bluuebunny/crossref_metadata_2025 huggingface dataset:
Network based identification of different mechanisms underlying pathogenesis of human papilloma virus‐active and human papilloma virus‐negative oropharyngeal squamous cell carcinoma
Authors: Iman Maryam , Narimani Zahra , Hamraz Iman , Ansari Ebrahim
Published: July 2018

A different molecular mechanism underlying human papilloma virus (HPV)‐negative and HPV‐active pathogenesis is responsible for better response to therapies in HPV‐associated oropharyngeal squamous cell carcinoma (OPSCC). In this study, we aim to provide an insight into molecular basis underlying this distinction and introduce possible targeted therapies for each phenotype. Using weighted gene co‐expression network analysis (WGCNA), our aim was to identify not only differentially expressed genes but also significant coexpressed gene modules responsible for genotype and phenotype distinctions between HPV‐active and HPV‐negative samples. Recognizing differentially expressed genes in each module indicates key regulators that may be ignored in an analysis only based on differential gene expression study. Two modules are investigated in detail in our analysis, related to JAK–STAT dysregulation in HPV‐negative samples, and disruption of cell fate commitment possibly induced by overexpression of BCL2 is observed in the HPV‐active cohort. The existence of differentially expressed oncogenes and potential miRNA role is investigated in our analysis. The other significant module related to keratinization, keratinocyte differentiation, and intermediate filament cytoskeleton organization was discovered in the resulting co‐expression network. A considerable number of genes was downregulated in HPV‐active samples in the relative module, postulating the impairment of cytoskeleton‐related gene expression caused by HPV intervention.
Electromyostimulation to fight atrophy and to build muscle: facts and numbers
Authors: Adams Volker
Published: July 2018

In recent years, electrical myostimulation (EMS) is becoming more and more popular to increase muscle function and muscle weight. Especially it is applied in healthy individual after injury to rebuild muscle mass and in severely atrophic patients who are not able or willing to perform conventional exercise training programs. Studies in experimental models as well as in human subjects confirmed that EMS can increase muscle mass by around 1% and improve muscle function by around 10–15% after 5–6 weeks of treatment. Despite a severe increase in circulating creatine kinase during the first session, EMS can be regarded as a safe therapeutic intervention. At the molecular level, EMS improves the anabolic/catabolic balance and stimulates the regenerative capacity of satellite cells. EMS intensity should be as high as individually tolerated, and a minimum of three sessions per week [large pulses (between 300–450 μs), high frequency (50–100 Hz in young and around 30 Hz in older individuals)] for at least 5–6 weeks should be performed. EMS improved functional performances more effectively than voluntary training and counteracted fast type muscle fibre atrophy, typically associated with sarcopenia. The effect of superimposing EMS on conventional exercise training to achieve more muscle mass and better function is still discussed controversially. Nevertheless, EMS should not be regarded as a replacement of exercise training per se, since the beneficial effect of exercise training is not just relying on building muscle mass but it also exerts positive effects on endothelial, myocardial, and cognitive function.
Anodic oxidation for the remediation of soils polluted with perchloroethylene
Authors: Muñoz‐Morales Martin , Sáez Cristina , Cañizares Pablo , Rodrigo Manuel Andrés
Published: July 2018

BACKGROUND

This work focuses on the removal of perchloroethylene (PCE) from soils spiked with this hazardous chlorinated hydrocarbon and oil by a combination of two technologies: soil washing and anodic oxidation with diamond electrodes. The first attains the transfer of the pollutant from the soil to a soil washing fluid (SWF), from which the organics are then efficiently removed.

RESULTS

Results show that high concentrations of sodium dodecyl sulphate (SDS) are required in the SWF for an efficient extraction of the chlorinated hydrocarbon and electrolysis has to be applied not only to the clarified liquid, but also to the interphase. The surfactant used interacts strongly with soil not only during the washing, but also during the electrolysis step. This interaction seems to play a protective role against the oxidation of SDS. The initial phase of the electrolysis is rather complex and there are several processes which modify the results importantly.

CONCLUSIONS

Removal of PCE by electrolysis from soil is less efficient than its removal from synthetic solutions of this chlorinated pollutant. There are two first‐order kinetic zones, which indicate an important competition for the oxidation of the different organics contained in the SWF during the electrolysis. © 2018 Society of Chemical Industry
Linkage to care, mobility and retention of HIV‐positive postpartum women in antiretroviral therapy services in South Africa
Authors: Phillips Tamsin K , Clouse Kate , Zerbe Allison , Orrell Catherine , Abrams Elaine J , Myer Landon
Published: July 2018

Introduction

Linkage to care and mobility postpartum present challenges to long‐term retention after initiating antiretroviral therapy (ART) in pregnancy, but there are few insights from sub‐Saharan Africa. We aimed to describe postpartum linkage to care, mobility, retention and viral suppression after ART initiation in pregnancy.

Methods

Using routine electronic data we assessed HIV‐specific health contacts and clinic movements among women initiating ART in an integrated antenatal care (ANC) and ART clinic in Cape Town, South Africa. The local care model includes mandatory transfer to general ART clinics postpartum. We investigated linkage to care after leaving the integrated clinic and mobility to new clinics until 30 months on ART. We used Poisson regression to explore predictors of linkage, retention (accessing care at least once at both 12 [6 to <18] and 24 [18 to <30] months on ART), and viral suppression (HIV viral load [VL] ≤50 and ≤1000 copies/mL after 12 months on ART).

