bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: mRNA vaccination-mediated STAT3 overactivation with agranulocytosis and clonal T-LGL expansion
Authors: Hirsiger Julia R. , Tzankov Alexandar , Alborelli Ilaria , Recher Mike , Daikeler Thomas , Parmentier Stefani , Berger Christoph T.
Published: February 2023

Vaccines against SARS-CoV-2 are the most effective measure against the COVID-19 pandemic. The safety profile of mRNA vaccines in patients with rare diseases has not been assessed systematically in the clinical trials, as these patients were typically excluded. This report describes the occurrence of agranulocytosis within days following the first dose of an mRNA-1273 vaccination against COVID-19 in a previously healthy older adult. The patient was diagnosed with a suspected STAT3 wild-type T-cell large granular lymphocytic leukaemia (T-LGL). Neutropenia was successfully treated with IVIG, glucocorticoids, and G-CSF. In vitro experiments aimed at elucidating the pathways potentially causing the mRNA vaccine-associated neutropenia indicated that the mRNA, but not the adenoviral Ad26.COV2.S vector vaccine, triggered strong IL-6/STAT3 activation in vitro, resulting in excessive T-cell activation and neutrophil degranulation in the patient but not in controls. mRNA-1273 activated TLR-3 suggesting TLR mediated IL-6/STAT3 pathway activation. To complete the primary series of COVID-19 immunization, we used a single dose of Ad26.COV2.S vector vaccine without reoccurrence of neutropenia. The T-LGL clone remained stable during the follow-up of more than 12 months without ongoing therapy. Our data suggest that switching the immunization platform may be a reasonable approach in subjects with rare associated hematologic side effects due to excess STAT3-mediated stimulation following mRNA vaccination. Using in vitro testing before re-administration of a (COVID) vaccine also has relevance for other rare immune events after (mRNA) vaccination.
Paternity patterns in a long-term resident bottlenose dolphin community
Authors: Duffield Debbie , Wells Randall
Published: February 2023

Genetic analyses, initiated in 1984, have played a major role in our understanding of the structure and social relationships of the long-term resident community of common bottlenose dolphins (Tursiops truncatus) in Sarasota Bay, Florida (SBDC). One component of our ongoing study of the community’s social system involves using blood samples from periodic catch-and-release sampling for life history and health assessment studies, as well as skin from biopsy dart sampling studies and strandings, to investigate paternity and mating strategies in this community. These analyses, covering a span of four generations of calves, were originally based on chromosomes and protein electrophoresis, but with the advent of microsatellite DNA technology, the latter has become our analysis of choice. We have performed paternity analyses on 204 known mother-calf pairs. For 151 of the calves (74%), sires were identified within the SBDC, but for the remaining 26% of the calves all sampled males associated with the community were excluded and it is likely that a substantial contribution of paternity to the SBDC comes from outside the community. Of the SBDC males, only 52 males of the more than 200 potential sires were sires. The age of sires at time of conception of a calf ranged from 10 to 43 years, averaging 24 years old. These males have sired 1-7 calves during a documented period of reproductive tenure of as much as 24 years (average = 21.4 years). Four males have sired 6-7 calves each, these males siring calves in the community for more than 20 years. Another 19 males have each sired 3-5 calves and the remaining 30 males were identified as sires of 1-2 calves. Paired males sired 75% of the calves while 25% of the calves were sired by unpaired males. Females with multiple offspring generally had multiple sires for these offspring. These paternity analyses support the hypothesis that a major avenue of gene flow in the SBDC is through the males given their greater ranges, with occasional exchangeviavisits from males from other areas, as well as the occasional brief movements of females from outside the community range into the community.
Research on non-contact wet mateable connector for optical communication and power transmission
Authors: Duan Zhiyong , Zhang Yurui , Hu Jiaqi , He Bohao , Yang Canjun
Published: February 2023

At present, contact watertight connectors are commonly utilized for the connection between underwater electromechanical equipment and the seabed observation network. Such traditional watertight connectors are easy to be irreversibly worn when plugging and unplugging, however, they have complicated sealing structures and limited service life. This paper designs a Non-contact Wet Mateable connector for Optical Communication and Power Transmission (OCPT-NWMC), which is based on technology of Contactless Power Transmission (CLPT) and optical communication. Docking structure of the sockets and plugs are designed, facilitating Remotely Operated Vehicle (ROV) to operate. A prototype of the OCPT-NWMC was established. The experimental results show that the connector designed can achieve 200W power transmission, with a maximum power transmission efficiency of 94%. The communication bandwidth reaches 18MHz. The OCPT-NWMC can assist the rapid and safe deployment and operation of seabed observation network.
Cu-loaded polyurethane to reduce ureteral stent microbes adherence and regulation of the inflammation response to RAW264.7
Authors: Li Hongwei , Zhao Jing , Wang Zhenyu , Hu Jiyuan , Zhao Jinlong , Awonusi Bukola O. , Li Jianzhong , Fan Lianhui
Published: February 2023

Introduction: Ureteral stents blocked with encrustation are a common clinical complication and affect bacteria colonization and inflammatory response. In this study, different concentrations of copper (0.25, 0.5, 1, 1.5, and 2 g/L) were immobilized on polyurethane (PU) that showed functionalization of microbe resistance and regulation of the inflammation response to RAW264.7.

