Continuous flow synthesis of atom-precise platinum clusters.

Subnanometer clusters with precise atom numbers hold immense potential for applications in catalysis, as single atoms can significantly impact catalytic properties. Typically, inorganic clusters are produced using batch processes with high dilutions, making the scale-up of these processes time-consuming and its reproducibility challenging. While continuous-flow systems have been employed for organic synthesis and, more recently, nanoparticle preparation, these approaches have only rarely been applied to cluster synthesis. In a flexible, continuous flow synthesis platform, we integrate multiple continuous stirred tank reactors (CSTR) into a cascade to synthesize clusters with a precise number of atoms, demonstrating the potential of this approach for atom precise cluster synthesis and expanding the application of continuous-flow systems beyond organic synthesis.

Toxicokinetic analysis of the highly toxic nerve agent VX in commercially available multi-organ-chips - Ways to overcome compound absorption.

Organ-on-a-chip technology is considered a next-generation platform in pharmacology and toxicology. Nevertheless, this novel technology still faces several challenges concerning the respective materials which are used for these microfluidic devices. Currently available organ-chips are most often based on polydimethylsiloxane (PDMS). However, this material has strong limitations regarding compound binding. The current study investigated options to reduce compound absorption of the highly toxic nerve agent VX (1000 µmol/L) in a commercially available organ-chip. In addition, surface effects on degradation products of VX were investigated. The alternative polymer cyclic olefin copolymers (CoC) showed significantly less compound absorption compared to PDMS. Furthermore, a coating of PDMS- and CoC-based chips was investigated. The biocompatible polymer polyethyleneimine (PEI) successfully modified PDMS and CoC surfaces and further reduced compound absorption. A previously examined VX concentration after 72 h of 141 ± 10 µmol/L VX could be increased to 442 ± 54 µmol/L. Finally, the respective concentrations of VX and degradation products accounted for > 90% of the initial concentration of 1000 µmol/L VX. The currently described surface modification might be a first step towards the optimization of organ-on-a-chip surfaces, facilitating a better comparability of different studies and results.

3D assessment after maxillary sinus grafting with a porcine, a bovine and a synthetical bone substitute material. A randomized controlled clinical trial.

AIM: This randomized controlled clinical study focused on graft volume alterations after sinus floor augmentation with a deproteinized bovine bone mineral (DBBM, Geistlich Bio-Oss®), deproteinized porcine bone mineral (DPBM, THE GRAFT®) or a biphasic calcium phosphate (BCP, OSOPIA®). MATERIAL AND METHODS: 28 patients with edentulous situations in the posterior maxilla with less or equal to 5 mm of residual bone height received a two- staged external sinus grafting procedure with DBBM, DPBM or BCP. CBCT scans were performed prior surgery (CBCT1), directly after surgery (CBCT2) and after a healing period of 4-6 months prior implant placement (CBCT3). CBCT scans were used to analyze volumetric alterations of the sinus grafts by virtual 3D model matching of CBCT1- CBCT2 (situation after sinus grafting) and CBCT1 and CBCT2 (situation prior implant placement). RESULTS: The volume of the bone graft in the maxillary sinus (volume (VOL%) directly after grafting rated as 100%) was stable after the healing period in the DBBM (VOL%: 103±4%) and the PBBM groups (VOL%: 112± 23) with no statistically significant differences concerning 3D measurements. In the BCP group, the grafted volume declined to 66± 25% (VOL%), statistically inferior to the DBBM and DPBM groups. CONCLUSION: Concerning bone graft stability/ 25 volume DBBM and DPBM show comparable outcomes. Due to resorption, BCP showed inferior bone graft volume after healing (statistically significant) compared to DBBM and DPBM.

The suitability of a polydimethylsiloxane-based (PDMS) microfluidic two compartment system for the toxicokinetic analysis of organophosphorus compounds.

