bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study
Authors: Retornaz Frédérique , Rebaudet Stanislas , Stavris Chloé , Jammes Yves
Published: September 2022

Background

Patients with long-COVID often complain of continuous fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise. No data are available on EMG recording of evoked myopotentials (M-waves) or exercise-induced alterations in long-COVID patients, providing evidence of muscle membrane fatigue. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops in more than half of patients after an infectious disease, particularly viral diseases. A large proportion (around 70%) of these patients have neuromuscular disorders with M-wave alterations during and after exercise. Our hypothesis was that M-wave alterations would be also found in long-COVID patients, in association with neuromuscular symptoms, similar to ME/CFS.

Methods

This retrospective observational ColGEM (Covid LonG Encéphalomyelite Myalgique) study compared 59 patients with long-COVID and 55 ME/CFS patients with a history of severe infection who presented before the COVID pandemic. All of these patients underwent the same protocol consisting of a questionnaire focusing on neural and neuromuscular disorders and M-wave recording in the rectus femoris muscle before, during, and 10 min after a progressive cycling exercise. Maximal handgrip strength (MHGS) and maximal exercise power were also measured. The frequency of symptoms and magnitude of M-wave changes in the two groups were compared using non-parametric and parametric tests.

Results

The frequency of fatigue, myalgia, sleep problems, cognitive dysfunction, and post-exertional malaise as well as the magnitude of exercise-induced M-wave alterations were the same in the two groups. By contrast, digestive problems were less present in long-COVID. M-wave alterations were greater in ME/CFS patients as in those with long-COVID when the highest muscle strength and highest exercise performance were measured.

Conclusions

These high clinical and biological similarities between long-COVID and ME/CFS support the hypothesis that SARS-Cov-2 infection can cause ME/CFS symptoms.

Trial registration Registered retrospectively.
Effect of lunch with different calorie and nutrient balances on dinner-induced postprandial glucose variability
Authors: Kuwahara Mai , Kim Hyeon-Ki , Furutani Akiko , Mineshita Yui , Nakaoka Takashi , Shibata Shigenobu
Published: September 2022

Aim

This study aimed to examine the effect of lunches with different caloric contents (Study 1) and nutrient balances (Study 2) on dinner-induced postprandial glucose fluctuation.

Methods

Energy trial (Study 1): Thirteen healthy young participants (n = 10 men, n = 3 women) were investigated to determine the effects of different caloric intakes at lunch on glucose level variability. The study was comprised of four trials (no lunch, low lunch, standard lunch, and high-energy lunch). Energy balance trial (Study 2): Fourteen healthy young adults (n = 8 men, n = 6 women) were investigated to determine the effect of different nutrient balances during lunch on glucose level variability. The study consisted of four trials (standard, protein-rich, fat-rich, and carbohydrate-rich). In studies 1 and 2, each trial was spaced at least 24 full hours apart, and breakfast and dinner were tested as meals. The mealtimes for each trial were then aligned. Continuous glucose monitoring was used to assess the blood glucose fluctuations.

Results

Study 1: The no-lunch (95% CI 95.5–149.7) and low-energy lunch (95% CI 90.8–143.1) trials had significantly higher values in the incremental area under the curve (iAUC) of postprandial blood glucose at dinner compared to the standard (95% CI 55.4–90.0) and high-energy lunch (95% CI 29.3–54.6) trials (P = 0.006,P = 0.001 vs. none), (P = 0.004,P = 0.001 vs. low-energy trial). Study 2: A significantly higher postprandial blood glucose iAUC for dinner was found in the fat-rich trial (95% CI 58.5–114.0) than that in the protein-rich (95% CI 25.6–63.9) and standard (95% CI 25.6–112.4) trials, (P = 0.006,P = 0.035 vs. fat-rich trial).

Conclusions

Our findings indicate that skipping lunch and low-calorie or high-lipid intake increased postprandial blood glucose levels after dinner.
Identification of citrus diseases based on AMSR and MF-RANet
Authors: Yang Ruoli , Liao Tingjing , Zhao Peirui , Zhou Wenhua , He Mingfang , Li Liujun
Published: September 2022

Background

As one of the most widely planted fruit trees in southern China, citrus occupies an important position in the agriculture field and forestry economy in China. There are many kinds of citrus diseases. If citrus infected with diseases cannot be controlled in time, it easily seriously affects citrus production and causes large economic losses. Timely monitoring of disease characteristics in the citrus growth process is important for implementing timely control measures. Citrus images are easily disturbed by environmental factors such as dust, low light, clouds or leaf shadows. This makes it easy for some disease spot features in citrus pictures to be obscured. Occluded lesions cannot be effectively extracted and recognized. Second, similar characteristics of different diseases also make it difficult to distinguish the different types of diseases. However, the existing machine vision technology for identifying citrus diseases still has some difficulties in dealing with the above problems.

