bluuebunny/crossref_metadata_2025 huggingface dataset:
MRI-based kinematics of the menisci through full knee range of motion
Authors: Yamamoto Tadashi , Taneichi Hiroshi , Seo Yoshiteru , Yoshikawa Katsuhisa
Published: May 2021

Purpose:

The meniscal kinematics in the full knee range of motion (ROM) have not been demonstrated by MRI, because the narrow bore of the superconducting magnet prevents full knee motion. The purpose of this study was to the investigate meniscal kinematics associated with femorotibial kinematics using an open-structure MRI unit that allows kinematic analysis of the menisci in full knee ROM.

Methods:

Non-weight-bearing MR images of the right knee of 10 subjects were acquired at six angles of knee flexion (0°, 30°, 60°, 90°, 120°, and full flexion) using a compact 0.2-T MRI system. The positions of the anterior and posterior horns of the medial and lateral menisci (MM/LM) and the medial and lateral femoral condyles (MFC/LFC) were measured at each angle of flexion.

Results:

Significant posterior LFC movement was observed in all sets of adjacent flexion angles of 60°–90° or more, indicating medial pivot motion of the femur. Significant differences in LM position were observed between adjacent flexion angles of 60°–90° or more. The positional relationship between the posterior horn of MM and the MFC was statistically significant in all but 60° flexion. The positional relationship between LM and LFC was significant at flexion angles of ≤90° in the anterior horn and at 60°, 90°, and full flexion in the posterior horn.

Conclusion:

Motion patterns of the menisci were analogous to those of the femoral condyle. Medial pivot motion of the femur caused the greatest posterior movement of the LM. Meniscal kinematics followed the femorotibial kinematics. Comprehension of meniscal kinematics in full knee ROM is important for understanding of injury mechanisms, planning meniscus transplant, and making postoperative care program for meniscus surgery.
Effect of tranexamic acid in arthroscopic anterior cruciate ligament repair: A systematic review and meta-analysis of randomised clinical trials
Authors: Tan Tze Khiang , Ng Ka Ting , Lim Hui Jane , Radic Ross
Published: May 2021

Purpose:

Perioperative blood loss remains a major challenge to surgeons in anterior cruciate ligament reconstruction (ACLR) surgery, despite of the introduction of minimally invasive approach. Tranexamic acid (TXA) is believed to reduce blood loss, which may minimise the complication of postoperative haemarthrosis with insufficient evidence on its effectiveness in ACLR. The primary aim of this study was to examine the effect of TXA on postoperative blood loss and other secondary outcomes in patients undergoing arthroscopic ACLR surgery.

Method:

PUBMED, EMBASE, MEDLINE and CENTRAL database were systematically searched from its inception until November 2020. All randomised clinical trials (RCTs) comparing TXA (intravenous or intra-articular) versus placebo in the arthroscopic ACLR surgery were included. Case series, case report and editorials were excluded.

Results:

Five RCTs comprising of a total of 580 patients (291 in TXA group, 289 in control group) were included for qualitative and quantitative meta-analysis. In comparison to placebo, TXA group was significantly associated with lower postoperative blood loss (mean difference (MD): −81.93 ml; 95% CI −141.80 to −22.05) and lower incidence of needing knee aspiration (odd ratio (OR): 0.19; 95% CI 0.08 to 0.44). Patients who randomised to TXA were also reported to have better range of movement (MD: 2.86; 95% CI 0.54 to 5.18), lower VAS Pain Score (MD: −1.39; 95% CI −2.54 to −0.25) and higher Lysholm Score (MD: 7.38; 95% CI 2.75 to 12.01).

Conclusion:

In this meta-analysis, TXA reduced postoperative blood loss with lesser incidence of needing knee aspiration along with better range of knee movement and Lysholm score in patients undergoing arthroscopic ACLR surgery.
A Rare Case of Guillain-Barré Syndrome With Severe Pandysautonomia
Authors: Tagaloa Eneti , Venter Frederick , Liang Li , Bhaika Jasbir , Aguirre David , Patel Janushe , Nasrawi Faisal
Published: May 2021

Acute pandysautonomia is a rare disorder characterized by autonomic failure affecting sympathetic, parasympathetic, and enteric functions. We present a case of acute inflammatory demyelinating polyneuropathy (AIDP) with severe pandysautonomia in a young, otherwise healthy, female who presented with gastrointestinal symptoms and sensory demyelinating polyneuropathy, which progressively worsened and subsequently developed bladder dysfunction and orthostatic hypotension. We discuss the challenges with diagnostic workup as well as the challenges we encountered as part of the management.
Interleaved Acoustic Environments: Impact of an Auditory Scene Classification Procedure on Speech Perception in Cochlear Implant Users
Authors: Eichenauer Anja , Baumann Uwe , Stöver Timo , Weissgerber Tobias
Published: May 2021

