bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Improved Survival in Early-Stage Pancreatic Cancer Worth the Extra Cost at High-Volume Centers?
Authors: Perry Lauren M. , Bateni Sarah B. , Bold Richard J. , Hoch Jeffrey S.
Published: March 2021

BACKGROUND:

Volume of operative cases may be an important factor associated with improved survival for early-stage pancreatic cancer. Most high-volume pancreatic centers are also academic institutions, which have been associated with additional healthcare costs. We hypothesized that at high-volume centers, the value of the extra survival outweighs the extra cost.

STUDY DESIGN:

This retrospective cohort study used data from the California Cancer Registry linked to the Office of Statewide Health Planning and Development database from January 1, 2004 through December 31, 2012. Stage I-II pancreatic cancer patients who underwent resection were included. Multivariable analyses estimated overall survival and 30-day costs at low- vs high-volume pancreatic surgery centers. The incremental cost-effectiveness ratio (ICER) and incremental net benefit (INB) were estimated, and statistical uncertainty was characterized using net benefit regression.

RESULTS:

Of 2,786 patients, 46.5% were treated at high-volume centers and 53.5% at low-volume centers. There was a 0.45-year (5.4 months) survival benefit (95% CI 0.21–0.69) and a $7,884 extra cost associated with receiving surgery at high-volume centers (95% CI $4,074–$11,694). The ICER was $17,529 for an additional year of survival (95% CI $7,997–$40,616). For decision-makers willing to pay more than $20,000 for an additional year of life, high-volume centers appear cost-effective.

CONCLUSIONS:

Although healthcare costs were greater at high-volume centers, patients undergoing pancreatic surgery at high-volume centers experienced a survival benefit (5.4 months). The extra cost of $17,529 per additional year is quite modest for improved survival and is economically attractive by many oncology standards.
Fibrinolysis Shutdown in COVID-19: Clinical Manifestations, Molecular Mechanisms, and Therapeutic Implications
Authors: Meizoso Jonathan P. , Moore Hunter B. , Moore Ernest E.
Published: March 2021

The COVID-19 pandemic has introduced a global public health threat unparalleled in our history. The most severe cases are marked by ARDS attributed to microvascular thrombosis. Hypercoagulability, resulting in a profoundly prothrombotic state, is a distinct feature of COVID-19 and is accentuated by a high incidence of fibrinolysis shutdown. The aims of this review were to describe the manifestations of fibrinolysis shutdown in COVID-19 and its associated outcomes, review the molecular mechanisms of dysregulated fibrinolysis associated with COVID-19, and discuss potential implications and therapeutic targets for patients with severe COVID-19.
Investigating cyber attacks using domain and DNS data
Authors: Anderson Chad , Conwell John ‘Turbo’ , Saleh Tarik
Published: March 2021

In July 2020, more than 130 high-profile, verified Twitter accounts were compromised. The accounts, which included the personal accounts of Elon Musk, Bill Gates, Kanye West and then-US presidential candidate Joe Biden, shared tweets calling for people to send money to a bitcoin wallet with the promise that they would be sent back double the amount in return. 1

The majority of cyber attacks leverage the central role that DNS plays in facilitating Internet traffic.

From botnets spreading disinformation and undertaking distributed denial of service (DDoS) attacks to sophisticated spear-phishing campaigns, attackers typically will set up dozens, hundreds or even thousands of malicious domains to stay one step ahead of detection systems and blacklists. These leave a trail that can provide insight into the attackers’ real motivations and even lead to the perpetrators, explain Chad Anderson, John ‘Turbo’ Conwell and Tarik Saleh of DomainTools.
Cyberthreats are going mobile and it's time to take action
Authors: Davison Tom
Published: March 2021

The world recently experienced an accelerated shift towards a remote working environment under Covid-19. Before the pandemic, workforces primarily relied on desktops and corporate network servers, with only 5% of UK workers operating from home. 1 That number is now 72%. As many of us continue to work away from the office and try to juggle personal responsibilities, we are finding new ways to stay productive – this includes using our mobile devices more.
Going round the twist—an empirical analysis of shell coiling in helicospiral gastropods
Authors: Collins Katie S. , Klapaukh Roman , Crampton James S. , Gazley Michael F. , Schipper C. Ian , Maksimenko Anton , Hines Benjamin R.
Published: March 2021

The logarithmic helicospiral has been the most widely accepted model of regularly coiled molluscan form since it was proposed by Moseley and popularized by Thompson and Raup. It is based on an explicit assumption that shells are isometric and grow exponentially, and an implicit assumption that the external form of the shell follows the internal shape, which implies that the parameters of the spiral could be reconstructed from the external whorl profile. In this contribution, we show that these assumptions fail on all 25 gastropod species we examine. Using a dataset of 176 fossil and modern gastropod shells, we construct an empirical morphospace of coiling using the parameters of whorl expansion rate, translation rate, and rate of increasing distance from coiling axis, plus rate of aperture shape change, from their best-fit models. We present a case study of change in shell form through geologic time in the austral family Struthiolariidae to demonstrate the utility of our approach for evolutionary paleobiology. We fit various functions to the shell-coiling parameters to demonstrate that the best morphological model is not the same for each parameter. We present a set of R routines that will calculate helicospiral parameters from sagittal sections through coiled shells and allow workers to compare models and choose appropriate sets of parameters for their own datasets. Shell-form parameters in the Struthiolariidae highlight a hitherto neglected hypothesis of relationship between Antarctic Perissodonta and the enigmatic Australian genus Tylospira that fits the biogeographic and stratigraphic distribution of both genera.
La Hora de la Salsa: Nicolás Maduro and the Political Dimensions of Salsa in Venezuela
Authors: Bellaviti Sean
Published: March 2021

