Evaluating Nondestructive Quantification of Composition Gradients in Metal-Organic Frameworks by MeV Ion Microbeam Analysis.

We evaluate a method to quantify composition depth gradients in intact metal-organic framework (MOF) single crystals and thereby derive diffusion coefficients of postsynthetically incorporated active sites by nondestructive ion-beam microanalysis. Zr-based UiO-67-bpy (bpy = 2,2'-bipyridine-5,5'-dicarboxylic acid) MOFs were synthesized on Si substrates and then metalated postsynthetically with NiCl2 for 2-48 h, resulting in different Ni depth distributions. Simultaneous micro-Rutherford backscattering spectrometry (µ-RBS) and micro-particle induced X-ray emission (µ-PIXE) analysis were used for the spatially resolved chemical analysis of the MOF single crystals. Qualitative assessment of the µ-RBS spectra indicated the presence of elemental depth gradients and hinted at the governing process of the postsynthetic Ni incorporation, in the present case, molecular diffusion. Quantitative evaluation of the resulting composition depth profiles directly provided the diffusion length and, thereby, the diffusion coefficient of the system. Virtual gradients caused by overhanging tips/edges of the truncated octahedral crystal shape are considered. Furthermore, in the case of insufficient probing depth for µ-RBS, µ-PIXE was still capable of providing qualitative information. In the present system the diffusion coefficient for NiCl2 is found to be (1.72 ± 0.18) × 10-16 m2s-1. The long-term stability of the synthesized and postsynthetically modified MOFs is proved by repeated measurements.

Delayed Sentinel Lymph Node Dissection in Patients with a Preoperative Diagnosis of Ductal Cancer In Situ by Preoperative Injection with Superparamagnetic Iron Oxide (SPIO) Nanoparticles: The SentiNot Study.

BACKGROUND: Difficulty in preoperatively assessing the risk for occult invasion or surgery that precludes future accurate axillary mapping in patients with ductal cancer in situ (DCIS) account for overutilization of SLND. METHODS: Prospective, multicenter, cohort study, including women with any DCIS planned for mastectomy or DCIS grade 2 and > 20 mm, any DCIS grade 3, any mass-forming DCIS and any planned surgery. Patients received an interstitial SPIO injection during breast surgery, but no upfront SLND was performed. If invasion was identified on final pathology, delayed SLND (d-SLND) was performed separately with the coadministration of isotope ± blue dye (BD). Study outcomes were proportion of upfront SLNDs that were avoided, detection rates during d-SLND, and impact on healthcare costs. RESULTS: In total, 78.7% of study participants (N = 254, mean age 60 years, mean DCIS size 37.8 mm) avoided upfront SLND. On d-SLND (median 28 days, range 9-46), SPIO outperformed Tc99 with (98.2% vs. 63.6%, p < 0.001) or without BD (92.7% vs. 50.9%, p < 0.001) and had higher nodal detection rate (86.9% vs. 32.3%, p < 0.001) and with BD (93.9% vs. 41.4%, p < 0.001). Only 27.9% of all SLNs retrieved were concordant for Tc99 and SPIO. Type of breast procedure (WLE vs. oncoplastic BCT vs. mastectomy) affected these outcomes and accounted for the low performance of Tc99 (p < 0.001). d-SLND resulted in a 28.1% total cost containment for women with pure DCIS on final pathology (4190 vs. 5828 USD, p < 0.001). CONCLUSIONS: Marking the SLN with SPIO may avoid overtreatment and allow for accurate d-SLND in patients with DCIS.

Prenatal and postnatal genetic testing toward personalized care: The non-invasive perinatal testing.

This article investigates how non-invasive prenatal testing and the incorporation of genomic sequencing into newborn screening postnatally are transforming perinatal care. They improve the accuracy of prenatal and neonatal screening, allowing for early interventions and personalized therapies. Non-invasive prenatal testing before birth and saliva-sample-based newborn genomic sequencing after birth can be collectively referred to as non-invasive perinatal testing. Non-invasive prenatal testing is particularly useful for aneuploidy, whereas performance markers worsen as DNA abnormalities shrink in size. Screening for clinically actionable diseases in childhood would be crucial to personalized medical therapy, as the postnatal period remains appropriate for screening for the great majority of monogenic disorders. While genomic data can help diagnose uncommon diseases, challenges like ethics and equity necessitate joint approaches for appropriate integration in this revolutionary journey toward personalized care.

