bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatio‐temporal heterogeneity in soil water stable isotopic composition and its ecohydrologic implications in semiarid ecosystems
Authors: Oerter Erik J. , Bowen Gabriel J.
Published: March 2019

Spatio‐temporal heterogeneity in soil water content is recognized as a common phenomenon, but heterogeneity in the hydrogen and oxygen isotope composition of soil water, which can reveal processes of water cycling within soils, has not been well studied. New advances are being driven by measurement approaches allowing sampling with high density in both space and time. Using in situ soil water vapour probe techniques, combined with conventional soil and plant water vacuum distillation extraction, we monitored the hydrogen and oxygen stable isotopic composition of soil and plant waters at paired sites dominated by grasses and Gambel's oak (Quercus gambelii) within a semiarid montane ecosystem over the course of a growing season. We found that sites spaced only 20 m apart had profoundly different soil water isotopic and volumetric conditions. We document patterns of depth‐ and time‐explicit variation in soil water isotopic conditions at these sites and consider mechanisms for the observed heterogeneity. We found that soil water content and isotopic variability were damped under Q. gambelii, perhaps due in part to hydraulic redistribution of deep soil water or groundwater by Q. gambelii in these soils relative to the grass‐dominated site. We also found some support for H isotope discrimination effects during water uptake by Q. gambelii. In this ecosystem, the soil water content was higher than that at the neighbouring Grass site, and thus, 25% more water was available for transpiration by Q. gambelii compared with the Grass site. This work highlights the role of plants in governing soil water variation and demonstrates that they can also strongly influence the isotope ratios of soil water. The resulting fine‐scale heterogeneity has implications for the use of isotope tracers to study soil hydrology and evaporation and transpiration fluxes to improve understanding of water cycling through the soil–plant–atmosphere continuum.
Retracted: Decreased expression of long noncoding RNA XLOC_013703 promotes cell growth via NF‐κB pathway in multiple myeloma
Authors: Pu Jiang , Huang Hongming , Su Jianyou , Yuan Jie , Cong Hui , Wang Xudong , Ju Shaoqing
Published: March 2019

Long noncoding RNAs (lncRNAs) are dysregulated in cancer and involved in oncogenic or tumor inhibitory processes. The aim of the study was to investigate the expression pattern of lncRNA XLOC_013703 in multiple myeloma (MM) and to evaluate its biological role and potential significance. We found that XLOC_013703 was significantly decreased in CD138 positive plasma cells and serum of MM patients compared to normal controls, and the decreased XLOC_013703 expression was correlated with β2‐MG, serum‐free light chain (s‐FLC) and revised international staging system. RNA‐fluorescence in situ hybridization results revealed that XLOC_013703 was distributed both in the nucleus and in the cytoplasm of MM cells including H929, RPMI8226, and U266. Overexpression of XLOC_013703 inhibited the proliferation of U266 cells and blocked the cell cycle in G1 stage, thus contributing to MM cell apoptosis. By contrast, knockdown of XLOC_013703 promoted the growth of H929 cells. Western blot analysis confirmed that the expression of p‐IκBα and nuclear P65 was substantially increased in shRNA transfection groups compared to control groups, whereas overexpression of XLOC_013703 reduced these expressions. In conclusion, we confirmed that the decreased expression of a novel lncRNA, XLOC_013703, in MM. XLOC_013703 was involved in MM cell survival and proliferation via nuclear factor‐κB pathway which represents a potential therapeutic target for MM. © 2019 IUBMB Life, 71(9):1240–1251, 2019
Intraoperative multispectral and hyperspectral label‐free imaging: A systematic review of in vivo clinical studies
Authors: Shapey Jonathan , Xie Yijing , Nabavi Eli , Bradford Robert , Saeed Shakeel R , Ourselin Sebastien , Vercauteren Tom
Published: March 2019

Multispectral and hyperspectral imaging (HSI) are emerging optical imaging techniques with the potential to transform the way surgery is performed but it is not clear whether current systems are capable of delivering real‐time tissue characterization and surgical guidance. We conducted a systematic review of surgical in vivo label‐free multispectral and HSI systems that have been assessed intraoperatively in adult patients, published over a 10‐year period to May 2018. We analysed 14 studies including 8 different HSI systems. Current in‐vivo HSI systems generate an intraoperative tissue oxygenation map or enable tumour detection. Intraoperative tissue oxygenation measurements may help to predict those patients at risk of postoperative complications and in‐vivo intraoperative tissue characterization may be performed with high specificity and sensitivity. All systems utilized a line‐scanning or wavelength‐scanning method but the spectral range and number of spectral bands employed varied significantly between studies and according to the system's clinical aim. The time to acquire a hyperspectral cube dataset ranged between 5 and 30 seconds. No safety concerns were reported in any studies. A small number of studies have demonstrated the capabilities of intraoperative in‐vivo label‐free HSI but further work is needed to fully integrate it into the current surgical workflow.
Bowman‐Birk inhibitor modifies transcription of autophagy and apoptosis genes in an in vitro model of Alzheimer's disorder
Authors: Akbari Samaneh , Akrami Hassan , Mostafaei Ali , Kiani Sudabeh
Published: March 2019

