bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential clinical significance of COL5A1 and COL5A2 in tongue squamous cell carcinoma
Authors: Chen Hung‐Chih , Tseng Yu‐Kai , Shu Chih‐Wen , Weng Ta‐Jung , Liou Huei‐Han , Yen Liang‐Ming , Hsieh I‐Chien , Wang Cheng‐Ching , Wu Pi‐Chuan , Shiue Yow‐Ling , Fu Ting‐Ying , Tsai Kuo‐Wang , Ger Luo‐Ping , Liu Pei‐Feng
Published: April 2019

Background

Type V collagen (COL5), in the functional heterotrimer [α1(V)2α2(V)] isoform, participates in the malignancies of various cancers. However, its role in tongue squamous cell carcinoma (TSCC) remains unclear.

Materials and Methods

The expression levels of COL5A1 and COL5A2 polypeptide chains were examined using the tissue microarray from 245 TSCC patients with immunohistochemistry. Paired t test and Wilcoxon signed‐rank test were performed for comparisons among the groups. Survival rates were estimated by using the Kaplan‐Meier method and compared with log‐rank tests. A Cox proportional hazards model was used to evaluate the impact of protein expression level on survival rate.

Results

Expression level of COL5A1 was significantly increased in tumor tissues (P < 0.001) compared to that in corresponding adjacent normal tissues. High expression level of COL5A1 was associated with advanced pathological stage (III, IV, P = 0.015) and lymph node metastasis (P = 0.005) of TSCC patients. High expression level of COL5A1 was also correlated with poor disease‐specific survival (DSS, P = 0.001) and disease‐free survival (DFS, P = 0.003) in TSCC patients. However, high expression level of COL5A2 was correlated with better DFS in TSCC patients (P = 0.043). Moreover, co‐expression level of high (COL5A1)2/low (COL5A2) heterotrimer was correlated with worse DSS (P = 0.004) and DFS (P = 0.004).

Conclusion

COL5A1 is an unfavorable factor for tumorigenesis, clinicopathological outcomes, and prognosis, whereas COL5A2 is only a favorable factor for prognosis in TSCC. The co‐expression of high (COL5A1)2/low (COL5A2) heterotrimer is a more potential unfavorable factor for prognosis in TSCC.
Genetic variation in FCER1A predicts peginterferon alfa‐2a‐induced hepatitis B surface antigen clearance in East Asian patients with chronic hepatitis B
Authors: Wei Lai , Pavlovic Vedran , Bansal Aruna T. , Chen Xiaoping , Foster Graham R. , He Hua , Kao Jia‐Horng , Lampertico Pietro , Liaw Yun‐Fan , Motoc Adriana , Papatheodoridis George V. , Piratvisuth Teerha , Plesniak Robert , Wat Cynthia
Published: April 2019

In a multicentre, genome‐wide association study to identify host genetic factors associated with treatment response in adult chronic hepatitis B patients, genotype data were obtained by microarray analysis from 1669 patients who received peginterferon alfa‐2a for ≥ 24 weeks with/without a nucleos(t)ide analog. Treatment response was assessed at least 24 weeks post‐treatment, using serological and/or virological endpoints. Thirty‐six single‐marker analyses and a gene‐by‐gene analysis were conducted. No single nucleotide polymorphisms (SNPs) achieved genome‐wide significance (P < 5 × 10−8) in single‐marker analyses, but suggestive associations (P < 1 × 10−5) were identified for 116 SNPs. In gene‐by‐gene analyses, one gene, FCER1A (rs7549785), reached genome‐wide significance (P = 2.65 × 10−8) in East Asian patients for hepatitis B surface antigen (HBsAg) clearance, with a moderate effect size (odds ratio = 4.74). Eleven of 44 carriers (25%) of the A allele at rs7549785 achieved HBsAg clearance compared with 69/1051 (7%) noncarriers. FCER1A encodes the alpha subunit of the immunoglobulin E receptor. In a post hoc analysis of a homogenous patient subset, the strongest intragenic association was for rs7712322 (POLR3G, P = 7.21 × 10−7). POLR3G encodes the G subunit of the polymerase (RNA) III enzyme, involved in sensing and limiting infection by intracellular bacteria and DNA viruses, and as a DNA sensor in innate immune responses. FCER1A (rs7549785) and possibly POLR3G (rs7712322) are shown to be associated with peginterferon alfa‐2a response in adult patients with chronic hepatitis B. Independent confirmation of these findings is warranted (clinicaltrials.gov number NCT01855997).
Nonfertilizing sperm in Lepidoptera show little evidence for recurrent positive selection
Authors: Mongue Andrew J. , Hansen Megan E. , Gu Liuqi , Sorenson Clyde E. , Walters James R.
Published: April 2019

Sperm are among the most variable cells in nature. Some of this variation results from nonadaptive errors in spermatogenesis, but many species consistently produce multiple sperm morphs, the adaptive significance of which remains unknown. Here, we investigate the evolution of dimorphic sperm in Lepidoptera, the butterflies and moths. Males of this order produce both fertilizing sperm and a secondary, nonfertilizing type that lacks DNA. Previous organismal studies suggested a role for nonfertilizing sperm in sperm competition, but this hypothesis has never been evaluated from a molecular framework. We combined published data sets with new sequencing in two species, the monandrous Carolina sphinx moth and the highly polyandrous monarch butterfly. Based on population genetic analyses, we see evidence for increased adaptive evolution in fertilizing sperm, but only in the polyandrous species. This signal comes primarily from a decrease in nonsynonymous polymorphism in sperm proteins compared to the rest of the genome, suggesting stronger purifying selection, consistent with selection via sperm competition. Nonfertilizing sperm proteins, in contrast, do not show an effect of mating system and do not appear to evolve differently from the background genome in either species, arguing against the involvement of nonfertilizing sperm in direct sperm competition. Based on our results and previous work, we suggest that nonfertilizing sperm may be used to delay female remating in these insects and decrease the risk of sperm competition rather than directly affect its outcome.
Enhanced notch signaling modulates unproductive revascularization in response to nitric oxide‐angiopoietin signaling in a mouse model of peripheral ischemia
Authors: Machado Maria J. C. , Boardman Rachel , Riu Federica , Emanueli Costanza , Benest Andrew V. , Bates David O.
Published: April 2019

