bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of spontaneous preterm birth in singleton pregnancies conceived after IVF/ICSI treatment: meta‐analysis of cohort studies
Authors: Cavoretto P. , Candiani M. , Giorgione V. , Inversetti A. , Abu‐Saba M. M. , Tiberio F. , Sigismondi C. , Farina A.
Published: January 2018

Objective

Preterm birth (PTB) is more common in pregnancies conceived by in‐vitro fertilization (IVF) as compared with those conceived naturally. However, the extent to which this is attributed to spontaneous labor or to iatrogenic indications has not been determined. The aim of this study was to quantify the risk of spontaneous PTB (sPTB) in singleton pregnancies resulting from IVF or intracytoplasmic sperm injection (ICSI) treatment as compared with that in spontaneously conceived pregnancies.

Methods

An electronic search of PubMed/MEDLINE, Scopus and Web of Science to September 2017 and manual search of reference lists identified articles comparing the risk of sPTB in IVF/ICSI vs spontaneously conceived singleton pregnancies. Inclusion criteria were singleton conception with IVF/ICSI, PTB defined as delivery before 37 weeks' gestation and cohort design with clear distinction between spontaneous and indicated PTB. The primary outcome was sPTB < 37 weeks. Relevant secondary outcomes were also analyzed, including sPTB < 34 and < 32 weeks, preterm prelabor rupture of membranes, stillbirth, perinatal mortality, neonatal sepsis, respiratory distress syndrome and gastrointestinal morbidity. A meta‐analysis provided the estimation of risk of sPTB in IVF/ICSI pregnancies.

Results

In total, 674 records were identified from the search, of which 15 met the inclusion criteria and were included in the meta‐analysis. A pooled crude analysis of the primary outcome generated a total sample size of 61 677 births, including 8044 singletons conceived after IVF/ICSI and 53 633 conceived spontaneously. A pooled crude data analysis showed a significant increase in the incidence of sPTB < 37 weeks in singleton IVF/ICSI pregnancies compared with those conceived spontaneously (810/8044 (10.1%) vs 2932/53 633 (5.5%); odds ratio (OR), 1.75; 95% CI, 1.50–2.03; I2 = 39%). A subgroup analysis of studies matching for maternal age and parity confirmed the finding (OR, 1.63; 95% CI, 1.30–2.05; I2 = 33%). A pooled crude analysis of secondary outcomes showed a significant increase in the incidence of sPTB < 34 weeks in pregnancies conceived after IVF/ICSI compared with those conceived spontaneously (37/1012 (3.6%) vs 24/1107 (2.2%); OR, 1.78; 95% CI, 1.03–3.08; I2 = 6%) and did not show any significant difference for any of the other secondary outcomes analyzed. The quality of evidence, rated using the GRADE criteria, was low for the outcome sPTB < 37 weeks and very low for sPTB < 34 weeks.

Conclusions

The risk of sPTB in singleton pregnancies resulting from IVF/ICSI is significantly greater than that in spontaneously conceived singletons. These findings should be interpreted with caution given the low quality of the available evidence. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Re: Outcome of assisted reproduction in women with congenital uterine anomalies: a prospective observational study. M. Prior, A. Richardson, S. Asif, L. Polanski, M. Parris‐Larkin, J. Chandler, L. Fogg, P. Jassal, J. G. Thornton, N. J. Raine‐Fenning. Ultrasound Obstet Gynecol 2018; 51: 110–117.
Authors: Ludwin A.
Published: January 2018

Linked Comment: Ultrasound Obstet Gynecol 2018; 51: 110–117
The cochlear implant and possibilities for narrowing the remaining gaps between prosthetic and normal hearing
Authors: Wilson Blake S.
Published: January 2018

Background

The cochlear implant has become the standard of care for severe or worse losses in hearing and indeed has produced the first substantial restoration of a lost or absent human sense using a medical intervention. However, the devices are not perfect and many efforts to narrow the remaining gaps between prosthetic and normal hearing are underway.

Objective

To assess the present status of cochlear implants and to describe possibilities for improving them.

Results

The present‐day devices work well in quiet conditions for the great majority of users. However, not all users have high levels of speech reception in quiet and nearly all users struggle with speech reception in typically noisy acoustic environments. In addition, perception of sounds more complex than speech, such as most music, is generally poor unless residual hearing at low frequencies can be stimulated acoustically in conjunction with the electrical stimuli provided by the implant. Possibilities for improving the present devices include increasing the spatial specificity of neural excitation by reducing masking effects or with new stimulus modes; prudent pruning of interfering or otherwise detrimental electrodes from the stimulation map; a further relaxation in the criteria for implant candidacy, based on recent evidence from persons with high levels of residual hearing and to allow many more people to benefit from cochlear implants; and “top down” or “brain centric” approaches to implant designs and applications.