Results

This paper proposes a new citrus disease identification framework. First, a citrus image enhancement algorithm based on the MSR-AMSR algorithm is proposed, which can enhance the image and highlight the disease characteristic information. The AMSR algorithm can also greatly alleviate the interference of clouds and low light on image lesions, making the image features clearer. Second, an MF-RANet network is proposed to recognize citrus disease images. MF-RANet is composed of a main feature frame and a detail feature frame. The main feature frame uses the cross stacking structure of ResNet50 and RAM to extract the main features in the citrus image dataset. RAM is used to extract the attention weight in the feature layer, which enables RAM to give higher weight to disease features. The detailed feature frame path uses AugFPN to extract features from multiple scales and fuse the main feature frame path. AugFPN enables the network to retain more detailed features, so it can effectively distinguish similar features in different diseases. In addition, we use the ELU activation function not only to solve the problem of gradient explosion and gradient disappearance but also to effectively use the negative input of the network. Finally, we use the label smoothing regularization method to prevent overfitting the network in the classification process. Finally, the experimental results show that the highest detection accuracy of the network for Huanglong disease, Corynespora blight of citrus, fat spot macular disease, citrus scab, citrus canker and healthy citrus is 96.77%, 96.22%, 95.96%, 95.93%, 94.04% and 97.55%, respectively.

Conclusions

The citrus disease algorithm based on AMSR and MF-RANet can effectively perform the disease detection function. It has a high recognition rate for different kinds of citrus diseases. With the addition of AMSR preprocessing, RAM, AugFPN, ELU activation function and other structures, the MF-RANet network performance improves.
Accelerating effect of Shilajit on osteogenic property of adipose-derived mesenchymal stem cells (ASCs)
Authors: Kangari Parisa , Roshangar Leila , Iraji Aida , Talaei-Khozani Tahereh , Razmkhah Mahboobeh
Published: September 2022

Background

Shilajit has been widely used remedy for treating a numerous of illness such as bone defects in Iran traditional folk medicine since hundreds of years ago. The aim of the present study was to explore the effect of Shilajit on the osteogenic differentiation of human adipose-derived mesenchymal stem cells (ASCs) in two- (2D) and three-dimensional (3D) cultures.

Materials and methods

ASCs were seeded in 3D 1% alginate (Alg) hydrogel with or without Shilajit (500 µg/mL) and compared with 2D cultures. Then, characterization was done using electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDX), alkaline phosphatase (ALP) activity, alizarin red staining and Raman confocal microscopy.

Results

Adding Shilajit had no impact on the Alg scaffold degradability. In the 3D hydrogel and in the presence of osteogenic medium (OM), Shilajit acted as enhancer to increase ALP activity and also showed osteoinductive property in the absence of OM compared to the 2D matched groups at all time points (days 7 and 21 both P = 0.0006, for 14 days P = 0.0006 and P = 0.002, respectively). In addition, calcium deposition was significantly increased in the cultures exposed to Shilajit compared to 2D matched groups on days 14 (P < 0.0001) and 21 (P = 0.0003 and P = 0.003, respectively). In both 3D and 2D conditions, Shilajit induced osteogenic differentiation, but Shilajit/Alg combination starts osteogenic differentiation in a short period of time.

Conclusion

As Shilajit accelerates the differentiation of ASCs into the osteoblasts, without changing the physical properties of the Alg hydrogel, this combination may pave the way for more promising remedies considering bone defects.
Application of dual-trajectory screws in revision surgery for lumbar adjacent segment disease: a finite element study
Authors: Wu Jincheng , Yang Dongmei , Han Ye , Xu Hanpeng , Wen Wangqiang , Xu Haoxiang , Li Kepeng , Liu Yong , Miao Jun
Published: September 2022

Background

Advancements in medicine and the popularity of lumbar fusion surgery have made lumbar adjacent segment disease (ASDz) increasingly common, but there is no mature plan for guiding its surgical treatment. Therefore, in this study, four different finite element (FE) ASDz models were designed and their biomechanical characteristics were analysed to provide a theoretical basis for clinical workers to choose the most appropriate revision scheme for ASDz.

Methods

According to whether internal fixation was retained, different FE models were created to simulate ASDz revision surgery, and flexion, extension, axial rotation and lateral bending were simulated by loading. The biomechanical characteristics of the adjacent segments of the intervertebral disc and the internal fixation system and the range of motion (ROM) of the lumbar vertebrae were analysed.

Results

The difference in the ROM of the fixed segment between FE models that did or did not retain the original internal fixation was less than 0.1°, and the difference was not significant. However, the stress of the screw–rod system when the original internal fixation was retained and prolonged fixation was performed with dual-trajectory screws was less than that when the original internal fixation was removed and prolonged fixation was performed with a long bar. Especially in axial rotation, the difference between models A and B is the largest, and the difference in peak stress reached 30 MPa. However, for the ASDz revision surgery segment, the endplate stress between the two models was the lowest, and the intradiscal pressure (IDP) of the adjacent segment was not significantly different between different models.

Conclusion

Although ASDz revision surgery by retaining the original internal fixation and prolonging fixation with dual-trajectory screws led to an increase in stress in the fusion segment endplate, it provides stability similar to ASDz revision surgery by removing the original internal fixation and prolonging fixation with a long bar and does not lead to a significant change in the IDP of the adjacent segment while avoiding a greater risk of rod fracture.
Machine Learning Algorithms for understanding the determinants of under-five Mortality
Authors: Saroj Rakesh Kumar , Yadav Pawan Kumar , Singh Rajneesh , Chilyabanyama Obvious.N.
Published: September 2022

Background

Under-five mortality is a matter of serious concern for child health as well as the social development of any country. The paper aimed to find the accuracy of machine learning models in predicting under-five mortality and identify the most significant factors associated with under-five mortality.