Introduction

Arteriolargenesis can be induced by concomitant stimulation of nitric Oxide (NO)‐Angiopoietin receptor (Tie)‐Vascular Endothelial Growth Factor (VEGF) signaling in the rat mesentery angiogenesis assay. We hypothesized that the same combination of exogenously added growth factors would also have a positive impact on arteriolargenesis and, consequently, the recovery of blood flow in a model of unilateral hindlimb ischemia.

Results and Methods

NO‐Tie mice had faster blood flow recovery compared to control mice, as assessed by laser speckle imaging. There was no change in capillary density within the ischemic muscles, but arteriole density was higher in NO‐Tie mice. Given the previously documented beneficial effect of VEGF signaling, we tested whether NO‐Tie‐VEGF mice would show further improvement. Surprisingly, these mice recovered no differently from control, arteriole density was similar and capillary density was lower. Dll4 is a driver of arterial specification, so we hypothesized that Notch1 expression would be involved in arteriolargenesis. There was a significant upregulation of Notch1 transcripts in NO‐Tie‐VEGF compared with NO‐Tie mice. Using soluble Dll4 (sDll4), we stimulated Notch signaling in the ischemic muscles of mice. NO‐Tie‐sDll4 mice had significantly increased capillary and arteriole densities, but impaired blood flow recovery.

Conclusion

These results suggest that Dll4 activation early on in revascularization can lead to unproductive angiogenesis and arteriolargenesis, despite increased vascular densities. These results suggest spatial and temporal balance of growth factors needs to be perfected for ideal functional and anatomical revascularisation.
Does the rapid response of an antidepressant contribute to better cost‐effectiveness? Comparison between mirtazapine and SSRIs for first‐line treatment of depression in Japan
Authors: Sado Mitsuhiro , Wada Masataka , Ninomiya Akira , Nohara Hiroyoshi , Kosugi Teppei , Arai Mayuko , Endo Ryusuke , Mimura Masaru
Published: April 2019

Aim

Previous studies indicate that mirtazapine is unique in its quick responsiveness compared to other antidepressants. Although some other studies have evaluated its cost‐effectiveness, they have not considered its early stage remission rate. The aim of this study was to address this research gap by using precise clinical data to evaluate the cost‐effectiveness of mirtazapine in Japan.

Methods

We developed a Markov model to reflect the week‐by‐week transition probabilities. The Markov cycle was set as 1 week. While our clinical parameters were obtained largely from existing meta‐analyses, cost data were derived from government reports. Cost‐effectiveness was evaluated by incremental cost‐effectiveness ratios (ICERs) per quality‐adjusted life year estimated based on the probability sensitivity analyses. The ICERs were estimated at 2, 8, 26, and 52 weeks.

Results

In severe depression, the ICERs ranged between JPY 872 153 and 1 772 723. The probability of mirtazapine being cost‐effective ranged from 0.75 to 0.99 when the ICER threshold was JPY 5 000 000. In moderate depression, the ICERs ranged between JPY 2 356 499 and 4 770 145. The probability of mirtazapine being cost‐effective ranged from 0.55 to 0.83 when the ICER threshold was JPY 5 000 000.

Conclusion

When considering the early stage efficacy of mirtazapine, it appeared to be cost‐effective compared to selective serotonin reuptake inhibitors, especially for severe depression and in the early stage treatment in the Japanese setting. However, our study has some limitations. First, mirtazapine is compared with batched selective serotonin reuptake inhibitors rather than individual ones. Second, we did not consider antidepressant combination therapy as treatment options.
Kidney disease and organ transplantation in methylmalonic acidaemia
Authors: Noone Damien , Riedl Magdalena , Atkison Paul , Avitzur Yaron , Sharma Ajay P , Filler Guido , Siriwardena Komudi , Prasad Chitra
Published: April 2019

Objectives

MMA is associated with chronic tubulointerstitial nephritis and a progressive decline in GFR. Optimal management of these children is uncertain. Our objectives were to document the pre‐, peri‐, and post‐transplant course of all children with MMA who underwent liver or combined liver‐kidney transplant in our centers.

Design and methods

Retrospective chart review of all cases of MMA who underwent organ transplantation over the last 10 years.

Results

Five children with MMA underwent liver transplant (4/5) and combined liver‐kidney transplant (1/5). Three were Mut0 and two had a cobalamin B disorder. Four of five were transplanted between ages 3 and 5 years. Renal dysfunction prior to transplant was seen in 2/5 patients. Post‐transplant (one liver transplant and one combined transplant) renal function improved slightly when using creatinine‐based GFR formula. We noticed in 2 patients a big discrepancy between creatinine‐ and cystatin C‐based GFR calculations. One patient with no renal disease developed renal failure post–liver transplantation. Serum MMA levels have decreased in all to <300 μmol/L. Four patients remain on low protein diet, carnitine, coenzyme Q, and vitamin E post‐transplant.

