bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Novel Biallelic Variants in DNAJC21 Causing an Inherited Bone Marrow Failure Spectrum Phenotype: An Odyssey to Diagnosis
Authors: Chirita-Emandi Adela , Petrescu Carmen-Angela-Maria , Zimbru Cristian G. , Stoica Florina , Marian Catalin , Ciubotaru Andreea , Bataneant Mihaela , Puiu Maria
Published: April 2022

Bone marrow failure represents an umbrella diagnosis for several life-threatening disorders. In many people, the etiology remains unknown for a long time, leading to an odyssey to diagnosis, with numerous tests performed and sometimes inappropriate treatment. Biallelic pathogenic variants in the DNAJC21 gene were recently discovered to cause bone marrow failure syndrome type 3, having phenotypic overlap with Fanconi anemia, dyskeratosis congenita, Shwachman–Diamond syndrome, and Diamond–Blackfan anemia. Herein, we report an 8-year-old boy, with normal intellect, presenting bone marrow failure; growth retardation; failure to thrive; recurrent infections (including sepsis); cryptorchidia; skeletal, skin, teeth, and hair abnormalities; joint hypermobility; eczema; palpebral ptosis; high myopia; rod–cone retinal dystrophy; and short telomeres. He underwent several tests and evaluations, including genetic investigations (panel and exome sequencing), before the DNAJC21 gene was known to cause disease. Whole-genome sequencing performed at the age of 7 years, identified two novel, pathogenic, and compound heterozygous variants in the DNAJC21 gene: NM_001012339.3:c.148C>T (stopgain-maternal origin), p.Gln50∗ and c.643_644delinsTTT (frameshift paternal origin), and p.Lys215Phefs∗71. He received aggressive treatments for his multisystem disease: blood cell transfusions, high-dose corticosteroids, immunoglobulins, multiple antibiotics, vitamins, growth hormone, and others. However, allogeneic hematopoietic stem cell transplantation was avoided. The clinical evolution of bone marrow failure and recurrent infections stabilized with age, yet the myopia progressed. Exocrine pancreatic insufficiency was not detected. This report widens the molecular and clinical understanding of bone marrow failure syndrome type 3. Genome sequencing directed a precise diagnosis that improved patient management and enabled family genetic counseling.
Case Report: An Unusual Course of Angiosarcoma After Lung Transplantation
Authors: Bos Saskia , Daniëls Liesbeth , Michaux Lucienne , Vanden Bempt Isabelle , Vermeer Sascha , Woei-A-Jin FJ Sherida H , Schöffski Patrick , Weynand Birgit , Sciot Raf , Declercq Sabine , Ceulemans Laurens J. , Godinas Laurent , Verleden Geert M. , Van Raemdonck Dirk E. , Dupont Lieven J. , Vos Robin ,   the Leuven Lung Transplant Group
Published: April 2022

A 35-year-old woman underwent bilateral lung transplantation for primary ciliary dyskinesia and developed vascular tumors over a slow time course. Initial presentation of non-specific vascular tumors in the lungs and liver for up to 6 years after transplantation evolved toward bilateral ovarian angiosarcoma. Tumor analysis by haplotyping and human leukocyte antigen typing showed mixed donor chimerism, proving donor origin of the tumoral lesions. In retrospect, the donor became brain dead following neurosurgical complications for a previously biopsy-proven cerebral hemangioma, which is believed to have been a precursor lesion of the vascular malignancy in the recipient. Donor-transmitted tumors should always be suspected in solid organ transplant recipients in case of uncommon disease course or histology, and proper tissue-based diagnosis using sensitive techniques should be pursued.
Bivalve Haemocyte Subpopulations: A Review
Authors: de la Ballina Nuria R. , Maresca Francesco , Cao Asunción , Villalba Antonio
Published: April 2022

Bivalve molluscs stand out for their ecological success and their key role in the functioning of aquatic ecosystems, while also constituting a very valuable commercial resource. Both ecological success and production of bivalves depend on their effective immune defence function, in which haemocytes play a central role acting as both the undertaker of the cellular immunity and supplier of the humoral immunity. Bivalves have different types of haemocytes, which perform different functions. Hence, identification of cell subpopulations and their functional characterisation in immune responses is essential to fully understand the immune system in bivalves. Nowadays, there is not a unified nomenclature that applies to all bivalves. Characterisation of bivalve haemocyte subpopulations is often combined with 1) other multiple parameter assays to determine differences between cell types in immune-related physiological activities, such as phagocytosis, oxidative stress and apoptosis; and 2) immune response to different stressors such as pathogens, temperature, acidification and pollution. This review summarises the major and most recent findings in classification and functional characterisation of the main haemocyte types of bivalve molluscs.
Extracellular Vesicle Therapy for Type 1 Diabetes
Authors: Soltani Setareh , Mansouri Kamran , Emami Aleagha Mohammad Sajad , Moasefi Narges , Yavari Niloofar , Shakouri Seyed Kazem , Notararigo Sara , Shojaeian Ali , Pociot Flemming , Yarani Reza
Published: April 2022

Type 1 diabetes (T1D) is a chronic disorder characterized by immune-mediated destruction of pancreatic insulin-producing β-cells. The primary treatment for T1D is multiple daily insulin injections to control blood sugar levels. Cell-free delivery packets with therapeutic properties, extracellular vesicles (EVs), mainly from stem cells, have recently gained considerable attention for disease treatments. EVs provide a great potential to treat T1D ascribed to their regenerative, anti-inflammatory, and immunomodulatory effects. Here, we summarize the latest EV applications for T1D treatment and highlight opportunities for further investigation.
Recent Advances in IL-13Rα2-Directed Cancer Immunotherapy
Authors: Knudson Karin M. , Hwang SuJin , McCann Mondona S. , Joshi Bharat H. , Husain Syed R. , Puri Raj K.
Published: April 2022