Method

The data was taken from the National Family Health Survey (NFHS-IV) of Uttar Pradesh. First, we used multivariate logistic regression due to its capability for predicting the important factors, then we used machine learning techniques such as decision tree, random forest, Naïve Bayes, K- nearest neighbor (KNN), logistic regression, support vector machine (SVM), neural network, and ridge classifier. Each model’s accuracy was checked by a confusion matrix, accuracy, precision, recall, F1 score, Cohen’s Kappa, and area under the receiver operating characteristics curve (AUROC). Information gain rank was used to find the important factors for under-five mortality. Data analysis was performed using, STATA-16.0, Python 3.3, and IBM SPSS Statistics for Windows, Version 27.0 software.

Result

By applying the machine learning models, results showed that the neural network model was the best predictive model for under-five mortality when compared with other predictive models, with model accuracy of (95.29% to 95.96%), recall (71.51% to 81.03%), precision (36.64% to 51.83%), F1 score (50.46% to 62.68%), Cohen’s Kappa value (0.48 to 0.60), AUROC range (93.51% to 96.22%) and precision-recall curve range (99.52% to 99.73%). The neural network was the most efficient model, but logistic regression also shows well for predicting under-five mortality with accuracy (94% to 95%)., AUROC range (93.4% to 94.8%), and precision-recall curve (99.5% to 99.6%). The number of living children, survival time, wealth index, child size at birth, birth in the last five years, the total number of children ever born, mother’s education level, and birth order were identified as important factors influencing under-five mortality.

Conclusion

The neural network model was a better predictive model compared to other machine learning models in predicting under-five mortality, but logistic regression analysis also shows good results. These models may be helpful for the analysis of high-dimensional data for health research.
Wild-type IDH1 inhibition enhances chemotherapy response in melanoma
Authors: Zarei Mehrdad , Hajihassani Omid , Hue Jonathan J. , Graor Hallie J. , Loftus Alexander W. , Rathore Moeez , Vaziri-Gohar Ali , Asara John M. , Winter Jordan M. , Rothermel Luke D.
Published: September 2022

Background

Alternative treatment strategies in melanoma beyond immunotherapy and mutation-targeted therapy are urgently needed. Wild-type isocitrate dehydrogenase 1 (wtIDH1) has recently been implicated as a metabolic dependency in cancer. The enzyme protects cancer cells under metabolic stress, including nutrient limited conditions in the tumor microenvironment. Specifically, IDH1 generates NADPH to maintain redox homeostasis and produces α-ketoglutarate to support mitochondrial function through anaplerosis. Herein, the role of wtIDH1 in melanoma is further explored.

Methods

The expression of wtIDH1 was determined by qRT-PCR, and Western blot in melanoma cell lines and the effect of wtIDH1 on metabolic reprogramming in melanoma was interrogated by LC-MS. The impact of wtIDH1 inhibition alone and in combination with chemotherapy was determined in cell culture and mouse melanoma models.

Results

Melanoma patients express higher levels of the wtIDH1 enzyme compared to normal skin tissue, and elevated wtIDH1 expression portends poor patient survival. Knockdown of IDH1 by RNA interference inhibited cell proliferation and migration under low nutrient levels. Suppression of IDH1 expression in melanoma also decreased NADPH and glutathione levels, resulting in increased reactive oxygen species. An FDA-approved inhibitor of mutant IDH1, ivosidenib (AG-120), exhibited potent anti-wtIDH1 properties under low magnesium and nutrient levels, reflective of the tumor microenvironment in natura. Thus, similar findings were replicated in murine models of melanoma. In light of the impact of wtIDH1 inhibition on oxidative stress, enzyme blockade was synergistic with conventional anti-melanoma chemotherapy in pre-clinical models.

Conclusions

These results demonstrate the clinical potential of wtIDH1 inhibition as a novel and readily available combination treatment strategy for patients with advanced and refractory melanoma.

Graphical Abstract

Schematic shows increased wild-type IDH1 expression and activity as an adaptive response to metabolic stress induced by chemotherapy.
Differences in characteristics between patients ≥ 65 and < 65 years of age with orthopaedic injuries after severe trauma
Authors: Slørdal Tora Julie , Brattebø Guttorm , Geisner Thomas , Kristoffersen Målfrid Holen
Published: September 2022

Aim

Many trauma patients have associated orthopaedic injuries at admission. The existing literature regarding orthopaedic trauma often focuses on single injuries, but there is a paucity of information that gives an overview of this group of patients. Our aim was to describe the differences in characteristics between polytrauma patients ≥ 65 and < 65 years of age suffering orthopaedic injuries.

Methods

Patients registered in the Norwegian Trauma Registry (NTR) with an injury severity score (ISS) > 15 and orthopaedic injuries, who were admitted to Haukeland University Hospital in 2016–2018, were included. Data retrieved from the patients’ hospital records and NTR were analysed. The patients were divided into two groups based on age.

