bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of clearance on volumetric efficiency in 2D piston pumps
Authors: Huang Yu , Ruan Jian , Ding Chuan , Li Sheng
Published: October 2021

In order to solve the limitations of the friction pairs in axial piston pumps on rotational speed and mechanical efficiency, a 2D piston pump whose 2D piston has two-degree-of-freedom motions of rotation and reciprocating motion was proposed by the author team. The volumetric efficiency of 2D pumps predicted by the original volumetric efficiency model is higher than the experimental results. A new mathematical model of the volumetric efficiency is researched by considering effect of clearance between the cone roller and the guiding rail. In previous studies, the volumetric losses of the 2D pump were considered to be composed of leakage and compressibility loss. However, it is found that the effect of the clearance on the volumetric efficiency in 2D pumps is greater than that of leakage and compressibility loss. The experimental results show that the difference between the prediction of the new model and the volumetric efficiency of the tested pump with 0.19 mm clearance is reduced from 8% to 1.5% comparing with the original model. The volumetric efficiency of the tested pump without the clearance is 96.5% at 5000 rpm rotational speed and 8 MPa load pressure.
A Social-Identity Theory of Information-Access Regulation (SITIAR): Understanding the Psychology of Sharing and Withholding
Authors: Bingley William J. , Greenaway Katharine H. , Haslam S. Alexander
Published: October 2021

Secrecy, privacy, confidentiality, concealment, disclosure, and gossip all involve sharing and withholding access to information. However, existing theories do not account for the fundamental similarity between these concepts. Accordingly, it is unclear when sharing and withholding access to information will have positive or negative effects and why these effects might occur. We argue that these problems can be addressed by conceptualizing these phenomena more broadly as different kinds of information-access regulation. Furthermore, we outline a social-identity theory of information-access regulation (SITIAR) that proposes that information-access regulation shapes shared social identity, explaining why people who have access to information feel a sense of togetherness with others who have the same access and a sense of separation from those who do not. This theoretical framework unifies diverse findings across disparate lines of research and generates a number of novel predictions about how information-access regulation affects individuals and groups.
Automatically binding relevant and irrelevant features in visual working memory
Authors: Zhao Chenxiao , Li Xinyu , Failing Michel , Wang Benchi
Published: October 2021

It is generally assumed that, to save storage space, features are stored as integrated objects in visual working memory (VWM). Although such an object-based account does not always hold because features can be processed in parallel, a previous study has shown that different features can be automatically bound with their locations (task-irrelevant feature) into an integrated unit, resulting in improved memory performance. The present study was designed to further explore this phenomenon by investigating whether other features, which are not spatial in origin, can act as the binding cue to form such automatic binding. To test this, we used three different features as binding cues (i.e., colour, spatial frequency, and shape) over multiple separate experiments. The results consistently showed that when two features shared the same binding cue, memory performance was better relative to when each of those features had their own binding cue. We conclude that any task-irrelevant feature can act as a binding cue to automatically bind with task-relevant features even across different objects, resulting in memory enhancement.
Tear size, general health status and smoking influence functional outcome at 5 years following arthroscopic rotator cuff repair
Authors: Lawson Olivia , Nicholson Jaimie A , Clement Nicholas D , Rudge Will , MacDonald Deborah J , McBirnie Julie
Published: October 2021

Introduction

There is limited medium-term outcome data regarding the predictors of functional outcome and patient satisfaction after arthroscopic rotator cuff repair.

Methods

287 patients that underwent arthroscopic rotator cuff repair under a high-volume single surgeon were contacted at a minimum of 4 years following surgery. Patient demographics, tear size and co-morbidities were pre-operatively recorded. The Oxford shoulder score, EuroQol 5-dimensional score and patient satisfaction were recorded at final follow-up.

Results

234 (81.5%) patients completed follow-up at a mean of 5.5 (4–9) years. There were 126 males and 108 females with a mean age of 60 (range 25–83) years. The majority of patients ( n = 211, 90%) were satisfied with their final outcome. Multivariate linear regression analysis ( R2 = 0.64) identified that increasing tear size ( p = 0.04), worsening general health assessed by the EuroQol 5-Dimensional ( p < 0.001), and smoking ( p = 0.049) were associated with a worse Oxford shoulder score. Logistic regression analysis ( R2 = 0.13) identified that worsening general health assessed by the EuroQol 5-Dimensional ( p < 0.001), and smoking ( p = 0.01) were associated with an increased risk of patient dissatisfaction.

Conclusion

General health status and smoking are independent predictors of functional outcome and patient satisfaction at medium-term follow-up following arthroscopic rotator cuff repair.
A case of sub-acute compartment syndrome of bilateral pectoralis major, deltoid and triceps muscles
Authors: Kalaskar A , Paniker J , Gavai P
Published: October 2021

A 19-year-old healthy bodybuilder presented to the emergency department with gradually worsening pain in both his upper arms and shoulders and inability to fully flex his elbows. The haematological investigations revealed a markedly raised Creatinine Kinase (74,400 U/L) and myoglobinuria. The patient required an emergency surgical decompression of the pectoral and the anterior and posterior compartments of arms of both upper limbs with secondary closure after 48 h. The patient had an uneventful post-op and recovery of his functions with some initial restriction of full flexion of his left elbow and some weakness in his triceps, all of which gradually improved.
Prevalence and risk factors for pseudarthrosis in humeral shaft fractures treated by minimally invasive plate osteosynthesis: A 10-year review
Authors: Mouraria Guilherme G , Santos Júnior José A S , Kikuta Fernando K , Zogbi Daniel R , Brigatto Rafael M , de Paula Coelho Sérgio , Cruz Márcio A , Etchebehere Maurício
Published: October 2021

Introduction

Fractures of the humeral shaft account for about 3% to 5% of all fractures. Although conservative treatment remains the first choice, there are a number of surgical indications. Minimally invasive plate osteosynthesis shows good functional results. However, complications have been reported, such as non-union.