Conclusions

Progress in the development of the cochlear implant and related treatments has been remarkable but room remains for improvements. The future looks bright as there are multiple promising possibilities for improvements and many talented teams are pursuing them.
[No Title]
Authors: MacHale S. M. , Lawrie S. M. , Cavanagh J. T. , Glabus M. F. , Marray C. L. , Ebmeier K. P. , Goodwin G. M.
Published: January 2018

As explained in the method section, the potential participants were screened by excluding those scoring above case threshold in the Hospital Anxiety and Depression (HAD) scale, a self-rating scale that does not require a detailed interview. The remaining participants were then interviewed using the Schedule for Affective Disorders and Schizophrenia to further exclude any current mental illness.
Supping with the Devil? Indicators and the rise of managerial rationality in law
Authors: Amariles David Restrepo
Published: January 2018

Managerial devices are rapidly developing as a means for driving the legal performance of organisations, including those of states and corporations. This paper explores the managerial rationality underpinning global legal indicators, and the constraints they convey on institutional behaviour. In particular, it argues that indicators are better understood as part of a system of management control and distributed governance, which is steadily eroding state-centred forms of authority, including state law. In this context, legitimacy and reactivity are contingent to their cycle of production and implementation, which is fourfold: data-collecting, benchmarking, auditing and allocating incentives. Each process is meant to generate respectively subjectification, self-knowledge by comparison, accountability and stimulus for action. Indicators with higher degrees of legitimacy become entrenched in institutional practices and legal decision-making processes. The paper concludes that regulatory spaces where indicators unfold need critical and political scrutiny to expose their pernicious effects, undesirable uses and inevitable misuses.
Nachsorge beim diffusen grosszelligen B-Zell-Lymphom – Evidenz und Empfehlung
Authors: Vollmer Kathrin , Mamot Christoph
Published: January 2018

Zusammenfassung. Aufgrund der verbesserten therapeutischen Möglichkeiten kann mittels Immunochemotherapie eine beträchtliche Anzahl der Patienten mit diffusem grosszelligem B-Zell-Lymphom geheilt werden. In diesem Zusammenhang stellt sich die Frage nach der korrekten Nachsorge zur Früherkennung eines Rezidivs. Die im Rahmen dieses Mini-Reviews dargelegte Evidenz zeigt, dass weder mit Routinebildgebungen noch mit entsprechender routinemässiger Labordiagnostik die Früherkennung von asymptomatischen Rezidiven gelingt. Auch kann die Früherkennung des Rezidivs die Prognose der Patienten nicht verbessern. Das Rezidiv wird meist klinisch diagnostiziert mit neuen Symptomen oder Befunden. Die Nachsorge, die klinisch orientiert durchgeführt werden sollte, soll in erster Linie der Erkennung von Spätfolgen und zur Wiedereingliederung in Beruf und Gesellschaft dienen.
Digitalis purpurea: ein Suizidversuch
Authors: Iten Manuela , Studhalter Michael , Lampert Markus , Walter Philipp , Paganoni Reto
Published: January 2018

Zusammenfassung. Wir präsentieren den Fall einer 23-jährigen Patientin, die in suizidaler Absicht Blätter des Roten Fingerhutes sammelte und einnahm. Trotz Einnahme einer relevanten Dosis hatte sie jedoch nur geringe Symptome. Intoxikationen mit Herzglykosiden sind selten, können aber relevante Herzrhythmusstörungen verursachen. Die einzige wirksame Behandlung stellt die frühzeitige und ggf. prophylaktische Gabe von digitalisspezifischen Fab-Antikörpern dar.
When Are Individuals Innovative?
Authors: Park Ho Hwan , Zhou Youjia , Choi Myungweon
Published: January 2018

Abstract. This study aims to explain: (a) what types of individuals are likely to exhibit innovative behavior and (b) when they are more likely to do so. For this purpose, the study uses trait activation theory ( Tett & Burnett, 2003 ; Tett & Guterman, 2000 ) as a theoretical framework and simultaneously examines the characteristics of the individual performing the job (openness to experience), the context within which the job is performed (innovative climate), and the nature of the job (job complexity). An analysis of survey data collected in China suggests that innovative climate and job complexity have a joint moderating effect on the relationship between openness to experience and innovative behavior. Based on the results, implications for research and practice are discussed.
Practical Considerations for Conducting Job Analysis Linkage Exercises
Authors: Robinson-Morral Erika J. , Hendrickson Cheryl , Gilbert Sarah , Myers Tara , Simpson Kaila , Loignon Andrew C.
Published: January 2018

Abstract. To follow best practices in creating selection tools, an important phase in job analysis is gathering linkage ratings between knowledge, skills, abilities, and other characteristics (KSAOs) and job tasks. However, the literature provides little guidance on best practices for collecting linkage ratings. Two studies were conducted to contribute to the limited research. Study 1 examined the interrater agreement of different types of raters: job incumbents, managers, or job analysts. Results revealed that job analysts have the highest interrater agreement. Study 2 examined the impact of a frame-of-reference (FOR) training for raters. Results suggested that a brief consensus training session vastly improved agreement among raters. These studies provide more guidance on best practices for obtaining high-quality linkage ratings.
Freshwater lake to salt-water sea causing widespread hydrate dissociation in the Black Sea
Authors: Riboulot Vincent , Ker Stephan , Sultan Nabil , Thomas Yannick , Marsset Bruno , Scalabrin Carla , Ruffine Livio , Boulart Cédric , Ion Gabriel
Published: January 2018

Gas hydrates, a solid established by water and gas molecules, are widespread along the continental margins of the world. Their dynamics have mainly been regarded through the lens of temperature-pressure conditions. A fluctuation in one of these parameters may cause destabilization of gas hydrate-bearing sediments below the seafloor with implications in ocean acidification and eventually in global warming. Here we show throughout an example of the Black Sea, the world’s most isolated sea, evidence that extensive gas hydrate dissociation may occur in the future due to recent salinity changes of the sea water. Recent and forthcoming salt diffusion within the sediment will destabilize gas hydrates by reducing the extension and thickness of their thermodynamic stability zone in a region covering at least 2800 square kilometers which focus seepages at the observed sites. We suspect this process to occur in other world regions (e.g., Caspian Sea, Sea of Marmara).
Structure function and engineering of multifunctional non-heme iron dependent oxygenases in fungal meroterpenoid biosynthesis
Authors: Nakashima Yu , Mori Takahiro , Nakamura Hitomi , Awakawa Takayoshi , Hoshino Shotaro , Senda Miki , Senda Toshiya , Abe Ikuro
Published: January 2018

