bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographical Landscape and Transmission Dynamics of SARS-CoV-2 Variants Across India: A Longitudinal Perspective
Authors: Jha Neha , Hall Dwight , Kanakan Akshay , Mehta Priyanka , Maurya Ranjeet , Mir Quoseena , Gill Hunter Mathias , Janga Sarath Chandra , Pandey Rajesh
Published: December 2021

Globally, SARS-CoV-2 has moved from one tide to another with ebbs in between. Genomic surveillance has greatly aided the detection and tracking of the virus and the identification of the variants of concern (VOC). The knowledge and understanding from genomic surveillance is important for a populous country like India for public health and healthcare officials for advance planning. An integrative analysis of the publicly available datasets in GISAID from India reveals the differential distribution of clades, lineages, gender, and age over a year (Apr 2020–Mar 2021). The significant insights include the early evidence towards B.1.617 and B.1.1.7 lineages in the specific states of India. Pan-India longitudinal data highlighted that B.1.36* was the predominant clade in India until January–February 2021 after which it has gradually been replaced by the B.1.617.1 lineage, from December 2020 onward. Regional analysis of the spread of SARS-CoV-2 indicated that B.1.617.3 was first seen in India in the month of October in the state of Maharashtra, while the now most prevalent strain B.1.617.2 was first seen in Bihar and subsequently spread to the states of Maharashtra, Gujarat, and West Bengal. To enable a real time understanding of the transmission and evolution of the SARS-CoV-2 genomes, we built a transmission map available on https://covid19-indiana.soic.iupui.edu/India/EmergingLineages/April2020/to/March2021. Based on our analysis, the rate estimate for divergence in our dataset was 9.48 e-4 substitutions per site/year for SARS-CoV-2. This would enable pandemic preparedness with the addition of future sequencing data from India available in the public repositories for tracking and monitoring the VOCs and variants of interest (VOI). This would help aid decision making from the public health perspective.
Combined Transcriptome and Proteome Analysis of Anthers of AL-type Cytoplasmic Male Sterile Line and Its Maintainer Line Reveals New Insights into Mechanism of Male Sterility in Common Wheat
Authors: Hao Miaomiao , Yang Wenlong , Li Tingdong , Shoaib Muhammad , Sun Jiazhu , Liu Dongcheng , Li Xin , Nie Yingbin , Tian Xiaoming , Zhang Aimin
Published: December 2021

Cytoplasmic male sterility (CMS) plays an essential role in hybrid seeds production. In wheat, orf279 was reported as a CMS gene of AL-type male sterile line (AL18A), but its sterility mechanism is still unclear. Therefore, transcriptomic and proteomic analyses of the anthers of AL18A and its maintainer line (AL18B) were performed to interpret the sterility mechanism. Results showed that the electron transport chain and ROS scavenging enzyme expression levels changed in the early stages of the anther development. Biological processes, i.e., fatty acid synthesis, lipid transport, and polysaccharide metabolism, were abnormal, resulting in pollen abortion in AL18A. In addition, we identified several critical regulatory genes related to anther development through combined analysis of transcriptome and proteome. Most of the genes were enzymes or transcription factors, and 63 were partially homologous to the reported genic male sterile (GMS) genes. This study provides a new perspective of the sterility mechanism of AL18A and lays a foundation to study the functional genes of anther development.
Microhomology-Mediated Nonhomologous End Joining Caused Rearrangement of EMD and FLNA in Emery-Dreifuss Muscular Dystrophy
Authors: Song Danyu , Li Xiaomei , Wei Wei , Liu Xueqin , Wu Lin , Xiong Hui
Published: December 2021

Background: Emery–Dreifuss muscular dystrophy (EDMD) is a rare disease characterized by early joint contractures, slowly progressive muscular dystrophy, and cardiac involvement, which includes arrhythmia, dilated cardiomyopathy, hypertrophic cardiomyopathy, heart failure, and sudden death.

Methods: Clinical data of the proband and family members were collected. The next-generation sequencing technology was used to analyze the pathogenic variants and copy number variations. Polymerase chain reaction was used to sequence the breakpoints of gene locus rearrangements.

Results: Here, we report two siblings with EDMD in a family. The proband, a 17-year-old boy, manifested a dilated right heart, bradycardia, mild muscle weakness, and joint contractures. His younger brother only showed a mild bowing limitation with elevated creatine kinase. Next-generation sequencing revealed the complete deletion of EMD and a rearrangement in FLNA (exon29_48dup) in these two patients. The EMD deletion and partial FLNA duplication were accompanied by a 5 bp overlap (GTCCC) on the background of the FLNA-EMD inversion. These findings support the pathogenic mechanism of microhomology-mediated nonhomologous end joining.

Conclusion: We report two siblings with complete EMD deletion and FLNA duplication in a family. A microhomology-mediated nonhomologous end joining event involving EMD and FLNA acts as the underlying mechanism.
Positive LGI1 Antibodies in CSF and Relapse Relate to Worse Outcome in Anti-LGI1 Encephalitis
Authors: Cui Li-li , Boltze Johannes , Zhang Yan
Published: December 2021

Objective

This single-center study was conducted in a cohort of patients with anti-LGI1 encephalitis to investigate the factors related to their functional recovery.

Methods

We retrospectively collected the clinical information of patients admitted to Xuanwu Hospital from January 2014 until December 2019, and followed up for at least 12 months.

