bluuebunny/crossref_metadata_2025 huggingface dataset:
Bivariate logistic Bayesian LASSO for detecting rare haplotype association with two correlated phenotypes
Authors: Yuan Xiaochen , Biswas Swati
Published: September 2019

In genetic association studies, joint modeling of related traits/phenotypes can utilize the correlation between them and thereby provide more power and uncover additional information about genetic etiology. Moreover, detecting rare genetic variants are of current scientific interest as a key to missing heritability. Logistic Bayesian LASSO (LBL) has been proposed recently to detect rare haplotype variants using case‐control data, that is, a single binary phenotype. As there is currently no haplotype association method that can handle multiple binary phenotypes, we extend LBL to fill this gap. We develop a bivariate model by using a latent variable to induce correlation between the two outcomes. We carry out extensive simulations to investigate the bivariate LBL and compare with the univariate LBL. The bivariate LBL performs better or similar to the univariate LBL in most settings. It has the highest gain in power when a haplotype is associated with both traits and it affects at least one trait in a direction opposite to the direction of the correlation between the traits. We analyze two data sets—Genetic Analysis Workshop 19 sequence data on systolic and diastolic blood pressures and a genome‐wide association data set on lung cancer and smoking and detect several associated rare haplotypes.
HBx Protein Contributes to Liver Carcinogenesis by H3K4me3 Modification Through Stabilizing WD Repeat Domain 5 Protein
Authors: Gao Weiwu , Jia Zhengcai , Tian Yi , Yang Penghui , Sun Hui , Wang Chenhui , Ding Yi , Zhang Mengjie , Zhang Yi , Yang Di , Tian Zhiqiang , Zhou Jian , Ruan Zhihua , Wu Yuzhang , Ni Bing
Published: September 2019

Background and Aims

Cancer is typically considered as a genetic and epigenetic disease. Although numerous studies have indicated that an aberrant structure, function, or expression level of epigenetic enzymes contribute to many tumor types, precisely how the epigenetic mechanisms are involved in the hepatitis B virus (HBV)‐induced hepatocellular carcinoma (HCC) remains unknown.

Approach and Results

In this study, we found that the WD repeat domain 5 protein (WDR5)—a core subunit of histone H3 lysine 4 methyltransferase complexes, which catalyze the generation of histone H3 lysine 4 trimethylation (H3K4me3) modification—is highly expressed in HBV‐related HCC and promotes HCC development. WDR5 plays a critical role in HBV‐driven cell proliferation and tumor growth in mice, and the WDR5‐0103 small‐molecule inhibitor of WDR5 activity compromises HBV‐ and hepatitis B x protein (HBx)‐driven tumor proliferation. The aberrantly high WDR5 protein level was found to involve HBx through its stabilization of the WDR5 protein by inhibiting the interaction between the damage‐specific DNA‐binding protein 1/cullin‐4 and WDR5, causing decreased ubiquitination of the WDR5 protein. HBx was found to colocalize with WDR5 on chromatin genome wide and promotes genome‐wide H3K4me3 modification by means of WDR5. Furthermore, the recruitment of HBx to promoters of target genes relied on its interaction with WDR5 through its α‐helix domain. WDR5 was also found to promote HBV transcription through H3K4 modification of covalently closed circular DNA minichromosome, and WDR5‐0103 was able to inhibit HBV transcription. Finally, the in vitro and in vivo data further proved that HBx exerted its tumor‐promoting function in a WDR5‐dependent manner.

Conclusions

Our data reveals that WDR5 is a key epigenetic determinant of HBV‐induced tumorigenesis and that the HBx‐WDR5‐H3K4me3 axis may be a potential therapeutic target in HBV‐induced liver pathogenesis.
The effect of a periodic tangential magnetic field on the stability of a horizontal magnetic fluid sheet
Authors: Moatimid Galal M. , Eldabe Nabil T. , Sayed Aya
Published: September 2019

The current article aims at investigating the effect of a periodic tangential magnetic field on the stability of a horizontal flat sheet. The media were considered porous, the three viscous‐fluid layers were initially streaming with uniform velocities, and the magnetic field admitted the presence of free‐surface currents. Furthermore, the transfer of mass and heat phenomenon was taken into account. The analysis, in this paper, was followed by the viscous potential theory. Moreover, the stability of the boundary‐value problem resulted in coupled second‐order linear differential equations with damping and complex coefficients. In regard to the uniform and periodic magnetic field, the standard normal mode approach was applied to deduce a general dispersion relation and judge the stability criteria. In addition, several unfamiliar cases were reported, according to appropriate data choices. The stability conditions were theoretically analyzed, and the influences of the various parameters in the stability profile were identified through a set of diagrams. In accordance wth the oscillating field, the coupled dispersion equations were combined to give the established Mathieu equation. Therefore, the governed transition curves were, theoretically, obtained. Finally, the results were numerically confirmed.
Catalytic Formation of C−N Bonds: ICS Symposium Honoring Wolf Prize Laureates Stephen L. Buchwald and John F. Hartwig: May 29, 2019, Technion‐Israel Institute of Technology, Haifa, Israel
Authors: Keinan Ehud
Published: September 2019

