bluuebunny/crossref_metadata_2025 huggingface dataset:
Using clinical trial registries to inform Copas selection model for publication bias in meta‐analysis
Authors: Huang Ao , Komukai Sho , Friede Tim , Hattori Satoshi
Published: June 2021

Prospective registration of study protocols in clinical trial registries is a useful way to minimize the risk of publication bias in meta‐analysis, and several clinical trial registries are available nowadays. However, they are mainly used as a tool for searching studies and information submitted to the registries has not been utilized as efficiently as it could. In addressing publication bias in meta‐analyses, sensitivity analysis with the Copas selection model is a more objective alternative to widely‐used graphical methods such as the funnel‐plot and the trim‐and‐fill method. Despite its ability to quantify the potential impact of publication bias, the Copas selection model relies on sensitivity analyses, in which some parameters are varied across a certain range. This may result in some difficulty in interpreting the results. In this paper, we propose an alternative inference procedure for the Copas selection model by utilizing information from clinical trial registries. Our method provides a simple and accurate way to estimate all unknown parameters of the Copas selection model. A simulation study revealed that our proposed method resulted in smaller biases and more accurate confidence intervals than existing methods. Furthermore, three published meta‐analyses were re‐analyzed to demonstrate how to implement the proposed method in practice.
Effective selection of the optimal virtual reality (VR) lens interval of VR devices using the test patterns of the different shapes for the left and right eyes
Authors: Kang Hyungoo , Hong Hyungki
Published: June 2021

Selection of the optimal virtual reality (VR) lens interval LI between two convex lenses of a VR device is important for the comfort of viewers. This study examined how the participants selected LI for two types of test patterns. Twenty‐one participants with interpupillary distances (IPDs) of 59–68 mm were selected. When the participants were asked to change the LI to match specific positions of the test pattern in which the shapes for the two eyes were different, the selected values of LI did not depend on the initial lens distances. When they were asked to change LI for their best viewing distances using the test pattern with the same shapes for two eyes, the selected values strongly depended on the initial lens conditions. This dependence can be attributed to the finite range of eye rotation inside which binocular fusion can occur. No noticeable dependence of the selected values on IPD was observed. Excessive eye rotation to enable binocular fusion can cause eye strain. In the former test pattern, binocular fusion does not occur, and each eye is aligned along its fusion‐free eye position with little eye strain. Hence, the former test pattern using the different shapes is preferable for controlling the lens interval.
Reference Intervals of Fetal Cardiac Volume Between 14 and 40 Weeks of Gestation
Authors: Thammavong Keooudone , Luewan Suchaya , Tongsong Theera
Published: June 2021

Objectives

To construct the reference intervals for the cardiac volume (CV) of normal fetuses between 14 and 40 weeks of pregnancy.

Methods

Low risk singleton pregnancies with normal fetuses were prospectively recruited to acquire 4D‐cardio‐spatiotemporal image correlation volume datasets (VDS). Subsequent off‐line analyses of VDS were anonymously performed to calculate CV using the Virtual Organ Computer‐aided AnaLysis technique. The reference intervals were established as a function of gestational age (GA), biparietal diameter (BPD), head circumference (HC), and estimated fetal weight (EFW) based on the best‐fitted models for both mean and standard deviation (SD).

Results

A total of 668 VDS were successfully calculated for CV. The best‐fitted models for the means and SDs are as follow: 1) GA in week = 6.422 + e(−100.653 × GA) (SD = 0.641 − (0.170 × GA) + (0.009 × GA2)). 2) BPD = 0.016 × (BPD)3.589 (SD = 2.663 − (1.410 × BPD) + (0.224 × BPD2)). 3) HC = 0.00017 × (HC)3.537 (SD = 2.341 − (0.341 × HC) + (0.015 × HC2)). The CV progressively increased with advancing fetal age (GA) and size (BPD, HC).

Conclusions

The reference intervals of CV, theoretically best representing cardiac size, in relation to GA, BPD, HC, and EFW were first established and Z‐score was readily calculated. These will be helpful in detection of cardiac abnormalities, especially those associated with cardiomegaly.
The Host‐Defense‐Peptide‐Mimicking Synthetic Polypeptides Effectively Enhance Antitumor Immunity through Promoting Immunogenic Tumor Cell Death
Authors: Wang Ye , Shen Wei , Liu Shuhan , Zhu Ge , Meng Xiandi , Mao Kuirong , Wang Jialiang , Yang Yong‐Guang , Xiao Chunsheng , Sun Tianmeng
Published: June 2021

Cancer immunotherapy is to artificially stimulate the immune system against tumor cells. Effectively increasing the immunogenicity of dying tumor cells has great potential to stimulate the anticancer immune responses. Recently, a synthetic cationic anticancer polypeptide (ACPP) is prepared, which mimics the host defense peptides, to effectively inhibit tumor growth by directly inducing rapid necrosis of cancer cells through a membrane‐lytic mechanism. Thus, this ACPP has the potential ability to induce immunogenic cancer cell death (ICD) and promote antitumor immunity. Herein, it is reported that ACPP successfully induces ICD in mouse colon cancer cells, resulting in effectively promoting T‐cell‐dependent antitumor immune responses by enhanced activation of dendritic cells. Interestingly, the level of natural killer cells, which are another kind of antitumor effector cell, in tumor microenvironment is also significantly increased by ACPP. The ratio of M1/M2 tumor‐associated macrophages is further obviously increased, indicating that tumor immunosuppressive microenvironment has been effectively reprogramed. More importantly, it is found that the anticancer immunity induced by ACPP is dose dependent. Finally, 40% of the established CT26 tumors are completely eliminated by ACPP treatment with an optimized dose. This study proposes a simple and effective strategy for promoting cancer immunotherapy.
When doing good will not save us: Revisiting the buffering effect of CSR following service failures
Authors: Antonetti Paolo , Crisafulli Benedetta , Maklan Stan
Published: June 2021

