bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperthermia depletes Oct4 in mouse blastocysts and stem cells
Authors: Cheng Mo-bin , Wang Xue , Huang Yue , Zhang Ye
Published: May 2020

Temperature is an important microenvironmental factor that functions epigenetically in normal embryonic development. However, the effect of hyperthermia in the stem cells is not fully understood. Oct4 is a tightly regulated master regulator of pluripotency maintenance in stem cells and during early embryonic development. We report here that Oct4 protein level was significantly reduced under hyperthermia in mouse blastocysts and embryonic stem cells. The reduction in Oct4 in the mouse embryonic stem cells under hyperthermia was mediated by a ubiquitin-proteasome pathway that was dependent on the activity of death-associated protein kinase 1 (Dapk1) to phosphorylate its substrate, Pin1. Our results imply that the depletion of Oct4 via brief hyperthermia, such as a high fever, during early pregnancy might severely impair the growth of the mammalian embryo or even cause its death.
Assessing the information content of structural and protein–ligand interaction representations for the classification of kinase inhibitor binding modes via machine learning and active learning
Authors: Rodríguez-Pérez Raquel , Miljković Filip , Bajorath Jürgen
Published: May 2020

For kinase inhibitors, X-ray crystallography has revealed different types of binding modes. Currently, more than 2000 kinase inhibitors with known binding modes are available, which makes it possible to derive and test machine learning models for the prediction of inhibitors with different binding modes. We have addressed this prediction task to evaluate and compare the information content of distinct molecular representations including protein–ligand interaction fingerprints (IFPs) and compound structure-based structural fingerprints (i.e., atom environment/fragment fingerprints). IFPs were designed to capture binding mode-specific interaction patterns at different resolution levels. Accurate predictions of kinase inhibitor binding modes were achieved with random forests using both representations. The performance of IFPs was consistently superior to atom environment fingerprints, albeit only by less than 10%. An active learning strategy applying information entropy-based selection of training instances was applied as a diagnostic approach to assess the relative information content of distinct representations. IFPs were found to capture more binding mode-relevant information than atom environment fingerprints, leading to highly predictive models even when training instances were randomly selected. By contrast, for atom environment fingerprints, the derivation of accurate models via active learning depended on entropy-based selection of informative training compounds. Notably, higher information content of IFPs confirmed by active learning only resulted in small improvements in global prediction accuracy compared to models derived using atom environment fingerprints. For practical applications, prediction of binding modes of new kinase inhibitors on the basis of chemical structure is highly attractive.
Comparison of diagnostic sensitivity of [18F]fluoroestradiol and [18F]fluorodeoxyglucose positron emission tomography/computed tomography for breast cancer recurrence in patients with a history of estrogen receptor-positive primary breast cancer
Authors: Chae Sun Young , Son Hye Joo , Lee Dong Yun , Shin Eonwoo , Oh Jungsu S. , Seo Seung Yeon , Baek Sora , Kim Ji Young , Na Sae Jung , Moon Dae Hyuk
Published: May 2020

Background

To compare the diagnostic sensitivity of [18F]fluoroestradiol ([18F]FES) and [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) for breast cancer recurrence in patients with estrogen receptor (ER)-positive primary breast cancer.

Methods

Our database of consecutive patients enrolled in a previous prospective cohort study to assess [18F]FES PET/CT was reviewed to identify eligible patients who had ER-positive primary breast cancer with suspected first recurrence at presentation and who underwent [18F]FDG PET/CT. The sensitivity of qualitative [18F]FES and [18F]FDG PET/CT interpretations was assessed, comparing them with histological diagnoses.

Results

Of the 46 enrolled patients, 45 were confirmed as having recurrent breast cancer, while one was diagnosed with chronic granulomatous inflammation. Forty (89%) patients were ER-positive, four (9%) were ER-negative, and one (2%) patient did not undergo an ER assay. The sensitivity of [18F]FES PET/CT was 71.1% (32/45, 95% CI, 55.7–83.6), while that of [18F]FDG PET/CT was 80.0% (36/45, 95% CI, 65.4–90.4) with a threshold of positive interpretation, and 93.3% (42/45, 95% CI, 81.7–98.6) when a threshold of equivocal was used. There was no significant difference in sensitivity between [18F]FES and [18F]FDG PET/CT (P = 0.48) with a threshold of positive [18F]FDG uptake, but the sensitivity of [18F]FDG was significantly higher than [18F]FES (P = 0.013) with a threshold of equivocal [18F]FDG uptake. One patient with a benign lesion showed negative [18F]FES but positive [18F]FDG uptake.

