bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of a wideband square slot bandpass frequency‐selective surface using phase range analysis
Authors: Singh Chitra , Jha Kumud R. , Sharma Satish K. , Jibran Zahoor A. Pandit , Singh Ghanshyam
Published: January 2020

This article presents the design of a wideband bandpass frequency‐selective surface (FSS). The structure is designed using the analysis of the generalized scattering matrix (GSM)‐based transmission phase range. A relationship between the transmission phase range and the bandpass fractional bandwidth (FBW) is developed. The analysis reveals that the FBW of the FSS unit‐cell is proportional to the phase range. Based on the interpretation of results, a design curve has been drawn, and using this curve, a simple square slot FSS on a low‐cost FR‐4 substrate has been fabricated and measured. Using the design curve, a 53% FBW has been predicted. The simulated results show a 52% FBW with the 3.52‐GHz center frequency (fo). The response for the transverse electric (TE) and transverse magnetic (TM) modes has been measured. The structure has a bandpass FBW equal to 50% and 53.3% in TE and TM modes, respectively. The method presented in this article may be used to increase the bandpass response of different FSS topologies.
Bioengineered three‐dimensional transparent eggshell as a chicken embryo experimentation platform for biomedical research
Authors: Ishak Noreen , Chan Marcus , Ang Sook C. , Cheung Christine , Teoh Swee‐Hin
Published: January 2020

The chicken embryo is widely used as an experimental model in the areas of regenerative medicine, tumor biology, and angiogenesis. Eggshell opacity and rigidity present restricted three‐dimensional (3D) viewing and accessibility to the embryo and its circulatory network despite egg windowing. The ability to engineer an eggshell, which eliminates the opacity yet provides 3D access for manipulation is beneficial and would potentially make it enticing for the use of chicken embryo as a cheaper alternative vertebrate model. Here, we present the feasibility of fabricating a morphologically analogous transparent chicken eggshell made of polydimethylsiloxane using a biaxial rotation computer‐controlled bioreactor to achieve uniform thickness. By culturing chicken embryo in the bioengineered eggshell, we demonstrated success in meeting developmental milestones and its practicality as an experimental platform by visualizing both embryo and vasculature development using common laboratory imaging tools. Although the viability of the embryo in the bioengineered eggshell was lower than in the normal egg, this was attributed to the absence of calcium source. The bioengineered eggshell, in its initial stage of development, provides a platform to be used to investigate beyond gross observations of the embryo and vascular network in 3D optical clarity and its imaging capabilities has the potential to be extended to other imaging modalities. We have developed a transparent ex ovo eggshell, biomimicking the elliptical geometry to address the lack of 3D optical clarity contributed by the eggshell opacity. This retains the natural shape that may support the development of the chicken embryo and allows easy access to the embryo, its circulatory system and respective organ development in far reaching applications.
Review of the safety of application of cosmetic products containing parabens
Authors: Matwiejczuk Natalia , Galicka Anna , Brzóska Małgorzata M.
Published: January 2020

Cosmetics are a source of lifetime exposure to various substances including parabens, being the most popular synthetic preservatives. Because the use of cosmetics shows an increasing trend and some adverse health outcomes of parabens present in these products have been reported, the present review focused on the safety of dermal application of these compounds. Special attention has been paid to the absorption of parabens and their retention in the human body in the intact form, as well as to their toxicological characteristics. Particular emphasis has been placed on the estrogenic potential of parabens. Based on the available published data of the concentrations of parabens in various kinds of cosmetics, the average ranges of systemic exposure dose (SED) for methylparaben, ethylparaben, propylparaben, and butylparaben have been calculated. Safety evaluations [margin of safety (MoS)] for these compounds, based on their aggregate exposure, have also been performed. Moreover, evidence for the negative impact of methylparaben on skin cells has been provided, and the main factors that may intensify dermal absorption of parabens and their impact on the skin have been described. Summarizing, the use of single cosmetics containing parabens should not pose a hazard for human health; however, using excessive quantities of cosmetic preparations containing these compounds may lead to the development of unfavorable health outcomes. Due to the real risk of estrogenic effects, as a result of exposure to parabens in cosmetics, simultaneous use of many cosmetic products containing these preservatives should be avoided.
miR‐133a‐3p/FOXP3 axis regulates cell proliferation and autophagy in gastric cancer
Authors: Li Jia‐Peng , Zhang Hui‐Min , Liu Mei‐Jun , Xiang Yuan , Li Hui , Huang Feng , Li Han‐Han , Dai Zhou‐Tong , Gu Chao Jiang , Liao Xing‐Hua , Zhang Tong‐Cun
Published: January 2020

Although many methods and new therapeutic drugs have been developed, the overall survival rate and long‐term survival rate of patients with gastric cancer (GC) are still not satisfactory. In this study, we investigated the effects of microRNA miR‐133a‐3p and transcription factor FOXP3 on proliferation and autophagy of GC cells and their interactions. Our results showed that knockdown of FOXP3 increased the proliferation and autophagy of GC cells. The relationship between FOXP3 and autophagy has not been reported previously. In addition, FOXP3 could directly bind the promoter region of TP53 and inhibit its expression. miR‐133a‐3p increased the proliferation and autophagy via decreasing the protein level of FOXP3 by targeting its 3′‐UTR. Our research provides new insights into the development of GC and provides new ideas and theoretical basis for the clinical treatment of GC and the development of new drug targets.
Long noncoding RNA LINC01234 promoted cell proliferation and invasion via miR‐1284/TRAF6 axis in colorectal cancer
Authors: Liao Xin , Zhan Wei , Zhang Jiandong , Cheng Zhongsheng , Li Lianghe , Tian Tian , Yu Lei , Li Rui
Published: January 2020

