bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Evaluation of Transanal Irrigation With a Validated Pediatric Neurogenic Bowel Dysfunction Scoring System
Authors: Fernandez Jenelle , Patel Samit , Hopson Puanani , Safder Shaista
Published: January 2022

Objectives:

To evaluate the efficacy of transanal irrigation (TAI) in pediatric patients with neurogenic bowel dysfunction (NBD) who were treatment naïve to catheter‐based TAI using Peristeen device (Coloplast).

Methods:

Prospective recruitment of patients with NBD who were unsatisfied with their bowel regimen or had no bowel regimen in place, were assessed using the neurogenic bowel dysfunction score (NBDS) before initiating treatment (Time 0) with Peristeen. NBDS scores were reassessed twice: within the first 6 months (Time 1) of initiation of Peristeen and again after greater than 6 months of usage with Peristeen (Time 2).

Results:

Over a 26‐month period, 104 patients with NBD were enrolled. Mean age was 10.6 years ± 4.7 (range 3–18 years). The NBDS at Time 1 had an average reduction of 14 points from the original score. A similar trajectory was seen at Time 2, with an average reduction of 13 points from original score. There was a statistically significant decrease of 14 points, P < 0.001 at Time 1 and this response was sustained at Time 2 with a statistically significant decrease in scores from initiation by 13 points, P < 0.001. Improved patient satisfaction and quality of life with Peristeen was seen at Time 1 and Time 2.

Conclusion:

Our results suggest that Peristeen can improve quality of life in pediatric patients with NBD. Significant improvement in NBDS occurred in our pediatric patients with NBD when initiated on Peristeen. Lower scores were seen at both Time 1 and Time 2, which indicated an improvement in their overall NBD.
A Whole-Brain 3D Myeloarchitectonic Atlas: Mapping the Vogt-Vogt Legacy to the Cortical Surface
Authors: Foit Niels A. , Yung Seles , Lee Hyo Min , Bernasconi Andrea , Bernasconi Neda , Hong Seok-Jun
Published: January 2022

Building precise and detailed parcellations of anatomically and functionally distinct brain areas has been a major focus in Neuroscience. Pioneer anatomists parcellated the cortical manifold based on extensive histological studies of post-mortem brain, harnessing local variations in cortical cyto- and myeloarchitecture to define areal boundaries. Compared to the cytoarchitectonic field, where multiple neuroimaging studies have recently translated this old legacy data into useful analytical resources, myeloarchitectonics, which parcellate the cortex based on the organization of myelinated fibers, has received less attention. Here, we present the neocortical surface-based myeloarchitectonic atlas based on the histology-derived maps of the Vogt-Vogt school and its 2D translation by Nieuwenhuys. In addition to a myeloarchitectonic parcellation, our package includes intracortical laminar profiles of myelin content based on Vogt-Vogt-Hopf original publications. Histology-derived myelin density mapped on our atlas demonstrate close overlap within vivoquantitative MRI markers for myelin and relates to cytoarchitectural features. Complementing the existing battery of approaches for digital cartography, the whole-brain myeloarchitectonic atlas offers an opportunity to validate imaging surrogate markers of myelin in both health and disease.

Highlights

Our myeloarchitectonic atlas builds on extensive meta-analyses-derived and ground-truth histological data.

Our atlas provides qualitative and quantitative 3D information on cortical myelin architecture.

MRI surrogate markers of myelin demonstrate close overlap with histological cortical parcellations, supporting biological validity of non-invasive metrics.

This atlas can be seamlessly integrated into widely used neuroimaging analysis software to inform studies in health and disease.
Probabilistic quotient’s work & pharmacokinetics’ contribution: countering size effect in metabolic time series measurements
Authors: Gotsmy Mathias , Brunmair Julia , Büschl Christoph , Gerner Christopher , Zanghellini Jürgen
Published: January 2022

Metabolomic time course analyses of biofluids are highly relevant for clinical diagnostics. However, many sampling methods suffer from unknown sample sizes commonly known as size effects. This prevents absolute quantification of biomarkers. Recently, several mathematical post acquisition normalization methods have been developed to overcome these problems either by exploiting already known pharmacokinetic information or by statistical means.

Here we present an improved normalization method, MIX, that combines the advantages of both approaches. It couples two normalization terms, one based on a pharmacokinetic model (PKM) and the other representing a popular statistical approach, probabilistic quotient normalization (PQN), in a single model.

To test the performance of MIX, we generated synthetic data closely resembling real finger sweat metabolome measurements. We show that MIX normalization successfully tackles key weaknesses of the individual strategies: it (i) reduces the risk of overfitting with PKM, and (ii) contrary to PQN, it allows to compute sample volumes. Finally, we validate MIX by using real finger sweat as well as blood plasma metabolome data and demonstrate that MIX allows to better and more robustly correct for size effects.

