bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial Metabolic Potential and Micro-Eukaryotes Enriched in Stony Coral Tissue Loss Disease Lesions
Authors: Rosales Stephanie M. , Huebner Lindsay K. , Clark Abigail S. , McMinds Ryan , Ruzicka Rob R. , Muller Erinn M.
Published: January 2022

The epizootic disease outbreak known as stony coral tissue loss disease (SCTLD) is arguably the most devastating coral disease in recorded history. SCTLD emerged off the coast of South Florida in 2014 and has since moved into the Caribbean, resulting in coral mortality rates that have changed reef structure and function. Currently, the cause of SCTLD is unknown, but there is evidence from 16S rRNA gene sequencing and bacterial culture studies that the microbial community plays a role in the progression of SCTLD lesions. In this study, we applied shotgun metagenomics to characterize the potential function of bacteria, as well as the composition of the micro-eukaryotic community, associated with SCTLD lesions. We re-examined samples that were previously analyzed using 16S rRNA gene high-throughput sequencing from four coral species: Stephanocoenia intersepta, Diploria labyrinthiformis, Dichocoenia stokesii, and Meandrina meandrites. For each species, tissue from apparently healthy (AH) corals, and unaffected tissue (DU) and lesion tissue (DL) on diseased corals, were collected from sites within the epidemic zone of SCTLD in the Florida Keys. Within the micro-eukaryotic community, the taxa most prominently enriched in DL compared to AH and DU tissue were members of Ciliophora. We also found that DL samples were relatively more abundant in less energy-efficient pathways like the pentose phosphate pathways. While less energy-efficient processes were identified, there were also relatively higher abundances of nucleotide biosynthesis and peptidoglycan maturation pathways in diseased corals compared to AH, which suggests there was more bacteria growth in diseased colonies. In addition, we generated 16 metagenome-assembled genomes (MAGs) belonging to the orders Pseudomonadales, Beggiatoales, Rhodobacterales, Rhizobiales, Rs-D84, Flavobacteriales, and Campylobacterales, and all MAGs were enriched in DL samples compared to AH samples. Across all MAGs there were antibiotic resistance genes that may have implications for the treatment of SCTLD with antibiotics. We also identified genes and pathways linked to virulence, such as nucleotide biosynthesis, succinate dehydrogenase, ureases, nickel/iron transporters, Type-1 secretion system, and metalloproteases. Some of these enzymes/pathways have been previously targeted in the treatment of other bacterial diseases and they may be of interest to mitigate SCTLD lesion progression.
Larval Fish Assemblages and Distribution Patterns in the Zhongsha Atoll (Macclesfield Bank, South China Sea)
Authors: Huang Delian , Chen Jing , Xu Lei , Wang Xuehui , Ning Jiajia , Li Yafang , Wang Lianggen , Liu Shuangshuang , Lin Zhaojin , Du Feiyan
Published: January 2022

The remote coral reef in the deep sea is one of the most important nursery grounds for many marine fishes in the South China Sea. Diversity studies on larval fishes in this area are few, and the fish information on the coral reefs ecosystem is lacking. In this study, larval fishes were sampled during the summer of 2019 from the Zhongsha Atoll in the South China Sea and identified using DNA barcodes for the first time. Ninety-five larval fish species were recognized, belonging to 37 families and 12 orders based on morphological classification and DNA barcoding identification. The larval fish collected could be assigned to three categories as reef-associated, deep-sea, and pelagic. Most of the species were small fish with low commercial value but would play an essential role in the coral reef ecosystem. Some commercial fishes, including Auxis thazard, Euthynnus affinis, Sarda orientalis, Decapterus macarellus, Lutjanus viridis, and Centropyge vrolikii, were the dominant species higher than 2% total catch. The larval fish assemblage showed distinct spatial differences responding well with the geographical conditions. The most reef-associated fish occurred inside the Atoll, and the abyssal fish presented near the edge. In addition, larval fish spread over from the southwest to northeast may reflect the oceanography effect.
Assessing Tolerance to the Hydrodynamic Exposure of Posidonia oceanica Seedlings Anchored to Rocky Substrates
Authors: Zenone Arturo , Badalamenti Fabio , Alagna Adriana , Gorb Stanislav N. , Infantes Eduardo
Published: January 2022

Among a suite of abiotic and biotic factors, the hydrodynamic regime strongly influences the success of seagrass recruitment through sexual propagules. Uprooting of propagules by drag forces exerted by currents and waves is one of the main causes for the failed establishment and the consequent recruitment. Substrate type and stability play a key role in determining the success of colonization through sexual propagules, as seedling establishment probabilities proved to be significantly higher on rocky bottoms than on unstable unconsolidated substrates. In this research, the current and wave flow intensity thatPosidonia oceanicaseedlings anchored to rocky substrates can withstand before uprooting were evaluated and the influence of substrate complexity on seedling anchorage success and anchorage strength was investigated.P. oceanicaseedlings withstood the current velocity of 70 cm s–1and increased orbital flow velocities up to 25 cm s–1. Seedling adhesion strength ranged from 3.92 to 29.42 N. Results of the present study corroborate the hypothesis that substrate complexity at scales relevant to the size of propagules is a crucial feature forP. oceanicaseedling establishment. The intensity of unidirectional and oscillatory flow that seedlings can withstand without being dislodged assessed in this study support the hypothesis thatP. oceanicasexual propagules, once adhered to a consolidated substrate, are able to tolerate high hydrodynamic stress. The results of the present study contribute to re-evaluation of the habitat requirements ofP. oceanica, assessing the range of hydrodynamic conditions that this species can tolerate during the early stages of its life history.
Isolation and Identification of a Rare Spike Gene Double-Deletion SARS-CoV-2 Variant From the Patient With High Cycle Threshold Value
Authors: Liu Li-Teh , Tsai Jih-Jin , Chen Chun-Hong , Lin Ping-Chang , Tsai Ching-Yi , Tsai Yan-Yi , Hsu Miao-Chen , Chuang Wan-Long , Chang Jer-Ming , Hwang Shang-Jyh , Chong Inn-Wen
Published: January 2022