Results

A total of 67 patients were included, and 57 completed the 12-month follow-up. Most of the patients (55/57, 96.5%) achieved functional improvement after immunotherapy, and 26 (45.6%) became symptom-free. Compared to patients with complete recovery, patients with partial or no recovery had significantly higher incidences of consciousness disorders (25.8% vs. 0%, P<0.05) and positive LGI1 antibodies in cerebrospinal fluid (CSF) (71.0% vs. 46.2%, P<0.05). These patients also had a lower Barthel Index both upon admission and at discharge, as well as a higher incidence of relapse (25.8% vs. 3.8%; P<0.05 each). Univariate logistic regression showed that positive LGI1 antibodies in CSF and relapse were associated with incomplete recovery at 1-year follow-up (both P<0.05), but only relapse remained statistically significant after multivariate logistic regression (P=0.034).

Conclusion

Patients with LGI1 antibodies in CSF and those who relapsed were more likely to experience worse outcome. Early recognition of these patients, combined with more aggressive immunotherapy may result in better recovery.
Identification of Profound Metabolic Alterations in Human Dendritic Cells by Progesterone Through Integrated Bioinformatics Analysis
Authors: Zhang Sainan , Liu Su , Hong Ling , Wang Xiaohui , Diao Lianghui , Cai Songchen , Yin Tailang , Zeng Yong
Published: December 2021

Maintaining the homeostasis of the decidual immune microenvironment at the maternal-fetal interface is essential for reproductive success. Dendritic cells (DCs) are the professional antigen-presenting cells and dominate this balance of immunogenicity and tolerance. Progesterone (P4) is highlighted as the “hormone of pregnancy” in most eutherian mammals because of its regulatory role in immune-endocrine behavior during pregnancy. Recent studies have shown that P4 is associated with the differentiation and function of DCs, however, the underlying mechanisms remain unidentified. In addition, while progress in the field of immunometabolism has highlighted the intimate connections between the metabolism phenotype and the immunogenic or tolerogenic fate of DCs, whether P4 can affect DCs metabolism and thus exert a functional manipulation has not yet been explored. In this study, we acquired human peripheral blood monocyte-derived DCs and conducted RNA sequencing (RNA-seq) on immature DCs (iDCs), P4-treated DCs (pDCs), and mature DCs (mDCs), aiming to comprehensively assess the effects of P4 on DCs. Our results showed pDCs performed a distinct differentially expressed genes (DEGs) profile compared with iDCs or mDCs. Further functional enrichment and weighted gene co-expression network (WGCNA) analysis found that these DEGs were related not only to the cellular components but also to the significant metabolic activities, including mitochondrial oxidative phosphorylation (OXPHOS) and fatty acid metabolism. In addition, these changes may be involved in the activation of various signaling pathways of PI3K/Akt/mTOR, AMPK/PGC1-α, and PPAR-γ. In summary, our work suggested that P4 induced profound metabolic alterations of mitochondrial OXPHOS and fatty acid metabolism in DCs. Our findings may provide new insights into the role of P4 in DCs.
Mini Review: Forensic Value of Aquaporines
Authors: Prangenberg Julian , Doberentz Elke , Madea Burkhard
Published: December 2021

Forensic pathologists are routinely confronted with unclear causes of death or findings. In some scenarios, it can be difficult to answer the specific questions posed by criminal investigators or prosecutors. Such scenarios may include questions about wound vitality or causes of death when typical or landmark findings are difficult to find. In addition to the usual subsequent examinations to clarify unclear causes of death or special questions, immunohistochemical analysis has become increasingly important since its establishment in the early 40s of the 20th century. Since then, numerous studies have been conducted to determine the usefulness and significance of immunohistochemical investigations on various structures and proteins. These proteins include, for example, aquaporins, which belong to the family of water channels. They enable the transport of water and of small molecules, such as glycerol, through biological channels and so far, 13 classes of aquaporins could have been identified in vertebrates. The classic aquaporin channels 1, 2, 4 and 5 are only permeable to water. The aquaporin channels 3, 7, 9, and 10 are also called aquaglycerolporins since they can also transport glycerol. This mini review discusses the immunohistochemical research on aquaporins, their range of applications, and respective forensic importance, their current limitations, and possible further implementations in the future.
Effects of Oat Varieties and Growing Locations on Seed-Borne Fungal Communities
Authors: Wang Jianjun , Wei Xuekai , Chen Taixiang , White James F. , Zhao Guiqin , Li Chunjie
Published: December 2021

Many species of seed-borne fungi are closely allied with seed varieties and growing regions, including many seed-borne pathogens, but their species richness and distribution remain largely unknown. This study was conducted to explore the seed-borne fungal composition, abundance and diversity in Avena sativa (B7) and A. nuda (B2) seed samples collected from Baicheng (BB), Dingxi (DB) and Haibei (HB) city, using Illumina sequencing techniques. Our results show that a total of 543,707 sequences were obtained and these were assigned to 244 operational taxonomic units (OTUs) with 97% similarity. Oat varieties and growing locations had a significant difference on seed-borne fungal diversity. HB had a higher fungal diversity than BB and DB, Shannon diversity and ACE richness index of fungal in HB seeds was significantly higher than in BB and DB (P < 0.05). In different varieties, both taxon richness and evenness of B7 seeds was significantly higher than B2 (P < 0.05). A total of 4 fungal phyla and 26 fungal genera were detected. Ascomycota was the dominant phylum and Alternaria sp. was the most abundant genus in B2 and B7 oat seeds from different regions. Mycosphaerella sp. had a higher abundance in HB7 and DB7, respectively, Epicoccum sp. had a higher abundance in HB7 and BB7. The results of alpha and beta diversity analysis revealed the presence of different effects in fungal communities of different varieties and regions of oat, especially in seed pathogenic fungi distribution. Structural equation modeling also explained oat varieties and growing regions have significant influences on seed-borne fungal abundance, composition and diversity. This study demonstrated that the differences of varieties and regions are the main factors resulting in the changes of seed-borne fungal community of oat.
Advances in Metagenomics and Its Application in Environmental Microorganisms
Authors: Zhang Lu , Chen FengXin , Zeng Zhan , Xu Mengjiao , Sun Fangfang , Yang Liu , Bi Xiaoyue , Lin Yanjie , Gao YuanJiao , Hao HongXiao , Yi Wei , Li Minghui , Xie Yao
Published: December 2021