Non-heme iron and α-ketoglutarate (αKG) oxygenases catalyze remarkably diverse reactions using a single ferrous ion cofactor. A major challenge in studying this versatile family of enzymes is to understand their structure–function relationship. AusE from Aspergillus nidulans and PrhA from Penicillium brasilianum are two highly homologous Fe(II)/αKG oxygenases in fungal meroterpenoid biosynthetic pathways that use preaustinoid A1 as a common substrate to catalyze divergent rearrangement reactions to form the spiro-lactone in austinol and cycloheptadiene moiety in paraherquonin, respectively. Herein, we report the comparative structural study of AusE and PrhA, which led to the identification of three key active site residues that control their reactivity. Structure-guided mutagenesis of these residues results in successful interconversion of AusE and PrhA functions as well as generation of the PrhA double and triple mutants with expanded catalytic repertoire. Manipulation of the multifunctional Fe(II)/αKG oxygenases thus provides an excellent platform for the future development of biocatalysts.
Publisher Correction: Hierarchical self-entangled carbon nanotube tube networks
Authors: Schütt Fabian , Signetti Stefano , Krüger Helge , Röder Sarah , Smazna Daria , Kaps Sören , Gorb Stanislav N. , Mishra Yogendra Kumar , Pugno Nicola M. , Adelung Rainer
Published: January 2018

The original version of this Article was missing the ORCID ID of Professor Nicola Pugno.Also in the original version of this Article, the third to last sentence of the fourth paragraph of the Results incorrectly read ‘However, the stepwise addition of CNTs increases the self-entanglement and thereby the compressive strength value as well as the Young’s modulus (up to 2.5 MPa (normalized by density 6.4) and 24.5 MPa (normalized by density 62 MPa cm3 g−1).’ The correct version adds the units ‘MPa cm3 g−1’ to ‘6.4’.Finally, in the original version of this Article, the y-axis label of Figure 3f incorrectly read ‘Comp. strengthy’. The new version corrects that to ‘Comp. Strength’.These errors have now been corrected in both the PDF and the HTML versions of the Article.
Punctuated evolution of canonical genomic aberrations in uveal melanoma
Authors: Field Matthew G. , Durante Michael A. , Anbunathan Hima , Cai Louis Z. , Decatur Christina L. , Bowcock Anne M. , Kurtenbach Stefan , Harbour J. William
Published: January 2018

Cancer is thought to arise through the accumulation of genomic aberrations evolving under Darwinian selection. However, it remains unclear when the aberrations associated with metastasis emerge during tumor evolution. Uveal melanoma (UM) is the most common primary eye cancer and frequently leads to metastatic death, which is strongly linked to BAP1 mutations. Accordingly, UM is ideally suited for studying the clonal evolution of metastatic competence. Here we analyze sequencing data from 151 primary UM samples using a customized bioinformatic pipeline, to improve detection of BAP1 mutations and infer the clonal relationships among genomic aberrations. Strikingly, we find BAP1 mutations and other canonical genomic aberrations usually arise in an early punctuated burst, followed by neutral evolution extending to the time of clinical detection. This implies that the metastatic proclivity of UM is “set in stone” early in tumor evolution and may explain why advances in primary treatment have not improved survival.
Integrated omics dissection of proteome dynamics during cardiac remodeling
Authors: Lau Edward , Cao Quan , Lam Maggie P. Y. , Wang Jie , Ng Dominic C. M. , Bleakley Brian J. , Lee Jessica M. , Liem David A. , Wang Ding , Hermjakob Henning , Ping Peipei
Published: January 2018

Transcript abundance and protein abundance show modest correlation in many biological models, but how this impacts disease signature discovery in omics experiments is rarely explored. Here we report an integrated omics approach, incorporating measurements of transcript abundance, protein abundance, and protein turnover to map the landscape of proteome remodeling in a mouse model of pathological cardiac hypertrophy. Analyzing the hypertrophy signatures that are reproducibly discovered from each omics data type across six genetic strains of mice, we find that the integration of transcript abundance, protein abundance, and protein turnover data leads to 75% gain in discovered disease gene candidates. Moreover, the inclusion of protein turnover measurements allows discovery of post-transcriptional regulations across diverse pathways, and implicates distinct disease proteins not found in steady-state transcript and protein abundance data. Our results suggest that multi-omics investigations of proteome dynamics provide important insights into disease pathogenesis in vivo.
The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading
Authors: Gardner Brooke M. , Castanzo Dominic T. , Chowdhury Saikat , Stjepanovic Goran , Stefely Matthew S. , Hurley James H. , Lander Gabriel C. , Martin Andreas
Published: January 2018