Coronavirus disease 2019 (COVID-19) is an emerging life-threatening pulmonary disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, Hubei Province, China, in December 2019. COVID-19 develops after close contact via inhalation of respiratory droplets containing SARS-CoV-2 during talking, coughing, or sneezing by asymptomatic, presymptomatic, and symptomatic carriers. This virus evolved over time, and numerous genetic variants have been reported to have increased disease severity, mortality, and transmissibility. Variants have also developed resistance to antivirals and vaccination and can escape the immune response of humans. Reverse transcription polymerase chain reaction (RT–PCR) is the method of choice among diagnostic techniques, including nucleic acid amplification tests (NAATs), serological tests, and diagnostic imaging, such as computed tomography (CT). The limitation of RT–PCR is that it cannot distinguish fragmented RNA genomes from live transmissible viruses. Thus, SARS-CoV-2 isolation by using cell culture has been developed and makes important contributions in the field of diagnosis, development of antivirals, vaccines, and SARS-CoV-2 virology research. In this research, two SARS-CoV-2 strains were isolated from four RT–PCR-positive nasopharyngeal swabs using VERO E6 cell culture. One isolate was cultured successfully with a blind passage on day 3 post inoculation from a swab with a Ct > 35, while the cells did not develop cytopathic effects without a blind passage until day 14 post inoculation. Our results indicated that infectious SARS-CoV-2 virus particles existed, even with a Ct > 35. Cultivable viruses could provide additional consideration for releasing the patient from quarantine. The results of the whole genome sequencing and bioinformatic analysis suggested that these two isolates contain a spike 68-76del+spike 675-679del double-deletion variation. The double deletion was confirmed by amplification of the regions spanning the spike gene deletion using Sanger sequencing. Phylogenetic analysis revealed that this double-deletion variant was rare (one per million in public databases, including GenBank and GISAID). The impact of this double deletion in the spike gene on the SARS-CoV-2 virus itself as well as on cultured cells and/or humans remains to be further elucidated.
Long-Reads-Based Metagenomics in Clinical Diagnosis With a Special Focus on Fungal Infections
Authors: Hoang Minh Thuy Vi , Irinyi Laszlo , Hu Yiheng , Schwessinger Benjamin , Meyer Wieland
Published: January 2022

Identification of the causative infectious agent is essential in the management of infectious diseases, with the ideal diagnostic method being rapid, accurate, and informative, while remaining cost-effective. Traditional diagnostic techniques rely on culturing and cell propagation to isolate and identify the causative pathogen. These techniques are limited by the ability and the time required to grow or propagate an agent in vitro and the facts that identification based on morphological traits are non-specific, insensitive, and reliant on technical expertise. The evolution of next-generation sequencing has revolutionized genomic studies to generate more data at a cheaper cost. These are divided into short- and long-read sequencing technologies, depending on the length of reads generated during sequencing runs. Long-read sequencing also called third-generation sequencing emerged commercially through the instruments released by Pacific Biosciences and Oxford Nanopore Technologies, although relying on different sequencing chemistries, with the first one being more accurate both platforms can generate ultra-long sequence reads. Long-read sequencing is capable of entirely spanning previously established genomic identification regions or potentially small whole genomes, drastically improving the accuracy of the identification of pathogens directly from clinical samples. Long-read sequencing may also provide additional important clinical information, such as antimicrobial resistance profiles and epidemiological data from a single sequencing run. While initial applications of long-read sequencing in clinical diagnosis showed that it could be a promising diagnostic technique, it also has highlighted the need for further optimization. In this review, we show the potential long-read sequencing has in clinical diagnosis of fungal infections and discuss the pros and cons of its implementation.
Transcriptome and Metabolome Profiling of a Novel Isolate Chlorella sorokiniana G32 (Chlorophyta) Displaying Enhanced Starch Accumulation at High Growth Rate Under Mixotrophic Condition
Authors: Zhu Qingling , Zhang Mengmeng , Liu Bingying , Wen Fang , Yang Zhili , Liu Jianhua
Published: January 2022

