bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Population Migration and Socioeconomic Factors on the COVID-19 Epidemic at County Level in Guangdong, China
Authors: Xu Jianhui , Deng Yingbin , Yang Ji , Huang Wumeng , Yan Yingwei , Xie Yichun , Li Yong , Jing Wenlong
Published: February 2022

Coronavirus disease 2019 (COVID-19) has become a major public health concern worldwide. In this study, we aimed to analyze spatial clusters of the COVID-19 epidemic and explore the effects of population emigration and socioeconomic factors on the epidemic at the county level in Guangdong, China. Data on confirmed cases, population migration, and socioeconomic factors for 121 counties were collected from 1 December 2019 to 17 February 2020, during which there were a total of 1,328 confirmed cases. County-level infected migrants of Guangdong moving from Hubei were calculated by integrating the incidence rate, population migration data of Baidu Qianxi, and the resident population. Using the spatial autocorrelation method, we identified high-cluster areas of the epidemic. We also used a geographical detector to explore infected migrants and socioeconomic factors associated with transmission of COVID-19 in Guangdong. Our results showed that: 1) the epidemic exhibited significant positive global spatial autocorrelation; high–high spatial clusters were mainly distributed in the Pearl River Estuary region; 2) city-level population migration data corroborated with the incidence rate of each city in Hubei showed significant association with confirmed cases; 3) in terms of potential factors, infected migrants greatly contributed to the spread of COVID-19, which has strong ability to explain the COVID-19 epidemic; besides, the companies, transport services, residential communities, restaurants, and community facilities were also the dominant factors in the spread of the epidemic; 4) the combined effect produced by the intersecting factors can increase the explanatory power. The infected migrant factor interacted strongly with the community facility factor with the q value of 0.895. This indicates that the interaction between infected migrants and community facilities played an important role in transmitting COVID-19 at the county level.
The First Mitochondrial Genome of Ciborinia camelliae and Its Position in the Sclerotiniaceae Family
Authors: Valenti Irene , Degradi Luca , Kunova Andrea , Cortesi Paolo , Pasquali Matias , Saracchi Marco
Published: February 2022

Ciborinia camelliae is the causal agent of camellia flower blight (CFB). It is a hemibiotrophic pathogen, inoperculate Discomycete of the family Sclerotiniaceae. It shows host and organ specificity infecting only flowers of species belonging to the genus Camellia, causing serious damage to the ornamental component of the plant. In this work, the first mitochondrial genome of Ciborinia camellia is reported. The mitogenome was obtained by combining Illumina short read and Nanopore long read technology. To resolve repetitive elements, specific primers were designed and used for Sanger sequencing. The manually curated mitochondrial DNA (mtDNA) of the Italian strain DSM 112729 is a circular sequence of 114,660 bp, with 29.6% of GC content. It contains two ribosomal RNA genes, 33 transfer RNAs, one RNase P gene, and 62 protein-coding genes. The latter include one gene coding for a ribosomal protein (rps3) and the 14 typical proteins involved in the oxidative metabolism. Moreover, a partial mtDNA assembled from a contig list was obtained from the deposited genome assembly of a New Zealand strain of C. camelliae. The present study contributes to understanding the mitogenome arrangement and the evolution of this phytopathogenic fungus in comparison to other Sclerotiniaceae species and confirms the usefulness of mitochondrial analysis to define phylogenetic positioning of this newly sequenced species.
Impact of OXTR Polymorphisms on Subjective Well-Being: The Intermediary Role of Attributional Style
Authors: Ji Lei , Chen Changfeng , Hou Binyin , Ren Decheng , Yuan Fan , Liu Liangjie , Bi Yan , Guo Zhenming , Yang Fengping , Wu Xi , Chen Fujun , Li Xingwang , Liu Chuanxin , Zuo Zhen , Zhang Rong , Yi Zhenghui , Xu Yifeng , He Lin , Shi Yi , Yu Tao , He Guang
Published: February 2022

Polymorphisms in the oxytocin receptor (OXTR) gene are related to individual differences in negative emotions, such as depressive symptoms and anxiety. However, it remains unclear what the potential roles of OXTR polymorphisms are in subjective well-being (SWB), which is negatively correlated with depressive symptoms. We examined attributional styles as mediator between SWB and five polymorphisms of the oxytocin receptor gene (OXTR rs53576, rs2254298, rs1042778, rs2268494, and rs2268490) among 627 full-time college freshmen (Mage = 20.90, SD = 0.82 for male; Mage = 20.81, SD = 0.92 for female) using structural equation modeling. The results showed that individuals with the OXTR rs2254298 AA genotype and rs53576 AA/GA genotype reported higher scores on SWB, which suggested that individuals with this genotype experienced more happiness. Moreover, external attributional style partially mediated the association between OXTR rs2254298 polymorphism and SWB (β = 0.019, 95%CI [0.001, 0.036], p = 0.035). In conclusion, our findings demonstrated that the genetic variations of OXTR played a role in the individual differences of SWB, and external attribution style could mediate the association.
Discovery of Differentially Expressed MicroRNAs in Porcine Ovaries With Smaller and Larger Litter Size
Authors: Xu Gaoxiao , Hu Yamei , Yu Dongling , Chen Xingfa , Li Xiao , Duan Saixing , Zhang Ning , Xu Gaoyu , Hu Jianhong , Yang Gongshe , Sun Shiduo , Liu Yong
Published: February 2022