Metagenomics is a new approach to study microorganisms obtained from a specific environment by functional gene screening or sequencing analysis. Metagenomics studies focus on microbial diversity, community constitute, genetic and evolutionary relationships, functional activities, and interactions and relationships with the environment. Sequencing technologies have evolved from shotgun sequencing to high-throughput, next-generation sequencing (NGS), and third-generation sequencing (TGS). NGS and TGS have shown the advantage of rapid detection of pathogenic microorganisms. With the help of new algorithms, we can better perform the taxonomic profiling and gene prediction of microbial species. Functional metagenomics is helpful to screen new bioactive substances and new functional genes from microorganisms and microbial metabolites. In this article, basic steps, classification, and applications of metagenomics are reviewed.
Yeast β-Glucan Altered Intestinal Microbiome and Metabolome in Older Hens
Authors: Zhen Wenrui , Liu Yuchen , Shao Yujing , Ma Yanbo , Wu Yuanyuan , Guo Fangshen , Abbas Waseem , Guo Yuming , Wang Zhong
Published: December 2021

The prebiotics- and probiotics-mediated positive modulation of the gut microbiota composition is considered a useful approach to improve gut health and food safety in chickens. This study explored the effects of yeast β-glucan (YG) supplementation on intestinal microbiome and metabolites profiles as well as mucosal immunity in older hens. A total of 256 43-week-old hens were randomly assigned to two treatments, with 0 and 200 mg/kg of YG. Results revealed YG-induced downregulation of toll-like receptors (TLRs) and cytokine gene expression in the ileum without any effect on the intestinal barrier. 16S rRNA analysis claimed that YG altered α- and β-diversity and enriched the relative abundance of class Bacilli, orders Lactobacillales and Enterobacteriales, families Lactobacillaceae and Enterobacteriaceae, genera Lactobacillus and Escherichia–Shigella, and species uncultured bacterium-Lactobacillus. Significant downregulation of cutin and suberin, wax biosynthesis, atrazine degradation, vitamin B6 metabolism, phosphotransferase system (PTS), steroid degradation, biosynthesis of unsaturated fatty acids, aminobenzoate degradation and quorum sensing and upregulation of ascorbate and aldarate metabolism, C5-branched dibasic acid metabolism, glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions, steroid biosynthesis, carotenoid biosynthesis, porphyrin and chlorophyll metabolism, sesquiterpenoid and triterpenoid biosynthesis, lysine degradation, and ubiquinone and other terpenoid-quinone biosyntheses were observed in YG-treated hens, as substantiated by the findings of untargeted metabolomics analysis. Overall, YG manifests prebiotic properties by altering gut microbiome and metabolite profiles and can downregulate the intestinal mucosal immune response of breeder hens.
Glymphatic Drainage Blocking Aggravates Brain Edema, Neuroinflammation via Modulating TNF-α, IL-10, and AQP4 After Intracerebral Hemorrhage in Rats
Authors: Liu Xichang , Wu Gang , Tang Na , Li Li , Liu Cuimin , Wang Feng , Ke Shaofa
Published: December 2021

Objective: The “Glymphatic” system, a network of perivascular tunnels wrapped by astrocyte endfeet, was reported to be closely associated with the diseases of the central nervous system. Here, we investigated the role of the glymphatic system in intracerebral hemorrhage (ICH) and its protective mechanism.

Method: Experimental ICH model was induced by type IV collagenase in rats. Cerebral lymphatic blockage was induced by ligation and removal of cervical lymph nodes. The experimental rats were divided into sham-operated (SO) group, ICH group, and cerebral lymphatic blocking and ICH (ICH + CLB) group. Neurological scores were measured using the Garcia scoring system on the third and seventh day after ICH. Active caspase-3 was immunostained to evaluate neuronal apoptosis. Brain water content was calculated using the dry-wet specific gravity method. The expression of inflammatory factors TNF-α, IL-1β, and IL-10 were detected using ELISA. Aquaporins-4 (AQP-4) and glial fibrillary acidic protein (GFAP) were detected using western blot analysis.

Results: The neurological scores of rats in the CLB + ICH group were significantly lower than those in the in ICH group. The number of active caspase-3 neurons was significantly higher in the CLB + ICH group compared to the ICH group. CLB significantly aggravated ICH-induced brain edema 3 d after ICH. There was an increase in the expression of TNF-α, IL-1β, IL-10, AQP-4, GFAP after ICH. The expression of TNF-α was significantly higher in the CLB + ICH group compared to ICH group 3 d after ICH while there was no difference 7 d after ICH. There was no statistical difference in the expression of IL-1β between the ICH group and CLB + ICH group. However, the expression of IL-10 in the CLB + ICH group was significantly lower than that in the ICH group. Lastly, AQP-4 expression was significantly lower in the CLB + ICH group compared to the ICH group while the expression of GFAP was higher in the CLB + ICH group compared to the ICH group.