Alzheimer, a current neurodegenerative disorder has adverse effects on memory and behavior. β‐Amyloid peptide accumulations are the hallmarks of Alzheimer. Dysfunction of autophagy and apoptosis is detected in Alzheimer's disease. The effect of Bowman‐Birk inhibitor (BBI), purified from soybean, was investigated in autophagy and apoptosis in Alzheimer treatment. Treated‐PC12 cells with 1000 nM HgCl2 induced amyloid β (Aβ) accumulation. Treatment of PC12 cells with 1000 nM HgCl
2 and then 500 μg/mL BBI could decrease the expression ratio of Bax/Bcl2 and increase the expression of beclin1, Bnip3, Atg5, and autophagy‐related genes. These results indicated that BBI could inhibit Aβ accumulation by inducing autophagy, and also the neuroprotective effect was detected through decreasing apoptosis in the in vitro model of Alzheimer's disease. These results provided further evidence for the potential effectiveness of BBI in the treatment of Alzheimer's disease.
Importin‐4 functions as a driving force in human primary gastric cancer
Authors: Xu Xia , Zhang Xinchao , Xing Huaixin , Liu Zhifang , Jia Jihui , Jin Chunyuan , Zhang Yingjie
Published: March 2019

Objectives

Importin‐4 (IPO4) is responsible for transporting histones H3 and H4 into the nucleus for chromatin assembly. But, the role of IPO4 in cancer, especially in gastric cancer (GC), has not been fully understood. We aim to determine the expression and function of IPO4 in GC.

Materials and Methods

Bioinformatics analysis was used to study the association of IPO4 and GC using GEO data and the Kaplan‐Meier plotter. The quantitative real‐time polymerase chain reaction and Western blot analysis were used to determine the IPO4 level in GC cells and tissues. Small interfering RNAs (siRNAs) were used to knockdown endogenous IPO4 expression in GC cells. Cell counting kit‐8 (CCK‐8), colony formation and transwell assays were used to examine the effect of IPO4 on cell proliferation and migration.

Results

IPO4 mRNA is overexpressed in GC tissues using bioinformatics analysis of three groups’ transcriptome data, and high level of IPO4 is negatively correlated with poor long‐term survival using the Kaplan‐Meier plotter analysis. Western blot analysis further shows that IPO4 protein levels are also overexpressed in GC tissues and a number of GC cell lines. Endogenous IPO4 level can be inhibited by specific siRNA effectively. Importantly, CCK‐8, colony formation, and transwell assays demonstrate that IPO4 knockdown by siRNA impairs GC cell proliferation and migration.

Conclusions

Our data suggest that IPO4 contributes to GC progression and poor prognosis, and may function as a driving force in GC progression.
The potential regulatory role of miR16 to the interplay between interferon and transforming growth factor beta pathways through IRF3 and SMAD7 in hepatitis C virus infected patients
Authors: Hany Noha Mohamed , Hammouda Abd‐El‐Rahman M. A. , Nabih Enas Samir , Mohamed Sherif Moneir
Published: March 2019

Background

The defensive strategy against hepatitis C virus (HCV) infection depends on two antiviral pathways; interferon (IFN) and transforming growth factor β (TGFβ). We aimed at verifying the relation between TGFβ and IFN antiviral pathways in HCV infection through SMAD7 and IRF3, and whether a possible regulatory role for microRNA‐16 (miR16) on the interplay between IFN and TGFβ signaling pathways exists or not.

Methods

We evaluated miR16, IRF3 and SMAD7 expression by real‐time polymerase chain reaction in HCV infected patients and age and gender matched healthy controls.

Results

miR16 expression was significantly higher while IRF3 and SMAD7 expression was significantly lower in HCV patients compared with healthy controls. Meanwhile, miR16 was negatively correlated to SMAD7 in HCV patients while IRF3 and SMAD7 were positively correlated.

Conclusions

The interplay between IFN and TGFβ pathways through IRF3 and SMAD7 in the context of immunity against HCV infection could be under the control of miR16.
Inhibition of lncRNA MEG3 protects renal tubular from hypoxia‐induced kidney injury in acute renal allografts by regulating miR‐181b/TNF‐α signaling pathway
Authors: Pang Xinlu , Feng Guiwen , Shang Wenjun , Liu Lei , Li Jingfeng , Feng Yonghua , Xie Hongchang , Wang Junxiang
Published: March 2019

Early damage to transplanted organs initiates excess inflammation that deteriorates existing injury, which is a leading cause of graft loss. Long noncoding RNAs (lncRNAs) are recently thought to play a significant role in cellular homeostasis during pathological process of kidney diseases. The aim of this study was to assess the function and mechanism of lncRNA, maternally expressed gene 3 (MEG3), on early renal allografts pathogenesis. Real‐time polymerase chain reaction (RT‐PCR) analysis found that the levels of MEG3 and miR‐181b‐5p were increased and decreased respectively in grafted kidney. The Western blot assay showed that TNF‐alpha was upregulated in the kidney and in HK‐2 cells. Administering MEG3‐specific small interfering RNA (siRNA) in mice silenced MEG3 expression and protected kidney renal allograft from injury. Bioinformatical analysis and luciferase assay indicated that MEG3 is a target of miR‐181b‐5p. MEG3 inhibition and overexpression promoted and suppressed miR‐181b‐5p levels respectively. In addition, Western blot and immunohistochemical staining suggested that decreased TNF‐alpha expression was observed in the kidney. In contrary to MEG3, miR181b overexpression attenuated hypoxia‐induced HK‐2 cell apoptosis, as well as suppressed hypoxia‐induced TNF‐alpha upregulation. In luciferase reporter assay, we confirmed that miR‐181b directly bound to the 3′‐untranslated region (3′‐UTR) of TNF‐alpha, thereby negatively regulating the TNF‐alpha expression. Our data suggested that MEG3 functions as a competing endogenous RNA for miR‐181b to regulate the TNF‐alpha expression in hypoxia‐induced kidney injury in acute renal allografts.
Plant latex thrombin‐like cysteine proteases alleviates bleeding by bypassing factor VIII in murine model
Authors: Urs Amog P. , Rudresha G. V. , Manjuprasanna V. N. , Suvilesh K. N. , Gowda M. D. Milan , Yariswamy M. , Hiremath Vilas , Ramakrishnan Chandrasekaran , Savitha M. N. , Jayachandra K. , Sharanappa P. , Vishwanath B. S.
Published: March 2019