The number of live births in a litter is an important reproductive trait, and is one of the main indicators which reflect the production level and economic benefit of a pig farm. The ovary is an important reproductive organ of the sow, and it undergoes a series of biological processes during each estrous cycle. A complex transcriptional network containing coding and non-coding RNAs in the ovary closely regulates the reproductive capability of sows. However, the molecular regulation mechanisms affecting sow litter size are still unclear. We investigated the expression profiles of microRNAs (miRNAs) in porcine ovaries from sows with smaller than average litter sizes (SLS) and those with larger litter sizes (LLS). In total, 411 miRNAs were identified, and of these 17 were significantly down-regulated and 16 miRNAs were up-regulated when comparing sows with LLS and SLS, respectively. We further characterized the role of miR-183 which was one of the most up-regulated miRNAs. CCK-8, EdU incorporation and western blotting assays demonstrated that miR-183 promoted the proliferation of granulosa cells (GCs) in pig ovaries. Moreover, miR-183 inhibited the synthesis of estradiol in GCs and promoted the synthesis of progesterone. These results will help in gaining understanding of the role of miRNAs in regulating porcine litter size.
Genomic Selection: A Tool for Accelerating the Efficiency of Molecular Breeding for Development of Climate-Resilient Crops
Authors: Budhlakoti Neeraj , Kushwaha Amar Kant , Rai Anil , Chaturvedi K K , Kumar Anuj , Pradhan Anjan Kumar , Kumar Uttam , Kumar Rajeev Ranjan , Juliana Philomin , Mishra D C , Kumar Sundeep
Published: February 2022

Since the inception of the theory and conceptual framework of genomic selection (GS), extensive research has been done on evaluating its efficiency for utilization in crop improvement. Though, the marker-assisted selection has proven its potential for improvement of qualitative traits controlled by one to few genes with large effects. Its role in improving quantitative traits controlled by several genes with small effects is limited. In this regard, GS that utilizes genomic-estimated breeding values of individuals obtained from genome-wide markers to choose candidates for the next breeding cycle is a powerful approach to improve quantitative traits. In the last two decades, GS has been widely adopted in animal breeding programs globally because of its potential to improve selection accuracy, minimize phenotyping, reduce cycle time, and increase genetic gains. In addition, given the promising initial evaluation outcomes of GS for the improvement of yield, biotic and abiotic stress tolerance, and quality in cereal crops like wheat, maize, and rice, prospects of integrating it in breeding crops are also being explored. Improved statistical models that leverage the genomic information to increase the prediction accuracies are critical for the effectiveness of GS-enabled breeding programs. Study on genetic architecture under drought and heat stress helps in developing production markers that can significantly accelerate the development of stress-resilient crop varieties through GS. This review focuses on the transition from traditional selection methods to GS, underlying statistical methods and tools used for this purpose, current status of GS studies in crop plants, and perspectives for its successful implementation in the development of climate-resilient crops.
Assessment of Associations Between Serum Lipoprotein (a) Levels and Atherosclerotic Vascular Diseases in Hungarian Patients With Familial Hypercholesterolemia Using Data Mining and Machine Learning
Authors: Németh Ákos , Daróczy Bálint , Juhász Lilla , Fülöp Péter , Harangi Mariann , Paragh György
Published: February 2022

Background and aims: Premature mortality due to atherosclerotic vascular disease is very high in Hungary in comparison with international prevalence rates, though the estimated prevalence of familial hypercholesterolemia (FH) is in line with the data of other European countries. Previous studies have shown that high lipoprotein(a)- Lp(a) levels are associated with an increased risk of atherosclerotic vascular diseases in patients with FH. We aimed to assess the associations of serum Lp(a) levels and such vascular diseases in FH using data mining methods and machine learning techniques in the Northern Great Plain region of Hungary.

Methods: Medical records of 590,500 patients were included in our study. Based on the data from previously diagnosed FH patients using the Dutch Lipid Clinic Network scores (≥7 was evaluated as probable or definite FH), we trained machine learning models to identify FH patients.

Results: We identified 459 patients with FH and 221 of them had data available on Lp(a). Patients with FH had significantly higher Lp(a) levels compared to non-FH subjects [236 (92.5; 698.5) vs. 167 (80.2; 431.5) mg/L, p < .01]. Also 35.3% of FH patients had Lp(a) levels >500 mg/L. Atherosclerotic complications were significantly more frequent in FH patients compared to patients without FH (46.6 vs. 13.9%). However, contrary to several other previous studies, we could not find significant associations between serum Lp(a) levels and atherosclerotic vascular diseases in the studied Hungarian FH patient group.

Conclusion: The extremely high burden of vascular disease is mainly explained by the unhealthy lifestyle of our patients (i.e., high prevalence of smoking, unhealthy diet and physical inactivity resulting in obesity and hypertension). The lack of associations between serum Lp(a) levels and atherosclerotic vascular diseases in Hungarian FH patients may be due to the high prevalence of these risk factors, that mask the deleterious effect of Lp(a).
Evolution of Guanylate Binding Protein (GBP) Genes in Muroid Rodents (Muridae and Cricetidae) Reveals an Outstanding Pattern of Gain and Loss
Authors: Côrte-Real João Vasco , Baldauf Hanna-Mari , Melo-Ferreira José , Abrantes Joana , Esteves Pedro José
Published: February 2022