Conclusion: CLB exacerbated cerebral edema, neuroinflammation, neuronal apoptosis and caused neurological deficits in rats with ICH via down-regulating AQP-4, up-regulating inflammatory TNF-α and inhibiting IL-10 expression. The glymphatic drainage system protects against neurologic injury after ICH induction in rats under normal physiological conditions.
Genome-Wide Association Study of 2,093 Cases With Idiopathic Polyneuropathy and 445,256 Controls Identifies First Susceptibility Loci
Authors: Winsvold Bendik S. , Kitsos Ioannis , Thomas Laurent F. , Skogholt Anne Heidi , Gabrielsen Maiken E. , Zwart John-Anker , Nilsen Kristian Bernhard
Published: December 2021

Background: About one third of patients with chronic polyneuropathy have no obvious underlying etiology and are classified as having idiopathic polyneuropathy. The lack of knowledge about pathomechanisms and predisposing factors limits the development of effective prevention and treatment for these patients. We report the first genome-wide association study (GWAS) of idiopathic polyneuropathy.

Methods: Cases with idiopathic polyneuropathy and healthy controls were identified by linkage to hospital records. We performed genome-wide association studies using genetic data from two large population-based health studies, the Trøndelag Health Study (HUNT, 1,147 cases and 62,204 controls) and UK Biobank (UKB, 946 cases and 383,052 controls). In a two-stage analysis design, we first treated HUNT as a discovery cohort and UK Biobank as a replication cohort. Secondly, we combined the two studies in a meta-analysis. Downstream analyses included genetic correlation to other traits and diseases. We specifically examined previously reported risk loci, and genes known to cause hereditary polyneuropathy.

Results: No replicable risk loci were identified in the discovery-replication stage, in line with the limited predicted power of this approach. When combined in a meta-analysis, two independent loci reached statistical significance (rs7294354 in B4GALNT3, P-value 4.51 × 10−8) and (rs147738081 near NR5A2, P-value 4.75 × 10−8). Idiopathic polyneuropathy genetically correlated with several anthropometric measures, most pronounced for height, and with several pain-related traits.

Conclusions: In this first GWAS of idiopathic polyneuropathy we identify two risk-loci that indicate possible pathogenetic mechanisms. Future collaborative efforts are needed to replicate and expand on these findings.
Atypical Neural Responses of Cognitive Flexibility in Parents of Children With Autism Spectrum Disorder
Authors: Cheng Xin , Li Yu , Cui Xiwen , Cheng Hong , Li Chunyan , Fu Linyan , Jiang Jiying , Hu Zhenyu , Ke Xiaoyan
Published: December 2021

Impaired cognitive flexibility has been repeatedly demonstrated in autism spectrum disorder (ASD). There is strong evidence for genetic involvement in ASD. First-degree relatives of individuals with ASD may show mild deficits in cognitive inflexibility. The present study investigated cognitive flexibility and its neuroelectrophysiological mechanisms in first-degree relatives of individuals with ASD to assess its potential familiality. Forty-five biological parents of individuals/children with ASD (pASD) and thirty-one biological parents of typically developing individuals/children (pTD), matched by gender, age, and IQ, were enrolled. The broad autism phenotype questionnaire (BAPQ) and cognitive flexibility inventory (CFI) were used to quantitatively assess autistic traits and cognitive flexibility in daily life, respectively. The task-switching paradigm was used to evaluate the behavioral flexibility in a structured assessment situation. Event-related potentials (ERPs) induced by this paradigm were also collected. Results showed that compared with the pTD group, the pASD group had lower CFI scores (t = −2.756, p < 0.01), while both groups showed an equivalent “switch cost” in the task-switching task (p > 0.05). Compared with the pTD group, the pASD group induced greater N2 amplitude at F3, F4, Fz, and C4 (F = 3.223, p < 0.05), while P3 amplitude and latency did not differ between the two groups. In addition, there was a significant negative correlation between the CFI total scores and BAPQ total scores in the pASD group (r = −0.734, p < 0.01). After controlling for age and IQ, the N2 amplitude in the frontal lobe of pASD was negatively correlated with the CFI total scores under the repetition sequence (r = −0.304, p = 0.053). These results indicated that pASD had deficit in cognitive flexibility at the self-reported and neurological levels. The cognitive flexibility difficulties of parents of children with ASD were related to autistic traits. These findings support that cognitive flexibility is most likely a neurocognitive endophenotype of ASD, which is worthy of further investigation.
Preoperative Chronic Pain as a Risk Factor for Early Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Hip Joint Replacement Surgery: A Prospective Observational Cohort Study
Authors: Huai Xiaorong , Jiao Yingfu , Gu Xiyao , Zhu Huichen , Chen Lingke , Fan Yichen , Yu Weifeng , Su Diansan , Xie Hong
Published: December 2021

Background: Although major joint replacement surgery has a high overall success rate, postoperative cognitive dysfunction (POCD) is a common complication after anesthesia and surgery, increasing morbidity and mortality. Identifying POCD risk factors would be helpful to prevent and decrease the occurrence of POCD. We hypothesized that preoperative chronic pain increases the risk of POCD.

Methods: A single-center, observational, prospective cohort study was conducted from January 2018 to March 2020. All consecutive elderly patients (>65 years) who underwent elective total hip arthroplasty or hemiarthroplasty with general anesthesia by the same surgeon were enrolled. The patients underwent neuropsychological testing preoperatively and at 7 days and 2 months after surgery. To determine POCD, a nonsurgical control group was recruited from the general community.