In conclusion, the MIX method improves the reliability and robustness of quantitative biomarker detection in finger sweat and other biofluids, paving the way for biomarker discovery and hypothesis generation from metabolomic time course data.
SNP calling for the Illumina Infinium Omni5-4 SNP BeadChip kit using the butterfly method
Authors: Andersen Mikkel Meyer , Christiansen Steffan Noe , Andersen Jeppe Dyrberg , Eriksen Poul Svante , Morling Niels
Published: January 2022

We introduce the “butterfly method” for SNP calling with the Illumina Infinium Omni5-4 BeadChip kit without the use of Illumina GenomeStudio software. The method is a within-sample method and does not use other samples nor population frequencies to call SNPs. The butterfly method is based on a three-component mixture of normal distributions, in which parameters are easily found using the open-source statistical software R. This makes the method transparent, straight-forward to change parameters according to the user’s needs, and easy to analyse the data within R after the SNPs have been called. We contribute with two open-source R packages that make SNP calling easy by helping with bookkeeping and by giving easy access to meta-information about the SNPs on the Illumina Infinium Omni5-4 BeadChip Kit (including chromosome, probe type, and SNP bases). We test our method on > 4 mio. SNPs and compare the results with those obtained with the GenTrain method used by Illumina GenomeStudio as well as SNPs obtained by PCR-free whole genome sequencing (WGS). We demonstrate two variants of our method: one where we account for potential probe type bias by estimating a separate model for each probe type (type I and type II) and another that uses a general model such that the model’s parameter estimates do not depend on the sample that is being analysed. We focused on varying the no-call rate and show how it changed the concordance with that of WGS. This is done by using a threshold on the a posteriori probability of belonging to a SNP cluster and by using the number of beads to adjust the stringency of the no-call mechanism. With the butterfly method, we achieve a SNP call rate of around 99% and a SNP concordance of around 99% with the WGS data. By lowering the a posteriori probability threshold for no-calls, we can get a higher call rate fraction than the GenomeStudio and by using a higher a posteriori probability threshold, we can achieve a higher concordance with the WGS data than the GenomeStudio.
Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration
Authors: Williams Audrey M. , Donoughe Seth , Munro Edwin , Horne-Badovinac Sally
Published: January 2022

For a group of cells to migrate together, each cell must couple the polarity of its migratory machinery with that of the other cells in the cohort. Although collective cell migrations are common in animal development, little is known about how protrusions are coherently polarized among groups of migrating epithelial cells. We address this problem in the collective migration of the follicular epithelial cells in Drosophila melanogaster. In this epithelium, the cadherin Fat2 localizes to the trailing edge of each cell and promotes the formation of lamellipodia at the leading edge of the cell behind. We show that Fat2 performs this function by acting in trans to restrict WAVE complex activity to one long-lived region along each cell’s leading edge. Without Fat2, the WAVE complex distribution expands around the cell perimeter and fluctuates over time, resulting in reduced, unpolarized protrusive activity. We further show that Fat2’s influence is very local, with sub-micron-scale puncta of Fat2 concentrating the WAVE complex in corresponding puncta just across the leading-trailing cell-cell interface. These findings demonstrate that a trans interaction between Fat2 and the WAVE complex creates stable regions of protrusive activity in each cell and aligns the cells’ protrusions across the epithelium for directionally persistent collective migration.
Increased early sodium current causes familial atrial fibrillation and dampens effect of flecainide
Authors: O’Reilly M , Sommerfeld LC , O’Shea C , Broadway-Stringer S , Andaleeb S , Reyat JS , Kabir SN , Stastny D , Malinova A , Delbue D , Fortmueller L , Gehmlich K , Pavlovic D , Skryabin BV , Holmes AP , Kirchhof P , Fabritz L
Published: January 2022

(1)

Aims

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Pathogenic variants in genes encoding ion channels are associated with familial AF. The point mutation M1875T in the SCN5A gene, which encodes the α-subunit of the cardiac sodium channel Nav1.5, has been associated with increased atrial excitability and familial AF.

(2)

Methods

We designed a new murine model carrying the Scn5a-M1875T mutation enabling us to study the effects of the Nav1.5 mutation in detail in vivo and in vitro using patch clamp and microelectrode recording of atrial cardiomyocytes, optical mapping, ECG, echocardiography, gravimetry, histology and biochemistry.

(3)

Results

Atrial cardiomyocytes from newly generated adult Scn5a-M1875T+/- mice showed a selective increase in the early (peak) cardiac sodium current, larger action potential amplitude and a faster peak upstroke velocity. Conduction slowing caused by the sodium channel blocker flecainide was less pronounced in Scn5a-M1875T+/- compared to wildtype atria. Overt hypertrophy or heart failure in Scn5a-M1875T+/- mice could be excluded.

(4)

Conclusion

The Scn5a-M1875T point mutation causes gain-of-function of the cardiac sodium channel. Our results suggest increased atrial peak sodium current as a potential trigger for increased atrial excitability and thus AF.

What’s new

The point mutation M1875T in the C-terminal domain of the cardiac sodium channel Nav1.5 causes an increase in early peak sodium current in left atria.

The observed changes induced by this point mutation suggest an increase in peak sodium current as a cause of familial atrial fibrillation (AF).

Our findings provide a possible explanation for the variable effectiveness of sodium channel blockers in patients with AF. Carriers of such sodium channel gain-of-function mutations may benefit more from tailored treatments.

