Incorporation of time-lapse imaging in the field of IVF has provided much information about embryo development. The combination of the embryo appearance (morphology) and the importance of when and ...how the cellular processes that lead to this appearance occur (kinetics) are now integrated into the unique concept of morphokinetics. At present, efforts are focused on using this information to improve embryo selection and existing success rates without losing sight of the ever-present objective of implementing a single ET strategy to avoid multiple gestations. Several investigative groups have identified predictive morphokinetic variables for embryo viability and implantation potential. Promising supplementary models of embryo selection based on time-dependent markers have been proposed and are currently being verified in prospective trials. Pending further results of these studies that confirm the clinical validity of time-lapse imaging, the present article tries to summarize the studies conducted to date to take stock of what has been done and the prospects that are emerging from this technology.
Hybrid devices based on spin‐crossover (SCO)/2D heterostructures grant a highly sensitive platform to detect the spin transition in the molecular SCO component and tune the properties of the 2D ...material. However, the fragility of the SCO materials upon thermal treatment, light irradiation, or contact with surfaces and the methodologies used for their processing have limited their applicability. Here, an easily processable and robust SCO/2D hybrid device with outstanding performance based on the sublimable SCO Fe(Pyrz)2 molecule deposited over chemical vapor deposition (CVD) graphene is reported, which is fully compatible with electronics industry protocols. Thus, a novel methodology based on growing an elusive polymorph of Fe(Pyrz)2 (tetragonal phase) over graphene is developed that allows a fast and effective light‐induced spin transition in the devices (≈50% yield in 5 min) to be detected electrically. Such performance can be enhanced even more when a flexible polymeric layer of poly(methyl methacrylate) is inserted in between the two active components in a contactless configuration, reaching a ≈100% yield in 5 min.
Hybrid devices formed by sublimable spin‐crossover molecules deposited over graphene are fabricated. The novel device preparation protocol used results in fast and efficient photoinduced spin transitions, and is even enhanced in devices with a contactless configuration. This methodology allows further integration of spin‐crossover molecules in thermal or light‐addressable spintronic and straintronic devices based on 2D materials.
Analysis of somatic mutations provides insight into the mutational processes that have shaped the cancer genome, but such analysis currently requires large cohorts. We develop deconstructSigs, which ...allows the identification of mutational signatures within a single tumor sample.
Application of deconstructSigs identifies samples with DNA repair deficiencies and reveals distinct and dynamic mutational processes molding the cancer genome in esophageal adenocarcinoma compared to squamous cell carcinomas.
deconstructSigs confers the ability to define mutational processes driven by environmental exposures, DNA repair abnormalities, and mutagenic processes in individual tumors with implications for precision cancer medicine.
To determine whether incubation in the integrated EmbryoScope time-lapse monitoring system (TMS) and selection supported by the use of a multivariable morphokinetic model improve reproductive ...outcomes in comparison with incubation in a standard incubator (SI) embryo culture and selection based exclusively on morphology.
Prospective, randomized, double-blinded, controlled study.
University-affiliated private in vitro fertilization (IVF) clinic.
Eight hundred forty-three infertile couples undergoing intracytoplasmic sperm injection (ICSI).
No patient intervention; embryos cultured in SI with development evaluated only by morphology (control group) and embryos cultured in TMS with embryo selection was based on a multivariable model (study group).
Rates of embryo implantation, pregnancy, ongoing pregnancy (OPR), and early pregnancy loss.
Analyzing per treated cycle, the ongoing pregnancy rate was statistically significantly increased 51.4% (95% CI, 46.7–56.0) for the TMS group compared with 41.7% (95% CI, 36.9–46.5) for the SI group. For pregnancy rate, differences were not statistically significant at 61.6% (95% CI, 56.9–66.0) versus 56.3% (95% CI, 51.4–61.0). The results per transfer were similar: statistically significant differences in ongoing pregnancy rate of 54.5% (95% CI, 49.6–59.2) versus 45.3% (95% CI, 40.3–50.4) and not statistically significant for pregnancy rate at 65.2% (95% CI, 60.6–69.8) versus 61.1% (95% CI, 56.2–66.1). Early pregnancy loss was statistically significantly decreased for the TMS group with 16.6% (95% CI, 12.6–21.4) versus 25.8% (95% CI, 20.6–31.9). The implantation rate was statistically significantly increased at 44.9% (95% CI, 41.4–48.4) versus 37.1% (95% CI, 33.6–40.7).
The strategy of culturing and selecting embryos in the integrated EmbryoScope time-lapse monitoring system improves reproductive outcomes.
NCT01549262.
Double perovskite structure (A2BB′O6) oxides exhibit a breadth of multifunctional properties with a huge potential range of applications in fields as diverse as spintronics, magneto‐optic devices, or ...catalysis, and most of these applications require the use of thin films and heterostructures. Chemical solution deposition techniques are appearing as a very promising methodology to achieve epitaxial oxide thin films combining high performance with high throughput and low cost. In addition, the physical properties of these materials are strongly dependent on the ordered arrangement of cations in the double perovskite structure. Thus, promoting spontaneous cationic ordering has become a relevant issue. In this work, our recent achievements by using polymer‐assisted deposition (PAD) of environmentally friendly, water‐based solutions for the growth of epitaxial ferromagnetic insulating double perovskite La2CoMnO6 and La2NiMnO6 thin films on SrTiO3 and LaAlO3 single‐crystal substrates are presented. It is shown that the particular crystallization and growth process conditions of PAD (very slow rate, close to thermodynamic equilibrium conditions) promote high crystallinity and quality of the films, as well as favors spontaneous B‐site cationic ordering.