Results: Of the 141 patients who finished the neuropsychological testing 7 days after surgery, 61 (43.2%) had preoperative chronic pain. Of the 61 patients, 17 (27.9%) developed POCD; of the 79 patients with no chronic pain, 10 (12.7%) had developed POCD by 7 days after surgery. Multivariate logistic regression analysis identified preoperative chronic pain as a risk factor of POCD assessed 7 days after surgery (odds ratio 6.527; P = 0.009). There was no significant difference in the POCD incidence 2 months after surgery between patients with and without preoperative chronic pain.

Conclusion: Preoperative chronic pain was a risk factor of developing POCD within 7 days after surgery in elderly patients following hip joint replacement surgery.

Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03393676].
Functional Subdivisions of the Cerebellum in Naturalistic Paradigm Functional Magnetic Resonance Imaging
Authors: Hao Jianing , Hu Xintao , Wang Liting , Guo Lei , Han Junwei
Published: December 2021

Compelling evidence has suggested that the human cerebellum is engaged in a wide range of cognitive tasks besides traditional opinions of motor control, and it is organized into a set of distinct functional subregions. The existing model-driven cerebellum parcellations through resting-state functional MRI (rsfMRI) and task-fMRI are relatively coarse, introducing challenges in resolving the functions of the cerebellum especially when the brain is exposed to naturalistic environments. The current study took the advantages of the naturalistic paradigm (i.e., movie viewing) fMRI (nfMRI) to derive fine parcellations via a data-driven dual-regression-like sparse representation framework. The parcellations were quantitatively evaluated by functional homogeneity, and global and local boundary confidence. In addition, the differences of cerebellum–cerebrum functional connectivities between rsfMRI and nfMRI for some exemplar parcellations were compared to provide qualitatively functional validations. Our experimental results demonstrated that the proposed study successfully identified distinct subregions of the cerebellum. This fine parcellation may serve as a complementary solution to existing cerebellum parcellations, providing an alternative template for exploring neural activities of the cerebellum in naturalistic environments.
Serum Neurofilament Light Chain: A Marker of Nervous System Damage in Myopathies
Authors: Saak Annika , Benkert Pascal , Akgün Katja , Willemse Eline , Kuhle Jens , Ziemssen Tjalf , Jackson Sandra , Schaefer Jochen
Published: December 2021

Purpose: Neurofilament light chain in serum (sNfL) has been suggested as a biomarker for the assessment of neuroaxonal damage. Since NfL are not expressed in muscle, elevated sNfL in patients with primary myopathies suggest additional nervous system involvement. To verify this hypothesis, we measured sNfL in a series of patients with myopathies.

Methods: sNfL were determined in 62 patients with molecular proven primary myopathies in whom some nervous system involvement may be predicted: myotonic dystrophy type I and II (DM I, II) and mitochondrial disease. In addition, sNfL were measured in 8 patients with facioscapulohumeral muscular dystrophy (FSHD) and in a disease control group caused by genetic defects exclusively expressed in muscle.

Results: sNfL values were significantly elevated in the DM I, the DM II and the mitochondrial group, with FSHD patients showing the lowest sNfL elevations. sNfL levels in the disease control group were not different from the healthy controls. A significant correlation between repeat length and sNfL levels was found in the DM I patients, but not in the DM II patients. Mitochondrial patients with encephalopathy showed significantly higher sNfL concentrations compared to patients with only muscular symptoms.

Conclusion: sNfL levels are elevated in myopathies with, based on the underlying molecular defect or clinical features, established nervous system involvement, i.e., myotonic dystrophies and mitochondrial disorders. sNfL were also raised in FSHD, where involvement of the nervous system is not usually clinically apparent. Thus, sNfL concentrations may serve as a biomarker for additional neuronal damage in primary myopathies.
Preliminary Exploration of the Sequence of Nerve Fiber Bundles Involvement for Idiopathic Normal Pressure Hydrocephalus: A Correlation Analysis Using Diffusion Tensor Imaging
Authors: Huang Wenjun , Fang Xuhao , Li Shihong , Mao Renling , Ye Chuntao , Liu Wei , Lin Guangwu
Published: December 2021

The study preliminarily explored the sequence and difference of involvement in different neuroanatomical structures in idiopathic normal pressure hydrocephalus (INPH). We retrospectively analyzed the differences in diffusion tensor imaging (DTI) parameters in 15 ROIs [including the bilateral centrum semiovale (CS), corpus callosum (CC) (body, genu, and splenium), head of the caudate nucleus (CN), internal capsule (IC) (anterior and posterior limb), thalamus (TH), and the bilateral frontal horn white matter hyperintensity (FHWMH)] between 27 INPH patients and 11 healthy controls and the correlation between DTI indices and clinical symptoms, as evaluated by the INPH grading scale (INPHGS), the Mini-Mental State Examination (MMSE), and the timed up and go test (TUG-t), before and 1 month after shunt surgery. Significant differences were observed in DTI parameters from the CS (pFA1 = 0.004, pADC1 = 0.005) and the genu (pFA2 = 0.022; pADC2 = 0.001) and body (pFA3 = 0.003; pADC3 = 0.002) of the CC between the groups. The DTI parameters from the CS were strongly correlated with the MMSE score both pre-operatively and post-operatively. There was association between apparent diffusion coefficient (ADC) values of anterior and posterior limbs of the IC and MMSE. The DTI parameters of the head of the CN were correlated with motion, and the ADC value was significantly associated with the MMSE score. The FA value from TH correlated with an improvement in urination after shunt surgery. We considered that different neuroanatomical structures are affected differently by disease due to their positions in neural pathways and characteristics, which is further reflected in clinical symptoms and the prognosis of shunt surgery.
Development and Validation of a Plasma FAM19A5 and MRI-Based Radiomics Model for Prediction of Parkinson’s Disease and Parkinson’s Disease With Depression
Authors: Li Xue-ning , Hao Da-peng , Qu Mei-jie , Zhang Meng , Ma An-bang , Pan Xu-dong , Ma Ai-jun
Published: December 2021

Background: Prediction and early diagnosis of Parkinson’s disease (PD) and Parkinson’s disease with depression (PDD) are essential for the clinical management of PD.