Chlorella sorokiniana is one of the most productive microalgal species with a high potential for the production of biofuels and other high value-added molecules. Many studies have focused on its capability of mixotrophic growth using reduced organic carbon and growth pattern shift between autotrophic and mixotrophic conditions. In this study, we investigated growth patterns of a novel isolate, C. sorokiniana G32, under mixotrophic growth conditions supplemented with a low level (1.25 g L–1) and a high level (5 g L–1) of glucose. Physiological, transcriptomic (i.e., RNA-seq), and metabolomic (i.e., LC-MS/MS) methods were used. We showed that peak growth based on OD680nm absorbance is ∼4-fold higher with high glucose vs. low glucose supplementation. Photosynthetic efficiency (Fv/Fm) in G32 mixotrophic cultures with high or low glucose supplementation remains identical to that of G32 phototrophic growth. We also found that the conversion rate between absorbance-based cell density and cell dry weight with high glucose supplementation was lower than with low glucose. This suggests that more cell biomass is produced under high glucose treatment than with low glucose. The result was confirmed via sucrose density gradient centrifugation. It is likely that accumulation of high concentration of starch may account for this effect. Transcriptomic analysis of G32 cultures (i.e., via RNA-seq) in response to reciprocal change of glucose levels reveals that expression of a subset of differentially expressed genes (DEGs) is correlated with the amount of glucose supplementation. These DEGs are designated as glucose-specific responsive (GSR) genes. GSR genes are enriched for a number of energy metabolic pathways. Together with metabolomics data (i.e., LC-MS/MS), we show that under high-level supplementation, glucose is preferentially oxidized through an oxidative pentose phosphate pathway. Collectively, our results indicate the mechanism of regulation of glucose assimilation and energy metabolism in G32 under mixotrophic conditions with different levels of glucose supplementation revealed by transcriptomic and metabolomic analyses. We propose that C. sorokiniana G32 has the potential for the production of high value-added molecules.
Emergence and Genomic Characterization of a KPC-2-, NDM-1-, and IMP-4-Producing Klebsiella michiganensis Isolate
Authors: Zhang Yanyan , Gu Danxia , Yang Xuemei , Wu Yuchen , Liu Congcong , Shen Zhangqi , Zhang Rong
Published: January 2022

A rectal swab sample was collected from a patient with Guillain–Barré syndrome and enriched in lysogeny broth. Carbapenem-resistant bacteria were selected by China Blue agar plates containing 0.3 μg/ml meropenem. Carbapenemase-producing Klebsiella michiganensis was identified and characterized by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), immune colloidal gold technique, a conjugation experiment, PCR analysis, and antimicrobial susceptibility testing. The genome of K. michiganensis was determined by whole genome sequencing. Antimicrobial susceptibility testing showed that the K. michiganensis was resistant to imipenem, meropenem, ertapenem, cefmetazole, ceftazidime, cefotaxime, piperacillin/tazobactam, sulbactam/cefoperazone, ceftazidime/avibactam, cefepime, and aztreonam while susceptible to polymyxin B, ciprofloxacin, tigecycline, and amikacin. Immune colloidal gold technique suggested that this strain co-produced three different carbapenemases [Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), and Imipenem (IMP)]. Whole genome sequencing analysis indicated that this strain belonged to ST91, and blaKPC–2, blaNDM–1, and blaIMP–4 were carried on different conjugative plasmids. Besides, the co-existence and transferability of blaKPC–2, blaNDM–1, and blaIMP–4 in K. michiganensis facilitates the potential horizontal dissemination and nosocomial spread of resistance genes among multidrug-resistant organisms.
Sitafloxacin Expresses Potent Anti-Mycobacterium abscessus Activity
Authors: He Siyuan , Guo Qi , Zhao Lan , Xu Liyun , Fan Junsheng , Wu Wenye , Zhang Zhemin , Li Bing , Chu Haiqing
Published: January 2022

Therapeutic options for treating Mycobacterium abscessus infections are extremely limited; quinolones are important. The in vitro anti-M. abscessus activities of nine quinolones, emphasizing sitafloxacin, were investigated. Antimicrobial susceptibility testing was performed on 10 non-tuberculous mycobacterium reference strains and 194 clinical, M. abscessus isolates. The activity of sitafloxacin against intracellular M. abscessus residing within macrophages was also evaluated. A checkerboard assay was conducted to determine synergy between sitafloxacin and 10 clinically important antibiotics. Among the nine quinolones tested, sitafloxacin exhibited the greatest anti-M. abscessus activity with MIC50 and MIC90 of 1 and 2 mg/L, respectively. Sitafloxacin exerted a bacteriostatic effect on M. abscessus and inhibited the intracellular growth of M. abscessus at concentrations equivalent to clarithromycin. No antagonism between sitafloxacin and 10 clinically important anti-M. abscessus antibiotics was evident. In summary, sitafloxacin exhibited a significant advantage relative to other quinolones in inhibiting the growth of M. abscessus in vitro, suggesting the potential inclusion of sitafloxacin in new strategies to treat M. abscessus infections.
High-Frequency Cochlear Amplifier Dysfunction: A Dominating Contribution to the Cognitive-Ear Link
Authors: Wang Yao , Li Xiao , Ren Fuxin , Liu Siqi , Ma Wen , Zhang Yue , Qi Zhihang , Yang Jing , Li Honghao , Fu Xinxing , Wang Huiquan , Gao Fei
Published: January 2022

Objective: The objective of this study was to investigate the role of the high-frequency cochlear dysfunction in the cognitive-ear link.

Methods: Seventy-four presbycusis patients (PC group) and seventy-one age-, sex-, and education-level matched normal hearing controls (NH group) were recruited in this study. Participants underwent a battery of cognitive tests estimated by Montreal Cognitive Assessment (MoCA), Stroop Color-Word Interference Test (Stroop), Symbol Digit Modalities Test (SDMT), Auditory Verbal Learning Test (AVLT), and Trail-Making Test (TMT-A and B), as well as auditory tests including distortion product otoacoustic emission (DPOAE), pure tone (PT) thresholds, and speech reception thresholds (SRT). Data were analyzed using the factor analysis, partial correlation analysis, multiple linear regression models, and mediation models.

