bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroimaging features of whole‐brain functional connectivity predict attack frequency of migraine
Authors: Mu Junya , Chen Tao , Quan Shilan , Wang Chen , Zhao Ling , Liu Jixin 
Published: November 2019

AbstractMigraine is a chronic neurological disorder characterized by attacks of moderate or severe headache accompanying functionally and structurally maladaptive changes in brain. As the headache days/month is often measured by patient self‐report and tends to be overestimated than actually experienced, the possibility of using neuroimaging data to predict migraine attack frequency is of great interest. To identify neuroimaging features that could objectively evaluate patients' headache days, a total of 179 migraineurs were recruited from two data center with one dataset used as the training/test cohort and the other used as the validating cohort. The guidelines for controlled trials of prophylactic treatment of chronic migraine in adults were used to identify the frequency of attacks and migraineurs were divided into low (MOl) and high (MOh) subgroups. Whole‐brain functional connectivity was used to build multivariate logistic regression models with model iteration optimization to identify MOl and MOh. The best model accurately discriminated MOh from MOl with AUC of 0.91 (95%CI [0.86, 0.95]) in the training/test cohort and 0.79 in the validating cohort. The discriminative features were mainly located within the limbic lobe, frontal lobe, and temporal lobe. Permutation tests analysis demonstrated that the classification performance of these features was significantly better than chance. Furthermore, the indicator of functional connectivity had a higher odds ratio than behavioral variables with implementing a holistic regression analysis. The current findings suggested that the migraine attack frequency could be distinguished by using machine‐learning algorithms, and highlighted the role of brain functional connectivity in revealing underlying migraine‐related neurobiology.
The surgical treatment of cerebrospinal fistula: Qualitative and quantitative analysis of indications and results
Authors: Iavarone Alessandra , Luparello Paolo , Lazio Maria Silvia , Comini Lara Valentina , Martelli Federica , De Luca Oliviero , Santoro Giovanni Paolo , Santoro Roberto , Alderotti Giammarco , Mannelli Giuditta 
Published: November 2019

AbstractCerebrospinal fistula might occur in different ways. CSF closure techniques have undergone significant evolution that has led to the consolidation of the transnasal endoscopic approach. Despite the existence of multiple publications, meaningful information is still lacking in clinical practice and the literature about the ideal method, material, and timing for repair of CSF. The purpose of this review was to summarize the success rate of endoscopic CSF leak repair as well as whether specific techniques or materials influence the primary success rate through a review of the latest advancements in endoscopic CSF management published in the past 10 years. The principles of multilayer reconstructions and the routine use of vascularized flaps in expanded endonasal surgery have reduced postoperative CSF leaks' failure rates between 5% and 10% (4% in this meta‐analysis). Effective endoscopic anterior skull base (ASB) closure may be achieved by multiple reconstructive techniques, which should be tailored case by case according to the patient and defect conditions.
Analysis of skin dose distribution for the prediction of severe radiation dermatitis in head and neck squamous cell carcinoma patients treated with concurrent chemo‐radiotherapy
Authors: Bonomo Pierluigi , Talamonti Cinzia , Desideri Isacco , Marrazzo Livia , Pezzulla Donato , Rampini Andrea , Bertocci Silvia , De Majo Roberta , Gasperi Chiara , Curion Assunta Simona , Lastrucci Luciana , Dominici Luca , Pallotta Stefania , Livi Lorenzo , Caini Saverio 
Published: November 2019

AbstractBackgroundWe investigated whether the pattern of intensity‐modulated radiotherapy (IMRT) dose distribution to the skin can be correlated with the development of G3/G4 radiation dermatitis (RD).MethodsA frequency‐matched cohort analysis was perfomed on patients treated with IMRT and concurrent cisplatin or cetuximab. Risk ratios were obtained by fitting Poisson regression models.ResultsThe incidence of G3/G4 RD was 41.1% in 90 patients included (50% vs 36.6% in the cetuximab and cisplatin cohorts, respectively). In multivariate analysis, PS ≥ 1 and weight loss at RT completion >10 kg were the only factors that retained significance. The best dosimetric predictive accuracy was provided by 19.9 cc and 5.8 cc of skin ring 2 mm V50 and V60, respectively (AUC: 0.61 for both).ConclusionAlong with clinical factors, the pattern of dose distribution to a ring structure localized 2 mm below the patient's surface may help predict the development of severe RD.
Clinical characteristics and prognostic factors of malignant tumors involving pterygopalatine fossa
Authors: Woo Hyun‐Jae , Hwang Peter H. , Kaplan Michael J. , Choby Garret 
Published: November 2019