Methods: X-ray photoelectron spectroscopy (XPS), atomic force microscope (AFM) and static water contact angles were used to analyze the surface characterization. Proteus mirabilis resistance test and adhesion of cells by SEM were carried out to evaluate the antibacterial property of Cu-bearing samples. Cell cytotoxicity assay and apoptosis were used to obtain acceptable concentrations of PU-Cu. The morphology of cells was used to observe the occurrence of pseudopodia after contact with PU-Cu. Would healing assay and Transwell invasion assay were carried out to observe the migration and recovery of macrophages. IL-6 and IL-10 were used to evaluate the secretion of pro-/anti-inflammatory cytokines.

Results: X-ray photoelectron spectroscopy (XPS), atomic force microscope (AFM), and static water contact angle measurement were used to confirm successful immobilization of Cu on PU. Plate counting assay and observation of adhered cells by SEM demonstrated that the antibacterial performance of PU-Cu against Proteus mirabilis increased with the amount of Cu loading in a dependent manner. Furthermore, the CCK-8 assay and apoptosis test suggested an acceptable cytotoxicity of PU-Cu at concentrations of 0.25, 0.5, and 1 g/L. The morphology of cells observed by SEM showed reduced occurrence of pseudopodia after contact with PU-Cu. Wound healing and transwell invasion assays manifested that migration and recovery of macrophages were improved by PU-Cu. ELISA of IL-6 and IL-10 demonstrated that PU-Cu could regulate inflammatory cytokines toward anti-inflammatory functionalization.
Literature review on COVID-19 vaccine efficacy in the immunocompromised population, and possible implications to future vaccination in kidney transplant patients
Authors: Park Joo Kyung , Bhandari Sunil
Published: February 2023

Since the emergence of the virulent coronavirus in 2019, efforts to tackle the coronavirus-disease-2019 (COVID-19) pandemic have been made globally. The development of the coronavirus disease (COVID) vaccine was a significant breakthrough in ways to tackle the virus. Various research studies have been conducted to identify how the virus works and ways to manage COVID, including the efficacy of the vaccines. However, there is limited data on how these measures work for the immunocompromised, despite the grave impact of these virulent strains in this population. Specifically, this review aims to focus on kidney transplant recipients (KTRs). Studies have suggested that there is significantly lower vaccine response in some immunocompromised groups despite additional booster doses, and hence warrants an augmented or alternative protection against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for these patients. This suggests a need for alternative or more tailored approach in providing adequate protection against the COVID-19 in these cohorts. Some suggested ways include withholding immunosuppressants before and/or after vaccination, increasing the vaccine doses or reducing intervals and providing a mixture of monoclonal antibody (mAb) or antiviral therapy. However, the appropriate degree of alteration and augmentation, as well as its safety and effectiveness remains to be determined. Furthermore, continuous emergence of more virulent strains, such as the Omicron and its sub-lineages or the Deltacron, emphasises the need for ongoing research to assess the effectiveness of the current treatment against these new variants. Overall, active interest and appropriate updates to COVID-19 guidelines is necessary.
Skeletal standardized uptake values obtained using quantitative SPECT/CT for the detection of bone metastases in patients with lung adenocarcinoma
Authors: Lin Lin , Zheng Rong , Geng Jianhua , Wang Xuejuan , Li Meng , Fan Rong , Zheng Yiqing , Yang Ke
Published: February 2023

Purpose

To assess the utility of skeletal standardized uptake values (SUVs) obtained using quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) in differentiating bone metastases from benign lesions, particularly in patients with lung adenocarcinoma.

Methods

Patients with lung adenocarcinoma who had undergone whole-body Tc-99m methyl-diphosphonate (99mTc-MDP) bone scans and received late phase SPECT/CT were retrospectively analyzed in this study. The maximum SUV (SUVmax); Hounsfield units (HUs); and volumes of osteoblastic, osteolytic, mixed, CT-negative metastatic and benign bone lesions, and normal vertebrae were compared. Receiver operating characteristic curves were used to determine the optimal cutoff SUVmax between metastatic and benign lesions as well as the cutoff SUVmax between CT-negative metastatic lesions and normal vertebrae. The linear correlation between SUVmax and HUs of metastatic lesions as well as that between SUVmax and the volume of all bone lesions were investigated.

Results

A total of 252 bone metastatic lesions, 140 benign bone lesions, and 199 normal vertebrae from 115 patients with lung adenocarcinoma were studied (48 males, 67 females, median age: 59 years). Metastatic lesions had a significantly higher SUVmax (23.85 ± 14.34) than benign lesions (9.67 ± 7.47) and normal vertebrae (6.19 ± 1.46; P < 0.0001). The SPECT/CT hotspot of patients with bone metastases could be distinguished from benign lesions using a cutoff SUVmax of 11.10, with a sensitivity of 87.70% and a specificity of 80.71%. The SUVmax of osteoblastic (29.16 ± 16.63) and mixed (26.62 ± 14.97) lesions was significantly greater than that of osteolytic (15.79 ± 5.57) and CT-negative (16.51 ± 6.93) lesions (P < 0.0001, P = 0.0003, and 0.002). SUVmax at the cutoff value of 8.135 could distinguish CT-negative bone metastases from normal vertebrae, with a sensitivity of 100.00% and a specificity of 91.96%. SUVmax showed a weak positive linear correlation with HUs in all bone metastases and the volume of all bone lesions.