Results

The study comprised 175 patients, of which 128 (73%) and 47 (27%) were aged < 65 (Group 1) and ≥ 65 years (Group 2), respectively. The ISS and the new injury severity score (NISS) were similar in both groups. The dominating injury mechanism was traffic-related and thoracic injury was the most common location of main injury in both groups. The groups suffered a similar number of orthopaedic injuries. A significantly higher proportion of Group 1 underwent operative treatment for their orthopaedic injuries than in Group 2 (74% vs. 53%). The mortality in Group 2 was significantly higher than that in Group 1 (15% vs. 3%). In Group 2 most deaths were related to traffic injuries (71%). High energy falls and traffic-related incidents caused the same number of deaths in Group 1. In Group 1 abdominal injuries resulted in most deaths, while head injuries was the primary reason for deaths in Group 2.

Conclusions

Although the ISS and NISS were similar, mortality was significantly higher among patients aged ≥ 65 years compared to patients < 65 years of age. The younger age group underwent more frequently surgery for orthopaedic injuries than the elderly. There may be multiple reasons for this difference, but our study does not have sufficient data to draw any conclusions. Future studies may provide a deeper understanding of what causes treatment variation between age groups, which would hopefully help to further develop strategies to improve outcome for the elderly polytrauma patient.
The impact of interactive book sharing on child cognitive and socio-cognitive development (the REaL trial): study protocol for a randomized controlled trial
Authors: Forssman Linda , Gottwald Janna M.
Published: September 2022

Background

The quality of children’s early home learning environment has an influence on their cognitive development, preliteracy skills, and subsequent educational outcomes. Early intervention programs that promote positive parenting behaviors and child cognition have great potential to positively influence children’s school readiness and thereby support social equality. One often advocated parental practice for promoting child language and cognition is interactive book sharing.

Methods

We have conducted a randomized controlled trial to evaluate the effects of a parent-child interactive book sharing intervention on early child language, cognition, and parental behaviors. Participating caregivers and their 10-month-old child were randomized to an interactive book sharing intervention group (n = 59) or to an active control group (n = 56). The intervention was delivered by a facilitator to small groups of parent-child dyads on a weekly basis over 5 weeks. The primary outcomes were child language and socio-cognition; secondary outcomes were child executive function and parental scaffolding, sensitivity and reciprocity during book sharing, and problem-solving tasks. Data were collected at baseline, post-intervention, and at 6 and 12 months post-intervention.

Discussion

The Roadmap to Executive function and Language (REaL) trial aims to evaluate the impact of a brief early parenting intervention on key factors for child development, including child cognition and parental behaviors. If this intervention is beneficial for child outcomes, that would be of significance for the development of early interventions to promote child development.

Trial registration

The REaL trial is registered on the International Standard Randomized Controlled Trial Number database, registration number ISRCTN22319305. Retrospectively registered on 7 February 2020.
A novel 2B4 receptor leads to worse pregnancy outcomes by facilitating TNF-α and IFN-γ production in dNK cells during Toxoplasma gondii infection
Authors: Xu Xiaoyan , Zheng Guangmei , Ren Yushan , He Xiaohua , Peng Biwen , Hu Xuemei , Liu Wanhong
Published: September 2022

Background

Infections are a major threat to human reproductive health because they can induce pregnancy failure, including recurrent abortion, stillbirth, and preterm birth.Toxoplasma gondii(T. gondii) infection can result in adverse pregnancy outcomes by affecting certain immune molecules and cytokines. However, the detailed mechanisms behindT. gondii-induced pregnancy failure are poorly understood.

Methods

Toxoplasma gondii-infected wild-type (WT) pregnant mice and 2B4 knockout (2B4−/−) pregnant mice were established for in vivo study. Human decidual natural killer (dNK) cells were cultured for in vitro study. Abnormal pregnancy outcomes were observed, and the expression of 2B4, functional molecules (CD69, CD107a, tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ]), and signaling molecules (SHP-2, Fyn, p-ERK, p-P38) in dNK cells were detected by flow cytometry, Western blot, reverse transcriptase polymerase chain reaction (RT-PCR), and/or immunofluorescence. The direct interactions (2B4 interacts with SHP-2 and Fyn; SHP-2 interacts with p-P38 and 2B4; Fyn interacts with p-ERK and 2B4) were verified by co-immunoprecipitation (co-IP) in NK-92 cells.

Results

Here, results showed that 2B4 was significantly downregulated afterT. gondiiinfection. Subsequently, infected 2B4−/−pregnant mice displayed worse pregnancy outcomes compared with infected WT pregnant mice. Also, increased TNF-α and IFN-γ expression and elevated dNK cell cytotoxicity were found in 2B4−/−pregnant mice duringT. gondiiinfection. In contrast, reduced TNF-α and IFN-γ expression and decreased human dNK cell activity were found following 2B4 activation duringT. gondiiinfection. Interestingly, results showed that 2B4 binds to adaptor SHP-2 or Fyn, which then triggers different signaling pathways to regulate TNF-α and IFN-γ expression in dNK cells duringT. gondiiinfection. Further, SHP-2 binds 2B4 and p-P38 directly after 2B4 activation, which generates an inhibitory signal for TNF-α and IFN-γ in NK-92 cells. In addition, Fyn can bind to 2B4 and p-ERK after activation of 2B4, thereby inhibiting TNF-α and IFN-γ expression in NK-92 cells followingT. gondiiinfection.