Pex1 and Pex6 form a heterohexameric motor essential for peroxisome biogenesis and function, and mutations in these AAA-ATPases cause most peroxisome-biogenesis disorders in humans. The tail-anchored protein Pex15 recruits Pex1/Pex6 to the peroxisomal membrane, where it performs an unknown function required for matrix-protein import. Here we determine that Pex1/Pex6 from S. cerevisiae is a protein translocase that unfolds Pex15 in a pore-loop-dependent and ATP-hydrolysis-dependent manner. Our structural studies of Pex15 in isolation and in complex with Pex1/Pex6 illustrate that Pex15 binds the N-terminal domains of Pex6, before its C-terminal disordered region engages with the pore loops of the motor, which then processively threads Pex15 through the central pore. Furthermore, Pex15 directly binds the cargo receptor Pex5, linking Pex1/Pex6 to other components of the peroxisomal import machinery. Our results thus support a role of Pex1/Pex6 in mechanical unfolding of peroxins or their extraction from the peroxisomal membrane during matrix-protein import.
Unidirectional spin-Hall and Rashba−Edelstein magnetoresistance in topological insulator-ferromagnet layer heterostructures
Authors: Lv Yang , Kally James , Zhang Delin , Lee Joon Sue , Jamali Mahdi , Samarth Nitin , Wang Jian-Ping
Published: January 2018

The large spin−orbit coupling in topological insulators results in helical spin-textured Dirac surface states that are attractive for topological spintronics. These states generate an efficient spin−orbit torque on proximal magnetic moments. However, memory or logic spin devices based upon such switching require a non-optimal three-terminal geometry, with two terminals for the writing current and one for reading the state of the device. An alternative two-terminal device geometry is now possible by exploiting the recent discovery of the unidirectional spin Hall magnetoresistance in heavy metal/ferromagnet bilayers and unidirectional magnetoresistance in magnetic topological insulators. Here, we report the observation of such unidirectional magnetoresistance in a technologically relevant device geometry that combines a topological insulator with a conventional ferromagnetic metal. Our devices show a figure of merit (magnetoresistance per current density per total resistance) that is more than twice as large as the highest reported values in all-metal Ta/Co bilayers.
Differential Pd-nanocrystal facets demonstrate distinct antibacterial activity against Gram-positive and Gram-negative bacteria
Authors: Fang Ge , Li Weifeng , Shen Xiaomei , Perez-Aguilar Jose Manuel , Chong Yu , Gao Xingfa , Chai Zhifang , Chen Chunying , Ge Cuicui , Zhou Ruhong
Published: January 2018

Noble metal-based nanomaterials have shown promise as potential enzyme mimetics, but the facet effect and underlying molecular mechanisms are largely unknown. Herein, with a combined experimental and theoretical approach, we unveil that palladium (Pd) nanocrystals exhibit facet-dependent oxidase and peroxidase-like activities that endow them with excellent antibacterial properties via generation of reactive oxygen species. The antibacterial efficiency of Pd nanocrystals against Gram-positive bacteria is consistent with the extent of their enzyme-like activity, that is {100}-faceted Pd cubes with higher activities kill bacteria more effectively than {111}-faceted Pd octahedrons. Surprisingly, a reverse trend of antibacterial activity is observed against Gram-negative bacteria, with Pd octahedrons displaying stronger penetration into bacterial membranes than Pd nanocubes, thereby exerting higher antibacterial activity than the latter. Our findings provide a deeper understanding of facet-dependent enzyme-like activities and might advance the development of noble metal-based nanomaterials with both enhanced and targeted antibacterial activities.
Tectonically-triggered sediment and carbon export to the Hadal zone
Authors: Bao Rui , Strasser Michael , McNichol Ann P. , Haghipour Negar , McIntyre Cameron , Wefer Gerold , Eglinton Timothy I.
Published: January 2018

Sediments in deep ocean trenches may contain crucial information on past earthquake history and constitute important sites of carbon burial. Here we present 14C data on bulk organic carbon (OC) and its thermal decomposition fractions produced by ramped pyrolysis/oxidation for a core retrieved from the >7.5 km-deep Japan Trench. High-resolution 14C measurements, coupled with distinctive thermogram characteristics of OC, reveal hemipelagic sedimentation interrupted by episodic deposition of pre-aged OC in the trench. Low δ13C values and diverse 14C ages of thermal fractions imply that the latter material originates from the adjacent margin, and the co-occurrence of pre-aged OC with intervals corresponding to known earthquake events implies tectonically triggered, gravity-flow-driven supply. We show that 14C ages of thermal fractions can yield valuable chronological constraints on sedimentary sequences. Our findings shed new light on links between tectonically driven sedimentological processes and marine carbon cycling, with implications for carbon dynamics in hadal environments.
Phf8 histone demethylase deficiency causes cognitive impairments through the mTOR pathway
Authors: Chen Xuemei , Wang Shuai , Zhou Ying , Han Yanfei , Li Shengtian , Xu Qing , Xu Longyong , Zhu Ziqi , Deng Youming , Yu Lu , Song Lulu , Chen Adele Pin , Song Juan , Takahashi Eiki , He Guang , He Lin , Li Weidong , Chen Charlie Degui
Published: January 2018

Epigenomic abnormalities caused by genetic mutation in epigenetic regulators can result in neurodevelopmental disorders, deficiency in neural plasticity and mental retardation. As a histone demethylase, plant homeodomain finger protein 8 (Phf8) is a candidate gene for syndromal and non-specific forms of X-chromosome-linked intellectual disability (XLID). Here we report that Phf8 knockout mice displayed impaired learning and memory, and impaired hippocampal long-term potentiation (LTP) without gross morphological defects. We also show that mTOR signaling pathway is hyperactive in hippocampus in Phf8 knockout mouse. Mechanistically, we show that demethylation of H4K20me1 by Phf8 results in transcriptional suppression of RSK1 and homeostasis of mTOR signaling. Pharmacological suppression of mTOR signaling with rapamycin in Phf8 knockout mice recovers the weakened LTP and cognitive deficits. Together, our results indicate that loss of Phf8 in animals causes deficient learning and memory by epigenetic disruption of mTOR signaling, and provides a potential therapeutic drug target to treat XLID.
Click beetle luciferase mutant and near infrared naphthyl-luciferins for improved bioluminescence imaging
Authors: Hall Mary P. , Woodroofe Carolyn C. , Wood Monika G. , Que Ivo , van’t Root Moniek , Ridwan Yanto , Shi Ce , Kirkland Thomas A. , Encell Lance P. , Wood Keith V. , Löwik Clemens , Mezzanotte Laura
Published: January 2018