Conclusions

The restaging of patients who had ER-positive primary breast cancer and present with recurrent disease may include [18F]FES PET/CT as an initial test when standard imaging studies are equivocal or suspicious.
Characterization of FsXEG12A from the cellulose-degrading ectosymbiotic fungus Fusarium spp. strain EI cultured by the ambrosia beetle
Authors: Sakai Kiyota , Yamaguchi Aya , Tsutsumi Seitaro , Kawai Yuto , Tsuzuki Sho , Suzuki Hiromitsu , Jindou Sadanari , Suzuki Yoshihito , Kajimura Hisashi , Kato Masashi , Shimizu Motoyuki
Published: May 2020

Despite the threat of Fusarium dieback posed due to ambrosia fungi cultured by ambrosia beetles such as Euwallacea spp., the wood-degradation mechanisms utilized by ambrosia fungi are not fully understood. In this study, we analyzed the 16S rRNA and 18S rRNA genes of the microbial community from the Ficus tree tunnel excavated by Euwallacea interjectus and isolated the cellulose-degrading fungus, Fusarium spp. strain EI, by enrichment culture with carboxymethyl cellulose as the sole carbon source. The cellulolytic enzyme secreted by the fungus was identified and expressed in Pichia pastoris, and its enzymatic properties were characterized. The cellulolytic enzyme, termed FsXEG12A, could hydrolyze carboxymethyl cellulose, microcrystalline cellulose, xyloglucan, lichenan, and glucomannan, indicating that the broad substrate specificity of FsXEG12A could be beneficial for degrading complex wood components such as cellulose, xyloglucan, and galactoglucomannan in angiosperms. Inhibition of FsXEG12A function is, thus, an effective target for Fusarium dieback caused by Euwallacea spp.
Metabolic enzyme clustering by coiled coils improves the biosynthesis of resveratrol and mevalonate
Authors: Fink Tina , Stevović Bojana , Verwaal René , Roubos Johannes A. , Gaber Rok , Benčina Mojca , Jerala Roman , Gradišar Helena
Published: May 2020

The clustering of biosynthetic enzymes is used in nature to channel reaction products and increase the yield of compounds produced by multiple reaction steps. The coupling of multiple enzymes has been shown to increase the biosynthetic product yield. Different clustering strategies have particular advantages as the spatial organization of multiple enzymes creates biocatalytic cascades with a higher efficiency of biochemical reaction. However, there are also some drawbacks, such as misfolding and the variable stability of interaction domains, which may differ between particular biosynthetic reactions and the host organism. Here, we compared different protein-based clustering strategies, including direct fusion, fusion mediated by intein, and noncovalent interactions mediated through small coiled-coil dimer-forming domains. The clustering of enzymes through orthogonally designed coiled-coil interaction domains increased the production of resveratrol in Escherichia coli more than the intein-mediated fusion of biosynthetic enzymes. The improvement of resveratrol production correlated with the stability of the coiled-coil dimers. The coiled-coil fusion-based approach also increased mevalonate production in Saccharomyces cerevisiae, thus demonstrating the wider applicability of this strategy.
Emerging functions and clinical applications of exosomes in human oral diseases
Authors: Peng Qiao , Yang Jing-ya , Zhou Gang
Published: May 2020

Exosomes are cell-derived membranous vesicles of endosomal origin secreted by all type of cells and present in various body fluids. Exosomes are enriched in peptides, lipids, and nucleic acids, emerging as vital modulators in intercellular communication. Exosomes are increasingly being evaluated as biomarkers for diagnosis and prognosis of diseases, because the constituents of exosomes could be reprogrammed depending on the states of diseases. These features also make exosomes a research hotspot in oral diseases in recent years. In this review, we outlined the characteristics of exosomes, focused on the differential expressions and altered biological functions of exosomes in oral diseases, including oral squamous cell carcinoma, oral leukoplakia, periodontitis, primary Sjögren’s syndrome, oral lichen planus, as well as hand foot and mouth disease. Besides, accumulated evidence documents that it is implementable to consider the natural nanostructured exosomes as a new strategy for disease treatment. Herein, we highlighted the therapeutic potential of exosomes in oral tissue regeneration, oncotherapy, wound healing, and their superiority as therapeutic drug delivery vehicles.
Metoprolol alleviates arginine vasopressin-induced cardiomyocyte hypertrophy by upregulating the AKT1–SERCA2 cascade in H9C2 cells
Authors: Zhao Jieqiong , Lei Yonghong , Yang Yanping , Gao Haibo , Gai Zhongchao , Li Xue
Published: May 2020

Background

Arginine vasopressin (AVP) is elevated in patients with heart failure, and the increase in the AVP concentration in plasma is positively correlated with disease severity and mortality. Metoprolol (Met) is a beta blocker that is widely used in the clinic to treat pathological cardiac hypertrophy and to improve heart function. However, the specific mechanism by which Met alleviates AVP-induced pathological cardiac hypertrophy is still unknown. Our current study aimed to evaluate the inhibitory effects of Met on AVP-induced cardiomyocyte hypertrophy and the underlying mechanisms.

Methods

AVP alone or AVP plus Met was added to the wild type or AKT1-overexpressing rat cardiac H9C2 cell line. The cell surface areas and ANP/BNP/β-MHC expressions were used to evaluate the levels of hypertrophy. Western bolting was used to analyze AKT1/P-AKT1, AKT2/P-AKT2, total AKT, SERCA2, and Phospholamban (PLN) expression. Fluo3-AM was used to measure the intracellular Ca2+ stores.