Clinical speech perception tests with simple presentation conditions often overestimate the impact of signal preprocessing on speech perception in complex listening environments. A new procedure was developed to assess speech perception in interleaved acoustic environments of different complexity that allows investigation of the impact of an automatic scene classification (ASC) algorithm on speech perception. The procedure was applied in cohorts of normal hearing (NH) controls and uni- and bilateral cochlear implant (CI) users. Speech reception thresholds (SRTs) were measured by means of a matrix sentence test in five acoustic environments that included different noise conditions (amplitude modulated and continuous), two spatial configurations, and reverberation. The acoustic environments were encapsulated in a randomized, mixed order single experimental run. Acoustic room simulation was played back with a loudspeaker auralization setup with 128 loudspeakers. 18 NH, 16 unilateral, and 16 bilateral CI users participated. SRTs were evaluated for each individual acoustic environment and as mean-SRT. Mean-SRTs improved by 2.4 dB signal-to-noise ratio for unilateral and 1.3 dB signal-to-noise ratio for bilateral CI users with activated ASC. Without ASC, the mean-SRT of bilateral CI users was 3.7 dB better than the SRT of unilateral CI users. The mean-SRT indicated significant differences, with NH group performing best and unilateral CI users performing worse with a difference of up to 13 dB compared to NH. The proposed speech test procedure successfully demonstrated that speech perception and benefit with ASC depend on the acoustic environment.
Noise exposure of the residential areas close to urban expressways in a high-rise mountainous city
Authors: Li Heng , Xie Hui
Published: May 2021

Urban expressways can generate excessive noise in the surrounding urban areas, and it tends to be more complex in mountainous cities, due to the undulating terrain, dense population and compact urban structures. This article aims to investigate the objective acoustic environment and road traffic noise exposure, including the noisy evaluation, annoyance and effect of roadside apartments in residential areas close to urban expressways in the high-density, high-rise, mountainous city of Chongqing. Three housing estates were selected for a series of field measurements, questionnaire surveys and noise mapping. There was a significant negative correlation between night-time noise levels and the distances to the urban expressway ( p <  0.01). Moreover, the differences between the daytime and night-time noise levels were generally insignificant (0.7 to 3.6 dBA) at the roadside locations. Differences in reaction to noise exposure in a variety of both person-related and housing condition variables were found, especially between roadside and non-roadside locations or residents. In addition, 75.0% of roadside residents identified the traffic noise as ‘very’ or ‘extremely’ annoying, and 66.7% of them regarded the acoustic environment as the priority environmental factor that needs to be improved. Difference in the ‘bedroom-window orientation’ had a significant effect on subjective noise evaluation. Rectangular-shaped apartments along the roadside obtain better noise reduction capacities than tower-blocks through the simulation. The acoustic performance of road cuttings, as an appropriately designed earth embankment, is improved along with deeper vertical alignment, and slope angles of 30° and 75° should be avoided.
Burden of migraine and unmet needs from the patients’ perspective: a survey across 11 specialized headache clinics in Korea
Authors: Kim Byung-Kun , Chu Min Kyung , Yu Soo Jin , Dell’Agnello Grazia , Han Jeong Hee , Cho Soo-Jin
Published: May 2021

Background

Migraine is a neurological, primary headache disorder affecting more than 1 billion people worldwide, with a multi-faceted burden that can significantly impact the everyday life of a patient, both during and between attacks. However, studies on patient awareness, burden, and clinical management of migraine in Korea are limited and outdated. The aim of this study was to comprehensively investigate the current difficulties and unmet needs that Korean patients with migraine encounter from their perspective.

Methods

A total of 207 patients with episodic or chronic migraine aged between 15 and 76 years, completed a survey designed to cover the following topics: diagnosis, understanding of the disease, treatment experience, disability, and quality of life. Patients were recruited by their neurologists from 11 specialized headache clinics in Korea and completed the survey between 22 July and 19 August 2019. Validated scales such as the Migraine Disability Assessment (MIDAS) questionnaire and Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) were used to assess levels of disability and quality of life, respectively, in patients.

Results

On average, it took 10.1 years from onset of symptoms to diagnosis and a mean of 3.9 hospitals were visited for treatment prior to the patient’s current hospital. There was a lack of understanding among respondents about migraine, with 55.6% believing that unilateral headache is a unique feature of migraine compared with other headache disorders. On average, high levels of disability and poor quality of life were reported by patients, as assessed by MIDAS and MSQv2.1, respectively, but only 23.7% had regularly taken preventive medication in the past. Overall satisfaction with previous doctor-patient relationships was reported by 29.5% of respondents, and satisfaction with preventive and acute medications by only 40.8% and 27.1% of the respondents, respectively.

Conclusion

Korean patients with migraine experience significant disability and reduced quality of life as a result of the disease and have clear unmet needs in terms of diagnosis, understanding of the disease, and disease management including treatment.
A new mouse SNP genotyping assay for speed congenics: combining flexibility, affordability, and power
Authors: Andrews Kimberly R. , Hunter Samuel S. , Torrevillas Brandi K. , Céspedes Nora , Garrison Sarah M. , Strickland Jessica , Wagers Delaney , Hansten Gretchen , New Daniel D. , Fagnan Matthew W. , Luckhart Shirley
Published: May 2021

Background

Speed congenics is an important tool for creating congenic mice to investigate gene functions, but current SNP genotyping methods for speed congenics are expensive. These methods usually rely on chip or array technologies, and a different assay must be developed for each backcross strain combination. “Next generation” high throughput DNA sequencing technologies have the potential to decrease cost and increase flexibility and power of speed congenics, but thus far have not been utilized for this purpose.