Conclusions

MMA is a complex metabolic disorder. Renal disease can continue to progress post–liver transplant and close follow‐up is warranted. More research is needed to clarify best screening GFR method in patients with MMA. Whether liver transplant alone, continued protein restriction, or the addition of antioxidants post‐transplant can halt the progression of renal disease remains unclear.
Why ‘Swampman’ Would Not Even Get as Far as Thinking it Was Davidson: On the Spatio‐temporal Basis of Davidson's Conjuring Trick
Authors: Read Rupert , Allesøe Bo
Published: April 2019

In this article, we analyse one of the most famous recent thought‐experiments in philosophy, namely Donald Davidson's Swampman. Engaging recent commentators on Davidson's Swampman as well as analysing the spatio‐temporal conditions of the thought‐experiment, we will show how the ‘experiment’ inevitably fails. For it doesn't take seriously some of its own defining characteristics: crucially, Swampman's creation of a sudden in a place distinct from Davidson's. Instead of denigrating philosophical thought‐experiments per se, our analysis points towards considering thought‐experiments in a different sense: imaginary scenarios helpfully self‐deconstructing rather than constituting substantive philosophical resources.
Immune effector mechanisms in malaria: An update focusing on human immunity
Authors: Moormann Ann M. , Nixon Christina E. , Forconi Catherine S.
Published: April 2019

The past decade has witnessed dramatic decreases in malaria‐associated mortality and morbidity around the world. This progress has largely been due to intensified malaria control measures, implementation of rapid diagnostics and establishing a network to anticipate and mitigate antimalarial drug resistance. However, the ultimate tool for malaria prevention is the development and implementation of an effective vaccine. To date, malaria vaccine efforts have focused on determining which of the thousands of antigens expressed by Plasmodium falciparum are instrumental targets of protective immunity. The antigenic variation and antigenic polymorphisms arising in parasite genes under immune selection present a daunting challenge for target antigen selection and prioritization, and is a given caveat when interpreting immune recall responses or results from monovalent vaccine trials. Other immune evasion strategies executed by the parasite highlight the myriad of ways in which it can become a recurrent infection. This review provides an update on immune effector mechanisms in malaria and focuses on our improved ability to interrogate the complexity of human immune system, accelerated by recent methodological advances. Appreciating how the human immune landscape influences the effectiveness and longevity of antimalarial immunity will help explain which conditions are necessary for immune effector mechanisms to prevail.
Toward a Bright Future: Politics of Potential in a Ugandan Village
Authors: Bocast Brooke
Published: April 2019

This article demonstrates how female students in rural Uganda experience education sponsorship in ways that belie international development discourse about girls’ empowerment. Since the 1990s, international development organizations have promoted community‐based programming alongside efforts to empower individual subjects. I examine the intersection of these trends through the lens of an American nongovernmental organization's (NGO) scholarship program in a Ugandan village. Drawing from recent work on the politics of potentiality, I argue three nested points: (1) NGOs and the various groups that interact with them construct the community as a site for intervention; (2) notions of potential are key to these constructions; and (3) the community–potential nexus is gendered in ways that reconfigure young women's networks of support and obligation with kin, local leaders, and NGO staff. This analysis illuminates larger tensions surrounding notions of individual autonomy and community obligation in Uganda and rural sub‐Saharan Africa more broadly.
Violence, Law, and the Archive: How Dossiers of Memory Challenge Enforced Disappearances in the War on Terror in Pakistan
Authors: Hussain Salman
Published: April 2019

This article examines the politics of protest in Pakistan as practiced by the human rights activists and litigants seeking justice for people who have been “disappeared” by the state's military and intelligence services. Based on fieldwork among the family members and friends of these “missing” persons, it discusses how they create dossiers of memory to retain the memory of the disappeared within public sphere and records. Most studies of state bureaucracy and legality trace their history—assumed to be embedded in official files and documents—in state archives. The dossiers assembled by families and friends challenge the state narrative on its war against terrorism and serve as counter‐archives through which state violence can be traced politically and ethnically and mapped geographically. The article draws attention to how marginalized groups use law and its documentary forms against the state in order to hold it accountable for the excesses committed against them.
P0 protein of cotton leafroll dwarf virus‐atypical isolate is a weak RNA silencing suppressor and the avirulence determinant that breaks the cotton Cbd gene‐based resistance
Authors: Agrofoglio Y. C. , Delfosse V. C. , Casse M. F. , Hopp H. E. , Bonacic Kresic I. , Ziegler‐Graff V. , Distéfano A. J.
Published: April 2019