Guanylate binding proteins (GBPs) are paramount in the host immunity by providing defense against invading pathogens. Multigene families related to the immune system usually show that the duplicated genes can either undergo deletion, gain new functions, or become non-functional. Here, we show that in muroids, the Gbp genes followed an unusual pattern of gain and loss of genes. Muroids present a high diversity and plasticity regarding Gbp synteny, with most species presenting two Gbp gene clusters. The phylogenetic analyses revealed seven different Gbps groups. Three of them clustered with GBP2, GBP5 and GBP6 of primates. Four new Gbp genes that appear to be exclusive to muroids were identified as Gbpa, b, c and d. A duplication event occurred in the Gbpa group in the common ancestor of Muridae and Cricetidae (~20 Mya), but both copies were deleted from the genome of Mus musculus, M. caroli and Cricetulus griseus. The Gbpb gene emerged in the ancestor of Muridae and Cricetidae and evolved independently originating Gbpb1 in Muridae, Gbpb2 and Gbpb3 in Cricetidae. Since Gbpc appears only in three species, we hypothesize that it was present in the common ancestor and deleted from most muroid genomes. The second Gbp gene cluster, Gbp6, is widespread across all muroids, indicating that this cluster emerged before the Muridae and Cricetidae radiation. An expansion of Gbp6 occurred in M. musculus and M. caroli probably to compensate the loss of Gbpa and b. Gbpd is divided in three groups and is present in most muroids suggesting that a duplication event occurred in the common ancestor of Muridae and Cricetidae. However, in Grammomys surdaster and Mus caroli, Gbpd2 is absent, and in Arvicanthis niloticus, Gbpd1 appears to have been deleted. Our results further demonstrated that primate GBP1, GBP3 and GBP7 are absent from the genome of muroids and showed that the Gbp gene annotations in muroids were incorrect. We propose a new classification based on the phylogenetic analyses and the divergence between the groups. Extrapolations to humans based on functional studies of muroid Gbps should be re-evaluated. The evolutionary analyses of muroid Gbp genes provided new insights about the evolution and function of these genes.
Serum Eicosanoids Metabolomics Profile in a Mouse Model of Renal Cell Carcinoma: Predicting the Antitumor Efficacy of Anlotinib
Authors: Du Ping , Xuan Lingling , Hu Ting , An Zhuoling , Liu Lihong
Published: February 2022

Anlotinib (ANL) shows promising efficacy in patients with renal cell cancer (RCC). Here, for the first time, a serum eicosanoid metabolomics profile and pharmacodynamics in Renca syngeneic mice treated with ANL was performed and integrated using our previous HPLC-MS/MS method and multivariate statistical analysis. The tumor growth inhibition rates of ANL were 39% and 52% at low (3 mg/kg) and high (6 mg/kg) dose levels, without obvious toxicity. A total of 15 disturbed metabolites were observed between the normal group and the model group, and the intrinsic metabolic phenotype alterations had occurred due to the treatment of ANL. A total of eight potential metabolites from the refined partial least squares (PLS) model were considered as potential predictive biomarkers for the efficacy of ANL, and the DHA held the most outstanding sensitivity and specificity with an area under the receiver operating characteristic curve of 0.88. Collectively, the results of this exploratory study not only provide a powerful reference for understanding eicosanoid metabolic reprogramming of ANL but also offer an innovative perspective for the development of therapeutic targets and strategies, the discovery of predictive biomarkers, and the determination of effective tumor monitoring approaches.
Bryostatin Activates CAR T-Cell Antigen-Non-Specific Killing (CTAK), and CAR-T NK-Like Killing for Pre-B ALL, While Blocking Cytolysis of a Burkitt Lymphoma Cell Line
Authors: Wang Lingyan , Zhang Yue , Anderson Eden , Lamble Adam , Orentas Rimas J.
Published: February 2022

The advent of CAR-T cell therapy has changed the face of clinical care for relapsed and refractory pre-B-acute lymphocytic leukemia (B-ALL) and lymphoma. Although curative responses are reported, long-term cures remain below 50%. Different CAR T-cell leukemia targets appear to have different mechanisms of CAR-T escape. For CD22, therapeutic evasion is linked to down-modulation of the number CD22 proteins expressed on the extracellular aspect of the leukemia cell plasma membrane. Recently, pharmacologic agents known to induce cellular differentiation or epigenetic modification of leukemia have been shown to impact CD22 and CD19 expression levels on B-ALL, and thereby increase sensitivity to CAR-T mediated cytolysis. We explored the impact of epigenetic modifiers and differentiation agents on leukemia cell lines of B cell origin, as well as normal B cells. We confirmed the activity of bryostatin to increase CD22 expression on model cell lines. However, bryostatin does not change CD22 levels on normal B cells. Furthermore, bryostatin inhibited CAR-T mediated cytolysis of the Raji Burkitt lymphoma cell line. Bryostatin increased the cytolysis by CD22 CAR-T for B-ALL cell lines by at least three mechanisms: 1) the previously reported increase in CD22 target cell numbers on the cell surface, 2) the induction of NK ligands, and 3) the induction of ligands that sensitize leukemia cells to activated T cell antigen-non-specific killing. The opposite effect was seen for Burkitt lymphoma, which arises from a more mature B cell lineage. These findings should caution investigators against a universal application of agents shown to increase killing of leukemia target cells by CAR-T in a specific disease class, and highlights that activation of non-CAR-mediated killing by activated T cells may play a significant role in the control of disease. We have termed the killing of leukemia targets, by a set of cell-surface receptors that does not overlap with NK-like killing “CTAK,” CAR-T Cell antigen-non-specific killing.
Planktic Foraminiferal Assemblages in Surface Sediments From the Subpolar North Atlantic Ocean
Authors: Sahoo Nibedita , Saalim Syed Mohammad , Matul Alexander , Mohan Rahul , Tikhonova Anna , Kozina Nina
Published: February 2022