Objective

To assess the prevalence and risk factors for non-union after treatment of humeral shaft fractures using minimally invasive plate osteosynthesis.

Materials and methods

This retrospective study was carried out in patients treated by minimally invasive plate osteosynthesis between 2009 and 2019. Demographic data and variables related to the fracture that could influence bone healing were analysed. The unpaired t-test and Mann–Whitney test were used for the statistical analyses. Categorical variables were analysed using the chi-square test or Fisher's exact test

Results

The study population showed a male predominance (53 of 75, 70.7%). The average time for fracture healing was 19.8 ± 15.3 weeks. Seven patients developed non-union. Only the presence of an open fracture increased the likelihood of non-union.

Conclusions

The prevalence of non-union in patients treated by minimally invasive plate osteosynthesis was 9.3%. Patients with open fractures were six times more likely to progress to non-union. Fracture characteristics (Arbeitsgemeinschaft für Osteosynthesefragen classification, fracture location and plate working length) did not influence progression to non-union.
Disease Avoidance Motives Trade-Off Against Social Motives, Especially Mate-Seeking, to Predict Social Distancing: Evidence From the COVID-19 Pandemic
Authors: Gul Pelin , Keesmekers Nils , Elmas Pinar , Köse Fatma Ebru , Koskun Tolga , Wisman Arnaud , Kupfer Tom R.
Published: October 2021

A range of studies have sought to understand why people’s compliance with social distancing varied during the COVID-19 pandemic. Recent theory suggests that pathogen avoidance behavior is based not only on perceived risk but on a trade-off between the perceived costs of pathogen exposure and the perceived benefits of social contact. We hypothesized that compliance with social distancing may therefore be explained by a trade-off between pathogen avoidance and various social motives such as mate-seeking. Two studies conducted during the COVID-19 pandemic showed that social distancing was positively associated with disease avoidance motives but negatively associated with social motives, especially mating motives. These associations remained after controlling for predictors identified by previous research, including risk perception and personality. Findings indicate that people who are more interested in seeking new romantic partners (e.g., young men) may be less inclined to socially distance and be more at risk of pathogen transmission.
Rights and Responsibilities Are Substitutable Framings That Differentially Affect Judgment
Authors: Vishkin Allon , Ginges Jeremy
Published: October 2021

Do employers have a responsibility to treat their workers equally or do employees have a right to be treated equally? In common discourse, rights and responsibilities are often used as substitutable framings for the same event, but they may differentially shape judgment. In this investigation, we develop an experimental manipulation of rights versus responsibilities and evaluate whether framing an arrangement between two parties in terms of rights, versus responsibilities, affects people’s judgment. We found that people judged unequal distributions between two parties as less fair when framed in terms of rights than in terms of responsibilities. Furthermore, people judged a rights framing as fairer for an unequal (vs. equal) contractual agreement. Thus, a subtle framing manipulation can increase or decrease people’s sensitivity to unequal distributions. We discuss potential mechanisms for this effect and implications for behavioral law as well as the potential to nudge people’s sensitivity to inequality.
Choice of platform for online classes at Well-Known Institute of Management
Authors: Dhurkari Ram Kumar
Published: October 2021

Well-Known Institute of Management is situated in New Delhi, India, and offers a 2-year fully residential post-graduate programme in management (MBA). Dr. Vivek Gupta joined the Well-Known Institute of Management in the year 2018 as an assistant professor in the area of information technology and system management. He is also heading the IT team of the institute. The critical and unprecedented COVID-19 situation brought another challenge for Dr. Gupta and his team. Going virtual is inevitable. But which platform will serve the purpose of running the next academic session in virtual mode? The IT team proposed a three-stage process in deciding and recommending a plausible online platform for conducting online classes. In the first stage, requirements for conducting online classes are to be analysed and recorded. In the second stage, the options available in the market are explored followed by their assessment based on the requirements recorded in Stage 1. The IT team simplified the assessment by first mapping these requirements with 20 important functionalities of these five platforms. However, the outcome was not favourable. Not a single platform is meeting all the requirements. The IT team is back to square one. In addition, there are other major considerations that needed thorough analysis like managing the desirable behaviour from the users of the selected online platform. The next few months are going to be a real challenge for Dr. Gupta and his team in aligning the institute with a new norm in the upcoming academic year.
Comparing the Use of Flexible and Rigid Reaming Systems Through an Anteromedial Portal for Femoral Tunnel Creation During Anterior Cruciate Ligament Reconstruction: A Systematic Review
Authors: Moran Thomas E. , Ignozzi Anthony J. , Werner Brian C.
Published: October 2021

Background:

Recent studies have suggested that femoral tunnel drilling during anterior cruciate ligament (ACL) reconstruction (ACLR) with the use of a flexible reaming system through a standard anteromedial portal (AM-FR) may result in a different tunnel geometry compared with a rigid reamer through an accessory anteromedial portal with hyperflexion (AM-RR).