In this article I examine how, during a period of extreme social unrest, Venezuelan President Nicolás Maduro took up the role of a salsa radio deejay as a show of confidence in his hold on political power and of his solidarity with ordinary Venezuelans. I argue that this all but unprecedented and, for many, controversial course of action by a sitting president provides us with an unusual opportunity to analyse Venezuela's long-standing political crisis. In particular, I highlight how Maduro harnessed salsa's long association with poor Latin Americans, its connection to Venezuela and its pleasurable character to bolster his socialist credentials, and I show how this strategy unleashed a public exchange of criticisms with one legendary salsero (salsa musician), Rubén Blades. By exploring the way music intersects with politics, I show how popular culture is neither ancillary to nor derivative of the country's ever-deepening strife but, rather, constitutive of it.
“Against Right and Reason”: The Bold but Smooth French Take-Over of Dutch Cayenne (1655–1664)
Authors: van den Bel Martijn
Published: March 2021

The Dutch loss of Brazil in 1654 favoured the resettlement of Dutch merchants along the Wild Coast and in the Lesser Antilles and the establishment of new colonies. Cayenne Island was one of them. One WIC patent was handed to Jan Claes Langedijck, who settled at the former French fort of Cépérou, and another patent was given to David Nassy, who settled in the Anse de Rémire, situated at the opposite part of the former island. Both colonies were taken by the French in May 1664 as part of the imperial French expansion under King Louis XIV and Jean-Baptist Colbert. It is argued here that the main French goal was to gain control of the sugar plantations of the Sephardic community located there, and, to a lesser extent, the much-desired territorial control of this region as proposed by the newly established French West India Company. The Dutch were aware of the attack, but could not intervene as it was already too late to send support to the poorly defended Cayenne colony. Both parties negotiated the take-over and the majority of the Dutch settlers stayed under French rule, as was suggested by the Dutch government and hoped for by the French.
LEAST SQUARES AND IVX LIMIT THEORY IN SYSTEMS OF PREDICTIVE REGRESSIONS WITH GARCH INNOVATIONS
Authors: Magdalinos Tassos
Published: March 2021

The paper examines the effect of conditional heteroskedasticity on least squares inference in stochastic regression models of unknown integration order and proposes an inference procedure that is robust to models within the (near) I(0)–(near) I(1) range with GARCH innovations. We show that a regressor signal of exact order$O_{p}\left ( n\kappa _{n}\right ) $for arbitrary$\,\kappa _{n}\rightarrow \infty $is sufficient to eliminate stationary GARCH effects from the limit distributions of least squares based estimators and self-normalized test statistics. The above order dominates the$O_{p}\left ( n\right ) $signal of stationary regressors but may be dominated by the$O_{p}\left ( n^{2}\right ) $signal of I(1) regressors, thereby showing that least squares invariance to GARCH effects is not an exclusively I(1) phenomenon but extends to processes with persistence degree arbitrarily close to stationarity. The theory validates standard inference for self normalized test statistics based on the ordinary least squares estimator when$\kappa _{n}\rightarrow \infty $and$\kappa _{n}/n\rightarrow 0$and the IVX estimator (Phillips and Magdalinos (2009a), Econometric Inference in the Vicinity of Unity. Working paper, Singapore Management University; Kostakis, Magdalinos, and Stamatogiannis, 2015a,Review of Financial Studies28(5), 1506–1553.) when$\kappa _{n}\rightarrow \infty $and the innovation sequence of the system is a covariance stationary vec-GARCH process. An adjusted version of the IVX–Wald test is shown to also accommodate GARCH effects in purely stationary regressors, thereby extending the procedure’s validity over the entire (near) I(0)–(near) I(1) range of regressors under conditional heteroskedasticity in the innovations. It is hoped that the wide range of applicability of this adjusted IVX–Wald test, established in Theorem 4.4, presents an advantage for the procedure’s suitability as a tool for applied research.
BEYOND LINGUISTIC FEATURES
Authors: Nagle Charles L. , Trofimovich Pavel , O’Brien Mary Grantham , Kennedy Sara
Published: March 2021

Comprehensibility, or ease of understanding, has emerged as an important construct in second language (L2) speech research. Many studies have examined the linguistic features that underlie this construct, but there has been limited work on behavioral and affective predictors. The goal of this study was therefore to examine the extent to which anxiety and collaborativeness predict interlocutors’ perception of one another’s comprehensibility. Twenty dyads of L2 English speakers completed three interactive tasks. Throughout their 17-minute interaction, they were periodically asked to evaluate their own and each other’s anxiety and collaborativeness and to rate their partner’s comprehensibility using 100-point scales. Mixed-effects models showed that partner anxiety and collaborativeness predicted comprehensibility, but the relative importance of each predictor depended on the nature of the task. Self-collaborativeness was also related to comprehensibility. These findings suggest that comprehensibility is sensitive to a range of linguistic, behavioral, and affective influences.
Exploring into contributing factors to young seafarer turnover: empirical evidence from China
Authors: Bao Junzhong , Li Yan , Zheng Guoping , Zhang Pengfei
Published: March 2021