Organ-on-a-chip platforms are an emerging technology in experimental and regulatory toxicology (species-specific differences, ethical considerations). They address gaps between in vivo and in vitro models. However, there are still certain limitations considering material, setup and applicability. The current study examined the suitability of a commercially available polydimethylsiloxane-based (PDMS) organ-chip for the toxicokinetic characterization of the highly toxic nerve agent VX and the organophosphate pesticide parathion. The respective concentrations of 1000 µmol/L and 100 µmol/L VX and parathion were chosen deliberately high in order to study concentrations even if high compound absorption by PDMS might occur. Neuronal and liver spheroids, totaling 2 × 106 cells were used to study concentration changes of VX and parathion. In addition, VX enantiomers were quantified. The current study suggests a significant absorption of VX, respectively parathion by PDMS. This might require future investigation of alternative materials or coatings to limit absorption for organophosphorus compounds in toxicokinetic studies.

Triplet-Encoded Prebiotic RNA Aminoacylation.

The encoding step of translation involves attachment of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases, themselves the product of coded peptide synthesis. So, the question arises─before these enzymes evolved, how were primordial tRNAs selectively aminoacylated? Here, we demonstrate enzyme-free, sequence-dependent, chemoselective aminoacylation of RNA. We investigated two potentially prebiotic routes to aminoacyl-tRNA acceptor stem-overhang mimics and analyzed those oligonucleotides undergoing the most efficient aminoacylation. Overhang sequences do not significantly influence the chemoselectivity of aminoacylation by either route. For aminoacyl-transfer from a mixed anhydride donor strand, the chemoselectivity and stereoselectivity of aminoacylation depend on the terminal three base pairs of the stem. The results support early suggestions of a second genetic code in the acceptor stem.

Assessment of the bioaccumulation potential of four commonly used phenolic benzotriazoles based on in silico and experimental in vivo data.

Phenolic benzotriazoles (BTZs) are used globally as light stabilizers in various plastic products to protect them from photooxidative degradation. The same physical-chemical properties that confer their functionality, like a sufficient photostability and a high octanol-water partition coefficient, also raise concerns on their potential for environmental persistence and bioaccumulation based on in silico predictive tools. To evaluate their bioaccumulation potential in aquatic organisms, standardized fish bioaccumulation studies according to OECD TG 305 were conducted with four of the most commonly used BTZs: UV 234, UV 329, UV P, and UV 326. The resulting growth- and lipid-corrected BCF values revealed that UV 234, UV 329, and UV P were below the bioaccumulation threshold (BCF ≤ 2000), but UV 326 is considered very bioaccumulative (BCF ≥ 5000) with respect to the bioaccumulation criteria under REACH. Comparing these experimentally derived data with quantitative structure activity related or other calculated values using a logarithmic partitioning coefficient octanol-water (log Pow ) driven mathematical formula revealed significant discrepancies demonstrating the weakness of current in silico approaches for this group of substances. Furthermore, available environmental monitoring data demonstrate that these rudimentary in silico approaches can lead to unreliable bioaccumulation estimates for this chemical class due to considerable uncertainties in underlying assumptions (e.g., concentration and route of exposure). However, using more sophisticated in silico methods (i.e., CATALOGIC base-line model), the derived BCF values were better aligned with the experimentally derived ones.

A clinical trial: Aqualizer ™ therapy and its effects on myopathies or temporomandibular dysfunctions. Part II: Subjective parameters.

OBJECTIVE: Temporomandibular dysfunction (TMD) reduces patients' quality of life (QoL). The aim was to assess the effects of initial Aqualizer™ therapy. METHODS: Group 1 (initial Aqualizer™ therapy) before definitive splint therapy or Group 2 (no initial therapy). Patients with arthrosis, partial/total prosthesis, or were undergoing splint therapy were excluded. Subjective parameters were evaluated: duration and intensity of pain, influence on wellbeing, changes in the head/neck area, handling and improvement of the Aqualizer™, improvement in QoL. The statistical significance level was 5% (p < 0.05). RESULTS: In 53 patients (Group 1 n = 25; Group 2 n = 28), the improvement in patients' well-being and intensity of pain in both groups was significant (p < 0.001). An improvement in QoL was found in 84% of patients in Group 1 and 75% in Group 2. CONCLUSION: Initial Aqualizer™ therapy can decrease the intensity of pain and increase patients'.

Investigation of the palatal soft tissue volume: a 3D virtual analysis for digital workflows and presurgical planning.