This report covers two exciting events in the scientific landscape of the State of Israel: the traditional Wolf Prize Symposium of the ICS and the Wolf Prize Ceremony in the Knesset. The symposium, dedicated to the science of Stephen L. Buchwald and John F. Hartwig, highlighted the catalytic formation of C−N bonds. In a general sense, the two Wolf Prize laureates may be considered as molecular architects who produced efficient molecular‐scale machines that make important molecules for the benefit of humanity. After receiving the Wolf Prize from Israel's President, Buchwald commented, “There are many who believe that support for research should focus exclusively on endeavors that have specific practical applications in mind. With this mindset, our work would have never been possible. Time and time again experience shows that it is exceedingly difficult to predict which scientific discoveries will lead to major advances. So often, it is the scientist following his or her own intellectual curiosity whose work leads to a breakthrough. I believe that basic curiosity‐driven research and societal and economic progress are inextricably linked.” And Hartwig comments, “We all know the principles of science know no boundaries, but maybe less appreciated, or taken for granted, is that the assembly of research teams in many places knows no boundaries. If we recognize and nurture talent in people from all corners and all backgrounds we can address and maybe solve today's most important problems in health, energy, and environmental sustainability that are urgently facing us.”
Association between person‐centered maternity care and newborn complications in Kenya
Authors: Sudhinaraset May , Landrian Amanda , Afulani Patience A. , Diamond‐Smith Nadia , Golub Ginger
Published: September 2019

Objective

Despite the recognized importance of person‐centered care, very little information exists on how person‐centered maternity care (PCMC) impacts newborn health.

Methods

Baseline and follow‐up data were collected from women who delivered in government health facilities in Nairobi and Kiambu counties in Kenya between August 2016 and February 2017. The final analytic sample included 413 respondents who completed the baseline survey and at least one follow‐up survey at 2, 6, 8, and/or 10 weeks. Data were analyzed using descriptive, bivariate, and multivariate statistics. Logistic regression was used to assess the relationship between PCMC scores and outcomes of interest.

Results

In multivariate analyses, women with high PCMC scores were significantly less likely to report newborn complications than women with low PCMC scores (adjusted odds ratio [aOR] 0.39, 95% confidence interval [CI] 0.16–0.98). Women reporting high PCMC scores also had significantly higher odds of reporting a willingness to return to the facility for their next delivery than women with low PCMC score (aOR 12.72, 95% CI 2.26–71.63). The domains of Respect/Dignity and Supportive Care were associated with fewer newborn complications and willingness to return to a facility.

Conclusion

PCMC could improve not just the experience of the mother during childbirth, but also the health of her newborn and future health‐seeking behavior.
Development of a cross‐validated model for predicting emergency cesarean for intrapartum fetal compromise at term
Authors: Flatley Christopher , Gibbons Kristen Stacey , Hurst Cameron , Kumar Sailesh
Published: September 2019

Objectives

To develop a model for predicting emergency cesarean for fetal distress (ECFD) at term using a combination of maternal and late pregnancy ultrasound parameters measured at more than 36 gestational weeks.

Methods

A study of prospectively collected data, including ultrasound scans at 36–38 weeks, for singleton non‐anomalous deliveries at Mater Mother's Hospital, Brisbane, Australia, between January 2010 and April 2017. Univariable and multivariable mixed‐effects generalized linear models were generated. The final model was validated by the K‐fold cross validation technique.

Results

Overall, 5439 women met the inclusion criteria; of these, 230 (4.2%) underwent ECFD. There were more nulliparous women and women with induction of labor (IOL) in the ECFD cohort (both P < 0.001). ECFD neonates had lower z‐scores for estimated fetal weight (EFW), cerebroplacental ratio (CPR), and middle cerebral artery pulsatility index; and higher scores for umbilical artery pulsatility index. Ethnicity, nulliparity, IOL, EFW z‐score, and CPR z‐score were included in the final prediction model, which showed high accuracy with an area under the receiver operator characteristic curve of 0.77.

Conclusion

The study shows that a prediction model combining the continuous standardized measures of CPR and EFW and several maternal factors was able to identify ECFD with improved accuracy.
LINC00365 promotes colorectal cancer cell progression through the Wnt/β‐catenin signaling pathway
Authors: Zhu Yiping , Bian Yinzhu , Zhang Qun , Hu Jing , Li Li , Yang Mi , Qian Hanqing , Yu Lixia , Liu Baorui , Qian Xiaoping
Published: September 2019

In the past decade, substantial evidence established that long noncoding RNAs are serious about mediating the evolution of malignancies. In previous studies, LINC00365, which has not been reported in colorectal cancer (CRC), was selected using the bioinformatics analysis in GSE109454 and GSE41655 data sets. However, the function and mechanism of LINC00365 are still obscure. In our study, LINC00365 was found upregulated in CRC specimens and intimately connected with the prognosis of patients with CRC. In addition, LINC00365 overexpression enhances the cell abilities of proliferation, migration, and invasion in vitro. Meanwhile, mechanistic studies showed that LINC00365 might involve in CRC cell progression by mediating the Wnt/β‐catenin pathway. Furthermore, LINC00365 upregulation increased CDK1 protein expression. In conclusion, this study suggests that LINC00365 acts as a vital part in facilitating CRC progression and might play as a therapeutic target for patients with CRC.
MicroRNA‐203 diminishes the stemness of human colon cancer cells by suppressing GATA6 expression
Authors: Lai Hung‐Tzi , Tseng Wen‐Ko , Huang Shi‐Wei , Chao Ta‐Chung , Su Yeu
Published: September 2019