Interleukin-13 receptor subunit alpha-2 (IL-13Rα2, CD213A), a high-affinity membrane receptor of the anti-inflammatory Th2 cytokine IL-13, is overexpressed in a variety of solid tumors and is correlated with poor prognosis in glioblastoma, colorectal cancer, adrenocortical carcinoma, pancreatic cancer, and breast cancer. While initially hypothesized as a decoy receptor for IL-13-mediated signaling, recent evidence demonstrates IL-13 can signal through IL-13Rα2 in human cells. In addition, expression of IL-13Rα2 and IL-13Rα2-mediated signaling has been shown to promote tumor proliferation, cell survival, tumor progression, invasion, and metastasis. Given its differential expression in tumor versus normal tissue, IL-13Rα2 is an attractive immunotherapy target, as both a targetable receptor and an immunogenic antigen. Multiple promising strategies, including immunotoxins, cancer vaccines, and chimeric antigen receptor (CAR) T cells, have been developed to target IL-13Rα2. In this mini-review, we discuss recent developments surrounding IL-13Rα2-targeted therapies in pre-clinical and clinical study, including potential strategies to improve IL-13Rα2-directed cancer treatment efficacy.
Th2-Oriented Immune Serum After SARS-CoV-2 Vaccination Does Not Enhance Infection In Vitro
Authors: Luan Ning , Li Tao , Wang Yunfei , Cao Han , Yin Xingxiao , Lin Kangyang , Liu Cunbao
Published: April 2022

The relatively lower protection rate of the alum-adjuvanted inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines reminds us of the antibody-dependent enhancement (ADE) phenomenon observed in preclinical studies during the development of vaccines for Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1). In this study, using the S1 segment of the SARS-CoV-2 spike protein or inactivated whole SARS-CoV-2 virus as an antigen and aluminum as an adjuvant, the risk of ADE of infection with T helper 2 (Th2)-oriented immune serum from mice (N=6) and humans (N=5) was examined in immune cell lines, which show different expression patterns of Fc receptors. Neither the immune serum from alum-adjuvanted S1 subunit vaccines nor inactivated SARS-CoV-2 vaccination enhanced SARS-CoV-2 S pseudotyped virus infection in any of the tested cell lines in vitro. Because both of these Th2-oriented immune sera could block SARS-CoV-2 infection without ADE of infection, we speculate that the lower protection rate of the inactivated SARS-CoV-2 vaccine may be attributed to the lower neutralizing antibody titers induced or the pulmonary eosinophilic immunopathology accompanied by eosinophilic infiltration in the lungs upon virus exposure. Adjustment of the immunization schedule to elevate the neutralizing antibody levels and skew adjuvants toward Th1-oriented responses may be considered to increase the efficacies of both inactivated and spike protein-based subunit SARS-CoV-2 vaccines.
Synthesis and Structural Characterization of Fly Ash Based Mineral Polymer Precursors
Authors: Miao Xia , Yimiao Nie , Shuxian Liu , Ling Wang , Long Wang , Sen Wang
Published: April 2022

Preparation of mineral polymer materials with fly ash is one of the effective ways to realize the green and comprehensive utilization of fly ash. Using the sol-gel method mineral aggregate material precursor, swe tudied the different sources of silicon and aluminum, synthesis temperature, different Si/Al ratio, different dosages of ethanol, and other influence factors under the conditions of the synthesis, and the structure of the sample using the means of XRD, SEM, TG, IR on the synthesis of silica-alumina precursor sample performance and structure are analyzed. The results showed that the optimum preparation conditions were obtained when the Si/Al ratio was 10:1, the synthesis temperature was 70°C, and the sample was calcined at 850°C for 3 h with the highest synthesis rate of 81.33%. The Si-Al precursors prepared are amorphous—phase amorphous grid—space structures. The infrared analysis indicated that the synthesized sample had a Si-O-Si bond, but the absorption peak and characteristic peak were obviously different under the conditions of different synthesis temperatures, different Si/Al ratios, and different ethanol dosage. For example, at 806 cm−1 and 1,395 cm−1, they correspond to the absorption peak of Si-OH bending vibration and shear bending vibration and plane bending vibration of C-H without complete reaction respectively. SEM observation shows that the size of the synthesized Silicon aluminum precursors sample is small and the distribution is uniform. The in-depth study on the preparation process and reaction mechanism of mineral polymer precursorswill bring broad prospects for the application and development of mineral polymer precursors themselves.
Modeling, Simulation and Testing of Atomization Temperature Change Point of Thermochromic Glass for Building Energy Saving
Authors: Kai Zeng , YuDai Liang , BaoRong Zhang , Quan Shi , JinBo Wu , WeiJia Wen
Published: April 2022

Thermochromic glass possesses great potential for reducing the energy demand and providing indoor comfort in buildings. Suitable atomization temperature change points have a great influence on the application of thermochromic glass. Based on energy consumption simulations and theoretical calculations by introducing solar radiation in a transparent envelope, this paper investigates the atomization temperature change point of thermochromic glass in hot summer and cold winter zones in Chongqing, showing that the suitable temperature change point of the thermochromic glass is 39°C with air conditioning and 42.9°C without air conditioning. Furthermore, the results of simulations and theoretical calculations are applied to a test model, revealing that thermochromic glass with the temperature change point of 42.9°C compared with Low-E glass can reduce the temperature of a sunlight room by up to 5°C in the summer and displays a certain thermal insulation effect in winter.
Monomer Recovery and Nano-Silica Separation From Biodegraded Waste Silicone Rubber Shed of Composite Insulator
Authors: Yang Shifang , Liu Yunpeng , Zhou Dasen
Published: April 2022