Colorectal cancer is one of the most common and leading malignancies globally. Long noncoding RNAs (lncRNAs) function as potentially critical regulator in colorectal cancer. LINC01234, a novel lncRNA in tumor biology, regulates the progression of various tumors. However, the tumorigenic mechanism of LINC01234 in colorectal cancer is still unclear. This study was performed with the aim to prospectively investigate clinical significance, effect, and mechanism of lncRNA LINC01234 in colorectal cancer. First, we found that LINC01234, localized in the cytoplasm, was increased in both colorectal cancer cell lines and tissues. Subsequent functional assays suggested LINC01234 knockdown suppressed cell proliferation, migration, and invasion of colorectal cancer cells, while blocked cell cycle and induced cell apoptosis. Moreover, we identified that miR‐1284 was target of LINC01234, we further demonstrated a negative correlation with LINC01234 in colorectal cancer tissues and cells. Furthermore, miR‐1284 targeted and suppressed tumor necrosis factor receptor–associated factor 6 (TRAF6). Loss‐of‐function assay revealed that LINC01234 silencing suppressed colorectal cancer progression through inhibition of miR‐1284. In vivo subcutaneous xenotransplanted tumor model indicated LINC01234 knockdown inhibited in vivo tumorigenic ability of colorectal cancer via downregulation of TRAF6. Collectively, this study clarified the biological significance of LINC01234/miR‐1284/TRAF6 axis in colorectal cancer progression, providing insights into LINC01234 as novel potential therapeutic target for colorectal cancer therapeutic from bench to clinic.
Downregulation of microRNA‐101‐3p participates in systemic lupus erythematosus progression via negatively regulating HDAC9
Authors: Sun Huanxia , Guo Fei , Xu Liming
Published: January 2020

This study aimed to investigate the mechanism of microRNA‐101‐3p (miR‐101‐3p) on the progression of systemic lupus erythematosus (SLE). The human peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples of SLE patients and healthy individuals, followed by cell culture and transfection. Moreover, the flow cytometry assay, quantitative real‐time reverse‐transcription polymerase chain reaction, Western blot, and enzyme‐linked immunoassay were used to assess the effect of miR‐101‐3p on PBMCs. Bioinformatics analysis was conducted to predict the putative target gene of miR‐101‐3p, luciferase reporter gene assay, and RNA pull‐down assay were applied to verify the interaction between them. Compared with healthy individuals, the expression level of miR‐101‐3p in PBMCs of SLE patients was significantly decreased, whereas interleukin (IL)‐17A, IL‐6, and interferon (IFN)‐γ were remarkably increased (all P < .001). Correlation analyses showed that there were negative correlations between miR‐101‐3p and IL‐17A, IL‐6 and IFN‐γ. The expression level of miR‐101‐3p in PBMCs of SLE patients was positively correlated with C3 expression (rs = .4075; P = .0229), while negatively associated with erythrocyte sedimentation rate (ESR) (rs = −.4238; P = .0175) and IgG expression (rs = −.4949; P = .0047). Overexpression of miR‐101‐3p could inhibit the differentiation of CD4 + T cells into Th17 lineage. Histone deacetylase 9 (HDAC9) was identified as a potential target gene of miR‐101‐3p. Furthermore, HDAC9 abolished the effect of miR‐101‐3p on Th17 cell differentiation and IL‐17A expression in SLE. In conclusion, downregulated miR‐101‐3p in PBMCs of SLE patients inhibited Th17 cell differentiation by directly targeting HDAC9, which could be used as a novel therapeutic therapy for SLE treatment.
Targeting Wnt/β‐catenin and PI3K/Akt/mTOR pathways in T‐cell acute lymphoblastic leukemia
Authors: Evangelisti Cecilia , Chiarini Francesca , Cappellini Alessandra , Paganelli Francesca , Fini Milena , Santi Spartaco , Martelli Alberto M. , Neri Luca M. , Evangelisti Camilla
Published: January 2020

T‐cell acute lymphoblastic leukemia (T‐ALL) is an aggressive hematological disorder that results from the clonal transformation of T‐cell precursors. Phosphatidylinositol 3‐kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) and canonical Wnt/β‐catenin signaling pathways play a crucial role in T‐cell development and in self‐renewal of healthy and leukemic stem cells. Notably, β‐catenin is a transcriptional regulator of several genes involved in cancer cell proliferation and survival. In this way, aberrations of components belonging to the aforementioned networks contribute to T‐ALL pathogenesis. For this reason, inhibition of both pathways could represent an innovative strategy in this hematological malignancy. Here, we show that combined targeting of Wnt/β‐catenin pathway through ICG‐001, a CBP/β‐catenin transcription inhibitor, and of the PI3K/Akt/mTOR axis through ZSTK‐474, a PI3K inhibitor, downregulated proliferation, survival, and clonogenic activity of T‐ALL cells. ICG‐001 and ZSTK‐474 displayed cytotoxic effects, and, when combined together, induced a significant increase in apoptotic cells. This induction of apoptosis was associated with the downregulation of Wnt/β‐catenin and PI3K/Akt/mTOR pathways. All these findings were confirmed under hypoxic conditions that mimic the bone marrow niche where leukemic stem cells are believed to reside. Taken together, our findings highlight potentially promising treatment consisting of cotargeting Wnt/β‐catenin and PI3K/Akt/mTOR pathways in T‐ALL settings.
Defining biological stress and stress responses based on principles of physics
Authors: Kültz Dietmar
Published: January 2020