Past research offers inconsistent evidence on whether CSR is an effective service recovery strategy. Current debates overlook the signals that service failures send about the company, and their interplay with CSR. We propose a moderated mediation model showing that CSR's effectiveness for service recovery depends upon failure type. For failures signaling a lack of skills and expertise, CSR enhances warmth which in turn lowers revenge. Warmth further increases perceived competence which influences conciliatory responses. CSR, however, does not help if the failure signals a lack of moral integrity. Both warmth and competence explain the CSR's buffering effect. Our study demonstrates that “doing good” helps only to the extent that service failures that do not raise doubts about the character of the company. Even in these circumstances, however, the buffering effect of CSR is observed only in case of customer–firm communal relationships. Consistent evidence from three experiments revisits more optimistic assessments of the ability of CSR to act as a recovery strategy and shows that CSR can help only under very circumscribed conditions. Managerially, we show how and when the CSR buffer applies in service contexts, offering insights on how managers can best reap the potential benefits of service brands' involvement in CSR.
Study assesses experiences of users seeking MH services digitally
Authors: Canady Valerie A.
Published: June 2021

Citing an objective to determine the needs of individuals seeking mental health treatment and supportive services and to quantify their experiences and satisfaction with available digital navigation tools, the National Alliance on Mental Illness (NAMI) authored a new study published in the Journal of Medical Internet Research Mental Health.
Optimal decay rates of a nonlinear suspension bridge with memories
Authors: Afilal Mounir , Feng Baowei , Soufyane Abdelaziz
Published: June 2021

In this paper, we investigate the decay properties of suspension bridge with memories in one dimension. To prove our results, we use the energy method to build some very delicate Lyapunov functionals that give the desired results.
A signal detection model for quantifying overregularization in nonlinear image reconstruction
Authors: Sidky Emil Y. , Phillips John Paul , Zhou Weimin , Ongie Greg , Cruz‐Bastida Juan P. , Reiser Ingrid S. , Anastasio Mark A. , Pan Xiaochuan
Published: June 2021

Many useful image quality metrics for evaluating linear image reconstruction techniques do not apply to or are difficult to interpret for nonlinear image reconstruction. The vast majority of metrics employed for evaluating nonlinear image reconstruction are based on some form of global image fidelity, such as image root mean square error (RMSE). Use of such metrics can lead to overregularization in the sense that they can favor removal of subtle details in the image. To address this shortcoming, we develop an image quality metric based on signal detection that serves as a surrogate to the qualitative loss of fine image details. The metric is demonstrated in the context of a breast CT simulation, where different equal‐dose configurations are considered. The configurations differ in the number of projections acquired. Image reconstruction is performed with a nonlinear algorithm based on total variation constrained least‐squares (TV‐LSQ). The resulting images are studied as a function of three parameters: number of views acquired, total variation constraint value, and number of iterations. The images are evaluated visually, with image RMSE, and with the proposed signal‐detection‐based metric. The latter uses a small signal, and computes detectability in the sinogram and in the reconstructed image. Loss of signal detectability through the image reconstruction process is taken as a quantitative measure of loss of fine details in the image. Loss of signal detectability is seen to correlate well with the blocky or patchy appearance due to overregularization with TV‐LSQ, and this trend runs counter to the image RMSE metric, which tends to favor the over‐regularized images. The proposed signal detection‐based metric provides an image quality assessment that is complimentary to that of image RMSE. Using the two metrics in concert may yield a useful prescription for determining CT algorithm and configuration parameters when nonlinear image reconstruction is used.
Technical Note: Practical implementation strategies of cycloidal computed tomography
Authors: Roche i Morgó Oriol , Vittoria Fabio , Endrizzi Marco , Olivo Alessandro , Hagen Charlotte K.
Published: June 2021

Purpose

Cycloidal computed tomography is a novel imaging concept which combines a highly structured x‐ray beam, offset lateral under‐sampling, and mathematical data recovery to obtain high‐resolution images efficiently and flexibly, even with relatively large source focal spots and detector pixels. The method reduces scanning time and, potentially, delivered dose compared to other sampling schemes. This study aims to present and discuss several implementation strategies for cycloidal computed tomography (CT) in order to increase its ease of use and facilitate uptake within the imaging community.

Methods

The different implementation strategies presented are step‐and‐shoot, continuous unidirectional, continuous back‐and‐forth, and continuous pixel‐wise scanning. In step‐and‐shoot scans the sample remains stationary while frames are acquired, whereas in all other cases the sample moves through the scanner continuously. The difference between the continuous approaches is the trajectory by which the sample moves within the field of view.

Results

All four implementation strategies are compatible with a standard table‐top x‐ray setup. With the experimental setup applied here, step‐and‐shoot acquisitions yield the best spatial resolution (around 30 µm), but are the most time‐consuming (1.4 h). Continuous unidirectional and back‐and‐forth images have resolution between 30 and 40 µm, and are faster (35 min). Continuous pixel‐wise images are equally time‐efficient, although technical challenges caused a small loss in image quality with a resolution of about 50 µm.