Results

We took advantage of the power of high throughput sequencing technologies to develop a cost-effective, high-density SNP genotyping assay that can be used across many combinations of backcross strains. The assay surveys 1640 genome-wide SNPs known to be polymorphic across > 100 mouse strains, with an expected average of 549 ± 136 SD diagnostic SNPs between each pair of strains. We demonstrated that the assay has a high density of diagnostic SNPs for backcrossing the BALB/c strain into the C57BL/6J strain (807–819 SNPs), and a sufficient density of diagnostic SNPs for backcrossing the closely related substrains C57BL/6N and C57BL/6J (123–139 SNPs). Furthermore, the assay can easily be modified to include additional diagnostic SNPs for backcrossing other closely related substrains. We also developed a bioinformatic pipeline for SNP genotyping and calculating the percentage of alleles that match the backcross recipient strain for each sample; this information can be used to guide the selection of individuals for the next backcross, and to assess whether individuals have become congenic. We demonstrated the effectiveness of the assay and bioinformatic pipeline with a backcross experiment of BALB/c-IL4/IL13 into C57BL/6J; after six generations of backcrosses, offspring were up to 99.8% congenic.

Conclusions

The SNP genotyping assay and bioinformatic pipeline developed here present a valuable tool for increasing the power and decreasing the cost of many studies that depend on speed congenics. The assay is highly flexible and can be used for combinations of strains that are commonly used for speed congenics. The assay could also be used for other techniques including QTL mapping, standard F2 crosses, ancestry analysis, and forensics.
Comparative efficacy of image-guided techniques in cardiac resynchronization therapy: a meta-analysis
Authors: Hu Xiao , Xu Hai , Hassea Shameer Raaj Avishkar , Qian Zhiyong , Wang Yao , Zhang Xinwei , Hou Xiaofeng , Zou Jiangang
Published: May 2021

Background

Several studies have illustrated the use of echocardiography, magnetic resonance imaging, and nuclear imaging to optimize left ventricular (LV) lead placement to enhance the response of cardiac resynchronization therapy (CRT) in heart failure patients. We aimed to conduct a meta-analysis to determine the incremental efficacy of image-guided CRT over standard CRT.

Methods

We searched PubMed, Cochrane library, and EMBASE to identify relevant studies. The outcome measures of cardiac function and clinical outcomes were CRT response, concordance of the LV lead to the latest sites of contraction (concordance of LV), heart failure (HF) hospitalization, mortality rates, changes of left ventricular ejection fraction (LVEF), and left ventricular end-systolic volume (LVESV).

Results

The study population comprised 1075 patients from eight studies. 544 patients underwent image-guided CRT implantation and 531 underwent routine implantation without imaging guidance. The image-guided group had a significantly higher CRT response and more on-target LV lead placement than the control group (RR, 1.33 [95% CI, 1.21 to 1.47];p < 0.01 and RR, 1.39 [95% CI, 1.01 to 1.92];p < 0.05, respectively). The reduction of LVESV in the image-guided group was significantly greater than that in the control group (weighted mean difference, − 12.46 [95% CI, − 18.89 to − 6.03];p < 0.01). The improvement in LVEF was significantly higher in the image-guided group (weighted mean difference, 3.25 [95% CI, 1.80 to 4.70];p < 0.01). Pooled data demonstrated no significant difference in HF hospitalization and mortality rates between two groups (RR, 0.89 [95% CI, 0.16 to 5.08];p = 0.90, RR, 0.69 [95% CI, 0.37 to 1.29];p = 0.24, respectively).

Conclusions

This meta-analysis indicates that image-guided CRT is correlated with improved CRT volumetric response and cardiac function in heart failure patients but not with lower hospitalization or mortality rate.
Endoscopic mucosal resection: still a reliable therapeutic option for gastrointestinal neuroendocrine tumors
Authors: Sivandzadeh Gholam Reza , Ejtehadi Fardad , Shoaee Shima , Aminlari Ladan , Niknam Ramin , Taghavi Ali Reza , Geramizadeh Bita , Hormati Ahmad , Safarpour Ali Reza , Bagheri Lankarani Kamran
Published: May 2021

Background

Neuroendocrine tumors (NETs), as a rare and heterogeneous category of solid tumors, feature various morphologies and behaviors. In recent years, the incidence of NETs has continued to increase. Endoscopic mucosal resection (EMR) is one of the therapeutic modalities for the treatment of gastric and rectal NETs.

Methods

We evaluated patients with well-differentiated NETs of the stomach, duodenum, or rectum between 2011 and 2018. In this study, all cases with tumors confined to the mucosal or submucosal layers and smaller than 20 mm were resected using the EMR technique. We used EUS, CT scan, or MRI to exclude patients with advanced disease. All patients were actively monitored for recurrence according to the recommended protocols.

Results

A total of 36 patients with NETs entered the study; 17 (47.2%) were female and the remaining 19 (52.8%) were male, with a total age range of 20–74 years (mean: 52.47 ± 13.47 years). Among the tumors, 31 cases (86.1%) were G1 and the remaining 5 (13.9%) were G2. Based on the pathology reports, 22 tumors (61.1%) were smaller than 1 cm, while the remaining 14 (38.9%) were between 1–2 cm. Twenty-two patients (61.1%) had a margin of specimen involved with the tumor. No recurrence was observed during the mean follow-up time of 63.5 ± 19.8 months (range: 39–103 months). All 36 cases survived during the study period.