The interaction between hyaluronan and CD44, an important cancer stem‐cell marker, stimulates various tumor cell‐specific functions such as the stemness of tumor cells. microRNA‐203 (miR‐203) can be downregulated by this interaction in human colorectal cancer (CRC) cells, which increases their stemness; however, the underlying mechanism is not yet defined. Here, we show that overexpression and sequestration of miR‐203 in HCT‐116 and HT‐29 human CRC cells reduces and enhances their stemness, respectively. We also show that GATA‐binding factor 6 (GATA6) is a direct target of miR‐203. Our results indicate that upregulated expression of this transcription factor not only restores the self‐renewal abilities of miR‐203‐overexpressing HCT‐116 and HT‐29 cells but also promotes the stemness properties of their parental counterparts. More important, we show that silencing the expression of either LRH‐1 or Hes‐1 is sufficient to diminish the stemness‐promoting effects of GATA6 in human CRC cells. Together, our findings delineate the stemness‐inhibitory mechanism of miR‐203 in human CRC cells and suggest that this miR is a potential therapeutic agent for colorectal cancer.
miR‐204‐5p regulates cell proliferation, invasion, and apoptosis by targeting IL‐11 in esophageal squamous cell carcinoma
Authors: Tang Jianwei , Li Zhihua , Zhu Quan , Wen Wei , Wang Jun , Xu Jing , Wu Weibin , Zhu Yining , Xu Honglei , Chen Liang
Published: September 2019

Esophageal cancer (EC) is the world's eighth most common malignant neoplasm and is ranked as the sixth leading cause of death related to cancer. Aberrant microRNA (miRNA) expression has been reported to be associated with esophageal squamous cell carcinoma. However, the molecular mechanism of miR‐204‐5p in esophageal squamous cell carcinoma (ESCC) is not clear. Therefore, the aim of this study was to investigate the potential role of miR‐204‐5p in ESCC. In the present study, we found that miR‐204‐5p could affect ESCC proliferation, invasion, apoptosis, and cell cycle in cell and mouse models. A dual‐luciferase reporter assay showed that miR‐204‐5p expression was negatively correlated with interleukin‐11 (IL‐11) expression. IL‐11 overexpression reversed the suppressive effects of miR‐204‐5p in the cell lines. These results indicated that miR‐204‐5p functions as a tumor suppressor by directly targeting IL‐11 in ESCC.
Virulence and DNA fingerprinting analysis of Xanthomonas oryzae pv. oryzae identify a new pathotype in Guangxi, South China
Authors: Chen Xiaolin , Wei Shanfu , Yan Qun , Huang Fengkuan , Ma Zengfeng , Li Ruifang , Cen Zhenlu , Yan Weihong , Li Kunhua
Published: September 2019

Bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most destructive diseases affecting rice worldwide. However, little is known about the population structure of this organism in Guangxi Zhuang Autonomous Region, South China. Here, pathotypic and DNA fingerprint analyses were conducted to characterize the isolates of Xoo collected from rice leaves in five districts of the region from 2013 to 2016. Their pathogenicity was tested by leaf clipping, and the DNA fingerprints were analyzed by repetitive sequence‐based polymerase chain reaction and endogenous insertion sequence element‐based polymerase chain reaction assays using the repetitive extragenic palindromic sequence and enterobacterial repetitive intergenic consensus primers, respectively. Pathogenicity assays of 70 representative isolates were conducted using a series of near‐isogenic lines and two new pathotypes were identified. All the pathotypes were found to be incompatible with xa5 and Xa7. One pathotype was virulent to Xa14, Xa21, and Xa23, whereas another virulent to Xa21 and Xa23, but incompatible with Xa14. A dendrogram generated for the data sets obtained from DNA fingerprinting suggested the prevalence of high genetic diversity of Xoo throughout Guangxi, and no association between the molecular haplotypes and pathotypes was identified.
lncRNA CCAT1 is a biomarker for the proliferation and drug resistance of esophageal cancer via the miR‐143/PLK1/BUBR1 axis
Authors: Hu Min , Zhang Qi , Tian Xiao‐Hui , Wang Jin‐Lin , Niu Ya‐Xuan , Li Gang
Published: September 2019

Recent evidence indicates that long noncoding RNA colon cancer‐associated transcript‐1 (lncRNA CCAT1) is abundantly expressed in esophageal cancer and is closely related to the occurrence, development, invasion, metastasis, and drug resistance of this disease. However, the role and molecular mechanisms of CCAT1 in the cell proliferation and chemoresistance of esophageal cancer are largely unknown. The correlation between CCAT1 expression and drug resistance to cisplatin (CDDP) in esophageal squamous cell carcinoma (ESCC) cells was analyzed using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide (MTT) and quantitative real‐time polymerase chain reaction (qRT‐PCR) assays. CCAT1 knockdown and miR‐143 overexpression or inhibition were used to verify the effects on proliferation and drug resistance via MTT, western blotting, flow cytometry, and immunofluorescence assays. qRT‐PCR and western blotting were applied to detect the potential regulatory relationship among CCAT1, miR‐143, PLK1, and BUBR1. A xenograft tumor assay was performed to validate the role of CCAT1 in vivo. The expression of CCAT1 was positively correlated with drug resistance in several ESCC cell lines. CCAT1 knockdown and miR‐143 overexpression inhibited cell proliferation and CDDP drug resistance. Moreover, the downstream target of CCAT1 was found to be miR‐143, which can regulate the expression of PLK1 and BUBR1. In vivo assays showed that CCAT1 knockdown suppressed tumor growth and enhanced the sensitivity of tumors to CDDP in nude mice. Taken together, we discovered a novel mechanism by which CCAT1 promotes cell proliferation and enhances drug resistance by regulating the miR‐143/PLK1/BUBR1 signaling axis both in vitro and in vivo. Our findings further suggest that lncRNA CCAT1 may be a potential therapeutic target for overcoming chemoresistance in esophageal cancer.
LncRNA DANCR promotes tumor growth and angiogenesis in ovarian cancer through direct targeting of miR‐145
Authors: Lin Xiaojuan , Yang Fan , Qi Xiaorong , Li Qingli , Wang Danqing , Yi Tao , Yin Rutie , Zhao Xia , Zhong Xiaomin , Bian Ce
Published: September 2019