Results

Among 617 women, 23% never linked to care; 71% and 65% were retained at 12 and 24 months on ART respectively, with 59% retained in care at both times. Those who linked (n = 485) accessed HIV care at 98 different clinics and 21% attended ≥2 clinics. Women >25 years, married/cohabiting or presenting early for ANC were more likely to link. Younger and unemployed women were more likely to attend ≥2 clinics (adjusted risk ratio [aRR] 1.10 95% confidence interval [CI] 1.02 to 1.18 and aRR 1.06 95% CI 0.99 to 1.12 respectively). Age >25 years (aRR 1.17 95% CI 1.02 to 1.33) and planned pregnancy (aRR 1.20 95% CI 1.09 to 1.33) were associated with being retained. Among 338 retained women with VL available, attending ≥2 clinics reduced the likelihood of viral suppression when defined as ≤50 copies/mL (aRR 0.81 95% CI 0.69 to 0.95). Distance moved was not associated with VL.

Conclusions

These data show that a substantial proportion of women do not link to postpartum ART care in this setting and, among those that do, long‐term retention remains a challenge. Women move to a variety of clinics and young women appear particularly vulnerable to attrition. Interventions promoting linkage and continued retention for women initiating ART during pregnancy warrant urgent consideration.
The impact of population dynamics on the population HIV care cascade: results from the ANRS 12249 Treatment as Prevention trial in rural KwaZulu‐Natal (South Africa)
Authors: Larmarange Joseph , Diallo Mamadou Hassimiou , McGrath Nuala , Iwuji Collins , Plazy Mélanie , Thiébaut Rodolphe , Tanser Frank , Bärnighausen Till , Pillay Deenan , Dabis François , Orne‐Gliemann Joanna ,   the ANRS 12249 TasP Study Group
Published: July 2018

Introduction

The universal test and treat strategy (UTT) was developed to maximize the proportion of all HIV‐positive individuals on antiretroviral treatment (ART) and virally suppressed, assuming that it will lead to a reduction in HIV incidence at the population level. The evolution over time of the cross‐sectional HIV care cascade is determined by individual longitudinal trajectories through the HIV care continuum and underlying population dynamics. The purpose of this paper is to quantify the contribution of each component of population change (in‐ and out‐migration, HIV seroconversion, ageing into the cohort and definitive exit such as death) on the HIV care cascade in the context of the ANRS 12249 Treatment as Prevention (TasP) cluster‐randomized trial, investigating UTT in rural KwaZulu‐Natal, South Africa, between 2012 and 2016.

Methods

HIV test results and information on clinic visits, ART prescriptions, viral load and CD4 count, migration and deaths were used to calculate residency status, HIV status and HIV care status for each individual on a daily basis. Position within the HIV care continuum was considered as a score ranging from 0 (undiagnosed) to 4 (virally suppressed). We compared the cascade score of each individual joining or leaving the population of resident adults living with HIV with the average score of their cluster at the time of entry or exit. Then, we computed the contribution of each entry or exit on the average cascade score and their annualized total contribution, by component of change.

Results

While the average cascade score increased over time in all clusters, that increase was constrained by population dynamics. Permanent exits and ageing into the people living with HIV cohort had a marginal effect. Both in‐migrants and out‐migrants were less likely to be retained at each step of the HIV care continuum. However, their overall impact on the cross‐sectional cascade was limited as the effect of in‐ and out‐migration balanced each other. The contribution of HIV seroconversions was negative in all clusters.

Conclusions

In a context of high HIV incidence, the continuous flow of newly infected individuals slows down the efforts to increase ART coverage and population viral suppression, ultimately attenuating any population‐level impact on HIV incidence.

Clinical Trial Number

NCT01509508 (clinicalTrials.gov)/DOH‐27‐0512‐3974 (South African National Clinical Trials Register).
Households, fluidity, and HIV service delivery in Zambia and South Africa – an exploratory analysis of longitudinal qualitative data from the HPTN 071 (PopART) trial
Authors: Hoddinott Graeme , Myburgh Hanlie , de Villiers Laing , Ndubani Rhoda , Mantantana Jabulile , Thomas Angelique , Mbewe Madalitso , Ayles Helen , Bock Peter , Seeley Janet , Shanaube Kwame , Hargreaves James , Bond Virginia , Reynolds Lindsey ,   the HPTN 071 (PopART) Study Team
Published: July 2018

Introduction

Population distributions, family and household compositions, and people's sense of belonging and social stability in southern Africa have been shaped by tumultuous, continuing large‐scale historical disruptions. As a result, many people experience high levels of geographic and social fluidity, which intersect with individual and population‐level migration patterns. We describe the complexities of household fluidity and HIV service access in South Africa and Zambia to explore implications for health systems and service delivery in contexts of high household fluidity.

Methods

HPTN 071 (PopART) is a three‐arm cluster randomized controlled trial implemented in 21 peri‐urban study communities in Zambia and South Africa between 2013 and 2018. A qualitative cohort nested in the trial included 148 purposively sampled households. Data collection was informed by ethnographic and participatory research principles. The analysis process was reflexive and findings are descriptive narrative summaries of emergent ideas.