Conclusion

The authors show that cycloidal CT can be implemented in a variety of ways with high quality results. They believe this posits cycloidal CT as a powerful imaging alternative to more time‐consuming and less flexible methods in the field.
Robust topology optimization under loading uncertainties via stochastic reduced order models
Authors: Torres Alberto P. , Warner James E. , Aguiló Miguel A. , Guest James K.
Published: June 2021

An efficient approach for topology optimization under uncertainty is presented. Stochastic reduced order models (SROMs) are leveraged for the modeling and propagation of uncertainties within a robust topology optimization (RTO) formulation. The SROM approach provides an alternative to existing uncertainty quantification methods and yields a substantial improvement in efficiency over a classical Monte Carlo based approach while retaining similar accuracy when representing the uncertainty in system parameters. In particular, random input parameters can be discrete or continuous and specified either analytically (standard distributions) or numerically (dataset samples). Furthermore, multiple random quantities need not be treated as uncorrelated; an SROM can seamlessly model random vectors with arbitrary correlation structure. The nonintrusive nature of the SROM method yields an implementation that can be seen as a drop‐in replacement for a simple RTO approach that leverages Monte Carlo simulation and is therefore straightforward to implement in existing topology optimization software. The proposed approach is demonstrated in the context of structural topology optimization with uncertainty in applied loads. Several numerical results are presented, covering a range of uncertainty distributions that illustrate the flexibility afforded by the general SROM method, while highlighting the efficiency and accuracy achieved in uncertainty propagation.
Nurses’ attitude towards patient advocacy in a single tertiary care hospital
Authors: Alanezi Fahad Zeed
Published: June 2021

Aim

To determine nurses’ attitude towards patient advocacy in a single tertiary care hospital.

Design

Descriptive/analytical cross‐sectional studies.

Methods

A comprehensive two‐part questionnaire about nurses’ views on nursing advocacy was administered to 371 nurses using a convenient random sampling. The first part included eight demographic variables, and the second part, the questionnaire, was used to measure nurses’ attitude towards patient advocacy.

Results

Nurses were more likely to act as patient advocate when their patient was in danger, and their employment was not at risk while acting as patient advocates. Female nurses scored higher than males; those with higher qualifications had higher behavioural and cognitive scores. A significant correlation was observed between cognitive (belief) aspects of attitude (p = .78, p ≤ .001) and behavioural (efficacy) aspects (p = .89, p ≤ .001).
The relationship between organizational communication and missed nursing care in oncology wards in Taiwan
Authors: Pan Shih‐Ping , Lin Chiou‐Fen
Published: June 2021

Aim

Unfavourable communication increases missed nursing care. Oncology wards have more communication complexity than general wards; therefore, creating a positive communication environment is important for ensuring quality care. This study aimed to understand the relationship between organizational communication satisfaction and missed nursing care in Taiwan.

Design

This cross‐sectional study was performed to measure organizational communication satisfaction and missed nursing care in six oncology wards at a stand‐alone cancer centre hospital in Taipei, Taiwan in December, 2018.

Methods

The study collected data using the Communication Satisfaction Questionnaire and the MISSCARE survey. The data were analysed using descriptive statistics, t test, analysis of variance and Pearson product–moment correlation analysis in December 16, 2018.

Results

A total of 111 questionnaires were collected, and the response rate was 92.5%. The study showed that nurses tended to miss nursing care when they were dissatisfied with the unit's manpower status organizational communication environment, horizontal and diagonal communication and informal communication.
Monte Carlo simulations study on gamma ray–neutron shielding characteristics for vinyl ester composites
Authors: Akkurt Iskender , Malidarre Roya Boodaghi , Kartal Ilyas , Gunoglu Kadir
Published: June 2021

The current study aims to report the gamma ray–neutron attenuation parameters of eight types of vinyl ester pumice (V‐P) composites for wide energy ranges of 511–2140 keV via MCNPX and FLUKA codes. The radiation shielding properties of these composites were presented graphically and are discussed in detail in this study. From the obtained results, it can be concluded that the MCNPX and FLUKA outcomes are in agreement with each other, and also the FLUKA code can be used as an alternative technique to determine the attenuation features of vinyl ester composites. Besides, the linear attenuation coefficient and total macroscopic cross sections' (∑t) dependencies on the density and also mass attenuation coefficient were found for all selected samples. To sum up, findings show that composite coded as V‐P50 can be a good competitive candidate in terms of gamma rays and neutron shielding.
Hospitalizations for opioid‐related overdose and timing of concurrent opioid and benzodiazepine use: A nested case‐control study
Authors: Alobaidi Ali , Pickard A. Simon , Jarrett Jennie B. , Lee Todd A.
Published: June 2021

Background

Concurrent opioid and benzodiazepine (BZD) use is a prevalent high‐risk prescribing behavior that increases the risk of opioid overdose. However, there is limited evidence on the relationship between timing of concurrent use and risk of opioid overdose.

Objective

To evaluate the likelihood of opioid‐related overdose across levels of duration, recency, and daily dose of concurrent use.

Design

A nested case‐control study was conducted using Truven MarketScan claims data (2009–2018).

Participants

Commercially insured adults (age 18–64 years old) with a new opioid dispensing in 2010–2018.