Conclusion

SUVmax of quantitative SPECT/CT is a useful index for distinguishing benign bone lesions from bone metastases in patients with lung adenocarcinoma, particularly in the diagnosis of CT-negative bone metastases, but other factors that may affect SUVmax should be considered.
Leishmaniasis: Recent epidemiological studies in the Middle East
Authors: Knight Chinyere A. , Harris David R. , Alshammari Shifaa O. , Gugssa Ayele , Young Todd , Lee Clarence M.
Published: February 2023

Leishmaniasis, one of the most neglected tropical diseases (NTDs), is the third most important vector-borne disease worldwide. This disease has a global impact and severity of the infection and is greatest in the Middle East. The agent of infection is a protozoan parasite of the genus, Leishmania, and is generally transmitted by blood-sucking female sandflies. In humans, there are three clinical forms of infection: (1) cutaneous (CL), (2) mucocutaneous (ML), and (3) visceral leishmaniasis (VL). This review aims to discuss the current epidemiological status of leishmaniasis in Saudi Arabia, Iraq, Syria, and Yemen with a consideration of treatment options. The elevated risk of leishmaniasis is influenced by the transmission of the disease across endemic countries into neighboring non-infected regions.
The sieve-element endoplasmic reticulum: A focal point of phytoplasma-host plant interaction?
Authors: Musetti Rita , Pagliari Laura , Mian Giovanni , De Oliveira Cantao Fernando R. , Bernardini Chiara , Santi Simonetta , van Bel Aart J. E.
Published: February 2023

The rough endoplasmic reticulum (r-ER) is of paramount importance for adaptive responses to biotic stresses due to an increased demand for de novo synthesis of immunity-related proteins and signaling components. In nucleate cells, disturbance of r-ER integrity and functionality leads to the “unfolded protein response” (UPR), which is an important component of innate plant immune signalling. In contrast to an abundance of reports on r-ER responses to biotic challenges, sieve-element endoplasmic reticulum (SE-ER) responses to phytoplasma infection have not been investigated. We found that morphological SE-ER changes, associated with phytoplasma infection, are accompanied by differential expression of genes encoding proteins involved in shaping and anchoring the reticulum. Phytoplasma infection also triggers an increased release of bZIP signals from the (SE-ER)/r-ER and consequent differential expression of UPR-related genes. The modified expression patterns seem to reflect a trade-off between survival of host cells, needed for the phytoplasmic biotrophic lifestyle, and phytoplasmas. Specialized plasmodesmata between sieve element and companion cell may provide a corridor for transfer of phytoplasma effectors inducing UPR-related gene expression in companion cells.
Advantages of long- and short-reads sequencing for the hybrid investigation of the Mycobacterium tuberculosis genome
Authors: Di Marco Federico , Spitaleri Andrea , Battaglia Simone , Batignani Virginia , Cabibbe Andrea Maurizio , Cirillo Daniela Maria
Published: February 2023

Introduction

In the fight to limit the global spread of antibiotic resistance, computational challenges associated with sequencing technology can impact the accuracy of downstream analysis, including drug resistance identification, transmission, and genome resolution. About 10% of Mycobacterium tuberculosis (MTB) genome is constituted by the PE/PPE family, a GC-rich repetitive genome region. Although sequencing using short read technology is widely used, it is well recognized its limit in the PE/PPE regions due to the unambiguously mapping process onto the reference genome. The aim of this study was to compare the performances of short-reads (SRS), long-reads (LRS) and hybrid-reads (HYBR) based analysis over different common investigative tasks: genome coverage estimation, variant calling and cluster analysis, drug resistance detection and de novo assembly.

Methods

For the study 13 model MTB clinical isolates were sequenced with both SRS and LRS. HYBR were produced correcting the long reads with the short reads. The fastq from the three approaches were then processed using a customized version of MTBseq for genome coverage estimation and variant calling and using two different assemblers for de novo assembly evaluation.

Results

Estimation of genome coverage performances showed lower 8X breadth coverage for SRS respect to LRS and HYBR: considering the PE/PPE genes, SRS showed low results for the PE_PGRS family, while obtained acceptable coverage in PE and PPE genes; LRS and HYBR reached optimal coverages in PE/PPE genes. For variant calling HYBR showed the highest resolution, detecting the highest percentage of uniquely identified mutations compared to LRS and SRS. All three approaches agreed on the identification of two major clusters, with HYBR identifying an higher number of SNPs between the two clusters. Comparing the quality of the assemblies, HYBR and LRS obtained better results than SRS.

Discussion

In conclusion, depending on the aim of the investigation, both SRS and LRS present complementary advantages and limitations implying that for a full resolution of MTB genomes, where all the mentioned analyses and both technologies are needed, the use of the HYBR approach represents a valid option and a well-rounded strategy.
Evolution characteristics of dynamic balance disorder over the course of PD and relationship with dopamine depletion
Authors: Gan Jing , Wu Xiaodong , Wan Ying , Zhao Jiahao , Song Lu , Wu Na , Wang Hui , Yin Yafu , Liu Zhenguo
Published: February 2023

Objective

This study aimed to assess the evolution of dynamic balance impairment during the course of Parkinson's disease (PD) and to clarify the contribution of striatal dopaminergic innervation to poor dynamic balance.