Results

Households in southern Africa are extremely fluid, with people having a tenuous sense of security in their social networks. This fluidity intersects with high individual and population mobility. To characterize fluidity, we describe thematic patterns of household membership and residence. We also identify reasons people give for moving around and shifting social ties, including economic survival, fostering interpersonal relationships, participating in cultural, traditional, religious, or familial gatherings, being institutionalized, and maintaining patterns of substance use. High fluidity disrupted HIV service access for some participants. Despite these challenges, many participants were able to regularly access HIV testing services and participants living with HIV were especially resourceful in maintaining continuity of antiretroviral therapy (ART). We identify three key features of health service interactions that facilitated care continuity: disclosure to family members, understanding attitudes among health services staff including flexibility to accommodate clients’ transient pressures, and participants’ agency in ART‐related decisions.

Conclusions

Choices made to manage one's experiential sense of household fluidity are intentional responses to livelihood and social support constraints. To enhance retention in care for people living with HIV, policy makers and service providers should focus on creating responsive, flexible health service delivery systems designed to accommodate many shifts in client circumstances.
Modulating effects of on‐line low frequency electromagnetic fields on hippocampal long‐term potentiation in young male Sprague‐Dawley rat
Authors: Dong Lei , Zheng Yu , Li Ze‐Yan , Li Gang , Lin Ling
Published: July 2018

The low frequency electromagnetic fields (LF‐EMFs) are attracting more attention and studied deeply because of their effects on human health and biology. Recent reports indicate that exposure of rats to LF‐EMFs induces persistent changes in neuronal activity. The studies used the following standard methods: the rats or rat brain slices were first stimulated in an external electromagnetic exposure system, and then moved to a patch clamp perfusion chamber to record electrophysiological characteristics (off‐line magnetic exposure). However, this approach is susceptible to many disturbances, such as the effects of brain slice movements. In this paper, we describe a novel patch‐clamp setup which is modified to allow accurate on‐line LF‐EMFs stimulation. We performed the computational simulations of the stimulation coils to describe the uniformity of the distribution of the on‐line magnetic field. The 0.5, 1, 2 mT magnetic field of 15 Hz, 50 Hz, and 100 Hz was produced and applied to slices to study the effect of LF‐EMFs on synaptic plasticity. We demonstrated that the slope of field excitatory postsynaptic potentials (fEPSPs) decreased significantly under the priming on‐line uninterrupted or pulsed sinusoidal LF‐EMFs stimulation. In the present study, we investigated whether LF‐EMFs can induce long‐term potentiation (LTP) in male Sprague‐Dawley rat hippocampal slices in vitro. Interestingly, these results highlight the role of 100 Hz pulsed sinusoidal LF‐EMFs only as a modulator, rather than an LTP inducer.
Surface molecularly imprinted polymers prepared by two‐step precipitation polymerization for the selective extraction of oleanolic acid from grape pomace extract
Authors: Lu Chunxia , Tang Zonggui , Liu Changbin , Ma Xiaomei
Published: July 2018

Surface molecularly imprinted polymers were successfully prepared by a novel two‐step precipitation polymerization method. The first‐step allowed the formation of 4‐vinylpyridine divinylbenzene and trimethylolpropane trimethacrylate copolymeric microspheres. In the second‐step precipitation polymerization, microspheres were modified with a molecularly imprinting layer of oleanolic acid as template, methacrylic acid as functional monomer, and divinylbenzene/ethylene glycol dimethacrylate as cross‐linker. The obtained polymers had an average diameter of 4.43 μm and a polydispersity index of 1.011; adsorption equilibrium was achieved within 40 min, with adsorption capacity reaching 27.4 mg/g. Subsequently, the polymers were successfully applied as the adsorbents of molecularly imprinted solid‐phase extraction to separate and purify the oleanolic acid from grape pomace. The content of oleanolic acid in the grape pomace extract was enhanced from 13.4 to 93.2% after using the molecularly imprinted solid‐phase extraction process. This work provides an efficient way for effective oleanolic acid separation and enrichment from complex matrices, which is especially valuable in industrial production.
The Value of Needle‐Guidance Technology in Ultrasound‐Guided Percutaneous Procedures Performed by Radiology Residents: A Comparison of Freehand, In‐Plane, Fixed‐Angle, and Electromagnetic Needle Tracking Techniques
Authors: England Joseph R. , Fischbeck Tucker , Tchelepi Hisham
Published: July 2018

Objectives

Radiology residents typically learn ultrasound‐guided procedures by performing supervised procedures on patients who may experience longer procedure times and higher complication rates. The purpose of this study was to determine if existing technologies, such as in‐plane, fixed‐angle guidance (IPFA) and electromagnetic needle tracking (ENT), can improve resident procedure time and accuracy.

Methods

Radiology residents (18 total) were randomized to 1 of 3 ultrasound‐guidance technique groups—freehand, IPFA, or ENT—and instructed to place a needle into 4 liver lesions in a humanoid phantom, each increasing in difficulty. For each lesion, residents were timed from skin puncture to needle placement, and the number of times the needle was pulled back and redirected (pullbacks) was recorded. Primary outcomes were total time and total number of pullbacks for all 4 lesions. Secondary outcomes were individual time and number of pullbacks for each lesion.

Results

Compared to the freehand group, the IPFA and ENT groups demonstrated lower procedural time and number of pullbacks both in total and for each individual lesion. Differences in total time and total number of pullbacks were significant (P < .001), as were differences for lesion 3 (P = .002–.02) and lesion 4 (P < .001). Differences for lesions 1 and 2 were not statistically significant.