The subpolar North Atlantic (SPNA) Ocean has complex hydrography, and moderates the global climate through the Atlantic Meridional Overturning Circulation (AMOC). The surface water mass dynamics in SPNA and the upper limb of AMOC, govern the plankton distribution. Specifically, the habitat of modern planktic foraminifera is strongly affected by the SPNA hydrography. In the present study, 25 surface sediment samples from the Labrador Sea to the Iceland-Faroe-Shetland Channel (IFSC) were examined for planktic foraminifera distribution along a latitudinal transect at 59.50°N. The planktic foraminifera distribution followed the transition in water mass structure in the study area from the Sub-Arctic water in the west to the warm North Atlantic water in the east. Temperature and salinity are two dominant ecological factors controlling planktic foraminifera assemblages in the region. This hydrographic contrast was also reflected in the ratio of Neogloboquadrina pachyderma/Neogloboquadrina incompta along the transect. Based on the cluster analysis, the planktic foraminifera assemblages could be assigned to three groups. A cold/polar group in the Labrador Sea, a mixed (both cold and warm) group in the Irminger Sea and IFSC, and a warmer temperate group in the eastern part of the transect were represented by different planktic foraminifera assemblages. Additionally, a decrease in Globorotalia inflata in the eastern transect and an increase in Turborotalita quinqueloba in the Iceland basin and Irminger Sea was observed in our study when compared with the published dataset. From this, we suggest a shift in planktic assemblages in the SPNA. The present study on the distribution of modern planktic foraminifera can help paleoceanographic reconstructions in the SPNA ocean.
Two Decades of Match-Mismatch in Northeast Arctic Cod – Feeding Conditions and Survival
Authors: Endo Clarissa Akemi Kajiya , Stige Leif Christian , Skogen Morten D. , Ciannelli Lorenzo , Vikebø Frode V.
Published: February 2022

The successful recruitment of Northeast Arctic (NEA) cod is thought to depend on sufficient and suitable prey for the newly hatched larvae, in particular the nauplii stages of the lipid-rich calanoid copepod species Calanus finmarchicus. The role of spatial and temporal variations in prey availability in combination with temperature and other factors in influencing growth and survival of cod larvae is, however, incompletely understood. By combining an individual based model for NEA cod larvae at the Norwegian coast with a high-resolution ocean model and a nutrient-phytoplankton-zooplankton-detritus model providing 18 years of daily environmental conditions and prey availability we assessed larval growth and survival until they settle in their feeding habitat in the Barents Sea in early fall. We find on average a two-week delay from the peak timing of first-feeding cod larvae to the peak in prey availability. In warm years, more larvae experience food limitation than in normal years. The positive effects of high temperature on growth, survival and ultimately recruitment are nonetheless larger than the negative effects of food limitation. Food limitation mainly affects larvae spawned in southern areas or late in the spawning season as these larvae experience the highest temperatures and have the highest energy requirements. Our findings highlight the spatial and temporal differences in mechanisms that regulate growth and survival of early life stages of NEA cod and suggest that spatially resolved data may be essential for understanding match-mismatch dynamics.
On the Relationship Between Tropical Instability Waves and Intraseasonal Equatorial Kelvin Waves in the Pacific From Satellite Observations (1993–2018)
Authors: Escobar-Franco M. Gabriela , Boucharel Julien , Dewitte Boris
Published: February 2022

Intraseasonal Kelvin waves (IKWs) and Tropical Instability Waves (TIWs) are essential components of the tropical Pacific coupled climate variability. While downwelling IKWs are precursors of ENSO (e.g., the El Niño Southern Oscillation), TIWs contribute to its asymmetry by mixing more/less warm off-equatorial and cold tongue waters during La Niña/El Niño. Theoretical studies and a few observational case studies also suggest that TIWs and IKWs can interact non-linearly. However, owing to the chaotic nature of TIWs, observational evidence that such a process occurs consistently has not been established thus far. Here, we document for the first time their interaction from satellite observations over a period spanning almost 30 years (1993–2018). From complex empirical orthogonal functions analysis and sea level decomposition into meridional modes, we evidence that a substantial share (∼42%) of the variance of TIWs-induced intraseasonal sea level anomalies are associated with IKWs activity. We show that non-linear dynamical heating (NDH) in the Eastern equatorial Pacific associated with this intraseasonal mode can be as large as that for interannual time scales. Implications for understanding the eastern tropical Pacific heat budget and ENSO variability are discussed.
Impact of Succinylcholine vs. Rocuronium on Apnea Duration for Rapid Sequence Induction: A Prospective Cohort Study
Authors: Tang Lijun , Zhao Xiao , Li Shitong , Huang Lina , Li Jinbao , Chen Lianhua , Huang Shiwei
Published: February 2022

Objective

The present study aimed to evaluate the impact of 1.5 mg/kg succinylcholine or 1.2 mg/kg rocuronium, vs. 1.0 mg/kg succinylcholine on apnea duration in patients underwent rapid sequence induction (RSI).