Hemostasis is a tightly regulated process which maintains a fluid state of blood within the vasculature and provides thrombotic response upon tissue injury. Various scientific studies have implicated the role of plant latex proteases in hemostasis using in vitro experiments. However, in vivo models substantiate their role in hemostasis. Therefore, in the present study, the effect of plant latex thrombin‐like proteases (PTLPs) on hemostasis was investigated systematically using mice tail bleeding as a preclinical model. In this direction, latex protease fractions (LPFs), which showed potent thrombin‐like activity, were selected as they act directly on fibrinogen to form clot and quickly stop bleeding. Thrombin‐like activity was exhibited mainly by cysteine proteases. Calotropis gigantea,
Carica papaya, Jatropha curcas, Oxystelma esculentum,
Tabernaemontana divaricata, and
Vallaris solanacea LPFs and papain from
C.
papaya latex significantly reduced bleeding on a topical application in normal and aspirin administered mice. In addition, PTLPs accelerated the clotting of factor VIII deficient plasma, while, papain brought back the clotting time to normal levels acting like a bypassing agent. Further, papain failed to show activity in the presence of specific cysteine protease inhibitor iodoacetic acid; confirming protease role in all the activities exhibited. At the tested dose, PTLPs except
C.
gigantea did not show toxicity. Further, structural and sequence comparison between PTLPs and human thrombin revealed structural and sequence dissimilarity indicating their unique nature. The findings of the present study may open up a new avenue for considering PTLPs including papain in the treatment of bleeding wounds.
Long noncoding RNA TALNEC2 regulates myocardial ischemic injury in H9c2 cells by regulating miR‐21/PDCD4‐medited activation of Wnt/β‐catenin pathway
Authors: Hao Lin , Wang Juan , Liu Na
Published: March 2019

The goal of this study was to explore the role of tumor associated long noncoding RNA expressed on chromosome 2 (TALNEC2) in protecting against myocardial ischemic injury, as well as its underlying molecular mechanism. We established a cell model of myocardial injury through treating H9c2 cells with hypoxia, and the expression level of TALNEC2 was analyzed. Further, in vitro studies investigated the functional role of TALNEC2 dysregulation in hypoxia injury by assessing cell proliferation, migration, invasion, and apoptosis. Moreover, the expression of miR‐21 was determined after dysregulation of TALNEC2, and whether TALNEC2‐regulated hypoxia injury in H9c2 cells via regulating miR‐21 expression were explored. Furthermore, the regulatory relationship between TALNEC2 and Wnt/β‐catenin pathway was also investigated. TALNEC2 was highly expressed in the serum from patients with myocardial ischemic compared with that in healthy persons. Hypoxia‐induced injury in H9c2 cells. Overexpression of TALNEC2 aggravated hypoxia injury in H9c2 cells. TALNEC2 could negative regulate the miR‐21 expression, and overexpression of TALNEC2 aggravated hypoxia injury by downregulation of miR‐21. Moreover, miR‐21 negatively regulated the PDCD4 expression, and PDCD4 was a target of miR‐21. Further studies disclosed that the overexpression of TALNEC2 further activated the Wnt/β‐catenin pathway in hypoxia‐treated H9c2 cells, implying that the Wnt/β‐catenin pathway was a downstream mechanism mediating the role of TALNEC2 in regulating hypoxia injury in H9c2 cells. These findings confirmed the key functions of TALNEC2 in regulating myocardial ischemic injury. Upregulation of TALNEC2 may aggravate hypoxia injury in H9c2 cells via regulating miR‐21/PDCD4‐medited activation of the Wnt/β‐catenin pathway. TALNEC2 may serve as a promising therapeutic target in myocardial ischemia.
A comprehensive study of CD44 rs 187115 variant and cancer risk in a central Chinese population
Authors: Chen Bifeng , Yi Can , Wang Jingdong , Wang Jieling , Zhang Jingli , Gu Xiuli , Feng Xianhong
Published: March 2019

The rs187115, an intronic variant of CD44 gene, has been previously reported to play a potential role in genetic susceptibility to cancer. Here, we comprehensively examined the association between CD44 rs187115 variant and cancer risk (breast cancer, cervical cancer, lung cancer, gastric cancer, liver cancer, colon cancer, and rectal cancer) in a central Chinese population. The rs187115 variant was genotyped with the polymerase chain reaction‐restriction fragment length polymorphism assay. In this study, we observed that rs187115 was associated with the risk of cervical, lung, and liver cancer, but not with the risk of breast, gastric, colon, rectal or colorectal cancer. Of note, the G allele and G allele genotypes of rs187115 conferred an increased risk of cervical, lung, and liver cancer. To improve the statistical strength, a followed meta‐analysis was conducted. The results demonstrated that rs187115 was significantly associated with cancer risk, and the significant association remained in the stratification analysis by ethnicity, genotyping method, and cancer type. Collectively, the CD44 rs187115 variant may be associated with the risk of cervical, lung, and liver cancer in the central Chinese population, and may be used as a potential biomarker for cancer predisposition in the Asian population, especially in the Chinese population.
LIMK1 depletion enhances fasudil‐dependent inhibition of urethral fibroblast proliferation and migration
Authors: Liang Ying‐Chun , Li Xiao‐Dong , Wu Yu‐Peng , Ke Zhi‐Bin , Liu Zhang‐Qi , Chen Shao‐Hao , Wei Yong , Zheng Qing‐Shui , Xue Xue‐Yi , Xu Ning
Published: March 2019