Conclusions

Radiology resident procedure time and procedure accuracy (as judged by number of pullbacks) are significantly improved by the use IPFA and ENT guidance technologies.
Regional variability in the atmospheric nitrogen deposition signal and its transfer to the sediment record in Greenland lakes
Authors: Anderson N. J. , Curtis C. J. , Whiteford E. J. , Jones V. J. , McGowan S. , Simpson G. L. , Kaiser J.
Published: July 2018

Disruption of the nitrogen cycle is a major component of global environmental change. δ15N in lake sediments is increasingly used as a measure of reactive nitrogen input but problematically, the characteristic depleted δ15N signal is not recorded at all sites. We used a regionally replicated sampling strategy along a precipitation and N‐deposition gradient in SW Greenland to assess the factors determining the strength of δ15N signal in lake sediment cores. Analyses of snowpack N and δ15N‐NO3 and water chemistry were coupled with bulk sediment δ15N. Study sites cover a gradient of snowpack δ15N (ice sheet: −6‰; coast
10‰), atmospheric N deposition (ice sheet margin: ∼ 0.2 kg ha−1 yr−1; coast: 0.4 kg ha−1 yr−1) and limnology. Three 210Pb‐dated sediment cores from coastal lakes showed a decline in δ15N of ca.
1‰ from ∼ 1860, reflecting the strongly depleted δ15N of snowpack N, lower in‐lake total N (TN) concentration (∼ 300 μg N L−1) and a higher TN‐load. Coastal lakes have 3.7–7.1× more snowpack input of nitrate than inland sites, while for total deposition the values are 1.7–3.6× greater for lake and whole catchment deposition. At inland sites and lakes close to the ice‐sheet margin, a lower atmospheric N deposition rate and larger in‐lake TN pool resulted in greater reliance on N‐fixation and recycling (mean sediment δ15N is 0.5–2.5‰ in most inland lakes; n = 6). The primary control of the transfer of the atmospheric δ15N deposition signal to lake sediments is the magnitude of external N inputs relative to the in‐lake N‐pool.
Predictive Factors for Survival in Children Receiving Liver Transplants for Wilson’s Disease: A Cohort Study Using European Liver Transplant Registry Data
Authors: Pfister Eva‐Doreen , Karch André , Adam René , Polak Wojciech G. , Karam Vincent , Mirza Darius , O’Grady John , Klempnauer Jürgen , Reding Raymond , Kalicinski Piotr , Coker Ahmet , Trunecka Pavel , Astarcioglu Ibrahim , Jacquemin Emmanual , Pratschke Johann , Paul Andreas , Popescu Irinel , Schneeberger Stefan , Boillot Oliver , Fischer Lutz , Mikolajczyk Rafael T. , Baumann Ulrich , Duvoux Christophe ,   for all European Liver Transplant Registry contributing centers and the European Liver Intestine Transplant Association
Published: July 2018

Liver transplantation (LT) is a rescue therapy for life‐threatening complications of Wilson’s disease (WD). However, data on the outcome of WD patients after LT are scarce. The aim of our study was to analyze a large pediatric WD cohort with the aim of investigating the longterm outcome of pediatric WD patients after LT and to identify predictive factors for patient and transplant survival. This is a retrospective cohort study using data of all children (<18 years) transplanted for WD enrolled in the European Liver Transplant Registry from January 1968 until December 2013. In total, 338 patients (57.6% female) transplanted at 80 different European centers (1‐26 patients per center) were included in this study. The median age at transplantation was 14.0 years (interquartile range [IQR], 11.2‐16.1 years); patients were followed up for a median of 5.4 years (IQR, 1.0‐10.9 years) after LT. Overall patient survival rates were high with 87% (1‐year survival), 84% (5‐year survival), and 81% (10‐year survival); survival rates increased considerably with the calendar year (P < 0.001). Early age at LT, living donation, and histidine tryptophan ketoglutarate preservation liquid were identified as risk factors for poor patient survival in the multivariate analysis. LT is an excellent treatment option for pediatric patients with WD and associated end‐stage liver disease. Longterm outcome in these patients is similar to other pediatric causes for LT. Overall patient and graft survival rates improved considerably over the last decades. To improve future research in the field, the vast variability of allocation strategies should be harmonized and a generally accepted definition or discrimination of acute versus chronic WD needs to be found.
Experiences and perceptions of the theory‐practice gap in nursing in a resource‐constrained setting: A qualitative description study
Authors: Salifu David Abdulai , Gross Janet , Salifu Mohammed Awal , Ninnoni Jerry PK
Published: July 2018

Aim

To describe experiences and perceptions of theory‐practice gap in nursing in a resource‐constrained setting. Theory‐practice gap is extensively discussed and studied in some parts of the world. Interventions to bridge the theory‐practice gap have been varied and depend on an understanding of the contextual healthcare environment. Experiences and perceptions of the theory‐practice gap in a resource‐constrained setting have not been comprehensively described.

Design

A qualitative description methodology was used.

Methods

Maximum variation sampling based on role in the events of theory‐practice gap was used to recruit student nurses, nurse faculty and clinicians from two study sites for focus group discussions. Data were analysed using conventional content analysis.