Results: Distortion product otoacoustic emission detection amplitudes and PT thresholds performed worse gradually from low to high frequencies in both the NH and PC groups. High-frequency DPOAE (H-DPOAE) was significantly correlated with cognitive domains in the PC group (AVLT: r = 0.30, p = 0.04; SDMT: r = 0.36, p = 0.01; Stroop: r = –0.32, p = 0.03; TMT-A: r = –0.40, p = 0.005; TMT-B: r = –0.34, p = 0.02). Multiple linear regression models showed that H-DPOAE predicted cognitive impairment effectively for aspects of memory (R2 = 0.27, 95% CI, 0.03 to 1.55), attention (R2 = 0.32, 95% CI, –6.18 to –0.40), processing speed (R2 = 0.37, 95% CI, 0.20 to 1.64), and executive function (TMT-A: R2 = 0.34, 95% CI, –5.52 to 1.03; TMT-B: R2 = 0.29, 95% CI, –11.30 to –1.12). H-DPOAE directly affected cognition and fully mediated the relationship between pure tone average (PTA)/SRT and cognitive test scores, excluding MoCA.

Conclusion: This study has demonstrated that the high-frequency cochlear amplifier dysfunction has a direct predictive effect on the cognitive decline and makes a large contribution to the cognitive-ear link.
Sex Differences in Brain and Cognition in de novo Parkinson's Disease
Authors: Oltra Javier , Uribe Carme , Campabadal Anna , Inguanzo Anna , Monté-Rubio Gemma C. , Martí Maria J. , Compta Yaroslau , Valldeoriola Francesc , Junque Carme , Segura Barbara
Published: January 2022

Background and Objective: Brain atrophy and cognitive impairment in neurodegenerative diseases are influenced by sex. We aimed to investigate sex differences in brain atrophy and cognition in de novo Parkinson's disease (PD) patients.

Methods: Clinical, neuropsychological and T1-weighted MRI data from 205 PD patients (127 males: 78 females) and 69 healthy controls (40 males: 29 females) were obtained from the PPMI dataset.

Results: PD males had a greater motor and rapid eye movement sleep behavior disorder symptomatology than PD females. They also showed cortical thinning in postcentral and precentral regions, greater global cortical and subcortical atrophy and smaller volumes in thalamus, caudate, putamen, pallidum, hippocampus, and brainstem, compared with PD females. Healthy controls only showed reduced hippocampal volume in males compared to females. PD males performed worse than PD females in global cognition, immediate verbal recall, and mental processing speed. In both groups males performed worse than females in semantic verbal fluency and delayed verbal recall; as well as females performed worse than males in visuospatial function.

Conclusions: Sex effect in brain and cognition is already evident in de novo PD not explained by age per se, being a relevant factor to consider in clinical and translational research in PD.
Neural Circuits Underlying Behavioral Flexibility: Insights From Drosophila
Authors: Devineni Anita V. , Scaplen Kristin M.
Published: January 2022

Behavioral flexibility is critical to survival. Animals must adapt their behavioral responses based on changes in the environmental context, internal state, or experience. Studies in Drosophila melanogaster have provided insight into the neural circuit mechanisms underlying behavioral flexibility. Here we discuss how Drosophila behavior is modulated by internal and behavioral state, environmental context, and learning. We describe general principles of neural circuit organization and modulation that underlie behavioral flexibility, principles that are likely to extend to other species.
Systematic Review of the Socioeconomic Consequences in Patients With Multiple Sclerosis With Different Levels of Disability and Cognitive Function
Authors: Kavaliunas Andrius , Danylaitė Karrenbauer Virginija , Binzer Stefanie , Hillert Jan
Published: January 2022

Multiple sclerosis (MS) is a challenging and disabling condition, predominantly affecting individuals in early adulthood. MS affects the physical, cognitive, and mental health of persons suffering from the disease as well as having a great impact on their financial status and quality of life. However, there is a lack of systematic approach toward assessing the socioeconomic consequences of MS. Our objective was to systematically review analytical observational studies investigating the socioeconomic consequences in persons with MS with different levels of physical disability and cognitive function. We conducted a systematic review on socioeconomic consequences of MS with a focus on employment-, income-, work ability-, and relationship-related outcomes in persons with MS with special focus on disability and cognition. Additionally, the educational characteristics were examined. From 4,957 studies identified, 214 were assessed for eligibility and a total of 19 studies were included in this qualitative assessment; 21 different outcomes were identified. All identified studies reported higher unemployment, higher early retirement, and higher risk of unemployment in relation to higher physical disability. Also, cognitive function was found to be a predictor of employment (unemployment). The studies pointed out significant correlations between greater disability and lower earnings and higher income from benefits. A study found the same correlation in relation to cognitive function. The studies reported higher work disability in relation to higher physical disability and lower cognitive function. In conclusion, this systematic review summarizes the pronounced differences in various socioeconomic outcomes between patients with MS with regards to their physical disability and cognitive function. In addition, we identified a lack of studies with longitudinal design in this field that can provide more robust estimates with covariate adjustments, such as disease modifying treatments.
BICS01 Mediates Reversible Anti-seizure Effects in Brain Slice Models of Epilepsy
Authors: Morris Gareth , Heiland Mona , Lamottke Kai , Guan Haifeng , Hill Thomas D. M. , Zhou Yijun , Zhu Qianjin , Schorge Stephanie , Henshall David C.
Published: January 2022

