Abstract
STUDY QUESTION
Can a reconstructed ovary using decellularized human ovarian tissue (DCT) support survival of pre-antral stage follicles?
SUMMARY ANSWER
We have demonstrated an effective ...protocol for decellularization of human ovarian tissues and successful recellularization with isolated human ovarian cells and pre-antral follicles.
WHAT IS KNOWN ALREADY
Survivors of leukemia or ovarian cancer run a risk of reintroducing malignancy when cryopreserved ovarian tissue is transplanted to restore fertility. A reconstructed ovary free of malignant cells could provide a safe alternative. Decellularization of ovarian tissue removes all cells from the extracellular matrix (ECM) including possible malignancies and leaves behind a physiological scaffold. The ECM offers the complex milieu that facilitates the necessary interaction between ovarian follicles and their surroundings to ensure their growth and development. Previous studies have shown that decellularized bovine ovarian scaffolds supported murine follicle growth and restoration of ovarian function in ovariectomized mice.
STUDY DESIGN, SIZE, DURATION
Optimizing a decellularization protocol for human ovarian tissues and testing biofunctionality of the decellularized scaffolds in vitro and in vivo by reseeding with both murine and human pre-antral follicles and ovarian cells.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Donated human ovarian tissue and isolated pre-antral follicles were obtained from women undergoing ovarian tissue cryopreservation for fertility preservation. Ovarian cortical and medullary tissues were decellularized using 0.1% sodium dodecyl sulfate (SDS) for 3, 6, 18 and 24 hours followed by 24 hours of 1 mg/mL DNase treatment and washing. Decellularization of ovarian tissues and preservation of ECM were characterized by morphological evaluation using Periodic Acid–Schiff (PAS) staining, DNA quantification, histochemical quantification of collagen content and immunofluorescence analysis for collagen IA, laminin, fibronectin and DNA. Human ovarian stromal cells and isolated human pre-antral follicles were reseeded on the DCT and cultured in vitro. Isolated murine (N = 241) and human (N = 20) pre-antral follicles were reseeded on decellularized scaffolds and grafted subcutaneously to immunodeficient mice for 3 weeks.
MAIN RESULTS AND THE ROLE OF CHANCE
Incubation in 0.1% SDS for 18–24 hours adequately decellularized both human ovarian medullary and cortical tissue by eliminating all cells and leaving the ECM intact. DNA content in DCT was decreased by >90% compared to native tissue samples. Histological examination using PAS staining confirmed that the cortical and medullary tissues were completely decellularized, and no visible nuclear material was found within the decellularized sections. DCT also stained positive for collagen I and collagen quantities in DCT constituted 88–98% of the individual baselines for native samples. Human ovarian stroma cells were able to recellularize the DCT and isolated human pre-antral follicles remained viable in co-culture. Xenotransplantation of DCT reseeded with human or murine pre-antral follicles showed, that the DCT was able to support survival of human follicles and growth of murine follicles, of which 39% grew to antral stages. The follicular recovery rates after three weeks grafting were low but similar for both human (25%) and murine follicles (21%).
LARGE SCALE DATA
N/A
LIMITATIONS, REASONS FOR CAUTION
Further studies are needed to increase recovery and survival of the reseeded follicles. Longer grafting periods should be evaluated to determine the developmental potential of human follicles. Survival of the follicles might be impaired by the lack of stroma cells.
WIDER IMPLICATIONS OF THE FINDINGS
This is the first time that isolated human follicles have survived in a decellularized human scaffold. Therefore, this proof-of-concept could be a potential new strategy to eliminate the risk of malignant cell re-occurrence in former cancer patients having cryopreserved ovarian tissue transplanted for fertility restoration.
STUDY FUNDING/COMPETING INTEREST(S)
This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. Furthermore, Project ITN REP-BIOTECH 675526 funded by the European Union, European Joint Doctorate in Biology and Technology of the Reproductive Health, the Research Pools of Rigshospitalet, the Danish Cancer Foundation and Dagmar Marshalls Foundation are thanked for having funded this study. The funders had no role in the study design, data collection and interpretation, or in the decision to submit the work for publication.
Based on the theory of characteristic modes (TCMs), this paper proposes a systematic design procedure to guide the design of a neutralization line (NL) for a dual-band multiple-input-multiple-output ...(MIMO) antenna to achieve high isolation. According to the direction of the current flow of significant characteristic modes, coupling and uncoupling modes are identified and a metal NL is appropriately designed to cancel the coupling modes. More specifically, it introduces new currents opposite in direction to the original coupling characteristic currents, thus reducing mutual coupling. Compared with the traditional NL design method, the proposed approach simplifies the optimization process and saves lots of optimal design time. As an illustration of the proposed design method, we design another dual-band antenna operating in the WLAN bands with a compact size of 50 mm × 48 mm × 0.8 mm and minimum edge‐to‐edge space between the radiating elements with 0.033λ0 of the lower band. The impedance bandwidths for S11 ≤ -10 dB are 0.42 GHz (2.27–2.69 GHz) and 0.24 GHz (5.6–5.84 GHz). A fabricated prototype shows good agreement between the measured and simulated results. The introduced NL improves the isolation degree by about 18 dB for the 5.8 GHz band, and the total efficiency of the antenna was also improved. In addition, the proposed antenna also has a low envelop correlation coefficient (ECC < 0.3), high diversity gains, and low total active reflection coefficient (TARC) in the frequency band of interest. Measurement results show that the proposed MIMO antenna system is suitable for WLAN applications.