Differentiation antagonizing non‐protein coding RNA (DANCR) is a newly identified oncogenic long noncoding RNA found in various cancers. However, the functional role of DANCR in tumor angiogenesis and the underlying mechanisms are still unclear. The expression of DANCR was determined in ovarian malignant tissues and cell lines. The functional role of DANCR in tumor angiogenesis was revealed by the following methods: CD31 staining of ovarian tumor tissues, matrigel‐plug assay tissues, HUVEC‐related tube formation assay, and invasion assay. Enzyme‐linked immunosorbent assay, Western blotting, luciferase assay, and rescue experiments were used to investigate the underlying mechanisms of DANCR‐regulating angiogenesis. DANCR was upregulated in ovarian malignant tissues and ovarian cancer cells. Knockdown of DANCR efficiently impaired ovarian tumor growth through inhibition of tumor angiogenesis. Furthermore, the conditional culture medium from DANCR‐knockdown ovarian cells significantly inhibited tube formation and invasion of HUVEC in vitro. Mechanistic investigation indicated that vascular endothelial growth factor A (VEGF‐A, VEGF) plays a crucial role during DANCR inhibition of tumor angiogenesis in ovarian cancer. Further results demonstrated that miR‐145 is the direct binding target of DANCR during regulation of VEGF expression and tumor angiogenesis in ovarian cancer cells. Collectively, DANCR plays a promotional role in tumor angiogenesis in ovarian cancer through regulation of miR‐145/VEGF axis. Therefore, DANCR may be a novel therapy target for ovarian cancer.
XRCC1‐mediated DNA repair is associated with progression‐free survival of multiple myeloma patients after autologous stem cell transplant
Authors: Persaud Avinash K. , Li Junan , Johnson Jasmine A. , Seligson Nathan , Sborov Douglas W. , Duah Ernest , Cho Yu Kyoung , Wang Danxin , Phelps Mitch A. , Hofmeister Craig C. , Poi Ming J.
Published: September 2019

Autologous stem cell transplant (ASCT) with high‐dose melphalan (HDM) is the standard treatment for fit multiple myeloma (MM) patients. It is generally believed that some DNA repair proteins impact the activity to repair melphalan‐induced DNA damage, thus potentially contributing to the patient's clinical response. However, knowledge of these proteins is limited. In the current study, we investigated the roles of XRCC1, a protein involved in base excision repair and single‐strand break repair, in melphalan response in MM cells. Small interfering RNA knockdown of XRCC1 significantly increased the accumulation of melphalan‐induced DNA damage in MM cells and sensitized them to melphalan treatment, indicating that genetic variation in XRCC1 may impact response to melphalan treatment. We then evaluated the association between an XRCC1 variant with reduced activity, rs25487 (R399Q), and clinical outcomes of 108 MM patients with melphalan therapy. Our results showed that XRCC1 rs25487 was associated with prolonged progression‐free survival (PFS) in MM patients. The adjusted hazard ratio for PFS between patients carrying rs25487 AA/AG and GG was 0.42 (95% confidence interval: 0.25, 0.84, P = .014). Taken together, these results indicate that XRCC1 is involved in the repair of melphalan‐induced DNA damage and XRCC1 rs25487 variant with impaired DNA repair function influences the clinical responses of HDM in MM patients.
Annual report raises red flags on youth access to care
Authors: Enos Gary
Published: September 2019

Mental Health America's (MHA's) latest State of Mental Health in America Report will have advocates rushing to see where their state ranks in addressing behavioral health issues, but the greater message may lie in the document's findings of ongoing concern about unaddressed mental health needs nationally.
Maternal transcripts in good and poor quality eggs from Japanese eel, Anguilla japonica—their identification by large‐scale quantitative analysis
Authors: Izumi Hikari , Gen Koichiro , Lokman P. Mark , Hagihara Seishi , Horiuchi Moemi , Tanaka Toshiomi , Ijiri Shigeho , Adachi Shinji
Published: September 2019

Our understanding of maternal control of development in vertebrates remains incomplete. In this study, we investigated levels of maternal transcripts in good and poor quality eggs from artificially matured Japanese eel, using RNA‐Seq and quantitative polymerase chain reaction (qPCR), to identify candidate maternal transcripts related to development. De novo assembly or mapping of reads to the eel draft genome yielded 619,029 contigs and 85,906 transcripts, respectively; normalized read counts to these assemblies were calculated using reads (RPKM) or fragments (FPKM) per kilobase of transcript per million mapped reads. In silico screening identified 1,594 contigs and 150 transcripts with lower RPKM or FPKM in poor than in good quality eggs, 245 contigs, and 85 transcripts of which could be annotated by BLASTx, respectively. From selected contigs or transcripts, six genes (dnajb4, gnpat, card14, pdp1, fcgbp, ttn) had significantly lower messenger RNA levels in poor than in good quality eggs by qPCR. Multiple regression analysis showed that five genes (gnpat, b4galnt1, acsl6, rtkn, trim24) significantly correlated with hatchability. Taken together, 10 genes were identified as candidate maternal transcripts, regulating development in Japanese eel. Our results contribute to understanding the molecular basis for maternal control of development in vertebrates.
Impact of Ice-Angling and Handling on Swimming Performance in Bluegill and Largemouth Bass
Authors: Bieber John F. , Louison Michael J. , Stein Jeffrey A. , Suski Cory D.
Published: September 2019