Main Measures

Cases of opioid‐related overdose were identified based on hospitalization diagnosis codes. Controls were matched to cases in a 10:1 ratio by age, sex, opioid start date, and cancer history. Concurrent use was classified based on duration, timing, and daily dose of overlapping opioids and BZDs during 90 days before the event. Conditional logistic regression models were used to evaluate the relationship between concurrent use and opioid‐related overdose.

Key Results

Among 11,137,866 dispensed a new opioid, a total of 3388 patients experienced opioid‐related overdose and were matched to 33,893 controls. Cases and controls were 34 years old on average and 54% female. Patients with concurrent use were significantly more likely to have opioid‐related overdose compared to patients receiving opioids, BZDs, or neither (OR 9.28; 95% CI 7.87, 10.93). Longer concurrent use of 1–7, 8–30, and 31–90 days was associated with 4.6, 12.1, and 26.7‐fold higher likelihood of opioid‐related overdose (p < 0.01). Patients with overlapping prescriptions during previous 0–30, 31–60, and 61–90 days were 13.2, 6.0, and 3.2‐times more likely to experience an overdose (p < 0.01).

Conclusions

Patients with an opioid‐related overdose were more likely to be prescribed concurrent opioid and BZD across all levels of duration, timing, and daily dose. Future policies and quality measures should be pursued to prevent concurrent use unless medically necessary.
Trends in respiratory management of transferred very preterm infants in the last two decades
Authors: Cavallin Francesco , Doglioni Nicoletta , Brombin Laura , Lolli Elisabetta , Loddo Cristina , Cavicchiolo Maria Elena , Mardegan Veronica , Magarotto Mariella , Mainini Nicoletta , Nardo Daniel , Peloso Rebecca Luisa , Piva Daniele , Priante Elena , Valerio Enrico , Baraldi Eugenio , Trevisanuto Daniele
Published: June 2021

Background

Among infants needing urgent transfer after birth, very preterm infants are a high‐risk sub‐group requiring special attention. This study aimed to assess trends in early respiratory management in a large series of very preterm infants undergoing postnatal transfer.

Methods

Trends in patient characteristics and early respiratory management were assessed in 798 very preterm infants who were transferred by the Eastern Veneto Neonatal Emergency Transport Service in 2000–2019. Trends were analyzed using joinpoint regression analysis and summarized as annual percentage changes (APCs).

Results

Proportion of neonates with birth weight less than 1 kg decreased from 33% to 16% (APC −3.82%). Use of nasal‐continuous‐positive‐airway pressure increased (at call: APC 15.39%; during transfer: APC 15.60%), while use of self‐inflating bag (at call: APC −12.09%), oxygen therapy (at call: APC −13.00%; during transfer: APC −23.77%) and mechanical ventilation (at call: APC −2.71%; during transfer: APC −2.99%) decreased. Use of oxygen concentrations at 21% increased (at call: APC 6.26%; during transfer: APC 7.14%), while oxygen concentrations above 40% decreased (at call: APC −5.73%; at transfer APC −8.89%). Surfactant administration at call increased (APC 3%–10%), while surfactant administration when arriving at referring hospital remained around 7‐11% (APC 2.55%).

Conclusion

Relevant trends toward “gentle” approaches in early respiratory management of very preterm infants undergoing postnatal transfer occurred during the last twenty years. In addition, the proportion of transferred extremely low birth weight infants halved. Clinicians and stakeholders should consider such information when allocating assets to both hospitals and transfer services and planning regional perinatal programs.
Melt Growth and Physical Properties of Bulk LaInO3 Single Crystals
Authors: Galazka Zbigniew , Irmscher Klaus , Ganschow Steffen , Zupancic Martina , Aggoune Wahib , Draxl Claudia , Albrecht Martin , Klimm Detlef , Kwasniewski Albert , Schulz Tobias , Pietsch Mike , Dittmar Andrea , Grueneberg Raimund , Juda Uta , Schewski Robert , Bergmann Sabine , Cho Hyeongmin , Char Kookrin , Schroeder Thomas , Bickermann Matthias
Published: June 2021

Large bulk LaInO3 single crystals are grown from the melt contained within iridium crucibles by the vertical gradient freeze (VGF) method. The obtained crystals are undoped or intentionally doped with Ba or Ce, and enabled wafer fabrication of size 10 × 10 mm2. High melting point of LaInO3 (≈1880 °C) and thermal instability at high temperatures require specific conditions for bulk crystal growth. The crystals do not undergo any phase transition up to 1300 °C, above which a noticeable thermal decomposition takes place. The good structural quality of the crystals makes them suitable for epitaxy. The onset of strong optical absorption shows orientation‐dependent behavior due to the orthorhombic symmetry of the LaInO3 crystals. Assuming direct transitions, optical bandgaps of 4.35 and 4.39 eV are obtained for polarizations along the [010] and the [100], [001] crystallographic directions, respectively. There is an additional weak absorption in the range between 2.8 and 4 eV due to oxygen vacancies. Density‐functional‐theory calculations support the interpretation of the optical absorption data. Cathodoluminescence spectra show a broad, structured emission band peaking at ≈2.2 eV. All bulk crystals are electrically insulating. The relative static dielectric constant is determined at a value of 24.6 along the [001] direction.
Surface Photovoltage Spectroscopy over Wide Time Domains for Semiconductors with Ultrawide Bandgap: Example of Gallium Oxide
Authors: Dittrich Thomas , Fengler Steffen , Nickel Norbert
Published: June 2021