Results

Five themes were identified: system inadequacies; resource constraints; challenges of the clinical learning environment; clinical placement and supervision; and nurse faculty factors. Systems inadequacy and resource constraints formed the spine of the challenges contributing to the theory‐practice gap in the research setting.
Synergetic effect of triglycine sulfate and graphite nanoplatelets on dielectric and piezoelectric properties of epoxy resin composites
Authors: Plyushch Artyom , Macutkevic Jan , Samulionis Vytautas , Banys Juras , Bychanok Dzmitry , Kuzhir Polina , Mathieu Sandrine , Fierro Vanessa , Celzard Alain
Published: July 2018

Epoxy resin composites with 30 wt% of triglycine sulfate (TGS) and up to 1 wt% of graphite nanoplatelets (GNP) were fabricated and studied by means of broadband dielectric spectroscopy (20 Hz–3 GHz). It was demonstrated that the dielectric properties are mainly governed by the Maxwell‐Wagner relaxation at lower frequencies (below 1 MHz) and by diffuse ferroelectric soft mode at higher frequencies (above 1 MHz). The ferroelectric origin of the phase transitions was also confirmed by piezoelectric investigations. Although the phase transition temperature is independent of GNP concentration, the piezoelectric and dielectric (above 1 MHz) properties of composites are strongly improved by GNP in a broad temperature range. This gives evidence for the strong synergy between GNP and ferroelectric particles. The synergy effect appears due to the better distribution of TGS particles in ternary composites and the creation of electric fields by GNP inside the composite. POLYM. COMPOS., 40:E1181–E1188, 2019. © 2018 Society of Plastics Engineers
Similar to And/Or Better than Oneself? Singles’ Ideal Partner Personality Descriptions
Authors: Liu Jie , Ludeke Steven , Haubrich Julia , Gondan–Rochon Matthias , Zettler Ingo
Published: July 2018

Using the HEXACO Model of Personality, we explored two kinds of ideal partner preferences regarding personality traits, namely, to what extent people prefer partners similar to themselves (similarity preference) and to what extent people prefer partners with more desirable trait levels than themselves (aspirational assortative preference). We conducted five studies (overall N > 900) across four countries (China, Denmark, Germany, and the USA), looking at both HEXACO factors and facets, using both self–report questionnaires and real–life data (personal profiles from a dating website), and comprising both student and more heterogeneous samples. The results provided support for both kinds of ideal partner preferences, with important differences across traits. Specifically, similarity preference was supported by all studies concerning all HEXACO traits, and aspirational assortative preference was supported by all four self–report studies (though not the dating website study) concerning all HEXACO traits except for Openness to Experience. Concerning differences in preferences among the HEXACO traits, similarity preference was particularly pronounced for Honesty–Humility and Openness to Experience, moderate for Agreeableness and Conscientiousness, and less pronounced for Emotionality and Extraversion. Aspirational assortative preference, by contrast, was particularly pronounced for Emotionality, Extraversion, and Agreeableness, moderate for Honesty–Humility, and inconsistent for Conscientiousness. © 2018 European Association of Personality Psychology
Fusarium graminearum‐induced shoot elongation and root reduction in maize seedlings correlate with later seedling blight severity
Authors: Zhou Shaoqun , Bae Justin S. , Bergstrom Gary C. , Jander Georg
Published: July 2018

Fusarium graminearum seedling blight is a common disease of maize (Zea mays). Development of genetic resistance to seedling blight in maize germplasm requires efficient and accurate quantitative assessment of disease severity. Through artificial inoculation experiments under controlled growth conditions, we determined that host genotype, pathogen genotype, and infection dose influence the extent to which F. graminearum induces shoot elongation and inhibits root growth in maize seedlings. A comparison of 15 maize inbred lines showed independent variation of these two fungus‐induced effects on seedling growth. In a broader survey with nine commercial maize hybrids and three field‐collected fungal isolates, there was significant correlation between these seedling growth responses, as well as with later seedling blight severity. Analysis of variance suggested that this variation and the observed correlative relationships were primarily driven by differing pathogenicity of the three fungal isolates. Together, our results indicate that F. graminearum‐induced shoot elongation and root reduction in maize seedlings have distinct underlying physiological mechanisms, and that early observations of seedling growth responses can serve as a proxy for investigating natural variation in host resistance and pathogen aggressiveness at later growth stages.
Relationship between PSA kinetics and Tc‐99m HYNIC PSMA SPECT/CT detection rates of biochemical recurrence in patients with prostate cancer after radical prostatectomy
Authors: Liu Chang , Zhu Yao , Su Hengchuan , Xu Xiaoping , Zhang Yingjian , Ye Dingwei , Hu Silong
Published: July 2018

Background

Prostate‐specific antigen (PSA) levels should reflect or be proportional to the size and the metabolic activity of prostatic metastases. Moreover, a rapid change in PSA kinetics, either before or after treatment, is an indicator of poor prognosis after radical prostatectomy. Therefore, the purpose of this study was to investigate the effect of total PSA at the time of Tc‐99m HYNIC PSMA SPECT/CT (trigger PSA), PSA velocity (PSAvel), and PSA doubling time (PSAdt) on the Tc‐99m HYNIC PSMA SPECT/CT detection rate in prostate cancer patients who showed biochemical recurrence after radical prostatectomy during follow‐up.

Methods

In total, 208 patients who showed an increase in PSA were evaluable for this retrospective analysis covering November 2015 to March 2017. Data were available for calculation of PSAvel in 112 patients and for PSAdt in 157 patients. Logistic regression analysis was used to determine whether there was a relationship between the PSA levels and PSA kinetics and the rate of detection of relapse using Tc‐99m HYNIC PSMA SPECT/CT.