BACKGROUND: In mucogingival and implant surgery, an autologous soft tissue graft from the palate is the gold standard for reconstructing missing keratinised soft tissue and volume. Previously, presurgical measurements of the graft harvesting site were described with two-dimensional (2D) linear measurements. The present observational clinical study aimed to evaluate a three-dimensional (3D) measurement method for determining the present palatal soft tissue volume for each patient individually. METHODS: Pre-existing cone beam computed tomography (CBCT) scans of 20 patients were converted into 3D Standard Tessellation Language models of the bone surface. Intraoral impressions of the maxilla were taken and digitised to visualise the gingival surface. The resulting virtual models of bone (reference value) and gingival (actual value) surfaces were merged, with tooth surfaces used for registration. The region between the central incisors and the hard palate was subdivided into 5 regions of interest (ROIs). The distance between palatal bone and gingival surface was analysed both volumetrically and linearly, and the results were statistically evaluated for the ROIs. RESULTS: The average gingival surface area on the palate was 19.1 cm2, and the mean volume was 58.2 cm3 (± 16.89). Among the ROIs, the mean linear value was highest in the most distal region, from the second molar to the hard palate (4.0 ± 1.09 mm) and lowest in the canine region (1.9 ± 0.63 mm). For mean distance, significant differences were found for the anterior palate and the most posterior palate in comparison with all other ROIs (p < 0.01). The volume measurements also declined significantly and steadily between the posterior (1.9 ± 1.0 cm3) and anterior palates (0.4 ± 0.2 cm3). CONCLUSIONS: By merging digital data, palatal soft tissue could be quantified virtually. The results were reliable and comparable to previous findings with linear measurement methods. This 3D soft tissue volume analysis method fully exploited the diagnostic potential of data that are frequently collected for presurgical planning in oral surgery (i.e., CBCT + surface scans). This evaluation method might be useful for volumetric and linear measurements in other applications in anatomy and for determining palatal soft tissue dimensions in the planning stage before surgical interventions. TRIAL REGISTRATION: This observational clinical trial was retrospectively registered in the German Clinical Trials Register, reference number: DRKS00023918.

Learning to rank Higgs boson candidates.

In the extensive search for new physics, the precise measurement of the Higgs boson continues to play an important role. To this end, machine learning techniques have been recently applied to processes like the Higgs production via vector-boson fusion. In this paper, we propose to use algorithms for learning to rank, i.e., to rank events into a sorting order, first signal, then background, instead of algorithms for the classification into two classes, for this task. The fact that training is then performed on pairwise comparisons of signal and background events can effectively increase the amount of training data due to the quadratic number of possible combinations. This makes it robust to unbalanced data set scenarios and can improve the overall performance compared to pointwise models like the state-of-the-art boosted decision tree approach. In this work we compare our pairwise neural network algorithm, which is a combination of a convolutional neural network and the DirectRanker, with convolutional neural networks, multilayer perceptrons or boosted decision trees, which are commonly used algorithms in multiple Higgs production channels. Furthermore, we use so-called transfer learning techniques to improve overall performance on different data types.

A Retrospective Data Analysis for the Risk Evaluation of the Development of Drug-Associated Jaw Necrosis through Dentoalveolar Interventions.

This study aimed to analyse the development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent surgical intervention to identify potential risk factors between three different groups sorted by the type of oral surgery (single tooth extraction, multiple extraction, osteotomy). Data from patients with this medical history between 2010 and 2017 were retrospectively analysed. The following parameters were collected: sex, age, medical status, surgical intervention location of dentoalveolar intervention and form of medication. A total of 115 patients fulfilled the criteria and underwent 115 dental surgical interventions (female n = 90, male n = 25). In total, 73 (63.47%) of them had metastatic underlying diseases, and 42 (36.52%) had osteoporotic ones. MRONJ occurred in 10 patients (8.70%) (female n = 5, male n = 5). The occurrence of MRONJ was significantly correlated (p ≤ 0.05) with the mandible site and male sex. Tooth removal at the mandible site remains the main risk factor for the development of MRONJ. The risk profile of developing MRONJ after dentoalveolar interventions could be expected as follows: tooth osteotomy > multiple extractions > single tooth extraction.