Elemental Depth Profiling of Intact Metal-Organic Framework Single Crystals by Scanning Nuclear Microprobe.

The growing field of MOF-catalyst composites often relies on postsynthetic modifications for the installation of active sites. In the resulting MOFs, the spatial distribution of the inserted catalysts has far-reaching ramifications for the performance of the system and thus needs to be precisely determined. Herein, we report the application of a scanning nuclear microprobe for accurate and nondestructive depth profiling of individual UiO-66 and UiO-67 (UiO = Universitetet i Oslo) single crystals. Initial optimization work using native UiO-66 crystals yielded a microbeam method which avoided beam damage, while subsequent analysis of Zr/Hf mixed-metal UiO-66 crystals demonstrated the potential of the method to obtain high-resolution depth profiles. The microbeam method was further used to analyze the depth distribution of postsynthetically introduced organic moieties, revealing either core-shell or uniform incorporation can be obtained depending on the size of the introduced molecule, as well as the number of carboxylate binding groups. Finally, the spatial distribution of platinum centers that were postsynthetically installed in the bpy binding pockets of UiO-67-bpy (bpy = 5,5'-dicarboxyy-2,2'-bipyridine) was analyzed by microbeam and contextualized. We expect that the method presented herein will be applicable for characterizing a wide variety of MOFs subjected to postsynthetic modifications and provide information crucial for their optimization as functional materials.

Predictive biomarkers of platinum and taxane resistance using the transcriptomic data of 1816 ovarian cancer patients.

OBJECTIVE: The first-line chemotherapy for ovarian cancer is based on a combination of platinum and taxane. To date, no reliable predictive biomarker has been recognized that is capable of identifying patients with pre-existing resistance to these agents. Here, we have established an integrated database and identified the most significant biomarker candidates for chemotherapy resistance in serous ovarian cancer. METHODS: Gene arrays were collected from the GEO and TCGA repositories. Treatment response was defined based on pathological response or duration of relapse-free survival. The responder and nonresponder cohorts were compared using the Mann-Whitney and receiver operating characteristic tests. An independent validation set was established to investigate the correlation between chemotherapy response for the top 8 genes. Statistical significance was set at p < 0.05. RESULTS: The entire database included 1816 tumor samples from 12 independent datasets. From analyzing all the genes for platinum + taxane response, we identified the eight strongest genes correlated to chemotherapy resistance: AKIP1 (p = 1.60E-08, AUC = 0.728), MARVELD1 (p = 2.70E-07, AUC = 0.712), AKIRIN2 (p = 2.60E-07, AUC = 0.704), CFL1 (p = 8.10E-08, AUC = 0.694), SERBP1 (p = 8.10E-07, AUC = 0.684), PDXK (p = 1.30E-04, AUC = 0.634), TFE3 (p = 7.90E-05, AUC = 0.631) and NCOR2 (p = 1.90E-03, AUC = 0.611). Of these, the independent validation confirmed TFE3 (p = 0.012, AUC = 0.718), NCOR2 (p = 0.048, AUC = 0.671), PDXK (p = 0.019, AUC = 0.702), AKIP1 (p = 0.002, AUC = 0.773), MARVELD1 (p = 0.044, AUC = 0.675) and AKIRIN2 (p = 0.042, AUC = 0.676). An online interface was set up to enable future validation and ranking of new biomarker candidates in an automated manner (www.rocplot.org/ovar). CONCLUSIONS: We compiled a large integrated database with available treatment and response information and used this to uncover new biomarkers of chemotherapy response in serous ovarian cancer.

Evidence for the Oocyte Mosaicism Selection model on the origin of Patau syndrome (trisomy 13).