Graphical abstract
pyNeurode: a real-time neural signal processing framework
Authors: Tam Wing-kin , Nolan Matthew F.
Published: January 2022

Accurate decoding of neural signals often requires assigning extracellular waveforms acquired on the same electrode to their originating neurons, a process known as spike sorting. While many offline sorters are available, accurate online sorting of spikes with many channels is still a challenging problem. Existing online sorters either use simple algorithms with low accuracy, can only process a handful of channels, or depend on a complex runtime environment that is difficult to set up. We have developed a state-of-the-art online spike sorting platform in Python that enables large-scale, fully automatic real-time spike sorting and decoding on hundreds of channels. Our system is cross-platform and works seamlessly with the Open Ephys suite of open-source hardware and software widely used in many neuroscience laboratories worldwide. It also comes with a user-friendly graphical user interface to monitor the cluster quality, spike waveforms and neuronal firing rate. Our platform has comparable accuracy to offline sorters and can achieve an end-to-end sorting latency of around 160 ms for 128-channel signals. It will be useful for research in fundamental neuroscience, closed-loop feedback neuromodulation and brain-computer interfaces.
CDC50 orthologues in Plasmodium falciparum have distinct roles in merozoite egress and trophozoite maturation
Authors: Patel Avnish , Nofal Stephanie D. , Blackman Michael J. , Baker David A.
Published: January 2022

In model organisms P4-ATPases require cell division control protein 50 (CDC50) chaperones for their phospholipid flipping activity. In the malaria parasite, P. falciparum, guanylyl cyclase alpha (GCα) is an integral membrane protein that is essential for release (egress) of merozoites from their host erythrocytes. GCα is unusual in that it contains both a C-terminal cyclase domain and an N-terminal P4-ATPase domain of unknown function. We sought to investigate whether any of the three CDC50 orthologues (denoted A, B and C) encoded by P. falciparum are required for GCα function. Using gene tagging and conditional gene disruption, we demonstrate that both CDC50B and CDC50C are expressed in the clinically important asexual blood stages and that CDC50B is a binding partner of GCα whereas CDC50C is the binding partner of another putative P4-ATPase, ATP2. Our findings indicate that CDC50B has no essential role for intraerythrocytic parasite maturation but modulates the rate of parasite egress by interacting with GCα for optimal cGMP synthesis. In contrast, CDC50C is essential for blood stage trophozoite maturation. Additionally, we find that the CDC50C-ATP2 complex may influence parasite endocytosis of host cell haemoglobin and consequently hemozoin formation.
Ubiquitinome analysis of articular cartilage post mechanical injury reveals a differential ubiquitination pattern of a subset of DUBs and proteins linked to the ERAD cellular response
Authors: Kaokhum Nitchakarn , Pinto-Fernández Adán , Wilkinson Mark , Kessler Benedikt , Ismail Heba
Published: January 2022

Understanding how connective tissue cells respond to mechanical stimulation is important to human health and disease processes in musculoskeletal diseases. Injury to articular cartilage is a key risk factor in predisposition to osteoarthritis. Here we identified a ubiquitin signature that is unique to injured articular cartilage tissue (the “injury ubiquitinome”). A total of 408 ubiquitinated peptides mapped to 114 proteins were identified, with an enrichment of ubiquitinated peptides of proteins involved in protein processing in the endoplasmic reticulum(ER), also known as the ER-associated degradation(ERAD) response, including YOD1, BRCC3, ATXN3 and USP5 as well as the ER stress regulators, RAD23B, VCP/p97 and Ubiquilin 1. Enrichment of these proteins suggested an injury-induced ER stress response and, for instance, ER stress markers DDIT3/CHOP and BIP/GRP78 were upregulated following cartilage injury on the protein and gene expression levels. Similar ER stress induction was also observed in response to tail fin injury in zebrafish larvae, suggesting a generic response to tissue injury. Furthermore, a rapid increase in global DUB activity following injury and significant activity in human osteoarthritic cartilage was observed using DUB specific activity probes. Inhibition of DUBs using a broad-spectrum inhibitor caused a reduction in the injury-induced inflammatory response in a zebrafish tail fin injury model. These results implicate the involvement of ubiquitination events and activation of a set of DUBs and ER stress regulators in cellular responses to cartilage tissue injury and osteoarthritis. This link through the ERAD pathway makes this protein set attractive for further investigation inin vivomodels of tissue injury and for targeting in osteoarthritis and related musculoskeletal diseases.
On the illusion of auxotrophy:met15Δyeast cells can grow on inorganic sulfur thanks to the previously uncharacterized homocysteine synthase Yll058w
Authors: Van Oss S. Branden , Parikh Saurin Bipin , Coelho Nelson Castilho , Wacholder Aaron , Belashov Ivan , Zdancewicz Sara , Michaca Manuel , Xu Jiazhen , Kang Yun Pyo , Ward Nathan P. , Yoon Sang Jun , McCourt Katherine M. , McKee Jake , Ideker Trey , VanDemark Andrew P. , DeNicola Gina M. , Carvunis Anne-Ruxandra
Published: January 2022