A nonconventional approach is proposed for the measurement of surface photovoltage (SPV) signals over very wide ranges in photon energy and time. Regimes for AC, DC, and combined AC–DC measurements are defined and applied for the characterization of a β‐Ga2O3 crystal by transient and modulated SPV spectroscopy, spectroscopy in the mode of a Kelvin probe and single‐pulse SPV transients from 10 ns to 1000 s with the same electrode. Numerous electronic transitions are distinguished in β‐Ga2O3 depending on the measurement regime, the time response and the history of measurement. An accumulation of negative charge at the surface of β‐Ga2O3 is observed at long times independent whether the SPV signals are positive or negative before. The nonconventional approach of measuring SPV signals opens new opportunities for investigating electronic properties of semiconductors with ultrawide bandgaps and any other photoactive materials.
Assessing safety at the end of clinical trials using system organ classes: A case and comparative study
Authors: Carragher Raymond , Robertson Chris
Published: June 2021

Recent approaches to the statistical analysis of adverse event (AE) data in clinical trials have proposed the use of groupings of related AEs, such as by system organ class (SOC). These methods have opened up the possibility of scanning large numbers of AEs while controlling for multiple comparisons, making the comparative performance of the different methods in terms of AE detection and error rates of interest to investigators. We apply two Bayesian models and two procedures for controlling the false discovery rate (FDR), which use groupings of AEs, to real clinical trial safety data. We find that while the Bayesian models are appropriate for the full data set, the error controlling methods only give similar results to the Bayesian methods when low incidence AEs are removed. A simulation study is used to compare the relative performances of the methods. We investigate the differences between the methods over full trial data sets, and over data sets with low incidence AEs and SOCs removed. We find that while the removal of low incidence AEs increases the power of the error controlling procedures, the estimated power of the Bayesian methods remains relatively constant over all data sizes. Automatic removal of low‐incidence AEs however does have an effect on the error rates of all the methods, and a clinically guided approach to their removal is needed. Overall we found that the Bayesian approaches are particularly useful for scanning the large amounts of AE data gathered.
Imidazoles and Oxazoles from Lapachones and Phenanthrene‐9,10‐dione: A Journey through their Synthesis, Biological Studies, and Optical Applications
Authors: Dias Gleiston G. , Paz Esther R. S. , Nunes Mateus P. , Carvalho Renato L. , Rodrigues Marieli O. , Rodembusch Fabiano S. , da Silva Júnior Eufrânio N.
Published: June 2021

Diverse structural frameworks are found in natural compounds and are well known for their chemical and biological properties; such compounds include the imidazoles and oxazoles. Researchers worldwide are continually working on the development of methods for synthesizing new molecules bearing these basic moiety and evaluating their properties and applications. To expand the knowledge related to azoles, this review summarizes important examples of imidazole and oxazole derivatives from 1,2‐dicarbonyl compounds, such as lapachones and phenanthrene‐9,10‐diones, not only regarding their synthesis and biological applications but also their photophysical properties and uses. The data concerning the latter are particularly scarce in the literature, which leads to underestimation of the potential applications that can be envisaged for these compounds.
Clinical and molecular data in cases of prenatal localized overgrowth disorder: major implication of genetic variants in PI3K‐AKT‐mTOR signaling pathway
Authors: Bourgon N. , Carmignac V. , Sorlin A. , Duffourd Y. , Philippe C. , Thauvin‐Robinet C. , Guibaud L. , Faivre L. , Vabres P. , Kuentz P. ,   Collaborators
Published: June 2021

Objectives

To describe clinical and molecular findings in a French multicenter cohort of fetuses with prenatal diagnosis of congenital abnormality and suspicion of a localized overgrowth disorder (LOD) suggestive of genetic variants in the PI3K‐AKT‐mTOR signaling pathway.

Methods

We analyzed retrospectively data obtained between 1 January 2013 and 1 May 2020 from fetuses with brain and/or limb overgrowth referred for molecular diagnosis of PI3K‐AKT‐mTOR pathway genes by next‐generation sequencing (NGS) using pathological tissue obtained by fetal autopsy. We also assessed the diagnostic yield of amniotic fluid.

Results

During the study period, 21 subjects with LOD suspected of being secondary to a genetic variant of the PI3K‐AKT‐mTOR pathway were referred for analysis. Of these, 17 fetuses had brain overgrowth, including six with isolated megalencephaly (MEG) and 11 with hemimegalencephaly (HMEG). Of the six with MEG, germline variants were identified in four cases, in either PIK3R2, AKT3 or MTOR, and a postzygotic PIK3R2 variant was found in the other two cases. Of the 11 with HMEG, a postzygotic PIK3CA variant was found in three fetuses with extracerebral features of PIK3CA‐related overgrowth spectrum, and in seven fetuses with isolated HMEG. No pathogenic variant was identified in the 11th case with HMEG. Four fetuses with limb overgrowth also had one or more lymphatic malformations (LM) and harbored a postzygotic PIK3CA variant. NGS on cultured amniocytes performed in 10 cases, of which nine had been found positive on analysis of pathological fetal tissue, showed variants in four, in either PIK3CA, PIK3R2 or AKT3.