Various studies suggest that the maritime industry will continue to face the challenge of seafarer shortages. Young seafarer turnover has become a serious issue that cannot be underestimated. This paper aims to identify the root causes of young seafarer attrition in China and explore relevant solutions. It collects information via semi-structured interviews and questionnaires. Independent sample t-test, one-way ANOVA and least-significant difference are utilised for the variance analysis. The findings of the study show that occupational recognition and family responsibility are the two major factors contributing to young seafarers’ outflow. Chinese seafarers’ health status is another important factor that has received little attention. In addition, young seafarers of 31–35 years old have the most possibility of turnover, due to a number of reasons discussed in this paper. Age 40 or thereabouts is viewed as the watershed moment in a seafarer's career, so efforts should be made to help young seafarers pass through the hard period in their early thirties. This paper suggests that a clear career plan could be a potential solution to retain this backbone group as prospective senior officers.
Dung on the Wall. Ontology and Relationality in Qurna: The Case of TT123
Authors: Pellini José Roberto
Published: March 2021

Based on the identification of modern dung remains on the TT123 tomb wall, I propose to think of TT123 in new ways, looking for other possible realities besides those produced by the processes of recognition, identification and categorization that dominate the archaeological interpretive process. The idea is to seek to understand TT123 from new traditions and new knowledge to produce something new. The idea is not to ask what TT123 means, but to understand how it works within the different possible encounters in which it is inserted. More than offering just another point of view in relation to those with epistemic privilege, I will try to demonstrate that other realities are possible and that such alternative realities can have political and material consequences. An alternative reality is not reality, it is only a potential reality.
An Illustrated Shiʿi Pilgrimage Scroll in the Collections of the Royal Asiatic Society
Authors: MARZOLPH ULRICH , RENAULD MATHILDE
Published: March 2021

The collections of the Royal Asiatic Society hold an illustrated pilgrimage scroll apparently dating from the first half of the nineteenth century. The scroll's hand painted images relate to the journey that a pious Shiʿi Muslim would have undertaken after the performance of the pilgrimage to Mecca. Its visual narrative continues, first to Medina and then to the Shiʿi sanctuaries in present-day Iraq, concluding in the Iranian city of Mashhad at the sanctuary of the eighth imam of the Twelver-Shiʿi creed, imam Riḍā (d. 818). The scroll was likely prepared in the early nineteenth century and acquired by the Royal Asiatic Society from its unknown previous owner sometime after 1857. In terms of chronology the pilgrimage scroll fits neatly into the period between the Niebuhr scroll, bought in Karbala in 1765, and a lithographed item most likely dating from the latter half of the nineteenth century, both of which depict a corresponding journey. The present essay's initial survey of the scroll's visual dimension, by Ulrich Marzolph, adds hitherto unknown details to the history of similar objects. The concluding report, by Mathilde Renauld, sheds light on the scroll's material condition and the difficulties encountered during the object's conservation and their solution.
Complex transformation of divorce in Vietnam under the forces of modernization and individualism
Authors: Thi Minh Thi Tran
Published: March 2021

After more than four decades since its reunification since 1975, Vietnam has achieved remarkable results in social and economic development. With the rapid speed of recent modernization, society has loosened numerous old values related to the family and promoted individual freedoms. Marriage and family affairs, including divorce, have modernized with liberal characteristics. The paper examines the trends of divorce and reasons for divorce using statistical data from the Vietnam People's Supreme Court and from the government's annual population statistics. The analysis compiled and analysed a database of every divorce case at six urban and rural districts in Can Tho province. The analysis highlights changes in the reasons for divorce in the South in comparison with previous divorce studies in the North of Vietnam, discussed in relation to modernization, individualism and gender equality. The analysis is supported by interview data with thirty male and female divorcees.
Reforming Qualifications: the how, the why and the who
Authors: Bristow Caroline
Published: March 2021

Like all teachers, when I was in the classroom, I knew inside out the syllabus I was teaching and the papers which would assess it. I also, however, gave very little thought to how these things had come to be. I had a vague sense that the ‘Exam Board’ had created them and awarded my students their grades, but they were a black box, moving in mysterious ways. I gave even less thought to the Powers That Be above and beyond the boards and the impact they had on me and my students.
Why I Wrote Clarke's Latin
Authors: Clarke Ed
Published: March 2021

Never has the phrase annus horribilis seemed more applicable than in this past dreadful year. Virgil's lacrimae rerum have, I imagine, been with us all throughout; though I doubt that it was ‘the tiers of things’ he had in mind.
Prevalence of Shallow Low‐Frequency Earthquakes in the Continental Crust
Authors: Nakajima Junichi , Hasegawa Akira
Published: March 2021