Methods

In our study, 89 patients with PD (divided into 2 groups according to the H-Y stage) and 39 controls were included. Kinematic data were recorded by a portable inertial measurement unit system. Dopaminergic loss in the striatal subregion was verified through the 11C-CFT PET examination. The severity of white matter hyperintensities (WMHs) was assessed by the Scheltens scale. The correlation between dynamic kinematic parameters and dopamine transporter availability was analyzed by multivariate regression analysis.

Results

Patients with early PD presented with imbalance featured by smaller three-dimensional trunk ROM with reduced trunk coronal angular velocity during walking and with reduced trunk sagittal angular velocity during the stand-to-sit task (all p < 0.05). These abnormalities were not more severe at a later stage. The ROM in the coronal and transverse planes during walking correlated with caudate DAT uptake (β = 0.832, p = 0.006, Q = 0.030, and β = 0.890, p = 0.003, Q = 0.030) after controlling for age, gender, and WMHs. As the disease progressed, the trunk sagittal and transverse angular velocities during walking and trunk sagittal angular velocity when turning and sitting-to-standing were slower, which was accompanied by reduced gait velocity gradually (all p < 0.05). These parameters related to disease progression have no association with striatal DAT uptake (all p > 0.05).

Conclusion

The dynamic balance in PD was impaired from the early stages, and the characteristics of the impairment changed differently as the disease progressed. Dopaminergic denervation has a lower contribution to dynamic balance disorders throughout PD.
Adaptive neural network projection analytical fault-tolerant control of underwater salvage robot with event trigger
Authors: Guo Gaoyang , Zhang Qiang , Zhang Yan , Tan Wenyi , Tao Zewen , Ma Sainan
Published: February 2023

Introduction

To solve the problem of control failure caused by system failure of deep-water salvage equipment under severe sea conditions, an event-triggered fault-tolerant control method (PEFC) based on proportional logarithmic projection analysis is proposed innovatively.

Methods

First, taking the claw-type underwater salvage robot as the research object, amore universal thruster fault model was established to describe the fault state of equipment failure, interruption, stuck, and poor contact. Second, the controller was designed by the proportional logarithmic projection analytical method. The system input signal was amplified and projected as a virtual input, which replaces the original input to isolate and learn the fault factor online by the analytical algorithm. The terminal sliding mode observer was used to compensate for the external disturbance of the system, and the adaptive neural network was used to fit the dynamic uncertainty of the system. The system input was introduced into the event-triggered mechanism to reduce the output regulation frequency of the fault thruster.

Results

Finally, the simulation results showed that the method adopted in this study reduced the power output by 28.95% and the update frequency of power output by 75% compared with the traditional adaptive overdrive fault-tolerant control (AOFC) method and realized accurate pose tracking under external disturbance and system dynamic uncertain disturbance.

Discussion

It has been proven that the algorithm used in this research can still reasonably allocate power to reduce the load of a fault thruster and complete the tracking task under fault conditions.
The nomogram to predict the occurrence of sepsis-associated encephalopathy in elderly patients in the intensive care units: A retrospective cohort study
Authors: Zhao Qing , Xiao Jianguo , Liu Xiaoli , Liu Hui
Published: February 2023

Background

Sepsis-associated encephalopathy (SAE) is a critical and common problem in elderly patients with sepsis, which is still short of efficient predictive tools. Therefore, this study aims to screen the risk factors and establish a useful predictive nomogram for SAE in elderly patients with sepsis in the intensive care unit (ICU).

Patients and methods

Elderly patients (age ≥ 65 years) with sepsis were selected from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Data from demographics and laboratory examinations were collected on the first day of admission to the ICU. SAE was defined by two criteria in the presence of sepsis: ① a Glasgow Coma Scale (GCS) score of < 15 or ② delirium. Differences in demographics and laboratory tests were calculated between SAE and non-SAE groups. Participants were randomly divided into a training set and a validation set without replacement at a ratio of 6:4. A predictive nomogram was constructed in the training set by logistic regression analysis and then validated. The predictive capability of the nomogram was demonstrated by receiver operating characteristic (ROC) analysis and calibration curve analysis.

Results

A total of 22,361 patients were selected, of which 2,809 patients (12.7%) died in the hospital and 8,290 patients (37.1%) had SAE. In-hospital mortality in the SAE group was higher than that in the non-SAE group (18.8 vs. 8.9%, p < 0.001). Based on the results of logistic regression analysis, a nomogram integrating age, Na+, Sequential Organ Failure Assessment (SOFA) score, heart rate, and body temperature were constructed. The area under the curve (AUC) of the nomogram was 80.2% in the training set and 80.9% in the validation set. Calibration curve analysis showed a good predictive capacity of the nomogram.