The sensitivity of bioluminescence imaging in animals is primarily dependent on the amount of photons emitted by the luciferase enzyme at wavelengths greater than 620 nm where tissue penetration is high. This area of work has been dominated by firefly luciferase and its substrate, D-luciferin, due to the system’s peak emission (~ 600 nm), high signal to noise ratio, and generally favorable biodistribution of D-luciferin in mice. Here we report on the development of a codon optimized mutant of click beetle red luciferase that produces substantially more light output than firefly luciferase when the two enzymes are compared in transplanted cells within the skin of black fur mice or in deep brain. The mutant enzyme utilizes two new naphthyl-luciferin substrates to produce near infrared emission (730 nm and 743 nm). The stable luminescence signal and near infrared emission enable unprecedented sensitivity and accuracy for performing deep tissue multispectral tomography in mice.
Picosecond pulse shaping of single photons using quantum dots
Authors: Pursley B. C. , Carter S. G. , Yakes M. K. , Bracker A. S. , Gammon D.
Published: January 2018

Quantum dots (QDs) are an excellent single-photon source that can be combined with a spin quantum memory. Many quantum technologies require increased control over the characteristics of emitted photons. A powerful approach is to trigger coherent Raman photons from QDs with a Λ energy-level system, such as the spin singlet–triplet system in two coupled QDs. The temporal and spectral behavior of single Raman photons can be varied simply by modifying the excitation source. Here, we demonstrate control of the single-photon pulse shape in a solid-state system on a timescale much shorter than the radiative lifetime, in addition to control of the frequency and bandwidth. We achieve a photon pulse width of 80 ps—an order of magnitude shorter than the exciton lifetime. Possible applications include time-bin encoding of quantum information, matching photons from different sources, and efficient single-photon transfer in a quantum network.
3D single-molecule super-resolution microscopy with a tilted light sheet
Authors: Gustavsson Anna-Karin , Petrov Petar N. , Lee Maurice Y. , Shechtman Yoav , Moerner W. E.
Published: January 2018

Tilted light sheet microscopy with 3D point spread functions (TILT3D) combines a novel, tilted light sheet illumination strategy with long axial range point spread functions (PSFs) for low-background, 3D super-localization of single molecules as well as 3D super-resolution imaging in thick cells. Because the axial positions of the single emitters are encoded in the shape of each single-molecule image rather than in the position or thickness of the light sheet, the light sheet need not be extremely thin. TILT3D is built upon a standard inverted microscope and has minimal custom parts. The result is simple and flexible 3D super-resolution imaging with tens of nm localization precision throughout thick mammalian cells. We validate TILT3D for 3D super-resolution imaging in mammalian cells by imaging mitochondria and the full nuclear lamina using the double-helix PSF for single-molecule detection and the recently developed tetrapod PSFs for fiducial bead tracking and live axial drift correction.
Nanoparticle elasticity directs tumor uptake
Authors: Guo Peng , Liu Daxing , Subramanyam Kriti , Wang Biran , Yang Jiang , Huang Jing , Auguste Debra T. , Moses Marsha A.
Published: January 2018

To date, the role of elasticity in drug delivery remains elusive due to the inability to measure microscale mechanics and alter rheology without affecting chemistry. Herein, we describe the in vitro cellular uptake and in vivo tumor uptake of nanolipogels (NLGs). NLGs are composed of identical lipid bilayers encapsulating an alginate core, with tunable elasticity. The elasticity of NLGs was evaluated by atomic force microscopy, which demonstrated that they exhibit Young’s moduli ranging from 45 ± 9 to 19,000 ± 5 kPa. Neoplastic and non-neoplastic cells exhibited significantly greater uptake of soft NLGs (Young’s modulus <1.6 MPa) relative to their elastic counterparts (Young’s modulus >13.8 MPa). In an orthotopic breast tumor model, soft NLGs accumulated significantly more in tumors, whereas elastic NLGs preferentially accumulated in the liver. Our findings demonstrate that particle elasticity directs tumor accumulation, suggesting that it may be a design parameter to enhance tumor delivery efficiency.
Mechanism and structural diversity of exoribonuclease-resistant RNA structures in flaviviral RNAs
Authors: MacFadden Andrea , O’Donoghue Zoe , Silva Patricia A. G. C. , Chapman Erich G. , Olsthoorn René C. , Sterken Mark G. , Pijlman Gorben P. , Bredenbeek Peter J. , Kieft Jeffrey S.
Published: January 2018