Purpose:

To summarize radiologic, anatomic, and clinical outcomes from available studies that directly compared the use of AM-FR versus AM-RR for independent femoral tunnel creation during ACLR.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

A literature search was performed using the MEDLINE (PubMed) and Web of Science databases to identify all studies that directly compared radiologic, anatomic, and clinical outcomes between the use of AM-FR and AM-RR. The literature search, data recording, and methodological quality assessment was performed by 2 independent reviewers. The outcomes analyzed included resultant ACL graft positioning and graft bending angle; femoral tunnel positioning, aperture morphology, length, and widening; posterior wall breakage; and distance from various posterolateral knee structures.

Results:

A total of 13 studies met the eligibility criteria for inclusion. There was no difference in femoral tunnel aperture location between techniques. There were conflicting findings among studies regarding which technique resulted in a more acute graft bending angle. One study reported greater femoral tunnel widening upon follow-up with the use of AM-FR. AM-FR produced longer and more anteverted femoral tunnels than did AM-RR. The difference in tunnel length was significant and more prominent in lesser degrees of knee flexion. With AM-FR, femoral tunnels were farther from the lateral collateral ligament and peroneal nerve, and 1 of 5 studies had fewer reports of posterior wall breakage. There has been no literature comparing the clinical or functional outcomes of these techniques.

Conclusion:

Although no clinical studies exist comparing AM-FR and AM-RR for femoral tunnel creation during ACLR, both systems allow for reproducible positioning of an anatomic femoral tunnel aperture. The use of AM-FR results in longer and more anteverted femoral tunnels than using AM-RR, with exit points on the lateral femur that are different but safe. Surgeons should be aware of the technical differences with each method; however, further study is needed to identify any clinically important difference that results.
The Danger Zone for Iatrogenic Neurovascular Injury in All-Inside Lateral Meniscal Repair in Relation to the Popliteal Tendon: An MRI Study
Authors: Chuaychoosakoon Chaiwat , Wuttimanop Watit , Tangjatsakow Preyanun , Charoenrattanawat Sasathorn , Parinyakhup Wachiraphan , Boonriong Tanarat , Chernchujit Bancha
Published: October 2021

Background:

Lateral meniscal repair can endanger the nearby neurovascular structure (peroneal nerve or popliteal artery). To our knowledge, there have been no studies to evaluate the danger zone of all-inside meniscal repair through the anteromedial (AM) and anterolateral (AL) portals in relation to the medial and lateral edges of the popliteal tendon (PT).

Purpose:

To establish the risk of neurovascular injury and the danger zone in repairing the lateral meniscus in relation to the medial and lateral edges of the PT.

Study Design:

Descriptive laboratory study.

Methods:

Using axial magnetic resonance imaging (MRI) studies at the level of the lateral meniscus, lines were drawn to simulate a straight, all-inside meniscal repair device, drawn from the AM and AL portals to both the medial and lateral edges of the PT. In cases in which the line passed through the neurovascular structure, a risk of iatrogenic neurovascular injury was deemed, and measurements were made to determine the danger zones of neurovascular injury in relation to the medial or lateral edges of the PT.

Results:

Axial MRI images of 240 adult patients were reviewed retrospectively. Repairing the body of the lateral meniscus through the AM portal had a greater risk of neurovascular injury than repairs made through the AL portal in relation to the medial edge of the PT ( P = .006). The danger zone in repairing the lateral meniscus through the AM portal extended 1.82 ± 1.68 mm laterally from the lateral edge of the PT and 3.13 ± 2.45 mm medially from the medial edge of the PT. Through the AL portal, the danger zone extended 2.81 ± 1.94 mm laterally from the lateral edge of the PT and 1.39 ± 1.53 mm medially from the medial edge of the PT.

Conclusion:

Repairing the lateral meniscus through either the AM or the AL portals in relation to the PT can endanger the peroneal nerve or popliteal artery.

Clinical Relevance:

The surgeon can minimize the risk of iatrogenic neurovascular injury in lateral meniscal repair by avoiding using the all-inside meniscal device in the danger zone area as described in this study.
Pleasure and Displeasure: Thunderclap Headache in a 13-Year-Old Boy
Authors: Guerrero Carlos M. , Bhatia Sonal
Published: October 2021

Primary headache associated with sexual activity (PHASA) is a rare headache syndrome characterized by an acute, maximally intense headache during sexual activity and/or orgasm. While rare, it is a diagnosis that is widely accepted in adults; but, scarcely documented in children and adolescents. We aim to highlight the diagnostic process of this interesting headache syndrome in the pediatric population and add to the small list of reported cases in this group. Herein, we describe the case of a 13-year-old boy who presented with thunderclap headaches (TCH) associated with sexual activity. While more commonly diagnosed in adults, PHASA should be considered in sexually active children, though more ominous diagnoses should also be contemplated prior to establishing this diagnosis.
Confronting Idea Stealers in the Workplace: The Unfortunate Moral Credentialing Granted to Power-Holders
Authors: Ploeger-Lyons Nicole A. , Bisel Ryan S.
Published: October 2021