AbstractBackgroundTo identify the clinical characteristics and prognostic factors of malignancies involving the pterygopalatine fossa (PPF).MethodsFifty‐seven patients who underwent curative surgery for malignant tumor involving PPF were reviewed.ResultsThe rates for three‐year local control (LC), five‐year disease‐free survival (DFS) and five‐year overall survival (OS) were 55.4%, 34.5%, and 52.7%, respectively. Perineural invasion (PNI) of the maxillary nerve with facial numbness (symptomatic V2 PNI) (P = .04) and cranial involvement (P = .03) were predictors for poor OS. Symptomatic V2 PNI was also a significant predictor for poor LC (P = .05) and DFS (P = .03). Within the subgroup analysis of patients with pathologically confirmed V2 PNI, asymptomatic V2 PNI patients had significantly better LC (71.2% vs 31.8%, P = .05) and DFS (43.8% vs 17.3%, P = .05) compared to symptomatic patients.ConclusionMalignant tumors involving the PPF have diverse pathologies and a poor prognosis. Symptomatic V2 PNI may be an independent poor prognostic factor.
Deficiency in Embryonic Stem Cell Marker Reduced Expression 1 Activates Mitogen‐Activated Protein Kinase Kinase 6–Dependent p38 Mitogen‐Activated Protein Kinase Signaling to Drive Hepatocarcinogenesis
Authors: Luk Steve T. , Ng Kai‐Yu , Zhou Lei , Tong Man , Wong Tin‐Lok , Yu Huajian , Lo Chung‐Mau , Man Kwan , Guan Xin‐Yuan , Lee Terence K. , Ma Stephanie 
Published: November 2019

Background and Aims
Embryonic stem‐cell–related transcription factors are central to the establishment and maintenance of stemness and pluripotency, and their altered expression plays key roles in tumors, including hepatocellular carcinoma (HCC), a malignancy with no effective treatment. Here, we report on the embryonic stem cell marker, reduced expression 1 (REX1; also known as zinc finger protein 42), to be selectively down‐regulated in HCC tumors.

Approach and Results
Deficiency of REX1 in HCC was attributed to a combination of hypermethylation at its promoter as well as histone modification by methylation and acetylation. Clinically, hypermethylation of REX1 was closely associated with neoplastic transition and advanced tumor stage in humans. Functionally, silencing of REX1 potentiated the tumor‐initiating and metastasis potential of HCC cell lines and xenografted tumors. Lentivirus‐mediated Rex1 ablation in liver of male immunocompetent mice with HCC, induced by hydrodynamic tail vein injection of proto‐oncogenes, enhanced HCC development. Transcriptome profiling studies revealed REX1 deficiency in HCC cells to be enriched with genes implicated in focal adhesion and mitogen‐activated protein kinase (MAPK) signaling. From this lead, we subsequently found REX1 to bind to the promoter region of mitogen‐activated protein kinase kinase 6 (MKK6), thereby obstructing its transcription, resulting in altered p38 MAPK signaling.

Conclusions
Our work describes a critical repressive function of REX1 in maintenance of HCC cells by regulating MKK6 binding and p38 MAPK signaling. REX1 deficiency induced enhancement of p38 MAPK signaling, leading to F‐actin reorganization and activation of nuclear factor erythroid 2‐related factor 2–mediated oxidative stress response, which collectively contributed to enhanced stemness and metastatic capabilities of HCC cells.
Pre‐training interventions to counteract seductive details in virtual reality training programs
Authors: Howard Matt C. , Lee Juseob 
Published: November 2019

AbstractWe propose that (a) certain aspects of virtual reality (VR) training programs are seductive details, (b) these seductive details prompt trainee distraction and/or cognitive overload, and (c) pre‐training interventions can benefit learning from VR training programs by targeting these mechanisms. In Study 1, we apply a meta‐cognitive strategy pre‐training intervention, which targets distraction, and a habituation pre‐training intervention, which targets cognitive overload. Habituation had no effect, whereas meta‐cognitive strategies worsened learning. Qualitative results indicated the meta‐cognitive strategy intervention prompted trainees to become more cognitively engaged in the distracting seductive details of the VR training program. In Study 2, we tested an alternative pre‐training intervention, attentional advice, to reduce distraction and increase learning. The attentional advice pre‐training intervention was successful, as trainees demonstrated greater learning when provided attentional advice. Together, all proposals were supported. VR can contain seductive details that cause distraction, and attentional advice can improve learning by reducing distraction.
Addressing burnout in clinical pharmacy: What can we learn from other health care disciplines?
Authors: Haase Krystal K. 
Published: November 2019