Flaviviruses such as Yellow fever, Dengue, West Nile, and Zika generate disease-linked viral noncoding RNAs called subgenomic flavivirus RNAs. Subgenomic flavivirus RNAs result when the 5′–3′ progression of cellular exoribonuclease Xrn1 is blocked by RNA elements called Xrn1-resistant RNAs located within the viral genome’s 3′-untranslated region that operate without protein co-factors. Here, we show that Xrn1-resistant RNAs can halt diverse exoribonucleases, revealing a mechanism in which they act as general mechanical blocks that ‘brace’ against an enzyme’s surface, presenting an unfolding problem that confounds further enzyme progression. Further, we directly demonstrate that Xrn1-resistant RNAs exist in a diverse set of flaviviruses, including some specific to insects or with no known arthropod vector. These Xrn1-resistant RNAs comprise two secondary structural classes that mirror previously reported phylogenic analysis. Our discoveries have implications for the evolution of exoribonuclease resistance, the use of Xrn1-resistant RNAs in synthetic biology, and the development of new therapies.
Peptidomimetic blockade of MYB in acute myeloid leukemia
Authors: Ramaswamy Kavitha , Forbes Lauren , Minuesa Gerard , Gindin Tatyana , Brown Fiona , Kharas Michael G. , Krivtsov Andrei V. , Armstrong Scott A. , Still Eric , de Stanchina Elisa , Knoechel Birgit , Koche Richard , Kentsis Alex
Published: January 2018

Aberrant gene expression is a hallmark of acute leukemias. MYB-driven transcriptional coactivation with CREB-binding protein (CBP)/P300 is required for acute lymphoblastic and myeloid leukemias, including refractory MLL-rearranged leukemias. Using structure-guided molecular design, we developed a peptidomimetic inhibitor MYBMIM that interferes with the assembly of the molecular MYB:CBP/P300 complex and rapidly accumulates in the nuclei of AML cells. Treatment of AML cells with MYBMIM led to the dissociation of the MYB:CBP/P300 complex in cells, its displacement from oncogenic enhancers enriched for MYB binding sites, and downregulation of MYB-dependent gene expression, including of MYC and BCL2 oncogenes. AML cells underwent mitochondrial apoptosis in response to MYBMIM, which was partially rescued by ectopic expression of BCL2. MYBMIM impeded leukemia growth and extended survival of immunodeficient mice engrafted with primary patient-derived MLL-rearranged leukemia cells. These findings elucidate the dependence of human AML on aberrant transcriptional coactivation, and establish a pharmacologic approach for its therapeutic blockade.
TDRD5 binds piRNA precursors and selectively enhances pachytene piRNA processing in mice
Authors: Ding Deqiang , Liu Jiali , Midic Uros , Wu Yingjie , Dong Kunzhe , Melnick Ashley , Latham Keith E. , Chen Chen
Published: January 2018

Pachytene piRNAs are the most abundant piRNAs in mammalian adult testes. They are generated from long precursor transcripts by the primary piRNA biogenesis pathway but the factors involved in pachytene piRNA precursors processing are poorly understood. Here we show that the Tudor domain-containing 5 (TDRD5) protein is essential for pachytene piRNA biogenesis in mice. Conditional inactivation of TDRD5 in mouse postnatal germ cells reveals that TDRD5 selectively regulates the production of pachytene piRNAs from abundant piRNA-producing precursors, with little effect on low-abundant piRNAs. Unexpectedly, TDRD5 is not required for the 5′ end processing of the precursors, but is crucial for promoting production of piRNAs from the other regions of the transcript. Furthermore, we show that TDRD5 is an RNA-binding protein directly associating with piRNA precursors. These observations establish TDRD5 as a piRNA biogenesis factor and reveal two genetically separable steps at the start of pachytene piRNA processing.
Weakly perturbative imaging of interfacial water with submolecular resolution by atomic force microscopy
Authors: Peng Jinbo , Guo Jing , Hapala Prokop , Cao Duanyun , Ma Runze , Cheng Bowei , Xu Limei , Ondráček Martin , Jelínek Pavel , Wang Enge , Jiang Ying
Published: January 2018

Scanning probe microscopy has been extensively applied to probe interfacial water in many interdisciplinary fields but the disturbance of the probes on the hydrogen-bonding structure of water has remained an intractable problem. Here, we report submolecular-resolution imaging of the water clusters on a NaCl(001) surface within the nearly noninvasive region by a qPlus-based noncontact atomic force microscopy. Comparison with theoretical simulations reveals that the key lies in probing the weak high-order electrostatic force between the quadrupole-like CO-terminated tip and the polar water molecules at large tip–water distances. This interaction allows the imaging and structural determination of the weakly bonded water clusters and even of their metastable states with negligible disturbance. This work may open an avenue for studying the intrinsic structure and dynamics of ice or water on surfaces, ion hydration, and biological water with atomic precision.
Guiding of relativistic electron beams in dense matter by laser-driven magnetostatic fields
Authors: Bailly-Grandvaux M. , Santos J. J. , Bellei C. , Forestier-Colleoni P. , Fujioka S. , Giuffrida L. , Honrubia J. J. , Batani D. , Bouillaud R. , Chevrot M. , Cross J. E. , Crowston R. , Dorard S. , Dubois J.-L. , Ehret M. , Gregori G. , Hulin S. , Kojima S. , Loyez E. , Marquès J.-R. , Morace A. , Nicolaï Ph. , Roth M. , Sakata S. , Schaumann G. , Serres F. , Servel J. , Tikhonchuk V. T. , Woolsey N. , Zhang Z.
Published: January 2018

