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For most functional oxides, structure‐selective synthesis is the key for the task‐specific production of nanomaterials. Herein, the low‐temperature synthesis in ionic liquids (ILs) is an attractive strategy to produce nanomaterials which are not accessible otherwise is described. In this study, a bench‐scale synthesis route toward Co3O4 by applying O3 on the molecular precursor Co2(CO)8 in IL medium is reported. The Co3O4 nanoparticles (NPs) are characterized by infrared (IR) spectroscopy, X‐ray diffraction (XRD), and transmission electron microscopy (TEM). This protocol yields Co3O4 with good crystallinity and narrow size distribution. In addition to conventional materials characterization, a new experimental approach is described in which the material synthesis in situ by IR reflection absorption spectroscopy (IRAS) (in situ IRAS) is followed. The in situ approach provides additional information on the growth mechanisms and kinetics and confirms that O3 treatment of Co2(CO)8 in IL exclusively yields pure Co3O4 without the formation of byproducts or intermediates. [ABSTRACT FROM AUTHOR]

An abstract of the article "The Belgian approach to meet the challenge in interpreting prenatal microarray results," by J. Muys and colleagues is presented.

Solid catalysts with ionic liquid layers (SCILLs) are heterogeneous catalysts which benefit significantly in terms of selectivity from a thin coating of an ionic liquid (IL). In the present work, we study the interaction of CO with a Pd model SCILL consisting of a 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)-imide ([C4C1Pyr][NTf2]) film deposited on Pd(111). We investigate the CO permeability and stability of the IL film via pressure modulation experiments by infrared reflection absorption spectroscopy (IRAS) in ultrahigh vacuum (UHV) and at ambient pressure conditions by time-resolved, temperature-programmed, and polarization-modulated (PM) IRAS experiments. In addition, we performed molecular dynamics (MD) simulations to identify adsorption motifs, their abundance, and the influence of CO. We find a strongly bound IL wetting monolayer (ML) and a potentially dewetting multilayer. Molecular reorientation of the IL at the interface and multilayer dewetting allow for the accumulation of CO at the metal/IL interface. Our results confirm that co-adsorption of CO changes the molecular structure of the IL wetting layer which confirms the importance to study model SCILL systems under in situ conditions. [ABSTRACT FROM AUTHOR]

Whole exome sequencing (WES) has become part of the postnatal diagnostic work-up of both pediatric and adult patients with a range of disorders. In the last years, WES is slowly being implemented in the prenatal setting as well, although some hurdles remain, such as quantity and quality of input material, minimizing turn-around times, and ensuring consistent interpretation and reporting of variants. We present the results of 1 year of prenatal WES in a single genetic center. Twenty-eight fetus-parent trios were analyzed, of which seven (25%) showed a pathogenic or likely pathogenic variant that explained the fetal phenotype. Autosomal recessive (4), de novo (2) and dominantly inherited (1) mutations were detected. Prenatal rapid WES allows for a timely decision-making in the current pregnancy, adequate counseling with the possibility of preimplantation or prenatal genetic testing in future pregnancies and screening of the extended family. With a diagnostic yield in selected cases of 25% and a turn-around time under 4 weeks, rapid WES shows promise for becoming part of pregnancy care in fetuses with ultrasound anomalies in whom chromosomal microarray did not uncover the cause. [ABSTRACT FROM AUTHOR]