Objectives: The present study aimed to develop a plasma Family with sequence similarity 19, member A5 (FAM19A5) and MRI-based radiomics nomogram to predict PD and PDD.

Methods: The study involved 176 PD patients and 181 healthy controls (HC). Sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure FAM19A5 concentration in the plasma samples collected from all participants. For enrolled subjects, MRI data were collected from 164 individuals (82 in the PD group and 82 in the HC group). The bilateral amygdala, head of the caudate nucleus, putamen, and substantia nigra, and red nucleus were manually labeled on the MR images. Radiomics features of the labeled regions were extracted. Further, machine learning methods were applied to shrink the feature size and build a predictive radiomics signature. The resulting radiomics signature was combined with plasma FAM19A5 concentration and other risk factors to establish logistic regression models for the prediction of PD and PDD.

Results: The plasma FAM19A5 levels (2.456 ± 0.517) were recorded to be significantly higher in the PD group as compared to the HC group (2.23 ± 0.457) (P < 0.001). Importantly, the plasma FAM19A5 levels were also significantly higher in the PDD subgroup (2.577 ± 0.408) as compared to the non-depressive subgroup (2.406 ± 0.549) (P = 0.045 < 0.05). The model based on the combination of plasma FAM19A5 and radiomics signature showed excellent predictive validity for PD and PDD, with AUCs of 0.913 (95% CI: 0.861–0.955) and 0.937 (95% CI: 0.845–0.970), respectively.

Conclusion: Altogether, the present study reported the development of nomograms incorporating radiomics signature, plasma FAM19A5, and clinical risk factors, which might serve as potential tools for early prediction of PD and PDD in clinical settings.
Prognostic Value of the Systemic Immune-Inflammation Index and Prognostic Nutritional Index in Patients With Medulloblastoma Undergoing Surgical Resection
Authors: Zhu Sihan , Cheng Zhuqing , Hu Yuanjun , Chen Zhenghe , Zhang Ji , Ke Chao , Yang Qunying , Lin Fuhua , Chen Yinsheng , Wang Jian
Published: December 2021

Background: The progression and metastasis of cancers are associated with systematic immune inflammation and nutritional dysfunction. The systemic immune-inflammation index and prognostic nutritional index (PNI) have shown a prognostic impact in several malignancies. Therefore, our study aimed to evaluate immune inflammation and nutritional index prognostic significance in patients with medulloblastoma (MB).

Methods: We retrospectively analyzed 111 patients with MB between 2001 and 2021 at our institution. The optimal cutoff values for systemic immune-inflammation index (SII), neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte counts ration (MLR), and PNI were evaluated with receiver operating characteristic (ROC) curve analysis. Clinical characteristics and SII, NLR, MLR, and PNI were tested with the Pearson's chi-squared test. The Kaplan–Meier survival curves and the Cox proportional hazards model were used to evaluate the effects of immune inflammation and nutritional index on overall survival (OS).

Results: Receiver operating characteristic curve analysis determined the optimal SII, NLR, MLR, and PNI cutoff values of 2,278, 14.83, 0.219, and 56.5 that significantly interacts with OS and divided the patients into two groups. Comparative survival analysis exhibited that the high-SII cohort had significantly shorter OS (p = 0.0048) than the low-SII cohort. For the univariate analysis, the results revealed that preoperative hydrocephalus (p = 0.01), SII (p = 0.006), albumin–bilirubin score (ALBI) (p = 0.04), and coSII–PNI were predictors of OS. In the multivariate analysis, preoperative hydrocephalus (p < 0.001), ALBI (p = 0.010), SII (p < 0.001), and coSII–PNI as independent prognostic factors were significantly correlated with OS.

Conclusion: The preoperative SII, ALBI, and coSII–PNI serve as robust prognostic biomarkers for patients with MB undergoing surgical resection.
Prognostic Value of Pretreatment Lymphocyte-to-Monocyte Ratio and Development of a Nomogram in Breast Cancer Patients
Authors: Yin Ying , Zhang Yong , Li Li , Zhang Shaotong , Liu Ning , Yuan Shuanghu
Published: December 2021

Purpose

The objective of this study was to explore the prognostic significance of pretreatment hematologic parameters in predicting disease-free survival (DFS) of breast cancer patients.

Materials and Methods

The medical records of 440 breast cancer patients in Shandong Cancer Hospital and Institute from 2003 to 2013 were analyzed retrospectively. Through the results of blood routine before treatment, the absolute lymphocyte count (ALC), absolute neutrophil count (ANC), absolute monocyte count (AMC), and absolute platelet count (APC) in peripheral blood were collected. The lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-monocyte ratio (NMR) were calculated. Cox proportional hazard model was used for univariate and multivariate analysis. The DFS was compared using Kaplan–Meier method. The prognostic nomogram of patients with breast cancer was developed.

Results

The median DFS for all patients was 64.10 months. Univariate analysis showed that the DFS was associated with surgical approach, TNM stage, molecular subtype, neoadjuvant chemotherapy, radiotherapy, and LMR (p < 0.05). TNM stage, molecular subtype, and LMR were independent prognostic factors of breast cancer in multivariate analysis (p < 0.05). According to the Kaplan–Meier survival curve analysis, patients with higher LMR (≥4.85) were associated with longer median DFS (median DFS, 85.83 vs. 60.90, p < 0.001). The proposed nomogram that incorporated LMR, TNM stage, and molecular subtype got a concordance index (c-index) of 0.69 in predicting 5-year DFS.