How and when do employees confront one another for stealing their ideas? Business communication literature on confronting unethical behavior is synthesized with moral licensing theory to better understand responses to unethical actors about unjustified credit taking in the workplace. In this message production experiment, working adults ( N = 344) were randomly assigned to respond to a supervisor, peer coworker, or subordinate who stole or ignored the participant’s intellectual contributions. Content and statistical analyses revealed subordinates were comparatively less direct when confronting bosses, suggesting third-party moral licensing and moral credentialing were measurable in communication patterns. Importantly, this dynamic was not attributable to perceptions of task interdependence. Instead, subordinates perceived the stealing or ignoring of their ideas to be less unethical than did bosses. Additionally, individuals whose ideas have been stolen in the workplace were less confrontational compared to those who have not. Thus, data suggest incremental acquiescence to this form of workplace wrongdoing, particularly when the transgressor holds high hierarchical status. Taken together, these data may explain how recognition for ideas tends to spread vertically to bosses (labeled here, vertical credit creep), which may function to reinforce established power arrangements and to perpetuate unjustified credit taking in the workplace.
Faculty Self- and Needs Assessment of Preparedness for Integrating Active Learning Based on Medina's Conceptual Framework
Authors: Joseph Merlyn , Farris Charlotte , Martinez Mardoqueo , Demps Elaine , Hernández-Muñoz José J.
Published: October 2021

BACKGROUND

Active learning (AL) is recognized as a valuable learning strategy.

OBJECTIVE

Using a conceptual framework, the objective of this study was to conduct a faculty self- and needs assessment to determine the extent to which the faculty at one college of pharmacy perceived they already carried out AL, describe faculty challenges, and evaluate faculty examples of AL techniques.

METHODS

A 19-question survey was administered in July 2017 to all 50 college faculty. Survey question types included multiple-choice single- or multiple-answer questions and open-ended questions. For validity, Medina's conceptual framework of 4 key elements for the effective administration of AL was used. For reliability, the draft survey questions were reviewed multiple times and revised accordingly.

RESULTS

Thirty-five faculty members, 70%, completed the survey in full. The majority of the faculty perceived that they carried out 3 of the 4 key elements during lectures: activate prior knowledge (74%), involve the majority of students (89%), and provide feedback (91%). However, only 37% stated they promoted metacognition, another key element. Our qualitative analysis identified (1) faculty had misconceptions about most of Medina's conceptual framework elements, (2) challenges to AL implementation included: need for more technology training, perception that AL requires cutting course material, beliefs that AL does not work, and fear of poor evaluations with AL implementation, and (3) suggestions to improve AL included: faculty development, training students on the importance of AL, and integrating AL throughout the curriculum.

CONCLUSIONS

Although most faculties indicated they integrated AL in their teaching, faculty misconceptions, and beliefs suggest the need for long-term faculty and organizational development using strategies aligned with or seeking to change the beliefs of the faculty and college system.
Achieving Complete Nasal Lining Closure at Primary Cleft Palate Repair When the Lesser Segments Have Collapsed
Authors: Calis Mert , Tse Raymond W.
Published: October 2021

Obtaining a tension-free 2-layer anatomic closure at cleft palate repair reduces risks of fistula and facilitates later alveolar bone grafting. Anterior nasal lining closure can be one of the most challenging aspects of repair but is rarely discussed. We present our approach to palatoplasty for BCLP and additional technical maneuvers for closure in the unfavorable configuration when the lesser segments are collapsed against the vomer: “inside-out” approach along the cleft margin provides access for accurate incision; elevation of medial pterygoid mucoperiosteum provides access further anteriorly to separate nasal lining from palatal shelf; mobilization of lining off of bone when 2 structures are in apposition opens a space for access; nasal lining can be drawn into view with a hook; and the nasal lining closure can be passed back through the space to heal in an anatomic relationship, cephalic to the bony shelves.
Comprehensive RNA sequencing in primary murine keratinocytes and fibroblasts identifies novel biomarkers and provides potential therapeutic targets for skin-related diseases
Authors: Wang Tiancheng , Zhou Zhenwei , Luo Enjing , Zhong Jinghong , Zhao Daqing , Dong Haisi , Yao Baojin
Published: October 2021

Background

Keratinocytes and fibroblasts represent the major cell types in the epidermis and dermis of the skin and play a significant role in maintenance of skin homeostasis. However, the biological characteristics of keratinocytes and fibroblasts remain to be elucidated. The purpose of this study was to compare the gene expression pattern between keratinocytes and fibroblasts and to explore novel biomarker genes so as to provide potential therapeutic targets for skin-related diseases such as burns, wounds, and aging.

Methods

Skin keratinocytes and fibroblasts were isolated from newborn mice. To fully understand the heterogeneity of gene expression between keratinocytes and fibroblasts, differentially expressed genes (DEGs) between the two cell types were detected by RNA-seq technology. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the known genes of keratinocytes and fibroblasts and verify the RNA-seq results.