LIM kinase 1 (LIMK1) is an important regulator of the cell cytoskeleton. This study aimed to examine the role of LIMK1 in mediating the effects of the Rho kinase (ROCK) inhibitor fasudil. In vitro cultures of urethral fibroblasts were divided into LIMK1 knockdown (LIMK1 KD) and LIMK1 control (LIMK1 NC) experimental groups. Each group was incubated with fasudil (50 μmol/L) with or without transforming growth factor β1 (10 ng/mL) for 24 hours. Wound healing and Transwell assays were performed to determine cell migration. Flow cytometry was used to determine apoptosis. LIMK1, collagen I, collagen III, phospho‐myosin light chain (p‐MLC), alpha smooth muscle actin (α‐SMA), and phospho‐Cofilin (p‐Cofilin) expression was examined by Western blot analysis. The expression of LIMK1 was further validated in human urethral scar tissues. Transwell and wound healing assays revealed that the cells of the LIMK1 KD group exhibited significantly attenuated migration, when compared with those of the LIMK1 NC group (
P < 0.05). Cell migration was also attenuated in the LIMK1 KD group treated with fasudil (
P < 0.05). Flow cytometry analysis revealed that apoptosis was higher in the LIMK1 KD group than that in LIMK1 NC group (
P < 0.05). Apoptosis was also enhanced in the LIMK1 KD group treated with fasudil (
P < 0.05). Western blot analysis demonstrated that LIMK1, collagen I, collagen III, p‐MLC, α‐SMA, and p‐Cofilin expression was significantly attenuated in both the fasudil‐treated and untreated LIMK1 KD groups (
P < 0.05). LIMK1 was positively expressed in human urethral scar tissues while it was negatively expressed in normal urethra tissues. In conclusion, loss of LIMK1 expression inhibits the Rho/ROCK pathway‐dependent proliferation and migration via downregulation of collagen I, collagen III, p‐Cofilin, and α‐SMA. LIMK1 loss can also enhance the inhibitory effects of fasudil on the proliferation and migration of urethral fibroblasts.
Genetic variants in promoter regions associated with type 2 diabetes mellitus: A large‐scale meta‐analysis and subgroup analysis
Authors: Wu Ling , Wang Chi Chiu
Published: March 2019

Background

Promoter plays important roles in regulating transcription of genes. Association studies of genetic variants in promoter region with type 2 diabetes (T2D) risk have been reported, but most were limited to small number of individual genetic variants and insufficient sample sizes. In addition, the effect of study populations and demographic characteristics were often neglected.

Methods

In this study, we conducted a large‐scale meta‐analysis and subgroup analysis of T2D associated genetic variants in the promoter regions to evaluate their contribution to the susceptibility in T2D. Alleles and genotypes from cohort or case‐controlled studies were extracted for future study. Total 41 742 cases and 50 493 controls for three loci were involved in 70 articles.

Results

Seventy case‐controlled studies of three genes with 41 742 cases and 50 493 controls were included. Meta‐analysis showed only rs266729 and rs17300539 of ADIPOQ, and rs1884613, rs2144908, and rs4810424 of
HNF4A were significantly associated with T2D risk. Subgroup analysis showed that both rs266729 and rs17300539 of
ADIPOQ were associated with the risk of T2D in Caucasian population, but only rs266729 of
ADIPOQ in Asian population and rs2144908 in other population including multinational North American. For diagnostic criteria, rs266729 of ADIPOQ and rs2144908 of HNF4A were associated with T2D risk when WHO/ADA diagnostic criteria were used. For genotyping methods, both rs266729 of ADIPOQ and rs2144908 of HNF4A were associated with T2D risk when other than Taqman and Sequencing methods were used.

Conclusions

T2D was significantly associated with promoter rs266729, rs17300539, rs1884613, rs2144908, and rs4810424, and the association of T2D risk were affected by study population, diagnostic criteria, and genotype methods.
Spectroscopic studies on the interaction of alpha‐eleostearic acid with calf thymus DNA
Authors: Liu Yufeng , Zhang Baixin , Chen Xiaomei , Guo Zhian , Wang Yi , Zhao Jingchan
Published: March 2019

Interaction between alpha‐eleostearic acid (α‐ESA) and calf thymus DNA in Tris‐HCl buffer (pH = 7.4) using neutral red (NR) dye as a spectral probe was investigated using UV–Vis absorption and fluorescence spectroscopy. Spectral data matrix of the complexed reaction between α‐ESA and NR with DNA was processed with an alternative least‐squares (ALS) algorithm, the obtained concentration profiles and the corresponding pure spectra for species (NR, DNA–NR, and DNA–NR–ESA) demonstrated three kinds of reactions might occur in the system. The major groove binding between α‐ESA and DNA was further validated using circular dichroism, viscosity, DNA melting, and ionic strength effect measurements. Moreover, the calculated values of thermodynamic parameters, such as enthalpy (ΔHθ, −22.04 kJ/mol) and entropy change (ΔSθ, 91.52 J K−1 mol−1), suggested binding between α‐ESA and DNA was mainly driven by hydrophobic interactions and hydrogen bonds without electrostatic force.
Up‐regulation of circular RNA hsa_circ_0037909 promotes essential hypertension
Authors: Bao Xingjie , He Xin , Zheng Shuying , Sun Jihan , Luo Yizhe , Tan Ronghui , Zhao Jinshun , Zhong Fade , Zhang Lina
Published: March 2019

Aims

Essential hypertension (EH) is a high prevalence disease facing a public health challenge. People were little known about the genetics of diagnosing the cause of EH. Circular RNAs that have a continuous cycle of covalent closure, without affected by RNA exonuclease, and are more stable and hard to degrade may involve into the molecule regulation mechanism of EH as an important biomedical.