Composite insulators are widely used in the external insulation of transmission lines due to their excellent pollution flashover resistance. However, the large amount of silicone rubber material is difficult to degrade naturally in decommissioned composite insulators resulting in great pressure on the environment. A method for recycling waste silicone rubber by microbial degradation was proposed. The insulator shed materials of composite insulators naturally retired under 10–15 years of operation are collected. Using dominant species to decompose silicone rubber, the decomposed product is obtained, and the chemical reaction process is deduced according to the three-dimensional structural characteristics of monomers. The biodegradation process does not require the participation of a strong acid and alkali, and the recovery method is safe and effective. At the same time, the nano-silicon dioxide is separated from the waste silicone rubber and modified by the surfactant. The particle size of nano-silica is reduced to ∼18 nm with an excellent dispersibility, indicating high economic value. It is demonstrated that microbial decomposition recycles polymeric materials with the ability to turn them into a valuable resource, which is a very-low-carbon green and environment-friendly method of recycling.
Optimization of Refill Friction Stir Spot Welded AA2024-T3 Using Machine Learning
Authors: Effertz P. S. , de Carvalho W. S. , Guimarães R. P. M. , Saria G. , Amancio-Filho S. T.
Published: April 2022

The Refill Friction Stir Spot Welding is an innovative spot like solid state process befitting of overlap joint configurations of similar and dissimilar materials. This process caught the interest and is rapidly growing in the aerospace sector due to its potential to substitute traditional mechanical fasteners, surpassing their mechanical performance while maintaining the so desired lightweight “rationale.” In the current study, process parameters, namely plunge depth, plunge time and rotational speed, are optimized in order to obtain the highest Ultimate Lap Shear Force (ULSF) of 2024-T3 Aluminum Alloy similar joints. The optimization campaign was carried out using a second order multivariate polynomial regression machine learning (ML) algorithm. The trained ML model was able to generalize and accurately predict the Ultimate Lap Shear Force on the holdout set, having aR2of 88.0%. Moreover, the model suggested an optimum parameter combination (Rotational Speed = 2,310 rpm, Welding Time = 5.3 s and Plunge Depth = 2.6 mm) from which the predicted maximum ULSF was computed. Confirmation tests were carried out to evaluate the agreement between the predicted and the experimental values.
Liver Fibrosis Scores and Clinical Outcomes in Patients With COVID-19
Authors: Zhang Jing , Liu Fuwei , Song Tiangang , Li Zhangwang , Xia Panpan , Tang Xiaoyi , Xu Minxuan , Shen Yunfeng , Ma Jianyong , Liu Xiao , Yu Peng
Published: April 2022

Background and Aims

We investigated the association between liver fibrosis scores and clinical outcomes in patients with COVID-19.

Methods

We performed a post-hoc analysis among patients with COVID-19 from the trial study Outcomes Related to COVID-19 treated with Hydroxychloroquine among Inpatients with symptomatic Disease (ORCHID) trial. The relationship between aspartate aminotransferase (AST) to platelet ratio index (APRI), non-alcoholic fatty liver disease fibrosis score (NFS), Fibrosis-4 index (FIB-4), and discharge and death during the 28-days of hospitalization was investigated.

Results

During the 28 days after randomization, 237 (80.6%) patients were discharged while 31 (10.5%) died among the 294 patients with COVID-19. The prevalence for advanced fibrosis was estimated to be 34, 21.8, and 37.8% for FIB-4 (>2.67), APRI (>1), and NFS (>0.676), respectively. In multivariate analysis, FIB-4 >2.67 [28-days discharge: hazard ratio (HR): 0.62; 95% CI: 0.46–0.84; 28-days mortality: HR: 5.13; 95% CI: 2.18–12.07], APRI >1 (28-days discharge: HR: 0.62; 95% CI: 0.44–0.87; 28-days mortality: HR: 2.85, 95% CI: 1.35–6.03), and NFS >0.676 (28-days discharge: HR: 0.5; 95% CI: 0.35–0.69; 28-days mortality: HR: 4.17; 95% CI: 1.62–10.72) was found to significantly reduce the discharge rate and increase the risk of death. Additionally, FIB-4, APRI, and NFS were found to have good predictive ability and calibration performance for 28-day death (C-index: 0.74 for FIB-4, 0.657 for APRI, and 0.745 for NFS) and discharge (C-index: 0.649 for FIB-4, 0.605 for APRI, and 0.685 for NFS).

Conclusion

In hospitalized patients with COVID-19, FIB-4, APRI, and NFS may be good predictors for death and discharge within 28 days. The link between liver fibrosis and the natural history of COVID-19 should be further investigated.
Prevalence of Metabolic Syndrome in Patients With Rheumatoid Arthritis: An Updated Systematic Review and Meta-Analysis
Authors: Cai Wei , Tang Xuemi , Pang Min
Published: April 2022

Introduction

Rheumatoid arthritis (RA) due to systemic inflammation and insulin resistance increases the risk of cardiovascular disease and reduces life expectancy. In order to develop cardiac death prevention strategies, it is necessary to estimate the prevalence of metabolic syndrome (MetS) in these patients.