Drug-resistant epilepsy remains a significant clinical and societal burden, with one third of people with epilepsy continuing to experience seizures despite the availability of around 30 anti-seizure drugs (ASDs). Further, ASDs often have substantial adverse effects, including impacts on learning and memory. Therefore, it is important to develop new ASDs, which may be more potent or better tolerated. Here, we report the preliminary preclinical evaluation of BICS01, a synthetic product based on a natural compound, as a potential ASD. To model seizure-like activity in vitro, we prepared hippocampal slices from adult male Sprague Dawley rats, and elicited epileptiform bursting using high extracellular potassium. BICS01 (200 μM) rapidly and reversibly reduced the frequency of epileptiform bursting but did not change broad measures of network excitability or affect short-term synaptic facilitation. BICS01 was well tolerated following systemic injection at up to 1,000 mg/kg. However, we did not observe any protective effect of systemic BICS01 injection against acute seizures evoked by pentylenetetrazol. These results indicate that BICS01 is able to acutely reduce epileptiform activity in hippocampal networks. Further preclinical development studies to enhance pharmacokinetics and accumulation in the brain, as well as studies to understand the mechanism of action, are now required.
Association of Interleukin-6–174G/C Polymorphism With Ischemic Stroke: An Updated Meta-Analysis
Authors: Chai Jie , Cao Xian-Ling , Lu Feng
Published: January 2022

Background: Although numerous epidemiological studies have investigated the association between −174G/C(rs1800795) polymorphism in the interleukin-6 (IL-6) gene-stimulatory region and the risk of ischemic stroke (IS), they failed to reach a unified conclusion. The true relationship between −174G/C(rs1800795) polymorphism and IS remains controversial and unclear. Therefore, in this meta-analysis, we aimed to analyze more precisely the association between −174G/C(rs1800795) single-nucleotide polymorphism (SNP) of IL-6 gene and IS in a larger pooled population.

Methods: A comprehensive literature search was performed in PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials until June 30, 2021. A fixed or random-effects model was utilized based on heterogeneity between studies. The odds ratios (ORs) and 95% confidence intervals (Cis) were calculated in the models of allele comparison (G vs. C), homozygote comparison (GG vs. CC) and (GC vs. CC), dominant (GG vs. GC + CC), hyper dominant (GG + CC vs. GC), and recessive (GG + GC vs. CC) to determine the strength of associations.

Results: This meta-analysis included 13 case-control studies in 35 articles with 5,548 individuals. Overall, no significant associations between IL-6 −174G/C(rs1800795) and IS were identified (G vs. C:OR [95% CI] = 0.99 [0.81, 1.21], P = 0.91; GG + CC vs. GC:0.97 [0.85, 1.11], P = 0.66; GG vs. GC + CC: 1.01 [0.81, 1.25], P = 0.94; GC vs. CC: OR [95% CI] = 1.01 [0.68, 1.5], P = 0.96; GG vs. CC:0.93 [0.57, 1.51], P = 0.76; GG + GC vs. CC:0.97 [0.64, 1.47], P = 0.89). In the subgroup analyses by ethnicity or HWE P-value, there was a statistically significant association between IL-6 −174G/C(rs1800795) polymorphisms and IS in the alleles model; (G vs. C: LogOR [95% CI] = 0.14 [−0.16,.45], P = 0.00), homozygote model (GG vs. CC: LogOR [95% CI] = 0.18 [−0.58,.95], P = 0.00) and (GC vs. CC: LogOR [95% CI] = 0.2 [−0.46,.85], P = 0.00), dominant model (GG vs. GC + CC: OR [95% CI] = 0.02 [−0.72, 0.77], P = 0.00), and recessive model (GG + GC vs. CC: OR [95% CI]= −0.17 [−0.86,.52], P = 0.00) of the European population and in the dominant model (GG vs. GC + CC: OR [95% CI] = −0.13 [−0.51, 0.24]) of the Asian population. No statistical significance was identified in both six models of HWE p ≥ 0.2 group (both P ≥ 0.05).

Conclusion: This meta-analysis revealed no correlation between IL-6 −174G/C(rs1800795) polymorphism and IS, whereas the subgroup analysis indicated that the relationship between IL-6 −174G/C(rs1800795) polymorphism and IS susceptibility varied significantly according to ethnicity and geography.
Exploratory Investigation of Brain MRI Lesions According to Whole Sample and Visual Function Subtyping in Children With Cerebral Visual Impairment
Authors: Sakki Hanna , Dale Naomi J. , Mankad Kshitij , Sargent Jenefer , Talenti Giacomo , Bowman Richard
Published: January 2022

Background: There is limited research on brain lesions in children with cerebral visual impairment (CVI) of heterogeneous etiologies and according to associated subtyping and vision dysfunctions. This study was part of a larger project establishing data-driven subtypes of childhood CVI according to visual dysfunctions. Currently there is no consensus in relation to assessment, diagnosis and classification of CVI and more information about brain lesions may be of potential diagnostic value.