Results

Tc‐99m HYNIC PSMA SPECT/CT detected disease relapse in 151 of 208 patients (72.6%). The PSA level (P < 0.0001) and PSAdt (P = 0.0036) were significantly different between SPECT‐positive patients (higher PSA level, shorter PSAdt) and SPECT‐negative patients (lower PSA, longer PSAdt). ROC analysis showed that a PSA level of 1.30 ng/mL and a PSAdt of 2.9 months were optimal cut‐off values. Patients with purely local recurrence had lower PSAvel and longer PSAdt values (P < 0.001). According to the multivariate analysis, a pathological positive SPECT/CT scan was associated with the PSA level (P < 0.001), PSAdt <6 months (P < 0.05), and Gleason scores (GSC) >7 (P < 0.05).

Conclusion

The Tc‐99m HYNIC PSMA SPECT/CT detection rate is influenced by trigger PSA, PSAdt, and PSAvel. Like PSA, PSAdt is an independent predictor of Tc‐99m HYNIC PSMA SPECT/CT. PSAdt should be taken into account by physicians especially when PSA <1 ng/mL.
Coil conversion to β‐strand induced by dimerization
Authors: Laibe Johanna , Caffrey Aaron , Broutin Melanie , Guiglion Solene , Pierscionek Barbara , Nebel Jean‐Christophe
Published: July 2018

Most molecular processes in living organisms rely on protein‐protein interactions, many of which are mediated by β‐sheet interfaces; this study investigates the formation of β‐sheet interfaces through the conversion of coils into β‐strands. Following an exhaustive search in the Protein Data Bank, the corresponding structural dimorphic fragments were extracted, characterized, and analyzed. Their short strand lengths and specific amino acid profiles indicate that dimorphic β‐strand interfaces are likely to be less stable than standard ones and could even convert to coil interfaces if their environment changes. Moreover, the construction of a simple classifier able to discriminate between the sequences of dimorphic and standard β‐strand interfaces suggests that the nature of those dimorphic sequences could be predicted, providing a novel means of identifying proteins capable of forming dimers.
Evolutionary couplings and sequence variation effect predict protein binding sites
Authors: Schelling Maria , Hopf Thomas A. , Rost Burkhard
Published: July 2018

Binding small ligands such as ions or macromolecules such as DNA, RNA, and other proteins is one important aspect of the molecular function of proteins. Many binding sites remain without experimental annotations. Predicting binding sites on a per‐residue level is challenging, but if 3D structures are known, information about coevolving residue pairs (evolutionary couplings) can predict catalytic residues through mutual information. Here, we predicted protein binding sites from evolutionary couplings derived from a global statistical model using maximum entropy. Additionally, we included information from sequence variation. A simple method using a weighted sum over eight scores substantially outperformed random (F1 = 19.3% ± 0.7% vs F1 = 2% for random). Training a neural network on these eight scores (along with predicted solvent accessibility and conservation in protein families) improved substantially (F1 = 26.2% ±0.8%). Although the machine learning was limited by the small data set and possibly wrong annotations of binding sites, the predicted binding sites formed spatial clusters in the protein. The source code of the binding site predictions is available through GitHub: https://github.com/Rostlab/bindPredict.
Robust Bayesian nonlinear mixed‐effects modeling of time to positivity in tuberculosis trials
Authors: Burger Divan Aristo , Schall Robert , Chen Ding‐Geng
Published: July 2018

Early phase 2 tuberculosis (TB) trials are conducted to characterize the early bactericidal activity (EBA) of anti‐TB drugs. The EBA of anti‐TB drugs has conventionally been calculated as the rate of decline in colony forming unit (CFU) count during the first 14 days of treatment. The measurement of CFU count, however, is expensive and prone to contamination. Alternatively to CFU count, time to positivity (TTP), which is a potential biomarker for long‐term efficacy of anti‐TB drugs, can be used to characterize EBA. The current Bayesian nonlinear mixed‐effects (NLME) regression model for TTP data, however, lacks robustness to gross outliers that often are present in the data. The conventional way of handling such outliers involves their identification by visual inspection and subsequent exclusion from the analysis. However, this process can be questioned because of its subjective nature. For this reason, we fitted robust versions of the Bayesian nonlinear mixed‐effects regression model to a wide range of TTP datasets. The performance of the explored models was assessed through model comparison statistics and a simulation study. We conclude that fitting a robust model to TTP data obviates the need for explicit identification and subsequent “deletion” of outliers but ensures that gross outliers exert no undue influence on model fits. We recommend that the current practice of fitting conventional normal theory models be abandoned in favor of fitting robust models to TTP data.
Pinosylvin enhances leukemia cell death via down‐regulation of AMPKα expression
Authors: Song Jina , Seo Youngsik , Park Heonyong
Published: July 2018

Resveratrol at high concentrations (50–100 μmol/L) is known to induce cell death in leukemia cells. Here, we investigated whether pinosylvin, a resveratrol analogue, induced cell death in leukemia cells. Cell death was found to be markedly elevated by 50‐ to 100‐μmol/L pinosylvin in THP‐1 and U937 cells. It was also shown that pinosylvin induced caspase‐3 activation, flip‐flop of phosphatidylserine, LC3‐II accumulation, LC3 puncta, and p62 degradation in both THP‐1 and U937 cells. These data indicate that pinosylvin‐induced cell death may occur through apoptosis and autophagy. In addition, we showed that pinosylvin down‐regulates AMP‐activated protein kinase α1 (AMPKα1) in leukemia cells. Therefore, we correlated AMPKα1 down‐regulation and leukemia cell death. AMPKα1 inhibition appeared to decrease pinosylvin‐induced apoptosis and autophagy in leukemia cells, implying that AMPK is a key regulator of leukemia cell death. Moreover, we found that both pinosylvin‐induced autophagy and apoptotic progress were reduced in AMPKα1‐overexpressed leukemia cells, when compared with vector‐transfected cells. Cell death was elevated by AMPKα1 overexpression, whereas pinosylvin‐induced cell death was markedly decreased by caspase‐3 inhibitors or autophagy inhibitors. These results suggest that pinosylvin‐induced depletion of AMPKα1 enhances cell death via apoptosis and autophagy in leukemia cells.
Azygos vein varix mimicking bronchial cysts
Authors: Miura Hiroyuki , Miura Jun , Hirano Hiroshi
Published: July 2018