Background: Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. Methods: We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients. Results: Pathogenic variants in ASPM and WDR62 were the most frequent causes in non‐consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non‐consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types. Conclusion: Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the accuracy and diagnostic value of genome-wide noninvasive prenatal testing (NIPT) for the detection of fetal aneuploidies in multiple gestations, with a focus on dichorionic-diamniotic twin pregnancies.Methods: We performed a retrospective cohort study including data from pregnant women with a twin or higher-order gestation who underwent genome-wide NIPT at one of the eight Belgian genetic centers between November 1, 2013, and March 1, 2020. Chorionicity and amnionicity were determined by ultrasonography. Follow-up invasive testing was carried out in the event of positive NIPT results. Sensitivity and specificity were calculated for the detection of trisomy 21, 18, and 13 in the dichorionic-diamniotic twin cohort.Results: Unique NIPT analyses were performed for 4,150 pregnant women with a multiple gestation and an additional 767 with vanishing gestations. The failure rate in multiple gestations excluding vanishing gestations ranged from 0% to 11.7% among the different genetic centers. Overall, the failure rate was 4.8%, which could be reduced to 1.2% after single resampling. There were no common fetal trisomies detected among the 86 monochorionic-monoamniotic and 25 triplet cases. Two monochorionic-diamniotic twins had an NIPT result indicative of a trisomy 21, which was confirmed in both fetuses. Among 2,716 dichorionic-diamniotic twin gestations, a sensitivity of 100% (95% CI 74.12-100%) and a specificity of 100% (95% CI 99.86-100%) was reached for trisomy 21 (n=12). For trisomy 18 (n=3), the respective values were 75% (95% CI 30.06-95.44%) sensitivity and 100% (95% CI 99.86-100%) specificity, and for trisomy 13 (n=2), 100% (95% CI 20.65-100%) sensitivity and 99.96% (95% CI 99.79-99.99%) specificity. In the vanishing gestation group, 28 NIPT results were positive for trisomy 21, 18, or 13, with only five confirmed trisomies.Conclusion: Genome-wide NIPT performed accurately for detection of aneuploidy in dichorionic-diamniotic twin gestations. [ABSTRACT FROM AUTHOR]

(c) cDNA sequencing from the hybrid mini-gene experiment: schematic representation of the in vitro mini-gene strategy used to analyse the splicing behaviour of the c.54+2T>A mutation. However, we now report the identification of further heterozygous mutations in I SNRPE i (NM 003094) - two novel mutations and one known mutation - in three ethnically diverse cases. The black lines underline the wild-type exon-exon junction and the red lines show the new splicing sites. [Extracted from the article]

Introduction: Preimplantation genetic diagnosis has been used successfully as a method of prenatal diagnosis for sex selection, in cases of X-linked disease, and for diagnosis in several monogenic diseases. Preimplantation genetic diagnosis for aneuploidy screening (PGS) offers the possibility to select euploid embryos for transfer, in an attempt to improve the IVF outcome for patients with recurrent implantation failure (more than three occurrences). Materials/Methods: Between January 2004 and December 2007, 133 cycles were started for PGS for repeated IVF failure. All patients had at least three failed IVF attempts. The pregnancy rate and implantation rate were compared with a control group (n = 139). This control group consisted of patients with repeated IVF failure (more than three cycles), but who preferred no PGS testing for different reasons. In the PGS group embryos were biopsied on day 3. One blastomere was examined for the chromosomes 13, 16, 18, 21 and 22 with the Multivysion™ PB kit (Vysis, France) and in the second FISH round for X and Y chromosomes. Transfer was performed on day 4. In the control group transfer was performed on day 2 or 3 based on morphological criteria. Results: In total 594 embryos were biopsied in 133 cycles. Mean age was 36 years. For 75 (56%) patients transfers were performed with a mean of 1.52 embryos per transfer in the PGS group. In the control group mean age was 36 years. More embryos were transferred with a mean of 2.2 per transfer. Distribution of age was similar in both groups: number of patients <36 years of age were 65 and 61 for control and PGS groups, respectively; for 36-40, 44 and 50; and for patients >40, 33 and 20. Pregnancy rate was higher in the control group: 37% versus 27% in the PGS group but implantation rate was identical in both groups (15% versus 14%). In patients <36 years of age, implantation rate in control versus PGS was 16% versus 15%, in the age group 36-39, it was 19% versus 18% and for patients ≥40, implantation rate in control group was 9% but no ongoing pregnancy was recorded in the PGS group. Multiple pregnancy rate was identical in both groups of 20%. There was one triplet pregnancy in the control group and none in the PGS group. Conclusion: Although analysis with PGS confirms a high rate of aneuploidy in patients with recurrent IVF failure, our study querying its use in these patient populations has not consistently shown an increase in ongoing pregnancy rates. Randomized controlled trials with large patient populations are needed before PGS can routinely be recommended as a means for increasing pregnancy rates in patients with recurrent IVF failure. [ABSTRACT FROM AUTHOR]