Stress represents a multi‐faceted force that is central for the evolution of life. Organisms evolve while adapting to stress and stressful contexts often represent selective bottlenecks. To understand stress effects on biological systems and corresponding coping strategies it is imperative to properly define stress and the resulting strain that triggers compensatory responses in cells and organisms. Here I am deriving such definitions for biological systems based on principles that are established in physics. The relationship between homeostasis of critical biological variables, the elastic limit, the cellular stress response (CSR), cellular homeostasis response (CHR), system dysregulation, and the breaking point (death of the system) is outlined. Dysregulation of homeostatic set‐points of biological variables perturbs the functional properties of the system, shifting them out of the evolutionarily optimized range. Such shifts are accompanied by elevated rates of macromolecular damage, which represents a nonspecific signal for induction of a universal response, the CSR. The CSR complements the CHR in re‐establishing homeostasis of the system as a whole. Moreover, the CSR is essential for coping with suboptimal conditions while the system is in a dysregulated state and for removing excessive damage that accumulates during such periods. The extreme complexity of biological systems and their emergent properties often necessitate monitoring stress effects on many biological variables simultaneously to properly deduce stress effects on the system as a whole. Therefore, increased utilization of systems biology (omics) approaches for characterizing cellular and organismal stress responses facilitates the reductionist dissection of biological stress response mechanisms.
Development of two‐dimensional gas chromatography (GC×GC) coupled with Orbitrap‐technology‐based mass spectrometry: Interest in the identification of biofuel composition
Authors: Hung Nguyen Viet , Mohabeer Chetna , Vaccaro Marie , Marcotte Stéphane , Agasse‐Peulon Valérie , Abdelouahed Lokmane , Taouk Bechara , Cardinael Pascal
Published: January 2020

Comprehensive gas chromatography (GC) has emerged in recent years as the technique of choice for the analysis of volatile and semivolatile compounds in complex matrices. Coupling it with high‐resolution mass spectrometry (MS) makes a powerful tool for identification and quantification of organic compounds. The results obtained in this study showed a significant improvement by using GC×GC‐EI‐MS in comparison with GC‐EI‐MS; the separation of chromatogram peaks was highly improved, which facilitated detection and identification. However, the limitation of Orbitrap mass analyzer compared with time‐of‐flight analyzer is the data acquisition rate; the frequency average was about 25 Hz at a mass resolving power of 15.000, which is barely sufficient for the proper reconstruction of the narrowest chromatographic peaks. On the other hand, the different spectra obtained in this study showed an average mass accuracy of about 1 ppm. Within this average mass accuracy, some reasonable elemental compositions can be proposed and combined with characteristic fragment ions, and the molecules can be identified with precision. At a mass resolving power of 7.500, the scan rate reaches 43 Hz and the GC×GC‐MS peaks can be represented by more than 10 data points, which should be sufficient for quantification. The GC×GC‐MS was also applied to analyze a cellulose bio‐oil sample. Following this, a highly resolved chromatogram was obtained, allowing EI mass spectra containing molecular and fragment ions of many distinct molecules present in the sample to be identified.
Performance Enhancement of Array Antennas using Metasurface Superstrates
Authors: Hakim Bandar , Kumar Ashwani , Yousaf Jawad , Sheikh Muntasir , Rmili Hatem , Mittra Raj
Published: January 2020

This work presents a novel design of a high gain circularly polarized (CP) crossed‐bowtie shaped antenna with cloverleaf arms which exhibits a wideband impedance match as well as 3dB axial ratio bandwidths. The designed wideband antenna is realized by employing a low‐cost phase shifting mechanism that uses a Metasurface (MTS) superstrate which is placed above the radiating surface of the antenna. A design chart is developed for the determination of the required phase variation based on the distance between MTS and the antenna radiator. Next, the concept of MTS placement above the antennas is extended to the cases of 3x3 and 5x5 cloverleaf‐shaped bowtie antenna arrays, with the goal of improving the gain and sidelobe levels (SLLs). The study includes a systematic analysis of the variation in gain and SLL of CP antenna arrays as we change the number of elements of the superstrate.
Functional analysis of a novel mutation in the TIMM8A gene that causes deafness‐dystonia‐optic neuronopathy syndrome
Authors: Neighbors Addison , Moss Tonya , Holloway Lynda , Yu Seok‐Ho , Annese Fran , Skinner Steve , Saneto Russell , Steet Richard
Published: January 2020

Background

The rare, X‐linked neurodegenerative disorder, Mohr–Tranebjaerg syndrome (also called deafness‐dystonia‐optic neuronopathy [DDON] syndrome), is caused by mutations in the TIMM8A gene. DDON syndrome is characterized by dystonia, early‐onset deafness, and various other neurological manifestations. The TIMM8A gene product localizes to the intermembrane space in mitochondria where it functions in the import of nuclear‐encoded proteins into the mitochondrial inner membrane. Frameshifts or premature stops represent the majority of mutations in TIMM8A that cause DDON syndrome. However, missense mutations have also been reported that result in loss of the TIMM8A gene product.

Methods

We report a novel TIMM8A variant in a patient with DDON syndrome that alters the initiation codon and employed functional analyses to determine the significance of the variant and its impact on mitochondrial morphology.