Methods

This prospective cohort study was conducted in the Department of Anesthesiology in Shanghai General Hospital from July 2020 to November 2020. Apnea duration was defined as the time from apnea prompted by the PETCO2 waveform to the time the point of oxygen saturation declined to 90% (T90) and 95% (T95) after succinylcholine or rocuronium administration. The primary outcome included T90 and T95 changes in 1.5 mg/kg vs. 1.0 mg/kg succinylcholine groups and 1.5 mg/kg succinylcholine vs. 1.2 mg/kg rocuronium groups.

Results

A total of 265 participants were subjected for analysis. The succinylcholine (1.0 mg/kg) group had a significantly longer T90 (50.72, 95% confidence interval [CI, 7.60, 94.38], P = 0.015) and T95 (48.09, 95% CI [7.11, 89.07], P = 0.012) than the succinylcholine (1.5 mg/kg) group. In addition, significantly longer T90 (56.84, 95% CI [16.24, 97.44], P = 0.003) and T95 (50.57, 95% CI [12.58, 88.57], P = 0.003) were observed in the rocuronium (1.2 mg/kg) group than those in the succinylcholine (1.5 mg/kg) group. No severe side events were observed during the operation.

Conclusion

Rocuronium and the lower dose of succinylcholine may be recommended to patients underwent RSI.
Molecular Chaperone BRICHOS Inhibits CADASIL-Mutated NOTCH3 Aggregation In Vitro
Authors: Oliveira Daniel V. , Svensson Julia , Zhong Xueying , Biverstål Henrik , Chen Gefei , Karlström Helena
Published: February 2022

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is the most common familial form of stroke, which is caused by mutations located in the epidermal growth factor (EGF)-like repeats of the NOTCH3 gene. Mutations cause the NOTCH3 (N3) protein to misfold and aggregate. These aggregates will be a component of granular osmiophilic material, which when accumulated around the arteries and arterioles is believed to cause the degradation of vascular smooth muscle cells (VSMC). VSMC degradation affects blood flow regulation and leads to white matter and neuronal death. Currently, there is no treatment for CADASIL. The dementia-relevant BRICHOS domain is a small multitalented protein with functions that include ATP-independent chaperone-like properties. BRICHOS has been shown to prevent the aggregation of both fibrillar and non-fibrillar structures. Therefore, the objective of this study is to investigate whether BRICHOS exhibits anti-aggregating properties on a recombinant CADASIL-mutated N3 protein consisting of the first five repeats of EGF (EGF1–5), harboring a cysteine instead of an arginine in the position 133, (R133C). We found that the N3 EGF1–5 R133C mutant is more prone to aggregate, while the wildtype is more stable. Recombinant human Bri2 BRICHOS is able to interact and stabilize the R133C-mutated N3 protein in a dose-dependent manner. These results suggest an anti-aggregating impact of BRICHOS on the N3 EGF1–5 R133C protein, which could be a potential treatment for CADASIL.
The Evolution of Visual Roles – Ancient Vision Versus Object Vision
Authors: Nilsson Dan-Eric
Published: February 2022

Just like other complex biological features, image vision (multi-pixel light sensing) did not evolve suddenly. Animal visual systems have a long prehistory of non-imaging light sensitivity. The first spatial vision was likely very crude with only few pixels, and evolved to improve orientation behaviors previously supported by single-channel directional photoreception. The origin of image vision was simply a switch from single to multiple spatial channels, which improved the behaviors for finding a suitable habitat and position itself within it. Orientation based on spatial vision obviously involves active guidance of behaviors but, by necessity, also assessment of habitat suitability and environmental conditions. These conditions are crucial for deciding when to forage, reproduce, seek shelter, rest, etc. When spatial resolution became good enough to see other animals and interact with them, a whole range of new visual roles emerged: pursuit, escape, communication and other interactions. All these new visual roles require entirely new types of visual processing. Objects needed to be separated from the background, identified and classified to make the correct choice of interaction. Object detection and identification can be used actively to guide behaviors but of course also to assess the over-all situation. Visual roles can thus be classified as either ancient non-object-based tasks, or object vision. Each of these two categories can also be further divided into active visual tasks and visual assessment tasks. This generates four major categories of vision into which I propose that all visual roles can be categorized.
Effect of Transcranial Direct Current Stimulation on the Mismatch Negativity Features of Deviated Stimuli in Children With Autism Spectrum Disorder
Authors: Sun Changcheng , Zhao Zhuoyue , Cheng Longlong , Tian Rong , Zhao Wenchang , Du Jingang , Zhang Ying , Wang Chunfang
Published: February 2022

Autism spectrum disorder (ASD) is a devastating mental disorder in children. Currently, there is no effective treatment for ASD. Transcranial direct current stimulation (tDCS), which is a non-invasive brain stimulation neuromodulation technology, is a promising method for the treatment of ASD. However, the manner in which tDCS changes the electrophysiological process in the brain is still unclear. In this study, we used tDCS to stimulate the dorsolateral prefrontal cortex area of children with ASD (one group received anode tDCS, and the other received sham tDCS) and investigated the changes in evoked EEG signals and behavioral abilities before and after anode and sham stimulations. In addition to tDCS, all patients received conventional rehabilitation treatment. Results show that although conventional treatment can effectively improve the behavioral ability of children with ASD, the use of anode tDCS with conventional rehabilitation can boost this improvement, thus leading to increased treatment efficacy. By analyzing the electroencephalography pre- and post-treatment, we noticed a decrease in the mismatch negativity (MMN) latency and an increase in the MMN amplitude in both groups, these features are considered similar to MMN features from healthy children. However, no statistical difference between the two groups was observed after 4 weeks of treatment. In addition, the MMN features correlate well with the aberrant behavior checklist (ABC) scale, particularly the amplitude of MMN, thus suggesting the feasibility of using MMN features to assess the behavioral ability of children with ASD.
Macromolecular Proton Fraction as a Myelin Biomarker: Principles, Validation, and Applications
Authors: Kisel Alena A. , Naumova Anna V. , Yarnykh Vasily L.
Published: February 2022