AbstractBurnout is a growing concern across health care disciplines. Burnout is a prolonged response to persistent work‐related stressors and includes elements of exhaustion, depersonalization, and perceived ineffectiveness. The body of literature exploring the causes and consequences of burnout has grown substantially. Rates of burnout in clinical pharmacists are similar to those reported for other health care professionals. However, many aspects of burnout have not been adequately characterized in clinical pharmacists. This manuscript outlines key findings from the literature on burnout in other health care disciplines and establishes relevant connections to clinical pharmacy. Burnout has negative consequences related to personal well‐being and is linked to stress‐related health outcomes. Burnout is associated with increased job turnover, decreased productivity, and quality concerns, including both patient safety and satisfaction. A variety of factors contribute to the development of burnout, including provider characteristics, practice specialization, type and quantity of work expectations, work environment, social and organizational support, and reward. Interventions that focus on individual providers have been shown to modestly improve burnout. Interventions that emphasize organizational change may have a more significant impact, and several groups have outlined organization‐focused strategies to improve well‐being in the workplace. Such strategies include enhancing communication, promoting true collaboration and community, addressing staffing shortages, empowering employee decision‐making, and developing and promoting institutional values. Best practices for improving well‐being within an organization include a multidisciplinary, multimodal approach that is supported by both resources and leadership engagement.
LncRNA PCED1B‐AS1 activates the proliferation and restricts the apoptosis of glioma through cooperating with miR‐194‐5p/PCED1B axis
Authors: Yang Jinghui , Yu Duo , Liu Xueshibojie , Changyong E. , Yu Shan 
Published: November 2019

AbstractGlioma with poor prognosis is accepted as a lethal, malignant intracranial tumor among central nervous system diseases. It has been frequently exhibited that long noncoding RNAs (lncRNAs) exert indispensable functions in glioma through regulating gene expression through various molecular mechanisms. To unveil a novel lncRNA functioning in glioma, we browsed the cancer genome atlas dataset and chose the lncRNA PC‐esterase domain containing 1B antisense RNA 1 (PCED1B‐AS1) for further investigations. Loss‐of‐function experiments depicted that the proliferation ability was restrained and apoptosis ability was induced in glioma cells by PCED1B‐AS1 silencing and this phenomenon was also observed when PCED1B was knocked down. In view of the position of PCED1B‐AS1 in the cytoplasm, we produced the Venn diagram and discovered one shared microRNA of PCED1B‐AS1 and PCED1B. The competing endogenous RNA network formed by PCED1B‐AS1, miR‐194‐5p, and PCED1B was attested by mechanism assays. Rescue experiments reconfirmed that miR‐194‐5p suppression or PCED1B overexpression neutralized the obstructive impacts of PCED1B‐AS1 silence on proliferation and the promoting effects of PCED1B‐AS1 silence on apoptosis. The modulation mechanism of the PCED1B‐AS1/miR‐194‐5p/PCED1B axis in glioma was investigated and affirmed, which supports researchers with a new insight into the therapy of patients with glioma.
Retracted: Silence of cZNF292 suppresses the growth, migration, and invasion of human esophageal cancer Eca‐109 cells via upregulating miR‐206
Authors: Liu Zengjia , Hu Guiju , Zhao Yan , Xiao Zuorun , Yan Mingzhe , Ren Mei 
Published: November 2019

AbstractCircular RNA (circRNA) cZNF292 has been previously revealed as a circular oncogenic RNA. This study attempted to illustrate the functions of cZNF292 in human esophageal carcinoma Eca‐109 cells. Eca‐109 cells were transfected with the short hairpin RNA specific against cZNF292 (sh‐cZNF292) and/or miR‐206 inhibitor. cZNF292 and miR‐206 expression was examined by quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR). Cell counting kit‐8 and flow cytometry were performed for detecting cell growth including cell viability as well as apoptosis. Various kinds of factors, which are involved in cell development including proliferation, apoptosis, migration, and invasion were determined by western blot analysis. Besides, the activation of AMP‐activated protein kinase (AMPK) and PI3K/AKT signaling was measured by western blot analysis. It was found that cZNF292 silencing decreased Eca‐109 cell viability and induced apoptosis. In the meantime, cZNF292 silencing inhibited cell migration and invasion. cZNF292 silencing upregulated miR‐206 expression. And miR‐206 downregulation impaired the suppressive effects of cZNF292 silence toward Eca‐109 cell growth, migration, and invasion. cZNF292 silencing activated AMPK signaling and inactivated PI3K/AKT signaling also via regulating miR‐206. In conclusion, silencing of cZNF292 abated growth, migration, and invasion of Eca‐109 cells by upregulating miR‐206, which subsequently modulated AMPK and PI3K/AKT signaling pathways.
RNA sequencing profiling reveals key mRNAs and long noncoding RNAs in atrial fibrillation
Authors: Ke Zun‐Ping , Xu Ying‐Jia , Wang Zhang‐Sheng , Sun Jian 
Published: November 2019