Conclusion

Conventional EMR procedure provides low chance of R0 (complete resection) achievement in gastrointestinal NETs smaller than 20 mm and limited to the mucosa or sub mucosa. However, it could be an option if patients are closely followed. Postoperative marginal involvement is not a reliable predictor of disease recurrence, which may be explained by the deleterious effect of heat coagulation and cauterization applied during tumor removal.
Optimal care for the management of older people non-weight bearing after lower limb fracture: a consensus study
Authors: Aloraibi S. , Gladman J. , Godfrey D. , Booth V. , Robinson K. , Lunt E. , Caswell A. , Kerr M. , Ollivere B. , Gordon A. L.
Published: May 2021

Background

Older people who are non-weight-bearing after a lower limb fracture are at risk of poor outcomes but there are no clinical guidelines for this group of patients. Given the paucity of the research evidence base, we conducted a consensus exercise to ascertain expert opinion about the management of this group.

Methods

A three-round e-Delphi technique was planned to use the online JISC survey tool with a multidisciplinary panel of health professionals. Panellists were invited by email via professional organisations and UK NHS Trusts. The initial statements for this study were prepared by the authors based upon the findings of their scoping review. Consensus required >/= 70% agreement with statements.

Results

Only 2 survey rounds were required. Ninety panellists, representing seven clinical disciplines, reached consensus for 24 statements about general issues (osteoporosis detection and management, falls risk reduction and nutrition) and specific non-weight bearing issues (such as the need for activity to be promoted during this period).

Conclusions

These findings can be used in the generation of a clinical guideline for this group of patients.
Association between anemia, physical performance and cognitive function in Iranian elderly people: evidence from Bushehr Elderly Health (BEH) program
Authors: Marzban Maryam , Nabipour Iraj , Farhadi Akram , Ostovar Afshin , Larijani Bagher , Darabi Amir Hossein , Shabankari Elnaz , Gholizade Mohamad
Published: May 2021

Background and objectives

The present study aimed to investigate the relation between anemia and hemoglobin (Hgb) concentration, physical performance, and cognitive function in a large sample of Iranian elderly population.

Methods

Data were collected from Bushehr elderly health (BEH) program. A total of 3000 persons aged ≥60 years were selected through multistage random sampling. Hemoglobin values lower than 12 and 13 g/dL were considered as anemia for women and men, respectively. The cognitive function was measured using the Mini-cog test and Category fluency test (CFT), and the physical function was measured using handgrip strength (muscle strength), Relative handgrip strength (RHGS), and 4.57-m usual gait speed. Univariate and adjusted multivariate logistic regression and linear regression with Stata MP (version 15) were run, and ap-value of < 0.05 was used as statistically significant for all analyses.

Results

Among participants, 7.43% were anemic, and 115 (51.57%) simultaneously had anemia and cognitive disorder. There were significant associations between red blood cell count (RBC), hemoglobin (Hgb), platelet count (PLT), and hematocrit percentage (HCT) with cognitive impairment. Additionally, Hgb concentration was significantly associated with all physical measures (Mean handgrip, Relative handgrip, and usual gait speed) and late recall (mini-cog) among the whole participants. This association remained statistically significant after considering multi-cofounders. In contrast, after stratifying the participants by gender, the association between Hgb concentration and usual gait speed was decreased in both men and women; moreover, Hgb association with cognitive measures (category fluency test and late recall) was no longer significant (allp-values > 0.05).

Conclusion

There was a cross-sectional and significant association between anemia and functional variables (e.g., Relative and mean handgrip) in Iranian elderly population, whereas Semantic memory, Late recall, and walking were more affected by gender.
Silent existence of eosinopenia in sepsis: a systematic review and meta-analysis
Authors: Lin Yao , Rong Jiabing , Zhang Zhaocai
Published: May 2021

Background

Sepsis is a life-threatening and time-critical medical emergency; therefore, the early diagnosis of sepsis is essential to timely treatment and favorable outcomes for patients susceptible to sepsis. Eosinopenia has been identified as a potential biomarker of sepsis in the past decade. However, its clinical application progress is slow and its recognition is low. Recent studies have again focused on the potential association between Eosinopenia and severe infections. This study analyzed the efficacy of Eosinopenia as a biomarker for diagnosis of sepsis and its correlation with pathophysiology of sepsis.

Method

The protocol for this meta-analysis is available in PROSPERO (CRD42020197664). We searched PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials CENTRAL databases to identify studies that met the inclusion criteria. Two authors performed data extraction independently. The pooled outcomes were calculated by TP (true positive), FP (false positive), FN (false negative), TN (true negative) by using bivariate meta-analysis model in STATA 14.0 software. Meanwhile, possible mechanisms of sepsis induced Eosinopenia was also analyzed.

Results

Seven studies were included in the present study with a total number of 3842 subjects. The incidence of Eosinopenia based on the enrolled studies varied from 23.2 to 92.7%. For diagnosis of sepsis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of Eosinopenia were 0.66 (95%CI [0.53–0.77]), 0.68 (95%CI [0.56–0.79]), 2.09 (95%CI [1.44–3.02]), 0.49 (95%CI [0.34–0.71]) and 4.23 (95%CI [2.15–8.31]), respectively. The area under the summary receiver operator characteristic curve (SROC) was 0.73 (95%CI [0.68–0.76]). Meta-regression analysis revealed that no single parameter accounted for the heterogeneity of pooled outcomes. For each subgroup of different eosinopenia cutoff values (50, 40, ≤25, 100), the sensitivity was 0.61, 0.79, 0.57, 0.54, and the specificity was 0.61, 0.75, 0.83, 0.51, respectively.