Organisms must either synthesize or assimilate essential organic compounds to survive. The homocysteine synthase Met15 has been considered essential for inorganic sulfur assimilation in yeast since its discovery in the 1970s. As a result,MET15has served as a genetic marker for hundreds of experiments that play a foundational role in eukaryote genetics and systems biology. Nevertheless, we demonstrate here through structural and evolutionary modeling,in vitrokinetic assays, and genetic complementation, that an alternative homocysteine synthase encoded by the previously uncharacterized gene YLL058W enables cells lacking Met15 to assimilate enough inorganic sulfur for survival and proliferation. These cells however fail to grow in patches or liquid cultures unless provided with exogenous methionine or other organosulfurs. We show that this growth failure, which has historically justified the status ofMET15as a classic auxotrophic marker, is largely explained by toxic accumulation of the gas hydrogen sulfide due to a metabolic bottleneck. When patched or cultured with a hydrogen sulfide chelator, and when propagated as colony grids, cells without Met15 assimilate inorganic sulfur and grow, and cells with Met15 achieve even higher yields. Thus, Met15 is not essential for inorganic sulfur assimilation in yeast. Instead,MET15is the first example of a yeast gene whose loss conditionally prevents growth in a manner that depends on local gas exchange. Our results have broad implications for investigations of sulfur metabolism, including studies of stress response, methionine restriction, and aging. More generally, our findings illustrate how unappreciated experimental variables can obfuscate biological discovery.
Ex Vivo Validation of Six FDA-Approved Non-Receptor Tyrosine Kinase Inhibitors (NRTKIs) as Antivirals to Pandemic and Seasonal Influenza A Viruses
Authors: Meineke Robert , Stelz Sonja , Busch Maximilian , Werlein Christopher , Kühnel Mark , Jonigk Danny , Rimmelzwaan Guus F. , Elbahesh Husni
Published: January 2022

Influenza viruses are important respiratory pathogens that cause substantial morbidity and mortality annually. In addition to seasonal influenza outbreaks, new emerging influenza A viruses (IAV) can cause pandemic influenza outbreaks. Apart from effective vaccines, there is a need for better treatment options to combat infections with these viruses when vaccines are not available or show reduced efficacy (e.g., in immmunocompromised patients). The limited range of licensed antiviral drugs and emergence of drug-resistance mutations highlight the need for novel intervention strategies like host-targeted antivirals. Repurposing FDA-approved kinase inhibitors may offer a fast-track for a new generation of host-targeted antivirals. Small molecule kinase inhibitors (SMKIs) can inhibit replication of viruses and improve survival in vivo; however, no SMKI has been approved for clinical use against IAV infections. In the present study, we tested eight non-receptor tyrosine kinase-inhibitors (NRTKIs) used to treat cancer and autoimmune diseases for their antiviral potential. Six of those potently inhibited virus replication (≥1,000-fold) in A549 cells infected with either A(H1N1)pdm09 or seasonal A(H3N2) strains. These compounds were validated in a biologically relevant ex vivo model of human precision-cut lung slices (hPCLS) to provide proof of principle and show efficacy against contemporary seasonal and pandemic IAVs. We identified the steps of the virus infection cycle affected by these inhibitors and assessed the effect of these NRTKIs on the host response. Considering their established safety profiles, our studies show that the use of these NRTKI shows promise and warrants further development as an alternative strategy to treat influenza virus infections.
Electric field simulations of field grading techniques in HVDC cable joints
Authors: Jörgens Christoph , Clemens Markus
Published: January 2022

Purpose

In high voltage direct current cable systems, cable joints are known as the least reliable components due to the use of multiple dielectrics. Resulting from the electric field and temperature depending conductivity of the different dielectrics, field enhancement at critical areas, e.g. triple points, may result in accelerated aging and the failure of the component. To reduce the stress, different field grading techniques are applied. The purpose of this study is to investigate different grading techniques for cable joints. Different shapes of the electrode and a varying nonlinear conductivity of field grading materials (FGM) are used for the simulation of the electric field.

Design/methodology/approach

Coupled electro-thermal field simulations are applied for different joint geometries, to obtain the stationary electric field. Electric field simulations in cable joint using geometric and nonlinear field grading techniques are shown.

Findings

Using the geometric field grading, the shape of the stress cone determines the field values in critical areas (triple points). High stress reduction is obtained for a certain curvature of the stress cone. For the nonlinear stress control, materials with a higher conductivity in comparison to the cable and the joint material are used. A field reduction is obtained by increasing the total conductivity. On the other hand, this is also increasing the insulation losses within the total FGM. More applicable is the decrease of the switching field or the increase of nonlinearity, which is only locally increase the conductivity and the insulation losses. Furthermore, simulations results show that an approximately constant field reduction is obtained, if the nonlinearity is above a certain threshold.

Research limitations/implications

This study is restricted to a field dependency of FGM only. For impulse voltages, high temperature and electric conductivity values my result in a thermal runaway. Furthermore, only direct current field grading techniques are studied.

Originality/value

The field grading of cable joints, using geometric and nonlinear techniques, is analyzed. A comparison between the electric field, by varying the curvature of the ground stress cone or the FGM conductivity constants in a complex joint geometry is novel. With its effect on the electric fields, general requirements for the geometry (geometric field grading) or the values of the FGM constants (nonlinear field grading) are defined to obtain a sufficient field grading.
Impact of nutrition service attributes on patient satisfaction: evidence from an outpatient clinic at a Lebanese-Middle Eastern hospital
Authors: Serhan Mireille , Toutounji Batoul , Serhan Carole
Published: January 2022

Purpose

The purpose of this paper is to explore the existing literature on the relationship between different service attributes and patient satisfaction at outpatient nutrition clinics to propose and test a culture-specific conceptual model interlinking the drivers of patient satisfaction.