Methods

This systematic review and meta-analysis was performed to estimate the prevalence of MetS among patients with RA. International databases (i.e., Scopus, PubMed, Web of Science, and Google Scholar) were searched during the period of October 1 and October 10, 20121. Heterogeneity among the included studies was assessed through the Cochrane Q test statistics and I2 test. Finally, a random-effects meta-analysis model was computed to estimate the pooled prevalence of MetS.

Results

Sixty-one articles with 96 groups and a sample size of 13,644 people were analyzed. The pooled prevalence of MetS was 32% (95% CI: 29.6–34.4). The highest prevalence of MetS is related to studies conducted in Asia (32.7%, 95% CI: 29–36.3) and Europe (32.7%, 95% CI: 27.5.37.9) and the lowest Prevalence was also related to studies conducted in Africa (28%, 95% CI: 28.8–32.2). The prevalence of MetS in men was 33% (95% CI: 26–39) and 34% (95% CI: 29–40) in women. Findings by diagnostic criteria showed that the highest and lowest prevalence of MetS was related to ATP III (37.5%, 95% CI: 30.9–44.2) and EGIR (14.4%, 95% CI: 10.5–18.5), respectively.

Conclusions

MetS is highly prevalent in patients with RA and identification of high-risk patients is necessary to prevent cardiovascular mortality.
Current Perspectives in Human T-Cell Leukemia Virus Type 1 Infection and Its Associated Diseases
Authors: Miura Michi , Naito Tadasuke , Saito Mineki
Published: April 2022

Human T-cell leukemia virus type 1 (HTLV-1) is a replication-competent human retrovirus associated with two distinct types of diseases: a malignancy of mature CD4+ T cells called adult T-cell leukemia-lymphoma (ATL) and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It was the first human retrovirus ever associated with a human cancer. Although most HTLV-1-infected individuals remain asymptomatic for life, a subpopulation develops ATL or HAM/TSP. Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence suggests that the complex virus-host interactions, as well as the host immune response against HTLV-1 infection, appear to regulate the development of HTLV-1-associated diseases. This review outlines and discusses the current understanding, ongoing developments, and future perspectives of HTLV-1 research.
Gut Microbiome Signatures Are Predictive of Cognitive Impairment in Hypertension Patients—A Cohort Study
Authors: Qu Lei , Dong Zhouyan , Ma Songcui , Liu Yaping , Zhou Wei , Wang Zitong , Wu Chen , Ma Rui , Jiang Xinze , Zu Tingting , Cheng Mei , Wu Yulong
Published: April 2022

Growing evidence has demonstrated that hypertension was associated with dysbiosis of intestinal flora. Since intestinal microbes could critically regulate neurofunction via the intestinal–brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. A cohort of 97 participants included 63 hypertension patients and 34 healthy controls. The structure of intestinal flora was analyzed by V3–V4 16S rRNA amplicon sequencing. The cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and 31 patients were considered to have cognitive impairment (MoCA < 26). Patients with cognitive impairment had considerable alterations in intestinal flora structure, composition, and function compared with normal-cognitive patients. In particular, the abundance of LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia–Shigella) and SCFA-producing taxon (Prevotella) significantly changed in cognition-impaired patients. Tax4Fun predication results showed downregulation of glycan biosynthesis and metabolism in hypertension patients with cognitive impairment. Additionally, the pathway was demonstrated to be significantly correlated with LPS-containing taxa (Proteobacteria, Gammaproteobacteria, Enterobacterales, Enterobacteriaceae, and Escherichia–Shigella) and SCFA-producing taxon Prevotella. Furthermore, the taxa-based multiple joint prediction model (9×) was demonstrated to have excellent diagnostic potential for cognitive impairment of hypertension patients (AUC = 0.944). The current study revealed the involvement of intestinal microbiota dysbiosis in cognition-impaired hypertension patients and provided an objective predictive index for this cognition disorder.
Nutrients Regulate the Effects of Arbuscular Mycorrhizal Fungi on the Growth and Reproduction of Cherry Tomato
Authors: Wang Lei , Chen Xin , Du Yeqin , Zhang Di , Tang Zhanhui
Published: April 2022

Arbuscular mycorrhizal fungi (AMF) colonize the rhizosphere of plants and form a symbiotic association with plants. Mycorrhizal symbionts have diversified ecological roles and functions which are affected by soil conditions. Understanding the effects of different AMF inoculation on plants under varied nutritional conditions is of great significance for further understanding the effects of the external environment regulating mycorrhizal symbiosis on plant phenotypic traits. In this study, the effects of four AMF inoculation treatments on the growth and reproductive performance of cherry tomato (Solanum lycopersicum var. cerasiforme) were investigated under three nutrient levels by pot experiment. It was found that the growth-promoting effect of AMF on cherry tomato decreased with nutrient reduction, and the effects of the same AMF inoculation treatment on cherry tomato were different at different nutrient levels. Nutrient levels and AMF had interactive effects on flower characteristics, fruit yield, resource allocation, and seed germination of the cherry tomato. In addition, AMF could promote sexual reproductive investment. Nutrient levels and AMF also affected the accumulation of nitrogen and phosphorus in cherry tomato, and there were significant differences among different AMF inoculation treatments. The results indicated that nutrient differences could affect the symbiosis between AMF and plants, and confirmed that there were differences in the effects of the four AMF inoculation treatments on the growth and reproductive traits of plants. The differences in growth and reproduction characteristics of cherry tomato between different AMF inoculation treatments at different nutrient levels indicated that the effects of AMF mycorrhizal on the traits of cherry tomato were regulated by nutrients.
Characterization and Function of the Interaction of Angiogenin With Alpha-Actinin 2
Authors: Weng Chunhua , Dong Haojie , Mao Jiajia , Lang Xiabing , Chen Jianghua
Published: April 2022