Results

The novel base change in the TIMM8A gene (c.1A>T, p.Met1Leu) results in no detectable protein and a reduction in TIMM8A transcript abundance. We observed a commensurate decrease in the steady‐state level of the Tim13 protein (the binding partner of Tim8a) but no decrease in TIMM13 transcripts. Patient fibroblasts exhibited elongation and/or increased fusion of mitochondria, consistent with prior reports.

Conclusion

This case expands the spectrum of mutations that cause DDON syndrome and demonstrates effects on mitochondrial morphology that are consistent with prior reports.
The effect of thymus transplantation on donor‐specific chimerism in the rat model of composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation
Authors: Zor Fatih , Bozkurt Mehmet , Cwykiel Joanna , Karagoz Huseyin , Kulahci Yalcin , Uygur Safak , Siemionow Maria
Published: January 2020

Introduction

Research on tolerance has proven that development of donor‐specific chimerism (DSC) may accompany tolerance induction in vascularized composite allotransplantation (VCA). In this study, we aimed to determine the effect of thymus transplantation on the induction of DSC in rat VCA model of osseomusculocutaneous sternum (OMCS) and osseomusculocutaneous sternum and thymus (OMCST) allotransplantation.

Materials and Methods

A total of 20 Lewis‐Brown Norway and Lewis rats, 5–6 weeks old, weighting between 120 and 150 g, were used in the study. OMCS (n = 5) and OMCST (n = 5) allografts were harvested from Lewis‐Brown Norway donors (RT1l + n) based on the common carotid artery and external jugular vein, and a heterotopic transplantation was performed to the inguinal region of the Lewis (RT1l) recipients under cyclosporine A monotherapy (16 mg/kg) protocol tapered to 2 mg/kg and maintained for the duration of the study. The peripheral blood chimerism levels (T‐cell, B‐cell, and monocyte/granulocyte/dendritic cell–MGDC populations) were evaluated at days 7, 14, 35, 63, 100, and 150 posttransplant by flow cytometry. At Day 150, thymus, spleen, and liver samples were assessed by polymerase chain reaction (PCR) in the presence of DSC.

Results

Total chimerism level increased in both OMCST and OMCS groups at all time points. At 150 days posttransplant, chimerism in OMCST group was significantly higher (12.91 ± 0.16%) than that in OMCS group (8.89 ± 0.53%%, p < .01), and PCR confirmed the presence of donor‐derived cells in the liver and spleen of all OMCST recipients and in one liver sample and two spleen samples in OMCS recipients without thymus transplant.

Conclusions

This study confirmed the direct effects of thymus transplantation on the induction and maintenance of DSC in T‐cell, B‐cell, and MGDC populations. These results confirm correlation between thymus transplantation and DSC induction.
Cigarette smoke induces the pyroptosis of urothelial cells through ROS/NLRP3/caspase‐1 signaling pathway
Authors: Wu Zonglong , Liu Qinggang , Zhu Kejia , Liu Yaxiao , Chen Lipeng , Guo Hongda , Zhou Nan , Li Yan , Shi Benkang
Published: January 2020

Aims

Cell death and inflammation are involved in the development of bladder dysfunction. Pyroptosis is programmed cell death, causing cytotoxic effects and local inflammation. As one of the biggest health threats in the world, smoking is also closely related to urinary system diseases. The aims of this study were to investigate the role of NLRP3 inflammasome‐mediated pyroptosis in the bladder after cigarette smoke exposure.

Methods

The expression of NLRP3 inflammasome and the activity of caspase‐1 in bladder tissue was investigated after cigarette smoke exposure. In vitro, bladder urothelial cells were stimulated by cigarette smoke extract and then the activity of caspase‐1 and the expression of NLRP3 inflammasome were measured. The role of oxidative stress was also assessed.

Results

The activity of caspase‐1 in bladder tissue increased by 50% after cigarette smoke exposure. Cigarette smoke caused oxidative stress injury and the activation of NLRP3 inflammasome. In addition, reactive oxygen species (ROS) inhibitor N‐acetyl‐cysteine alleviated the pyroptosis of urothelial cells.

Conclusions

Cigarette smoke‐induced pyroptosis of bladder tissue by activating ROS/NLRP3/caspase‐1 signaling pathway. Inhibition of bladder urothelial cell pyroptosis may be a new approach to alleviate bladder damage caused by smoking.
Ascleposide, a natural cardenolide, induces anticancer signaling in human castration‐resistant prostatic cancer through Na+/K+‐ATPase internalization and tubulin acetylation
Authors: Leu Wohn‐Jenn , Wang Ching‐Ting , Hsu Jui‐Ling , Chen Ih‐Sheng , Chang Hsun‐Shuo , Guh Jih‐Hwa
Published: January 2020

Background

Cardiac glycosides, which inhibit Na+/K+‐ATPase, display inotropic effects for the treatment of congestive heart failure and cardiac arrhythmia. Recent studies have suggested signaling downstream of Na+/K+‐ATPase action in the regulation of cell proliferation and apoptosis and have revealed the anticancer activity of cardiac glycosides. The study aims to characterize the anticancer potential of ascleposide, a natural cardenolide, and to uncover its primary target and underlying mechanism against human castration‐resistant prostate cancer (CRPC).