Many recreational anglers practice catch-and-release; however, research indicates that capture and handling has the potential to adversely affect fish. Numerous catch-and-release studies have been conducted during warmer months, but little work has been done during the winter when ice-anglers in temperate regions target fish. We conducted an ice angling simulation that quantified the impacts of air temperature and air exposure duration on swimming performance and gill physiology of Bluegill Lepomis macrochirus and Largemouth Bass Micropterus salmoides. In all experiments, fish were first subjected to a simulated angling bout in water at 5°C, followed by 30 s or 5 min of air exposure at above freezing (3–8°C) or subfreezing (−7°C) temperatures. The fish were then assessed for critical swimming speed (Bluegill), oxygen consumption (Bluegill), burst swimming (Largemouth Bass), or gill damage (Largemouth Bass). Results showed that Bluegill subjected to 5 min of air exposure at −7°C suffered impaired swimming, with a 47% loss in critical swimming speed (Ucrit) compared with the controls. Treatment had no impact on burst swimming or gill damage in Largemouth Bass. The results demonstrate the possible impacts of air exposure on fish, and we recommend that ice-anglers make an effort to minimize air exposure duration, especially when air temperatures are low.
A Protocol to Deliver Intensive Behavioral Therapy (IBT) for Obesity in Primary Care Settings: The MODEL‐IBT Program
Authors: Wadden Thomas A. , Tsai Adam G. , Tronieri Jena Shaw
Published: September 2019

Objective

The Centers for Medicare and Medicaid Services (CMS) initiated coverage of intensive behavioral therapy (IBT) for obesity in 2011, providing beneficiaries 14 to 15 brief, individual counseling visits in 6 months. CMS offered general recommendations for delivering IBT but did not provide an evidence‐based treatment protocol, which was the objective of the present research.

Methods

This review describes the evidence that CMS considered in developing its IBT benefit. It also examines weight losses produced by the intensive lifestyle intervention in the Diabetes Prevention Program (DPP), as well an adapted version of the DPP delivered (for the first 6 months) on the visit schedule recommended by CMS. This new protocol, which was evaluated in a recent randomized trial, provided 14 visits in the first 24 weeks, with 7 additional monthly visits through week 52.

Results

As reported previously, the 50 participants with obesity assigned to the new IBT protocol lost a mean of 5.4% of their initial weight at week 24; 46% of participants lost ≥ 5% of their baseline weight. At 1 year, the mean loss was 6.1%, and 44% of participants lost ≥ 5%.

Conclusions

With these generally favorable results, the IBT protocol is being posted online for practitioners and researchers to use.
Lipedema: A Call to Action!
Authors: Buso Giacomo , Depairon Michele , Tomson Didier , Raffoul Wassim , Vettor Roberto , Mazzolai Lucia
Published: September 2019

Lipedema is a chronic progressive disease characterized by abnormal fat distribution resulting in disproportionate, painful limbs. It almost exclusively affects women, leading to considerable disability, daily functioning impairment, and psychosocial distress. Literature shows both scarce and conflicting data regarding its prevalence. Lipedema has been considered a rare entity by several authors, though it may be a far more frequent condition than thought. Despite the clinical impact on women's health, lipedema is in fact mostly unknown, underdiagnosed, and too often misdiagnosed with other similarly presenting diseases. Polygenic susceptibility combined with hormonal, microvascular, and lymphatic disorders may be partly responsible for its development. Furthermore, consistent information on lipedema pathophysiology is still lacking, and an etiological treatment is not yet available. Weight loss measures exhibit minimal effect on the abnormal body fat distribution, resulting in eating disorders, increased obesity risk, depression, and other psychological complaints. Surgical techniques, such as liposuction and excisional lipectomy, represent therapeutic options in selected cases. This review aims to outline current evidence regarding lipedema epidemiology, pathophysiology, clinical presentation, differential diagnosis, and management. Increased awareness and a better understanding of its clinical presentation and pathophysiology are warranted to enable clinicians to diagnose and treat affected patients at an earlier stage.
Strategy to minimize radiation burden in infants and high‐risk medulloblastoma using intrathecal methotrexate and high‐dose chemotherapy: A prospective registry study in Japan
Authors: Yamasaki Kai , Okada Keiko , Soejima Toshinori , Sakamoto Hiroaki , Hara Junichi
Published: September 2019

Background

Most childhood medulloblastoma (MB) cases are curable using multimodal treatment, including craniospinal irradiation (CSI). However, late effects are a serious problem for survivors. This prospective registry study evaluated Japanese patients to determine whether a reduced radiation dose was feasible.