Results

In the current study, we found that AKT1 but not AKT2 mediated the pathogenesis of AVP-induced cardiomyocyte hypertrophy. Sustained stimulation (48 h) with AVP led to hypertrophy in the H9C2 rat cardiomyocytes, resulting in the downregulation of AKT1 (0.48 fold compared to control) and SERCA2 (0.62 fold), the upregulation of PLN (1.32 fold), and the increase in the cytoplasmic calcium concentration (1.52 fold). In addition, AKT1 overexpression increased the expression of SERCA2 (1.34 fold) and decreased the expression of PLN (0.48 fold) in the H9C2 cells. Moreover, we found that Met could attenuate the AVP-induced changes in AKT1, SERCA2 and PLN expression and decreased the cytoplasmic calcium concentration in the H9C2 cells.

Conclusions

Our results demonstrated that the AKT1–SERCA2 cascade served as an important regulatory pathway in AVP-induced pathological cardiac hypertrophy.
Use, timing and factors associated with tracheal intubation in septic shock: a prospective multicentric observational study
Authors: Darreau C. , Martino F. , Saint-Martin M. , Jacquier S. , Hamel J. F. , Nay M. A. , Terzi N. , Ledoux G. , Roche-Campo F. , Camous L. , Pene F. , Balzer T. , Bagate F. , Lorber J. , Bouju P. , Marois C. , Robert R. , Gaudry S. , Commereuc M. , Debarre M. , Chudeau N. , Labroca P. , Merouani K. , Egreteau P. Y. , Peigne V. , Bornstain C. , Lebas E. , Benezit F. , Vally S. , Lasocki S. , Robert A. , Delbove A. , Lerolle N.
Published: May 2020

Background

No recommendation exists about the timing and setting for tracheal intubation and mechanical ventilation in septic shock.

Patients and methods

This prospective multicenter observational study was conducted in 30 ICUs in France and Spain. All consecutive patients presenting with septic shock were eligible. The use of tracheal intubation was described across the participating ICUs. A multivariate analysis was performed to identify parameters associated with early intubation (before H8 following vasopressor onset).

Results

Eight hundred and fifty-nine patients were enrolled. Two hundred and nine patients were intubated early (24%, range 4.5–47%), across the 18 centers with at least 20 patients included. The cumulative intubation rate during the ICU stay was 324/859 (38%, range 14–65%). In the multivariate analysis, seven parameters were significantly associated with early intubation and ranked as follows by decreasing weight: Glasgow score, center effect, use of accessory respiratory muscles, lactate level, vasopressor dose, pH and inability to clear tracheal secretions. Global R-square of the model was only 60% indicating that 40% of the variability of the intubation process was related to other parameters than those entered in this analysis.

Conclusion

Neurological, respiratory and hemodynamic parameters only partially explained the use of tracheal intubation in septic shock patients. Center effect was important. Finally, a vast part of the variability of intubation remained unexplained by patient characteristics.

Trial registration Clinical trials NCT02780466, registered on May 23, 2016. https://clinicaltrials.gov/ct2/show/NCT02780466?term=intubatic&draw=2&rank=1.
Duration of prone position sessions: a prospective cohort study
Authors: Jochmans Sebastien , Mazerand Sandie , Chelly Jonathan , Pourcine Franck , Sy Oumar , Thieulot-Rolin Nathalie , Ellrodt Olivier , Mercier Des Rochettes Emmanuelle , Michaud Gaël , Serbource-Goguel Jean , Vinsonneau Christophe , Vong Ly Van Phach , Monchi Mehran
Published: May 2020

Background

Prone position (PP) is highly recommended in moderate-to-severe ARDS. However, the optimal duration of PP sessions remains unclear. We searched to evaluate the time required to obtain the maximum physiological effect, and to search for parameters related to patient survival in PP.

Methods and results

It was a prospective, monocentric, physiological study. We included in the study all prone-positioned patients in our ICU between June 2016 and January 2018. Pulmonary mechanics, data from volumetric capnography and arterial blood gas were recorded before prone positioning, 2 h after proning, before return to a supine position (SP) and 2 h after return to SP. Dynamic parameters were recorded before proning and every 30 min during the session until 24 h. 103 patients (ARDS 95%) were included performing 231 PP sessions with a mean length of 21.5 ± 5 h per session. They presented a significant increase in pH, static compliance and PaO2/FiO2with a significant decrease in PaCO2, Pplat, phase 3 slope of the volumetric capnography, PetCO2,VD/VT-phyand ΔP. The beneficial physiological effects continued after 16 h of PP and at least up to 24 h in some patients. The evolution of the respiratory parameters during the first session and also during the pooled sessions did not find any predictor of response to PP, whether before, during or 2 h after the return in SP.

Conclusions

PP sessions should be prolonged at least 24 h and be extended in the event that the PaO2/FiO2ratio at 24 h remains below 150, especially since no criteria can predict which patient will benefit or not from it.