Design/methodology/approach

Over a 7-week period in Fall 2019 (November 2–December 19), 600 patients from a Lebanese-Middle Eastern hospital (396 females and 204 males) completed an anonymous-designed survey with closed questions (n = 30). Statements were considered to represent specific attributes of nutrition services. In order to measure the existence and degree of significant relationships between different research variables, Pearson correlation coefficients and Fisher'sZtest were employed to analyze the collected data, before and while joining the clinic, during and after the appointment. Means of scores and frequencies were calculated.

Findings

The results show that the nutrition service attributes with reference to “after the appointment” may improve the patients' satisfaction level more than attributes with reference to “while joining the clinic” and “during the appointment”. Most patients were satisfied with their overall outpatient clinic experience. The patient experience is a direct result of positive interactions with the entire services offered.

Practical implications

The conceptual model sets the foundations for testing and for further research to develop. Moreover, the findings of this study are important for assessing the quality of nutrition service attributes and for reporting on the ability of this service to meet the needs and preferences of patients in the health care sector.

Originality/value

This study attempts to fill the gap in knowledge on nutrition service quality as indicators for overall patient satisfaction, while opening clear research avenues for further studies to follow. It is the basis for the development of clinical practice guidelines and other quality enhancement tools.
Multiple butterfly recognition based on deep residual learning and image analysis
Authors: Xi Tianyu , Wang Jiangning , Han Yan , Lin Congtian , Ji Liqiang
Published: January 2022

Insect recognition is crucial for taxonomy. It helps researchers to process tremendous and various ecology data. Most studies focus on fine‐tuning the deep learning network or altering the algorithm to enhance the identification accuracy, and some useful tools have been generated with these methods. This study focuses on the influence of image data on the recognition model. The single data set source of the existing automated identification tools is relatively simple, and the competition‐based data set released only focuses on evaluating the model at present. For the first time, this article integrates butterfly image data sets from multiple sources, covered illustrated books, and popular butterfly science websites. The image types include standard specimen images, illustrated book scan images and camera shots. In addition, these images included not only fixed poses, but also various other images of butterflies in natural poses. The size of these images is also various. The testing data set is new data that does not belong to the training set, which also verifies the generalizability of the model, indicating that in practical applications this model can identify new images. This testing method is a breakthrough compared to the previous work. We designed different data sets using the ResNet18 network to train a classifier, which achieves a validation accuracy of 86% in the end of the analysis. By adjusting the data sets, the accuracy changes as well. This study provides a method to recognize hundreds of butterfly species and analyzes the testing progress from the point of view of data. It is the first to combine butterflies from multiple countries in a single data set, with a recognition accuracy that outperforms previous experiments, to the best of our knowledge. We further analyze the testing results of butterfly recognition at the family and genus level. We perform two more experiments to demonstrate the model in the case of similar species or genus.
Disseminated drug‐resistant tuberculosis and multiple autoimmune syndrome in a child with selective IgA deficiency—An uncustomary combination
Authors: Nori Harshita , Vohra Viresh , Banday Aaqib Zaffar , Jindal Ankur Kumar , Tyagi Reva , Sodhi Mandeep Kaur , Bal Amanjit , Suri Deepti
Published: January 2022

Polyautoimmunity or multiple autoimmune syndrome (MAIS) is increasingly being recognized in pediatric clinical practice, often in conjunction with systemic lupus erythematosus (SLE). Besides multi‐organ autoimmunity, children with SLE are often at a higher risk of developing infections including tuberculosis. The tendency to develop infections and multiple autoimmune diseases in childhood SLE often occurs in the absence of monogenic primary immunodeficiency disease. Conversely, children with inborn errors of immunity, of which selective IgA deficiency (sIgAD) is the most common, may develop recurrent infections and autoimmune disorders including SLE. Herein, we report a child with MAIS (including SLE) and sIgAD who developed drug‐resistant tuberculosis, which was managed successfully with second‐line anti‐tubercular drug therapy. To the best of our knowledge, this combination of rare findings has not been reported previously in the pediatric literature. Although a majority of patients with sIgAD are either asymptomatic or have mild infections/autoimmunity, the index child had a myriad of infectious illnesses and multi‐organ autoimmunity. Our case highlights the prudence of thoroughly evaluating children with SLE for other autoimmune diseases and vice versa. Given the higher probability of inherited disorders, including early complement deficiencies and monogenic interferonopathies, in childhood SLE compared with adult SLE, it may be prudent to perform a basic immunological workup (for example, immunoglobulin levels, 50% hemolytic complement) in such patients. A more extensive immunological and genetic evaluation (including next‐generation sequencing) may also be required in the presence of unusual clinical or laboratory features, a positive family history, or a complicated clinical course.
Group size and matching protocol in contests
Authors: Baik Kyung Hwan , Chowdhury Subhasish M. , Ramalingam Abhijit
Published: January 2022

We investigate the effects of group size and matching protocol in Tullock contest experiments. In a 2 × 2 factorial design, we implement partner and random stranger‐matching protocols in contests between two and between three players. Group size does not affect overall absolute bid levels, but the rate of overbidding is lower in two‐player groups across matching protocols. Matching protocol does not affect bidding behaviour for three‐player groups, but a partner matching reduces both the level and dispersion of bids in two‐player groups. These results show the joint effect of group size and matching protocol and suggest that identifiability in repeated play facilitates tacit collusion.
Endoscopic approach in the diagnosis of high‐grade pancreatic intraepithelial neoplasia
Authors: Hanada Keiji , Shimizu Akihiro , Kurihara Keisuke , Ikeda Morito , Yamamoto Takuya , Okuda Yasuhiro , Tazuma Susumu
Published: January 2022