Cotton blue disease (CBD) is the most important disease present in cotton crops in South America and cotton leafroll dwarf virus (CLRDV) is the causal agent. The disease has been controlled by sowing cotton varieties resistant to CLRDV. However, in the 2009/10 growing season, an outbreak due to an atypical CLRDV isolate (CLRDV‐at) occurred in northwest Argentina. Although CLRDV and CLRDV‐at genomes are very closely related, the symptoms they produce in cotton plants are quite different. P0 is the most divergent protein between the isolates and in CLRDV is a silencing suppressor protein. This work characterized the silencing suppressor activity of the P0 protein encoded by CLRDV‐at (P0CL‐at) and evaluated its role in Cbd‐resistance break in cotton plants. It was demonstrated that P0CL‐at, despite having a mutation in the consensus of the F‐box‐like motif, was able to suppress local RNA silencing, but displayed lower activity than P0CL. P0CL and P0CL‐at showed no differences in the interaction with Gossypium hirsutum SKP1 orthologue (GSK1) and Nicotiana benthamiana SKP1 and both P0 proteins triggered destabilization of ARGONAUTE1. However, when the ability to enhance PVX symptoms was evaluated, P0CL‐at was shown to be a weaker pathogenicity factor than P0CL in N. benthamiana. Interestingly, trans‐expressed P0CL‐at enabled CLRDV to systemically infect CBD‐resistant plants, and a chimeric CLRDV‐P0CL‐at infectious clone succeeded in establishing infection in CBD‐resistant cotton varieties with symptoms resembling those produced by CLRDV‐at. These results strongly suggest that P0CL‐at is the avirulence (Avr) determinant involved in breaking cotton Cbd gene‐based resistance.
Multidisciplinary team working for vocal cord dysfunction: Now it's GO time
Authors: Hull James H.
Published: April 2019

See related Article
Convergence clustering in the Chinese provinces: New evidence from several macroeconomic indicators
Authors: Gozgor Giray , Lau Chi Keung Marco , Lu Zhou
Published: April 2019

In this paper, the convergence clustering in 31 Chinese provinces regarding several important economic indicators over the period 1952 to 2016 was empirically investigated. Several provincial clusters were identified in the per capita (real) gross domestic product (GDP), consumption–income ratio, retail price, and consumer price inflation rates, using a club convergence and clustering procedure. The empirical findings are as follows. First, it was found that all series of the original data contain a significant nonlinear component. Second, it was observed that there are five significant clusters for the per capita income in China. Third, it was found that there are four significant clusters for the consumption–income ratio. Fourth, it was observed that there are four significant clusters for the retail inflation rates and two significant clusters for the consumer inflation rates in China. These results will enable local and central planners to implement economic growth, savings and price adjustment policies for different groups of provinces.
The effects of fragility and financial inequalities on inclusive growth in African countries
Authors: Fowowe Babajide , Folarin Emmanuel Oludele
Published: April 2019

Africa has the largest number and proportion of fragile states in the world. Fragile states are characterized by slower economic growth, higher incidences of poverty, and persistent inequality. Thus, there is a circular relationship between fragility, inequality, and slow economic growth. This study examines the relationship between fragility, financial inequalities, and inclusive growth in African countries. We introduce a novel way of examining inclusive growth in African countries by developing a unified measure of inclusive growth that captures the two dimensions of inclusive growth: income growth and income distribution. This enables us to adequately assess not just increased opportunities arising from economic growth, but also see how those new opportunities are distributed across all segments of the population. We captured the fragile status of African countries by using an index of fragility. We measured financial inequalities using new data on financial inclusion. The data analysis suggested negative relationships between fragility and inclusive growth in African countries. In addition, the results suggest positive relationships between financial inclusion and inclusive growth. Thus, inclusive growth can be fostered through policies that reduce financial inequalities. Therefore, a less fragile environment is conducive to inclusive growth both directly and indirectly through financial inclusion.
When Less Is More in Boosting Survey Response Rates*
Authors: Conn Katharine M. , Mo Cecilia Hyunjung , Sellers Laura M.
Published: April 2019

Objectives

Previous general population survey research has found that, relative to monetary incentives, altruistic appeals are ineffective in increasing survey response and that offering additional monetary incentives is always desirable. We consider an alternative population—a pro‐social population—and ask whether these same conclusions apply.

Methods

To evaluate the relative effectiveness of different incentive strategies, we randomly assign individuals to one of five conditions. We consider altruistic incentives (a narrative appeal or a charitable donation) and monetary incentives (three separate lotteries).

Results

Among pro‐social individuals, “less is more”: altruistic appeals are just as effective, if not more effective, than costly monetary incentives. Moreover, the simplest lottery structure (fewer large‐payoff prizes) is the most cost effective of the lotteries.

Conclusions

The target population of interest matters when designing survey incentive strategies. Moreover, increasing the incentives budget is not always beneficial.
Public Opposition to Sanctuary Cities in Texas: Criminal Threat or Immigration Threat?*
Authors: Collingwood Loren , O'Brien Gonzalez Benjamin
Published: April 2019

Objectives

To assess predictors of sanctuary city attitudes in Texas. Specifically, to assess whether a criminal threat or immigration threat hypothesis better explains attitudes toward sanctuary cities.

Methods

Pooled representative sample surveys of Texas respondents conducted during the first half of 2017, combined with county‐level Census and crime data. Regression analysis and Monte Carlo simulations.

Results

Compared to the criminal threat hypothesis (as measured by county change in crime rates), the immigration threat hypothesis (as measured by Latino growth and Latino population) better explains Texans' attitudes toward sanctuary cities.

Conclusions

Despite elite and media narratives linking sanctuary cities to crime, respondents' attitudes toward sanctuary cities are unrelated to physical crime threat and are structured by localized experience with immigration—specifically—Latino growth.
The Chief Justice as Effective Administrative Leader: The Impact of Policy Scope and Interbranch Relations*
Authors: Vining Richard L. , Wilhelm Teena , Hughes David A.
Published: April 2019

Objectives

We examine the conditions under which the Chief Justice of the United States achieves congressional approval for his requests for institutional reforms to the federal courts. Specifically, we investigate whether legislators are more likely to enact these requests when they are limited in scope and members of Congress are similar ideologically to the chief justice or federal judiciary.

Methods

Our analysis uses the chief justice's Year‐End Report on the Federal Judiciary to identify reform proposals requested by the federal judiciary.