Trial registrationThe trial has been registered on 28 June 2016 in ClinicalTrials.gov (NCT 02816190) (https://clinicaltrials.gov/ct2/show/NCT02816190?term=propocap&rank=1).
Efficient authentication and re-authentication protocols for 4G/5G heterogeneous networks
Authors: Alezabi Kamal Ali , Hashim Fazirulhisyam , Hashim Shaiful J. , Ali Borhanuddin M. , Jamalipour Abbas
Published: May 2020

In the next-generation heterogeneous wireless networks, designing authentication protocols that meet the demand of mobile users/applications is a challenge. This paper proposes authentication and re-authentication protocols for 4G wireless networks, in particular, LTE-Advanced (LTE-A), WLAN, and WiMAX-Advanced (WiMAX-A) interworking architecture. The proposed protocols are applicable to 5G networks. With the consideration of the existing standard authentication protocols, a new set of authentication and re-authentication protocols has been reinvented to provide fast and secure handovers (HO) in the current 4G and the next 5G networks. The proposed authentication protocols can be invoked when the users perform a vertical HO (between different networks) for the first time, whereas the re-authentication protocols can be invoked when the users perform a horizontal HO (within the same network domain). These protocols provide an efficient method to protect user identity and reduce the burden on the authentication server (AS) during the sequential handovers. The results of the analytical model show that the proposed protocols achieve better performance than standard and other protocols. The reduction of handover cost, handover delay, and energy consumption in the proposed protocols reaches up to 22%, 44%, and 17%, respectively. In addition, the verification tools show that the proposed protocols are secure, dependable, and prevent all types of authentication and secrecy attacks.
New two types of semi-implicit viscosity iterations for approximating the fixed points of nonexpansive operators associated with contraction operators and applications
Authors: Xiong Ting-jian , Lan Heng-you
Published: May 2020

Motivated and inspired by the growing contribution with respect to iterative approximations from some researchers in the literature, we design and investigate two types of brand-new semi-implicit viscosity iterative approximation methods for finding the fixed points of nonexpansive operators associated with contraction operators in complete ${\operatorname{CAT}(0)}$CAT(0) spaces and for solving related variational inequality problems. Under some suitable assumptions, strong convergence theorems of the sequences generated by the approximation iterative methods are devised, and a numerical example and some applications to related variational inequality problems are included to verify the effectiveness and practical utility of the convergence theorems. Our main results presented in this paper do not only improve, extend and refine some corresponding consequences in the literature, but also show that the additional variational inequalities, general variational inequality systems and equilibrium problems can be solved via approximation of the iterative sequences. Finally, we provide an open question for future research.
Unique identification of a multi-layered fluid–solid medium
Authors: Cui Yanli , Li Xiliang , Qu Fenglong
Published: May 2020

This paper is concerned with the inverse scattering of time-harmonic acoustic plane waves by a multi-layered fluid–solid medium in the three dimensional space. We establish the global uniqueness in identifying the embedded penetrable solid obstacle, the surrounding fluid medium and its wave number from the acoustic far-field pattern for all incident plane waves at a fixed frequency. The proof depends on constructing different kinds of interior transmission problems in appropriate small domains and the a priori estimates derived for both the elastic wave fields in the embedded solid obstacle and the acoustic wave fields in the surrounding fluid medium.
Pretreatment HIV drug resistance in adults initiating antiretroviral therapy in China, 2017
Authors: Kang Rui-Hua , Liang Shu-Jia , Ma Yan-Ling , Liang Shu , Xiao Lin , Zhang Xin-Hui , Lu Hong-Yan , Xu Xiao-Qin , Luo Shui-Bin , Sun Xiao-Guang , Chen Lin , He Jian-Mei , Wu Guo-Hui , Liao Ling-Jie , Xing Hui , Shao Yi-Ming , Ruan Yu-Hua
Published: May 2020

Background

After the scale-up of antiretroviral therapy (ART) for HIV infected people, increasing numbers of patients have pretreatment drug resistance (PDR). In this study, the prevalence of PDR was evaluated in adults initiating antiretroviral therapy in China.

Methods

Blood samples were obtained from 1943 patients who initiated antiretroviral therapy (ART) in 2017 from 13 provinces or cities in China. Pol sequences were used to analyze drug resistance and construct transmission networks. Logistic regression model was used to estimate the potential factors associated with PDR.

Results

In total, 1711 eligible patients (76.0% male; 87.8% aged ≥ 25 years) were included, of which 117 (6.8%) had PDR. The highest rates of PDR were 12.2% in Liangshan Prefecture of Sichuan and 9.3 and 8.9% in Dehong and Lincang Prefecture of Yunnan. A multivariate logistic regression analysis revealed that PDR was significantly higher among intravenous drug users (adjusted Odds Ratio (aOR) = 2.64, 95%CI: 1.57–4.44) and individuals from Liangshan, Dehong, and Lincang (aOR = 2.04, 95%CI: 1.26–3.30). In total, 754 sequences were used to generate 164 transmission networks. Five transmission networks had two or three sequences containing the same mutations, two networks contained subjects from Liangshan, and one network contained subjects from Dehong.