Patients and Methods

Patients with MB were classified as an infant group (<3 years old) and a high‐risk (HR) group (≥3 years old with metastasis). The HR group received intrathecal methotrexate (IT‐MTX) and high‐dose chemotherapy (HDC) using thiotepa and melphalan, as well as concomitant radiotherapy with a recommended CSI dose of 18 Gy and a total local dose of 50 Gy. Radiotherapy was only considered for infants if residual tumors were present after the HDC.

Results

Between 1997 and 2006, we identified 28 HR patients (M1: 9, M2/3: 19) and 17 infant patients (M0: 11, M1: 3, M2/3: 3). During the median follow‐up of 9.4 years for the entire HR group, the 5‐year progression‐free survival (PFS) rate was 82.1 ± 7.2% and the 5‐year overall survival (OS) rate was 85.7 ± 6.6%. Subanalyses of the patients who received the recommended treatment revealed that the 5‐year PFS and OS rates were both 90.5 ± 6.4%. In the infant group, the 5‐year PFS rate was 52.9 ± 12.1% and the 5‐year OS rate was 51.8 ± 12.4%. There were no serious adverse events associated with the IT‐MTX and HDC treatments.

Conclusion

Intensified chemotherapy using HDC and IT‐MTX might allow for a reduced prophylactic radiation dose in patients with MB with metastases. Further studies are needed to validate these findings.
Conformity to masculinity ideology, a predictor of academic‐related attitudes and behaviors
Authors: Liang Christopher T. H. , Rocchino Gabrielle H. , Gutekunst Malaïka H. C. , Smithson Annalisa
Published: September 2019

Masculinity ideology is argued to be associated with academic outcomes. However, relatively few studies have examined these associations. This study examines the associations between masculinity ideology and academic skepticism, self‐presentation of low achievement, academic engagement, academic initiative, and self‐regulation, above and beyond academic self‐efficacy, among a diverse sample of urban youth. With a sample of 135 eighth‐grade students from a Northeastern middle school, 5 separate multiple hierarchical regression analyses were used to examine whether students’ endorsement of masculinity ideology predicted the criterion variables above and beyond academic self‐efficacy. The sample was comprised of 54 girls and 74 boys ages 12–14 years (M = 13.14; SD = .37). Results showed academic self‐efficacy significantly predicted academic engagement (B = 1.26; β = .53, p < .001; f2 = .39), academic initiative (B = .98; β = .37; p < .001, f2 = .16), and behavioral regulation (B = .61; β = .24; p < .05; f2 = .09) and explained an additional 8 and 10% of the variance in self‐presentation of low achievement (B = .54; β = .33; p = .001; f2 = .14) and academic skepticism (B = .56; β = .35; p < .001; f2 = .15), respectively, over and above academic self‐efficacy. Gender, which was dummy coded and entered as a covariate, only predicted self‐presentation of low achievement. Findings from this study point to the need to foster positive academic outcomes through bolstering academic self‐efficacy and, perhaps more important, addressing masculinity ideology.
Characterisation of volume and surface dielectric barrier discharges in N2–O2 mixtures using optical emission spectroscopy
Authors: Kogelheide Friederike , Offerhaus Björn , Bibinov Nikita , Krajinski Philip , Schücke Lars , Schulze Julian , Stapelmann Katharina , Awakowicz Peter
Published: September 2019

A volume and a twin surface dielectric barrier discharge (VDBD and SDBD) are generated in different nitrogen–oxygen mixtures at atmospheric pressure by applying damped sinusoidal voltage waveforms with oscillation periods in the microsecond time scale. Both electrode configurations are located inside vacuum vessels and operated in a controlled atmosphere to exclude the influence of surrounding air. The discharges are characterised with different spatial and temporal resolution by applying absolutely calibrated optical emission spectroscopy in conjunction with numerical simulations and current–voltage measurements. Plasma parameters, namely the electron density and the reduced electric field, and the dissipated power are found to depend strongly on the oxygen content in the working gas mixture. Different spatial and temporal distributions of plasma parameters and dissipated power are explained by surface and residual volume charges for different O2 admixtures due to their effects on the electron recombination rate. Thus, the oxygen admixture is found to strongly influence the breakdown process and plasma conditions of a VDBD and a SDBD.
Cation‐Modulated HER and OER Activities of Hierarchical VOOH Hollow Architectures for High‐Efficiency and Stable Overall Water Splitting
Authors: Zhang Jian , Cui Renjie , Gao Chencheng , Bian Linyi , Pu Yong , Zhu Xinbao , Li Xing'ao , Huang Wei
Published: September 2019

Atom‐scale modulation of electronic regulation in nonprecious‐based electrocatalysts is promising for efficient catalytic activities. Here, hierarchically hollow VOOH nanostructures are rationally constructed by partial iron substitution and systematically investigated for electrocatalytic water splitting. Benefiting from the hierarchically stable scaffold configuration, highly electrochemically active surface area, the synergistic effect of the active metal atoms, and optimal adsorption energies, the 3% Fe (mole ratio) substituted electrocatalyst (VOOH‐3Fe) exhibits a low overpotential of 90 and 195 mV at 10 mA cm−2 for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline media, respectively, superior than the other samples with a different substituted ratio. To the best of current knowledge, 195 mV overpotential at 10 mA cm−2 is the best value reported for V or Fe (oxy)hydroxide‐based OER catalysts. Moreover, the electrolytic cell employing the VOOH‐3Fe electrode as both the cathode and anode exhibits a cell voltage of 0.30 V at 10 mA cm−2 with a remarkable stability over 60 h. This work heralds a new pathway to design efficient bifunctional catalysts toward overall water splitting.
Purification and Characterization of a Thermostable Starch‐Saccharifying Alpha‐1,4‐Glucan‐Glucohydrolase Produced by Bacillus licheniformis
Authors: Ghani Maria , Ansari Asma , Haider Muhammad Samee , Asif Tayyaba , Ibrahim Fariha , Qader Shah Ali Ul , Aman Afsheen
Published: September 2019