Strigo-D2-a bio-sensor for monitoring spatio-temporal strigolactone signaling patterns in intact plants.

Strigolactones (SLs) are a class of plant hormones that mediate biotic interactions and modulate developmental programs in response to endogenous and exogenous stimuli. However, a comprehensive view on the spatio-temporal pattern of SL signaling has not been established, and tools for a systematic in planta analysis do not exist. Here, we present Strigo-D2, a genetically encoded ratiometric SL signaling sensor that enables the examination of SL signaling distribution at cellular resolution and is capable of rapid response to altered SL levels in intact Arabidopsis (Arabidopsis thaliana) plants. By monitoring the abundance of a truncated and fluorescently labeled SUPPRESSOR OF MAX2 1-LIKE 6 (SMXL6) protein, a proteolytic target of the SL signaling machinery, we show that all cell types investigated have the capacity to respond to changes in SL levels but with very different dynamics. In particular, SL signaling is pronounced in vascular cells but low in guard cells and the meristematic region of the root. We also show that other hormones leave Strigo-D2 activity unchanged, indicating that initial SL signaling steps work in isolation from other hormonal signaling pathways. The specificity and spatio-temporal resolution of Strigo-D2 underline the value of the sensor for monitoring SL signaling in a broad range of biological contexts with highly instructive analytical depth.

Who can take advantage of medically assisted reproduction in Germany?

Compared with other European societies, access to medically assisted reproduction (MAR) in Germany is rather restrictive. Surprisingly little is known about the actual utilization of MAR in Germany and its social selectivity, primarily due to a lack of appropriate data. This article studies the use of MAR by drawing on 11 waves of the German Family Panel (pairfam), an annual survey that collects data on partnership and family dynamics in Germany. In estimating pooled logistic regression models that take into account whether or not MAR has been used, the following treatments were included: (i) in-vitro fertilization or micro-fertilization; (ii) intrauterine insemination; and (iii) any type of surgery performed to treat infertility. The highest odds of seeking medical help for infertility were found among married, childless couples who had a higher income, a strong desire to have children, a poor self-assessed health status, and who reported having problems conceiving a child prior to the year of the interview. Among these married couples, those with an above-average income were particularly likely to use MAR. These findings indicate that social selectivity in the uptake of MAR is based on economic resources and on the importance of marriage as the cultural ideal for a 'normal family'.

Kobra Surgery Simulator-A Possibility to Improve Digital Teaching? A Case-Control Study.

Computer-aided simulations have long been of great importance in university teaching; however, to date, there is limited use of such simulations in the dental surgical sector. For this purpose, an oral surgery simulator, "Kobra", was implemented in student training and was evaluated for dental education. Dental students (group 1, third-year and group 2, fourth-year) and dentists of the faculty (control group) were trained to use the simulator. The outcomes for group 1 (apicoectomy of an upper lateral incisor with Kobra), group 2 (removal of an impacted lower wisdom tooth with Kobra) and the control group (both procedures with Kobra) were evaluated. For evaluation purposes, subjective parameters (improvement of practical skills, comparison between conventional training and Kobra simulation, and implementation of simulation-based teaching) and objective parameters (removal of bone, tooth substance and soft tissue measured while performing the Kobra simulation) were assessed using questionnaires with a scale ranging from 1-5. A total of 49 students (third-year n = 29, with 22 women and 7 men; fourth-year n = 20, with 17 women and 3 men) and 10 dentists (women n = 5 and men n = 5) participated. Compared to the Kobra simulation, the conventional training method with plastic models was still favored (the difference was non-significant). Compared to the dentists, the simulation data showed a less precise surgical performance of the students (the difference was not significant). The Kobra simulation may offer an additional method to conventional surgery training using plastic models, with benefits for students and faculty staff.

A clinical trial: Aqualizer ™ therapy and its effects on myopathies or temporomandibular dysfunctions. Part I: Objective parameters.