Conclusion

SAE is an independent risk of in-hospital mortality in elderly patients in the intensive care unit. The nomogram has an excellent predictive capability of SAE and helps in clinical practice.
A parameter-optimization framework for neural decoding systems
Authors: Xie Jing , Chen Rong , Bhattacharyya Shuvra S.
Published: February 2023

Real-time neuron detection and neural activity extraction are critical components of real-time neural decoding. They are modeled effectively in dataflow graphs. However, these graphs and the components within them in general have many parameters, including hyper-parameters associated with machine learning sub-systems. The dataflow graph parameters induce a complex design space, where alternative configurations (design points) provide different trade-offs involving key operational metrics including accuracy and time-efficiency. In this paper, we propose a novel optimization framework that automatically configures the parameters in different neural decoders. The proposed optimization framework is evaluated in depth through two case studies. Significant performance improvement in terms of accuracy and efficiency is observed in both case studies compared to the manual parameter optimization that was associated with the published results of those case studies. Additionally, we investigate the application of efficient multi-threading strategies to speed-up the running time of our parameter optimization framework. Our proposed optimization framework enables efficient and effective estimation of parameters, which leads to more powerful neural decoding capabilities and allows researchers to experiment more easily with alternative decoding models.
Differential neural reward reactivity in response to food advertising medium in children
Authors: Yeum Dabin , Jimenez Courtney A. , Emond Jennifer A. , Meyer Meghan L. , Lansigan Reina K. , Carlson Delaina D. , Ballarino Grace A. , Gilbert-Diamond Diane , Masterson Travis D.
Published: February 2023

Introduction

Food cues including food advertisements (ads) activate brain regions related to motivation and reward. These responses are known to correlate with eating behaviors and future weight gain. The objective of this study was to compare brain responses to food ads by different types of ad mediums, dynamic (video) and static (images), to better understand how medium type impacts food cue response.

Methods

Children aged 9–12 years old were recruited to complete a functional magnetic resonance imaging (fMRI) paradigm that included both food and non-food dynamic and static ads. Anatomical and functional images were preprocessed using the fMRIPrep pipeline. A whole-brain analysis and a targeted region-of-interest (ROI) analysis for reward regions (nucleus accumbens, orbitofrontal cortex, amygdala, insula, hypothalamus, ventral tegmental area, substantia nigra) were conducted. Individual neural responses to dynamic and static conditions were compared using a paired t-test. Linear mixed-effects models were then constructed to test the differential response by ad condition after controlling for age, sex, BMI-z, physical activity, and % of kcal consumed of a participant’s estimated energy expenditure in the pre-load prior to the MRI scan.

Results

A total of 115 children (mean=10.9 years) completed the fMRI paradigm. From the ROI analyses, the right and left hemispheres of the amygdala and insula, and the right hemisphere of the substantia nigra showed significantly higher responses for the dynamic food ad medium after controlling for covariates and a false discovery rate correction. From the whole-brain analysis, 21 clusters showed significant differential responses between food ad medium including the precuneus, middle temporal gyrus, superior temporal gyrus, and inferior frontal gyrus, and all regions remained significant after controlling for covariates.

Discussion

Advertising medium has unique effects on neural response to food cues. Further research is needed to understand how this differential activation by ad medium ultimately affects eating behaviors and weight outcomes.
Meshed neuronal mitochondrial networks empowered by AI-powered classifiers and immersive VR reconstruction
Authors: Li Shu-Jiao , Liu Hui , Wu Fei-Fei , Feng Da-Yun , Zhang Shuai , Zheng Jie , Wang Lu , Tian Fei , Yang Yan-Ling , Wang Ya-Yun
Published: February 2023

Mitochondrial networks are defined as a continuous matrix lumen, but the morphological feature of neuronal mitochondrial networks is not clear due to the lack of suitable analysis techniques. The aim of the present study is to develop a framework to capture and analyze the neuronal mitochondrial networks by using 4-step process composed of 2D and 3D observation, primary and secondary virtual reality (VR) analysis, with the help of artificial intelligence (AI)-powered Aivia segmentation an classifiers. In order to fulfill this purpose, we first generated the PCs-Mito-GFP mice, in which green fluorescence protein (GFP) could be expressed on the outer mitochondrial membrane specifically on the cerebellar Purkinje cells (PCs), thus all mitochondria in the giant neuronal soma, complex dendritic arborization trees and long projection axons of Purkinje cells could be easily detected under a laser scanning confocal microscope. The 4-step process resolved the complicated neuronal mitochondrial networks into discrete neuronal mitochondrial meshes. Second, we measured the two parameters of the neuronal mitochondrial meshes, and the results showed that the surface area (μm2) of mitochondrial meshes was the biggest in dendritic trees (45.30 ± 53.21), the smallest in granular-like axons (3.99 ± 1.82), and moderate in soma (27.81 ± 22.22) and silk-like axons (17.50 ± 15.19). These values showed statistically different among different subcellular locations. The volume (μm3) of mitochondrial meshes was the biggest in dendritic trees (9.97 ± 12.34), the smallest in granular-like axons (0.43 ± 0.25), and moderate in soma (6.26 ± 6.46) and silk-like axons (3.52 ± 4.29). These values showed significantly different among different subcellular locations. Finally, we found both the surface area and the volume of mitochondrial meshes in dendritic trees and soma within the Purkinje cells in PCs-Mito-GFP mice after receiving the training with the simulating long-term pilot flight concentrating increased significantly. The precise reconstruction of neuronal mitochondrial networks is extremely laborious, the present 4-step workflow powered by artificial intelligence and virtual reality reconstruction could successfully address these challenges.
Novel maternal autoantibodies in autism spectrum disorder: Implications for screening and diagnosis
Authors: Mazón-Cabrera Rut , Liesenborgs Jori , Brône Bert , Vandormael Patrick , Somers Veerle
Published: February 2023

Introduction

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which early recognition is a major challenge. Autoantibodies against fetal brain antigens have been found in the blood of mothers of children with ASD (m-ASD) and can be transferred to the fetus where they can impact neurodevelopment by binding to fetal brain proteins. This study aims to identify novel maternal autoantibodies reactive against human fetal brain antigens, and explore their use as biomarkers for ASD screening and diagnosis.