Conclusions

Overall, the PDR prevalence was moderate, with a particularly high prevalence in areas with severe HIV epidemics. These results indicate the importance of continuous PDR monitoring in patients initiating antiretroviral therapy.
Brucellosis in China: history, progress and challenge
Authors: Jiang Hai , O’Callaghan David , Ding Jia-Bo
Published: May 2020

Brucellosis is a neglected zoonosis. It causes acute febrile illness and a potentially debilitating chronic infection in humans, and livestock infection has substantial socioeconomic impact. Over the past two decades, improvements have been made to better understand the various aspects of human and animal brucellosis. Meanwhile, especially in the developing world, immense challenges that remain in controlling and eradicating brucellosis are novel diagnostics tools and efficacious vaccines. Here, we will focus on the remarkable issues on epidemiological survey, as well as the priority and challenge of brucellosis in China. Brucellosis will be controlled with meaningful collaboration between local and public partnerships effectively applying a One Health framework.
Tectonic plates in 3D mantle convection model with stress-history-dependent rheology
Authors: Miyagoshi Takehiro , Kameyama Masanori , Ogawa Masaki
Published: May 2020

Plate tectonics is a key feature of the dynamics of the Earth’s mantle. By taking into account the stress-history-dependent rheology of mantle materials, we succeeded in realistically producing tectonic plates in our numerical model of mantle convection in a three-dimensional rectangular box. The calculated lithosphere is separated into several pieces (tectonic plates) that rigidly move. Deformation of the lithosphere caused by the relative motion of adjacent plates is concentrated in narrow bands (plate margins) where the viscosity is substantially reduced. The plate margins develop when the stress exceeds a threshold and the lithosphere is ruptured. Once formed, the plate margins persist, even after the stress is reduced below the threshold, allowing the plates to stably move over geologic time. The vertical component of vorticity takes a large value in the narrow plate margins. Secondary convection occurs beneath old tectonic plates as two-dimensional rolls with their axes aligned to the direction of plate motion. The surface heat flow decreases with increasing distance from divergent plate margins (ridges) in their vicinity in the way the cooling half-space model predicts, but it tends towards a constant value away from ridges as observed for the Earth because of the heat transport by the secondary convection.
A review of epileptic seizure detection using machine learning classifiers
Authors: Siddiqui Mohammad Khubeb , Morales-Menendez Ruben , Huang Xiaodi , Hussain Nasir
Published: May 2020

Epilepsy is a serious chronic neurological disorder, can be detected by analyzing the brain signals produced by brain neurons. Neurons are connected to each other in a complex way to communicate with human organs and generate signals. The monitoring of these brain signals is commonly done using Electroencephalogram (EEG) and Electrocorticography (ECoG) media. These signals are complex, noisy, non-linear, non-stationary and produce a high volume of data. Hence, the detection of seizures and discovery of the brain-related knowledge is a challenging task. Machine learning classifiers are able to classify EEG data and detect seizures along with revealing relevant sensible patterns without compromising performance. As such, various researchers have developed number of approaches to seizure detection using machine learning classifiers and statistical features. The main challenges are selecting appropriate classifiers and features. The aim of this paper is to present an overview of the wide varieties of these techniques over the last few years based on the taxonomy of statistical features and machine learning classifiers—‘black-box’ and ‘non-black-box’. The presented state-of-the-art methods and ideas will give a detailed understanding about seizure detection and classification, and research directions in the future.
Epileptic spikes detector in pediatric EEG based on matched filters and neural networks
Authors: Mera-Gaona Maritza , López Diego M. , Vargas-Canas Rubiel , Miño María
Published: May 2020

The electroencephalogram (EEG) is a tool for diagnosing epilepsy; by analyzing it, neurologists can identify alterations in brain activity associated with epilepsy. However, this task is not always easy to perform because of the duration of the EEG or the subjectivity of the specialist in detecting alterations.

Aim

To propose the use of an epileptic spike detector based on a matched filter and a neural network for supporting the diagnosis of epilepsy through a tool capable of automatically detecting spikes in pediatric EEGs.

Results

Automatic detection of spikes from an EEG waveform involved the creation of an epileptic spike template. The template was used in order to detect spikes by using a matched filter, and each spike detected was confirmed by a Neural Network to improve sensitivity and specificity. Thus, the detector developed achieved a sensitivity of 99.96% which is better than the range of what has been reported in the literature (82.68% and 94.4%), and a specificity of 99.26%, improving the specificity found in the best-reviewed studies.

Conclusions

Considering the results obtained in the evaluation, the solution becomes a promising alternative to support the automatic identification of epileptic spikes by neurologists.
School of golden touch? A study of school effectiveness in improving student academic performance
Authors: Xie Guihua , Zhang Yangyang
Published: May 2020

This paper explores whether different schools exhibit varying levels of effectiveness in improving student academic performance and, if so, which factors might affect school effectiveness. Using data from the China Education Panel Survey (CEPS), this research examines the influence of various school features on dynamic changes in middle school student academic performance. It finds that schools of higher socioeconomic status, with more academically proficient students and with more complete school facilities, are more effective in improving students’ academic performance. Meanwhile, the work shows that local community school rankings, the average quality of school teachers, and academically related practices do not have a significant impact on a school’s effectiveness. In summary, this research extends previous studies on student education attainment from a focus on student performance to a focus on changes in performance. It illustrates the essential roles played by the capacities of enrolled students and of individual/aggregated family socioeconomic status in improving student academic performance.
Awareness of a mesenteric mass as a common manifestation of ileal neuroendocrine tumor
Authors: Kasai Yosuke , Nakakura Eric K.
Published: May 2020

Omori et al. reported a case of multiple liver metastases originating from synchronous double cancer of “primary mesenteric neuroendocrine tumor” and rectal cancer. However, the “primary mesenteric neuroendocrine tumor” might be a misrecognition of mesenteric metastasis from ileal neuroendocrine tumor. Ileal neuroendocrine tumor is extremely rare in Japan. Herein, we aim to describe the characteristics of ileal neuroendocrine tumor and mesenteric mass as its common manifestation in reference to their reported case.
A Pragmatic Approach to Resolving Technological Unfairness: the Case of Nike’s Vaporfly and Alphafly Running Footwear
Authors: Dyer Bryce
Published: May 2020

Background

Technology is often introduced into sport to facilitate it or to improve human performance within it. On occasion, some forms of novel technology require regulation or prevention entirely to ensure that a sport remains fair and accessible. Recently, the Nike Vaporfly and Alphafly shoes have received some concerns over their appropriateness for use in competitive distance running.