Conclusions

These data suggest that 2B4 may be a novel danger-signaling molecule that is implicated in pregnancy failure duringT. gondiiinfection. Unraveling the mechanism by which 2B4 regulates dNK cell activity will provide novel insights to aid our understanding ofT. gondii-induced adverse pregnancy outcomes.

Graphical Abstract
Single-cell RNA transcriptome analysis of CNS immune cells reveals CXCL16/CXCR6 as maintenance factors for tissue-resident T cells that drive synapse elimination
Authors: Rosen Sarah F. , Soung Allison L. , Yang Wei , Ai Shenjian , Kanmogne Marlene , Davé Veronica A. , Artyomov Maxim , Magee Jeffrey A. , Klein Robyn S.
Published: September 2022

Background

Emerging RNA viruses that target the central nervous system (CNS) lead to cognitive sequelae in survivors. Studies in humans and mice infected with West Nile virus (WNV), a re-emerging RNA virus associated with learning and memory deficits, revealed microglial-mediated synapse elimination within the hippocampus. Moreover, CNS-resident memory T (TRM) cells activate microglia, limiting synapse recovery and inducing spatial learning defects in WNV-recovered mice. The signals involved in T cell-microglia interactions are unknown.

Methods

Here, we examined immune cells within the murine WNV-recovered forebrain using single-cell RNA sequencing to identify putative ligand-receptor pairs involved in intercellular communication between T cells and microglia. Clustering and differential gene analyses were followed by protein validation and genetic and antibody-based approaches utilizing an established murine model of WNV recovery in which microglia and complement promote ongoing hippocampal synaptic loss.

Results

Profiling of host transcriptome immune cells at 25 days post-infection in mice revealed a shift in forebrain homeostatic microglia to activated subpopulations with transcriptional signatures that have previously been observed in studies of neurodegenerative diseases. Importantly, CXCL16/CXCR6, a chemokine signaling pathway involved in TRM cell biology, was identified as critically regulating CXCR6 expressing CD8+ TRM cell numbers within the WNV-recovered forebrain. We demonstrate that CXCL16 is highly expressed by all myeloid cells, and its unique receptor, CXCR6, is highly expressed on all CD8+ T cells. Using genetic and pharmacological approaches, we demonstrate that CXCL16/CXCR6 not only is required for the maintenance of WNV-specific CD8 TRM cells in the post-infectious CNS, but also contributes to their expression of TRM cell markers. Moreover, CXCR6+CD8+ T cells are required for glial activation and ongoing synapse elimination.

Conclusions

We provide a comprehensive assessment of the role of CXCL16/CXCR6 as an interaction link between microglia and CD8+ T cells that maintains forebrain TRM cells, microglial and astrocyte activation, and ongoing synapse elimination in virally recovered animals. We also show that therapeutic targeting of CXCL16 in mice during recovery may reduce CNS CD8+ TRM cells.
Reduced gut microbiota diversity in patients with congenital generalized lipodystrophy
Authors: Montenegro Junior Renan Magalhães , Ponte Clarisse Mourão Melo , Castelo Maria Helane Costa Gurgel , de Oliveira Silveira Alessandro Conrado , Fernandes Virgínia Oliveira , D’Alva Catarina Brasil , Oliveira Luiz Felipe Valter , Hristov Angélica Domingues , Bandeira Silviane Praciano , da Cruz Paiva Grayce Ellen , Levi José Eduardo
Published: September 2022

Background

Previous studies suggest intestinal dysbiosis is associated with metabolic diseases. However, the causal relationship between them is not fully elucidated. Gut microbiota evaluation of patients with congenital generalized lipodystrophy (CGL), a disease characterized by the absence of subcutaneous adipose tissue, insulin resistance, and diabetes since the first years of life, could provide insights into these relationships.

Methods

A cross-sectional study was conducted with patients with CGL (n = 17) and healthy individuals (n = 17). The gut microbiome study was performed by sequencing the 16S rRNA gene through High-Throughput Sequencing (BiomeHub Biotechnologies, Brazil).

Results

The median age was 20.0 years old, and 64.7% were female. There was no difference between groups in pubertal stage, BMI, ethnicity, origin (rural or urban), delivery, breastfeeding, caloric intake, macronutrient, or fiber consumption. Lipodystrophic patients presented a lower alpha diversity (Richness index: 54.0 versus 67.5; p = 0.008). No differences were observed in the diversity parameters when analyzing the presence of diabetes, its complications, or the CGL subtype.

Conclusion

In this study, we demonstrate for the first time a reduced gut microbiota diversity in individuals with CGL. Dysbiosis was present despite dietary treatment and was also observed in young patients. Our findings allow us to speculate that the loss of intestinal microbiota diversity may be due to metabolic abnormalities present since the first years of life in CGL. Longitudinal studies are needed to confirm these findings, clarifying the possible causal link between dysbiosis and insulin resistance in humans.
The failure of success: four lessons learned in five years of research on research integrity and research assessments
Authors: Aubert Bonn Noémie , De Vries Raymond G. , Pinxten Wim
Published: September 2022