Macromolecular proton fraction (MPF) is a quantitative MRI parameter describing the magnetization transfer (MT) effect and defined as a relative amount of protons bound to biological macromolecules with restricted molecular motion, which participate in magnetic cross-relaxation with water protons. MPF attracted significant interest during past decade as a biomarker of myelin. The purpose of this mini review is to provide a brief but comprehensive summary of MPF mapping methods, histological validation studies, and MPF applications in neuroscience. Technically, MPF maps can be obtained using a variety of quantitative MT methods. Some of them enable clinically reasonable scan time and resolution. Recent studies demonstrated the feasibility of MPF mapping using standard clinical MRI pulse sequences, thus substantially enhancing the method availability. A number of studies in animal models demonstrated strong correlations between MPF and histological markers of myelin with a minor influence of potential confounders. Histological studies validated the capability of MPF to monitor both demyelination and re-myelination. Clinical applications of MPF have been mainly focused on multiple sclerosis where this method provided new insights into both white and gray matter pathology. Besides, several studies used MPF to investigate myelin role in other neurological and psychiatric conditions. Another promising area of MPF applications is the brain development studies. MPF demonstrated the capabilities to quantitatively characterize the earliest stage of myelination during prenatal brain maturation and protracted myelin development in adolescence. In summary, MPF mapping provides a technically mature and comprehensively validated myelin imaging technology for various preclinical and clinical neuroscience applications.
Synapse Maturation and Developmental Impairment in the Medial Nucleus of the Trapezoid Body
Authors: Chokr Sima M. , Milinkeviciute Giedre , Cramer Karina S.
Published: February 2022

Sound localization requires rapid interpretation of signal speed, intensity, and frequency. Precise neurotransmission of auditory signals relies on specialized auditory brainstem synapses including the calyx of Held, the large encapsulating input to principal neurons in the medial nucleus of the trapezoid body (MNTB). During development, synapses in the MNTB are established, eliminated, and strengthened, thereby forming an excitatory/inhibitory (E/I) synapse profile. However, in neurodevelopmental disorders such as autism spectrum disorder (ASD), E/I neurotransmission is altered, and auditory phenotypes emerge anatomically, molecularly, and functionally. Here we review factors required for normal synapse development in this auditory brainstem pathway and discuss how it is affected by mutations in ASD-linked genes.
The Role of Non-canonical and Canonical Inflammasomes in Inflammaging
Authors: Cyr Brianna , Hadad Roey , Keane Robert W. , de Rivero Vaccari Juan Pablo
Published: February 2022

Neurodegenerative diseases currently affect millions of people worldwide and continues to increase in the expanding elderly population. Neurodegenerative diseases usually involve cognitive decline and are among the top causes of death. Thus, there is a critical need for the development of treatments and preventive strategies for neurodegenerative diseases. One of the risk factors of neurodegeneration is inflammaging, a low level of chronic inflammation due to old age. We have previously shown that the inflammasome contributes to inflammaging in the central nervous system (CNS). The inflammasome is a multiprotein complex of the innate immune response consisting of a sensor protein, apoptosis speck-like protein containing a CARD (ASC), and caspase-1. Our lab has developed a humanized monoclonal antibody against ASC (anti-ASC). Here, we analyzed cortical lysates from young (3 months old), aged (18 months old), and aged anti-ASC treated mice for the expression of canonical and non-canonical inflammasome proteins. We show that the protein levels of NLRP1, ASC, caspase-1, and caspase-8 were elevated in the cortex of aged mice, and that anti-ASC decreased the expression of these proteins, consistent with lower levels of the pro-inflammatory cytokine interleukin (IL)-1β. Additionally, we show that these proteins form a novel NLRP1-caspase-8 non-canonical inflammasome comprised of NLRP1, caspase-8 and ASC. Moreover, these inflammasome proteins were present in neurons in young and aged mice. Together, these results indicate that a novel NLRP1-caspase-8 non-canonical inflammasome is present in the cortex of mice and that anti-ASC is a potential therapeutic to decrease inflammasome-mediated inflammaging in the CNS.
The Application of Brain Organoids in Assessing Neural Toxicity
Authors: Fan Pan , Wang YuanHao , Xu Min , Han Xiao , Liu Yan
Published: February 2022

The human brain is a complicated and precisely organized organ. Exogenous chemicals, such as pollutants, drugs, and industrial chemicals, may affect the biological processes of the brain or its function and eventually lead to neurological diseases. Animal models may not fully recapitulate the human brain for testing neural toxicity. Brain organoids with self-assembled three-dimensional (3D) structures provide opportunities to generate relevant tests or predictions of human neurotoxicity. In this study, we reviewed recent advances in brain organoid techniques and their application in assessing neural toxicants. We hope this review provides new insights for further progress in brain organoid application in the screening studies of neural toxicants.
Dietary Transitions and Health Outcomes in Four Populations – Systematic Review
Authors: Pressler Mariel , Devinsky Julie , Duster Miranda , Lee Joyce H. , Glick Courtney S. , Wiener Samson , Laze Juliana , Friedman Daniel , Roberts Timothy , Devinsky Orrin
Published: February 2022

Importance

Non-communicable chronic diseases (NCDs) such as obesity, type 2 diabetes, heart disease, and cancer were rare among non-western populations with traditional diets and lifestyles. As populations transitioned toward industrialized diets and lifestyles, NCDs developed.