Recent findings of new Higgs modes in unconventional superconductors require a classification and characterization of the modes allowed by nontrivial gap symmetry. Here we develop a theory for a ...tailored nonequilibrium quantum quench to excite all possible oscillation symmetries of a superconducting condensate. We show that both a finite momentum transfer and quench symmetry allow for an identification of the resulting Higgs oscillations. These serve as a fingerprint for the ground state gap symmetry. We provide a classification scheme of these oscillations and the quench symmetry based on group theory for the underlying lattice point group. For characterization, analytic calculations as well as full scale numeric simulations of the transient optical response resulting from an excitation by a realistic laser pulse are performed. Our classification of Higgs oscillations allows us to distinguish between different symmetries of the superconducting condensate.
Metagenomic and bioinformatic approaches were used to characterize plant biomass conversion within the foregut microbiome of Australia's "model" marsupial, the Tammar wallaby (Macropus eugenii). Like ...the termite hindgut and bovine rumen, key enzymes and modular structures characteristic of the "free enzyme" and "cellulosome" paradigms of cellulose solubilization remain either poorly represented or elusive to capture by shotgun sequencing methods. Instead, multigene polysaccharide utilization loci-like systems coupled with genes encoding β-1,4-endoglucanases and β-1,4-endoxylanases—which have not been previously encountered in metagenomic datasets—were identified, as were a diverse set of glycoside hydrolases targeting noncellulosic polysaccharides. Furthermore, both rrs gene and other phylogenetic analyses confirmed that unique clades of the Lachnospiraceae, Bacteroidales, and Gammaproteobacteria are predominant in the Tammar foregut microbiome. Nucleotide composition-based sequence binning facilitated the assemblage of more than two megabase pairs of genomic sequence for one of the novel Lachnospiraceae clades (WG-2). These analyses show that WG-2 possesses numerous glycoside hydrolases targeting noncellulosic polysaccharides. These collective data demonstrate that Australian macropods not only harbor unique bacterial lineages underpinning plant biomass conversion, but their repertoire of glycoside hydrolases is distinct from those of the microbiomes of higher termites and the bovine rumen.
Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct ...patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in ...2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.
Over the last two decades, silicon nanowire field-effect transistors (SiNW-FETs) with prominent merits of high surface-to-volume ratio, excellent biocompatibility and mature fabrication with standard ...silicon technology, have been widely studied as ultrahigh sensitive biosensors for the detection of target biomolecules, such as proteins, nucleic acids, cells and viruses so on. Herein we present a comprehensive review of the fundamental aspects of SiNW-FET biosensors, involving the working principle and the device fabrication, surface functionalization, and system integration with fluid exchange and electrical detection. Futhermore, we emphatically discuss the electrical detection of cardiac-specific biomarkers related to acute myocardial infarction disease. SiNW-FET biosensors are being increasingly exploited as promising diagnostic devices, which provide high sensitivity, high integration density, high speed sampling, strong specificity, and real-time and label-free detection for simple and cheap clinical testing.
A novel technique, namely periodic characteristic mode (CM) analysis (PCMA) method, is proposed for the solution of CMs of large-scale finite periodic arrays. This technique first adopts a small set ...of CMs of the reference element of the array with larger modal significance (MS) to construct the entire-domain basis functions defined on each array element and then applies them to expand the characteristic currents of the entire array. By using these newly constructed CM-based entire-domain basis functions, the proposed PCMA method can achieve great reduction in the matrix dimension of the resultant generalized eigenvalue problem governed by the entire array structure, thereby significantly reducing the computational time and memory requirement for solving CMs of the entire large-scale finite periodic array. Several typical examples are presented to demonstrate the efficiency and accuracy of the proposed method.
When writing a research paper, the author has to select information to include in the paper to support various arguments. The information has to be organized and synthesized into a coherent whole ...through relationships and information structures. There is hardly any research on the information structure of research papers, and how information structure supports rhetorical and argument structures. Thus, this study is focused on information organization in the Abstract and Introduction sections of sociology research papers, analyzing the information structure of research objective, question, hypothesis, and result statements. The study is limited to research papers reporting research that investigated cause–effect relations between two concepts. Two semantic frames were developed to specify the types of information associated with cause–effect and comparison relations, and used as coding schemes to annotate the text for different information types. Six link patterns between the two frames were identified—showing how comparisons are used to support the claim that the cause‐effect relation is valid. This study demonstrated how semantic frames can be incorporated in discourse analysis to identify deep structures underlying the argument structure. The results carry implications for the knowledge representation of academic research in knowledge graphs, for semantic relation extraction, and teaching of academic writing.
PDF