Low‐frequency earthquakes (LFEs) that predominantly occur at depths of 20–30 km are categorized as a particular class of earthquakes whose spectral power is concentrated at 1–4 Hz. While the tectonic LFEs along megathrust boundaries occur as shear failure, the genesis of LFEs in the continental plate is poorly understood due to the diversity of focal mechanism solutions. Here we conduct a systematic survey of LFEs using two metrics (frequency index and peak frequency) that characterize the frequency content of the waveforms, and show that LFEs are prevalent in the upper crust beneath the Japanese Islands, even in non‐volcanic regions. Shallow LFEs are most common near tectonic boundaries and are temporarily activated in the aftershock sequences of large (M ≥ 6.5) crustal earthquakes. The widespread distribution of shallow LFEs suggests that a lower crustal rheology is not necessary for their genesis. We infer that failure along frictionally weakened faults due to high pore‐fluid pressures is a primary control for the enrichment of low‐frequency energy. The observed differences in the frequency content are probably due to differences in the pore‐fluid pressure along each fault, which influences the rupture velocity and magnitude of the tensile component during shear failure. Our observations may lead to a more unified model of earthquake generation, thereby providing a better understanding of how earthquakes release the stress accumulated in the Earth.
Surf Zone Waves at the Onset of Breaking: 1. LIDAR and IR Data Fusion Methods
Authors: Carini Roxanne J. , Chickadel C. Chris , Jessup Andrew T.
Published: March 2021

This is the first of a 2‐part series concerning remote observation and wave‐by‐wave analysis of the onset of breaking in the surf zone. In the surf zone, breaking waves drive nearshore circulation, suspend sediment, and promote air‐sea gas exchange. Nearshore wave model predictions often diverge fromin situmeasurements near the break point location because common parameterizations do not account for the rapid changes that occur near the onset of breaking. This work presents extensive methodology to combine data from a line‐scanning LIDAR and thermal infrared cameras to detect breaking, classify breaker type, and measure geometric wave parameters on a wave‐by‐wave basis, which can be used to improve breaker parameterizations. Over 2,600 non‐breaking and 1,600 breaking waves are analyzed from data collected at the USACE Field Research Facility in Duck, NC, including 413 spilling and 111 plunging waves for which the onset of breaking was observed. Wave height is estimated using a spatio‐temporal method for wave tracking that preserves the sea surface elevation maximum and overcomes field of view limitations. Methods for estimating instantaneous wave speed are refined by fitting a skewed Gaussian function to each wave profile before tracking the peaks. Wave slope is estimated from a linear fit to the upper 80% of the wave face, which provides a robust metric and strong correlation with geometric wave slope defined relative to mean sea level. Finally, breaking wave face foam coverage is analyzed to assess common model assumptions about roller length for wave energy dissipation parameterizations.
Developmental programming of offspring adipose tissue biology and obesity risk
Authors: Rodgers Amanda , Sferruzzi-Perri Amanda N.
Published: March 2021

Obesity is reaching epidemic proportions and imposes major negative health crises and an economic burden in both high and low income countries. The multifaceted nature of obesity represents a major health challenge, with obesity affecting a variety of different organs and increases the risk of many other noncommunicable diseases, such as type 2 diabetes, fatty liver disease, dementia, cardiovascular diseases, and even cancer. The defining organ of obesity is the adipose tissue, highlighting the need to more comprehensively understand the development and biology of this tissue to understand the pathogenesis of obesity. Adipose tissue is a miscellaneous and highly plastic endocrine organ. It comes in many different sizes and shades and is distributed throughout many different locations in the body. Though its development begins prenatally, quite uniquely, it has the capacity for unlimited growth throughout adulthood. Adipose tissue is also a highly sexually dimorphic tissue, patterning men and women in different ways, which means the risks associated with obesity are also sexually dimorphic. Recent studies show that environmental factors during prenatal and early stages of postnatal development have the capacity to programme the structure and function of adipose tissue, with implications for the development of obesity. This review summarizes the evidence for a role for early environmental factors, such as maternal malnutrition, hypoxia, and exposure to excess hormones and endocrine disruptors during gestation in the programming of adipose tissue and obesity in the offspring. We will also discuss the complexity of studying adipose tissue biology and the importance of appreciating nuances in adipose tissue, such as sexual dimorphism and divergent responses to metabolic and endocrine stimuli. Given the rising levels of obesity worldwide, understanding how environmental conditions in early life affects adipose tissue phenotype and the subsequent development of obesity is of absolute importance.
Use of a non-invasive accelerometric method for diagnosing gastroesophageal reflux in premature infants
Authors: Gewolb Ira H. , Vice Frank L.
Published: March 2021

Objective

To evaluate the clinical usefulness of a non-invasive accelerometric device to diagnose GER in preterm babies.

Study design

An accelerometer was taped over the sub-xiphoid process in 110 preterm (GA 29.6 ± 3.3 wk) infants (133 studies). Low frequency, sub-audible signals were captured via digital recording (sampling rate 200 Hz), then re-sampled (rate = 60 Hz) to create a spectrogram (focused range 0–30 Hz). Mean amplitude in the focused range was calculated.

Results

Of 85 studies with simultaneous pH-metry and accelerometry, 18 had concurrent positive and 23 had concurrent negative scores, 42 had negative pH scores when accelerometry was positive (≥1 µV), consistent with non-acid reflux. Eleven infants at high risk of aspiration received surgical interventions. All but 1 had negative pH scores while 10/11 had positive accelerometry.