Angiogenin (ANG) is the first human tumor-derived angiogenic protein, which can promote angiogenesis and tumor growth. In a previous study, we identified alpha-actinin 2 (ACTN2), a cytoskeletal protein, as a direct interacting protein with angiogenin. However, the interaction between ANG and ACTN2 was not characterized in detail, which may provide information on the molecular mechanisms of ANG functions. In this study, we mapped the accurate binding domain and sites in ANG and ACTN2, respectively. In ANG, the residues from 83 to 105 are the smallest motif that can bind to ACTN2. We then use site mutation analysis to identify the precise binding sites of ANG in the interaction and found that the 101st residue arginine (R101) represents the critical residue involved in the ANG–ACTN2 interaction. In ACTN2, the residues from 383 to 632, containing two spectrin domains in the middle of the rod structure of ACTN2, play an important role in the interaction. Furthermore, we validated the interaction of ACTN2-383–632 to ANG by glutathione-S-transferase (GST) pull-down assay. In functional analysis, overexpressed ACTN2-383–632 could impair tumor cell motility observably, including cell migration and invasion. Meanwhile, ACTN2-383–632 overexpression inhibited tumor cell proliferation and survival as well. These data suggest that an excess expression of ACTN2 segment ACTN2-383–632 can inhibit tumor cell motility and proliferation by interfering with the interaction between ANG and ACTN2, which provides a potential mechanism of ANG action in tumor growth and metastasis.
Adult-Onset Neuronal Ceroid Lipofuscinosis With a Novel DNAJC5 Mutation Exhibits Aberrant Protein Palmitoylation
Authors: Huang Qiang , Zhang Yong-Fang , Li Lin-Jie , Dammer Eric B. , Hu Yong-Bo , Xie Xin-Yi , Tang Ran , Li Jian-Ping , Wang Jin-Tao , Che Xiang-Qian , Wang Gang , Ren Ru-Jing
Published: April 2022

Neuronal ceroid lipofuscinosis (NCL) is composed of a group of inherited neurodegenerative diseases, with the hallmark of lipofuscin deposit (a mixture of lipids and proteins with metal materials) inside the lysosomal lumen, which typically emits auto-fluorescence. Adult-onset NCL (ANCL) has been reported to be associated with a mutation in the DNAJC5 gene, including L115R, L116Δ, and the recently identified C124_C133dup mutation. In this study, we reported a novel C128Y mutation in a young Chinese female with ANCL, and this novel mutation caused abnormal palmitoylation and triggered lipofuscin deposits.
Dysfunction in the Interaction of Information Between and Within the Bilateral Primary Sensory Cortex
Authors: Xing Xiang-Xin , Ma Zhen-Zhen , Wu Jia-Jia , Ma Jie , Duan Yu-Jie , Hua Xu-Yun , Zheng Mou-Xiong , Xu Jian-Guang
Published: April 2022

Background

Interhemispheric and intrahemispheric long-range synchronization and information communication are crucial features of functional integration between the bilateral hemispheres. Previous studies have demonstrated that disrupted functional connectivity (FC) exists in the bilateral hemispheres of patients with carpal tunnel syndrome (CTS), but they did not clearly clarify the phenomenon of central dysfunctional connectivity. This study aimed to further investigate the potential mechanism of the weakened connectivity of primary somatosensory cortex (S1) based on a precise template.

Methods

Patients with CTS (n = 53) and healthy control subjects (HCs) (n = 23) participated and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We used FC to investigate the statistical dependency of the whole brain, effective connectivity (EC) to analyze time-dependent effects, and voxel-mirrored homotopic connectivity (VMHC) to examine the coordination of FC, all of which were adopted to explore the change in interhemispheric and intrahemispheric S1.

Results

Compared to the healthy controls, we significantly found a decreased strength of the two connectivities in the interhemispheric S1hand, and the results of EC and VMHC were basically consistent with FC in the CTS. The EC revealed that the information output from the dominant hemisphere to the contralateral hemisphere was weakened.

Conclusion

This study found that maladjusted connections between and within the bilateral S1 revealed by these methods are present in patients with CTS. The dominant hemisphere with deafferentation weakens its effect on the contralateral hemisphere. The disturbance in the bilateral S1 provides reliable evidence to understand the neuropathophysiological mechanisms of decreased functional integration in the brains of patients with CTS.
Neurobiology of Loneliness, Isolation, and Loss: Integrating Human and Animal Perspectives
Authors: Vitale Erika M. , Smith Adam S.
Published: April 2022