In the past 5 years, we captured the perspectives from a broad array of research stakeholders to better understand the impact that current approaches to success and research assessment may have on the integrity and the quality of research. Here, we translate our findings in four actions that are urgently needed to foster better research. First, we need to address core research structures to overcome systemic problems of the research enterprise; second, we must realign research assessments to value elements that advance and strengthen science; third, we need to remodel, diversify, and secure research careers; and finally, we need to unite and coordinate efforts for change.
Does shift-and-persist strategy buffer career choice anxiety and affect career exploration?
Authors: Lee Sumin , Kobayashi Ryota , Oda Mami , Noritake Yoshihide , Nakashima Ken’ichiro
Published: September 2022

Objective

The transition from school to the workforce is important for concrete future planning. During this period, people are more likely to experience psychological health problems, such as anxiety and feelings of hopelessness and helplessness. In particular, job hunting in individuals with low socioeconomic status (SES) leads to various impulsive behaviors and physical and psychological problems due to a scarcity of economic and time resources. There is a lack of research examining career education and intervention approaches that consider the backgrounds of those experiencing adversities and difficulties due to low SES. Considering these situations, we examined whether shift-and-persist coping strategies (S-P) could buffer the career choice anxiety of individuals with low SES and improve career exploration.

Results

The results from 311 students who preparing/doing for job hunting showed a negative association between S-P and career choice anxiety and a positive association with career exploration. There are no significant effects of the direct link between SES to career exploration and the indirect link between SES and career exploration via career choice anxiety. There was also no buffering effect of S-P use on the above mediating process.
Atypical gaze patterns in autistic adults are heterogeneous across but reliable within individuals
Authors: Keles Umit , Kliemann Dorit , Byrge Lisa , Saarimäki Heini , Paul Lynn K. , Kennedy Daniel P. , Adolphs Ralph
Published: September 2022

Background

Across behavioral studies, autistic individuals show greater variability than typically developing individuals. However, it remains unknown to what extent this variability arises from heterogeneity across individuals, or from unreliability within individuals. Here, we focus on eye tracking, which provides rich dependent measures that have been used extensively in studies of autism. Autistic individuals have an atypical gaze onto both static visual images and dynamic videos that could be leveraged for diagnostic purposes if the above open question could be addressed.

Methods

We tested three competing hypotheses: (1) that gaze patterns of autistic individuals are less reliable or noisier than those of controls, (2) that atypical gaze patterns are individually reliable but heterogeneous across autistic individuals, or (3) that atypical gaze patterns are individually reliable and also homogeneous among autistic individuals. We collected desktop-based eye tracking data from two different full-length television sitcom episodes, at two independent sites (Caltech and Indiana University), in a total of over 150 adult participants (N = 48 autistic individuals with IQ in the normal range, 105 controls) and quantified gaze onto features of the videos using automated computer vision-based feature extraction.

Results

We found support for the second of these hypotheses. Autistic people and controls showed equivalently reliable gaze onto specific features of videos, such as faces, so much so that individuals could be identified significantly above chance using a fingerprinting approach from video epochs as short as 2 min. However, classification of participants into diagnostic groups based on their eye tracking data failed to produce clear group classifications, due to heterogeneity in the autistic group.

Limitations

Three limitations are the relatively small sample size, assessment across only two videos (from the same television series), and the absence of other dependent measures (e.g., neuroimaging or genetics) that might have revealed individual-level variability that was not evident with eye tracking. Future studies should expand to larger samples across longer longitudinal epochs, an aim that is now becoming feasible with Internet- and phone-based eye tracking.

Conclusions

These findings pave the way for the investigation of autism subtypes, and for elucidating the specific visual features that best discriminate gaze patterns—directions that will also combine with and inform neuroimaging and genetic studies of this complex disorder.
The SP-ET index is a new index for assessing the vertical position of patella
Authors: Li Jia , Yuan Mao , Qiu Lanyu , Sheng Bo , Yu Fan , Yang Haitao , Lv Furong , Lv Fajin , Huang Wei
Published: September 2022

Background

Some parameters in previous studies did not better reflect the vertical position of the patella relative to the femoral trochlear. This study aimed to assess the value of the most superior point of patella-entrance of femoral trochlea distance ratio (SP-ET index) as a newer index in defining the vertical position of patella relative to the trochlea, correlate it with the Insall–Salvati ratio, and investigate the effect of the new index on patellar cartilage lesions.

Methods

A total of 99 knees of 77 patients with patellar cartilage lesions were retrospectively analyzed using magnetic resonance imaging (MRI) data. The Insall–Salvati ratio and SP-ET index were measured on MR images. Ninety-nine knees just with meniscus rupture were enrolled as the control group. The two parameters of the patellar cartilage lesions were compared with those of the control group.

Results

The Insall–Salvati ratio and SP-ET index in the patellar cartilage lesions group were significantly higher than those in the control group (p < 0.001). The SP-ET index showed a moderate positive correlation with the Insall–Salvati ratio (r = 0.307, p < 0.001). Receiver operating characteristic (ROC) analysis showed that the diagnostic efficiency of the SP-ET index was better than that of the Insall–Salvati ratio in patients with patellar cartilage lesions.