Conclusions

The non-invasiveness of this accelerometric technique allows for GER screening and for repeated testing to assess efficacy of interventions.
Prenatally traumatized mice reveal hippocampal methylation and expression changes of the stress-related genes Crhr1 and Fkbp5
Authors: Plank Anne-Christine , Frey Stefan , Basedow Lukas Andreas , Solati Jalal , Canneva Fabio , von Hörsten Stephan , Kratz Oliver , Moll Gunther H. , Golub Yulia
Published: March 2021

In our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.
Renal effects of the serine protease inhibitor aprotinin in healthy conscious mice
Authors: Wörner Stefan , Bohnert Bernhard N. , Wörn Matthias , Xiao Mengyun , Janessa Andrea , Birkenfeld Andreas L. , Amann Kerstin , Daniel Christoph , Artunc Ferruh
Published: March 2021

Treatment with aprotinin, a broad-spectrum serine protease inhibitor with a molecular weight of 6512 Da, was associated with acute kidney injury, which was one of the reasons for withdrawal from the market in 2007. Inhibition of renal serine proteases regulating the epithelial sodium channel ENaC could be a possible mechanism. Herein, we studied the effect of aprotinin in wild-type 129S1/SvImJ mice on sodium handling, tubular function, and integrity under a control and low-salt diet. Mice were studied in metabolic cages, and aprotinin was delivered by subcutaneously implanted sustained release pellets (2 mg/day over 10 days). Mean urinary aprotinin concentration ranged between 642 ± 135 (day 2) and 127 ± 16 (day 8) µg/mL . Aprotinin caused impaired sodium preservation under a low-salt diet while stimulating excessive hyperaldosteronism and unexpectedly, proteolytic activation of ENaC. Aprotinin inhibited proximal tubular function leading to glucosuria and proteinuria. Plasma urea and cystatin C concentration increased significantly under aprotinin treatment. Kidney tissues from aprotinin-treated mice showed accumulation of intracellular aprotinin and expression of the kidney injury molecule 1 (KIM-1). In electron microscopy, electron-dense deposits were observed. There was no evidence for kidney injury in mice treated with a lower aprotinin dose (0.5 mg/day). In conclusion, high doses of aprotinin exert nephrotoxic effects by accumulation in the tubular system of healthy mice, leading to inhibition of proximal tubular function and counterregulatory stimulation of ENaC-mediated sodium transport.
Loss of QKI in macrophage aggravates inflammatory bowel disease through amplified ROS signaling and microbiota disproportion
Authors: Wang Wenwen , Zhai Dongsheng , Bai Yongquan , Xue Ke , Deng Lele , Ma Lirong , Du Tianshu , Ye Zicheng , Qu Di , Xiang An , Chen Guo , Zhao Yi , Wang Li , Lu Zifan
Published: March 2021

Inflammatory bowel disease (IBD) is a refractory chronic inflammatory illness of the gastrointestinal (GI) tract. Macrophage exerts an important role in IBD development. QKI, as an RNA binding protein, was related with inflammatory responses in bacterial infections by regulating the polarization of macrophages. Therefore, we suspected that QKI-regulated macrophages have the potential to play a certain role in IBD and the underlying mechanism. Our results demonstrated that the mice with macrophage-specific deletion of QKI induced with dextran sodium sulfate (DSS) are more susceptible to IBD development, exhibited a severe leaky gut barrier phenotype and higher intense oxidative stress, which are rescued by treating with butylated hydroxyanisole (BHA), an agonist of NRF2. Mechanically, we observed that Keap1 mRNA in the nucleus was exported to the cytoplasm after LPS stimuli in parallel with QKI reductions, and the removal of QKI by shRNA facilitated Keap1 mRNA nuclear exporting and expression in cytoplasm, consequently NRF2 activation in nucleus was weakened, and led to the impaired antioxidant abilities. In addition, mice models of fecal microbiota transplant (FMT) and the co-culturing of mice epithelia cells with feces derived from the DSS-treated QKI-deficit mice revealed consistently aggravated colitis along with a severe oxidative stress; 16S sequencing analysis substantiated the altered compositions of commensal bacteria too. Overall, the current study represents the first effort to explore the anti-oxidant role of QKI in the intestinal macrophage via post-transcriptional regulation of Keap1 mRNA localization and the relevant NRF2 antioxidant signaling, and the disproportional changes in the microbiota were attributable to the mediation of pathogenic damage in the IBD development of QKI-deficit mice.
Translation error clusters induced by aminoglycoside antibiotics
Authors: Wohlgemuth Ingo , Garofalo Raffaella , Samatova Ekaterina , Günenç Aybeg Nafiz , Lenz Christof , Urlaub Henning , Rodnina Marina V.
Published: March 2021

Aminoglycoside antibiotics target the ribosome and induce mistranslation, yet which translation errors induce bacterial cell death is unclear. The analysis of cellular proteins by quantitative mass spectrometry shows that bactericidal aminoglycosides induce not only single translation errors, but also clusters of errors in full-length proteins in vivo with as many as four amino acid substitutions in a row. The downstream errors in a cluster are up to 10,000-fold more frequent than the first error and independent of the intracellular aminoglycoside concentration. The prevalence, length, and composition of error clusters depends not only on the misreading propensity of a given aminoglycoside, but also on its ability to inhibit ribosome translocation along the mRNA. Error clusters constitute a distinct class of misreading events in vivo that may provide the predominant source of proteotoxic stress at low aminoglycoside concentration, which is particularly important for the autocatalytic uptake of the drugs.
Quantum measurement arrow of time and fluctuation relations for measuring spin of ultracold atoms
Authors: Jayaseelan Maitreyi , K. Manikandan Sreenath , Jordan Andrew N. , Bigelow Nicholas P.
Published: March 2021