Objective

We performed a systematic literature review to examine the effects of diet and lifestyle transitions on NCDs.

Evidence Review

We identified 22 populations that underwent a nutrition transition, eleven of which had sufficient data. Of these, we chose four populations with diverse geographies, diets and lifestyles who underwent a dietary and lifestyle transition and explored the relationship between dietary changes and health outcomes. We excluded populations with features overlapping with selected populations or with complicating factors such as inadequate data, subgroups, and different study methodologies over different periods. The selected populations were Yemenite Jews, Tokelauans, Tanushimaru Japanese, and Maasai. We also review transition data from seven excluded populations (Pima, Navajo, Aboriginal Australians, South African Natal Indians and Zulu speakers, Inuit, and Hadza) to assess for bias.

Findings

The three groups that replaced saturated fats (SFA) from animal (Yemenite Jews, Maasai) or plants (Tokelau) with refined carbohydrates had negative health outcomes (e.g., increased obesity, diabetes, heart disease). Yemenites reduced SFA consumption by >40% post-transition but men's BMI increased 19% and diabetes increased ~40-fold. Tokelauans reduced fat, dramatically reduced SFA, and increased sugar intake: obesity and diabetes rose. The Tanushimaruans transitioned to more fats and less carbohydrates and used more anti-hypertensive medications; stroke and breast cancer declined while heart disease was stable. The Maasai transitioned to lower fat, SFA and higher carbohydrates and had increased BMI and diabetes. Similar patterns were observed in the seven other populations.

Conclusion

The nutrient category most strongly associated with negative health outcomes – especially obesity and diabetes – was sugar (increased 600–650% in Yemenite Jews and Tokelauans) and refined carbohydrates (among Maasai, total carbohydrates increased 39% in men and 362% in women), while increased calories was less strongly associated with these disorders. Across 11 populations, NCDs were associated with increased refined carbohydrates more than increased calories, reduced activity or other factors, but cannot be attributed to SFA or total fat consumption.
Respiratory 4D-Gating F-18 FDG PET/CT Scan for Liver Malignancies: Feasibility in Liver Cancer Patient and Tumor Quantitative Analysis
Authors: Cheung Anson H. Y. , Wu Vincent W. C. , Cheung Andy L. Y. , Cai Jing
Published: February 2022

Purpose

To evaluate the potential clinical role and effectiveness of respiratory 4D-gating F-18 FDG PET/CT scan for liver malignancies, relative to routine (3D) F-18 FDG PET/CT scan.

Materials and Methods

This study presented a prospective clinical study of 16 patients who received F-18 FDG PET/CT scan for known or suspected malignant liver lesions. Ethics approvals were obtained from the ethics committees of the Hong Kong Baptist Hospital and The Hong Kong Polytechnic University. Liver lesions were compared between the gated and ungated image sets, in terms of 1) volume measurement of PET image, 2) accuracy of maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and 3) accuracy of total lesion glycoses (TLG). Statistical analysis was performed by using a two-tailed paired Student t-test and Pearson correlation test.

Results

The study population consisted of 16 patients (9 males and 7 females; mean age of 65) with a total number of 89 lesions. The SUVmax and SUVmean measurement of the gated PET images was more accurate than that of the ungated PET images, compared to the static reference images. An average of 21.48% (p < 0.001) reduction of the tumor volume was also observed. The SUVmax and SUVmean of the gated PET images were improved by 19.81% (p < 0.001) and 25.53% (p < 0.001), compared to the ungated PET images.

Conclusions

We have demonstrated the feasibility of implementing 4D PET/CT scan for liver malignancies in a prospective clinical study. The 4D PET/CT scan for liver malignancies could improve the quality of PET image by improving the SUV accuracy of the lesions and reducing image blurring. The improved accuracy in the classification and identification of liver tumors with 4D PET image would potentially lead to its increased utilization in target delineation of GTV, ITV, and PTV for liver radiotherapy treatment planning in the future.
Hydrocephalus Shunting in Supratentorial Glioblastoma: Functional Outcomes and Management
Authors: El Rahal Amir , Cipriani Debora , Fung Christian , Hohenhaus Marc , Sveikata Lukas , Straehle Jakob , Shah Mukesch Johannes , Heiland Henrik Dieter , Beck Jürgen , Schnell Oliver
Published: February 2022

Background

Glioblastoma is the most common and the most challenging to treat adult primary central nervous system tumor. Although modern management strategies modestly improved the overall survival, the prognosis remains dismal associated with poor life quality and the clinical course often dotted by treatment side effects and cognitive decline. Functional deterioration might be caused by obstructive or communicating hydrocephalus but due to poor overall prognosis surgical treatment options are often limited and its optimal management strategies remain elusive. We aimed to investigate risk factors, treatment options and outcomes for tumor-associated hydrocephalus in a contemporary 10 years cohort of glioblastoma patients.