Azygos vein varix is a very rare disease associated with a risk of rupture or thrombosis. Here, we report a case of azygos vein varix mimicking bronchogenic cysts. A 79‐year‐old female patient presented with abnormal shadows on a chest X‐ray during an annual check‐up. A plain chest computed tomography (CT) showed a well‐defined tumour, approximately 66 X 65 X 45 mm in size, behind the trachea. An enhanced CT scan was refused due to asthma complications. A high signal on T2W1 images from magnetic resonance imaging (MRI) indicated a cystic tumour. Diagnosed as a bronchogenic cyst, a cyst excision was scheduled. Upon observation with a thoracoscope, a dark purple‐red saccular tumour was observed continuing on to the azygos vein and was removed using linear staplers. The patient is alive and well 4 years after the operation. If a cystic tumour located in the right upper mediastinum is observed, the presence of azygos vein varix should be considered.
Flood energy dissipation in anabranching channels
Authors: Entwistle Neil , Heritage George , Milan David
Published: July 2018

This study examines the character of developing anabranched channel networks on the River Wear, north England, using metre‐scale aerial LiDAR. DSM‐DTM interpretation reveals a well‐developed vegetation structure and a locally diverse terrain, dominated by an interlinked channel network split by low‐elevation depositional areas with the gross morphology of the reach resembling that of a strongly active meandering/wandering channel suggesting that an anabranching network may develop within systems that were initially active meandering and wandering, evolving in line with floodplain vegetative succession. Utilization of the LiDAR DEM in the hydrological component of the CAESAR‐Lisflood (version 1.4) morphodynamic model has generated local hydraulic variable estimates through the anabranched reaches for a range of flows. These data clearly demonstrate how elevated flows are transferred out of the primary channel and distributed along the interconnected secondary channel network, creating a diverse set of hydraulic environments. Areas between the channels rapidly become inundated as flows increase, dissipating flow energy. Shear stress estimates throughout the study site reveal a generally reduced ability to mobilize sediments and erode channel margins, in comparison with a single‐thread reach immediately downstream. Anabranched secondary channels appear to operate in disequilibrium and act predominantly as aggradational zones, although with some evidence of scour at channel bifurcation and confluence points. It would appear that the topographic character of anabranching sites efficiently manages flood flow energy, activating secondary channels and low‐elevation areas to distribute flood flows. These findings contrast with the hydraulic data from an adjacent single‐thread reach, characterized by flood flows concentrated in‐channel creating a high erosive potential. We propose that anabranching rivers could play an important role in natural flood and sediment management in many U.K. river systems.
Mixed Anhydrides of Nucleotides and Amino Acids Give Dipeptides: A Model System for Studying the Origin of the Genetic Code?
Authors: Wang Tao , Zhang Pengbo , Hu Gaobo , Gao Yuzhen , Wu Yile , Xu Pengxiang , Liu Yan , Zhao Yufen
Published: July 2018

The genetic code recognition system in modern ribosome is a very complicated system and it is not easy to touch the core of the problem. We built up a simplified chemical model which only consists of phosphorous compounds, silylated amino acids and silylated nucleosides to study the origin of the genetic code. It was found that the yields of the “translation products”, namely dipeptides, for each of the six amino acids (Phe, Trp, Tyr, His, Val and Leu) behaved differently with the presence of different nucleosides. The proposed mechanism involves a five‐membered cyclic pentacoordinated nucleoside‐phosphoric acid‐amino acid anhydride (NPA) as a key intermediate. This reaction mechanism could explain why nucleosides may have affected the synthesis of dipeptides in processes that eventually led to translation and the genetic code.
Novel Benzylic Substituted Imidazolinium, Tetrahydropyrimidinium and Tetrahydrodiazepinium Salts: Potent Carbonic Anhydrase and Acetylcholinesterase Inhibitors
Authors: Yiğit Beyhan , Yiğit Murat , Barut Celepci Duygu , Gök Yetkin , Aktaş Aydın , Aygün Muhittin , Taslimi Parham , Gülçin İlhami
Published: July 2018