Conclusion

In breast cancer patients, higher LMR was associated with longer median DFS and the nomogram including LMR, TNM stage, and molecular subtype could accurately predict the prolonged 5-year DFS of breast cancer patients.
Longitudinal Follow-Up With Radiologic Screening for Recurrence and Secondary Hiatal Hernia in Neonates With Open Repair of Congenital Diaphragmatic Hernia—A Large Prospective, Observational Cohort Study at One Referral Center
Authors: Zahn Katrin B. , Schaible Thomas , Rafat Neysan , Weis Meike , Weiss Christel , Wessel Lucas
Published: December 2021

Objective: After neonatal repair of congenital diaphragmatic hernia (CDH) recurrence is the most severe surgical complication and reported in up to 50% after patch implantation. Previous studies are difficult to compare due to differences in surgical techniques and retrospective study design and lack of standardized follow-up or radiologic imaging. The aim was to reliably detect complication rates by radiologic screening during longitudinal follow-up after neonatal open repair of CDH and to determine possible risk factors.

Methods: At our referral center with standardized treatment algorithm and follow-up program, consecutive neonates were screened for recurrence by radiologic imaging at defined intervals during a 12-year period.

Results: 326 neonates with open CDH repair completed follow-up of a minimum of 2 years. 68 patients (21%) received a primary repair, 251 (77%) a broad cone-shaped patch, and 7 a flat patch (2%). Recurrence occurred in 3 patients (0.7%) until discharge and diaphragmatic complications in 28 (8.6%) thereafter. Overall, 38 recurrences and/or secondary hiatal hernias were diagnosed (9% after primary repair, 12.7% after cone-shaped patch; p = 0.53). Diaphragmatic complications were significantly associated with initial defect size (r = 0.26). In multivariate analysis left-sided CDH, an abdominal wall patch and age below 4 years were identified as independent risk factors. Accordingly, relative risks (RRs) were significantly increased [left-sided CDH: 8.5 (p = 0.03); abdominal wall patch: 3.2 (p < 0.001); age ≤4 years: 6.5 (p < 0.002)]. 97% of patients with diaphragmatic complications showed no or nonspecific symptoms and 45% occurred beyond 1 year of age.

Conclusions: The long-term complication rate after CDH repair highly depends on surgical technique: a comparatively low recurrence rate seems to be achievable in large defects by implantation of a broad cone-shaped, non-absorbable patch. Longitudinal follow-up with regular radiologic imaging until adolescence is essential to reliably detecting recurrence to prevent acute incarceration and chronic gastrointestinal morbidity with their impact on prognosis. Based on our findings and literature review, a risk-stratified approach to diaphragmatic complications is proposed.
Biological Prescience: The Role of Anticipation in Organismal Processes
Authors: Deans Carrie
Published: December 2021

Anticipation is the act of using information about the past and present to make predictions about future scenarios. As a concept, it is predominantly associated with the psychology of the human mind; however, there is accumulating evidence that diverse taxa without complex neural systems, and even biochemical networks themselves, can respond to perceived future conditions. Although anticipatory processes, such as circadian rhythms, stress priming, and cephalic responses, have been extensively studied over the last three centuries, newer research on anticipatory genetic networks in microbial species shows that anticipatory processes are widespread, evolutionarily old, and not simply reserved for neurological complex organisms. Overall, data suggest that anticipatory responses represent a unique type of biological processes that can be distinguished based on their organizational properties and mechanisms. Unfortunately, an empirically based biologically explicit framework for describing anticipatory processes does not currently exist. This review attempts to fill this void by discussing the existing examples of anticipatory processes in non-cognitive organisms, providing potential criteria for defining anticipatory processes, as well as their putative mechanisms, and drawing attention to the often-overlooked role of anticipation in the evolution of physiological systems. Ultimately, a case is made for incorporating an anticipatory framework into the existing physiological paradigm to advance our understanding of complex biological processes.
Monocyte to High-Density Lipoprotein Cholesterol Ratio at the Nexus of Type 2 Diabetes Mellitus Patients With Metabolic-Associated Fatty Liver Disease
Authors: Jia Jue , Liu Ruoshuang , Wei Weiping , Yu Fan , Yu Xiawen , Shen Yirong , Chen Caiqin , Cai Zhensheng , Wang Chenxi , Zhao Zhicong , Wang Dong , Yang Ling , Yuan Guoyue
Published: December 2021

Background: Recently, monocyte to high-density lipoprotein cholesterol ratio (MHR) as a novel inflammatory biomarker has drawn lots of attention. This study was conducted in patients with type 2 diabetes mellitus (T2DM) to investigate the correlation between MHR and metabolic-associated fatty liver disease (MAFLD).

Methods: Totally, 1,051 patients with T2DM from the Affiliated Hospital of Jiangsu University were enrolled and classified as MAFLD (n = 745) group and non-MAFLD (n = 306) group according to the MAFLD diagnostic criteria. In contrast, patients were also separated into four groups based on MHR quartiles. Anthropometric and biochemical measurements were performed. The visceral fat area (VFA) and subcutaneous fat area (SFA) of participants were measured by dual bioelectrical impedance. Fatty liver was assessed by ultrasonography.