Results

Transcriptomic data showed a total of 4309 DEGs (fold-change > 1.5 and q-value < 0.05). Among them, 2197 genes were highly expressed in fibroblasts and included 10 genes encoding collagen, 16 genes encoding transcription factors, and 14 genes encoding growth factors. Simultaneously, 2112 genes were highly expressed in keratinocytes and included 7 genes encoding collagen, 14 genes encoding transcription factors, and 8 genes encoding growth factors. Furthermore, we summarized 279 genes specifically expressed in keratinocytes and 33 genes specifically expressed in fibroblasts, which may represent distinct molecular signatures of each cell type. Additionally, we observed some novel specific biomarkers for fibroblasts such as Plac8 (placenta-specific 8), Agtr2 (angiotensin II receptor, type 2), Serping1 (serpin peptidase inhibitor, clade G, member 1), Ly6c1 (lymphocyte antigen 6 complex, locus C1), Dpt (dermatopontin), and some novel specific biomarkers for keratinocytes such as Ly6a (lymphocyte antigen 6 complex, locus A) and Lce3c (late cornified envelope 3C), Ccer2 (coiled-coil glutamate-rich protein 2), Col18a1 (collagen, type XVIII, alpha 1) and Col17a1 (collagen type XVII, alpha 1). In summary, these data provided novel identifying biomarkers for two cell types, which can provide a resource of DEGs for further investigations.
Vegetarian diet duration’s influence on women’s gut environment
Authors: Deng Xinqi , Si Jiangtao , Qu Yonglong , Jie Li , He Yuansong , Wang Chunguo , Zhang Yuping
Published: October 2021

Background

Nutrient composition of vegetarian diets is greatly different from that of omnivore diets, which may fundamentally influence the gut microbiota and fecal metabolites. The interactions between diet pattern and gut environment need further illustration. This study aims to compare the difference in the gut microbiota and fecal metabolites between vegetarian and omnivore female adults and explore associations between dietary choices/duration and gut environment changes.

Methods

In this study, investigations on the fecal metabolome together with the gut microbiome were performed to describe potential interactions with quantitative functional annotation. In order to eliminate the differences brought by factors of gender and living environment, 80 female adults aged 20 to 48 were recruited in the universities in Beijing, China. Quantitative Insights Into Microbial Ecology (QIIME) analysis and Ingenuity Pathway Analysis (IPA) were applied to screen differential data between groups from gut microbiota and fecal metabolites. Furthermore, weighted gene correlation network analysis (WGCNA) was employed as the bioinformatics analysis tool for describing the correlations between gut microbiota and fecal metabolites. Moreover, participants were further subdivided by the vegetarian diet duration for analysis.

Results

GPCR-mediated integration of enteroendocrine signaling was predicted to be one of the regulatory mechanisms of the vegetarian diet. Intriguingly, changes in the gut environment which occurred along with the vegetarian diet showed attenuated trend as the duration increased. A similar trend of returning to “baseline” after a 10-year vegetarian diet was detected in both gut microbiota and fecal metabolome.

Conclusions

The vegetarian diet is beneficial more than harmful to women. Gut microbiota play roles in the ability of the human body to adapt to external changes.
Spatial rank-based multifactor dimensionality reduction to detect gene–gene interactions for multivariate phenotypes
Authors: Park Mira , Jeong Hoe-Bin , Lee Jong-Hyun , Park Taesung
Published: October 2021

Background

Identifying interaction effects between genes is one of the main tasks of genome-wide association studies aiming to shed light on the biological mechanisms underlying complex diseases. Multifactor dimensionality reduction (MDR) is a popular approach for detecting gene–gene interactions that has been extended in various forms to handle binary and continuous phenotypes. However, only few multivariate MDR methods are available for multiple related phenotypes. Current approaches use Hotelling’s T2statistic to evaluate interaction models, but it is well known that Hotelling’s T2statistic is highly sensitive to heavily skewed distributions and outliers.

Results

We propose a robust approach based on nonparametric statistics such as spatial signs and ranks. The new multivariate rank-based MDR (MR-MDR) is mainly suitable for analyzing multiple continuous phenotypes and is less sensitive to skewed distributions and outliers. MR-MDR utilizes fuzzy k-means clustering and classifies multi-locus genotypes into two groups. Then, MR-MDR calculates a spatial rank-sum statistic as an evaluation measure and selects the best interaction model with the largest statistic. Our novel idea lies in adopting nonparametric statistics as an evaluation measure for robust inference. We adopt tenfold cross-validation to avoid overfitting. Intensive simulation studies were conducted to compare the performance of MR-MDR with current methods. Application of MR-MDR to a real dataset from a Korean genome-wide association study demonstrated that it successfully identified genetic interactions associated with four phenotypes related to kidney function. The R code for conducting MR-MDR is available athttps://github.com/statpark/MR-MDR.