Methods

A custom-made human fetal brain cDNA phage display library was constructed, and screened for antibody reactivity in m-ASD samples from the Simons Simplex Collection (SSC) of the Simons Foundation Autism Research Initiative (SFARI). Antibody reactivity against 6 identified antigens was determined in plasma samples of 238 m-ASD and 90 mothers with typically developing children (m-TD).

Results

We identified antibodies to 6 novel University Hasselt (UH)-ASD antigens, including three novel m-ASD autoantigens, i.e., ribosomal protein L23 (RPL23), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and calmodulin-regulated spectrin-associated protein 3 (CAMSAP3). Antibody reactivity against a panel of four of these targets was found in 16% of m-ASD samples, compared to 4% in m-TD samples (p = 0.0049).

Discussion

Maternal antibodies against 4 UH-ASD antigens could therefore provide a novel tool to support the diagnosis of ASD in a subset of individuals.
Remodeling of the brain correlates with gait instability in cervical spondylotic myelopathy
Authors: Wu Xianyong , Wang Ying , Chang Jianchao , Zhu Kun , Zhang Siya , Li Yan , Zuo Junxun , Chen Senlin , Jin Weiming , Yan Tingfei , Yang Kun , Xu Peng , Song Peiwen , Wu Yuanyuan , Qian Yinfeng , Shen Cailiang , Yu Yongqiang , Dong Fulong
Published: February 2023

Introduction

Cervical spondylotic myelopathy (CSM) is a common form of non-traumatic spinal cord injury (SCI) and usually leads to remodeling of the brain and spinal cord. In CSM with gait instability, the remodeling of the brain and cervical spinal cord is unclear. We attempted to explore the remodeling of these patients’ brains and spinal cords, as well as the relationship between the remodeling of the brain and spinal cord and gait instability.

Methods

According to the CSM patients’ gait, we divided patients into two groups: normal gait patients (nPT) and abnormal gait patients (aPT). Voxel-wise z-score transformation amplitude of low-frequency fluctuations (zALFF) and resting-state functional connectivity (rs-FC) were performed for estimating brain changes. Cross-sectional area (CSA) and fractional anisotropy (FA) of the spinal cord were computed by Spinal cord toolbox. Correlations of these measures and the modified Japanese Orthopedic Association (mJOA) score were analyzed.

Results

We found that the zALFF of caudate nucleus in aPT was higher than that in healthy controls (HC) and lower than that in nPT. The zALFF of the right postcentral gyrus and paracentral lobule in HC was higher than those of aPT and nPT. Compared with the nPT, the aPT showed increased functional connectivity between the caudate nucleus and left angular gyrus, bilateral precuneus and bilateral posterior cingulate cortex (PCC), which constitute a vital section of the default mode network (DMN). No significantly different FA values or CSA of spinal tracts at the C2 level were observed between the HC, nPT and aPT groups. In CSM, the right paracentral lobule’s zALFF was negatively correlated with the FA value of fasciculus gracilis (FCG), and the right caudate zALFF was positively correlated with the FA value of the fasciculus cuneatus (FCC). The results showed that the functional connectivity between the right caudate nucleus and DMN was negatively correlated with the CSA of the lateral corticospinal tract (CST).

Discussion

The activation of the caudate nucleus and the strengthening functional connectivity between the caudate nucleus and DMN were associated with gait instability in CSM patients. Correlations between spinal cord and brain function might be related to the clinical symptoms in CSM.
Functional connectivity of the amygdala and the antidepressant and antisuicidal effects of repeated ketamine infusions in major depressive disorder
Authors: Liu Haiyan , Wang Chengyu , Lan Xiaofeng , Li Weicheng , Zhang Fan , Fu Ling , Ye Yanxiang , Ning Yuping , Zhou Yanling
Published: February 2023

Background

Dysfunction of the amygdala is the core pathogenesis of major depressive disorder (MDD). However, it remains unclear whether ketamine treatment could modulate characteristics of amygdala-related networks. We aimed to explore the relationship between changes in the resting-state functional connectivity (RSFC) of the amygdala and the treatment of ketamine in MDD patients and to identify important neuroimaging predictors of treatment outcome.

Methods

Thirty-nine MDD patients received six subanesthetic dose infusions of ketamine. Depressive and suicidal symptoms were assessed and magnetic resonance imaging (MRI) scans were performed before and after six ketamine infusions. Forty-five healthy controls also underwent once MRI scans. Seed-based RSFC analyses were performed, focusing on the bilateral amygdala.

Results

After ketamine treatment, the RSFC between the left amygdala (LA) and the left medial superior frontal gyrus (mSFG) of MDD patients enhanced significantly, and this change was positively correlated with the reduction in depressive symptoms (r = 0.40, p = 0.012). The combination baseline RSFC of LA – right putamen and right amygdala (RA) – right putamen was related to the antidepressant and antisuicidal effects of ketamine. The combination baseline RSFC of LA – right putamen and RA – right putamen could predict the ineffective antidepressant (AUC = 0.739, p = 0.011) and antisuicidal effects of ketamine (AUC = 0.827, p = 0.001).

Conclusion

Ketamine can regulate the relevant circuits of amygdala and mSFG, and the baseline RSFC between bilateral amygdala and right putamen may be a predictor of the response of ketamine’s antidepressant and antisuicidal treatment.