The origin of macroscopic irreversibility from microscopically time-reversible dynamical laws—often called the arrow-of-time problem—is of fundamental interest in both science and philosophy. Experimentally probing such questions in quantum theory requires systems with near-perfect isolation from the environment and long coherence times. Ultracold atoms are uniquely suited to this task. We experimentally demonstrate a striking parallel between the statistical irreversibility of wavefunction collapse and the arrow of time problem in the weak measurement of the quantum spin of an atomic cloud. Our experiments include statistically rare events where the arrow of time is inferred backward; nevertheless we provide evidence for absolute irreversibility and a strictly positive average arrow of time for the measurement process, captured by a fluctuation theorem. We further demonstrate absolute irreversibility for measurements performed on a quantum many-body entangled wavefunction—a unique opportunity afforded by our platform—with implications for studying quantum many-body dynamics and quantum thermodynamics.
Adipocyte PHLPP2 inhibition prevents obesity-induced fatty liver
Authors: Kim KyeongJin , Kang Jin Ku , Jung Young Hoon , Lee Sang Bae , Rametta Raffaela , Dongiovanni Paola , Valenti Luca , Pajvani Utpal B.
Published: March 2021

Increased adiposity confers risk for systemic insulin resistance and type 2 diabetes (T2D), but mechanisms underlying this pathogenic inter-organ crosstalk are incompletely understood. We find PHLPP2 (PH domain and leucine rich repeat protein phosphatase 2), recently identified as the Akt Ser473 phosphatase, to be increased in adipocytes from obese mice. To identify the functional consequence of increased adipocyte PHLPP2 in obese mice, we generated adipocyte-specific PHLPP2 knockout (A-PHLPP2) mice.A-PHLPP2mice show normal adiposity and glucose metabolism when fed a normal chow diet, but reduced adiposity and improved whole-body glucose tolerance as compared to Cre- controls with high-fat diet (HFD) feeding. Notably, HFD-fedA-PHLPP2mice show increased HSL phosphorylation, leading to increased lipolysis in vitro and in vivo. Mobilized adipocyte fatty acids are oxidized, leading to increased peroxisome proliferator-activated receptor alpha (PPARα)-dependent adiponectin secretion, which in turn increases hepatic fatty acid oxidation to ameliorate obesity-induced fatty liver. Consistently, adipose PHLPP2 expression is negatively correlated with serum adiponectin levels in obese humans. Overall, these data implicate an adipocyte PHLPP2-HSL-PPARα signaling axis to regulate systemic glucose and lipid homeostasis, and suggest that excess adipocyte PHLPP2 explains decreased adiponectin secretion and downstream metabolic consequence in obesity.
Author Correction: Please give me a copy of my child’s raw genomic data
Authors: Chad Lauren , Szego Michael J.
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41525-021-00191-y
Examining changes in personality following shamanic ceremonial use of ayahuasca
Authors: Weiss Brandon , Miller Joshua D. , Carter Nathan T. , Keith Campbell W.
Published: March 2021

The present study examines the association between the ceremonial use of ayahuasca—a decoction combining the Banistereopsis caapi vine and N,N-Dimethyltryptamine-containing plants—and changes in personality traits as conceived by the Five-Factor model (FFM). We also examine the degree to which demographic characteristics, baseline personality, and acute post-ayahuasca experiences affect personality change. Participants recruited from three ayahuasca healing and spiritual centers in South and Central America (N = 256) completed self-report measures of personality at three timepoints (Baseline, Post, 3-month Follow-up). Informant-report measures of the FFM were also obtained (N = 110). Linear mixed models were used to examine changes in personality and the moderation of those changes by covariates. The most pronounced change was a reduction in Neuroticism dzself-reportT1–T2 =  − 1.00; dzself-reportT1–T3 =  − .85; dzinformant-reportT1–T3 =  − .62), reflected in self- and informant-report data. Moderation of personality change by baseline personality, acute experiences, and purgative experiences was also observed.
Tracking the formation and degradation of fatty-acid-accumulated mitochondria using label-free chemical imaging
Authors: Zhang Chi , Boppart Stephen A.
Published: March 2021

The mitochondrion is one of the key organelles for maintaining cellular homeostasis. External environmental stimuli and internal regulatory processes may alter the metabolism and functions of mitochondria. To understand these activities of mitochondria, it is critical to probe the key metabolic molecules inside these organelles. In this study, we used label-free chemical imaging modalities including coherent anti-Stokes Raman scattering and multiphoton-excited fluorescence to investigate the mitochondrial activities in living cancer cells. We found that hypothermia exposure tends to induce fatty-acid (FA) accumulation in some mitochondria of MIAPaCa-2 cells. Autofluorescence images show that the FA-accumulated mitochondria also have abnormal metabolism of nicotinamide adenine dinucleotide hydrogen, likely induced by the dysfunction of the electron transport chain. We also found that when the cells were re-warmed to physiological temperature after a period of hypothermia, the FA-accumulated mitochondria changed their structural features. To the best of our knowledge, this is the first time that FA accumulation in mitochondria was observed in live cells. Our research also demonstrates that multimodal label-free chemical imaging is an attractive tool to discover abnormal functions of mitochondria at the single-organelle level and can be used to quantify the dynamic changes of these organelles under perturbative conditions.
Author Correction: Assessment of nanoindentation in stiffness measurement of soft biomaterials: kidney, liver, spleen and uterus
Authors: Wu Guanlin , Gotthardt Michael , Gollasch Maik
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The nickel-chelator dimethylglyoxime inhibits human amyloid beta peptide in vitro aggregation
Authors: Benoit Stéphane L. , Maier Robert J.
Published: March 2021