Conclusions

Intensive simulation studies comparing MR-MDR with several current methods showed that the performance of MR-MDR was outstanding for skewed distributions. Additionally, for symmetric distributions, MR-MDR showed comparable power. Therefore, we conclude that MR-MDR is a useful multivariate non-parametric approach that can be used regardless of the phenotype distribution, the correlations between phenotypes, and sample size.
Identification, visualization, statistical analysis and mathematical modeling of high-feedback loops in gene regulatory networks
Authors: Nordick Benjamin , Hong Tian
Published: October 2021

Background

Feedback loops in gene regulatory networks play pivotal roles in governing functional dynamics of cells. Systems approaches demonstrated characteristic dynamical features, including multistability and oscillation, of positive and negative feedback loops. Recent experiments and theories have implicated highly interconnected feedback loops (high-feedback loops) in additional nonintuitive functions, such as controlling cell differentiation rate and multistep cell lineage progression. However, it remains challenging to identify and visualize high-feedback loops in complex gene regulatory networks due to the myriad of ways in which the loops can be combined. Furthermore, it is unclear whether the high-feedback loop structures with these potential functions are widespread in biological systems. Finally, it remains challenging to understand diverse dynamical features, such as high-order multistability and oscillation, generated by individual networks containing high-feedback loops. To address these problems, we developed HiLoop, a toolkit that enables discovery, visualization, and analysis of several types of high-feedback loops in large biological networks.

Results

HiLoop not only extracts high-feedback structures and visualize them in intuitive ways, but also quantifies the enrichment of overrepresented structures. Through random parameterization of mathematical models derived from target networks, HiLoop presents characteristic features of the underlying systems, including complex multistability and oscillations, in a unifying framework. Using HiLoop, we were able to analyze realistic gene regulatory networks containing dozens to hundreds of genes, and to identify many small high-feedback systems. We found more than a 100 human transcription factors involved in high-feedback loops that were not studied previously. In addition, HiLoop enabled the discovery of an enrichment of high feedback in pathways related to epithelial-mesenchymal transition.

Conclusions

HiLoop makes the study of complex networks accessible without significant computational demands. It can serve as a hypothesis generator through identification and modeling of high-feedback subnetworks, or as a quantification method for motif enrichment analysis. As an example of discovery, we found that multistep cell lineage progression may be driven by either specific instances of high-feedback loops with sparse appearances, or generally enriched topologies in gene regulatory networks. We expect HiLoop’s usefulness to increase as experimental data of regulatory networks accumulate. Code is freely available for use or extension athttps://github.com/BenNordick/HiLoop.
Privacy-preserving storage of sequenced genomic data
Authors: Hekel Rastislav , Budis Jaroslav , Kucharik Marcel , Radvanszky Jan , Pös Zuzana , Szemes Tomas
Published: October 2021

Background

The current and future applications of genomic data may raise ethical and privacy concerns. Processing and storing of this data introduce a risk of abuse by potential offenders since the human genome contains sensitive personal information. For this reason, we have developed a privacy-preserving method, named Varlock providing secure storage of sequenced genomic data. We used a public set of population allele frequencies to mask the personal alleles detected in genomic reads. Each personal allele described by the public set is masked by a randomly selected population allele with respect to its frequency. Masked alleles are preserved in an encrypted confidential file that can be shared in whole or in part using public-key cryptography.

Results

Our method masked the personal variants and introduced new variants detected in a personal masked genome. Alternative alleles with lower population frequency were masked and introduced more often. We performed a joint PCA analysis of personal and masked VCFs, showing that the VCFs between the two groups cannot be trivially mapped. Moreover, the method is reversible and personal alleles in specific genomic regions can be unmasked on demand.

Conclusion

Our method masks personal alleles within genomic reads while preserving valuable non-sensitive properties of sequenced DNA fragments for further research. Personal alleles in the desired genomic regions may be restored and shared with patients, clinics, and researchers. We suggest that the method can provide an additional security layer for storing and sharing of the raw aligned reads.
Severe drug-associated colitis with Crohn’s features in setting of ixekizumab therapy for chronic plaque psoriasis
Authors: Mu Xin , Fardy John , Reid Stephanie , Trahey Julia
Published: October 2021

Background

Ixekizumab is monoclonal antibody targeted against interleukin-17 (IL-17) and has been approved for use in chronic plaque psoriasis. Despite its efficacy in treating psoriasis, concerns have been raised regarding Ixekizumab’s potential to induce and exacerbate inflammatory bowel disease (IBD).

Case presentation

Here we report the new onset of severe drug-associated colitis with surgical complications in a 45-year-old male patient who was receiving Ixekizumab therapy for chronic plaque psoriasis. Review of the patient’s colonic pathology demonstrated acute inflammatory changes with features of Crohn’s disease. The patient remained disease-free 9-months following his hospitalization and cessation of Ixekizumab.

Conclusions

This case raises suspicion for an association between Ixekizumab and IBD and calls on clinicians to have heightened awareness of potential risks before prescribing anti-IL-17 agents.
The geriatric nutritional risk index mediated the relationship between serum uric acid and hypertension: a mediation analysis
Authors: Cao Zhongnan , Dai Sui , Liu Xun
Published: October 2021

Background

The elevated serum uric acid (SUA) is associated with an increased risk of hypertension and nutritional status. Malnutrition might modify the association of SUA with hypertension. Therefore, the aims of this study were to examine the mediation effect of malnutrition on the association of SUA with the risk of hypertension in Chinese population.

Methods

The study was based on the China Health and Nutrition Survey in 2009. Participants aged ≥ 60 years with complete analyzed data were eligible. The Geriatric Nutritional Risk Index (GNRI) was calculated by serum albumin (ALB) and BMI. Participants were identified as hypertension if systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or receiving antihypertensive drug.