Slow films: The use of polymers to control the growth of ceramic thin films can make it easier to produce materials for spintronic applications, which use electron spin instead of charge to carry information. Water‐soluble polymers bind to metal cations and slow down crystallization rates so that the most thermodynamically favored double perovskite structure films, with an optimal orientation and high magnetism for device applications, are formed.
OBJECTIVE: To evaluate embryos with direct cleavage (≤5 hours) from two to three cells (DC2–3) and correlate this morphokinetic parameter to implantation and ongoing pregnancy. DESIGN: Clinical ...multicenter retrospective study. SETTING: Private in vitro fertilization (IVF) centers. PATIENT(S): From three clinics, a total of 979 treatments including 5,225 embryos using autologous or donated oocytes, of which 1,659 embryos were transferred. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy confirmed by ultrasound in week 7. RESULT(S): Of the total embryo cohort, 715 (13.7%) underwent direct cleavage from two to three cells, 1,659 embryos were transferred to recipients, and 109 of the transferred embryos cleaved directly from two to three cells (6.6%). Only one DC2–3 embryo was known to result in a clinical pregnancy (1%) and 80 (73.4%) DC2–3 embryos did not implant. Of the 1,550 embryos transferred not showing DC2–3, 203 embryos were from treatments with 100% implantation (13.1%), and 804 (51.8%) embryos did not implant. The known implantation rate of DC2–3 embryos was statistically significantly lower than for embryos with a normal cleavage pattern (1.2% vs. 20.2%, respectively). CONCLUSION(S): Embryos with DC2–3 had a statistically significantly lower implantation rate than embryos with a normal cleavage pattern, suggesting that rejection of these embryos for transfer could improve the implantation rate.
Abstract
The synthesis and characterization of a new Co(II) spin‐crossover (SCO) complex based on 4′‐(4‐carboxyphenyl)−2,2′:6′,2″‐terpyridine ligand are reported. This complex can be successfully ...grafted on silver surface maintaining the SCO behavior. Thus, atomic force microscopy (AFM), matrix assisted laser desorption ionization – time‐of‐flight mass spectrometry (MALDI‐TOF MS), Raman spectroscopy, and XPS measurements, upon surface deposition, evidence the formation of a monolayer of intact molecules grafted through carboxylate groups to the Ag surface. Three different techniques: Raman spectroscopy, X‐ray photoelectron spectroscopy (XPS), and X‐ray absorption spectroscopy (XAS), supported by first‐principles calculations, confirm that the deposited molecules undergo a gradual spin transition with temperature. This phenomenon is unprecedented for a monolayer of molecules directly grafted onto a metallic surface from solution.
Phylogenetic inference is generally performed on the basis of multiple sequence alignments (MSA). Because errors in an alignment can lead to errors in tree estimation, there is a strong interest in ...identifying and removing unreliable parts of the alignment. In recent years several automated filtering approaches have been proposed, but despite their popularity, a systematic and comprehensive comparison of different alignment filtering methods on real data has been lacking. Here, we extend and apply recently introduced phylogenetic tests of alignment accuracy on a large number of gene families and contrast the performance of unfiltered versus filtered alignments in the context of single-gene phylogeny reconstruction. Based on multiple genome-wide empirical and simulated data sets, we show that the trees obtained from filtered MSAs are on average worse than those obtained from unfiltered MSAs. Furthermore, alignment filtering often leads to an increase in the proportion of well-supported branches that are actually wrong. We confirm that our findings hold for a wide range of parameters and methods. Although our results suggest that light filtering (up to 20% of alignment positions) has little impact on tree accuracy and may save some computation time, contrary to widespread practice, we do not generally recommend the use of current alignment filtering methods for phylogenetic inference. By providing a way to rigorously and systematically measure the impact of filtering on alignments, the methodology set forth here will guide the development of better filtering algorithms,
Cohesin and CTCF are master regulators of genome topology. How these ubiquitous proteins contribute to cell-type specific genome structure is poorly understood. Here, we explore quantitative aspects ...of topologically associated domains (TAD) between pluripotent embryonic stem cells (ESC) and lineage-committed cells. ESCs exhibit permissive topological configurations which manifest themselves as increased inter- TAD interactions, weaker intra-TAD interactions, and a unique intra-TAD connectivity whereby one border makes pervasive interactions throughout the domain. Such 'stripe' domains are associated with both poised and active chromatin landscapes and transcription is not a key determinant of their structure. By tracking the developmental dynamics of stripe domains, we show that stripe formation is linked to the functional state of the cell through cohesin loading at lineage-specific enhancers and developmental control of CTCF binding site occupancy. We propose that the unique topological configuration of stripe domains represents a permissive landscape facilitating both productive and opportunistic gene regulation and is important for cellular identity.
Microrobots and metal-organic frameworks (MOFs) have been identified as promising carriers for drug delivery applications. While clinical applications of microrobots are limited by their low drug ...loading efficiencies and the poor degradability of the materials used for their fabrication, MOFs lack motility and targeted drug delivery capabilities. The combination of these two fields marks the beginning of a new era; MOF-based small-scale robots (MOFBOTs) for biomedical applications. Yet, biodegradability is a major hurdle in the field of micro- and nanoswimmers including small-scale robots. Here, a highly integrated MOFBOT that is able to realize magnetic locomotion, drug delivery, and selective degradation in cell cultures is reported for the first time. The MOF used in the investigations does not only allow a superior loading of chemotherapeutic drugs and their controlled release via a pH-responsive degradation but it also enables the controlled locomotion of enzymatically biodegradable gelatin-based helical microrobots under magnetic fields. The degradation of the integrated MOFBOT is observed after two weeks, when all its components fully degrade. Additionally, drug delivery studies performed in cancer cell cultures show reduced viability upon delivery of Doxorubicin within short time frames. This MOFBOT system opens new avenues for highly integrated fully biodegradable small-scale robots.
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