In social species such as humans, non-human primates, and even many rodent species, social interaction and the maintenance of social bonds are necessary for mental and physical health and wellbeing. In humans, perceived isolation, or loneliness, is not only characterized by physical isolation from peers or loved ones, but also involves negative perceptions about social interactions and connectedness that reinforce the feelings of isolation and anxiety. As a complex behavioral state, it is no surprise that loneliness and isolation are associated with dysfunction within the ventral striatum and the limbic system – brain regions that regulate motivation and stress responsiveness, respectively. Accompanying these neural changes are physiological symptoms such as increased plasma and urinary cortisol levels and an increase in stress responsivity. Although studies using animal models are not perfectly analogous to the uniquely human state of loneliness, studies on the effects of social isolation in animals have observed similar physiological symptoms such as increased corticosterone, the rodent analog to human cortisol, and also display altered motivation, increased stress responsiveness, and dysregulation of the mesocortical dopamine and limbic systems. This review will discuss behavioral and neuropsychological components of loneliness in humans, social isolation in rodent models, and the neurochemical regulators of these behavioral phenotypes with a neuroanatomical focus on the corticostriatal and limbic systems. We will also discuss social loss as a unique form of social isolation, and the consequences of bond disruption on stress-related behavior and neurophysiology.
Color Constancy via Multi-Scale Region-Weighed Network Guided by Semantics
Authors: Wang Fei , Wang Wei , Wu Dan , Gao Guowang
Published: April 2022

In obtaining color constancy, estimating the illumination of a scene is the most important task. However, due to unknown light sources and the influence of the external imaging environment, the estimated illumination is prone to color ambiguity. In this article, a learning-based multi-scale region-weighed network guided by semantic features is proposed to estimate the illuminated color of the light source in a scene. Cued by the human brain's processing of color constancy, we use image semantics and scale information to guide the process of illumination estimation. First, we put the image and its semantics into the network, and then obtain the region weights of the image at different scales. After that, through a special weight-pooling layer (WPL), the illumination on each scale is estimated. The final illumination is calculated by weighting each scale. The results of extensive experiments on Color Checker and NUS 8-Camera datasets show that the proposed approach is superior to the current state-of-the-art methods in both efficiency and effectiveness.
The Role of Oxidative Stress and Inflammation in X-Link Adrenoleukodystrophy
Authors: Yu Jiayu , Chen Ting , Guo Xin , Zafar Mohammad Ishraq , Li Huiqing , Wang Zhihua , Zheng Juan
Published: April 2022

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease caused by a mutation in the ABCD1 gene encoding a peroxisomal transmembrane protein. It is characterized by the accumulation of very-long-chain fatty acids (VLCFAs) in body fluids and tissues, leading to progressive demyelination and adrenal insufficiency. ALD has various phenotypes, among which the most common and severe is childhood cerebral adrenoleukodystrophy (CCALD). The pathophysiological mechanisms of ALD remain unclear, but some in vitro/in vivo research showed that VLCFA could induce oxidative stress and inflammation, leading to damage. In addition, the evidence that oxidative stress and inflammation are increased in patients with X-ALD also proves that it is a potential mechanism of brain and adrenal damage. Therefore, normalizing the redox balance becomes a critical therapeutic target. This study focuses on the possible predictors of the severity and progression of X-ALD, the potential mechanisms of pathogenesis, and the promising targeted drugs involved in oxidative stress and inflammation.
Characterisation of Zamorano-Leonese Donkey Milk as an Alternative Sustainably Produced Protein Food
Authors: Albertos Irene , López María , Jiménez José-María , Cao María José , Corell Alfredo , Castro-Alija María José
Published: April 2022

The Zamorano-Leonese donkey is the local breed of the Castilla y León region of Spain and is a protected endangered species. The best way to preserve it is to explore viable alternatives such as milk production. Unlike other donkey breeds, this one has not been previously characterised. The aim of this work is the complete nutritional characterisation of its milk for human consumption, either directly or as an ingredient, to meet the new consumer expectations of sustainability and health concerns. This breed did not differ from others in terms of amino acid and protein profile. Its low concentration of β-lactoglobulin may be correlated to a low allergenicity. The presence of lactozyme and lactoferrin, which are potent antimicrobials, stand out among the proteins. This milk presented a higher content of unsaturated fatty acids, being oleic fatty acid the main one. Zamorano-Leonese donkey milk did have a higher content of vitamin C, riboflavin, folic acid and vitamin E than the other donkey breeds. It also had a high concentration of vitamin D despite its low-fat content. However, its mineral concentration was lower than other donkey breeds in line with its lower ash content. In terms of micronutrients, it had a high amount of zinc and selenium. Based on these results we can conclude that donkey milk is a food and/or ingredient with beneficial effects on cardiovascular health and the proper functioning of the immune system, as well as being a good source of protein. Therefore, donkey milk from this local species from Spain is a food and/or ingredient with beneficial nutritional properties and sustainable from an environmental point of view.
Automatic Prostate Gleason Grading Using Pyramid Semantic Parsing Network in Digital Histopathology
Authors: Qiu Yali , Hu Yujin , Kong Peiyao , Xie Hai , Zhang Xiaoliu , Cao Jiuwen , Wang Tianfu , Lei Baiying
Published: April 2022

Purpose

Prostate biopsy histopathology and immunohistochemistry are important in the differential diagnosis of the disease and can be used to assess the degree of prostate cancer differentiation. Today, prostate biopsy is increasing the demand for experienced uropathologists, which puts a lot of pressure on pathologists. In addition, the grades of different observations had an indicating effect on the treatment of the patients with cancer, but the grades were highly changeable, and excessive treatment and insufficient treatment often occurred. To alleviate these problems, an artificial intelligence system with clinically acceptable prostate cancer detection and Gleason grade accuracy was developed.

Methods

Deep learning algorithms have been proved to outperform other algorithms in the analysis of large data and show great potential with respect to the analysis of pathological sections. Inspired by the classical semantic segmentation network, we propose a pyramid semantic parsing network (PSPNet) for automatic prostate Gleason grading. To boost the segmentation performance, we get an auxiliary prediction output, which is mainly the optimization of auxiliary objective function in the process of network training. The network not only includes effective global prior representations but also achieves good results in tissue micro-array (TMA) image segmentation.