Conclusions

Isolated MEG or HMEG may lead to identification of genetic variants in the PI3K‐AKT‐mTOR signaling pathway. Cases of limb overgrowth and LM or isolated HMEG are likely associated with PIK3CA variants. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Prognostic value of orthogeriatric assessment parameters on mortality: a 2-year follow-up
Authors: Wiedl Andreas , Förch Stefan , Fenwick Annabel , Mayr Edgar
Published: June 2021

Introduction

Since the arise of orthogeriatric co-management patients’ outcome and survival has improved. There are several assessment parameters that screen the precondition of orthogeriatric patients including mobility, activities of daily living, comorbidities, place of residence and need for care just to name a few. In a 2-year follow-up on an orthogeriatric co-managed ward the fracture-independent predictive value of typical assessment parameters and comorbidities on the associated mortality was examined.

Methods

All patients treated on an orthogeriatric co-managed ward from February 2014 to January 2015 were included. No fracture entity was preferred. Emphasis was set on following parameters: age, gender, Parker-Mobility Score (PMS), Barthel Index (BI), Charlson-Comorbidity Index (CCI), dementia, depression, sarcopenia, frequent falling, length of stay (LOS), care level (CL) and place of residence (POR). In a 2-year follow-up the patients’ death rates were acquired. SPSS (IBM Corp., Armonk, New York, USA) and Cox regression was used to univariately analyze the expression of the mentioned parameters and mortality course over 2 years from discharge. In a multivariate analysis intercorrelations and independent relationships were examined.

Results

A follow-up rate of 79.6% by assessing 661 patients was achieved. In the univariate analysis linear inverse correlation between PMS and BI and mortality and a linear positive correlation between CCI and higher mortality were observed. There was also a significant relationship between lower survival and age, dementia, sarcopenia, frequent falling, higher institutionalized place of residence and higher CL. No univariate correlation between 2-year mortality and gender, depression and LOS was found. In the multivariate Cox regression, the only independent risk factors remaining were lower PMS (HR: 1.81; 95%CI: 1.373–2.397), lower BI (HR: 1.64; 95%CI: 1.180–2.290) and higher age per year (HR: 1.04; 95%CI: 1.004–1.067).

Conclusion

Age, PMS, BI, CCI, preexisting dementia, sarcopenia, frequent falling, POR and CL are univariate predictors of survival in the orthogeriatric context. An independency could only be found for PMS, BI and age in our multivariate model. This underlines the importance of preexisting mobility and capability of self-support for the patient’s outcome in terms of survival.
Laugier-Hunziker-Syndrom
Authors: Korsing Sören , Boede Marcel , Ebrahimsade Schokufe , Meier Katharina
Published: June 2021

Das Laugier-Hunziker-Syndrom (LHS) ist durch lentiginöse Hyperpigmentierungen der Mundschleimhaut und Lippen gekennzeichnet. Zusätzlich können longitudinale bzw. striäre Melanonychien und palmoplantare Pigmentläsionen auftreten. Es handelt sich um eine klinische Ausschlussdiagnose. Wir berichten hier über eine 66-jährige Patientin mit LHS. Die klinischen und histopathologischen Merkmale des LHS werden vorgestellt und wichtige Differenzialdiagnosen diskutiert.
Definition und Darstellung der verschiedenen Typen des Nasenzyklus mittels Langzeitrhinometrie
Authors: Reins E. F. , Weindel C. , Hoffmann T. K. , Sommer F. , Stupp F. , Halbig A.-S. , Lindemann J.
Published: June 2021

Hintergrund

Als „klassischer Nasenzyklus“ gilt ein streng wechselseitiges An- und Abschwellen der Mukosa der linken und rechten Nasenseite. Erfahrungen aus dem klinischen Alltag und Berichte in der Literatur lassen jedoch auf ein komplexeres Bild schließen. Die Erkenntnisse über den Nasenzyklus beruhten bisher auf Einzelmessungen. Die Langzeitrhinometrie (LRM) ermöglicht nun erstmals eine kontinuierliche Untersuchung des nasalen Luftflusses. Ziel dieser Untersuchung war daher die Evaluation des Nasenzyklus mit der LRM in einem nasengesunden Probandenkollektiv über 24 h.

Methodik

Bei 55 rhinologisch gesunden Probanden wurde eine LRM mit dem tragbaren Messsystem Rhino-Move© (Happersberger Otopront, Hohenstein) über 24 h durchgeführt.

Ergebnisse

Neben der erwarteten streng wechselseitigen Schwellung der Mukosa im Sinne des „klassischen Nasenzyklus“ zeigten sich weitere wiederkehrende Zyklustypen: der „in-concert“ Typ mit simultaner Fluktuation des Luftstromes auf beiden Nasenseiten, der „einseitige Typ“ mit An- und Abschwellen der Schleimhaut auf nur einer Nasenseite und der „non-cycle“ Typ ohne darstellbare Veränderung des Luftstromes auf beiden Seiten. Die meisten Probanden zeigten innerhalb der 24 h eine Kombination verschiedener Zyklustypen („gemischter Typ“), die sich häufig bei Tag und Nacht unterschieden.