Aim: This study aimed to investigate overall patterns of brain lesions and associations with level of visual dysfunction and to compare the patterns between the classification subgroups in children with CVI.

Methods: School-aged children with CVI received ophthalmological and neuro-psychological/developmental assessments to establish CVI-related subtyping. Other pediatric information was collected from medical records. MRI scans were coded according to a semi-quantitative template including brain regions (right hemisphere, left hemisphere, visual pathways) and summed for total scores. Non-parametric analyses were conducted.

Results: 28 children had clinical brain MRI scans available [44% of total sample, Group A (lower severity of visual dysfunctions) n = 16, Group B (higher severity) n = 12]. Total brain scores ranged between 0 and 18 (Group A mdn = 7, IQR = 0.8–10.0, Group B mdn = 10, IQR = 6.5–11.8) and were widespread across regions. 71 per cent had post-geniculate visual pathway damage. The median total brain and hemisphere scores of Group B were higher than subgroup A but differences did not reach statistical significance. No statistically significant associations were found between brain scores and vision variables (acuity, contrast sensitivity).

Conclusion: This study found a spread of lesions across all regions on the brain scans in children with congenital CVI. The majority had damage in the postgeniculate visual pathways and visual cortex region suggesting this is an area of interest and potentially informative for diagnosis. However the subtyping classification did not show differences in number or region of lesions though the trend was higher toward Group B. This study confirms the complex diffuse and variable nature of brain lesions in children with congenital CVI, many of whom have other neurological impairments.
Sleep-Dependent Anomalous Cortical Information Interaction in Patients With Depression
Authors: Lian Jiakai , Luo Yuxi , Zheng Minglong , Zhang Jiaxi , Liang Jiuxing , Wen Jinfeng , Guo Xinwen
Published: January 2022

Depression is a prevalent mental illness with high morbidity and is considered the main cause of disability worldwide. Brain activity while sleeping is reported to be affected by such mental illness. To explore the change of cortical information flow during sleep in depressed patients, a delay symbolic phase transfer entropy of scalp electroencephalography signals was used to measure effective connectivity between cortical regions in various frequency bands and sleep stages. The patient group and the control group shared similar patterns of information flow between channels during sleep. Obvious information flows to the left hemisphere and to the anterior cortex were found. Moreover, the occiput tended to be the information driver, whereas the frontal regions played the role of the receiver, and the right hemispheric regions showed a stronger information drive than the left ones. Compared with healthy controls, such directional tendencies in information flow and the definiteness of role division in cortical regions were both weakened in patients in most frequency bands and sleep stages, but the beta band during the N1 stage was an exception. The computable sleep-dependent cortical interaction may provide clues to characterize cortical abnormalities in depressed patients and should be helpful for the diagnosis of depression.
Multiple Molecular Pathways Are Influenced by Progranulin in a Neuronal Cell Model–A Parallel Omics Approach
Authors: Chitramuthu Babykumari P. , Campos-García Víctor R. , Bateman Andrew
Published: January 2022

Progranulin (PGRN) is critical in supporting a healthy CNS. Its haploinsufficiency results in frontotemporal dementia, while in experimental models of age-related neurodegenerative diseases, the targeted expression of PGRN greatly slows the onset of disease phenotypes. Nevertheless, much remains unclear about how PGRN affects its target cells. In previous studies we found that PGRN showed a remarkable ability to support the survival of NSC-34 motor neuron cells under conditions that would otherwise lead to their apoptosis. Here we used the same model to investigate other phenotypes of PGRN expression in NSC-34 cells. PGRN significantly influenced morphological differentiation, resulting in cells with enlarged cell bodies and extended projections. At a molecular level this correlated with pathways associated with the cytoskeleton and synaptic differentiation. Depletion of PGRN led to increased expression of several neurotrophic receptors, which may represent a homeostatic mechanism to compensate for loss of neurotrophic support from PGRN. The exception was RET, a neurotrophic tyrosine receptor kinase, which, when PGRN levels are high, shows increased expression and enhanced tyrosine phosphorylation. Other receptor tyrosine kinases also showed higher tyrosine phosphorylation when PGRN was elevated, suggesting a generalized enhancement of receptor activity. PGRN was found to bind to multiple plasma membrane proteins, including RET, as well as proteins in the ER/Golgi apparatus/lysosome pathway. Understanding how these various pathways contribute to PGRN action may provide routes toward improving neuroprotective therapies.
Benchmarking cEEGrid and Solid Gel-Based Electrodes to Classify Inattentional Deafness in a Flight Simulator
Authors: Somon Bertille , Giebeler Yasmina , Darmet Ludovic , Dehais Frédéric
Published: January 2022