AbstractLong noncoding RNAs (lncRNAs) are an emerging class of RNA species that could participate in some critical pathways and disease pathogenesis. However, the underlying molecular mechanism of lncRNAs in atrial fibrillation (AF) is still not fully understood. In the present study, we analyzed RNA‐seq data of paired left and right atrial appendages from five patients with AF and other five patients without AF. Based on the gene expression profiles of 20 samples, we found that a majority of genes were aberrantly expressed in both left and right atrial appendages of patients with AF. Similarly, the dysregulated pathways in the left and right atrial appendages of patients with AF also bore a close resemblance. Moreover, we predicted regulatory lncRNAs that regulated the expression of adjacent protein‐coding genes (PCGs) or interacted with proteins. We identified that NPPA and its antisense RNA NPPA‐AS1 may participate in the pathogenesis of AF by regulating the muscle contraction. We also identified that RP11 − 99E15.2 and RP3 − 523K23.2 could interact with proteins ITGB3 and HSF2, respectively. RP11 − 99E15.2 and RP3 − 523K23.2 may participate in the pathogenesis of AF via regulating the extracellular matrix binding and the transcription of HSF2 target genes, respectively. The close association of the lncRNA‐interacting proteins with AF further demonstrated that these two lncRNAs were also associated with AF. In conclusion, we have identified key regulatory lncRNAs implicated in AF, which not only improves our understanding of the lncRNA‐related molecular mechanism underlying AF but also provides computationally predicted regulatory lncRNAs for AF researchers.
Exploring beta amyloid cleavage enzyme‐1 inhibition and neuroprotective role of benzimidazole analogues as anti‐alzheimer agents
Authors: Gurjar Archana S. , Solanki Vivek S. , Meshram Ankita R. , Vishwakarma Suchita S. 
Published: November 2019

AbstractBeta amyloid cleavage enzyme‐1 (BACE1) is the key enzyme involved in Aβ peptide formation in Alzheimer's disease pathogenesis. We intend to target this enzyme by exploring benzimidazole analogues against BACE1 as potential anti‐Alzheimer agents. Docking studies were performed to determine the hydrogen bond interactions between the designed molecules and the target protein's active site. Research indicates the relationship between oxidative stress and Aβ effect in precipitating neurodegeneration; hence, the series was also studied in vitro to ascertain its neuroprotective role by performing the lipid peroxidation assay. In silico absorption, distribution, metabolism, and excretion studies were undertaken to assess the drug‐like suitability of the analogues. To judge the effect of the synthesized analogues on central nervous system (CNS), toxicity and memory model studies were conducted on mice. Thus, overall results showcase analogues 11 and 14 as the most promising ones with the dual role of BACE1 inhibition and neuroprotection, along with memory retention.
AMPKα promotes basal autophagy induction in Dictyostelium discoideum
Authors: Maurya Ranjana , Kumar Rakesh , Saran Shweta 
Published: November 2019

AbstractAutophagy is a degradation process, wherein long‐lived proteins, damaged organelles, and protein aggregates are degraded to maintain cellular homeostasis. Upon starvation, 5′‐AMP‐activated protein kinase (AMPK) initiates autophagy. We show that ampkα− cells exhibit 50% reduction in pinocytosis and display defective phagocytosis. Re‐expression of AMPKα in ampkα− cells co‐localizes with red fluorescence protein‐tagged bacteria. The ampkα− cells show reduced cell survival and autophagic flux under basal and starvation conditions. Co‐immunoprecipitation studies show conservation of the AMPK–ATG1 axis in basal autophagy. Computational analyses suggest that the N‐terminal region of DdATG1 is amenable for interaction with AMPK. Furthermore, β‐actin was found to be a novel interacting partner of AMPK, attributed to the alteration in macropinocytosis and phagocytosis in the absence of AMPK. Additionally, ampkα− cells exhibit enhanced poly‐ubiquitinated protein levels and allied large ubiquitin‐positive protein aggregates. Our findings suggest that AMPK provides links among pinocytosis, phagocytosis, autophagy, and is a requisite for basal autophagy in Dictyostelium.
Catalytic hydrolysis of cellulose to total reducing sugars with superior recyclable magnetic multifunctional MCMB‐based solid acid as a catalyst
Authors: Li Heng‐Xiang , Shi Wen‐Jing , Zhang Xiaohua , Liu Puxu , Cao Qing , Jin Li'e 
Published: November 2019