Results

Our method is validated using 321 biopsies from the Vancouver Prostate Centre and ranks the first on the MICCAI 2019 prostate segmentation and classification benchmark and the Vancouver Prostate Centre data. To prove the reliability of the proposed method, we also conduct an experiment to test the consistency with the diagnosis of pathologists. It demonstrates that the well-designed method in our study can achieve good results. The experiment also focused on the distinction between high-risk cancer (Gleason pattern 4, 5) and low-risk cancer (Gleason pattern 3). Our proposed method also achieves the best performance with respect to various evaluation metrics for distinguishing benign from malignant.

Availability

The Python source code of the proposed method is publicly available at https://github.com/hubutui/Gleason. All implementation details are presented in this paper.

Conclusion

These works prove that the Gleason grading results obtained from our method are effective and accurate.
Current Prognostic and Predictive Biomarkers for Endometrial Cancer in Clinical Practice: Recommendations/Proposal from the Italian Study Group
Authors: Zannoni Gian Franco , Bragantini Emma , Castiglione Francesca , Fassan Matteo , Troncone Giancarlo , Inzani Frediano , Pesci Anna , Santoro Angela , Fraggetta Filippo
Published: April 2022

Endometrial carcinoma (EC) is the most common gynecological malignant disease in high-income countries, such as European countries and the USA. The 2020 edition of the World Health Organization (WHO) Classification of Tumors of the Female Genital Tract underlines the important clinical implications of the proposed new histomolecular classification system for ECs. In view of the substantial genetic and morphological heterogeneity in ECs, both classical pthological parameters and molecular classifiers have to be integrated in the pathology report. This review will focus on the most commonly adopted immunohistochemical and molecular biomarkers in daily clinical characterization of EC, referring to the most recent published recommendations, guidelines, and expert opinions.
VEGF-D Serum Level as a Potential Predictor of Lymph Node Metastasis and Prognosis in Vulvar Squamous Cell Carcinoma Patients
Authors: Ravaggi Antonella , Gambino Angela , Ferrari Federico , Olivari Alessandro , Zanotti Laura , Romani Chiara , Ardighieri Laura , Antonelli Paolo , Garganese Giorgia , Gallo Daniela , Scambia Giovanni , Bignotti Eliana , Sartori Enrico , Calza Stefano , Odicino Franco
Published: April 2022

Background

Radical surgical resection of the primary tumor with mono/bilateral inguinofemoral lymph node dissection is the standard treatment for invasive vulvar squamous cell carcinoma (VSCC) and is frequently related to severe morbidity. Tailoring surgical treatment is of paramount importance, and a comprehensive preoperative evaluation is mandatory. Vascular endothelial growth factor D (VEGF-D) is considered a regulator of lymphangiogenesis involved in tumor spread via lymphatic vessels. The aim of this study was to evaluate the potential of VEGF-D in the prediction of inguinofemoral lymph node metastasis.

Methods

We analyzed the preoperative levels of serum VEGF-D (sVEGF-D) from two independent cohorts of patients with VSCC by enzyme-linked immunosorbent assay and its protein expression on tumor tissue by immunohistochemistry. Logistic regression was performed to identify the independent risk factors for lymph node metastasis, and Cox proportional hazard model was used for survival analysis.

Results

High levels of sVEGF-D, but not tissue VEGF-D, significantly correlated with positive groin nodes and a more advanced International Federation of Gynecologists and Obstetricians (FIGO) stage. In multivariable analysis, a high sVEGF-D level was an independent predictor of lymph node metastasis and worse prognosis. A prediction model based on sVEGF-D, tumor grade assessed on biopsy, tumor diameter, and lymph node clinical evaluation was able to predict lymph node metastasis, reaching C-index values of 0.79 and 0.73 in the training and validation cohorts, respectively.

Conclusions

The preoperative sVEGF-D level might be a reliable biomarker for the prediction of lymph node metastasis and prognosis in patients with VSCC, supporting better clinical/surgical decision. Multicenter prospective studies are required to confirm our findings.
Diagnosis of Subcortical Ischemic Vascular Cognitive Impairment With No Dementia Using Radiomics of Cerebral Cortex and Subcortical Nuclei in High-Resolution T1-Weighted MR Imaging
Authors: Liu Bo , Meng Shan , Cheng Jie , Zeng Yan , Zhou Daiquan , Deng Xiaojuan , Kuang Lianqin , Wu Xiaojia , Tang Lin , Wang Haolin , Liu Huan , Liu Chen , Li Chuanming
Published: April 2022

Purpose

To investigate whether the combination of radiomics derived from brain high-resolution T1-weighted imaging and automatic machine learning could diagnose subcortical ischemic vascular cognitive impairment with no dementia (SIVCIND) accurately.

Methods

A total of 116 right-handed participants involving 40 SIVCIND patients and 76 gender-, age-, and educational experience-matched normal controls (NM) were recruited. A total of 7,106 quantitative features from the bilateral thalamus, hippocampus, globus pallidus, amygdala, nucleus accumbens, putamen, caudate nucleus, and 148 areas of the cerebral cortex were automatically calculated from each subject. Six methods including least absolute shrinkage and selection operator (LASSO) were utilized to lessen the redundancy of features. Three supervised machine learning approaches of logistic regression (LR), random forest (RF), and support vector machine (SVM) employing 5-fold cross-validation were used to train and establish diagnosis models, and 10 times 10-fold cross-validation was used to evaluate the generalization performance of each model. Correlation analysis was performed between the optimal features and the neuropsychological scores of the SIVCIND patients.