Conclusion

The SP-ET index may be a useful complement parameter to define the vertical position of the patella relative to the femoral trochlear. Increased SP-ET index may be an important risk factor for patellar cartilage lesions.
Renal imaging at 5 T versus 3 T: a comparison study
Authors: Zheng Liyun , Yang Chun , Sheng Ruofan , Dai Yongming , Zeng Mengsu
Published: September 2022

Background

Recently, a whole-body 5 T MRI scanner was developed to open the door of abdominal imaging at high-field strength. This prospective study aimed to evaluate the feasibility of renal imaging at 5 T and compare the image quality, potential artifacts, and contrast ratios with 3 T.

Methods

Forty healthy volunteers underwent MRI examination both at 3 T and 5 T. MRI sequences included T1-weighted gradient-echo (GRE), T2-weighted fast spin echo, diffusion-weighted imaging, and multi-echo GRE T2* mapping. Image quality and presence of artifacts were assessed for all sequences using four-point scales. For anatomical imaging, the signal-to-noise ratio (SNR) and contrast ratio (CR) of abdomen organ tissues were calculated. Besides, for functional imaging, the contrast-to-noise ratio of cortex/medulla was calculated. Wilcoxon signed rank-sum test was used to compare the visual evaluation scores and quantitative measurements between 3 and 5 T images.

Results

Compared to 3 T examination, T1-weighted sequence at 5 T showed significantly better image quality with higher conspicuity of the renal veins and arteries, and comparable artifacts. Image quality was comparable between both field strengths on T2-weighted images, whereas a significantly higher level of artifacts was observed at 5 T. Besides, 5 T MRI contributed to higher SNR and CR for abdomen organ tissues. For functional imaging, 5 T MRI showed improved corticomedullar discrimination. There was no significant difference between apparent diffusion coefficient of renal at 3 T and 5 T, while 5 T MRI resulted in significantly shorter T2* values in both cortex and medulla.

Conclusions

5 T MRI provides anatomical and functional images of the kidney with sufficient image quality.
Feasibility study of three-dimensional printing knee model using the ultra-low-dose CT scan for preoperative planning and simulated surgery
Authors: Zhang Meng , Lei Ming , Zhang Jie , Li Hongyi , Lin Fenghuan , Chen Yanxia , Chen Jun , Xiao Mengqiang
Published: September 2022

Objective

To explore the feasibility of the three-dimensional printing (3DP) knee model using the ultra-low-dose computed tomography (CT) scan for preoperative planning and simulated surgery.

Methods

Thirty-six patients were divided into the standard-dose protocol group (A) and ultra-low-dose protocol group (B). The anteroposterior diameter, left and right diameter of femur, anteroposterior diameter of tibial plateau (APTP), left and right diameter, distance from the intercondylar ridge to tibial tuberosity, lower femur angle, and upper tibial angle were measured on CT images. On the 3D printed knee joint model, Vernier calipers were used to measure: anteroposterior diameter, left and right diameter of the internal and external condyles of femur; left and right diameters, anteroposterior diameters of tibial plateau; upper and lower meridian, left and right diameters of patella.

Results

With group A as reference, the effective radiation dose in group B was significantly reduced to 97.0% (36.4 ± 3.7 uSv and 1.1 ± 0.2 uSv, respectively). There was no difference in objective parameters for 3DP model (p = 0.31–0.84). None of the quantitative parameters of image quality showed significant difference (p = 0.11–0.96). Despite lower score of image quality and 3DP model in group B (3.0 ± 0.0 vs. 2.1 ± 0.2, 2.9 ± 0.3 vs. 2.2 ± 0.4; p < 0.05), the diagnostic performance was consistent in the two groups (all scores ≥ 2). Image quality and 3DP printed models were highly consistent (k = 0.97).

Conclusions

Ultra-low-dose protocol reduces the radiation dose while maintaining the image quality of knee. It meets the requirement for 3DP model, internal fixation model selection, and simulated surgery.
Radiomics analysis of the optic nerve for detecting dysthyroid optic neuropathy, based on water-fat imaging
Authors: Wu Hongyu , Luo Ban , Zhao Yali , Yuan Gang , Wang Qiuxia , Liu Ping , Zhai Linhan , Lv Wenzhi , Zhang Jing
Published: September 2022

Objective

Detecting dysthyroid optic neuropathy (DON) in the early stages is vital for clinical decision-making. The aim of this study was to determine the feasibility of using an optic-nerve-based radiomics nomogram on water-fat imaging for detecting DON.

Methods

This study included 104 orbits (83 in the training cohort) from 59 DON patients and 131 orbits (80 in the training cohort) from 69 thyroid-associated ophthalmopathy (TAO) without DON patients. Radiomic features were extracted from the optic-nerve T2-weighted water-fat images for each patient. Selected radiomics features were retrained to construct the radiomic signature model and calculate the radiomic score (Rad-score). The conventional MRI evaluation model was constructed based on apical crowding sign, optic-nerve stretching sign and muscle index. The radiomics nomogram model combining the Rad-score and conventional MRI evaluation factors was then developed. Predictive performance of the three models was assessed using ROC curves.

Results

Eight radiomics features from water-fat imaging were selected to build the radiomics signature. The radiomics nomogram (based on Rad-score, apical crowding sign and optic-nerve stretching sign) had superior diagnostic performance than did the conventional MRI evaluation model (AUC in the training set: 0.92 vs 0.80, the validation set:0.88 vs 0.75). Decision curve analysis confirmed the clinical usefulness of the radiomics nomogram.