Methods

Cell proliferation was examined in CRPC PC‐3 and DU‐145 cells using sulforhodamine B assay, carboxyfluorescein succinimidyl ester staining assay and clonogenic examination. Flow cytometric analysis was used to detect the distribution of cell cycle phase, mitochondrial membrane potential, intracellular Na+ and Ca2+ levels, and reactive oxygen species production. Protein expression was examined using Western blot analysis. Endocytosis of Na+/K+‐ATPase was determined using confocal immunofluorescence microscopic examination.

Results

Ascleposide induced an increase of intracellular Na+ and a potent antiproliferative effect. It also induced a decrease of G1 phase distribution while an increase in both G2/M and apoptotic sub‐G1 phases, and downregulated several cell cycle regulator proteins, including cyclins, Cdk, p21, and p27 Cip/Kip proteins, Rb and c‐Myc. Ascleposide decreased the expression of antiapoptotic Bcl‐2 members (eg, Bcl‐2 and Mcl‐1) but upregulated proapoptotic member (eg, Bak), leading to a significant loss of mitochondrial membrane potential and activation of both caspase‐9 and caspase‐3. Ascleposide also dramatically induced tubulin acetylation, leading to inhibition of the catalytic activity of Na+/K+‐ATPase. Notably, extracellular high K+ (16 mM) significantly blunted ascleposide‐mediated effects. Furthermore, ascleposide induced a p38 MAPK‐dependent endocytosis of Na+/K+‐ATPase and downregulated the protein expression of Na+/K+‐ATPase α1 subunit.

Conclusion

Ascleposide displays antiproliferative and apoptotic activities dependent on the inhibition of Na+/K+‐ATPase pumping activity through p38 MAPK‐mediated endocytosis of Na+/K+‐ATPase and downregulation of α1 subunit, which in turn cause tubulin acetylation and cell cycle arrest. Cell apoptosis is ultimately triggered by the activation of caspase cascade attributed to mitochondrial damage through the downregulation of Bcl‐2 and Mcl‐1 protein expressions while upregulation of Bak protein levels. The data also suggest the potential of ascleposide in anti‐CRPC development.
Etching Asymmetric Germanium Membranes with Hydrogen Peroxide for High‐Capacity Lithium‐Ion Battery Anodes
Authors: Wu Ji , Jin Congrui , Larson Emilee , Williams Logan
Published: January 2020

Germanium (Ge) is deemed as one of the most promising alloying anodes for rechargeable lithium‐ion batteries (LIBs) due to its large theoretical capacity, high electrical conductivity, fast lithium‐ion diffusivity, and mechanical robustness. However, Ge‐based anodes suffer from large volume changes during lithiation and delithiation, which can deteriorate their electrochemical performance rapidly. Herein, the large volume change issue is effectively addressed using an asymmetric membrane structure that is prepared using a phase‐inversion method in combination with hydrogen peroxide etching and surface coating. The asymmetric Ge membrane etched by ≈30 wt% H2O2 at 90 °C for 30 s demonstrates a capacity retention higher than 80% in 50 cycles at 160 mA g−1. Coating the H2O2‐etched Ge membrane with carbonaceous membranes can further improve the retention up to 95% in 50 cycles at 160 mA g−1, whereas ≈100% capacity of 700 mAh g−1 can be maintained in 170 cycles at 400 mA g−1. A combination of electron microscopy, spectrophotometry, and X‐ray analyses confirms the electrochemical performance of asymmetric Ge membranes as the LIB anode can be significantly affected by membrane geometry, the duration of hydrogen peroxide etching, carbonaceous membrane coating, and Ge concentration.
Leveraging historical data into oncology development programs: Two case studies of phase 2 Bayesian augmented control trial designs
Authors: Smith Claire L. , Thomas Zachary , Enas Nathan , Thorn Katharine , Lahn Michael , Benhadji Karim , Cleverly Ann
Published: January 2020

Leveraging historical data into the design and analysis of phase 2 randomized controlled trials can improve efficiency of drug development programs. Such approaches can reduce sample size without loss of power. Potential issues arise when the current control arm is inconsistent with historical data, which may lead to biased estimates of treatment efficacy, loss of power, or inflated type 1 error. Consideration as to how to borrow historical information is important, and in particular, adjustment for prognostic factors should be considered. This paper will illustrate two motivating case studies of oncology Bayesian augmented control (BAC) trials. In the first example, a glioblastoma study, an informative prior was used for the control arm hazard rate. Sample size savings were 15% to 20% by using a BAC design. In the second example, a pancreatic cancer study, a hierarchical model borrowing method was used, which enabled the extent of borrowing to be determined by consistency of observed study data with historical studies. Supporting Bayesian analyses also adjusted for prognostic factors. Incorporating historical data via Bayesian trial design can provide sample size savings, reduce study duration, and enable a more scientific approach to development of novel therapies by avoiding excess recruitment to a control arm. Various sensitivity analyses are necessary to interpret results. Current industry efforts for data transparency have meaningful implications for access to patient‐level historical data, which, while not critical, is helpful to adjust for potential imbalances in prognostic factors.
Reliability modeling of correlated competitions and dependent components with random failure propagation time
Authors: Xing Liudong , Zhao Guilin , Wang Yujie , Xiang Yisha
Published: January 2020