OBJECTIVE: Symptoms of temporomandibular dysfunction (TMD) may include pain in the muscles or restrictions opening the mouth. The aim of this study was to assess the effects of initial Aqualizer™ therapy. METHODS: Group 1 received initial Aqualizer™ therapy before definitive hard splint; Group 2 received no initial therapy. Patients with arthrosis, partial/total prosthesis or undergoing splint therapy were excluded. Objective (temporomandibular joint palpation, temporomandibular joint auscultation, palpation of the chewing muscles, and mobility of the lower jaw) parameters were evaluated. The level of statistical significance was 5% (p < 0.05). RESULTS: In 53 patients (Group 1 n = 25; Group 2 n = 28), a significant improvement (p < 0.001) was found in Group 1 in pain on palpation (masseter muscle, temporal muscle, post-mandibular region, lateral pterygoid muscle, and suboccipital region), but no significant differences in jaw mobility were found. CONCLUSION: Aqualizer™ therapy produces significant improvement of primary symptoms.

Free Gingival Graft and Collagen Matrix Revascularization in an Enoral Open Wound Situation.

PURPOSE: Vestibuloplasty with free gingival grafting is a frequently performed surgical procedure to generate sufficient keratinized mucosa (KM) around dental implants. Avascular porcine collagen matrices (CM) have been proclaimed to be sufficient substitutes as alternatives to free gingival grafts (FGGs). However, the process of graft integration and vascularization is still incompletely understood. METHODS: In 18 patients a vestibuloplasty in the lower edentulous jaw situation was performed during implant exposure, either with FGGs from the palate or a porcine CM (mucoderm). Tissue perfusion of the soft tissue grafts was measured using laser-doppler-spectrophotometer intraoperatively and on postoperative days 2, 5, 10, 30 and between days 60 and 90. With graft perfusion expressed by oxygen saturation [SO2%], the relative amount of hemoglobin [rHb], blood flow, and velocity [AU] was detected and compared between groups and the surrounding mucosa. RESULTS: Healing was uneventful in both groups, with mature KM around dental implants after healing. Blood flow and velocity significantly increased until postoperative day 10, comparable to perfusion values of the surrounded mucosa. Intergroup comparisons revelated no significant differences concerning the flow between CM and FGGs. Oxygen saturation also significantly increased within the first 5 postoperative days in both groups. Hemoglobin content did not show any differences during the investigated period. CONCLUSIONS: The perfusion mainly progresses within the first postoperative week with only minimal further detectable alterations until the final investigation, comparable in both groups. Although integration of FGGs (revascularized) and the CM (new tissue formation) is biologically different, both transplants show comparable perfusion patterns, leading to sufficient KM.

Prevalence of SARS-CoV-2 Infection in Children and Their Parents in Southwest Germany.

Importance: School and daycare closures were enforced as measures to confine the novel coronavirus disease 2019 (COVID-19) pandemic, based on the assumption that young children may play a key role in severe acute respiratory coronavirus 2 (SARS-CoV-2) spread. Given the grave consequences of contact restrictions for children, a better understanding of their contribution to the COVID-19 pandemic is of great importance. Objective: To describe the rate of SARS-CoV-2 infections and the seroprevalence of SARS-CoV-2 antibodies in children aged 1 to 10 years, compared with a corresponding parent of each child, in a population-based sample. Design, Setting, and Participants: This large-scale, multicenter, cross-sectional investigation (the COVID-19 BaWü study) enrolled children aged 1 to 10 years and a corresponding parent between April 22 and May 15, 2020, in southwest Germany. Exposures: Potential exposure to SARS-CoV-2. Main Outcomes and Measures: The main outcomes were infection and seroprevalence of SARS-CoV-2. Participants were tested for SARS-CoV-2 RNA from nasopharyngeal swabs by reverse transcription-polymerase chain reaction and SARS-CoV-2 specific IgG antibodies in serum by enzyme-linked immunosorbent assays and immunofluorescence tests. Discordant results were clarified by electrochemiluminescence immunoassays, a second enzyme-linked immunosorbent assay, or an in-house Luminex-based assay. Results: This study included 4964 participants: 2482 children (median age, 6 [range, 1-10] years; 1265 boys [51.0%]) and 2482 parents (median age, 40 [range, 23-66] years; 615 men [24.8%]). Two participants (0.04%) tested positive for SARS-CoV-2 RNA. The estimated SARS-CoV-2 seroprevalence was low in parents (1.8% [95% CI, 1.2-2.4%]) and 3-fold lower in children (0.6% [95% CI, 0.3-1.0%]). Among 56 families with at least 1 child or parent with seropositivity, the combination of a parent with seropositivity and a corresponding child with seronegativity was 4.3 (95% CI, 1.19-15.52) times higher than the combination of a parent who was seronegative and a corresponding child with seropositivity. We observed virus-neutralizing activity for 66 of 70 IgG-positive serum samples (94.3%). Conclusions and Relevance: In this cross-sectional study, the spread of SARS-CoV-2 infection during a period of lockdown in southwest Germany was particularly low in children aged 1 to 10 years. Accordingly, it is unlikely that children have boosted the pandemic. This SARS-CoV-2 prevalence study, which appears to be the largest focusing on children, is instructive for how ad hoc mass testing provides the basis for rational political decision-making in a pandemic.