Methods

This paper evaluates the use of these shoes against an existing framework for sports technology discourse and adopts a pragmatic approach to attempt to resolve them.

Results

It is proposed that the three concerns regarding cost, access and coercion cannot be ruled out but likely remain short-term issues. As a result, it is proposed that these running shoes are acceptable forms of technology but that ongoing vigilance will be required as such technologies develop further in the future.

Conclusions

The Nike Vaporfly/Alphafly shoes do push the perceived acceptability of running shoes to the limits of the current sports regulations. However, the alleged gains have not manifested themselves to a level that could be considered excessive when reviewing historical performances or when evaluated against a set of well-cited criteria. The sport will need to adopt a stance of ongoing vigilance as such technologies continue to develop or be optimised in the future.
Evaluation of pre-hospital use of a valsalva assist device in the emergency treatment of supraventricular tachycardia [EVADE]: a randomised controlled feasibility trial
Authors:   EVADE study SWASFT collaborators, Appelboam Andrew , Green Jonathan , Ewings Paul , Black Sarah
Published: May 2020

Background

The valsalva manoeuvre is an internationally recommended initial treatment for supraventricular tachycardia (SVT). The pre-hospital use of a valsalva assist device, to help deliver this manoeuvre, could improve cardioversion rates and reduce the need for patients to attend hospital.

Methods

We conducted a randomised controlled feasibility trial comparing ambulance clinician use of a valsalva assist device versus standard care to treat adult patients presenting to an ambulance service in the south west of England. Eligible consenting participants were randomised 1:1 to device or standard care with trial procedures mirroring a proposed definitive trial.

Feasibility was assessed upon ambulance clinician and participant recruitment rates and feedback, data completeness and potential future primary outcome rates.

Results

Over a 6 months period (1 July to 31 December 2018), 276 (23%) of 1183 eligible ambulance clinicians were trained and they recruited 34 participants; approximately 10% of patients presenting with suspected SVT during that time. Seventeen participants were randomised to each arm and all underwent their allocated valsalva strain method. All trial data and 63/68 (93%) of pre and post-valsalva ECGs were available. Seven (21%) participants had ineligible initial rhythms on retrospective expert ECG review. Valsalva assist device use was associated with cardioversion and non-conveyance in 4 (24%) and 2 (12%) participants respectively. No participants assigned to standard care were cardioverted and all were conveyed. Participant feedback highlighted the challenges of retaining trial information during an SVT attack.

Conclusions

The trial achieved efficient clinician training, randomisation and data collection, and there was an encouraging effect signal associated with device use. However, trial design changes should be considered to address the relatively small proportion of eligible patients recruited and challenges identified with consent and confirmation of cardioversion as a primary outcome.

Trial registration

The trial was registered withClinicalTrials.gov(NCT03514628) on 2 May 2018.
Changes in young women’s contraceptive use in the Netherlands: findings from three sex under the age of 25 surveys
Authors: Marra Elske , Meijer Suzanne , de Graaf Hanneke
Published: May 2020

Prevention of unintended pregnancy among adolescents and young adults under 25 years is pivotal from an individual as well as societal perspective. In the USA, the use of long-acting reversible contraceptive (LARC) has been shown to increase, with no or little change in the use of short-acting reversible contraceptive (SARC). We assessed trends in no contraceptive, SARC, and LARC use by young women, aged between 12 and 25 years, and differences in trends within demographic groups (age, religion, ethnic background, and educational level) among these young women in the Netherlands. Data of sexually active young women aged 12–25 years from three cross-sectional representative surveys, 2005, 2012, and 2017, were used for this study. In total, 11,229 Dutch young women were included with a median age of 20 years (interquartile range 18–23 years). Overall, the proportion of young women using SARC decreased significantly between 2005 and 2017 from 88 to 76%. LARC use increased significantly between 2005 and 2017 from 3 to 16%. These trends varied by religious groups and educational level, emphasizing potential for tailored preventative measures for these groups. A shift towards LARC use might eventually lead to a further decrease in unwanted pregnancy and potentially abortion because of the lower risk of user errors.
Biotechnological and chemical analysis of Egyptian Diospyros kaki L. cv. Costata grown in Egypt
Authors: El-Hawary Seham Salah El-din , Tadros Soad Hanna , Taha Hussein , Abdelmohsen Mona , Nazif Naglaa Mohamed , El Sheikh Iman , El-Nasr Medhat Seif
Published: May 2020