The new imidazolinium, tetrahydropyrimidinium and tetrahydrodiazepinium salts were synthesized in good yield by the reaction of the corresponding N,N’‐dialkylalkanediamine with triethyl orthoformate in the presence of ammonium chloride. All of the compounds were obtained, and spectroscopically characterized. The crystal structure for the 1,3‐bis(4‐benzyloxy‐3‐methoxybenzyl)‐3,4,5,6‐tetrahydropyrimidinium chloride (5 g) was determined by single‐crystal X‐ray diffraction. The biological properties of all novel compounds were tested and the influence of ring size and benzylic N‐substituents on the biological activities were examined. Also, they were found as effective inhibitors against cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase (AChE) enzyme. Among these compounds, 1,3‐bis(4‐(1‐piperidinyl)benzyl)‐3,4,5,6‐tetrahydropyrimidinium chloride (5 f) demonstrated the the best inhibition effects against hCA I, 1,3‐bis(4‐benzyloxy‐3‐methoxybenzyl)‐3,4,5,6‐tetrahydropyrimidinium chloride (5 g) demonstrated the the best inhibition effects against cytosolic hCA II isoenzyme. On the other hand, 1,3‐Bis(4‐methylthiobenzyl)‐3,4,5,6‐tetrahydropyrimidinium chloride, (5e) demonstrated the the best inhibition effects against AChE enzyme.
Dithiophosphorus‐Palladium Complexes as a Catalyst in the Heck Reaction via Pd(II)/Pd(IV) Catalytic Cycle: A Combined Experimental and Computational Study
Authors: Gholivand Khodayar , Salami Rasoul , Rastegar Somayeh F. , Roe S. Mark
Published: July 2018

The palladium‐catalyzed Heck reaction is the most effective method for vinylation of unsaturated halides. Here, new thermally stable palladium(II) complexes {(4OMe−Ph) RPS2}2Pd [R= C5H11NH (1); R= CH3CH2NHCH3 (2); R=OCH3 (3)] were readily synthesized in a high yield by the reaction of PdCl2 with dithiophosphorus ligands. The molecular structures of 1 and 2 were determined by means of X‐ray diffraction analysis. The catalytic activity of all complexes was evaluated in Heck reaction. The results revealed that the complexes are highly active catalysts in coupling of aryl bromides with styrene. The Hammett plot of the competition experiments of various aryl bromides with styrene, catalyzed by the complexes, displayed very good linear correlation with a positive slope (ρ) within a range of 3.99‐4.39 for 1–3. The absence of any decomposition signs together with negative Hg‐poisoning tests indicated that the liberation of Pd(0) species in the catalytic cycle is unlikely. So, it was supposed that the palladium(II)‐catalyzed Heck reaction might not proceed via classical Pd(0)/Pd(II) catalytic cycle. To find the most probable mechanism, density functional theory calculations were performed and the predicted data compared with the experimental results. Upon the obtained results, the Pd(II)/Pd(IV) catalytic cycle was proposed as the most plausible mechanism. The overall free energy profile showed that the first step of the mechanism (oxidative addition) with a free energy barrier of 33.8 kcal/mol involves the highest energy barrier and can be considered as the rate determining step of the mechanism.
Photo/Electrocatalytic Properties of Nanocrystalline ZnO and La–Doped ZnO: Combined DFT Fundamental Semiconducting Properties and Experimental Study
Authors: Ahsaine Hassan Ait , Slassi Amine , Naciri Yassin , Chennah Ahmed , Jaramillo‐Páez Cesar , Anfar Zakaria , Zbair Mohamed , Benlhachemi Abdeljalil , Navío Jose Antonio
Published: July 2018

This work reports the synthesis of nanocrystalline ZnO and 5% La‐doped ZnO (La/ZnO) materials for photo/electrocatalytic degradation of Rhodamine B. The samples were characterized by X‐Ray diffraction, scanning and transmission electron microscopy, X‐Ray photoelectron spectroscopy and diffuse reflectance spectra. The effect of La doping on electronic structure was investigated using density functional theory calculations (DFT), La‐doped ZnO showed an n‐type metallic nature compared to pristine ZnO and La doping creates occupied states within the band gap edge. Under UV light, La/ZnO showed higher kinetic constant and efficiency than ZnO. A possible mechanism was elaborated on the basis of DFT and active trapping measurements. Different initial Rhodamine B concentration were studied to assess the electro‐oxidation of RhB. The electrochemical degradation of RhB over La/ZnO spindles electrode was pronounced with three time's high kinetic constant. The superior electro/photoactivity of La/ZnO was due to its unique morphology, high charge separation of the charge carriers and higher conductivity induced by La‐doping (intermediary levels). Superoxide ions and holes were the main active species for the photodegradation. Whereas, synergetic effect of hydroxyl radicals and hypochlorite ions were responsible of the high RhB electrocatalytic degradation.
Organocatalytic Asymmetric Cascade Reactions Based on Gamma‐Nitro Carbonyl Compound
Authors: Li Xiang , Guo Li , Peng Cheng , Han Bo
Published: July 2018

The significant advancements in asymmetric organocascade reactions have been accomplished during the past decades, paving the way to the efficient and stereoselective construction of structurally complex scaffolds from simple and readily available starting materials. Nitro‐containing cyclic compounds have become a privileged molecular library given their broad and promising activities in various therapeutic areas. In various approaches to build these valuable scaffolds, the utility of γ‐nitrocarbonyl intermediates is one of the most efficient approaches due to its high efficiency, reliability and versatility. The strategies and catalyst systems described here highlight recent advances in the enantioselective synthesis of nitro‐containing cyclic molecules via organocascade strategies based on γ‐nitrocarbonyl intermediates. Various organocatalysts with distinct activation modes have found application in providing these sophisticated compounds. This review is organized according to the types of organocatalyst. These methods are of importance for the construction of complex chiral cyclic frameworks and the design of new pharmaceutical compounds. We believe that compounds based on nitro‐containing cyclic skeletons have the potential to provide novel therapeutic agents and useful biological tools.