INTRODUCTION: In 2008, Hultén et al hypothesized that maternal ovarian trisomy 21 mosaicism might be the primary causative factor for fetal Down syndrome. We hypothesize that this theory can be extended to trisomy 13. MATERIAL AND METHODS: We collected fetal ovarian tissue from seven female fetuses between 16 and 23 gestational weeks, following the termination of the pregnancy for non-genetic reasons. All procedures were performed with informed consent and ethical approval from the local ethics committee. We used touch preparation techniques from fetal ovarian tissues and an anti-stromal antigen 3 antibody against the meiosis-specific stromal antigen 3 protein to differentiate between germ cells, ovarian stromal cells and the cells entering their first meiotic prophase. We used fluorescence in situ hybridization analysis to determine chromosome 13 numbers in each cell. RESULTS: We were able to detect a proportion of trisomy 13 cells in all cases. The average incidence of trisomy 13 cells was 2.04% in stromal antigen 3-positive and 0.91% in the stromal antigen 3-negative cells. The number of the trisomic cells increased significantly with gestational age (for stromal antigen 3-positive cells r = 0.93, P = 0.0038, for stromal antigen 3-negative cells r = 0.85, P = 0.0071). CONCLUSIONS: This study indicates that besides trisomy 21, the Oocyte Mosaicism Selection model could be extended to trisomy 13 as well. The crucial factor for trisomy 13 seems to be the pre-meiotic/mitotic trisomy 13 mosaicism, leading to a so-called secondary meiotic nondisjunction of those oocytes having three copies of chromosome 13.

[Longer oral contraception history as a possible preventive factor against fetal trisomy 21 in advanced maternal age pregnancies]. / A terhességet megelozoen alkalmazott hosszabb távú orális fogamzásgátlás mint a magzati 21-es triszómia lehetséges kockázatcsökkento tényezoje idos anyai életkorban vállalt terhességben.

Down syndrome is the most common autosomal chromosomal abnormality. According to the classical interpretation, it is the result of meiotic nondisjunction. Its occurrence is more common in advanced maternal age. Despite intensive research, pathophysiology of this genetic disorder is not fully understood. According to recent studies, a different kind of mechanism may be found in the background of trisomy 21 than was previously considered. Based on the ovarian mosaicism model, the cause of trisomy 21 (or any common trisomy) is a segregation error of a chromosome in premeiotic mitosis. The cell entering meiosis will be an oocyte with preexisting trisomy, where its (so-called "secondary") nondisjunction is essential. Maturation of the trisomic oocytes appears to fall behind the disomic oocytes, resulting in their relative accumulation in the ovaries as time progresses. The ratio of trisomic/disomic cells becomes less favorable in maternal maturity. If ovulation is inhibited - although the number of oocytes will continue to decline due to apoptosis - it can be assumed that the trisomic/disomic oocyte ratio remains more favorable with the progression of age. In our summary report, presenting and updating our previous data, we would like to propose that - according to ovarian mosaicism model - long-term oral contraception in the anamnesis may be beneficial in pregnancies with advanced maternal age. Orv Hetil. 2018; 159(28): 1146-1152.

Tilted pillar array fabrication by the combination of proton beam writing and soft lithography for microfluidic cell capture: Part 1 Design and feasibility.

Design, fabrication, integration, and feasibility test results of a novel microfluidic cell capture device is presented, exploiting the advantages of proton beam writing to make lithographic irradiations under multiple target tilting angles and UV lithography to easily reproduce large area structures. A cell capture device is demonstrated with a unique doubly tilted micropillar array design for cell manipulation in microfluidic applications. Tilting the pillars increased their functional surface, therefore, enhanced fluidic interaction when special bioaffinity coating was used, and improved fluid dynamic behavior regarding cell culture injection. The proposed microstructures were capable to support adequate distribution of body fluids, such as blood, spinal fluid, etc., between the inlet and outlet of the microfluidic sample reservoirs, offering advanced cell capture capability on the functionalized surfaces. The hydrodynamic characteristics of the microfluidic systems were tested with yeast cells (similar size as red blood cells) for efficient capture.

[Rare case of a pregnancy in a woman with paroxysmal nocturnal hemoglobinuria. Case report]. / Paroxysmalis nocturnalis haemoglobinuriával szövodött várandósság ritka esete.