Methods

We reviewed electronic health records of 1800 glioblastoma patients operated at the Department of Neurosurgery, Medical Center – University of Freiburg from 2009 to 2019. Demographics, clinical characteristics and radiological features were analyzed. Univariate analysis for nominal variables was performed either by Fisher’s exact test or Chi-square test, as appropriate.

Results

We identified 39 glioblastoma patients with symptomatic communicating hydrocephalus treated by ventricular shunting (incidence 2.1%). Opening of the ventricular system during a previous tumor resection was associated with symptomatic hydrocephalus (p<0.05). There was also a trend toward location (frontal and temporal) and larger tumor volume. Number of craniotomies before shunting was not considered as a risk factor. Shunting improved hydrocephalus symptoms in 95% of the patients and Karnofsky Performance Score (KPS) could be restored after shunting. Of note, 75% of the patients had a post-shunting oncological treatment such as radiotherapy or chemotherapy, most prevalently chemotherapy. Infection (7.7%) and over- or under drainage (17.9%) were the most common complications requiring shunt revision in ten patients (25.6%), No peritoneal metastasis was found. The median overall survival (OS) was 385 days and the median post shunting survival was 135 days.

Conclusion

Ventricular system opening was identified as a risk factor for communicating hydrocephalus in glioblastoma patients. Although glioblastoma treatment remains challenging, shunting improved hydrocephalus-related functional status and may be considered even in a palliative setting for symptom relief.
MYC/MAX-Activated LINC00958 Promotes Lung Adenocarcinoma by Oncogenic Transcriptional Reprogramming Through HOXA1 Activation
Authors: Zhang Tao , Su Fei , Lu Yong-bin , Ling Xiao-ling , Dai Huan-yu , Yang Tian-ning , Zhang Bin , Zhao Da , Hou Xiao-ming
Published: February 2022

Background

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. The role of the long non-coding RNA (lncRNA) LINC00958, which regulates the malignant behavior of multiple tumors, in LUAD has not been elucidated.

Methods

Tissue microarray, FISH, and qRT-PCR were used to detect the expression of LINC00958. Plasmid and viral infections were used to manipulate gene expression. The role of LINC00958 in LUAD was studied by cell proliferation analysis, cell apoptosis analysis, cell migration and invasion analysis, and subcutaneous inoculation of animal models. At the same time, RNA-Seq, RNA pull-down, ChIRP, ChIP, and luciferase reporter gene assays were performed to clarify the mechanism.

Results

The expression of LINC00958 in LUAD tissues was significantly upregulated when compared with that in adjacent tissues and could independently predict poor survival of patients with LUAD. LINC00958 knockdown significantly inhibited the growth and metastasis of lung cancer cells in vitro and in vivo. LINC00958 localized to the nucleus, regulated oncogenes and metabolism-related and immune response-related genes, and interacted with histones. The targets of LINC00958 were TRPV3, STAP2, and EDN2 promoters with motifs of HOXA1, NANOG, FOSL2, JUN, and ATF4. Moreover, HOXA1 overexpression mitigated the LINC00958 knockdown-induced oncogenic phenotype. MYC/MAX motif, which was detected at the cis-element of LINC00958, trans-activated the LINC00958 promoter.

Conclusions

MYC/MAX-trans-activated LINC00958 promotes the malignant behavior of LUAD by recruiting HOXA1 and inducing oncogenic reprogramming.
Functional Bowel Complaints and the Impact on Quality of Life After Colorectal Cancer Surgery in the Elderly
Authors: Ketelaers Stijn H. J. , van Heinsbergen Maarten , Orsini Ricardo G. , Vogelaar F. Jeroen , Konsten Joop L. M. , Nieuwenhuijzen Grard A. P. , Rutten Harm J. T. , Burger Jacobus W. A. , Bloemen Johanne G.
Published: February 2022

Background

The Low Anterior Resection Syndrome (LARS) is commonly reported after colorectal cancer surgery and significantly impairs quality of life. The prevalence and impact of LARS in the elderly after rectal cancer as well as colon cancer surgery is unclear. We aimed to describe the prevalence of LARS complaints and the impact on quality of life in the elderly after colorectal cancer surgery.

Materials and Methods

Patients were included from seven Dutch hospitals if they were at least one year after they underwent colorectal cancer surgery between 2008 and 2015. Functional bowel complaints were assessed by the LARS score. Quality of life was assessed by the EORTC QLQ-C30 and EORTC QLQ-CR29 questionnaires. Outcomes in patients ≥70 years were compared to a reference group of patients <70 years.

Results

In total 440 rectal cancer and 1183 colon cancer patients were eligible for analyses, of whom 133 (30.2%) rectal and 536 (45.3%) colon cancer patients were ≥70 years. Major LARS was reported by 40.6% of rectal cancer and 22.2% of colon cancer patients ≥70 years. In comparison, patients <70 years reported major LARS in 57.3% after rectal cancer surgery (p=0.001) and in 20.4% after colon cancer surgery (p=0.41). Age ≥70 years was independently associated with reduced rates of major LARS after rectal cancer surgery (OR 0.63, p=0.04). Patients with major LARS reported significantly impaired quality of life on almost all domains.

Conclusion

Elderly should not be withheld a restorative colorectal cancer resection based on age alone. However, a substantial part of the elderly colorectal cancer patients develops major LARS after surgery, which often severely impairs quality of life. Since elderly frequently consider quality of life and functional outcomes as one of the most important outcomes after treatment, major LARS and its impact on quality of life should be incorporated in the decision-making process.