Results

There were 2371 participants included in the final analysis. In total, there was a significant mediation effect of the GNRI on the relationship between SUA level with hypertension (P < 0.001; OR: 1.096; and 95 % CI: 1.048–1.146). And the proportion mediated was 17.77 %. The results stratified by sex were consistent with those of total population. The significant mediation effects of the GNRI were found in the 60–69 years and 70–79 years groups (P = 0.002 and 0.032; OR: 1.099 and 1.075; and 95 % CI: 1.036–1.165 and 1.006–1.148, respectively) but not in the 80–99 years group (P = 0.303). The proportions mediated were16.22 % and 18.36 %, respectively.

Conclusions

The GNRI can mediate and account for approximately 17.77 % of the relationship between SUA level and the risk of hypertension. And this mediation effect was fully observed in both males and females, especially in the 60–79 years population.
Efficacy and safety of polymyxin B in carbapenem-resistant gram-negative organisms infections
Authors: Xia G. L. , Jiang R. L.
Published: October 2021

Objective

To investigate how to use polymyxin B rationally in order to produce the best efficacy and safety in patients with carbapenem-resistant gram-negative organisms (CRO) infection.

Methods

The clinical characteristics and microbiological results of 181 patients caused by CRO infection treated with polymyxin B in the First Affiliated Hospital from July 2018 to May 2020 were retrospectively analyzed. The bacterial clearance rate, clinical efficacy, adverse drug reactions and 28 days mortality were evaluated.

Results

The overall effective rate of 181 patients was 49.72%, the total bacterial clearance rate was 42.0%, and the 28 day all-cause mortality rate was 59.1%. The effective rate and bacterial clearance rate in the group of less than 24 h from the isolation of CRO to the use of polymyxin B were significantly higher than those in the group of more than 24 h. Logistics multivariate regression analysis showed that the predictive factors for effective treatment of CRO with polymyxin B were APACHEII score, duration of polymyxin B treatment, combination of polymyxin B and other antibiotics, and bacterial clearance. 17 cases (9.36%) of acute kidney injury were considered as polymyxin B nephrotoxicity and 4 cases (23.5%) recovered after polymyxin B withdrawal. After 14 days of polymyxin B use, 3 cases of polymyxin B resistance appeared, and there were 2 cases of polymyxin B resistance in the daily dose 1.5 mg/kg/day group.

Conclusion

For CRO infection, the treatment of polymyxin B should be early, combined, optimal dose and duration of treatment, which can achieve better clinical efficacy and microbial reactions, and reduce the adverse reactions and drug resistance.
Reliability of the freehand region-of-interest method in quantitative cerebral diffusion tensor imaging
Authors: Hakulinen Ullamari , Brander Antti , Ilvesmäki Tero , Helminen Mika , Öhman Juha , Luoto Teemu M. , Eskola Hannu
Published: October 2021

Background

Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique used for evaluating changes in the white matter in brain parenchyma. The reliability of quantitative DTI analysis is influenced by several factors, such as the imaging protocol, pre-processing and post-processing methods, and selected diffusion parameters. The region-of-interest (ROI) method is most widely used of the post-processing methods because it is found in commercial software. The focus of our research was to study the reliability of the freehand ROI method using various intra- and inter-observer analyses.

Methods

This study included 40 neurologically healthy participants who underwent diffusion MRI of the brain with a 3 T scanner. The measurements were performed at nine different anatomical locations using a freehand ROI method. The data extracted from the ROIs included the regional mean values, intra- and inter-observer variability and reliability. The used DTI parameters were fractional anisotropy (FA), the apparent diffusion coefficient (ADC), and axial (AD) and radial (RD) diffusivity.

Results

The average intra-class correlation coefficient (ICC) of the intra-observer was found to be 0.9 (excellent). The single ICC results were excellent (> 0.8) or adequate (> 0.69) in eight out of the nine regions in terms of FA and ADC. The most reliable results were found in the frontobasal regions. Significant differences between age groups were also found in the frontobasal regions. Specifically, the FA and AD values were significantly higher and the RD values lower in the youngest age group (18–30 years) compared to the other age groups.

Conclusions

The quantitative freehand ROI method can be considered highly reliable for the average ICC and mostly adequate for the single ICC. The freehand method is suitable for research work with a well-experienced observer. Measurements should be performed at least twice in the same region to ensure that the results are sufficiently reliable. In our study, reliability was slightly undermined by artifacts in some regions such as the cerebral peduncle and centrum semiovale. From a clinical point of view, the results are most reliable in adults under the age of 30, when age-related changes in brain white matter have not yet occurred.
Circulating endothelin-1 levels are positively associated with chronic kidney disease in women but not in men: a longitudinal study in the Vara-Skövde cohort
Authors: Hellgren Margareta I. , Jansson Per-Anders , Alayar Hormoz , Lindblad Ulf , Daka Bledar
Published: October 2021

Background

The vasoconstricting peptide endothelin-1 (ET-1) is associated with endothelial dysfunction. The aim of this paper was to investigate whether circulating ET-1 levels predicts chronic kidney disease (CKD) in a prospective population study.