Paroxysmal nocturnal hemoglobinuria is a rare hematological disease. It is associated with increased maternal and fetal complications to such an extent that pregnancy has been considered relatively contraindicated in woman with paroxysmal nocturnal haemoglobinuria. Recently, eculizumab, a monoclonal antibody, has been shown to decrease complications during pregnancies. The highest risk is thromboembolic complication and, therefore, anticoagulant is a standard therapy during pregnancy. In the presented case, a 29-year-old woman with a 5-year history of paroxysmal nocturnal haemoglobinuria had a pregnancy. It was her first pregnancy and was complicated by a sinus thrombosis at the 11th gestational week. After the introduction of eculizumab treatment, the remaining period of pregnancy and delivery were uncomplicated. There are only a few cases in the literature about pregnancy in woman with paroxysmal nocturnal hemoglobinuria who are treated with eculizumab. This monoclonal antibody seems to be safe and it likely prevents many of the complications otherwise observed.

[Next generation sequencing and its applications in non-invasive prenatal testing of aneuploidies]. / Új generációs szekvenálás és használata az aneuploidiák nem invazív praenatalis vizsgálatában.

The development of the new generation sequencing techniques brought a new era in the field of DNA sequencing, that also revolutionized the prenatal screening for aneuploidy. In order to provide a more complete view, the authors describe some first generation methods as well as the theoretical and technical background of the next generation methods. In the second part of this review, the authors focuse on non-invasive prenatal testing, which is a fetal cell-free DNA based method requiring advanced sequencing procedures. After discussing the theoretical and technical background, the authors review current application and utility of non-invasive prenatal testing. They conclude that non-invasive prenatal testing is the most effective screening test in high risk pregnancies and its efficiency can be justified in studies involving low risk pregnancies as well.

Optimizing post-synthetic metal incorporation in mixed-linker MOFs: insights from metalation studies on bipyridine-containing UiO-67 single crystals.

The postsynthetic metalation (PSM) of metal-organic frameworks (MOFs) with intrinsic metal binding sites is an intriguing strategy to introduce catalytic function into MOFs. The spatial distribution of the catalytic sites within the MOF crystal will affect the efficiency of the material, but the factors that govern depth distribution of the introduced metal sites are often not well understood. Herein, we employ Rutherford backscattering spectrometry (RBS) to investigate the metal distribution in a series of post-synthetically metalated mixed linker bpdc/BPY UiO-67 (UiO = Universitet i Oslo, bpdc = biphenyl-dicarboxylate, BPY = 2,2'-bipyridine-5,5'-dicarboxylate) single crystals as a function of linker ratio and metalation time. The RBS spectra reveal large differences in the depth distribution of inserted Ni2+ ions, and core/shell architectures are observed in high BPY materials at shorter incubation times. The incubation times to achieve uniform metal incorporation increases with increasing BPY ratios in the materials, suggesting that the presence of the BPY linkers slow down metal uptake. We propose a combination of ionic interactions and pore clogging, where coordinated ions reduce the available pore space for further ions to diffuse deeper into the framework as reasons for the observed trends. The observations are likely relevant for other mixed-linker MOF systems, and understanding the effect that linker ratios have on PSM and cation distribution will aid in future optimizations of catalytic MOFs.

Fabrication of Quasi-Sinusoidal Surface Relief Optical Transmission Gratings in Pyrex and IOG Glasses by Implantation with Oxygen and Nitrogen Ion Microbeams of the 5-6 MeV Energy Range.

A method for the fabrication of high diffraction efficiency optical transmission gratings with quasi-sinusoidal profile in glasses by microbeams of medium-mass ions of 5-6 MeV energy was devised and demonstrated. Gratings with a 30 µm grating constant have been manufactured and characterized by interference microscopy and microprofilometry. The obtained surface profiles of the gratings were found to be quasi-sinusoidal with up to 265 nm amplitude. Measured highest first-order diffraction efficiencies were around 26% in both Pyrex and IOG glasses. Such gratings could serve as coupling elements in integrated optics and photonic integrated circuits.

Reflective, polarizing, and magnetically soft amorphous neutron optics with 11B-enriched B4C.