Conclusions

Our findings suggested that Eosinopenia has a high incidence in sepsis but has no superiority in comparison with conventional biomarkers for diagnosis of sepsis. However, eosinopenia can still be used in clinical diagnosis for sepsis as a simple, convenient, fast and inexpensive biomarker. Therefore, further large clinical trials are still needed to re-evaluate eosinopenia as a biomarker of sepsis.
The epigenetic regulator G9a attenuates stress-induced resistance and metabolic transcriptional programs across different stressors and species
Authors: Riahi Human , Fenckova Michaela , Goruk Kayla J. , Schenck Annette , Kramer Jamie M.
Published: May 2021

Background

Resistance and tolerance are two coexisting defense strategies for fighting infections. Resistance is mediated by signaling pathways that induce transcriptional activation of resistance factors that directly eliminate the pathogen. Tolerance refers to adaptations that limit the health impact of a given pathogen burden, without targeting the infectious agent. The key players governing immune tolerance are largely unknown. In Drosophila, the histone H3 lysine 9 (H3K9) methyltransferase G9a was shown to mediate tolerance to virus infection and oxidative stress (OS), suggesting that abiotic stresses like OS may also evoke tolerance mechanisms. In response to both virus and OS, stress resistance genes were overinduced in Drosophila G9a mutants, suggesting an intact but overactive stress response. We recently demonstrated that G9a promotes tolerance to OS by maintaining metabolic homeostasis and safeguarding energy availability, but it remained unclear if this mechanism also applies to viral infection, or is conserved in other species and stress responses. To address these questions, we analyzed publicly available datasets from Drosophila, mouse, and human in which global gene expression levels were measured in G9a-depleted conditions and controls at different time points upon stress exposure.

Results

In all investigated datasets, G9a attenuates the transcriptional stress responses that confer resistance against the encountered stressor. Comparative analysis of conserved G9a-dependent stress response genes suggests that G9a is an intimate part of the design principles of stress resistance, buffering the induction of promiscuous stress signaling pathways and stress-specific resistance factors. Importantly, we find stress-dependent downregulation of metabolic genes to also be dependent on G9a across all of the tested datasets.

Conclusions

These results suggest that G9a sets the balance between activation of resistance genes and maintaining metabolic homeostasis, thereby ensuring optimal organismal performance during exposure to diverse types of stress across different species. We therefore propose G9a as a potentially conserved master regulator underlying the widely important, yet poorly understood, concept of stress tolerance.
Extremes of age are associated with differences in the expression of selected pattern recognition receptor genes and ACE2, the receptor for SARS-CoV-2: implications for the epidemiology of COVID-19 disease
Authors: Bickler Stephen W. , Cauvi David M. , Fisch Kathleen M. , Prieto James M. , Sykes Alicia G. , Thangarajah Hariharan , Lazar David A. , Ignacio Romeo C. , Gerstmann Dale R. , Ryan Allen F. , Bickler Philip E. , De Maio Antonio
Published: May 2021

Background

Older aged adults and those with pre-existing conditions are at highest risk for severe COVID-19 associated outcomes.

Methods

Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts (GSE113957) we investigated whether age affects the expression of pattern recognition receptor (PRR) genes and ACE2, the receptor for SARS-CoV-2.

Results

Extremes of age are associated with increased expression of selected PRR genes, ACE2 and four genes that encode proteins that have been shown to interact with SAR2-CoV-2 proteins.

Conclusions

Assessment of PRR expression might provide a strategy for stratifying the risk of severe COVID-19 disease at both the individual and population levels.
Nonlinear relationship between visceral adiposity index and lung function: a population-based study
Authors: Wang Yide , Li Zheng , Li Fengsen
Published: May 2021

Background

As one of the critical indicators of obesity, the interaction between visceral fat content and lung disease is the focus of current research. However, the exact relationship between Visceral adipose index (VAI) and lung function is not fully understood. The purpose of this study was to evaluate the relationship between VAI and lung function,

Methods

Our study included all participants from the baseline survey population in Xinjiang in the Natural Population Cohort Study in Northwest China. A field survey was conducted in rural areas of Moyu County, Xinjiang, China, between 35 and 74 years old from June to December 2018. We collected standard questionnaires and completed physical examinations, visceral fat tests, and lung function measurements.

Results

The study included 2367 participants with a mean VAI of 10.35 ± 4.35, with males having a significantly higher VAI than females: 13.17 ± 3.91 vs. 7.58 ± 2.65. The piecewise linear spline models indicated a significant threshold effect between lung function and VAI in the general population and the males population, showing an inverted U-shaped curve. But there was no significant association between VAI and lung function in females. FEV1% predicted and FVC% predicted increased with the increase of VAI (β 0.76; 95% CI 0.30, 1.21) and (β 0.50; 95% CI 0.06, 0.94) in males with VAI ≤ 14, while FEV1% predicted and FVC% predicted decreased with the increase of VAI (β − 1.17; 95% CI − 1.90, − 0.45) and (β − 1.36; 95% CI − 2.08, − 0.64) in males with VAI ≥ 15.