Diskussion

Unsere Untersuchung bestätigt die Vermutung, dass der Nasenzyklus gemessen über 24 h wesentlich komplexer ist als in der Literatur beschrieben. Die meisten Probanden zeigen mehrere der hier beschriebenen 5 Zyklustypen. Die LRM hat sich dabei als leicht zu bedienende und zuverlässige Messmethode erwiesen. Der Zusammenhang zwischen Zyklustyp und körperlicher Aktivität sowie anderen Faktoren bleibt zu erforschen.
Families of monotone Lagrangians in Brieskorn–Pham hypersurfaces
Authors: Keating Ailsa
Published: June 2021

We present techniques, inspired by monodromy considerations, for constructing compact monotone Lagrangians in certain affine hypersurfaces, chiefly of Brieskorn–Pham type. We focus on dimensions 2 and 3, though the constructions generalise to higher ones. The techniques give significant latitude in controlling the homology class, Maslov class and monotonicity constant of the Lagrangian, and a range of possible diffeomorphism types; they are also explicit enough to be amenable to calculations of pseudo-holomorphic curve invariants. Applications include infinite families of monotone Lagrangian $$S^1 \times \Sigma _g$$

S
1

×

Σ
g

in $${\mathbb {C}}^3$$

C

3

, distinguished by soft invariants for any genus $$g \ge 2$$

g
≥
2

; and, for fixed soft invariants, a range of infinite families of Lagrangians in Brieskorn–Pham hypersurfaces. These are generally distinct up to Hamiltonian isotopy. In specific cases, we also set up well-defined counts of Maslov zero holomorphic annuli, which distinguish the Lagrangians up to compactly supported symplectomorphisms. Inter alia, these give families of exact monotone Lagrangian tori which are related neither by geometric mutation nor by compactly supported symplectomorphisms.
Homeostatic alterations related to total antioxidant capacity, elemental concentrations and isotopic compositions in aqueous humor of glaucoma patients
Authors: Aranaz Marta , Costas-Rodríguez Marta , Lobo Lara , García Montserrat , González-Iglesias Héctor , Pereiro Rosario , Vanhaecke Frank
Published: June 2021

Glaucoma is a multifactorial eye disease, characterized by progressive optic neurodegeneration. Elevation of the intraocular pressure is the main risk factor for glaucoma and is a consequence of an imbalance in the aqueous humor hydrodynamics, the physiology of which is influenced by the homeostatic equilibrium of essential elements, oxidative stress, and antioxidants. The aim of this work was to study local alterations in glaucomatous patients from two different, but connected, points of view: (i) the total antioxidant capacity (as an indicator of oxidative damage) and (ii) the concentration of mineral elements and their isotopic composition. Such objective was pursued using aqueous humor from patients diagnosed with pseudoexfoliation glaucoma (PEXG, n = 17) and primary open-angle glaucoma (POAG, n = 5) and age-matched control subjects (n = 16). The total antioxidant capacity (TAC) was examined in both aqueous humor and 60 serum samples (n = 20 controls, n = 20 for PEXG, and n = 20 for POAG), both showing higher TAC for the glaucoma population. The concentrations of the essential mineral elements (Cu, Fe, Mg, Na, P, and Zn) and the isotopic compositions of Cu and Zn were determined in aqueous humor using single-collector and multi-collector inductively coupled plasma–mass spectrometry, respectively. Significant differences were established for Mg and P levels when comparing the results for glaucomatous patients with those for the control population (p < 0.01 and p < 0.05 for Mg and P respectively, ANOVA and Kruskal-Wallis). The Zn isotopic composition was significantly shifted from that for the control population for PEXG patients. A significant difference in the isotopic composition of Zn was also established between the PEXG and POAG glaucoma cohorts.

Graphical abstract
Functional and morphological changes in hypoplasic posterior fossa
Authors: Bianchi Federico , Benato Alberto , Frassanito Paolo , Tamburrini Gianpiero , Massimi Luca
Published: June 2021

Background

The knowledge of the development and the anatomy of the posterior cranial fossa (PCF) is crucial to define the occurrence and the prognosis of diseases where the surface and/or the volume of PCF is reduced, as several forms of craniosynostosis or Chiari type I malformation (CIM). To understand the functional and morphological changes resulting from such a hypoplasia is mandatory for their correct management. The purpose of this article is to review the pertinent literature to provide an update on this topic.

Methods

The related and most recent literature addressing the issue of the changes in hypoplasic PCF has been reviewed with particular interest in the studies focusing on the PCF characteristics in craniosynostosis, CIM, and achondroplasia.

Results and conclusions

In craniosynostoses, namely, the syndromic ones, PCF shows different degrees of hypoplasia, according to the different pattern and timing of early suture fusion. Several factors concur to PCF hypoplasia and contribute to the resulting problems (CIM, hydrocephalus), as the fusion of the major and minor sutures of the lambdoid arch, the involvement of the basal synchondroses, and the occlusion of the jugular foramina. The combination of these factors explains the variety of the clinical and radiological phenotypes. In primary CIM, the matter is complicated by the evidence that, in spite of impaired PCF 2D measurements and theories on the mesodermal defect, the PCF volumetry is often comparable to healthy subjects. CIM is revealed by the overcrowding of the foramen magnum that is the result of a cranio-cerebral disproportion (altered PCF brain volume/PCF total volume). Sometimes, this disproportion is evident and can be demonstrated (basilar invagination, real PCF hypoplasia); sometimes, it is not. Some recent genetic observations would suggest that CIM is the result of an excessive growth of the neural tissue rather than a reduced growth of PCF bones. Finally, in achondroplasia, both macrocephaly and reduced 2D and 3D values of PCF occur. Some aspects of this disease remain partially obscure, as the rare incidence of hydrocephalus and syringomyelia and the common occurrence of asymptomatic upper cervical spinal cord damage. On the other hand, the low rate of CIM could be explained on the basis of the reduced area of the foramen magnum, which would prevent the hindbrain herniation.
Denture-related problems of patients in acute geriatric care
Authors: Nitschke Ina , Frank Frederick , Müller-Werdan Ursula , Eckardt-Felmberg Rahel , Stillhart Angela
Published: June 2021

Background

With increasing frailty and complaint-oriented utilization of dental care, the prevalence of oral diseases also increases.