Methods

In 2002–2005, 2816 participants (30–74 years) were randomly selected from two municipalities in South-Western Sweden and followed up in a representative sample of 1327 individuals after 10 years. Endothelin-1 levels were assessed at baseline. Outcome was defined as CKD stage 3 or above based on eGFR < 60 mL/min/1.73m2. Those 1314 participants with successful analysis of ET-1 were further analyzed using binary logistic regression.

Results

At follow-up, 51 (8%) men and 47 (7,8%) women had CKD stage 3 and above. Based on levels of ET-1 the population was divided into quintiles showing that women in the highest quintile (n = 132) had a significantly increased risk of developing CKD during the follow up period (OR = 2.54, 95% CI:1.19–5.45, p = 0.02) compared with the other quintiles (1–4). The association was borderline significant after adjusted for age, current smoking, alcohol consumption, hypertension, diabetes, BMI, high- sensitive CRP and LDL-cholesterol (OR = 2.25, 95% CI:0.97–5.24, p = 0.06). No significant differences were observed between quintiles of ET-1 and development of CKD in men (NS).

Conclusions

High levels of ET-1 are associated with development of CKD in women.
Expression of and correlational patterns among neuroinflammatory, neuropeptide, and neuroendocrine molecules from cerebrospinal fluid in cerebral palsy
Authors: Goracke-Postle Cory J. , Burkitt Chantel C. , Panoskaltsis-Mortari Angela , Ehrhardt Michael , Wilcox George L. , Graupman Patrick , Partington Michael , Symons Frank J.
Published: October 2021

Background

The underlying pathogenesis of cerebral palsy (CP) remains poorly understood. The possibility of an early inflammatory response after acute insult is of increasing interest. Patterns of inflammatory and related biomarkers are emerging as potential early diagnostic markers for understanding the etiologic diversity of CP. Their presence has been investigated in plasma and umbilical cord blood but not in cerebrospinal fluid (CSF).

Methods

A clinical CP sample was recruited using a single-time point cross-sectional design to collect CSF at point-of-care during a standard-of-care surgical procedure (intrathecal pump implant). Patient demographic and clinical characteristics were sourced from medical chart audit.

Results

Significant (p ≤ 0.001) associations were found among neuroinflammatory, neuroendocrine, and nociceptive analytes with association patterns varying by birth status (term, preterm, extremely preterm). When between birth-group correlations were compared directly, there was a significant difference between preterm and extremely preterm birth subgroups for the correlation between tumour necrosis factor alpha (TNFα) and substance P.

Conclusion

This investigation shows that CSF can be used to study proteins in CP patients. Differences in inter-correlational patterns among analytes varying by birth status underscores the importance of considering birth status in relation to possible mechanistic differences as indicated by biomarker signatures. Future work should be oriented toward prognostic and predictive validity to continue to parse the heterogeneity of CP’s presentation, pathophysiology, and response to treatment.
Prevalence and correlates of carotid artery stenosis in a cohort of Sri Lankan ischaemic stroke patients
Authors: Mettananda K. C. D. , Eshani M. D. P. , Wettasinghe L. M. , Somaratne S. , Nanayakkkara Y. P. , Sathkorala W. , Upasena A. , Sirigampola C. , Tilakaratna P. M. Y. , Pathmeswaran A. , Ranawaka U. K.
Published: October 2021

Background

Large artery atherosclerotic disease is an important cause of stroke, accounting for 15–46% of ischaemic strokes in population-based studies. Therefore, current guidelines from west recommend urgent carotid imaging in all ischaemic strokes or transient ischaemic attacks and referral for carotid endarterectomy. However, the clinical features and epidemiology of stroke in Asians are different from those in Caucasians and therefore the applicability of these recommendations to Asians is controversial. Data on the prevalence of carotid artery stenosis (CAS) among South Asian stroke patients is limited. Therefore, we sought to determine the prevalence and associated factors of significant CAS in a cohort of Sri Lankan patients with ischaemic stroke.

Methods

We prospectively studied all ischaemic stroke patients who underwent carotid doppler ultrasonography admitted to the stroke unit of a Sri Lankan tertiary care hospital over 5 years. We defined carotid stenosis as low (< 50%), moderate (50–69%) or severe (70–99%) or total-occlusion (100%) by North American Symptomatic Trial Collaborators (NASCET) criteria. We identified the factors associated with CAS ≥ 50% and ≥ 70% by stepwise multiple logistic regression analysis.

Results

A total of 550 ischaemic stroke patients (326 (59.3%) male, mean age was 58.9 ± 10.2 years) had carotid doppler ultrasonography. Of them, 528 (96.0%) had low-grade, 12 (2.2%) moderate and 7 (1.3%) severe stenosis and 3 (0.5%) had total occlusion. On multivariate logistic regression, age was associated with CAS ≥ 50% (OR 1.12, p = 0.001) and CAS ≥ 70% (OR 1.14, p = 0.016), but none of the other vascular risk factors studied (sex, hypertension, diabetes mellitus, smoking, past history of TIA, stroke or ischemic heart disease) showed significant associations.

Conclusions

Carotid stenosis is a minor cause of ischemic stroke in Sri Lankans compared to western populations with only 4.0% having CAS ≥ 50 and 3.5% eligible for carotid endarterectomy. Our findings have implications for the management of acute strokes in Sri Lanka.