Conclusions

The relationship between lung function and VAI in male participants showed an inverted U-shaped curve, with the turning point of VAI between 14 and 15. The association between visceral fat and lung function was more robust in males than in females.
Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli
Authors: Samaras Jasmin J. , Mauri Marta , Kay Emily J. , Wren Brendan W. , Micheletti Martina
Published: May 2021

Protein Glycan Coupling Technology (PGCT) uses purposely modified bacterial cells to produce recombinant glycoconjugate vaccines. This vaccine platform holds great potential in this context, namely due to its modular nature, the simplified production process in comparison to traditional chemical conjugation methods, and its amenability to scaled-up operations. As a result, a considerable reduction in production time and cost is expected, making PGCT-made vaccines a suitable vaccine technology for low-middle income countries, where vaccine coverage remains predominantly low and inconsistent. This work aims to develop an integrated whole-process automated platform for the screening of PGCT-made glycoconjugate vaccine candidates. The successful translation of a bench scale process for glycoconjugate production to a microscale automated setting was achieved. This was integrated with a numerical computational software that allowed hands-free operation and a platform adaptable to biological variation over the course of a production process. Platform robustness was proven with both technical and biological replicates and subsequently the platform was used to screen for the most favourable conditions for production of a pneumococcal serotype 4 vaccine candidate. This work establishes an effective automated platform that enabled the identification of the most suitable E. coli strain and genetic constructs to be used in ongoing early phase research and be further brought into preclinical trials.
Effect of plasma vitamin C levels on Parkinson’s disease and age at onset: a Mendelian randomization study
Authors: Liu Haijie , Zhang Yan , Zhang Haihua , Wang Longcai , Wang Tao , Han Zhifa , Wu Liyong , Liu Guiyou
Published: May 2021

Background

Until now, epidemiological evidence regarding the association between vitamin C intake (both diet and supplements) and Parkinson’s disease (PD) remains inconsistent. Hence, it is necessary to establish the causal link between vitamin C levels and PD, and further develop effective therapies or prevention.

Methods

We selected 11 newly identified plasma vitamin C genetic variants from a large-scale plasma vitamin C GWAS dataset (n = 52,018) as the effective instrumental variables, and extracted their corresponding GWAS summary statistics from PD (33,674 PD cases and 449,056 controls) and PD age at onset (AAO) (n = 28,568). We then performed a Mendelian randomization (MR) study to evaluate the causal association of plasma vitamin C levels with PD and PD AAO using inverse-variance weighted (IVW), the weighted median, MR-Egger, and MR-PRESSO test.

Results

We did not observe any significant association between genetically increased vitamin C levels and PD. Interestingly, we found a reduced trend of PD AAO (1.134 years) with 1 SD genetically increased vitamin C levels using IVW (beta = − 1.134, 95% CI: [− 2.515, 0.248],P = 0.108). Importantly, this trend was further successfully verified using both weighted median and MR-Egger. Each 1 SD genetically increased vitamin C levels could reduce PD AAO 1.75 and 2.592 years using weighted median (beta = − 1.750, 95% CI: [− 3.396, − 0.105],P = 0.037) and MR-Egger (beta = − 2.592, 95% CI: [− 4.623, − 0.560],P = 0.012).

Conclusions

We demonstrated the causal association between genetically increased plasma vitamin C levels and reduced PD AAO in people of European descent. Randomized controlled trials are required to clarify whether diet intake or supplement, or both could reduce the AAO of PD.
Clinical characteristics and genetic analysis of A20 haploinsufficiency
Authors: Zhang Dan , Su Gaixiu , Zhou Zhixuan , Lai Jianming
Published: May 2021

Purpose

To evaluate the clinical and genetic characteristics of 3 children with Haploinsufficiency of A20 (HA20). Methods:The clinical and genetic testing data of 3 children with HA20 treated at Capital Institute of Pediatrics (CIP) between August 2016 and October 2019 were retrospectively analysed.

Result

Patient 1 presented with arthritis and inflammatory bowel disease, patient 2 presented with axial spinal arthritis and lupus-like syndrome, and patient 3 presented with recurrent oral ulcers, gastrointestinal ulcers, and perianal abscesses. Regarding laboratory tests, patients were found to have elevated white blood cell (WBC) count, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The CRP and ESR was reported to be high in all the patients. The WBC was reported to be high in patient 1 and 3. Patient 2 was positive for antinuclear antibodies, anti-Sjögren’s syndrome antigen A, dsDNA, rheumatoid factor and Coombs test. Genetic testing showed that all three patients had heterozygous mutation in TNFAIP3 gene. As for the treatment, patient 1 was treated with TNFα antagonist, patient 2 was treated with TNF α antagonist and sulfasalazine, and patient 3 was treated with corticosteroids and thalidomide. Patients 1 and 2 were followed for four and 3 months, respectively. There was an improvement in joint and gastrointestinal symptoms; inflammatory indices and rheumatoid factor (RF) were normal, and dsDNA and Coombs test became negative. Patient 3 was treated at another hospital and showed gradual improvement in oral ulcers and perianal abscesses.