Aim

To clarify whether there is a need for dental prosthodontic treatment during residential acute geriatric rehabilitation.

Methods

Within 3 weeks in a hospital for acute geriatric patients, 79 out of 157 newly admitted patients were interviewed as study participants (age: median 79.0 years, range 66–96 years, female 51.9%), dental findings were recorded, treatment needs were determined but X‑rays were not taken.

Results

Of the participants 31.1% had not seen a dentist for more than 1 year and 18.2% were edentulous. The median number of teeth in dentate participants was 16 (range 1–28 teeth); based on all participants, there was a median of 12.0 teeth (range 0–28 teeth). Of the 52 denture wearers (45 upper jaw and 43 lower jaw), 5 each of the maxillary and mandibular dentures could not be assessed because they were not available at the hospital. Moderate denture deficiencies were present in 62.5% of participants wearing upper dentures (mandibular 55.3%).

Conclusion

Dental treatment is needed in this vulnerable patient group. Therefore, the oral cavity should be assessed as part of the geriatric assessment. The available data confirm that the use of validated assessment instruments, such as the mini dental assessment as part of the comprehensive geriatric assessment would be useful. In addition to an oral examination, simple dental treatment should be provided to reduce infections and improve chewing ability. The geriatrician should be informed of the urgency of treatment. The overall rehabilitative approach of acute geriatric treatment would be complete if oral health would not be excluded.
Correction to: Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome
Authors: Bien Christian G. , Bien Corinna I. , Onugoren Müjgan Dogan , De Simoni Desiree , Eigler Verena , Haensch Carl-Albrecht , Holtkamp Martin , Ismail Fatme S. , Kurthen Martin , Melzer Nico , Mayer Kristina , von Podewils Felix , Rauschka Helmut , Rossetti Andrea O. , Schäbitz Wolf-Rüdiger , Simova Olga , Witt Karsten , Höftberger Romana , May Theodor W.
Published: June 2021

A correction to this paper has been published: https://doi.org/10.1007/s00415-021-10634-2
Initial treatment strategy and clinical outcomes in Finnish MS patients: a propensity-matched study
Authors: Hänninen K. , Viitala M. , Atula S. , Laakso S. M. , Kuusisto H. , Soilu-Hänninen M.
Published: June 2021

Background

The optimal treatment strategy with disease-modifying therapies (DMTs) in relapsing–remitting multiple sclerosis (RRMS) remains uncertain.

Objective

To compare outcomes of initial treatment with infusion therapies and starting therapy with medium efficacy therapy in a propensity-matched cohort of Finnish RRMS patients.

Methods

A total of 154 RRMS patients initiating natalizumab, alemtuzumab, ocrelizumab or rituximab as first DMT (high efficacy DMT, heDMT group) and 1771 patients initially treated with injectable therapies, teriflunomide or dimethylfumarate and escalated based on disease activity (moderate efficacy DMT, meDMT group) were identified from the Finnish MS registry. Nearest neighbor propensity matching (1:1, caliper 0.1) was performed for age, sex, baseline Expanded Disability Status Scale (EDSS), annual relapse rate (ARR) one year prior DMT and time since MS symptom onset. Primary outcome was time to 6-month confirmed EDSS progression and the secondary outcome time to first relapse.

Results

In the propensity-matched group comparisons, the probability of 6-month confirmed disability progression (CDP) at 5 years after DMT start was 28.4% (95% CI 15.7–39.3) in the heDMT group (n = 66) and 47.0% (95% CI 33.1–58.1) in meDMT group (n = 66), p = 0.013. Probability of relapse at 5 years was 34.6% (95% CI 24.1–43.6) for heDMT (n = 105) and 47.2% (95% CI 36.6–56.1) for meDMT (n = 105), p = 0.019.

Conclusions

Initiating MS-therapy with heDMT significantly reduced the risk of 5-year disability progression and relapse compared to using meDMT as first DMT choice in propensity-matched groups of Finnish MS-patients.
Classification of human enteric neurons
Authors: Brehmer Axel
Published: June 2021

Major advances in our understanding of the functional heterogeneity of enteric neurons are driven by the application of newly developed, innovative methods. In contrast to this progress, both animal and human enteric neurons are usually divided into only two morphological subpopulations, “Dogiel type II” neurons (with several long processes) and “Dogiel type I” neurons (with several short processes). This implies no more than the distinction of intrinsic primary afferent from all other enteric neurons. The well-known chemical and functional diversity of enteric neurons is not reflected by this restrictive dichotomy of morphological data. Recent structural investigations of human enteric neurons were performed by different groups which mainly used two methodical approaches, namely detecting the architecture of their processes and target-specific tracing of their axonal courses. Both methods were combined with multiple immunohistochemistry in order to decipher neurochemical codes. This review integrates these morphological and immunohistological data and presents a classification of human enteric neurons which we believe is not yet complete but provides an essential foundation for the further development of human gastrointestinal neuropathology.