One of the hallmarks of the most common neurodegenerative disease, Alzheimer’s disease (AD), is the extracellular deposition and aggregation of Amyloid Beta (Aβ)-peptides in the brain. Previous studies have shown that select metal ions, most specifically copper (Cu) and zinc (Zn) ions, have a synergistic effect on the aggregation of Aβ-peptides. In the present study, inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the metal content of a commercial recombinant human Aβ40 peptide. Cu and Zn were among the metals detected; unexpectedly, nickel (Ni) was one of the most abundant elements. Using a fluorescence-based assay, we found that Aβ40 peptide in vitro aggregation was enhanced by addition of Zn2+ and Ni2+, and Ni2+-induced aggregation was facilitated by acidic conditions. Nickel binding to Aβ40 peptide was confirmed by isothermal titration calorimetry. Addition of the Ni-specific chelator dimethylglyoxime (DMG) inhibited Aβ40 aggregation in absence of added metal, as well as in presence of Cu2+ and Ni2+, but not in presence of Zn2+. Finally, mass spectrometry analysis revealed that DMG can coordinate Cu or Ni, but not Fe, Se or Zn. Taken together, our results indicate that Ni2+ ions enhance, whereas nickel chelation inhibits, Aβ peptide in vitro aggregation. Hence, DMG-mediated Ni-chelation constitutes a promising approach towards inhibiting or slowing down Aβ40 aggregation.
Circulating CXCL10 and IL-6 in solid organ donors after brain death predict graft outcomes
Authors: Piemonti Lorenzo , Sordi Valeria , Pellegrini Silvia , Scotti Giulia Maria , Scavini Marina , Sioli Viviana , Gianelli Castiglione Andrea , Cardillo Massimo
Published: March 2021

We tested the hypothesis that circulating CXCL10 and IL-6 in donor after brain death provide independent additional predictors of graft outcome. From January 1, 2010 to June 30, 2012 all donors after brain death managed by the NITp (n = 1100) were prospectively included in this study. CXCL10 and IL-6 were measured on serum collected for the crossmatch at the beginning of the observation period. Graft outcome in recipients who received kidney (n = 1325, follow-up 4.9 years), liver (n = 815, follow-up 4.3 years) and heart (n = 272, follow-up 5 years) was evaluated. Both CXCL-10 and IL-6 showed increased concentration in donors after brain death. The intensive care unit stay, the hemodynamic instability, the cause of death, the presence of risk factors for cardiovascular disease and the presence of ongoing infection resulted as significant determinants of IL-6 and CXCL10 donor concentrations. Both cytokines resulted as independent predictors of Immediate Graft Function. Donor IL-6 or CXCL10 were associated with graft failure after liver transplant, and acted as predictors of recipient survival after kidney, liver and heart transplantation. Serum donor IL-6 and CXCL10 concentration can provide independent incremental prediction of graft outcome among recipients followed according to standard clinical practice.
Development of a scale for early prediction of refractory Mycoplasma pneumoniae pneumonia in hospitalized children
Authors: Bi Ying , Zhu Yifan , Ma Xiao , Xu Jiejing , Guo Yun , Huang Tianyu , Zhang Siqing , Wang Xin , Zhao Deyu , Liu Feng
Published: March 2021

Now there is no clinical scale for early prediction of refractory Mycoplasma pneumoniae pneumonia (RMPP). The aim of this study is to identify indicators and develop an early predictive scale for RMPP in hospitalized children. First we conducted a retrospective cohort study of children with M. pneumoniae pneumonia admitted to Children’s Hospital of Nanjing Medical University, China in 2016. Children were divided into two groups, according to whether their pneumonia were refractory and the results were used to develop an early predictive scale. Second we conducted a prospective study to validate the predictive scale for RMPP in children in 2018. 618 children were included in the retrospective study, of which 73 with RMPP. Six prognostic indicators were identified and included in the prognostic assessment scale. The sensitivity of the prognostic assessment scale was 74.0% (54/73), and the specificity was 88.3% (481/545) in the retrospective study. 944 children were included in the prospective cohort, including 92 with RMPP, the sensitivity of the prognostic assessment scale was 78.3% (72/92) and the specificity was 86.2% (734/852). The prognostic assessment scale for RMPP has high diagnostic accuracy and is suitable for use in standard clinical practice.
Genome insight and description of antibiotic producing Massilia antibiotica sp. nov., isolated from oil-contaminated soil
Authors: Dahal Ram Hari , Chaudhary Dhiraj Kumar , Kim Jaisoo
Published: March 2021