Conclusion

HA20 is a single-gene auto-inflammatory disease caused by mutation in tumour necrosis factor (TNF)-α-induced protein 3 (TNFAIP3) gene. It may present as Behçet-like syndrome and resemble various other autoimmune diseases as well. Corticosteroids and immunosuppressive agents are effective treatments, and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing should be proactively performed for children with early-age onset or Behçet-like syndrome to achieve early diagnosis and accurate treatment.
Cerebral microemboli in mini-sternotomy compared to mini- thoracotomy for aortic valve replacement: a cross sectional cohort study
Authors: Bozhinovska Marija , Jenko Matej , Stupica Gordana Taleska , Klokočovnik Tomislav , Kšela Juš , Jelenc Matija , Podbregar Matej , Fabjan Andrej , Šoštarič Maja
Published: May 2021

Background

Recently adopted mini-thoracotomy approach for surgical aortic valve replacement has shown benefits such as reduced pain and shorter recovery, compared to more conventional mini-sternotomy access. However, whether limited exposure of the heart and ascending aorta resulting from an incision in the second intercostal space may lead to increased intraoperative cerebral embolization and more prominent postoperative neurologic decline, remains inconclusive. The aim of our study was to assess potential neurological complications after two different minimal invasive surgical techniques for aortic valve replacement by measuring cerebral microembolic signal during surgery and by follow-up cognitive evaluation.

Methods

Trans-cranial Doppler was used for microembolic signal detection during aortic valve replacement performed via mini-sternotomy and mini-thoracotomy. Patients were evaluated using Addenbrooke’s Cognitive Examination Revised Test before and 30 days after surgical procedure.

Results

A total of 60 patients were recruited in the study. In 52 patients, transcranial Doppler was feasible. Of those, 25 underwent mini-sternotomy and 27 had mini-thoracotomy. There were no differences between groups with respect to sex, NYHA class distribution, Euroscore II or aortic valve area. Patients in mini-sternotomy group were younger (60.8 ± 14.4 vs.72 ± 5.84,p = 0.003), heavier (85.2 ± 12.4 vs.72.5 ± 12.9,p = 0.002) and had higher body surface area (1.98 ± 0.167 vs. 1.83 ± 0.178,p = 0.006). Surgery duration was longer in mini-sternotomy group compared to mini-thoracotomy (158 ± 24 vs. 134 ± 30 min,p < 0.001, respectively). There were no differences between groups in microembolic load, length of ICU or total hospital stay. Total microembolic signals count was correlated with cardiopulmonary bypass duration (5.64, 95%CI 0.677–10.60,p = 0.027). Addenbrooke’s Cognitive Examination Revised Test score decreased equivalently in both groups (p = 0.630) (MS: 85.2 ± 9.6 vs. 82.9 ± 11.4,p = 0.012; MT: 85.2 ± 9.6 vs. 81.3 ± 8.8,p = 0.001).

Conclusion

There is no difference in microembolic load between the groups. Total intraoperative microembolic signals count was associated with cardiopulmonary bypass duration. Age, but not micorembolic signals load, was associated with postoperative neurologic decline.

Trial registry number

clinicaltrials.gov,NCT0269778614.
The genetic basis of classical galactosaemia in Polish patients
Authors: Jezela-Stanek Aleksandra , Bauer Anna , Wertheim-Tysarowska Katarzyna , Bal Jerzy , Rygiel Agnieszka Magdalena , Sykut-Cegielska Jolanta
Published: May 2021

Classic galactosemia (OMIM #230400) is an autosomal recessive disorder caused by homozygous or compound heterozygous pathogenic variants in the galactose-1-phosphate uridylyltransferase gene (GALT; 606999) on chromosome 9p13. Its diagnosis is established by detecting elevated erythrocyte galactose-1-phosphate concentration, reduced erythrocyte galactose-1-phosphate uridylyltransferase (GALT) enzyme activity. Biallelic pathogenic variants in the GALT gene is confirmed by DNA analysis. Our paper presents molecular characteristics of 195 Polish patients diagnosed with galactosemia I, intending to expand the current knowledge of this rare disease's molecular etiology. To the best of our knowledge, the described cohort of galactosemia patients is the largest single-center cohort presented so far.
Providing trial results to participants in phase III pragmatic effectiveness RCTs: a scoping review
Authors: Bruhn Hanne , Cowan Elle-Jay , Campbell Marion K. , Constable Lynda , Cotton Seonaidh , Entwistle Vikki , Humphreys Rosemary , Innes Karen , Jayacodi Sandra , Knapp Peter , South Annabelle , Gillies Katie
Published: May 2021

Background

There is an ethical imperative to offer the results of trials to those who participated. Existing research highlights that less than a third of trials do so, despite the desire of participants to receive the results of the trials they participated in. This scoping review aimed to identify, collate, and describe the available evidence relating to any aspect of disseminating trial results to participants.

Methods

A scoping review was conducted employing a search of key databases (MEDLINE, EMBASE, PsycINFO, and the Cumulative Index to Nursing & Allied Health Literature (CINAHL) from January 2008 to August 2019) to identify studies that had explored any aspect of disseminating results to trial participants. The search strategy was based on that of a linked existing review. The evidence identified describes the characteristics of included studies using narrative description informed by analysis of relevant data using descriptive statistics.

Results

Thirty-three eligible studies, including 12,700 participants (which included patients, health care professionals, trial teams), were identified and included. Reporting of participant characteristics (age, gender, ethnicity) across the studies was poor. The majority of studies investigated dissemination of aggregate trial results. The most frequently reported mode of disseminating of results was postal. Overall, the results report that participants evaluated receipt of trial results positively, with reported benefits including improved communication, demonstration of appreciation, improved retention, and engagement in future research. However, there were also some concerns about how well the dissemination was resourced and done, worries about emotional effects on participants especially when reporting unfavourable results, and frustration about the delay between the end of the trial and receipt of results.