Results

We find that the likelihood that the federal judiciary achieves reform goals is conditioned by policy scope and ideological congruence with Congress.

Conclusions

We conclude that congressional administration of the federal courts is politically strategic.
Six‐month outcomes after restrictive or liberal transfusion for cardiac surgery (TRICS III trial)
Authors: Estcourt L. J. , Roberts D. J.
Published: April 2019

Clinical question

Is transfusing red cell components using a restrictive transfusion threshold (Hb < 75 g L−1) as safe as a liberal transfusion threshold (Hb < 95 g L−1 in intensive care and < 85 g L−1 outside intensive care) during and after cardiac surgery for adults at moderate to high risk of death?

Evidence from trial

In adults undergoing cardiac surgery who were at moderate to high risk for death, using a restrictive red‐cell transfusion threshold was as safe as a liberal red cell transfusion threshold (composite outcome of death from any cause, myocardial infarction, stroke or new‐onset renal failure with dialysis at 6 months after surgery).
Risk‐based water resources planning in practice: a blueprint for the water industry in England
Authors: Hall Jim W. , Mortazavi‐Naeini Mohammad , Borgomeo Edoardo , Baker Bill , Gavin Helen , Gough Meyrick , Harou Julien J. , Hunt Douglas , Lambert Chris , Piper Ben , Richardson Nathan , Watts Glenn
Published: April 2019

Resilient water supplies in England need to be secured in the face of challenges of population growth, climate change and environmental sustainability. We propose a blueprint for water resources planning that uses system simulation modelling to estimate the frequency, duration and severity of water shortages at present and in the context of future plans and scenarios. We use multiobjective optimisation tools to explore trade‐offs between these risk metrics and cost of alternative plans, and we use sensitivity analysis to identify plans that robustly achieve targets for tolerable risk, alongside other performance objectives. The results of a case study in the Thames basin demonstrate that the proposed methodology is feasible given commonly available data sets and models. The proposed method provides evidence with which to develop water resource management plans that demonstrably balance the risks of water shortages, costs to water users and environmental constraints in an uncertain future.
Genomic and phylogenetic characterization of Shewanella xiamenensis isolated from giant grouper (Epinephelus lanceolatus) in Taiwan
Authors: Huang Yao‐Ting , Cheng Jan‐Fang , Wu Zong‐Yen , Tung Kwong‐Chung , Chen Ying‐Ju , Hong Yu‐Kai , Chen Shi‐Yu , Liu Po‐Yu
Published: April 2019

Shewanella xiamenensis is an emerging pathogen causing intra‐abdominal infection and intestinal colonization. Epidemiologic clues suggest its role as a potential food‐borne zoonotic agent. To date, four genome sequences of S. xiamenensis have been made publicly available. All of them were isolated from water samples. In this study, we characterized the genome of a S. xiamenensis strain isolated from a giant grouper in Taiwan. The genome of S. xiamenensis ZYW1 is 4,827,717 bp in length and encodes 4,239 open reading frames. Its genomic sequence shares high homology with other S. xiamenensis strains. blaOXA‐416 was identified. This is the first detection of S. xiamenensis in Taiwan. These genomic data and analyses contribute to our understanding of S. xiamenensis and may help to elucidate disease‐causing mechanisms in future studies.
Interconnect Fatigue Failure Parameter Isolation for Power Device Reliability Prediction in Alternative Accelerated Mechanical Cycling Test
Authors: Montazeri Mahsa , Marbut Cody J. , Huitink David
Published: April 2019

In this work, a rapid and low-cost accelerated reliability test methodology which was designed to simulate mechanical stresses induced in flip–chip bonded devices during the thermal cycling reliability test under isothermal conditions, is introduced and demonstrated using power device analogous test chips. By stressing these devices in a controlled environment, mechanical stresses become decoupled from the design and temperature, such that useful lifetimes can be predictable. Mechanical shear stress was cyclically applied directly to device relevant, flip–chip solder interconnects while monitoring for failure. Herein, finite element analysis (FEA) is used to extract various damage metrics of different solder materials, including PbSn37/63, SAC305, and nanosilver, in both thermal operation and the introduced alternative mechanical testing conditions. Plastic work density and strain are calculated in the critical solder interconnects as factors that indicate the amount of the damage accumulation per cycle during the mechanical cycling, thermal cycling, and power cycling tests. The number of cycles to failure for each test was calculated using the fatigue life model developed by Darveaux for eutectic PbSn solder, while for SAC305 Syed's method was used, and for nanosilver, the Knoerr et al. equations are applied. The effects of environmental temperature and shearing force frequency were studied for the mechanical cycling reliability test, where a modified Norris–Landzberg equation for mechanical cycling tests was explored using the simulation results. Finally, comparing the mechanical cycling with the equivalent thermal cycling and power cycling demonstrated a significant reduction in required test duration to achieve a reliability estimation.
Review Article: Synthesis, properties, and applications of fluorescent diamond particles
Authors: Shenderova Olga A. , Shames Alexander I. , Nunn Nicholas A. , Torelli Marco D. , Vlasov Igor , Zaitsev Alexander
Published: April 2019