An ivory-coloured, motile, Gram-stain-negative bacterium, designated TW-1T was isolated from oil-contaminated experimental soil in Kyonggi University. The phylogenetic analysis based on 16S rRNA gene sequence revealed, strain TW-1T formed a lineage within the family Oxalobacteraceae and clustered as members of the genus Massilia. The closest members were M. pinisoli T33T (98.8% sequence similarity), M. putida 6NM-7T (98.6%), M. arvi THG-RS2OT (98.5%), M. phosphatilytica 12-OD1T (98.3%) and M. niastensis 5516S-1T (98.2%). The sole respiratory quinone is ubiquinone-8. The major cellular fatty acids are hexadeconic acid, cis-9, methylenehexadeconic acid, summed feature 3 and summed feature 8. The major polar lipids are phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The DNA G + C content of the type strain is 66.3%. The average nucleotide identity (ANI) and in silico DNA–DNA hybridization (dDDH) relatedness values between strain TW-1T and closest members were below the threshold value for species demarcation. The genome size is 7,051,197 bp along with 46 contigs and 5,977 protein-coding genes. The genome showed 5 putative biosynthetic gene clusters (BGCs) that are responsible for different secondary metabolites. Cluster 2 showed thiopeptide BGC with no known cluster blast, indicating TW-1T might produce novel antimicrobial agent. The antimicrobial assessment also showed that strain TW-1T possessed inhibitory activity against Gram-negative pathogens (Escherichia coli and Pseudomonas aeruginosa). This is the first report of the species in the genus Massilia which produces antimicrobial compounds. Based on the polyphasic study, strain TW-1T represents novel species in the genus Massilia, for which the name Massilia antibiotica sp. nov. is proposed. The type strain is TW-1T (= KACC 21627T = NBRC 114363T).
Author Correction: Integrative network analyses of transcriptomics data reveal potential drug targets for acute radiation syndrome
Authors: Moore Robert , Puniya Bhanwar Lal , Powers Robert , Guda Chittibabu , Bayles Kenneth W. , Berkowitz David B. , Helikar Tomáš
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Current state of commercial point-of-care nucleic acid tests for infectious diseases
Authors: Zhang Jane Y. , Bender Andrew T. , Boyle David S. , Drain Paul K. , Posner Jonathan D.
Published: March 2021

The COVID-19 pandemic has put the spotlight on the urgent need for point-of-care nucleic acid tests (NATs) for infectious diseases.
The oxidation mechanism of gas-phase ozonolysis of limonene in the atmosphere
Authors: Wang Lingyu , Wang Liming
Published: March 2021

Ozonolysis of limonene in the atmosphere forms SOZs, OH radicals, dioxirane, and highly oxygenated multifunctional compounds as well as SOA.
Simultaneous speciation of arsenic and mercury in fish by high-performance liquid chromatography inductively coupled plasma mass spectrometry
Authors: Chen Yung-Chun , Jiang Shiuh-Jen
Published: March 2021

Liquid chromatography and dynamic reaction cell inductively coupled plasma mass spectrometry are used in tandem for the simultaneous speciation of arsenic and mercury in fish.
A microscopy-compatible temperature regulation system for single-cell phenotype analysis – demonstrated by thermoresponse mapping of microalgae
Authors: Andersson Martin , Johansson Sofia , Bergman Henrik , Xiao Linhong , Behrendt Lars , Tenje Maria
Published: March 2021

A heat-stage for spatiotemporal temperature control in microfluidic chips is developed. The technology is used for mapping thermoresponses of single cells ofSymbiodiniumin order to improve our understanding of temperature-induced coral bleaching.
Fabrication of high-performance symmetrical coin cell supercapacitors by using one step and green synthesis sulfur doped graphene powders
Authors: Arvas Melih Besir , Karatepe Nilgün , Gencten Metin , Sahin Yucel
Published: March 2021

In this work, symmetrical supercapacitors in the form of coin cell types were produced by using S-doped graphene powders.
Improved rotator cuff healing after surgical repair via suppression of reactive oxygen species by sustained release of Se
Authors: Fei Wenyong , Lin Jian , Gao Zijun , Zhang Hao , Zhang Junkai , Liu Xijian , Tan Jiyang , Deng Guoying
Published: March 2021

Porous Se@SiO2 nanocomposites showed effective results in promoting rotator cuff healing after surgical repair and have great potential in relevant clinical applications.
Targeted DNP for biomolecular solid-state NMR
Authors: Gauto Diego , Dakhlaoui Ons , Marin-Montesinos Ildefonso , Hediger Sabine , De Paëpe Gaël
Published: March 2021

IntargetedDNP, localization of polarizing agent at specific sites leads to new NMR approaches to improve sensitivity, background suppression for in-cell NMR, access to long-range constraints, andselectiveobservation of binding sites.
Nucleic acid amplification-based microfluidic approaches for antimicrobial susceptibility testing
Authors: Trinh Thi Ngoc Diep , Lee Nae Yoon
Published: March 2021

This review discusses the recent developments in microfluidics technology for antimicrobial susceptibility testing with a special emphasis on the nucleic acid amplification-based approach.
Bio-orthogonal chemistry enables solid phase synthesis and HPLC and gel-free purification of long RNA oligonucleotides
Authors: He Muhan , Wu Xunshen , Mao Song , Haruehanroengra Phensinee , Khan Irfan , Sheng Jia , Royzen Maksim
Published: March 2021

A bio-orthogonal chemistry-based strategy enables solid phase synthesis and purification of long RNA oligonucleotides.
Oxidative peptide bond formation of glycine–amino acid using 2-(aminomethyl)malononitrile as a glycine unit
Authors: Wang Xiaoling , Li Jing , Hayashi Yujiro
Published: March 2021

Amide linkage of glycine–amino acid was synthesized by coupling of substituted 2-(aminomethyl)malononitrile as a C-terminal glycine unit and N-terminal amine using CsOAc and O2in aqueous solution.