Transfer from experiments in the laboratory to real-life tasks is challenging due notably to the inability to reproduce the complexity of multitasking dynamic everyday life situations in a standardized lab condition and to the bulkiness and invasiveness of recording systems preventing participants from moving freely and disturbing the environment. In this study, we used a motion flight simulator to induce inattentional deafness to auditory alarms, a cognitive difficulty arising in complex environments. In addition, we assessed the possibility of two low-density EEG systems a solid gel-based electrode Enobio (Neuroelectrics, Barcelona, Spain) and a gel-based cEEGrid (TMSi, Oldenzaal, Netherlands) to record and classify brain activity associated with inattentional deafness (misses vs. hits to odd sounds) with a small pool of expert participants. In addition to inducing inattentional deafness (missing auditory alarms) at much higher rates than with usual lab tasks (34.7% compared to the usual 5%), we observed typical inattentional deafness-related activity in the time domain but also in the frequency and time-frequency domains with both systems. Finally, a classifier based on Riemannian Geometry principles allowed us to obtain more than 70% of single-trial classification accuracy for both mobile EEG, and up to 71.5% for the cEEGrid (TMSi, Oldenzaal, Netherlands). These results open promising avenues toward detecting cognitive failures in real-life situations, such as real flight.
Amino Acid and Proliferation PET/CT for the Diagnosis of Multiple Myeloma
Authors: Minamimoto Ryogo
Published: January 2022

Multiple myeloma (MM) is a hematologic malignancy characterized by infiltration of monoclonal plasma cells in the bone marrow (BM). The standard examination performed for the assessment of bone lesions has progressed from radiographic skeletal survey to the more advanced imaging modalities of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT). The Durie–Salmon PLUS staging system (upgraded from the Durie–Salmon staging system) applies 2-[18F]-fluoro-2-deoxy-glucose (18F-FDG) PET/CT, and MRI findings to the staging of MM, and18F-FDG PET/CT has been incorporated into the International Myeloma Working Group (IMWG) guidelines for the diagnosis and staging of MM. However,18F-FDG PET/CT has significant limitations in the assessment of diffuse BM infiltration and in the differentiation of MM lesions from inflammatory or infectious lesions. The potential of several new PET tracers that exploit the underlying disease mechanism of MM has been evaluated in terms of improving the diagnosis. L-type amino acid transporter 1 (LAT1), a membrane protein that transports neutral amino acids, is associated with cell proliferation and has strong ability to represent the status of MM. This review evaluates the potential of amino acid and proliferation PET tracers for diagnosis and compares the characteristics and accuracy of non-FDG tracers in the management of patients with MM.
“Can A Ballerina Eat Ice Cream?”: A Mixed-Method Study on Eating Attitudes and Body Image in Female Ballet Dancers
Authors: Santo André Heloisa C. , Pinto Ana Jessica , Mazzolani Bruna Caruso , Smaira Fabiana Infante , Ulian Mariana Dimitrov , Gualano Bruno , Benatti Fabiana Braga
Published: January 2022

Aim: We aimed to explore how a group of classical ballet dancers perceived their eating attitudes and their bodies, with special attention to the potential presence of eating disorders (EDs) symptoms and body image (dis)satisfaction.

Methods: A cross-sectional, mixed-method study was conducted on fourteen trained classical ballet dancers (18–30 years old). Their experiences, perceptions, and feelings regarding eating attitudes and body image concerning classical ballet were acquired through qualitative focus groups. The presence of EDs symptoms and perception and (dis)satisfaction with body image was analyzed quantitatively through self-report questionnaires.

Results: Participants reported concerning eating attitudes during the focus groups, such as the regular practice of several restrictive popular diets, constant restriction of foods considered “heavy” or “fatty,” meal skipping and ignoring signs of hunger, presence of overeating episodes due to stress and anxiety, feeling guilty about breaking their usual diet, classifying foods as “good” and “bad” or “lean” and “fat,” and excluding some of those foods from their usual diets. These reports were partially reflected in the questionnaires, with 50% of the ballerinas showing bulimic symptoms indicative of an unusual eating pattern (only two of them with a significant risk index), 7.1% showing symptoms of moderate binge eating, and 14.3% symptoms of EDs in general. Additionally, when considering their bodies in the context of everyday life, participants were satisfied; however, in the “classical ballet” context, they reported feeling dissatisfied with their shape. These findings were in line with results from the Stunkard's Scale, which revealed that 50% of the sample was dissatisfied with their current body shape and 57.1% indicated that their desired body shape was a leaner figure than one they considered healthy.

Conclusions: The constant practice of restrictive diets and other weight-loss strategies to achieve a leaner body were associated with symptoms of EDs and body dissatisfaction in this sample. Importantly, the questionnaires used seemed to underestimate the presence of a disordered eating pattern reported by the participants during focus groups. These data could help to inform psychological and nutritional strategies aimed at improving performance, physical and psychological well-being, and quality of life of ballet dancers.
Associations of Carbohydrate Intake With New-Onset Hypertension Subtypes: Results From the China Health and Nutrition Survey (2000–2011)
Authors: Qi Su-Fen , Cao Ya-Jing , Wang Hui-Jun , Zhang Bing , Yan Jing , Tian Qing-Bao
Published: January 2022

Background: The effects of carbohydrate intake on hypertension (HTN) subtypes are scarce. We examined the association of carbohydrate intake with new-onset HTN subtypes in Chinese adults.

Methods: Chinese Health and Nutrition Survey (CHNS) 2000–2011, 22,418 individuals were recorded using a 24-h recall method over three consecutive days. We excluded those who were pregnant women, lactating mothers, age <18 years, baseline age, blood pressure, and energy intake deficiency, extreme energy intake (male > 6,000 kcal or < 800 kcal; female > 4,000 kcal or < 600 kcal), and pulse pressure difference (Systolic Blood Pressure [SBP] - Diastolic Blood Pressure [DBP]) <10 mm Hg, HTN at baseline and data from only one survey. The total number of subjects who participated in at least two surveys was 7,930. The main outcome was new-onset HTN subtypes over 6.9 person years of follow-up.