Function dependence takes place in systems where the malfunction of certain trigger component(s) causes other system components (referred to as dependent components) to become unusable or inaccessible. Systems undergoing function dependence often exhibit diverse statuses due to competitions in the time domain between propagated failure from a dependent component and local failure of the corresponding trigger component. If the former wins (ie, occurring first), a failure propagation effect is induced, crashing the entire system. If the latter wins, a failure isolation effect may be induced quarantining the damage from the propagated failure (the isolation effect can occur in a deterministic or probabilistic manner depending on applications). Existing models addressing such competitions have restrictive assumptions such as uncorrelated competitions from multiple function dependence groups, zero or negligible failure propagation time, and deterministic failure isolation effect. This paper advances the state of the art by proposing a combinatorial reliability model for systems undergoing correlated, probabilistic competitions and random failure propagation time for dependent components. A case study of a wireless body area network system for patient monitoring is performed to illustrate the proposed methodology and effects of different model parameters on the system reliability.
Coupled water flow, heat transport, and solute transport in a seasonally frozen rangeland soil
Authors: Kelleners Thijs J.
Published: January 2020

Soil water flow, heat transport, and solute transport in cold regions exhibit complex interactions that are difficult to quantify with measurements alone. For example, dissolved ions will lower the freezing point of soil water, while frozen soil will limit solute transport. In this study, a vertical one‐dimensional numerical model for coupled water flow, heat transport, and solute transport was combined with 8 years of Hydra impedance sensor monitoring data to estimate solute transport parameters in a high elevation, cool, semi‐arid mixed‐grass rangeland near Laramie, WY. Model calibration focused on the linear adsorption coefficient and the dispersivity in the solute transport equation. The brute force method was used to examine the complete parameter space using bulk soil electrical conductivity (σb) alone, and σb divided by tortuosity (τ) in the objective function. The use of σb yielded positive Modeling Efficiency (ME) for three out of five sensor depths (ME ≤ 0.49), while use of σbτ−1 yielded negative ME ≤ −0.01 for all depths. The low ME for σbτ−1 was expected as this ratio serves as a proxy for solute storage, which is expected to fluctuate relatively little with time for most terrestrial ecosystems. Reliable adsorption and dispersion coefficients could be determined for the 0–10 cm depth, and to a lesser extent, the 10–30 cm depth. At deeper depths, solute transport was only sensitive to the adsorption coefficient, so that reliable values for dispersivity could not be determined.
Effect of soil texture on nitrogen mineralization from organic fertilizers in four common southeastern soils
Authors: Cassity‐Duffey Kate , Cabrera Miguel , Franklin Dory , Gaskin Julia , Kissel David
Published: January 2020

Previous studies have indicated that soil properties and texture could lead to differences in N mineralization from applied organic materials. We conducted a 100‐day (d) incubation study to measure net N mineralized from feather meal (14–0.1–0.1) and pellet mix (10–1–6) at 150 mg N kg soil−1(approximately 72 kg N ha−1) incorporated into four common southeastern soils: Cecil 1, Cecil 2, Greenville, and Tifton. A second 23‐d study was conducted to determine pH dynamics and the potential for ammonia volatilization from the same soils and materials. There were no differences in net N mineralized from pellet mix among soils, but net N mineralized from feather meal was lower in Greenville soil, which had the greatest clay content. Analysis of the first‐order dynamics of N mineralization indicated that even in soils that differ in clay content it may be possible to describe N mineralization from feather meal and pellet mix with a single model. Our results also suggest that the effect of pH on the N mineralization dynamics of these fertilizers may be more important than the effect of clay content. No ammonia loss was observed regardless of soil texture, soil pH buffering capacity, or initial soil pH.
Usefulness of shosaikoto for pneumonia in combination with antibiotics
Authors: Yamasaki Genzo , Suzuki Daisuke , Ose Ayako , Ono Takahiko
Published: January 2020

Aim

The value of Kampo medicine for the treatment of pneumonia is unclear. The aim of our study is to investigate the usefulness of shosaikoto for pneumonia in combination with antibiotics.

Methods

We retrospectively compared 39 cases treated only with Western medicine, including antibiotics (conventional group), with 22 cases treated with Western medicine, including antibiotics, and shosaikoto (combination group). We evaluated the duration of antibiotic treatment after admission, the febrile period, and the duration of oxygen treatment.

Results

The duration of antibiotic treatment was significantly shorter in the combination group (7 ± 2.25 days) than in the conventional group (8.46 ± 2.28 days; P < 0.05), and the febrile period was also significantly shorter in the combination group (2.95 ± 0.92 days) than in the conventional group (4.09 ± 2.08 days; P < 0.05). The duration of oxygen treatment was not shorter in the combination group (3.85 ± 1.77 days) than in the conventional group (4.11 ± 2.25 days; P = 0.951).

Conclusion

This study suggests that combination therapy with shosaikoto and antibiotics is useful for bacterial pneumonia.
Company engagement with supply chains to protect biodiversity and rare, threatened, and endangered species
Authors: Kashmanian Richard M.
Published: January 2020