To alleviate the difficulties of starch processing industries, it is necessary to improve the enzyme yield of commercially important alpha 1,4‐glucan‐glucohydrolase (glucoamylase) and explore new thermostable glucoamylases that have strong starch saccharifying capabilities. The current investigation is based on the purification and characterization of glucoamylase from wild and mutant strains of Bacillus licheniformis. Glucoamylase is purified up to homogeneity. The purified glucoamylase exhibits 67‐ and 506‐fold purification from wild (B. licheniformis KIBGE‐IB3) and mutant (B. licheniformis KIBGE‐IB3M67) strains, respectively, with a molecular weight of ≈185 kDa. Glucoamylase from wild and mutant strains hydrolyzes the starch at 50 °C in 5 min. Vmax and Km values from KIBGE‐IB3 are 107.07 kU mg−1 and 0.07 mg mL−1 whereas, for glucoamylase from KIBGE‐IB3M67 are 386.56 kU mg−1 and 0.12 mg mL−1, respectively. End product analysis reveals that glucoamylase from mutant strain have strong saccharifying capability for potato starch. N‐Terminal protein sequence discloses that the first two amino acids (SSNKLTTSWG) in the wild‐type are replaced by other amino acids in the mutant strain (MDNKLTTSWG). After reviewing potential kinetic properties of glucoamylase, it is suggested that glucoamylase from KIBGE‐IB3M67 has remarkable potential to withstand harsh industrial environment and can straightforwardly saccharify potato starch into glucose molecules.
Dynamic simulation of river water environmental capacity based on the subsection summation model
Authors: Zhang Xuan , Luo Jungang , Zhang Xiao , Xie Jiancang
Published: September 2019

There are noteworthy problems in current strategies to calculate river water environmental capacity (WEC), including the generalization of tributaries and water intakes, which results in inaccurate calculation results of the WEC, and the difficulty in adapting to dynamic changes in demands and hydrological conditions in terms of practical application. To address these flaws, the subsection summation model (SSM) was built for river WEC calculation. The SSM increases the number of control sections according to drain outlets, water intakes, and tributaries and acquires the WEC of the functional area section by section. The Wei River was taken as the study area for verification and application of the SSM. Supported by a comprehensive integration platform, the WEC simulation system of the Wei River was constructed. The results show that the SSM enhances the accuracy of the WEC calculation, and the results are closer to the actual situation. The simulation system could obtain the WEC according to the demands and changes in the hydrological conditions, thus providing technical means for policymakers.

Practitioner points

The subsection summation model provides a more accurate water environmental capacity (WEC) calculation method considering tributaries and water intakes avoiding generalization.

The simulation system should be established to make the WEC calculation adapt to the demands or changes in the hydrological conditions.

The model and system could supply the basis and technical means for decision‐making.
Organic micropollutants in groundwater of India—A review
Authors: Sackaria Merin , Elango Lakshmanan
Published: September 2019

Groundwater pollution due to organic micropollutants is a major cause of concern, especially in parts of the world where available water resources are on the decline. India is the largest user of groundwater where the presence of micropollutants in the subsurface environment has been the focus of many researchers. The objective of this study was to provide a detailed review of studies on micropollutants in Indian groundwater and to provide strategies for further work. It is found that the presence of pharmaceuticals, endocrine disrupting compounds, surfactants, phthalates, per‐ and poly‐fluoroalkyl substances, personal care products, artificial sweeteners, and pesticides in groundwater from different parts of India is reported. Pesticides and phthalate concentrations reported exceed the standard guideline values. This review points out the regions where the groundwater is prone to contamination due to micropollutants. An assessment of temporal variation in the concentration of micropollutants in groundwater has been done only by a few researchers. This study highlighted the need for more research on the possible presence of micropollutants in groundwater, especially in the major polluted rivers in cities where more pharmaceuticals, pesticides, and plastic industries are located.

Practitioner Points

Organic micropollutants were not new contaminants into the environment but the one entered even decades ago which has threatening effect.

The number of studies on organic micropollutants in groundwater is lesser than surface water or wastewater.

Scarcity on the studies of micropollutants was a result of definite technical lack in its analysis and complexity in sample preparation.

Most of the studies done were related to contamination sites and point sources.
Prasugrel effectively reduces the platelet reactivity units in patients with genetically metabolic dysfunction of cytochrome P450 2C19 who are treated with long-term dual antiplatelet therapy after undergoing drug-eluting stent implantation
Authors: Shimamatsu Junichiro , Sasaki Ken-ichiro , Katsuki Yoshio , Kawasaki Tomohiro , Murasato Yoshinobu , Ajisaka Hidehiko , Yokoi Hiroyoshi , Tashiro Hideki , Harada Atsushi , Hirakawa Yuji , Ishizaki Yuta , Ishimatsu Takashi , Kagiyama Kotaro , Fukumoto Yoshihiro , Kakuma Tatsuyuki , Ueno Takafumi
Published: September 2019

Dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitor is administered following percutaneous coronary intervention (PCI) with coronary stent implantation. Several studies have reported the effects of switching between P2Y12 inhibitors on platelet reactivity (P2Y12 reaction units: PRU), from acute to late phase after PCI. However, the effect of switching at very late phase is unknown. This study examined the effect on PRU in Japanese coronary heart disease patients with long-term DAPT (aspirin + clopidogrel) when switching from clopidogrel to prasugrel. Ninety-six patients were enrolled in this study. The median DAPT duration at enrollment was 1824.0 days. Twenty-three patients with PRU ≥ 208 at enrollment were randomly assigned into either continuing to receive clopidogrel (Continued Group; n = 11) or switching to prasugrel (Switched Group; n = 12). The primary endpoint was the rate of patients who achieved PRU < 208 at the end of 12 weeks of treatment, which was significantly higher in Switched Group relative to Continued Group (90.0% vs. 36.4%; P = 0.024). The secondary endpoint was the PRU at week 12 in groups subdivided according to cytochrome P450 (CYP) 2C19 genotypes. At week 12, extensive metabolizers (EM Group) had 202.3 ± 60.0 and 174.5 ± 22.3 in Continued Group and Switched Group (P = 0.591), respectively; intermediate and poor metabolizers (non-EM Group) had 229.4 ± 36.9 and 148.4 ± 48.4 in Continued Group and Switched Group (P = 0.002), respectively. The PRU for non-EM Group was significantly reduced in Switched Group. Thus, for patients with long-term DAPT (aspirin + clopidogrel) after PCI with coronary stent implantation, switching from clopidogrel to prasugrel resulted in a stable reduction in PRU, regardless of CYP2C19 polymorphism.
Online Clique Clustering
Authors: Chrobak Marek , Dürr Christoph , Fabijan Aleksander , Nilsson Bengt J.
Published: September 2019

Clique clustering is the problem of partitioning the vertices of a graph into disjoint clusters, where each cluster forms a clique in the graph, while optimizing some objective function. In online clustering, the input graph is given one vertex at a time, and any vertices that have previously been clustered together are not allowed to be separated. The goal is to maintain a clustering with an objective value close to the optimal solution. For the variant where we want to maximize the number of edges in the clusters, we propose an online algorithm based on the doubling technique. It has an asymptotic competitive ratio at most 15.646 and a strict competitive ratio at most 22.641. We also show that no deterministic algorithm can have an asymptotic competitive ratio better than 6. For the variant where we want to minimize the number of edges between clusters, we show that the deterministic competitive ratio of the problem is $$n-\omega (1)$$n-ω(1), where n is the number of vertices in the graph.
What is new in the 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy?
Authors: Lang Irene M.
Published: September 2019

Summary of key elements of the new 2018 European Society of Cardiology (ESC) guidelines for the management of cardiovascular diseases during pregnancy

Cardiovascular diseases during pregnancy are the most common causes of pregnancy-associated mortality.

Vaginal delivery is the preferred mode of birth in the majority of pregnancies.

It is recommended that patients with modified World Health Organization (mWHO) class IV risk are counselled against pregnancy.

Patients carrying mWHO II–III, III, and class IV risks should undergo prepregnancy counselling by a multidisciplinary pregnancy heart team to determine a delivery plan and define postpartum care.

Specific medications should not be principally withheld in pregnancy but the risk-benefit ratio should be carefully evaluated prior to administration.

Beta blockers are recommended during and after pregnancy for congenital long QT syndrome and catecholaminergic polymorphic ventricular tachycardia.

Low molecular weight heparin is the ideal substance for prophylaxis and treatment of venous thromboembolism in pregnancy under weekly monitoring of anti-factor Xa activity.
Chimpanzees use observed temporal directionality to learn novel causal relations
Authors: Tennie Claudio , Völter Christoph J. , Vonau Victoria , Hanus Daniel , Call Josep , Tomasello Michael
Published: September 2019

We investigated whether chimpanzees use the temporal sequence of external events to determine causation. Seventeen chimpanzees (Pan troglodytes) witnessed a human experimenter press a button in two different conditions. When she pressed the “causal button” the delivery of juice and a sound immediately followed (cause-then-effect). In contrast, she pressed the “non-causal button” only after the delivery of juice and sound (effect-then-cause). When given the opportunity to produce the desired juice delivery themselves, the chimpanzees preferentially pressed the causal button, i.e., the one that preceded the effect. Importantly, they did so in their first test trial and even though both buttons were equally associated with juice delivery. This outcome suggests that chimpanzees, like human children, do not rely solely on their own actions to make use of novel causal relations, but they can learn causal sequences based on observation alone. We discuss these findings in relation to the literature on causal inferences as well as associative learning.
On-wall and interior separation in a two-fluid boundary layer
Authors: Timoshin Sergei N. , Thapa Pallu
Published: September 2019

A two-fluid boundary layer is considered in the context of a high Reynolds number Poiseuille–Couette channel flow encountering an elongated shallow obstacle. The flow is laminar, steady and two-dimensional, with the boundary layer shown to have the pressure unknown in advance and a specified displacement (a condensed boundary layer). The focus is on the detail of the flow reversal triggered by the obstacle. The interface between the two fluids passes through the boundary layer which, in conjunction with the effects of gravity and distinct densities in the two fluids, leads to several possible topologies of the reversed flow, including a conventional on-wall separation, interior flow reversal above the interface, and several combinations of the two. The effect of upstream influence due to a transverse pressure variation under gravity is mentioned briefly.