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is essential for improving prognosis; however, diagnosing PDAC at an early stage is challenging. In patients with localized high‐grade pancreatic intraepithelial neoplasia (HG‐PanIN), whose tumorous lesion is undetectable on cross‐sectional images such as computed tomography or magnetic resonance image, long‐term survival is expected. Pancreatic cystic lesions or main pancreatic duct (MPD) dilatation are important indirect findings for the initial diagnosis of HG‐PanIN. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) should play important roles in detecting abnormal image findings, such as local irregular MPD stenosis, caliber MPD changes, small cystic lesions, or branch duct dilatation. Additionally, EUS could detect hypoechoic areas around the MPD stenosis in some patients with HG‐PanIN. Subsequently, endoscopic retrograde cholangiopancreatography (ERCP) and its associated pancreatic juice cytology, including serial pancreatic juice aspiration cytologic examination (SPACE) after placement of an endoscopic nasopancreatic drainage (ENPD) tube, may have high diagnostic accuracy for confirming the malignancy in HG‐PanIN. Although ERCP and its associated pancreatic cytology, including SPACE, may be associated with post‐ERCP pancreatitis (PEP), a recent randomized trial suggested that a 4‐Fr ENPD tube may reduce the incidence of PEP. In the future, further prospective multicenter studies are required to establish a standard method of SPACE. Additionally, further studies for novel biomarkers could help to establish evolutionary methods with duodenal fluid and pancreatic juice for the early and accurate diagnosis of early‐stage PDAC.
Guided discovery learning: A follow‐up study of try‐it‐yourself surgery and subsequent video‐assisted teaching for oral surgical skills training
Authors: Kniha Kristian , Bock Anna , Peters Florian , Heitzer Marius , Hölzle Frank , Raith Stefan , Modabber Ali , Möhlhenrich Stephan Christian
Published: January 2022

Introduction

The purpose of this follow‐up study was to assess the effects of discovery learning and subsequent standardised teaching on students’ advanced dental surgical skills.

Materials and Methods

A total of 29 dental students who had no theoretical education on the Rehrmann flap were included in the skills training programme. Without prior teaching, the students were initially asked to perform a discovery surgery with a subsequent multiple‐choice test (MCT) on the first day. This was followed by a video‐assisted teaching lecture. On the same day and after 122 days, the surgery and MCT were repeated. Aside from the practical and theoretical assessment forms, the training was evaluated by the students themselves.

Results

Regarding the evaluation of surgery (EOS), significant improvements were measured between the first surgery and the second and third surgeries (p > .001). In addition, the theoretical test scores showed significant improvements after the first test when compared with the second (p = .004) and third tests (p < .001). For both assessments, no significant difference was found between the second and third attempts. The MCT and EOS in the second and third attempts strongly correlated (r = .77 andr = .71 respectively).

Conclusion

The dental students in this study successfully learned a complex oral surgical procedure, the Rehrmann flap technique, for closing oro‐antral communications. The participants indicated their high satisfaction with the teaching approach. After 122 days of follow‐up, their practical and theoretical test scores remained high and presented no significant difference, which suggests that the newly learnt individual skills were retained.
Evaluation of anxiety‐provoking situations related to clinical training in dental education
Authors: Tokuc Muge , Alpkilic Dilara Seyma
Published: January 2022

Introduction

The aims of this study were to evaluate the situations that cause anxiety in clinical training and to discuss the precautions that can be taken to reduce clinical anxiety in dental education.

Materials and Methods

This multi‐centred survey‐based study was created through Google Docs, and 3rd, 4th and 5th grade dental students were included. The students were asked to rate their reactions on a 4‐point Likert scale “not anxious” to “very anxious” for 27 questions related to academics, communication and interaction, diagnosis, dental treatments, deficiencies and mistakes in the treatments.

Results

1332 students were reached, and 1320 students completed the questionnaire. Whilst extracting wrong tooth (3.53 ± 0.83), getting infected by patient (3.39 ± 0.85) and getting diagnosis wrong (3.31 ± 0.83) were identified as the 3 most anxiety‐provoking situations, taking panoramic radiograph (1.48 ± 0.71) and communication with patients and dental assistants/nurses (1.76 ± 0.87; 1.64 ± 0.76) were identified as 3 situations that cause the least anxiety. Female students reported higher anxiety levels than male students in most of the questions (p < .05). A statistically significant difference was observed between the grades of the students (p < .05). 3rd grade students showed statistically higher anxiety levels than higher grades in 16 out of 27 questions. No statistical significance was observed according to the status of the university (p > .05).

