bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundThe 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.MethodsWe 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.ResultsThe 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.ConclusionThis 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

AbstractIntroductionResearch 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 MethodsA 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.ResultsTotal 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.ConclusionsThis 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

AbstractAimsCell 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.MethodsThe 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.ResultsThe 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.ConclusionsCigarette 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

AbstractBackgroundCardiac 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).MethodsCell 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.ResultsAscleposide 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.ConclusionAscleposide 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.
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

SUMMARYLeveraging 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

AbstractFunction 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

AbstractSoil 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

AbstractPrevious 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

ABSTRACTAimThe 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.MethodsWe 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.ResultsThe 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).ConclusionThis 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

AbstractFuture 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

AbstractElectron 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

AbstractThe 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

AbstractWith 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.