Results: 2,521 participants were found to be HTN, which included 1,318 males (52.3%), 1,203 females (47.7%), 721 had systolic-diastolic hypertension (SDH, 28.6%), 655 had isolated systolic hypertension (ISH, 26.0%), and 993 had isolated diastolic hypertension (IDH, 39.4%). Compared with extreme quintiles of carbohydrate, multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for new-onset HTN, SDH, ISH and IDH associated with carbohydrate intake were 1.12 (0.97–1.30), 1.54 (1.18–2.00), 0.89 (0.67–1.19) and 1.15 (0.91–1.45), respectively. The HR of SDH compared with extreme quintiles of carbohydrates was 1.56 (95% CI, 1.08–2.25; Ptrend = 0.04) in men and 1.52 (95% CI, 1.02–2.26; Ptrend = 0.02) in women.

Conclusion: Carbohydrates were related to a higher risk of SDH, which were not observed with HTN, ISH, and IDH.
Malnutrition Contributes to Low Lymphocyte Count in Early-Stage Coronavirus Disease-2019
Authors: Zhang Kai , Qin Weidong , Zheng Yue , Pang Jiaojiao , Zhong Ning , Fei Jianchun , Li Yu , Jian Xiangdong , Hou Xinguo , Hu Zhao , Li Chen , Wang Hao , Chen Yuguo
Published: January 2022

Background and Aim: Lymphocytes play an important role in fighting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Low total lymphocyte count (TLC), which contributes to poor clinical outcomes, is common in persons with coronavirus disease 2019 (COVID-19). The current explanation for the cause of low TLC is that it is directly related to the invasiveness of SARS-CoV-2, which attacks lymphocytes. We hypothesized that malnutrition contributes to the development of low TLC in early-stage COVID-19.

Methods: We prospectively enrolled 101 patients with confirmed COVID-19. On their first day of hospitalization, we collected baseline and laboratory data, including clinical symptoms; the Sequential Organ Failure Assessment, Nutrition Risk Screening 2002 and Subjective Global Assessment were used to assess the malnutrition status of the patients. Multivariable logistic regression was used to identify independent risk factors for low TLC and severe COVID-19.

Results: Malnutrition was associated with lower TLC in COVID-19. Fifty-nine (58.4%) of the patients showed low TLC, 41 (40.6%) were at risk for malnutrition, and 18 of them were malnourished. Low TLC was an independent risk factor for severe COVID-19. Compared to patients with normal TLC, those with low TLC more often presented with anorexia, malnutrition, higher SOFA scores (P < 0.05) and comorbidities (diabetes and malignancies). Malnutrition (OR: 3.05, 95% CI: 1.5–6.19, P = 0.006) and SOFA scores (OR: 1.51, 95% CI: 1.04-2.43, P = 0.042) were identified as independent risk factors for low TLC.

Conclusions: Malnutrition was common among our patients with early-stage COVID-19, and it contributed to the occurrence of low TLC.
Homologous Recombination Deficiency Associated With Response to Poly (ADP-ribose) Polymerase Inhibitors in Ovarian Cancer Patients: The First Real-World Evidence From China
Authors: Ni Jing , Guo Wenwen , Zhao Qian , Cheng Xianzhong , Xu Xia , Zhou Rui , Gu Hongyuan , Chen Chen , Chen Xiaoxiang
Published: January 2022

Homologous recombination deficiency (HRD) is an approved predictive biomarker for Poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. However, the proportion of positive HRD in the real world and the relationship between HRD status and PARPi in Chinese ovarian cancer patients remain unknown. A total of 67 ovarian cancer patients who underwent PARPi, either olaparib or niraparib, were enrolled and passed inclusion criteria from August 2018 to January 2021 in the Affiliated Cancer Hospital of Nanjing Medical University. HRD status correlation with Progression-free survival (PFS) was analyzed and summarized with a log-rank test. Univariate and multiple cox-regression analyses were conducted to investigate all correlated clinical factors. Approximately 68.7% (46/67) patients were HRD positive and the rest 31.3% (21/67) were HRD negative. The PFS among HRD-positive patients was significantly longer than those HRD-negative patients (medium PFS 9.4 m vs 4.1 m, hazard ratio [HR]: 0.52, 95% CI: [0.38–0.71], p <0.001). Univariate cox-regression found that HRD status, Eastern Cooperative Oncology Group (ECOG) status, BRCA status, previous treatment lines, secondary cytoreductive surgery and R0 resection were significantly associated with PFS after PARPi treatment. After multiple regression correction, HRD status and ECOG were the independent factors to predict PFS (HR: 0.67, 95% CI: [0.49–0.92], p = 0.01; HR: 2.20, 95% CI: [1.14–4.23], p = 0.02, respectively). In platinum sensitivity evaluable subgroup (N = 49), HRD status and platinum sensitivity status remain significant to predict PFS after multiple regression correction (HR: 0.71, 95% CI: [0.51–0.98], p = 0.04; HR: 0.49, 95% CI: [0.24–1.0], p = 0.05, respectively). This is the first real-world study of HRD status in ovarian cancer patients in China, and we demonstrate that HRD is an independent predictive biomarker for PARP inhibitors treatment in Chinese ovarian cancer patients.