Introduction: Preimplantation genetic diagnosis (PGD) offers, to couples at high risk of passing on a serious genetic condition to their offspring, the possibility of detection of these specific genetic diseases on their embryos before implantation. By avoiding the psychologically difficult intervention of a therapeutic abortion, it offers a valid alternative to prenatal diagnosis. Materials/Methods: Retrospective analysis of 62 cycles of PGD were performed between January 2003 and December 2007 in 40 patients. Embryo biopsy was performed on day 3 by removal of two blastomeres from embryos with a minimum of six cells. For opening of the zona an acidified Tyrode's solution was used in 2004 and 2005 and laser was gradually introduced from 2006 onwards. In 15 cycles (nine patients), specific gene defects where looked after using PCR and this for the following indications: beta-thalassaemia with or without human leukocytes antigen typing (n = 4), spinal muscular atrophy (n = 3), GMI gangliosidosis (n = 3), cystic fibrosis (n = 1), Werdnig-Hoffmann syndrome (n = 2) and a combination of hand-foot-genital syndrome and synpolydactyly (n = 2). In 47 cycles, fluorescence in-situ hybridization was used for detection of reciprocal or Robertsonian translocations (31 patients). Embryo transfer was done on day 4 for the translocation group and on day 5 in the PCR group. Results: Mean age was 34 years (SD ± 4.8). Eight cycles were cancelled before biopsy because of poor embryo development. In the PCR group: mean age was 36 years (SD ± 4.4). 79 embryos were biopsied and diagnosis was obtained in 60 embryos (76%) on at least one of the blastomeres. 73% of the started cycles reached transfer (n = 11). 14 embryos were transferred with a mean of 1.3 embryos/transfer, resulting in three pregnancies (27%), one being a twin pregnancy. No miscarriage was noted. Implantation rate was 29%. Four healthy babies were delivered. In the translocation group, the mean age was 33 years (SD ± 4.8). 218 embryos were biopsied, resulting in 48 transferable embryos (22%). Only 51% of started cycles reached transfer. 24 transfers were performed with a mean of 1.3 embryos per transfer. Pregnancy rate was 25% with an implantation rate of 19%. Conclusion: With an overall implantation rate of 22%, these results confirm that preimplantation genetic diagnosis is useful as an alternative to prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background: The determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. The organisation of the immune response in the tumour microenvironment (TME) is expected to govern immunotherapy outcomes but spatial immunotypes remain poorly defined., Objective: We hypothesised that the deconvolution of spatial immune network architectures could identify clinically relevant immunotypes in HCC., Design: We conducted highly multiplexed imaging mass cytometry on HCC tissues from 101 patients. We performed in-depth spatial single-cell analysis in a discovery and validation cohort to deconvolute the determinants of the heterogeneity of HCC immune architecture and develop a spatial immune classification that was tested for the prediction of immune checkpoint inhibitor (ICI) therapy., Results: Bioinformatic analysis identified 23 major immune, stroma, parenchymal and tumour cell types in the HCC TME. Unsupervised neighbourhood detection based on the spatial interaction of immune cells identified three immune architectures with differing involvement of immune cells and immune checkpoints dominated by either CD8 T-cells, myeloid immune cells or B- and CD4 T-cells. We used these to define three major spatial HCC immunotypes that reflect a higher level of intratumour immune cell organisation: depleted, compartmentalised and enriched. Progression-free survival under ICI therapy differed significantly between the spatial immune types with improved survival of enriched patients. In patients with intratumour heterogeneity, the presence of one enriched area governed long-term survival., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

A growing number of druggable targets and national initiatives for precision oncology necessitate broad genomic profiling for many cancer patients. Whole exome sequencing (WES) offers unbiased analysis of the entire coding sequence, segmentation-based detection of copy number alterations (CNAs), and accurate determination of complex biomarkers including tumor mutational burden (TMB), homologous recombination repair deficiency (HRD), and microsatellite instability (MSI). To assess the inter-institution variability of clinical WES, we performed a comparative pilot study between German Centers of Personalized Medicine (ZPMs) from five participating institutions. Tumor and matched normal DNA from 30 patients were analyzed using custom sequencing protocols and bioinformatic pipelines. Calling of somatic variants was highly concordant with a positive percentage agreement (PPA) between 91 and 95% and a positive predictive value (PPV) between 82 and 95% compared with a three-institution consensus and full agreement for 16 of 17 druggable targets. Explanations for deviations included low VAF or coverage, differing annotations, and different filter protocols. CNAs showed overall agreement in 76% for the genomic sequence with high wet-lab variability. Complex biomarkers correlated strongly between institutions (HRD: 0.79-1, TMB: 0.97-0.99) and all institutions agreed on microsatellite instability. This study will contribute to the development of quality control frameworks for comprehensive genomic profiling and sheds light onto parameters that require stringent standardization., (© 2023. Nature Publishing Group UK.)