Diamond particles containing color centers—fluorescent crystallographic defects embedded within the diamond lattice—outperform other classes of fluorophores by providing a combination of unmatched photostability, intriguing coupled magneto-optical properties, intrinsic biocompatibility, and outstanding mechanical and chemical robustness. This exceptional combination of properties positions fluorescent diamond particles as unique fluorophores with emerging applications in a variety of fields, including bioimaging, ultrasensitive metrology at the nanoscale, fluorescent tags in industrial applications, and even potentially as magnetic resonance imaging contrast agents. However, production of fluorescent nanodiamond (FND) is nontrivial, since it requires irradiation with high-energy particles to displace carbon atoms and create vacancies—a primary constituent in the majority color centers. In this review, centrally focused on material developments, major steps of FND production are discussed with emphasis on current challenges in the field and possible solutions. The authors demonstrate how the combination of fluorescent spectroscopy and electron paramagnetic resonance provides valuable insight into the types of radiation-induced defects formed and their evolution upon thermal annealing, thereby guiding FND performance optimization. A recent breakthrough process allowing for production of fluorescent diamond particles with vibrant blue, green, and red fluorescence is also discussed. Finally, the authors conclude with demonstrations of a few FND applications in the life science arena and in industry.
How heteroepitaxy occurs on strontium titanate
Authors: Cook Seyoung , Letchworth-Weaver Kendra , Tung I-Cheng , Andersen Tassie K. , Hong Hawoong , Marks Laurence D. , Fong Dillon D.
Published: April 2019

In situ surface x-ray diffraction during deposition of LaTiO
3
on SrTiO
3
(001) shows that a TiO
2
adlayer participates in growth.
Targeting RalGAPα1 in skeletal muscle to simultaneously improve postprandial glucose and lipid control
Authors: Chen Qiaoli , Rong Ping , Zhu Sangsang , Yang Xinyu , Ouyang Qian , Wang Hong Yu , Chen Shuai
Published: April 2019

The RalGAPα1/β complex links insulin signaling to glucose and lipid metabolism in skeletal muscle through RalA activation.
Fully soluble self-doped poly(3,4-ethylenedioxythiophene) with an electrical conductivity greater than 1000 S cm
−1
Authors: Yano Hirokazu , Kudo Kazuki , Marumo Kazumasa , Okuzaki Hidenori
Published: April 2019

Fully soluble and highly conductive self-doped poly(3,4-ethylenedioxythiophene) was successfully synthesized.
Modified Mouse Model of Clostridioides difficile Infection as a Platform for Probiotic Efficacy Studies
Authors: De Wolfe T. J. , Kates A. E. , Barko L. , Darien B. J. , Safdar N.
Published: April 2019

Probiotics may represent a promising approach for reducingClostridioides(Clostridium)difficileinfections (CDIs). A clinical trial conducted by our group demonstrated that CDI patients undergoing adjunctive treatment withLactobacillusandBifidobacteriumprobiotics had a reduction in diarrheal duration and compositional changes in their stool microbiomes.
The
Edwardsiella piscicida
Type III Effector EseJ Suppresses Expression of Type 1 Fimbriae, Leading to Decreased Bacterial Adherence to Host Cells
Authors: Zhang Qian , He Tian Tian , Li Duan You , Liu Lu Yi , Nie Pin , Xie Hai Xia
Published: April 2019

The type III secretion system (T3SS) of
Edwardsiella piscicida
plays a crucial role in its pathogenesis. Our previous study indicated that the T3SS effector protein EseJ inhibits the bacterium’s adhesion to epithelioma papillosum cyprini (EPC) cells, while the mechanism of the inhibition remains elusive.
Guanidine Riboswitch-Regulated Efflux Transporters Protect Bacteria against Ionic Liquid Toxicity
Authors: Higgins Douglas A. , Gladden John M. , Kimbrel Jeff A. , Simmons Blake A. , Singer Steven W. , Thelen Michael P.
Published: April 2019

This study identifies bacteria that are tolerant to ionic liquid solvents used in the production of biofuels and industrial biochemicals. For industrial microbiology, it is essential to find less-harmful reagents and microbes that are resistant to their cytotoxic effects. We identified a family of small multidrug resistance efflux transporters, which are responsible for the tolerance of these strains. We also found that this resistance can be caused by mutations in the sequences of guanidine-specific riboswitches that regulate these efflux pumps. Extending this knowledge, we demonstrated that guanidine itself can promote ionic liquid tolerance. Our findings will inform genetic engineering strategies that improve conversion of cellulosic sugars into biofuels and biochemicals in processes where low concentrations of ionic liquids surpass bacterial tolerance.
Mechanisms of B-Cell Oncogenesis Induced by Epstein-Barr Virus
Authors: Saha Abhik , Robertson Erle S.
Published: April 2019

Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus which asymptomatically infects the majority of the world population. Under immunocompromised conditions, EBV can trigger human cancers of epithelial and lymphoid origin.
Which behaviour change techniques are most effective in improving healthcare utilisation in COPD self-management programmes? A protocol for a systematic review
Authors: Smalley Katelyn Rene , Aufegger Lisa , Flott Kelsey , Holt Gracie , Mayer Erik K , Darzi Ara
Published: April 2019

Introduction

Self-management interventions are often presented as a way to improve the quality of care for patients with chronic illness. However, self-management is quite broadly defined and it remains unclear which types of interventions are most successful. This review will use the Theoretical Domains Framework (TDF) as a lens through which to categorise self-management interventions regarding which programmes are most likely to be effective and under which circumstances.

The aim of this study is to (1) describe the types of self-management programmes that have been developed in chronic obstructive pulmonary disease (COPD) and identify the common elements between these to better classify self-management, and (2) evaluate the effect that self-management programmes have on the healthcare behaviour of patients with COPD by classifying those programmes by the behaviour change techniques used.