Future global megatrends project a population increase of 2 billion people between 2019 and 2050 and at least 1–2 billion people added to the global middle class between 2016 and 2030. In addition, 68% of the world's population is projected to be living in urban areas by 2050. With these projected large population increases and shifts, demand for food, water, and energy is projected to grow by approximately 35, 40, and 50%, respectively, between 2010 and 2030. In addition, between 1970 and 2014 there was an estimated 60% reduction in the number of wildlife in the world and an estimated net loss of 2.9 billion birds, or 29%, in North America between 1970 and 2018. Loss of species populations and number of species is interconnected with reduced health of biodiversity and ecosystems. Human activity has been the main catalyst for these substantial declines primarily through impacts on habitats. These losses are accelerating. Since a company's supply chain environmental impacts are often as great or greater than its own direct environmental impacts, it may be prudent for companies to engage with their supply chains to protect and enhance habitats and biodiversity and protect rare, threatened, and endangered species. As one example, companies may have opportunities and strategic reasons to include requirements in their supplier codes of conduct and supplier standards for suppliers to protect biodiversity and rare, threatened, and endangered species, as well as additional requirements to expand or enhance habitats and ecosystems to increase biodiversity. This article follows one pathway that companies could pursue further and with greater speed—to engage with their supply chains to strengthen supplier codes of conduct to protect biodiversity and rare, threatened, and endangered species. The importance of forests, private land, and landscape partnerships is discussed as means to protect much more of the planet's biodiversity and rare, threatened, and endangered species. Lastly, the article identifies examples of opportunities for companies to more formally incorporate biodiversity into their business, supply chain, and sustainability strategies.
Effect of build location on microstructural characteristics and corrosion behavior of EB-PBF built Alloy 718
Authors: Karimi P. , Sadeghi E. , Ålgårdh J. , Harlin P. , Andersson J.
Published: January 2020

Electron beam-powder bed fusion (EB-PBF), a high-temperature additive manufacturing (AM) technique, shows great promise in the production of high-quality metallic parts in different applications such as the aerospace industry. To achieve a higher build efficiency, it is ideal to build multiple parts together with as low spacing as possible between the respective parts. In the EB-PBF technique, there are many unknown variations in microstructural characteristics and functional performance that could be induced as a result of the location of the parts on the build plate, gaps between the parts and part geometry, etc. In the present study, the variations in the microstructure and corrosion performance as a function of the parts location on the build plate in the EB-PBF process were investigated. The microstructural features were correlated with the thermal history of the samples built in different locations on the build plate, including exterior (the outermost), middle (between the outermost and innermost), and interior (the innermost) regions. The cubic coupons located in the exterior regions showed increased level (~ 20 %) of defects (mainly in the form of shrinkage pores) and lower level (~ 30-35 %) of Nb-rich phase fraction due to their higher cooling rates compared to the interior and middle samples. Electrochemical investigations showed that the location indirectly had a substantial influence on the corrosion behavior, verified by a significant increase in polarization resistance (Rp) from the exterior (2.1 ± 0.3 kΩ.cm2) to interior regions (39.2 ± 4.1 kΩ.cm2).
Tracing the decision-making process for myelofibrosis: diagnosis, stratification, and management of ruxolitinib therapy in real-word practice
Authors: Breccia Massimo , Baratè Claudia , Benevolo Giulia , Bonifacio Massimiliano , Elli Elena Maria , Guglielmelli Paola , Maffioli Margherita , Malato Alessandra , Mendicino Francesco , Palumbo Giuseppe Alberto , Pugliese Novella , Rossi Elena , Rumi Elisa , Sant’Antonio Emanuela , Ricco Alessandra , Tiribelli Mario , Palandri Francesca
Published: January 2020

The management of patients with myelofibrosis (MF) has dramatically changed since the introduction of ruxolitinib as a tailored treatment strategy. However, the perceptions about the use of this drug in clinical practice remain, at times, a matter of discussion. We conducted a survey about the diagnostic evaluation, prognostic assessment, and management of ruxolitinib in real-life clinical practice in 18 Italian hematology centers. At diagnosis, most hematologists do not use genetically or molecularly inspired score systems to assess prognosis, mainly due to scarce availability of next-generation sequencing (NGS) methodology, with NGS conversely reserved only for a subset of lower-risk MF patients with the aim of possibly improving the treatment strategy. Some common points in the management of ruxolitinib were 1) clinical triggers for ruxolitinib therapy, regardless of risk category; 2) evaluation of infectious risk before the starting of the drug; and 3) schedule of monitoring during the first 12 weeks with the need, in some instances, of supportive treatment. Further development of international recommendations and insights will allow the achievement of common criteria for the management of ruxolitinib in MF, before and after treatment, and for the definition of response and failure.
An Efficient Scheme of Cloud Data Assured Deletion
Authors: Tian Yuechi , Shao Tong , Li Zhen
Published: January 2020

With the rapid development of cloud storage technology, cloud data assured deletion has received extensive attention. While ensuring the deletion of cloud data, users have also placed increasing demands on cloud data assured deletion, such as improving the execution efficiency of various stages of a cloud data assured deletion system and performing fine-grained access and deletion operations. In this paper, we propose an efficient scheme of cloud data assured deletion. The scheme replaces complicated bilinear pairing with simple scalar multiplication on elliptic curves to realize ciphertext policy attribute-based encryption of cloud data, while solving the security problem of shared data. In addition, the efficiency of encryption and decryption is improved, and fine-grained access of ciphertext is realized. The scheme designs an attribute key management system that employs a dual-server to solve system flaws caused by single point failure. The scheme is proven to be secure, based on the decisional Diffie-Hellman assumption in the standard model; therefore, it has stronger security. The theoretical analysis and experimental results show that the scheme guarantees security and significantly improves the efficiency of each stage of cloud data assured deletion.
Development of a conceptual framework to underpin a health-related quality of life outcome measure in paediatric chronic fatigue syndrome/myalgic encephalopathy (CFS/ME): prioritisation through card ranking
Authors: Parslow Roxanne M. , Anderson Nina , Byrne Danielle , Haywood Kirstie L. , Shaw Alison , Crawley Esther
Published: January 2020

Purpose

Chronic fatigue syndrome (CFS)/myalgic encephalopathy (ME) is relatively common in children and is disabling at an important time in their development. This study aimed to develop a conceptual framework of paediatric CFS/ME using the patient-perspective to ensure that the content of a new outcome measure includes the outcomesmostimportant to young people.