Conclusions

This optic-nerve-based radiomics nomogram showed better diagnostic performance than conventional MRI evaluation for differentiating DON from TAO without DON. The changes of the optic-nerve itself may deserve more consideration in the clinical decision-making process.
The relationship between perianal fistula activity and abdominal adipose tissue in Crohn’s disease: an observational study
Authors: Xiong Ziman , Zhou Ziling , Hao Luwen , Li Yuanqiu , Hu Xuemei , Hu Daoyu , Luo Yan , Wang Yanchun , Shen Yaqi , Li Zhen
Published: September 2022

Objective

The aim of this study was to analyze the relationship between abdominal adipose tissue and perianal fistula activity in patients with Crohn's disease (CD) using cross-sectional imaging.

Methods

Patients with perianal fistulizing CD who underwent pelvic magnetic resonance imaging (MRI) and abdominal computed tomography (CT) were retrospectively enrolled. We scored the fistulas in each patient's MRI images based on Van Assche's classification. The area and density of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) (at the third, fourth, and fifth lumbar (L3, L4, and L5) levels were measured by averaging five slices of measurements at each vertebral level in CT images, and areas were further standardized by the lumbar height2 (heightL1-5). The VAT/SAT ratio (VSR) and VAT/Total adipose tissue (VA/TA) index were calculated. Based on MRI scores, patients were divided into two groups with low and high activity, and their clinical, MRI features, and CT parameters were compared. We evaluated patients with follow-up MRI and compared the differences in clinical and radiological indicators among patients with different outcomes.

Results

Overall, 136 patients were included, 77 in the low-activity group and 59 in the high-activity group. Patients in the high activity group had lower subcutaneous adipose index (all levels, p < 0.05) and visceral adipose index (L3 level, p < 0.01), but higher SAT and VAT density (all levels, p < 0.01), VSR (L5 level, p = 0.07) and VA/TA index (L5 level, p < 0.05).

Conclusion

There were differences in adipose tissue composition among CD patients with different active perianal fistulas.
Priming mesenchymal stem cells with α-synuclein enhances neuroprotective properties through induction of autophagy in Parkinsonian models
Authors: Shin Jin Young , Kim Dong-Yeol , Lee Jieun , Shin Yu Jin , Kim Yi Seul , Lee Phil Hyu
Published: September 2022

Background

Mesenchymal stem cells (MSCs) may be one of candidates for disease-modifying therapy in Parkinsonian diseases. As knowledge regarding the therapeutic properties of MSCs accumulates, some obstacles still remain to be overcome, especially, successful clinical translation requires the development of culture systems that mimic the natural MSC niche, while allowing clinical-scale cell expansion without compromising quality and function of the cells. In recent years, priming approaches using bioactive peptide or complement components have been investigated to enhance the therapeutic potential of MSCs.

Methods

We investigated an innovative priming strategy by conditioning the MSCs with α-synuclein (α-syn). To induce priming, MSCs were treated with different concentrations of α-syn and various time course. We evaluated whether α-syn enhances stemness properties of MSCs and priming MSCs with α-syn would modulate autophagy-related gene expression profiles.

Results

Treatment of naïve MSCs with α-syn upregulated transcriptional factors responsible for regulation of stemness, which was associated with the elevated expression of genes involved in glycolysis and cell re-programming. Primed MSCs with α-syn enhanced the expression of autophagy-regulating miRNA, and exosomes derived from primed MSCs were packed with autophagy-associated miRNA. In α-syn-overexpressing neuronal cells, primed MSCs with α-syn enhanced neuronal viability relative to naïve MSCs, through the induction of autophagy and lysosome activity. Animal study using an α-syn-overexpressing mice showed that the pro-survival effect of MSCs on dopaminergic neurons was more prominent in primed MSC-treated mice compared with that in naïve MSC-treated mice.

Conclusions

The present data suggest that MSC priming with α-syn exerts neuroprotective effects through augmented stemness and possibly the enhancement of autophagy-mediated α-syn modulation in Parkinsonian models.
Unrelated umbilical cord blood can improve the prognosis of haploidentical hematopoietic stem cell transplantation
Authors: Yang Ying , Zhang Ming , Li Mengqi , Li Yingchun , Yang Wei , Liu Zhuogang , Wang Hongtao
Published: September 2022

Background

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is widely used as a curative treatment strategy for most types of hematological diseases. However, strategies for enhancing the graft versus leukemia (GVL) effect without aggravating the graft versus host disease (GVHD) effect are still being pursued.

Methods

A retrospective cohort study was performed to compare the outcomes between combined unrelated umbilical cord blood (UCB-haplo HSCT) and haplo HSCT.

Results

The results showed that neither acute GVHD (aGVHD) nor chronic GVHD (cGVHD) was increased in the UCB-haplo HSCT group, and the engraftment and infection rates were similar between the two groups. However, overall survival and progression-free survival were significantly improved, while transplantation-related mortality and relapse were significantly decreased in the UCB-haplo HSCT group by both univariate and multivariate analyses.

Conclusion

Our results indicated that the addition of a UCB unit could improve the prognosis of haplo-HSCT and enhance the GVL effect without increasing the incidence of GVHD.

Trial registration

The cohort study was retrospectively registered at https://www.chictr.org.cn as ChiCTR2100046681.