The utilization of polarized neutrons is of great importance in scientific disciplines spanning materials science, physics, biology, and chemistry. However, state-of-the-art multilayer polarizing neutron optics have limitations, particularly low specular reflectivity and polarization at higher scattering vectors/angles, and the requirement of high external magnetic fields to saturate the polarizer magnetization. Here, we show that, by incorporating 11B4C into Fe/Si multilayers, amorphization and smooth interfaces can be achieved, yielding higher neutron reflectivity, less diffuse scattering, and higher polarization. Magnetic coercivity is eliminated, and magnetic saturation can be reached at low external fields (>2 militesla). This approach offers prospects for substantial improvement in polarizing neutron optics with nonintrusive positioning of the polarizer, enhanced flux, increased data accuracy, and further polarizing/analyzing methods at neutron scattering facilities.

Early prenatal detection of a fast-growing fetal epignathus.

Epignathus is a rare congenital orofacial teratoma. We present a case of a fast-growing tumor, where early prenatal diagnosis was made and where fetopathological examination revealed the reason of the remarkable ultrasonographic signs and underlined the expected poor prognosis. Ultrasonographic examination at 18 weeks' gestation showed that there was a growing tumor protruding from the fetus's mouth. The fetal stomach could not be seen and extreme polyhydramnios was also detected. After counseling, the couple opted for a termination of pregnancy. Fetopathological examination showed that the tumorosus mass was not only protruding from the mouth, but also inexplicably grew downwards, was connected to the hard palate and the periosteum of the vertebral corpus, making an airway and esophageal obstruction, causing the ultrasonographic findings. Postnatal treatment and surgical removal of this tumor seemed to be impossible. In case of an early detection of a fast-growing fetal epignathus, pregnancy termination should be considered.

[Cell-free nucleic acid-based non-invasive prenatal diagnosis of fetal aneuploidies]. / Magzati aneuploidiák szabadnukleinsav-alapú, nem invazív diagnosztikája.

Prenatal detection of fetal aneuploidies is one of the main goals of the prenatal diagnostic approach. As a benefit of the development of advanced ultrasound equipment and advances in molecular biology in the last decade, there is a significant progress in screening methods for fetal aneuploidies, although invasive methods remain the gold standard for aneuploidy detection. Non-invasive prenatal diagnosis has substantial medical impact as it targets the development of safer and more effective methods to avoid the risk of fetal loss associated with currently used invasive methods. Identification of fetal-specific messenger ribonucleic acids, digital polymerase chain reaction and next-generation sequencing give the real chance for non-invasive prenatal diagnosis of fetal aneuploidies. Although all these methods have both advantages and limitations, some of them are moving closer to clinical implementation. In this review the authors highlight the most recent advances in methods for non-invasive prenatal diagnosis of aneuploidies.

Supporting Tourism by Assessing the Predictors of COVID-19 Vaccination for Travel Reasons.

The persistence of the SARS-CoV-2 virus imposed vaccination passports for traveling in most countries. We investigated psychological factors that predict the intention to vaccinate for travel. In a cross-sectional study, we examined how demographic variables, vaccination status, perceived risk of infection and severity of disease contracted at travel destination, safety and effectiveness of vaccines against contracting COVID-19 during travel, and conspiracy beliefs are related to intention to vaccinate for travel. Further analyses involved differences between vaccinated and unvaccinated individuals in a Romanian sample regarding conspiracy beliefs, attitudes about vaccines, and self-efficacy of controlling COVID-19 infection. Results showed that the intention to vaccinate for travel reasons is best predicted by vaccination status and perceptions of safety and efficacy of vaccines against COVID-19. Thus, vaccinated individuals believing that vaccines are safe and effective most probably will take another vaccine booster if it will allow them to travel. Positive relationships of the intention to vaccinate for travel reasons were found with age, vaccination status, conspiracy beliefs, perceptions of safety and effectiveness of vaccines, intention to travel, and a more cautious approach to travel. No significant relationships were found between perceptions of risk for self or for transmitting the disease to others, severity of disease, and the intention to vaccinate for travel. We also found significant differences between vaccinated and unvaccinated participants, as unvaccinated participants showed higher levels of conspiracy beliefs and less trust in the safety and efficacy of vaccines. We conclude that campaigns focused on promoting information on the safety and efficacy of vaccines is the most important direction for promoting vaccination in young travelers.

Comparison of prevalence of toxoplasma and cytomegalovirus infection in cases with fetal ultrasound markers in the second trimester of pregnancy.