Methods

qRT‐PCR was used to analyze circRNAs in total volume of human blood and the induced human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs). Our case‐control study was involved with 48 pairs of case controls with sex and age (±3 years) match. We conducted t test, Pearson's χ2 test, and receiver operating characteristics (ROC) curve analysis for the corresponding analysis.

Results

The expression level of hsa_circ_0037909 in EH patients was significantly higher than that in the healthy controls (P = 0.007), and the expression level of hsa‐miR‐637 in EH patients was significantly lower in than that in the healthy controls (P = 0.039); the same result appears in the HAECs and HUVECs. Hsa‐miR‐637 (adjusted P = 0.018), hsa_circ_0037909 (adjusted P = 0.005), HDL (adjusted P = 0.024), and serum creatinine (adjusted P = 0.014) were brought into the model which performed logistic regression analysis. The combination of two RNAs was excellent (P < 0.001) through ROC curve analysis. Hsa_circ_0037909 was significantly positively correlated with serum creatinine (P < 0.001) and low‐density lipoprotein (LDL) (P = 0.017).

Conclusions

Our findings suggested that the combination of hsa_circ_0037911 and hsa‐miR‐637 may be a significant important biomarker for early diagnosis of EH. Hsa_circ_0037909 may affect serum creatinine or LDL leading to the formation of EH.
Identifying and addressing mental health providers’ perceived barriers to clinical video telehealth utilization
Authors: Perry Kristen , Gold Sari , Shearer Erika M.
Published: March 2019

Objective

Clinical video telehealth (CVT) is an innovative modality to provide care directly to Veterans’ homes. Despite prior training initiatives, CVT remains underutilized. This project sought to better understand barriers to implementation and to compare responses of CVT utilizers versus nonutilizers.

Method

Mental health staff were invited to complete an online anonymous survey on their use of CVT in clinical practice.

Results

A total of 159 mental health staff completed the survey. Although the majority of the sample endorsed personal use of a video chat program, less than half reported using CVT for patient care. Among nonutilizers, lack of training was the most frequently endorsed barrier to CVT use whereas administrative burden was the most frequently endorsed barrier by utilizers.

Conclusions

This study extends existing literature by determining barriers to CVT adoption. It identifies several barriers among utilizers versus nonutilizers. Discussion includes potential guidelines for overcoming barriers to CVT utilization.
Misophonia: A scoping review of research
Authors: Potgieter Iskra , MacDonald Carol , Partridge Lucy , Cima Rilana , Sheldrake Jacqueline , Hoare Derek J.
Published: March 2019

Objective

To scope the literature describing misophonia populations, management, and research opportunities.

Method

Literature searches for research studies describing patients diagnosed with misophonia, defining a patient profile, or outlining development or testing of an intervention for misophonia. A data extraction form was developed and piloted before data from each article were independently charted by two researchers. Researchers then agreed on a final data set for each article.

Results

Thirty‐one records were included. The misophonia population was described in terms of onset age, triggers, reaction, coping strategies, and comorbid conditions. We identified nine outcome measures. Case studies on treatments included cognitive behavioral therapy, counterconditioning, mindfulness and acceptance, dialectical behavioral therapy, and pharmaceuticals. Future research priorities identified included clarifying the phenomenology and prevalence of misophonia, and randomized controlled trials of treatments.

Conclusion

Misophonia is under‐researched but there are strong foundations for future research to finalize diagnostic criteria, validate outcome measures, and trial treatments.
Melatonin‐mediated regulation of autophagy: Making sense of double‐edged sword in cancer
Authors: Mirza‐Aghazadeh‐Attari Mohammad , Mohammadzadeh Amir , Adib Ali , Darband Saber Ghazizadeh , Sadighparvar Shirin , Mihanfar Ainaz , Majidinia Maryam , Yousefi Bahman
Published: March 2019

Much research has been conducted to discover novel techniques to reverse the process of tumorigenesis and, cure already stablished malignancies. One well‐stablished approach has been the use of organic compounds and naturally found agents such as melatonin whose anticancer effects have been shown in multiple studies, signaling a unique opportunity regarding cancer prevention and treatment. Various agents use a variety of methods to exert their anticancer effects. Two of the most important of these methods are interfering with cell signaling pathways and changing cellular functions, such as autophagy, which is essential in maintaining cellular stability against multiple exogenous and endogenous sources of stress, and is a major tool to evade early cell death. In this study, the importance of melatonin and autophagy are discussed, and the effects of melatonin on autophagy, and its contribution in the process of tumorigenesis are then noted.
Hypermethylated and downregulated MEIS2 are involved in stemness properties and oxaliplatin‐based chemotherapy resistance of colorectal cancer
Authors: Wang Xiaojie , Ghareeb Waleed M. , Zhang Yiyi , Yu Qian , Lu Xingrong , Huang Ying , Huang Shenghui , Sun Yanwu , Chi Pan
Published: March 2019