Background

Diospyros kakiL. is considered one of the most important economical medicinal plant in Chinese herbal medicine belonging to family Ebenaceae as it contains varied secondary metabolites and used in treatment of many diseases. For there is an efficient and promising protocol for in vitro propagation ofDiospyros kakiL. cv. Costata was establishedDiospyros kakiL. cv. Costata although it is difficult to initiate it in sterilized artificial media due to the browning of tissue caused by oxidation of phenolics. An efficient sterilizing method for leaf and internode explants was obtained by using 0.2% mercuric chloride (Hg2Cl2) for 5 min. Woody plant medium(WPM) supplemented with 2 mg/l zeatin (Zt) + 5 mg/l isopentenyl adenine (2 iP). Calli were induced on Murashige and Skoog medium (MS) augmented with 10 mg/l Zt + 10 mg/l indole-3-acetic acid (IAA) + 500 mg/l polyvinylpyrolidone (PVP) + 0.1 mg/l thiamine HCL from internode explants. However, the regeneration efficiency was obtained with ½ MS-media fortified with 1 mg/l Zt + 2 mg/l IAA + 4 mg/l benzylaminopurine (BAp) + 0.5 g/l PVP from internode calli explants.

Results

The highest amounts of scopoletin 57.08, 26.42, and 25.30 (μg/g DW) were detected using reversed phase of high-performance liquid chromatography (RP-HPLC) in leaves extract of intact plant followed by regenerated and calli cultures of internod explants, respectively.

Conclusion

This study is the first record for in vitro propagation and production of secondary metabolites fromDiospyros kakiL. using biotechnology techniques. Chemical anaysis were carried out using HPLC technique.
A reproducible reference point for the common peroneal nerve during surgery at the posterolateral corner of the knee: a cadaveric study
Authors: Teo Hong Lee Terry , Ang Ke Xin Magneline , Loh Sir Young James
Published: May 2020

Background

This is an experimental study conducted to assess whether the fibular head is a reliable reference point to identify the position of the common peroneal nerve at the posterolateral corner of the knee.

Materials and methods

Twelve cadaveric knees were dissected through the lateral approach. The common peroneal nerve was identified and traced. The location where the common peroneal nerve crossed the posterior border of the biceps femoris and the posterior border of the fibular neck were designated as points B and N, respectively. The tip of the fibular head was designated F. Distances FB and FN were measured and the triangular area FBN was calculated at various degrees of knee flexion.

Results

During knee motion, distance FN showed minimal change and was not affected by variation in degrees of knee flexion (p = 0.131). Distance FB and distance BN were affected by variation in degrees of knee flexion (p < 0.001). Triangular area FBN increased in size up to 60° of knee flexion measuring 621.22 mm2 and subsequently decreased with further knee flexion.

Conclusion

The common peroneal nerve can consistently be found at approximately 20.7 ± 1 mm on the fibular neck with respect to the tip of the fibular head. The tip of the fibular head is a consistent landmark that can be used to predict the position of the exit point of the common peroneal nerve at the posterolateral corner of the knee.
Efforts towards a low-temperature-sensitive physics package for vapor cell atomic clocks
Authors: Hao Qiang , Xue Wenxiang , Xu Feng , Wang Kemu , Yun Peter , Zhang Shougang
Published: May 2020

Strong environmental dependence is an intractable problem for vapor cell clocks, for which the high-temperature sensitivity of the physics package is considered one of the dominant reasons. In this paper, we report the design and realization of a low-temperature-sensitive physics package for vapor cell clocks. The physics package comprises three layers of magnetic shields, three layers of heating ovens, and the cavity-cell assembly. The cavity-cell assembly employs a compact magnetron-type cavity and a Rb vapor cell sealed with N2-Ar mixed buffer gas. The dependence of the clock frequency on temperature fluctuation is evaluated to be 2 × 10−11/°C. In pursuit of the stable temperature, a three-stage temperature regulator is implemented on the physics package. It adopts a combination of open and
closed-loop control to address the problem of significant thermal coupling between the heating ovens. Under a laboratory environment, the measured Hadamard deviation of the temperature variation is 4 × 10−5 °C in 1 day of averaging.
Assessment of apolipoprotein B/apolipoprotein A-I ratio in non-ST segment elevation acute coronary syndrome patients
Authors: Galal Haitham , Samir Ayman , Shehata Mohamed
Published: May 2020

Background

The apolipoprotein B/apolipoprotein A-I ratio was shown to be strongly related to the risk of myocardial infarction in several large-scale studies. The current study aimed at exploring the diagnostic and short-term prognostic values of apolipoprotein B/apolipoprotein A-I ratio in patients presenting with non-ST segment elevation acute coronary syndrome. One hundred patients with non-ST segment elevation acute coronary syndrome were prospectively enrolled, in addition to a matched group of 100 patients with chronic stable angina. Serum levels of total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, and apolipoproteins B and A-I were quantified in both groups. Patients with non-ST segment elevation acute coronary syndrome underwent coronary angiography.