OBJECTIVES: To evaluate the prevalence of toxoplasma and cytomegalovirus (CMV) infections in cases of ultrasound anomalies detected in the second trimester of pregnancy. METHODS: Serological examinations for toxoplasma and CMV infection were carried out in 655 cases with sonographic findings suggestive of fetal infection, 612 cases with single ultrasound markers and 43 cases with two or more markers. RESULTS: In cases of single ultrasound markers, serological examination diagnosed recent toxoplasma infection in 107/612 cases (17.5%) and recent CMV infection in 75 cases (12.3%). Recent toxoplasma infection accounted for 13.8% (52/377) of the intracranial sonographic findings and 23.9% (45/188) of the abdominal findings, whereas recent CMV infections accounted for 12.2 (46/377) and 11.7% (22/188), respectively. Recent CMV infection with sonographic manifestations had higher rates of intracranial than intra-abdominal sonographic findings (46/75 or 61% vs 22/75 or 29%), whereas recent toxoplasma infection with sonographic manifestations had similar rates of intracranial (52/107 or 49%) and intra-abdominal (45/107 or 42%) findings. In cases of two or more ultrasound markers, serological examination diagnosed recent toxoplasma infection in 12/43 cases (27.9%) and recent CMV infection in 10/43 cases (23.3%). CONCLUSIONS: Ultrasound findings suspicious for toxoplasma and CMV infection are not pathognomonic for either pathologic entity.

Circulating levels of the anti-angiogenic thrombospondin 2 are elevated in pre-eclampsia.

An imbalance of maternal circulating pro- and anti-angiogenic factors may play a role in the pathogenesis of pre-eclampsia. Thrombospondin 2 (TSP-2) is a protein expressed mainly by activated endothelial cells, which acts as a potent anti-angiogenic agent. Our aim was to determine whether serum TSP-2 levels are altered in pre-eclampsia. We enrolled 35 pre-eclamptic patients and 35 healthy pregnant women in the study. Thrombospondin 2 levels were determined by enzyme-linked immunosorbent assay, while soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) concentrations were determined by electrochemiluminescence immunoassay. In patients with PE, we demonstrated 1.7-fold higher TSP-2 [13.2 (9.4-18.1) vs. 7.9 (7.2-11.2) ng/ml, p<0.001], 3.8-fold higher sFlt-1 and 4.3-fold lower PlGF levels compared with the control group. There were no associations between TSP-2 and sFlt-1 or PlGF concentrations. We suggest that circulating TSP-2 levels may contribute to the pathogenesis of PE via its anti-angiogenic properties, but in a distinct way from sFlt-1 and PlGF.

Shaping Sustainable Urban Environments by Addressing the Hydro-Meteorological Factors in Landslide Occurrence: Ciuperca Hill (Oradea, Romania).

Romania is one of the countries severely affected by numerous natural hazards, where landslides constitute a very common geomorphic hazard with strong economic and social impacts. The analyzed area, known as the "Ciuperca Hill", is located in Oradea (NW part of Romania) and it has experienced a number of landsliding events in previous years, which have endangered anthropogenic systems. Our investigation, focused on the main causal factors, determined that landslide events have rather complex components, reflected in the joint climatological characteristics, properties of the geological substrate, and human activity that further contributed to the intensive change of landscape and acceleration of slope instability. Analysis of daily precipitation displays the occurrence and intensive distribution between May and September. Higher values of rainfall erosivity (observed for the 2014-2017 period), are occurring between April and August. Erosivity density follows this pattern and indicates high intensity events from April until October. SPI index reveals the greater presence of various wet classes during the investigated period. Geological substrate has been found to be highly susceptible to erosion and landsliding when climatological conditions are suitable. Accelerated urbanization and reduced vegetation cover intensified slope instability. The authors implemented adequate remote-sensing techniques in order to monitor and assess the temporal changes in landslide events at local level. Potential solutions for preventative actions are given in order to introduce and conduct qualitative mitigation strategies for shaping sustainable urban environments. Results from this study could have implications for mitigation strategies at national, regional, county, and municipality levels, providing knowledge for the enhancement of geohazard prevention and appropriate response plans.