The resistance against oxaliplatin (L‐OHP) based regimens remains a major obstacle for its efficient usage in treating metastatic colorectal cancer (mCRC). In this study, we performed weighted gene coexpression network analysis (WGCNA) to systematically screen the relevant hub genes for L‐OHP resistance using the raw microarray data of 30 consecutive mCRC samples from our earlier study (GSE69657). The results were further confirmed through datasets from Gene Expression Omnibus (GEO). From L‐OHP resistance module, nine genes in both the coexpression and protein–protein interaction networks were chosen as hub genes. Among these genes, Meis Homeobox 2 (MEIS2) had the highest correlation with L‐OHP resistance (r = −0.443) and was deregulated in L‐OHP resistant tissues compared with L‐OHP sensitive tissues in both our own dataset and GSE104645 testing dataset. The receiver operating characteristic curve validated that MEIS2 had a good ability in predicting L‐OHP response in both our own dataset (area under the curve [AUC] = 0.802) and GSE104645 dataset (AUC = 0.746). Then, the down expression of MEIS2 was observed in CRC tissue compared with normal tissue in 12 GEO‐sourced datasets and The Cancer Genome Atlas (TCGA) and was correlated with poor event‐free survival. Furthermore, analyzing methylation data from TCGA showed that MEIS2 had increased promoter hypermethylation. In addition, MEIS2 expression was significantly decreased in CRC stem cells compared with nonstem cells in two GEO datasets (GSE14773 and GSE24747). Further methylation analysis from GSE104271 demonstrated that CRC stem cells had higher MEIS2 promoter methylation levels in cg00366722 and cg00610348 sites. Gene set enrichment analysis showed that MEIS2 might be involved in the Wnt/β‐catenin pathway. In the overall view, MEIS2 had increased promoter hypermethylation and was downregulated in poor L‐OHP response mCRC tissues. MEIS2 might be involved in the Wnt/β‐catenin pathway to maintain CRC stemness, which leads to L‐OHP resistance.
RA promotes proliferation of primordial germ cell‐like cells differentiated from porcine skin‐derived stem cells
Authors: Yan Hong‐Chen , Li Lin , Liu Jing‐Cai , Wang Yu‐Feng , Liu Xue‐Lian , Ge Wei , Dyce Paul W. , Li Lan , Sun Xiao‐Feng , Shen Wei , Cheng Shun‐Feng
Published: March 2019

Previous studies have shown that primordial germ cell‐like cells (PGCLCs) can be obtained from human, porcine and mouse skin‐derived stem cells (SDSCs). In this paper, we found retinoic acid (RA), the active derivative of vitamin A, accelerated the growth of porcine primordial germ cells (pPGCs) and porcine PGCLCs (pPGCLCs) which were derived from porcine SDSCs (pSDSCs). Moreover, flow cytometry results revealed that the proliferation promoting effect of RA was attenuated by U0126, a specific inhibitor of extracellular signal‐regulated kinase (ERK). Western blot analysis showed the protein level of ERK, phosphorylated ERK, cyclin D1 (CCND1), and cyclin‐dependent kinase 2 (CDK2) increased after stimulation with RA, and this effect could also be abolished by U0126. Our data revealed that ablation of ERK expression by U0126 should significantly decrease proliferation of pPGCLCS. This reduction was because CCND1 and CDK2 proteins level decrease and subsequently the pPGCLCs were arrested in the G0/G1 phase. In addition, we also confirmed RA indeed promoted the proliferation of pPGCs isolated from porcine fetal genital ridges in vitro. Furthermore, our data indicated that DNA methylation pattern were changed in pPGCLCs and this pattern were more similar to pPGCs.
Incorporation of Gene‐Environment Interaction Terms Improved the Predictive Accuracy of Tacrolimus Stable Dose Algorithms in Chinese Adult Renal Transplant Recipients
Authors: Tang Jie , Xu Jing , Zhang Yue‐Li , Liu Rong , Liu Mou‐Ze , Hu Yong‐Fang , Shao Ming‐Jie , Zhu Li‐Jun , Cao Shan , Xin Hua‐Wen , Feng Gui‐Wen , Shang Wen‐Jun , Meng Xiang‐Guang , Zhang Li‐Rong , Ming Ying‐Zi , Zhang Wei , Zhou Gan
Published: March 2019

The narrow therapeutic window of tacrolimus necessitates daily monitoring and predictive algorithms based on genetic and nongenetic factors. In this study, we constructed predictive algorithms for tacrolimus stable dose in a retrospective cohort of 1045 Chinese renal transplant recipients. All patients were genotyped forCYP3A420230T>C (rs2242480),CYP3A4T>C (rs4646437),CYP3A5*3 6898A>G (rs776746),ABCB1129T>C (rs3213619);ABCB1c.1236C>T (rs01128503),ABCB1c.2677G>T/A (rs2032582) andABCB1c.3435C>T (rs1045642) polymorphisms, and the effects of gene‐gene and gene‐environment interactions on the predictive accuracy of algorithm were evaluated. In wild‐typeCYP3A4rs2242480 (TT) carriers, patients who took calcium channel blockers had lower tacrolimus stable doses than those without the concomitant medications (P< 1 × 10−4). In contrast, there was no significant difference in mutant type patients. Similarly, the tacrolimus stable doses in wild‐typeCYP3A5rs776746 carriers who had hypertension were higher than those without hypertension (P= 4.10 × 10−3). More importantly, dose‐predictive algorithms with interaction terms showed higher accuracy and better performance than those without interaction terms. Our finding suggested that wild‐typeCYP3A4rs2242480 (TT) carriers should be more cautious to take tacrolimus when they are coadministrated with calcium channel blockers, andCYP3A5rs776746 (AA) carriers may need higher tacrolimus dosage when they are in combination with hypertension.
Delay discounting in the pigeon: In search of a magnitude effect
Authors: Holt Daniel D. , Wolf Matthew R.
Published: March 2019