The impact of economic uncertainty, precarious employment, and risk attitudes on the transition to parenthood.

This study investigates how precarious employment throughout the life course affects the fertility behavior of men and women in Germany, and how risk attitudes moderate exposure to objectively given uncertainty. Analyzing data from the German Socio-Economic Panel (SOEP) study from 1990 to 2015, I find that men and women have become quite similar in their fertility behavior: Stable employment accelerates family formation, whereas discontinuous and precarious employment delays it. With regard to risk attitudes, risk-averse women show the highest likelihood of family formation. They appear to choose a family- and parenthood-centered path in their life course that provides them with stability and social approval when unstable career prospects and uncertain employment are unable to provide these resources.

Volumetric soft tissue alterations in the early healing phase after peri- implant soft tissue contour augmentation with a porcine collagen matrix versus the autologous connective tissue graft: A controlled clinical trial.

AIM: This study evaluates the early volumetric changes after buccal soft tissue contour augmentation around implants with a porcine collagen matrix (CM) vs. the subepithelial connective tissue graft (SCTG) from the palate. MATERIALS AND METHODS: 14 patients were enrolled after early implant placement with simultaneous contour augmentation and persistent buccal tissue deficits. At implant exposure, buccal soft tissues were thickened with the CM (n = 7) or the SCTG (n = 7). Impressions were taken before and after surgery, after ten days, one, three and six months. Impressions were digitized and augmented regions 3D evaluated (soft tissue volume (mm3 , %)/thickness (mm)). RESULTS: Volume increase (mm3 ) after 6 months was 19.56 ± 8.95 mm3 (CM) and 61.75 ± 52.69 mm3 (SCTG) (insignificant, p = .058). In percentage, this was a volume loss of the initially augmented soft tissue volume (100%) of 81.76% in the CM group and 56.39% in the SCTG group (6 months). The mean soft tissue thickness increase (mm) in the buccal contour after 6 months was 0.30 ± 0.16 mm (CM) and 0.80 ± 0.61 mm (SCTG) (insignificant, p = .071). CONCLUSION: The early healing phase is associated with a significant volume loss of the soft tissues. The SCTG shows insignificant superiority compared to the CM.

Size-controlled synthesis of bioinspired polyserotonin nanoparticles with free radical scavenging activity.

Polyserotonin-based nanoparticles are a new class of bioinspired nanomaterial with recently demonstrated therapeutic potential for future clinical applications. It is therefore important to establish a robust and rapid method of synthesizing polyserotonin nanoparticles (PSeNP) in the size range ideal for in vivo utilization. Since the formation of PSeNP is base-catalyzed, here we report the influence of solution pH, in the presence of different base systems, on the kinetics of PSeNP formation and physico-chemical properties of the resulting nanoparticles. We show that the rate of formation and the size of PSeNP depend on both the nature of the base and the initial pH of the reaction. We have also improved the kinetics of particle formation by performing the synthesis at an elevated temperature (60 °C), leading to a dramatic reduction in synthesis time from days to hours. This presents a significant advance in the efficiency of PSeNP synthesis and provides a facile approach in tuning the size of nanoparticles to suit various applications. Furthermore, we show that similar to serotonin, PSeNP also exhibits free radical scavenging property. Our results demonstrate that PSeNP has the potential to become a key player in the advancement of nanotechnology-mediated antioxidative therapy.