Results

Thirteen features from the right amygdala, right hippocampus, left caudate nucleus, left putamen, left thalamus, and bilateral nucleus accumbens were included in the optimal subset. Among all the three models, the RF produced the highest diagnostic performance with an area under the receiver operator characteristic curve (AUC) of 0.990 and an accuracy of 0.948. According to the correlation analysis, the radiomics features of the right amygdala, left caudate nucleus, left putamen, and left thalamus were found to be significantly correlated with the neuropsychological scores of the SIVCIND patients.

Conclusions

The combination of radiomics derived from brain high-resolution T1-weighted imaging and machine learning could diagnose SIVCIND accurately and automatically. The optimal radiomics features are mostly located in the right amygdala, left caudate nucleus, left putamen, and left thalamus, which might be new biomarkers of SIVCIND.
Management of BRCA Tumour Testing in an Integrated Molecular Tumour Board Multidisciplinary Model
Authors: Azzollini Jacopo , Vingiani Andrea , Agnelli Luca , Tamborini Elena , Perrone Federica , Conca Elena , Capone Iolanda , Busico Adele , Peissel Bernard , Rosina Erica , Ducceschi Monika , Mantiero Mara , Lopez Salvatore , Raspagliesi Francesco , Niger Monica , Duca Matteo , Damian Silvia , Proto Claudia , de Braud Filippo , Pruneri Giancarlo , Manoukian Siranoush
Published: April 2022

Tumour testing of the BRCA1/2 genes is routinely performed in patients with different cancer histological subtypes. To accurately identify patients with tumour-detected germline pathogenic variants (PVs) is a relevant issue currently under investigation. This study aims at evaluating the performance of the tumour-to-germline diagnostic flowchart model defined at our Institutional Molecular Tumour Board (MTB). Results from tumour BRCA sequencing of 641 consecutive unselected cancer patients were discussed during weekly MTB meetings with the early involvement of clinical geneticists for appropriate referral to genetic counselling. The overall tumour detection rate of BRCA1/2 PVs was 8.7% (56/641), ranging from 24.4% (31/127) in high-grade ovarian cancer to 3.9% (12/304) in tumours not associated with germline BRCA1/2 PVs. Thirty-seven patients with PVs (66%) were evaluated by a clinical geneticist, and in 24 of them (64.9%), germline testing confirmed the presence of the PV in blood. Nine of these patients (37.5%) were not eligible for germline testing according to the criteria in use at our institution. Cascade testing was subsequently performed on 18 relatives. The tumour-to-germline diagnostic pipeline, developed in the framework of our institutional MTB, compared with guideline-based germline testing following genetic counselling, proved to be effective in identifying a higher number of germline BRCA PVs carriers.
Variation in Cancer Incidence Rates Among Non-Hispanic Black Individuals Disaggregated by Nativity and Birthplace, 2005-2017: A Population-Based Cancer Registry Analysis
Authors: Llanos Adana A. M. , Li Jie , Tsui Jennifer , Gibbons Joseph , Pawlish Karen , Nwodili Fechi , Lynch Shannon , Ragin Camille , Stroup Antoinette M.
Published: April 2022

Objectives

Compared to other racial and ethnic groups, little to no disaggregated cancer incidence data exist for subgroups of non-Hispanic Blacks (NHBs), despite heterogeneity in sociodemographic characteristics and cancer risk factors within this group. Our objective was to examine age-adjusted cancer incidence by nativity and birthplace among NHB cancer cases diagnosed in New Jersey.

Methods

Race, ethnicity, and birthplace data from the New Jersey State Cancer Registry were used to classify NHB cancer cases diagnosed between 2005-2017. Thirteen waves of population estimates (by county, nativity, gender, age-group) were derived from the American Community Survey using Integrated Public-Use Microdata to approximate yearly demographics. Age-adjusted cancer incidence rates (overall and by site) by birthplace were generated using SEER*Stat 8.3.8. Bivariate associations were assessed using chi-square and Fisher’s exact tests. Trend analyses were performed using Joinpoint 4.7.

Results

Birthplace was available for 62.3% of the 71,019 NHB cancer cases. Immigrants represented 12.3%, with African-born, Haitian-born, Jamaican-born, ‘other-Caribbean-born’, and ‘other-non-American-born’ accounting for 18.5%, 17.7%, 16.5%, 10.6%, and 36.8%, respectively. Overall, age-adjusted cancer incidence rates were lower for NHB immigrants for all sites combined and for several of the top five cancers, relative to American-born NHBs. Age-adjusted cancer incidence was lower among immigrant than American-born males (271.6 vs. 406.8 per 100,000) and females (191.9 vs. 299.2 per 100,000). Age-adjusted cancer incidence was lower for Jamaican-born (114.6 per 100,000) and other-Caribbean-born females (128.8 per 100,000) than African-born (139.4 per 100,000) and Haitian-born females (149.9 per 100,000). No significant differences in age-adjusted cancer incidence were observed by birthplace among NHB males. Age-adjusted cancer incidence decreased for all sites combined from 2005-2017 among American-born males, immigrant males, and American-born females, while NHB immigrant female rates remained relatively stable.

Conclusions

There is variation in age-adjusted cancer incidence rates across NHB subgroups, highlighting the need for more complete birthplace information in population-based registries to facilitate generating disaggregated cancer surveillance statistics by birthplace. This study fills a knowledge gap of critical importance for understanding and ultimately addressing cancer inequities.