Intense lasers interacting with dense targets accelerate relativistic electron beams, which transport part of the laser energy into the target depth. However, the overall laser-to-target energy coupling efficiency is impaired by the large divergence of the electron beam, intrinsic to the laser–plasma interaction. Here we demonstrate that an efficient guiding of MeV electrons with about 30 MA current in solid matter is obtained by imposing a laser-driven longitudinal magnetostatic field of 600 T. In the magnetized conditions the transported energy density and the peak background electron temperature at the 60-μm-thick target's rear surface rise by about a factor of five, as unfolded from benchmarked simulations. Such an improvement of energy-density flux through dense matter paves the ground for advances in laser-driven intense sources of energetic particles and radiation, driving matter to extreme temperatures, reaching states relevant for planetary or stellar science as yet inaccessible at the laboratory scale and achieving high-gain laser-driven thermonuclear fusion.
Zika virus infection induces host inflammatory responses by facilitating NLRP3 inflammasome assembly and interleukin-1β secretion
Authors: Wang Wenbiao , Li Geng , De Wu  , Luo Zhen , Pan Pan , Tian Mingfu , Wang Yingchong , Xiao Feng , Li Aixin , Wu Kailang , Liu Xiaohong , Rao Lang , Liu Fang , Liu Yingle , Wu Jianguo
Published: January 2018

Zika virus (ZIKV) infection is a public health emergency and host innate immunity is essential for the control of virus infection. The NLRP3 inflammasome plays a key role in host innate immune responses by activating caspase-1 to facilitate interleukin-1β (IL-1β) secretion. Here we report that ZIKV stimulates IL-1β secretion in infected patients, human PBMCs and macrophages, mice, and mice BMDCs. The knockdown of NLRP3 in cells and knockout of NLRP3 in mice inhibit ZIKV-mediated IL-1β secretion, indicating an essential role for NLRP3 in ZIKV-induced IL-1β activation. Moreover, ZIKV NS5 protein is required for NLRP3 activation and IL-1β secretion by binding with NLRP3 to facilitate the inflammasome complex assembly. Finally, ZIKV infection in mice activates IL-1β secretion, leading to inflammatory responses in the mice brain, spleen, liver, and kidney. Thus we reveal a mechanism by which ZIKV induces inflammatory responses by facilitating NLRP3 inflammasome complex assembly and IL-1β activation.
Computational modelling of meiotic entry and commitment
Authors: Bhola Tanvi , Kapuy Orsolya , Vinod P. K.
Published: January 2018

In response to developmental and environmental conditions, cells exit the mitotic cell cycle and enter the meiosis program to generate haploid gametes from diploid germ cells. Once cells decide to enter the meiosis program they become irreversibly committed to the completion of meiosis irrespective of the presence of cue signals. How meiotic entry and commitment occur due to the dynamics of the regulatory network is not well understood. Therefore, we constructed a mathematical model of the regulatory network that controls the transition from mitosis to meiosis in Schizosaccharomyces pombe. Upon nitrogen starvation, yeast cells exit mitosis and undergo conjugation and meiotic entry. The model includes the regulation of Mei2, an RNA binding protein required for conjugation and meiotic entry, by multiple feedback loops involving Pat1, a kinase that keeps cells in mitosis, and Ste11, a transcription activator required for the sexual differentiation. The model accounts for various experimental observations and demonstrates that the activation of Mei2 is bistable, which ensures the irreversible commitment to meiosis. Further, we show by integrating the meiosis-specific regulation with a cell cycle model, the dynamics of cell cycle exit, G1 arrest and entry into meiosis under nitrogen starvation.
Tunable geometrical frustration in magnonic vortex crystals
Authors: Behncke Carolin , Adolff Christian F. , Wintz Sebastian , Hänze Max , Schulte Benedikt , Weigand Markus , Finizio Simone , Raabe Jörg , Meier Guido
Published: January 2018

A novel approach to investigate geometrical frustration is introduced using two-dimensional magnonic vortex crystals. The frustration of the crystal can be manipulated and turned on and off dynamically on the timescale of milliseconds. The vortices are studied using scanning transmission x-ray microscopy and ferromagnetic resonance spectroscopy. They are arranged analogous to the nanomagnets in artificial spin-ice systems. The polarization state of the vortices is tuned in a way that geometrical frustration arises. We demonstrate that frustrated polarization states and non-frustrated states can be tuned to the crystal by changing the frequency of the state formation process.
Single, very low rituximab doses in healthy volunteers - a pilot and a randomized trial: implications for dosing and biosimilarity testing
Authors: Schoergenhofer Christian , Schwameis Michael , Firbas Christa , Bartko Johann , Derhaschnig Ulla , Mader Robert M , Plaßmann Raute Sunder , Jilma-Stohlawetz Petra , Desai Kalpna , Misra Priya , Jäger Ulrich , Jilma Bernd
Published: January 2018

There are no  dose-finding trials available for rituximab that could guide dosing in non-malignant diseases. We hypothesized that currently used doses (≥375 mg/m2) exceed several hundred-fold the half-maximal effective dose, which is most sensitive for detecting putative differences between biosimilars and important for dose finding. In an open label, exploratory trial healthy volunteers received single infusions of rituximab at doses of 0.1, 0.3 or 1.0 mg/m2. Subsequently, in a double-blind, randomized trial healthy volunteers received single infusions of two rituximab products at doses of 0.1 and 0.3 mg/m2. In the exploratory trial rituximab transiently depleted CD20+ cells by a mean 68% (range: 57–95%), 74% (55–82%) and 97% (94–100%) immediately after the infusion of 0.1 (n = 4), 0.3 (n = 4) and 1 mg/m2 (n = 8), respectively. In the randomized trial CD20+ cells decreased by a mean 48% (25–84%) − 55% (26–85%) and 81 (67–89%) – 87% (77–96%) after infusion of 0.1 mg/m2 (n = 12) or 0.3 mg/m2 (n = 8 proposed biosimilar, n = 4 reference product) of the proposed biosimilar or the reference product, respectively. It is important to understand that in healthy volunteers <1% of the authorized rituximab doses depletes almost all circulating B lymphocytes. Thus, for non-malignant diseases alternative, more cost-effective dosing regimens seem plausible, but require clinical testing. (EudraCT-No. 2010–023781–45; EudraCT-No. 2013–001077–24).
Precise phase demodulation of single carrier-frequency interferogram by pixel-level Lissajous figure and ellipse fitting
Authors: Liu Fengwei , Wu Yongqian , Wu Fan , König Niels , Schmitt Robert , Wan Yongjian , Xu Yan
Published: January 2018