Conclusion

Questions related to diagnosis, delivery of the dental treatments, deficiencies and mistakes in the treatments caused higher anxiety levels amongst dentistry students. As experience and time in the clinical training increase, the anxiety level of the students decreases. Orientation programmes and establishing an effective communication between grades are recommended. Also, gender‐based solutions must be taken into consideration.
The potential of a canister‐based single‐use negative‐pressure wound therapy system delivering a greater and continuous absolute pressure level to facilitate better surgical wound care
Authors: Orlov Aleksei , Gefen Amit
Published: January 2022

Two types of single‐use negative‐pressure wound therapy systems are currently available to treat surgical wounds: Canister‐based and canisterless. This work was aimed to evaluate the performance of a canister‐based vs a canisterless system, each with a different negative‐pressure setting and technology for fluid management. Continuous delivery of a specified level of negative pressure to the wound bed is hypothesised to be important for promoting surgical wound healing, by achieving continuous reduction of lateral tension in the wound, particularly through decrease of skin stress concentrations around suture insertion sites. To test the above hypothesis, we developed a computational modelling framework, a laboratory bench‐test for simulated clinical use and had further conducted a pre‐clinical study in a porcine model for closed incision. We specifically focussed on the impact of effective fluid management for continuous delivery of a stable, consistent negative pressure and the consequences of potential losses of the pressure level over the therapy period. We found that a greater (absolute) negative‐pressure level and its continuous, consistent delivery through controlled fluid management technology, by removing excess fluid from the dressing, provides far superior biomechanical performances. These conditions are more likely to result in better quality of the repaired tissues.
Associations of toddler mechanical/distress feeding problems with psychopathology symptoms five years later
Authors: Putnick Diane L. , Bell Erin M. , Ghassabian Akhgar , Polinski Kristen J. , Robinson Sonia L. , Sundaram Rajeshwari , Yeung Edwina
Published: January 2022

Background

Feeding problems are common in early childhood, and some evidence suggests that feeding problems may be associated with psychopathology. Few prospective studies have explored whether toddler feeding problems predict later psychopathology.

Methods

Mothers of 1,136 children from the Upstate KIDS cohort study provided data when children were 2.5 and 8 years of age. Food refusal (picky eating) and mechanical/distress feeding problems and developmental delays were assessed at 2.5 years. Child eating behaviors (enjoyment of food, food fussiness, and emotional under and overeating) and child psychopathology (attention‐deficit/hyperactivity (ADHD), oppositional‐defiant (OD), conduct disorder (CD), and anxiety/depression) symptoms were assessed at 8 years.

Results

Mechanical/distress feeding problems at age 2.5, but not food refusal problems, were associated with ADHD, problematic behavior (OD/CD), and anxiety/depression symptoms at 8 years in models adjusting for eating behaviors at 8 years and child and family covariates. Associations with mechanical/distress feeding problems were larger for ADHD and problematic behavior than anxiety/depression symptoms, though all were modest. Model estimates were similar for boys and girls.

Conclusions

Much of the research on feeding problems focuses on picky eating. This study suggests that early mechanical and mealtime distress problems may serve as better predictors of later psychopathology than food refusal. Parents and pediatricians could monitor children with mechanical/distress feeding problems for signs of developing psychopathology.
Effects of dietary starch sources on pellet‐processing characteristics, growth performance and caecal microflora of meat rabbits
Authors: Cong Xueyan , Li Xiuyi , Yang Guiqin , Guo Dongxin , Tian He , Li Jiantao
Published: January 2022

This study evaluated the effects of starch sources on pellet‐processing characteristics as well as the growth performance and caecal microflora of rabbits. Ninety‐six 35‐day‐old rabbits were randomly allocated to four groups with 24 rabbits per group and were fed diets with different starch sources (corn, wheat, potato or pea starch). The trial lasted for 40 days. The greatest hardness and lowest powder ratio of feed pellets was associated with the use of potato starch (p > 0.05). Pellet bulk density was the highest with corn starch, and the density was greater than that of pea starch by 5.91% (p < 0.05). The pulverisation ratio of corn starch pellets was the lowest, 43.67% lower than that of the pea starch pellets (p < 0.05). The average daily gain of rabbits in the corn starch group was higher than in the potato and pea starch groups, by 7.89% and 10.81%, respectively (p < 0.05). Rabbits in the corn starch group had the best feed conversion ratio (p > 0.05). The feed intake of rabbits in the potato starch group was higher than in the wheat and pea starch groups, by 4.30% and 5.16% respectively (p < 0.05). The dominant caecal bacteria phyla were Firmicutes, Bacteroidetes, Verrucomicrobia and Proteobacteria. There were 12 bacterial genera with proportions greater than 0.1%. The caecal proportion of Clostridium in the pea starch group was 1.8%, which was higher than those of the other groups (p = 0.057). There was no significant difference in caecal microbial diversity among groups (p > 0.05). The highest microbial clustering effect was found in the corn starch treatment. In conclusion, the best pellet quality was found using potato starch; for rabbit growth, the optimal source was corn starch.
The pituitary tumour‐transforming gene 1/delta‐like homologue 1 pathway plays a key role in liver fibrogenesis
Authors: Perramón Meritxell , Carvajal Silvia , Reichenbach Vedrana , Fernández‐Varo Guillermo , Boix Loreto , Macias‐Muñoz Laura , Melgar‐Lesmes Pedro , Bruix Jordi , Melmed Shlomo , Lamas Santiago , Jiménez Wladimiro
Published: January 2022

Background and Aims

PTTG1 is almost undetectable in adult livers but is highly expressed in hepatocarcinoma. While little is known about its involvement in liver fibrosis, PTTG1 expression is associated with DLK1. We assessed the role of the PTTG1/DLK1 pathway in fibrosis progression and the potential therapeutic effect of PTTG1 silencing in fibrosis.