Results: The MHR level of subjects in the MAFLD group was statistically greater than that in the non-MAFLD group (P < 0.05). Meanwhile, MHR was higher in the overweight or obese MAFLD group compared with that in the lean MAFLD group (P < 0.05). The area under the ROC Curve (AUC) assessed by MHR was larger than that of other inflammatory markers (P < 0.01). The cutoff value of MHR was 0.388, with a sensitivity of 61.74% and a specificity of 56.54%. For further study, binary logistic regression analyses of MAFLD as a dependent variable, the relationship between MHR and MAFLD was significant (P < 0.01). After adjusting for many factors, the relationship still existed. In the four groups based on MHR quartiles, groups with higher values of MHR had a significantly higher prevalence of MAFLD (P < 0.05). The percentage of patients with obese MAFLD increased as the MHR level increased (P < 0.01). Among different quartiles of MHR, it showed that with the increasing of MHR, the percentage of patients with MAFLD who had more than four metabolic dysfunction indicators increased, which was 46.39, 60.52, 66.79, and 79.91%, respectively, in each quartile.

Conclusion: Monocyte to high-density lipoprotein cholesterol ratio is a simple and practicable inflammatory parameter that could be used for assessing MAFLD in T2DM. T2DM patients with higher MHR have more possibility to be diagnosed as MAFLD. Therefore, more attention should be given to the indicator in the examination of T2DM.
Upregulation of Aquaporin 1 Mediates Increased Migration and Proliferation in Pulmonary Vascular Cells From the Rat SU5416/Hypoxia Model of Pulmonary Hypertension
Authors: Yun Xin , Philip Nicolas M. , Jiang Haiyang , Smith Zion , Huetsch John C. , Damarla Mahendra , Suresh Karthik , Shimoda Larissa A.
Published: December 2021

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by exuberant vascular remodeling leading to elevated pulmonary arterial pressure, maladaptive right ventricular remodeling, and eventual death. The factors controlling pulmonary arterial smooth muscle cell (PASMC) and endothelial cell hyperplasia and migration, hallmark features of the vascular remodeling observed in PAH, remain poorly understood. We previously demonstrated that hypoxia upregulates the expression of aquaporin 1 (AQP1), a water channel, in PASMCs, and that this upregulation was required for hypoxia-induced migration and proliferation. However, whether the same is true in a model of severe PAH and in pulmonary microvascular endothelial cells (MVECs) is unknown. In this study, we used the SU5416 plus hypoxia (SuHx) rat model of severe pulmonary hypertension, which mimics many of the features of human PAH, to determine whether AQP1 levels were altered in PASMCs and MVECs and contributed to a hyperproliferative/hypermigratory phenotype. Rats received a single injection of SU5416 (20 mg/kg) and then were placed in 10% O2 for 3 weeks, followed by a return to normoxic conditions for an additional 2 weeks. We found that AQP1 protein levels were increased in both PASMCs and MVECs from SuHx rats, even in the absence of sustained hypoxic exposure, and that in MVECs, the increase in protein expression was associated with upregulation of AQP1 mRNA levels. Silencing of AQP1 had no significant effect on PASMCs from control animals but normalized enhanced migration and proliferation observed in cells from SuHx rats. Loss of AQP1 also reduced migration and proliferation in MVECs from SuHx rats. Finally, augmenting AQP1 levels in MVECs from control rats using forced expression was sufficient to increase migration and proliferation. These results demonstrate a key role for enhanced AQP1 expression in mediating abnormal migration and proliferation in pulmonary vascular cells from a rodent model that reflects many of the features of human PAH.
Differences in Immune Response During Competition and Preparation Phase in Elite Rowers
Authors: Bizjak Daniel Alexander , Treff Gunnar , Zügel Martina , Schumann Uwe , Winkert Kay , Schneider Marion , Abendroth Dietmar , Steinacker Jürgen Michael
Published: December 2021

Background: Metabolic stress is high during training and competition of Olympic rowers, but there is a lack of biomedical markers allowing to quantify training load on the molecular level. We aimed to identify such markers applying a complex approach involving inflammatory and immunologic variables.

Methods: Eleven international elite male rowers (age 22.7 ± 2.4 yrs.; VO2max 71 ± 5 ml·min−1·kg−1) of the German National Rowing team were monitored at competition phase (COMP) vs. preparation phase (PREP), representing high vs. low load. Perceived stress and recovery were assessed by a Recovery Stress Questionnaire for Athletes (RESTQ-76 Sport). Immune cell activation (dendritic cell (DC)/macrophage/monocytes/T-cells) was evaluated via fluorescent activated cell sorting. Cytokines, High-Mobility Group Protein B1 (HMGB1), cell-free DNA (cfDNA), creatine kinase (CK), uric acid (UA), and kynurenine (KYN) were measured in venous blood.

Results: Rowers experienced more general stress and less recovery during COMP, but sports-related stress and recovery did not differ from PREP. During COMP, DC/macrophage/monocyte and T-regulatory cells (Treg-cell) increased (p = 0.001 and 0.010). HMGB1 and cfDNA increased in most athletes during COMP (p = 0.001 and 0.048), while CK, UA, and KYN remained unaltered (p = 0.053, 0.304, and 0.211). Pro-inflammatory cytokines IL-1β (p = 0.002), TNF-α (p < 0.001), and the chemokine IL-8 (p = 0.001) were elevated during COMP, while anti-inflammatory Il-10 was lower (p = 0.002).

Conclusion: COMP resulted in an increase in biomarkers reflecting tissue damage, with plausible evidence of immune cell activation that appeared to be compensated by anti-inflammatory mechanisms, such as Treg-cell proliferation. We suggest an anti-inflammatory and immunological matrix approach to optimize training load quantification in elite athletes.