Phase demodulation from a single carrier-frequency fringe pattern is becoming increasingly important particularly in areas of optical metrology such as dynamic interferometry, deflectometry and profilometry. The Fourier transform (FT) method and the spatial-carrier phase-shifting technique (SCPS) are two popular and well-established approaches to demodulation. However FT has the drawback of significant edge errors because of the Gibbs effect, whilst detuning errors for the local phase shift occur when SCPS is applied. A novel demodulation method based on pixel-level Lissajous figure and ellipse fitting (PLEF) is presented in this paper. Local demodulation in the spatial domain makes PLEF more flexible than the FT method, without spectral leakage. Based on a more adaptable approach, account is taken of variations in illumination and phase distribution over a few neighboring pixels. The mathematic demodulation model is of interest and has been demonstrated via simulation. Theoretical phase extraction error is as low as 10−4 rad. Experiments further corroborate the effectiveness of the proposed method. In conclusion, various influencing factors, e.g. variations of background/modulation, phase amplitude, carrier frequency, additive noise that may affect the precision of PLEF are discussed in detail.
Polyaniline cryogels: Biocompatibility of novel conducting macroporous material
Authors: Humpolíček Petr , Radaszkiewicz Katarzyna Anna , Capáková Zdenka , Pacherník Jiří , Bober Patrycja , Kašpárková Věra , Rejmontová Petra , Lehocký Marián , Ponížil Petr , Stejskal Jaroslav
Published: January 2018

Polyaniline cryogel is a new unique form of polyaniline combining intrinsic electrical conductivity and the material properties of hydrogels. It is prepared by the polymerization of aniline in frozen poly(vinyl alcohol) solutions. The biocompatibility of macroporous polyaniline cryogel was demonstrated by testing its cytotoxicity on mouse embryonic fibroblasts and via the test of embryotoxicity based on the formation of beating foci within spontaneous differentiating embryonic stem cells. Good biocompatibility was related to low contents of low-molecular-weight impurities in polyaniline cryogel, which was confirmed by liquid chromatography. The adhesion and growth of embryonic stem cells, embryoid bodies, cardiomyocytes, and neural progenitors prove that polyaniline cryogel has the potential to be used as a carrier for cells in tissue engineering or bio-sensing. The surface energy as well as the elasticity and porosity of cryogel mimic tissue properties. Polyaniline cryogel can therefore be applied in bio-sensing or regenerative medicine in general, and mainly in the tissue engineering of electrically excitable tissues.
The epidemiology of hepatitis C virus in Iran: Systematic review and meta-analyses
Authors: Mahmud Sarwat , Akbarzadeh Vajiheh , Abu-Raddad Laith J.
Published: January 2018

The aim of this study was to characterize hepatitis C virus (HCV) epidemiology in Iran and estimate the pooled mean HCV antibody prevalence in different risk populations. We systematically reviewed and synthesized reports of HCV incidence and/or prevalence, as informed by the Cochrane Collaboration Handbook, and reported our findings following the PRISMA guidelines. DerSimonian-Laird random effects meta-analyses were implemented to estimate HCV prevalence in various risk populations. We identified five HCV incidence and 472 HCV prevalence measures. Our meta-analyses estimated HCV prevalence at 0.3% among the general population, 6.2% among intermediate risk populations, 32.1% among high risk populations, and 4.6% among special clinical populations. Our meta-analyses for subpopulations estimated HCV prevalence at 52.2% among people who inject drugs (PWID), 20.0% among populations at high risk of healthcare-related exposures, and 7.5% among populations with liver-related conditions. Genotype 1 was the most frequent circulating strain at 58.2%, followed by genotype 3 at 39.0%. HCV prevalence in the general population was lower than that found in other Middle East and North Africa countries and globally. However, HCV prevalence was high in PWID and populations at high risk of healthcare-related exposures. Ongoing transmission appears to be driven by drug injection and specific healthcare procedures.
Effect of microstructure on the impact toughness and temper embrittlement of SA508Gr.4N steel for advanced pressure vessel materials
Authors: Yang Zhiqiang , Liu Zhengdong , He Xikou , Qiao Shibin , Xie Changsheng
Published: January 2018

The effect of microstructure on the impact toughness and the temper embrittlement of a SA508Gr.4N steel was investigated. Martensitic and bainitic structures formed in this material were examined via scanning electron microscopy, electron backscatter diffraction, transmission electron microscopy, and Auger electron spectroscopy (AES) analysis. The martensitic structure had a positive effect on both the strength and toughness. Compared with the bainitic structure, this structure consisted of smaller blocks and more high-angle grain boundaries (HAGBs). Changes in the ultimate tensile strength and toughness of the martensitic structure were attributed to an increase in the crack propagation path. This increase resulted from an increased number of HAGBs and refinement of the sub-structure (block). The AES results revealed that sulfur segregation is higher in the martensitic structure than in the bainitic structure. Therefore, the martensitic structure is more susceptible to temper embrittlement than the bainitic structure.