to ERK and JNK hyperactivation increasing downstream TP53 and p-ATM. The DUSP inhibitor, BCI, diminished the survival of NF1-deleted Schwann cells and MPNST cell lines through activation of JNK. In vivo, treatment of an established cell-line xenograft or a novel patient-derived xenograft (PDX) of MPNSTs with BCI increased ERK and JNK activation, caused tumor necrosis and fibrosis, and reduced tumor volume in one model.

Conclusions:
Targeting DUSP1 and DUSP6 genetically or with BCI effectively inhibits MPNST cell growth and promotes cell death, in vitro and in xenograft models. The data support further investigation of DUSP inhibition in MPNSTs.
One Clever Macrophage Checkpoint
Authors: Mantovani Alberto , Bonecchi Raffaella 
Published: April 2019

Abstract
Macrophages are a key component of the tumor microenvironment (TME). Blocking Clever-1, a molecule expressed in M2-like macrophages, unleashed macrophage and T-cell–mediated antitumor immunity. Myeloid checkpoints including Clever-1 hold promise as alternative or complementary immunotherapy strategies.
See related article by Viitala et al., p. 3289
EZH2 Inhibitors: Take It EZy, It Is All About Context
Authors: Velcheti Vamsidhar , Wong Kwok-Kin , Saunthararajah Yogen 
Published: April 2019

Abstract

Summary:
Even in diffuse large B-cell lymphoma (DLBCL), a cancer of professional antigen-presenting cells, response rates to immune checkpoint blockade therapy have been limited. One reason for DLBCL immune evasion is epigenetic repression instead of activation of the antigen-presenting MHC—a dissection of mechanisms underlying this repression suggests an opening for restoring B-cell maturation and, along the way, MHC expression as a novel modality of cytoreducing DLBCL and simultaneously augmenting possibilities for immunotherapy.
See related article by Ennishi et al., p. 546.