Methods and analysis

A systematic search of the literature will be performed in MEDLINE, EMBASE, HMIC and PsycINFO. This review will be limited to randomised controlled trials and quasi-experimental studies. The review will follow PRISMA-P guidelines, and will provide a PRISMA checklist and flowchart. Risk of bias in individual studies will be assessed using the Cochrane Risk of Bias criteria, and the quality of included studies will be evaluated using the GRADE criteria, and will be reported in a Summary of Findings table.

The primary analysis will be a catalogue of the interventions based on the components of the TDF that were used in the intervention. A matrix comparing included behaviour change techniques to improvements in utilisation will summarise the primary outcomes.

Ethics and dissemination

Not applicable, as this is a secondary review of the literature.

Prospero registration number

CRD42018104753.
Thermal Casimir effect in the Kerr spacetime with quintessence
Authors: Bezerra V. B. , Toledo J. M.
Published: April 2019

We calculate thermal corrections to the Casimir energy of a massless scalar field in the Kerr black hole surrounded by quintessence, taking into account the metrics derived by Ghosh [S. G. Ghosh, Eur. Phys. J. C 76, 222 (2016)] and Toshmatov et al. [B. Toshmatov, Z. Stuchlík and B. Ahmedov, Eur. Phys. J. Plus 132, 98 (2017)]. We compare both results and show that they are almost the same, except very close to the horizons. At [Formula: see text], equatorial plane, the results are the same, as should be expected, due to the fact that the metrics coincide in this region.
Cobaltosic oxide fiber/Carbon Fiber composites fabricated by hydrothermal for improved electromagnetic interference shielding properties
Authors: Gong Ming , Li Qiang , Sun Lin , Tian Ai-Qin , Sun Shou-Guang
Published: April 2019

In this paper, a newly designed composite of magnetic nano-Co3O4 fiber coated on carbon fiber (Cf) is prepared and characterized for the electromagnetic interference (EMI) shielding properties. XRD, SEM and TEM are used to investigate the micromorphology and microstructure evolution during the preparation. By hydrothermal method, the flowerlike clusters of single crystal flake-Co(OH)2 are first obtained on Cf. The firstly prepared Co(OH)2 sheets then turn into Co3O4 fibers during the next calcination step. The continuous and loose coating of magnetic Co3O4 nanofibers is finally obtained on the Cf. The loose coating is in proportion to the weight loss, and the wirelike Co3O4 is good for the interface strength for the Cf composite preparation. Based on the above work, the loose magnetic fibers coating on the Cf could be a feasible composite structure for the EMI composite materials integrated with absorbing and reflecting.
Identification of the expression of earthquake-induced surface flooding by groundwater using detailed regolith mapping at the buried Atlántida Deposit, northern Chile
Authors: Brown A. E. , Winterburn P. A. , Bissig T.
Published: April 2019

This paper describes saline pockets (10 cm–3 m in diameter) of fine-grained material distributed on alluvial surfaces. These saline pockets are localized along structural trends at the Atlántida buried porphyry-skarn Cu–Au–(Mo) deposit in the Atacama Region of Chile. The distribution and highly saline nature of the material suggest formation by the pooling and evaporation of groundwater forced through fractures to the surface during seismic activity. These saline pockets are a surface expression of the hydrological effects of seismic activity along faults. Saline pockets with similar distribution and characteristics were also identified at three additional alluvium-covered areas, all located in the Antofagasta Region of Chile. Identification and mapping of these saline pockets relies on the ability to identify the continuation of structures through overlying gravels. Regolith mapping using high-resolution drone imagery and digital elevation modelling identified geomorphic markers of faulting which aided mapping the distribution of saline pockets. Saline pockets provide a unique opportunity to sample the direct expression of transported groundwater reaching the surface from depth and provide a prime target medium for mineral exploration through transported gravels.
Coagulopathy implications using a multiscale model of traumatic bleeding matching macro- and microcirculation
Authors: Tsiklidis Evan J. , Sinno Talid , Diamond Scott L.
Published: April 2019

Quantifying the relationship between vascular injury and the dynamic bleeding rate requires a multiscale model that accounts for changing and coupled hemodynamics between the global and microvascular levels. A lumped, global hemodynamic model of the human cardiovascular system with baroreflex control was coupled to a local 24-level bifurcating vascular network that spanned diameters from the muscular artery scale (0.1–1.3 mm) to capillaries (5–10 μm) via conservation of momentum and conservation of mass boundary conditions. For defined injuries of severing all vessels at each nth-level, the changing pressures and flowrates were calculated using prescribed shear-dependent hemostatic clot growth rates (normal or coagulopathic). Key results were as follows: 1) the upstream vascular network rapidly depressurizes to reduce blood loss; 2) wall shear rates at the hemorrhaging wound exit are sufficiently high (~10,000 s−1) to drive von Willebrand factor unfolding; 3) full coagulopathy results in >2-liter blood loss in 2 h for severing all vessels of 0.13- to 0.005-mm diameter within the bifurcating network, whereas full hemostasis limits blood loss to <100 ml within 2 min; and 4) hemodilution from transcapillary refill increases blood loss and could be implicated in trauma-induced coagulopathy. A sensitivity analysis on length-to-diameter ratio and branching exponent demonstrated that bleeding was strongly dependent on these tissue-dependent network parameters. This is the first bleeding model that prescribes the geometry of the injury to calculate the rate of pressure-driven blood loss and local wall shear rate in the presence or absence of coagulopathic blood.