The magnitude effect, where larger outcomes are discounted proportionally less than smaller outcomes, is a well‐established phenomenon in delay discounting by human participants. To this point in the literature magnitude effects have not been reliably evidenced in nonhuman animals. , however, used a concurrent‐chains arrangement with pigeon and found evidence for a magnitude effect. Grace et al. suggested that in many delay discounting experimental arrangements with nonhuman animals (e.g., adjusting amount, adjusting delay) the organism is not given the opportunity to directly compare outcomes of different sizes. They suggest that because of the lack of direct comparison it is difficult for the organism to determine the relative size of each outcome, which in turn mutes the effect of the amount differences between outcomes. As a test of this “comparison hypothesis,” the present experiment was conducted to assess whether the magnitude effect would be evidenced in pigeon when using an adjusting amount procedure where outcomes of different amounts were presented proximally. In the present arrangement, pigeons were presented two choice panels in an operant chamber where each panel was associated with an independent adjusting amount delay discounting task, but with differing outcome amounts (i.e., a 32‐food pellet panel and an 8‐food pellet panel). In this arrangement the choice panels alternated in their availability within a session from trial block to trial block. The present findings indicate no reliable effect of amount, even when the outcomes were proximal and thus readily comparable. This result suggests that the lack of magnitude effect is not driven by the organism's ability to compare the difference in amount between choice alternatives.
c-Abl kinase regulates neutrophil extracellular trap formation, inflammation, and tissue damage in severe acute pancreatitis
Authors: Madhi Raed , Rahman Milladur , Mörgelin Matthias , Thorlacius Henrik
Published: March 2019

Neutrophil extracellular traps (NETs) are involved in acute pancreatitis (AP) but mechanisms controlling NET expulsion in AP are incompletely understood. Herein, we examined the role of c-Abelson (c-Abl) kinase in NET formation and tissue damage in severe AP. AP was induced by taurocholate infusion into pancreatic duct or intraperitoneal administration of l-arginine in mice. Pancreatic, lung, and blood samples were collected and levels of phosphorylated c-Abl kinase, citrullinated histone 3, DNA-histone complexes, myeloperoxidase, amylase, cytokines, and CXC chemokines were quantified. Citrullinated histone 3, reactive oxygen species (ROS), and NET formation were determined in bone marrow neutrophils. Taurocholate challenge increased phosphorylation of c-Abl kinase and levels of citrullinated histone 3 in the pancreas as well as DNA-histone complexes in the plasma. Administration of the c-Abl kinase inhibitor GZD824 not only abolished activation of c-Abl kinase but also decreased levels of citrullinated histone 3 in the pancreas and DNA-histone complexes in the plasma of animals with AP. Moreover, GZD824 decreased plasma levels of amylase, IL-6, and MMP-9 as well as edema, acinar cell necrosis, hemorrhage, CXC chemokine formation, and neutrophil infiltration in the inflamed pancreas. A beneficial effect of c-Abl kinase inhibition was confirmed in l-arginine-induced pancreatitis. In vitro, inhibition of c-Abl kinase reduced TNF-α-induced formation of ROS, histone 3 citrullination, and NETs in isolated bone marrow neutrophils. Our findings demonstrate that c-Abl kinase regulates NET formation in the inflamed pancreas. In addition, inhibition of c-Abl kinase reduced pancreatic tissue inflammation, and damage in AP. Thus, targeting c-Abl kinase might be a useful way to protect the pancreas in severe AP.
Mechanistic insights into intramolecular phosphate group transfer during collision induced dissociation of phosphopeptides
Authors: Bailey Laura S. , Alves Mélanie , Galy Nicolas , Patrick Amanda L. , Polfer Nicolas C.
Published: March 2019

We report on the rearrangement chemistry of model phosphorylated peptides during collision‐induced dissociation (CID), where intramolecular phosphate group transfers are observed from donor to acceptor residues. Such “scrambling” could result in inaccurate modification localization, potentially leading to misidentifications. Systematic studies presented herein provide mechanistic insights for the unusually high phosphate group rearrangements presented some time ago by Reid and coworkers (Proteomics 2013, 13 [6], 964‐973). It is postulated here that a basic residue like histidine can play a key role in mediating the phosphate group transfer by deprotonating the serine acceptor site. The proposed mechanism is consistent with the observation that fast collisional activation by collision‐cell CID and higher‐energy collisional dissociation (HCD) can shut down rearrangement chemistry. Additionally, the rearrangement chemistry is highly dependent on the charge state of the peptide, mirroring previous studies that less rearrangement is observed under mobile proton conditions.
Comparison of the efficacy of sofosbuvir plus ribavirin in Chinese patients with genotype 3a or 3b HCV infection
Authors: Huang Rui , Rao Huiying , Xie Qing , Gao Zhiliang , Li Wu , Jiang Deyuan , Mo Hongmei , Massetto Benedetta , Stamm Luisa M. , Brainard Diana M. , Wei Lai
Published: March 2019

Background and Aim

Genotype 3b hepatitis C virus (HCV) infection represents approximately 50% of patients with genotype 3 in China. We compared the efficacy of sofosbuvir (SOF) plus ribavirin (RBV) in Chinese patients with genotype 3a and 3b HCV.

Methods

The analyzed data are from a phase 3, open‐label study of SOF plus RBV for 24 weeks conducted in China. The primary endpoint for the trial was sustained virologic response at 12 weeks after the end of therapy (SVR12).

Results

Of 126 patients included in this analysis, 58 (46%) had genotype 3a and 68 (54%) had genotype 3b. Both the subtypes were similar in age, sex, body mass index, IL28B, and baseline HCV RNA. However, more treatment‐experienced and cirrhotic patients were in the genotype 3b group. All 100% of patients with genotype 3a (95% confidence interval [CI], 94‐100), and 91% (95% CI, 82‐97) of patients with genotype 3b achieved SVR12 (P = 0.030). For treatment‐experienced patients with genotype 3b, the SVR12 rate was 73% (95% CI, 39‐94) and 88% (95% CI, 64‐99) among patients with and without cirrhosis (P = 1.00), respectively.