Conclusions

This scoping review has highlighted that few high-quality evaluative studies have been conducted that can provide evidence on the best ways to deliver results to trial participants. There have been relatively few qualitative studies that explore perspectives from diverse populations, and those that have been conducted are limited to a handful of clinical areas. The learning from these studies can be used as a platform for further research and to consider some core guiding principles of the opportunities and challenges when disseminating trial results to those who participated.
Moving online: young people and parents’ experiences of adolescent eating disorder day programme treatment during the COVID-19 pandemic
Authors: Brothwood Phillipa Louise , Baudinet Julian , Stewart Catherine S. , Simic Mima
Published: May 2021

Background

This study examined the experiences of young people and their parents who attended an intensive day treatment programme for eating disorders online during the global COVID-19 pandemic.

Methods

Online questionnaires were completed by 14 adolescents (12–18 years) and their parents (n = 19). The questionnaires included a mixture of rating questions (Likert scale) and free text responses. Free text responses were analysed using reflexive thematic analysis.

Results

Three main themes were identified: 1) New discoveries, 2) Lost in translation and 3) The best of a bad situation. This study provides insight into the benefits and pitfalls of online treatment delivery in the adolescent day programme context, which has rapidly had to become part of the everyday therapeutic practice. Results indicate that there are advantages and disadvantages to this, and that parents and young people’s views differed.

Conclusions

This study suggests that the increased accessibility provided by online working does not necessarily translate to increased connection. Given the importance of therapeutic alliance in treatment outcomes, this will be an important consideration for future developments of online intensive treatments.
Pharmacokinetic-pharmacodynamic modelling of atazanavir in hair among adolescents on antiretroviral treatment in Zimbabwe
Authors: Ngara Bernard , Zvada Simbarashe , Chawana Tariro Dianah , Nhachi Charles Fungai Brian , Rusakaniko Simbarashe
Published: May 2021

Background

Drug potency is a pharmacological parameter defining dose or concentration of drug required to obtain 50% of the drug’s maximal effect. Pharmacokinetic-pharmacodynamic modelling and simulation allows estimation of potency and evaluate strategies improving treatment outcome. The objective of our study is to determine potency of atazanavir in hair, defined as atazanavir level in hair associated with 50% probability of failing to achieve viral load below 1000 copies/ml among adolescents, and explore the effect of participant specific variables on potency.

Methods

A secondary analysis was performed on data from a previous study conducted in HIV-infected adolescents failing 2nd line ART from Harare central hospital, Zimbabwe, between 2015 and 2016. We simulated atazanavir concentrations in hair using NONMEM (version 7.3) ADVAN 13, based on a previously established pharmacokinetic model. Logistic regression methods were used for PKPD analysis. Simulations utilising PKPD model focused on estimation of potency and exploring the effect of covariates.

Results

The potency of atazanavir in hair was found to be 4.5 ng/mg hair before adjusting for covariate effects. Participants at three months follow-up, reporting adequate adherence, having normal BMI-for-age, and cared for by mature guardians had increased potency of atazanavir in hair of 2.6 ng/mg, however the follow-up event was the only statistically significant factor at 5% level.

Conclusion

Atazanavir in hair in the range 2.6 to 4.5 ng/mg is associated with above 50% probability of early viral load suppression. Adherence monitoring to adolescents with lower potency of atazanavir is recommended. The effect self-reported adherence level, BMI-for-age, and caregiver status require further evaluation.
Using tri-axial accelerometer loggers to identify spawning behaviours of large pelagic fish
Authors: Clarke Thomas M. , Whitmarsh Sasha K. , Hounslow Jenna L. , Gleiss Adrian C. , Payne Nicholas L. , Huveneers Charlie
Published: May 2021

Background

Tri-axial accelerometers have been used to remotely describe and identify in situ behaviours of a range of animals without requiring direct observations. Datasets collected from these accelerometers (i.e. acceleration, body position) are often large, requiring development of semi-automated analyses to classify behaviours. Marine fishes exhibit many “burst” behaviours with high amplitude accelerations that are difficult to interpret and differentiate. This has constrained the development of accurate automated techniques to identify different “burst” behaviours occurring naturally, where direct observations are not possible.

Methods

We trained a random forest machine learning algorithm based on 624 h of accelerometer data from six captive yellowtail kingfish during spawning periods. We identified five distinct behaviours (swim, feed, chafe, escape, and courtship), which were used to train the model based on 58 predictive variables.

Results

Overall accuracy of the model was 94%. Classification of each behavioural class was variable; F1 scores ranged from 0.48 (chafe) – 0.99 (swim). The model was subsequently applied to accelerometer data from eight free-ranging kingfish, and all behaviour classes described from captive fish were predicted by the model to occur, including 19 events of courtship behaviours ranging from 3 s to 108 min in duration.

Conclusion

Our findings provide a novel approach of applying a supervised machine learning model on free-ranging animals, which has previously been predominantly constrained to direct observations of behaviours and not predicted from an unseen dataset. Additionally, our findings identify typically ambiguous spawning and courtship behaviours of a large pelagic fish as they naturally occur.