Clinical trial registration

https://www.chictr.org.cn/showproj.aspx?proj=20875, identifier ChiCTR-OOC-17012239.
Altered dynamic functional connectivity in the primary visual cortex in patients with primary angle-closure glaucoma
Authors: Li Dong-Jin , Huang Bing-Lin , Peng Yuan , Liang Ling-Yan , Liu Hui
Published: February 2023

Purpose

Glaucoma is the main blindness-causing disease in the world. Previous neuroimaging studies demonstrated that glaucoma not only causes the loss of optic ganglion cells but also leads to the abnormal function of the optic nerve pathway and the visual cortex. However, previous studies also reported that patients with glaucoma have dysfunction in the visual cortex in a static state. Whether or not patients with primary angle-closure glaucoma (PACG) were accompanied by dynamic functional connectivity (FC) changes in the primary visual cortex (V1) remains unknown.

Methods

A total of 34 patients with PACG (23 men and 11 women) and 34 well-matched healthy controls (HCs) were enrolled in the study. The dynamic functional connectivity (dFC) with the sliding window method was applied to investigate the dynamic functional connectivity changes in the V1.

Results

Compared with HCs, patients with PACG showed increased dFC values between left V1 and bilateral calcarine (CAL). Meanwhile, patients with PACG showed increased dFC values between right V1 and bilateral CAL.

Conclusion

Our study demonstrated that patients with PACG showed increased dFC within the visual network, which might indicate the increased variability FC in the V1 in patients with PACG.
Chrononutrition behavior during the COVID-19 pandemic and its relationship with body weight among college students
Authors: Juliana Norsham , Teng Nur Islami Mohd Fahmi , Hairudin Khairunnisa Fazira , Wan Abdul Fatah Wan Asma , Das Srijit
Published: February 2023

Introduction

Students in colleges are exposed to unhealthy lifestyles and poor dietary choices. They are at risk of being overweight, skipping meals, and developing eating disorders. However, there is a paucity of information on their chrononutrition behavior, which is very important, especially concerning the timing of food consumption across the day. Therefore, the present study aimed to investigate chrononutrition behavior and its potential association with body weight status among college students in Malaysia.

Methods

This cross-sectional study was conducted on 409 college students aged above 18 in Malaysia. The chrononutrition behavior was assessed using the validated Chrononutrition Profile Questionnaire (CP-Q). The questionnaire was distributed using an online platform. Participants self-reported their body weight and height, and the Body Mass Index (BMI) was computed. Data were analyzed using the SPSS software.

Results

A total of 409 participants were recruited, with a mean age of 21.5 ± 2.2 years. The prevalence of underweight, normal, and overweight was 24.7, 49.4, and 25.9%, respectively. The chrononutrition behavior revealed that participants ate breakfast about four times/week (mean 4.27 ± 2.43 days), and only 135 (33.0%) consumed breakfast daily. The largest meal consumed was during lunch (75.8%), and the mean of snacking after the last meal was 3.23 ± 2.01 days. The prevalence of night eating was low, and most participants (70.9) did not wake up at night to eat. The frequency, however, was significantly higher in the underweight group compared to the normal weight group (p < 0.05). We observed a significant association between BMI and eating window, evening latency, evening eating, and night eating. It was found that the underweight had a poor eating window (p < 0.01), poor evening latency (p < 0.01), poor evening eating (p < 0.01), and poor night eating (p < 0.05) compared to those with normal and overweight BMI groups. In contrast to predictions, poor chrononutrition behavior was more likely to predict being underweight compared to normal (p < 0.05).

Conclusion

Underweight young adults are more likely to have poor chrononutrition behavior. The results of the present study suggest that future nutrition education should also focus on the chrononutrition behavior of college students.
Case report: Application of morphology in the diagnosis of siderosis in a patient with tuberculosis infection
Authors: Zhou Yuli , Wang Ying , Liu Wenbing , Wang Haibin , He Daqiang , Jin Juan , Li Qiaoyun , Li Junying , Chen Qiong , Ruan Senlin , Wu Shenghai , Tang Jiyu
Published: February 2023

A 49-year-old male who had been working in welding for more than 30 years was admitted to the hospital for a medical checkup that revealed a lung shadow without specific symptoms such as coughing and sputum. Imaging studies showed diffuse ground-glass changes in both lungs, wall cavities with wall nodules, multiple peripheral nodules, and some nodules with calcification. The patient has been engaged in welding work for more than 30 years and exposed to iron dust. Lung tissue biopsy, routine morphological and pathological fluid basis examination of alveolar lavage fluid, can be considered as pulmonary iron particles, which can be regarded as iron dust lung. Acid-fast bacilli were detected in both fibrobronchoscopic brush extract and alveolar lavage fluid acid-fast staining. As the pathological examination revealed granulomatous inflammation showed caseation necrosis, the patient was judged to have concomitant pulmonary TB. After the diagnosis was made, the patient was no longer exposed to dust and was treated with appropriate anti- tuberculosis (TB) therapy. Lung lesions caused by welding have been reported, but the simultaneous finding of siderosis with pulmonary TB is specific to the case presented here. By describing the imaging features, combining different staining methods of alveolar lavage fluid and pathological examination of lung tissue, we showed various morphological manifestations of this case, aiming at improving the morphological diagnosis level of laboratory physicians and enabling patients to be diagnosed and treated early.
Prognostic biomarker NEIL3 and its association with immune infiltration in renal clear cell carcinoma
Authors: Sun Xiaomei , Liu Pengfei
Published: February 2023

Background

Kidney renal clear cell carcinoma (KIRC) is a malignant tumor with a high degree of immune infiltration. Identifying immune biomarkers is essential for the treatment of KIRC. Studies have identified the potential of NEIL3 to modulate the immune microenvironment and promote tumor progression. However, the role of NEIL3 in KIRC remains uncertain. This study was to investigate the effect of NEIL3 on the prognosis and immune infiltration of patients with KIRC.