Conclusion

SOF plus RBV for 24 weeks in patients with HCV genotype 3 infection resulted in high rates of SVR. However, the SVR12 rate among patients with genotype 3b was lower than that observed in patients with genotype 3a infection, particularly among treatment‐experienced patients with cirrhosis.
Ultra‐wideband antenna for wearable Internet of Things devices and wireless body area network applications
Authors: Mustaqim Muhammad , Khawaja Bilal A. , Chattha Hassan T. , Shafique Kinza , Zafar Muhammad J. , Jamil Mohsin
Published: March 2019

This paper presents a compact and planar ultra‐wideband (UWB) antenna, designed and characterized for the wearable Internet of Things (IoT) devices and wireless body area network (WBAN) applications. Two different substrates, ie, FR4 (h = 1.6 mm) and denim textile substrate (h = 1 mm), are used in the process of design and fabrication of the proposed antenna. The dimensions of the proposed antenna are 31 mm × 42 mm for FR4 substrate and 70 mm × 56 mm for denim textile substrate. The antenna structure consists of a rectangular radiating patch with two symmetrical staircase‐shaped slits. A reduced ground plane technique is used for the purpose of improving impedance bandwidth, which is further enhanced by the insertion of a small notch in the reduced ground plane which has improved the overall impedance matching characteristics of the proposed UWB antenna. The measured impedance bandwidth for S11 < −10 dB and gain of the FR4 and denim textile substrate UWB antennas are 7.71 GHz/5.12 dBi and 7.95 GHz/3.57 dBi, respectively. The ADS momentum simulator is used for antenna simulations, and the simulated and measured results are generally found in good agreements.
Meta‐analysis andMendelianrandomization: A review
Authors: Bowden Jack , Holmes Michael V.
Published: March 2019

Mendelian randomization (MR) uses genetic variants as instrumental variables to infer whether a risk factor causally affects a health outcome. Meta‐analysis has been used historically in MR to combine results from separate epidemiological studies, with each study using a small but select group of genetic variants. In recent years, it has been used to combine genome‐wide association study (GWAS) summary data for large numbers of genetic variants. Heterogeneity among the causal estimates obtained from multiple genetic variants points to a possible violation of the necessary instrumental variable assumptions. In this article, we provide a basic introduction to MR and the instrumental variable theory that it relies upon. We then describe how random effects models, meta‐regression, and robust regression are being used to test and adjust for heterogeneity in order to improve the rigor of the MR approach.
Enhanced laser surface ablation with an integrated photoacoustic imaging and high intensity focused ultrasound system
Authors: Hazlewood David , Yang Xinmai
Published: March 2019

Background and Objective

Combined laser and ultrasound treatments have been found to have synergistic effects, which may be of particular note in dermatology. We aim to investigate the potential of this technology for dermatology through in vitro and ex vivo experiments.

Methods

In vitro tissue phantoms made of agar and tattoo ink and tattooed ex vivo chicken breast tissue were used. An integrated photoacoustic imaging and high intensity focused ultrasound (HIFU) system, using a 5‐ns tunable OPO laser system and a 5 MHz HIFU transducer, was used to perform photoacoustic analysis to identify the optical contrast, and perform combined laser and ultrasound ablation. On the tissue phantoms, lines of ablation were created under various operating conditions. The samples were then quantified to determine the level of ablation. Same procedures were performed on the tattooed chicken breast tissue and the tattoo was removed by using combined laser and ultrasound.

Results

Ablation in the in vitro tissue phantoms was observed with properly synchronized laser and ultrasound while no ablation was found with either laser or ultrasound alone. Increases to the intensity or pulse duration of ultrasound caused an increase in ablation to the samples. The tattoo was removed from the ex vivo chicken breast using combined laser and ultrasound with a radiant exposure of 1.2 J/cm2 while laser and ultrasound alone were unable to remove the tattoo.

Conclusions

We determined that by supplementing nanosecond laser pulses with ultrasound, ablation, and tattoo removal can be achieved at laser radiant exposures levels would otherwise be ineffective. The area of ablation can be adjusted through changes in the intensity and duration of the ultrasound burst with a constant laser intensity. Additionally, the system can be used to perform photoacoustic analysis of the tissue to estimate the relative optical absorbance at various available wavelengths, allowing for pretreatment analysis. Lasers Surg. Med. 9999:1–9, 2019. © 2019 Wiley Periodicals, Inc.
Polyacrylic Acid‐Based Coordination Supramolecular Elastomer with High Strength, Excellent Fatigue‐Resistance, and Self‐Recovery Properties
Authors: Wu Jia , Niu Wenbin , Zhang Shufen , Wu Suli , Ma Wei , Tang Bingtao
Published: March 2019

Supramolecular elastomers have attracted extensive attention due to their excellent mechanical properties. Herein, inspired by the concept of a dual cross‐linked network structure, a dual‐component coordination supramolecular elastomer is prepared via photopolymerization of three monomers combined with zinc ion (Zn2+)‐crosslinked low molecular weight polyacrylic acid (PAA). The covalent network of three monomers serves as a soft component forming the supporting network. The network of Zn2+ crosslinked low molecular weight PAA forms the hard component. The covalent network is crosslinked and locked by the coordinated network. This compact network contributes to improving the comprehensive mechanical properties. The optimal elastomer is that the molar ratio of carboxylic of low molecular weight PAA with Zn2+ is 1:0.5. The tensile and compression stress of the optimal elastomer are 4.08 and 6.90 MPa, respectively. The loading–unloading cycles can reach 1000 times without fracture. The self‐recovery ratios of the tensile and compression modes reaches 80% and 95%, respectively.