Methods

We developed a child-centred interactive card ranking exercise that included health-related quality of life (HRQoL) outcomes identified from a previous review of the literature as well as qualitative work. Adolescents and their parents selected and ranked the outcomes most important to them and discussed each outcome in further detail. Adolescents were purposively sampled from a single specialist paediatric CFS/ME service in England. Interviews were audio recorded and transcribed verbatim, and thematic framework analysis was used to develop the final conceptual framework.

Results

We interviewed 43 participants in which there are 21 adolescents, 12–17 years of age with mild–moderate CFS/ME and their parents (20 mothers and 2 fathers). ‘Symptoms’, ‘tiredness’, ‘payback and crashing’ and ‘activities and hobbies’ were ranked most important to improve by both children and parents. Children ranked ‘school’ higher than parents and parents ranked ‘mood’ higher than children. A youth- specific CFS/ME conceptual framework of HRQoL was produced that included 4 outcome domains and 11 subdomains: sleep, tiredness, problems concentrating, individual symptoms, fluctuation and payback, daily and general activities, participation in school, leisure and social life, mood, anxiety and self-esteem.

Conclusions

An interactive card ranking exercise worked well for adolescents aged 12–17 to elicit the most important outcomes to them and explore each domain in further detail. We developed a final conceptual framework of HRQoL that forms the basis of a new paediatric patient-reported outcome measure (PROM) in CFS/ME.
Measuring Teacher Sense of Efficacy: Insights and Recommendations Concerning Scale Design and Data Analysis from Research with Preservice and Inservice Teachers in China
Authors: Ma Kang , Trevethan Robert , Lu Shuhong
Published: January 2020

In this study, issues concerning the design of scales for measuring teacher sense of efficacy (TSE) are first identified with particular attention to the Teacher Sense of Efficacy Scale (TSES). Psychometric issues concerning analysis and reporting of TSE data are subsequently identified. Recommendations are offered about all identified issues, and these recommendations are taken into account when obtaining and analyzing TSE data from Chinese mainland preservice and inservice teachers. Exploratory factor analyses yielded a single factor for both samples as well as for four subgroups within the inservice teacher sample. Results also provided insights about scale design as well as the TSES being limited for capturing the breadth of TSE. Suggestions are made for improvements in the assessment of TSE.
Energy Consumption and Greenhouse Gas Emissions During Ferromolybdenum Production
Authors: Wei Wenjing , Samuelsson Peter B. , Tilliander Anders , Gyllenram Rutger , Jönsson Pär G.
Published: January 2020

Molybdenum is mainly used as an alloy material in the iron and steel industry and typically in the form of ferromolybdenum (FeMo). The current study aims to evaluate the energy consumption and greenhouse gas emissions (GHG) of four ferromolybdenum production cases using inventory inputs from a process model based on mass and energy conservations. The total energy required for producing 1 tonne of FeMo can vary between 29.1 GJ/t FeMo and 188.6 GJ/t FeMo. Furthermore, the corresponding GHG emissions differ from 3.16 tCO2-eq/t FeMo to 14.79 tCO2-eq/t FeMo. The main variances are from the mining and beneficiation stages. The differences in these stages come from the beneficiation degree (ore grade) and the mine type (i.e., co-product from copper mining). Furthermore, the mine type has a larger impact on the total energy consumption and GHG emissions than the beneficiation degree. More specifically, FeMo produced as co-product from copper mining has a lower environmental impact measured as the energy consumption and GHG emission among all the four cases. The inventory, consumed energy or associated GHG emission is independent on the initial ore grade and mine type in the downstream production stages such as roasting and smelting. Also, transport has the least impact on the energy consumption and GHG emission among all production stages.
Acute whole apple consumption did not influence postprandial lipaemia: a randomised crossover trial
Authors: Lin Xinjie , Liddle Danyelle M. , Neizer Hannah R. , Robinson Lindsay E. , Wright Amanda J.
Published: January 2020

Whole apples are a source of pectin and polyphenols, both of which show potential to modulate postprandial lipaemia (PPL). The present study aimed to explore the effects of whole apple consumption on PPL, as a risk factor for CVD, in generally healthy but overweight and obese adults. A randomised, crossover acute meal trial was conducted with seventeen women and nine men (mean BMI of 34·1 (sem 0·2) kg/m2). Blood samples were collected for 6 h after participants consumed an oral fat tolerance test meal that provided 1 g fat/kg body weight and 1500 mg acetaminophen per meal for estimating gastric emptying, with and without three whole raw Gala apples (approximately 200 g). Plasma TAG (with peak postprandial concentration as the primary outcome), apoB48, chylomicron-rich fraction particle size and fatty acid composition, glucose, insulin and acetaminophen were analysed. Differences between with and without apples were identified by ANCOVA. Apple consumption did not alter postprandial TAG response, chylomicron properties, glucose or acetaminophen (P > 0·05), but did lead to a higher apoB48 peak concentration and exaggerated insulin between 20 and 180 min (P < 0·05). Overall, as a complex food matrix, apples did not modulate postprandial TAG when consumed with a high-fat meal in overweight and obese adults, but did stimulate insulin secretion, potentially contributing to an increased TAG-rich lipoprotein production.