Results

The mean age of the study population was 57 ± 6 years, 65% being males. The non-ST segment elevation acute coronary syndrome group showed significantly unfavorable lipid profile parameters, including apolipoprotein B/apolipoprotein A-I ratio. Higher apolipoprotein B/apolipoprotein A-I ratio was associated with more coronaries showing significant stenosis and more complex lesion morphology. Receiver operating characteristic curve analysis reached an optimal cut-off value of 0.93 for diagnosis of non-ST segment elevation acute coronary syndrome (sensitivity 70% and specificity 88%) and 0.82 for predicting the presence of multi-vessel disease (sensitivity 90% and specificity 97%).

Conclusion

Apolipoprotein B/apolipoprotein A-I ratio is a useful tool of risk assessment in patients presenting with non-ST segment elevation acute coronary syndrome including prediction of coronary multivessel affection.

Apolipoprotein B/apolipoprotein A-I ratio was shown to be strongly related to risk of myocardial infarction. Higher ratios of apolipoprotein B/apolipoprotein A-I were recorded in NSTE-ACS patients (versus stable angina patients). Higher apolipoprotein B/apolipoprotein A-I ratios were associated with more diseased coronaries and complex lesions. Apolipoprotein B/apolipoprotein A-I ratio is a useful tool for acute risk assessment in cardiac ischemic patients.
Enhancement of in vivo hypoglycemic effect of gliclazide by developing self-microemulsifying pellet dosage form
Authors: Patel Hetal , Pandey Niharika , Patel Bhoomi , Ranch Ketan , Bodiwala Kunjan , Vyas Bhavin
Published: May 2020

Background

The present research was aimed to develop a self-microemulsifying drug delivery system (SMEDDS) pellet to increase the dissolution rate and in vivo hypoglycemic effect of gliclazide. Gliclazide belongs to BCS class 2 and it exhibits dissolution rate-limited absorption. Thus, dissolution enhancement of gliclazide from its dosage form is a prime requirement to achieve a better therapeutic effect. The solubility of gliclazide was estimated in oils, surfactants, and co-surfactants. A most effective self-emulsification region was identified using pseudoternary phase diagrams. The optimized liquid SMEDDS gliclazide formulation was converted to SMEDDS pellets using the extrusion-spheronization technique. The in vitro release and hypoglycemic effect of SMEDDS was compared with the marketed product.

Results

The optimized liquid gliclazide SMEDDS formulations contained mixtures of Tween 80 and PEG 400 and Capmul MCM C8. The gliclazide SMEDDS in liquid preparation quickly formed a fine oil-in-water microemulsion having a globule size of 31.50 nm. In vitro release of gliclazide from SMEDDS pellets was 100.9% within 20 min. SMEDDS pellets exhibited a significant reduction in plasma glucose levels in albino mice compared to the marketed product.

Conclusion

The results indicated that SMEDDS pellets could be effectively used to improve the oral delivery of gliclazide.
A phase II study to evaluate the need for > two doses of nivolumab + ipilimumab combination (combo) immunotherapy.
Authors: Postow Michael A. , Goldman Debra A , Shoushtari Alexander Noor , Warner Allison Betof , Callahan Margaret K. , Momtaz Parisa , Naito Ellesa , Eton Omar , Nair Suresh , Wolchok Jedd D. , Panageas Katherine , Chapman Paul B.
Published: May 2020

10003

Background: Standard of care nivolumab (nivo) + ipilimumab (ipi) combo immunotherapy is given for 4 doses in patients (pts) with unresectable stage III/IV melanoma. Whether 4 doses are needed is questionable as retrospective data suggest pts treated with <4 doses of combo due to toxicity can have durable benefit. No prospective trials have evaluated the efficacy of intentionally giving <4 doses of combo in unresectable stage III/IV melanoma. Methods: In this phase 2, multicenter clinical trial (n=60), pts with unresectable stage III/IV melanoma received 2 doses of nivo (1mg/kg) + ipi (3mg/kg) followed by a CT scan at week 6. Pts with complete (CR) or partial responses (PR) by RECIST 1.1 or stable disease without an increase in total measurable tumor burden had protocol defined early favorable anti-tumor effect (FATE) and ceased combo, transitioning to maintenance nivo. Pts without FATE at week 6 received the standard third and fourth doses of combo followed by maintenance nivo. The primary endpoint was response rate by RECIST 1.1 at week 12. Secondary endpoints included additional efficacy assessments and safety. Results: 41 pts (68%) had FATE at week 6. The best overall response rates (CR + PR) by RECIST at week 12 or any time afterwards were 48% (95% CI: 35.2-61.6%) and 53% (95% CI: 40.0-66.3%), respectively. 18%, 58%, 12%, 10% had 1, 2, 3, 4 doses of combo, respectively. With a median follow-up of 11 months, any grade treatment-related toxicity occurred in 100% (57% grade 3-4) of pts. Three pts died due to treatment-related toxicity (2 myocarditis, 1 possible adrenal insufficiency). Among the 19 pts without FATE at week 6 and not selected to de-escalate combo after dose 2, no pts ultimately responded with ongoing combo dosing. Conclusions: The first 2 doses of nivo + ipi appear to drive combo’s response efficacy and toxicity. Early radiographic imaging at week 6 may be able to identify pts who do not respond to combo dosing beyond dose 2. Randomized studies are planned to evaluate 1 dose of combo to see if efficacy is maintained with reduced toxicity. Clinical trial information: NCT03122522.