Methods

TCGA and GEO databases were used to study the expression of NEIL3 in KIRC. Cox regression analysis was used to examine the relationship between the expression of NEIL3 and clinicopathological variables and survival. Furthermore, Gene Set Cancer Analysis (GSCA) was applied to study the impact of NEIL3 methylation on outcomes of KIRC. Through gene ontology (GO) and Gene set enrichment (GSEA) analysis, the biological processes and signal pathways related to NEIL3 expression were identified. In addition, immune infiltration analysis was conducted via CIBERSORT analysis, ssGSEA analysis and TISIDB database.

Results

NEIL3 was overexpressed in KIRC, and it was significantly related with histologic grade, pathologic stage, T stage, M stage, and vital status of KIRC patients (P < 0.001). The expression of NEIL3 was associated with worse outcomes. Univariate and multivariate Cox analysis showed that NEIL3 may be an indicator of adverse outcomes in KIRC. GSEA analysis revealed that NEIL3 may be involved in signal pathways including cell cycle, DNA replication, mismatch repair, P53 signal pathway, and antigen processing and presentation. In addition, immune infiltration analysis showed a positive correlation between NEIL3 expression and multiple immune cells (activated CD8 T cells, activated dendritic cells, myeloid-derived suppressor cells, follicular helper T cells, and regulatory T cells) and immunoinhibitors (PD1, CTLA4, LAG3, TIGHT, IL10, and CD96).

Conclusion

NEIL3 is a potential independent biomarker of KIRC, which is relevant to immune infiltration.
Advances in immune checkpoint inhibitor combination strategies for microsatellite stable colorectal cancer
Authors: Ros Javier , Balconi Francesca , Baraibar Iosune , Saoudi Gonzalez Nadia , Salva Francesc , Tabernero Josep , Elez Elena
Published: February 2023

Immune checkpoint inhibitors have reshaped the prognostic of several tumor types, including metastatic colorectal tumors with microsatellite instability (MSI). However, 90-95% of metastatic colorectal tumors are microsatellite stable (MSS) in which immunotherapy has failed to demonstrate meaningful clinical results. MSS colorectal tumors are considered immune-cold tumors. Several factors have been proposed to account for this lack of response to immune checkpoint blockade including low levels of tumor infiltrating lymphocytes, low tumor mutational burden, a high rate of WNT/β-catenin pathway mutations, and liver metastases which have been associated with immunosuppression. However, studies with novel combinations based on immune checkpoint inhibitors are showing promising activity in MSS colorectal cancer. Here, we review the underlying biological facts that preclude immunotherapy activity, and detail the different immune checkpoint inhibitor combinations evaluated, along with novel immune-based therapies, to overcome innate mechanisms of resistance in MSS colorectal cancer.
A radiomic biomarker for prognosis of resected colorectal cancer liver metastases generalizes across MRI contrast agents
Authors: Chen Jianan , Cheung Helen M. C. , Karanicolas Paul J. , Coburn Natalie G. , Martel Guillaume , Lee Albert , Patel Chirag , Milot Laurent , Martel Anne L.
Published: February 2023

Introduction

Contrast-enhanced MRI is routinely performed as part of preoperative work-up for patients with Colorectal Cancer Liver Metastases (CRLM). Radiomic biomarkers depicting the characteristics of CRLMs in MRI have been associated with overall survival (OS) of patients, but the reproducibility and clinical applicability of these biomarkers are limited due to the variations in MRI protocols between hospitals.

Methods

In this work, we propose a generalizable radiomic model for predicting OS of CRLM patients who received preoperative chemotherapy and delayed-phase contrast enhanced (DPCE) MRIs prior to hepatic resection. This retrospective two-center study included three DPCE MRI cohorts (n=221) collected between January 2006 and December 2012. A 10-minute delayed Gd-DO3A-butrol enhanced MRI discovery cohort was used to select features based on robustness across contrast agents, correlation with OS and pairwise Pearson correlation, and to train a logistic regression model that predicts 3-year OS.

Results

The model was evaluated on a 10-minute delayed Gd-DO3A-butrol enhanced MRI validation cohort (n=121), a 20-minute delayed Gd-EOB-DTPA (n=72) cohort from the same institute, and a 5-minute delayed Gd-DTPA cohort (n=28) from an independent institute. Two features were selected: minor axis length and dependence variance. The radiomic signature model stratified high-risk and low-risk CRLM groups in the Gd-DO3Abutrol (HR = 6.29, p = .007), Gd-EOB-DTPA (HR = 3.54, p = .003) and Gd-DTPA (HR = 3.16, p = .04) validation cohorts.

Discussion

While most existing MRI findings focus on a specific contrast agent, our study shows the potential of MRI features to be generalizable across main-stream contrast agents at delayed phase.