Methods

Pttg1 and Dlk1 were studied in liver and isolated cell populations of control and fibrotic rats and in human liver biopsies. The fibrotic molecular signature was analysed in Pttg1−/− and Pttg1+/+ fibrotic mice. Finally, Pttg1 silencing was evaluated in rats as a novel antifibrotic therapy.

Results

Pttg1 and Dlk1 mRNA selectively increased in fibrotic rats paralleling fibrosis progression. Serum DLK1 concentrations correlated with hepatic collagen content and systemic and portal haemodynamics. Human cirrhotic livers showed greater PTTG1 and DLK1 transcript abundance than non‐cirrhotic, and reduced collagen was observed in Pttg1 Pttg1−/− mice. The liver fibrotic molecular signature revealed lower expression of genes related to extracellular matrix remodelling including Mmp8 and 9 and Timp4 and greater eotaxin and Mmp13 than fibrotic Pttg1+/+ mice. Finally, interfering Pttg1 resulted in reduced liver fibrotic area, lower α‐Sma and decreased portal pressure than fibrotic animals. Furthermore, Pttg1 silencing decreased the transcription of Dlk1, collagens I and III, Pdgfrβ, Tgfrβ, Timp1, Timp2 and Mmp2.

Conclusions

Pttg1/Dlk1 are selectively overexpressed in the cirrhotic liver and participate in ECM turnover regulation. Pttg1 disruption decreases Dlk1 transcription and attenuates collagen deposition. PTTG1/DLK1 signalling is a novel pathway for targeting the progression of liver fibrosis.
Impact of sound levels on physiological and consciousness state of cardiovascular patients
Authors: Morales‐Cané Ignacio , Moral‐Arroyo Juan Antonio , Debbia Fabio , Guler Ipek , Llamas‐Recio Francisca , Jiménez‐Pastor José Manuel , de la Cruz López‐Carrasco Juan , Acuña‐Castroviejo Darío , Rodríguez‐Borrego María Aurora , López‐Soto Pablo Jesús
Published: January 2022

Background

Patients treated in intensive care units (ICUs) experience life‐threatening medical conditions but some external factors in ICUs do not help or even adversely affect and complicate their evolution. Among others, such factors include noise pollution due to alarms and medical clinical equipment, as well as the activities of the health care personnel themselves.

Aim

This study aimed to evaluate the influence of elevated sound levels on physiological variables and the consciousness state of patients treated in a cardiovascular area in an ICU.

Design

A longitudinal study with several observations was carried out during 1 month in the cardiovascular area of an ICU of a third‐level hospital in southern Spain.

Methods

Sound levels were monitored in different work shifts and patients' physiological data and consciousness status were recorded. Generalized additive mixed models (GAMMs) were developed to detect the variability of the sound levels together with the vital parameters of the patients in the ICU.

Results

Thirty‐eight patients were included. The mean sound level was 54.09 dBA. The GAMM sound levels analysis showed a significant increase in sound levels from 4:30 p.m. to 8:00 p.m. (1.83 dBA; P < .001) and 8:00 p.m. to 11:30 p.m. (3.06 dBA; P < .001). An increase in heart rate (3.66 bpm; P < .001), respiratory rate (2.62 rpm; P < .001) and the Glasgow Coma Scale (0.50 units; P = .002) was detected during the 4:30 p.m.–8:30 p.m. period.

Conclusions

Elevated sound levels in cardiovascular ICUs seem to influence positively the physiological and consciousness status of patients. Given the importance of the findings for patient safety, future intervention studies are recommended.

Relevance to Clinical Practice

The finding of this study could translate into structural changes in ICU facilities, as well as the development of clinical practice guidelines that influence the behaviour of health care professionals.
Detection of the HLA‐A*68:99:02 allele in a Russian unrelated hematopoietic cell donor
Authors: Loginova Maria , Smirnova Daria , Druzhinina Svetlana , Yaroshenko Kristina , Paramonov Igor
Published: January 2022

Identification of the novel HLA‐A*68:99:02 allele that differs from HLA‐A*68:99:01 in exon 2 and intron 7.
The Politics of Jewish Primitivism
Authors: Spinner Samuel J.
Published: January 2022

Chapter 4 explores the politics of Jewish primitivism, which ranged from the bohemian Left to the radical Right. This political breadth is evident in the poetic relationship between the German poet Else Lasker-Schüler and the Yiddish and Hebrew poet Uri Zvi Grinberg, the former ambivalent about Zionism, the latter a proponent of Zionism’s most radical wing. The idea of an originary Jewish identity rooted in an ancient but unspecified East was central to Lasker-Schüler’s poetry and visual art. Emerging from this landscape was her “Society of Savage Jews,” a utopian community of writers and artists that existed only in her writings and artwork; Grinberg borrowed this trope and used it for very different ends—his savage Jews were Zionist pioneers, creating a nation-state.
Introduction to the Idra Rabba
Authors: Hellner-Eshed Melila
Published: January 2022

What is the Idra Rabba? This chapter covers the place of the Idra Rabba in zoharic literature as well as its reception, history, and scholarship.
What Is the Idra Rabba Trying to Communicate?
Authors: Hellner-Eshed Melila
Published: January 2022

This chapter lays out the Zohar as a manifesto calling for the healing of the face of Jewish religion.
The Ancient of Ancients and Zeʿeir Anpin
Authors: Hellner-Eshed Melila
Published: January 2022

This chapter deals with the complex unity of the divine faces.