AbstractBACKGROUNDEffective cellulose hydrolysis has a huge potential for producing high value‐added biomass‐based platform chemicals, such as glucose, hydroxymethylfurfural, levulinic acid, and total reducing sugars (TRS). Particularly, a magnetic multifunctional solid acid catalyst (Fe3O4/Cl–MCMB–SO3H) was synthesized by loading the active groups on the magnetic mesocarbon microbead (MCMB) derived from the co‐calcination of coal tar pitch and ferroferric oxide, which was applied as a catalyst in the conversion of cellulose into TRS.RESULTSGiven the superior properties of MCMB, a novel magnetic MCMB‐based solid acid with cellulose‐binding domain (–Cl group) and catalytic domain (–SO3H group) was successfully prepared. Results indicated that this catalyst exhibited superior catalytic activity, recyclability and regenerability, and easy separation from the reactant. The acidic densities of –SO3H and –Cl in Fe3O4/Cl–MCMB–SO3H reached 1.77 and 1.32 mmol/g, respectively. The 68.6% TRS yield can be obtained from cellulose at 140 °C for 3 h in distilled water by using Fe3O4/Cl‐MCMB‐SO3H as the catalyst. The TRS yield still reached 61.1% after the catalyst was used six times. Importantly, through catalyst regeneration, the –SO3H density and TRS yield still reached 1.69 mmol/g and 67.3%, indicating that the catalyst exhibited excellent regenerability.CONCLUSIONSuch multifunctional magnetic catalyst would be a promising catalyst in the conversion of cellulose into biofuels, which was attributed to the efficient catalytic performance, magnetism, and excellent recyclability and regenerability. © 2019 Society of Chemical Industry
Human Placenta Blood Flow During Early Gestation With Pseudocontinuous Arterial Spin Labeling MRI
Authors: Liu Dapeng , Shao Xingfeng , Danyalov Alibek , Chanlaw Teresa , Masamed Rinat , Wang Danny J.J. , Janzen Carla , Devaskar Sherin U. , Sung Kyunghyun 
Published: November 2019

BackgroundNoninvasive measurement of placental blood flow is the major technical challenge for predicting ischemic placenta (IPD). Pseudocontinuous arterial spin labeling (pCASL) MRI was recently shown to be promising, but the potential value in predicting the subsequence development of IPD is not known.PurposeTo derive global and regional placental blood flow parameters from longitudinal measurements of pCASL MRI and to assess the associations between perfusion‐related parameters and IPD.Study TypeProspective.PopulationEighty‐four women completed two pCASL MRI scans (first; 14–18 weeks and second; 19–24 weeks) from prospectively recruited 118 subjects. A total of 69 subjects were included for the analysis, of which 15 subjects developed IPD.Field Strength/Sequence3T/T2‐weighted half‐Fourier single‐shot turbo spin‐echo (HASTE) and pCASL.AssessmentFour perfusion‐related parameters in the placenta were derived: placenta volume, placental blood flow (PBF), high PBF (hPBF), and relative hPBF. The longitudinal changes of the parameters and their association with IPD were tested after being normalizing to the 16th and 20th weeks of gestation.Statistical TestsComparisons between two gestational ages within subjects were performed using the paired Wilcoxon tests, and comparisons between normal and IPD groups were performed using the unpaired Wilcoxon tests.ResultsThe difference between the first and second MRI scans was statistically significant for volume (156.6 cm3 vs. 269.7 cm3, P < 0.001) and PBF (104.9 ml/100g/min vs. 111.3 ml/100g/min, P = 0.02) for normal subjects, indicating an increase in pregnancy with advancing gestation. Of the parameters tested, the difference between the normal and IPD subjects was most pronounced in hPBF (278.1 ml/100g/min vs. 180.7 ml/100g/min, P < 0.001) and relative hPBF (259.1% vs. 183.2%, P < 0.001) at 16 weeks.Data ConclusionThe high perfusion‐related image parameters for IPD were significantly decreased from normal pregnancy at 14–18 weeks of gestation.Level of Evidence2Technical Efficacy Stage1J. Magn. Reson. Imaging 2020;51:1247–1257.