NEW & NOTEWORTHY We developed a multiscale model that couples a lumped, global hemodynamic model of a patient to resolved, single-vessel wounds ranging from the small artery to capillary scale. The model is able to quantify wall shear rates, seal rates, and blood loss rates in the presence and absence of baroreflex control and hemodilution.
Profiling the Mutational Landscape in Known Driver Genes and Novel Genes in African American Non–Small Cell Lung Cancer Patients
Authors: Lusk Christine M. , Watza Donovan , Dyson Greg , Craig Douglas , Ratliff Valerie , Wenzlaff Angela S. , Lonardo Fulvio , Bollig-Fischer Aliccia , Bepler Gerold , Purrington Kristen , Gadgeel Shirish , Schwartz Ann G.
Published: April 2019

Purpose:

Identifying novel driver genes and mutations in African American non–small cell lung cancer (NSCLC) cases can inform targeted therapy and improve outcomes for this traditionally underrepresented population.

Experimental Design:

Tumor DNA, RNA, and germline DNA were collected from African American NSCLC patients who participated in research conducted at the Karmanos Cancer Institute (KCI) in Detroit, Michigan. Known mutations were ascertained through the Sequenom LungCarta panel of 214 mutations in 26 genes, RET/ROS1 fusions, amplification of FGFR1, and expression of ALK. Paired tumor and normal DNA was whole-exome sequenced for a subset of cases without known driver mutations.

Results:

Of the 193 tumors tested, 77 known driver mutations were identified in 66 patients (34.2%). Sixty-seven of the 127 patients without a known driver mutation were sequenced. In 54 of these patients, 50 nonsynonymous mutations were predicted to have damaging effects among the 26 panel genes, 47 of which are not found in The Cancer Genome Atlas NSCLC white or African American samples. Analyzing the whole-exome sequence data using MutSig2CV identified a total of 88 genes significantly mutated at FDR q < 0.1. Only 5 of these genes were previously reported as oncogenic.

Conclusions:

These findings suggest that broader mutation profiling including both known and novel driver genes in African Americans with NSCLC will identify additional mutations that may be useful in treatment decision-making.
Proteomics-Derived Biomarker Panel Improves Diagnostic Precision to Classify Endometrioid and High-grade Serous Ovarian Carcinoma
Authors: Dieters-Castator Dylan Z. , Rambau Peter F. , Kelemen Linda E. , Siegers Gabrielle M. , Lajoie Gilles A. , Postovit Lynne-Marie , Köbel Martin
Published: April 2019

Purpose:

Ovarian carcinomas are a group of distinct diseases classified by histotypes. As histotype-specific treatment evolves, accurate classification will become critical for optimal precision medicine approaches.

Experimental Design:

To uncover differences between the two most common histotypes, high-grade serous (HGSC) and endometrioid carcinoma, we performed label-free quantitative proteomics on freshly frozen tumor tissues (HGSC, n = 10; endometrioid carcinoma, n = 10). Eight candidate protein biomarkers specific to endometrioid carcinoma were validated by IHC using tissue microarrays representing 361 cases of either endometrioid carcinoma or HGSC.

Results:

More than 500 proteins were differentially expressed (P < 0.05) between endometrioid carcinoma and HGSC tumor proteomes. A ranked set of 106 proteins was sufficient to correctly discriminate 90% of samples. IHC validated KIAA1324 as the most discriminatory novel biomarker for endometrioid carcinoma. An 8-marker panel was found to exhibit superior performance for discriminating endometrioid carcinoma from HGSC compared with the current standard of WT1 plus TP53 alone, improving the classification rate for HGSC from 90.7% to 99.2%. Endometrioid carcinoma–specific diagnostic markers such as PLCB1, KIAA1324, and SCGB2A1 were also significantly associated with favorable prognosis within endometrioid carcinoma suggesting biological heterogeneity within this histotype. Pathway analysis of proteomic data revealed differences between endometrioid carcinoma and HGSC pertaining to estrogen and interferon signalling.

Conclusions:

In summary, these findings support the use of multi-marker panels for the differential diagnosis of difficult cases resembling endometrioid carcinoma and HGSC.
Antibody–Drug Conjugates: Future Directions in Clinical and Translational Strategies to Improve the Therapeutic Index
Authors: Coats Steven , Williams Marna , Kebble Benjamin , Dixit Rakesh , Tseng Leo , Yao Nai-Shun , Tice David A. , Soria Jean-Charles
Published: April 2019

Since the first approval of gemtuzumab ozogamicin (Mylotarg; Pfizer; CD33 targeted), two additional antibody–drug conjugates (ADC), brentuximab vedotin (Adcetris; Seattle Genetics, Inc.; CD30 targeted) and inotuzumab ozogamicin (Besponsa; Pfizer; CD22 targeted), have been approved for hematologic cancers and 1 ADC, trastuzumab emtansine (Kadcyla; Genentech; HER2 targeted), has been approved to treat breast cancer. Despite a clear clinical benefit being demonstrated for all 4 approved ADCs, the toxicity profiles are comparable with those of standard-of-care chemotherapeutics, with dose-limiting toxicities associated with the mechanism of activity of the cytotoxic warhead. However, the enthusiasm to develop ADCs has not been dampened; approximately 80 ADCs are in clinical development in nearly 600 clinical trials, and 2 to 3 novel ADCs are likely to be approved within the next few years. While the promise of a more targeted chemotherapy with less toxicity has not yet been realized with ADCs, improvements in technology combined with a wealth of clinical data are helping to shape the future development of ADCs. In this review, we discuss the clinical and translational strategies associated with improving the therapeutic index for ADCs.