bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of MCMC-Based Travel Simulation Framework Using Mobile Phone Data
Authors: Gong Suxia , Saadi Ismaïl , Teller Jacques , Cools Mario
Published: May 2021

An essential step in agent-based travel demand models is the characterization of the population, including transport-related attributes. This study looks deep into various mobility data in the province of Liège, Belgium. Based on the data stemming from the 2010 Belgian HTS, that is, BELDAM, a Markov chain Monte Carlo (MCMC) sampling method combined with a cross-validation process is used to generate sociodemographic attributes and trip-based variables. Besides, representative micro-samples are calibrated using data about the population structure. As a critical part of travel demand modeling for practical applications in the real-world context, validation using various data sources can contribute to the modeling framework in different ways. The innovation in this study lies in the comparison of outputs of MCMC with mobile phone data. The difference between modeled and observed trip length distributions is studied to validate the simulation framework. The proposed framework infers trips with multiple attributes while preserving the traveler’s sociodemographics. We show that the framework effectively captures the behavioral complexity of travel choices. Moreover, we demonstrate mobile phone data’s potential to contribute to the reliability of travel demand models.
Whole-Exome Sequencing Reveals a Rare Variant of OTOF Gene Causing Congenital Non-syndromic Hearing Loss Among Large Muslim Families Favoring Consanguinity
Authors: Fareed Mohd , Sharma Varun , Singh Inderpal , Rehman Sayeed Ur , Singh Gurdarshan , Afzal Mohammad
Published: May 2021

Non-syndromic hearing loss (NSHL) is one of the most frequent auditory deficits in humans characterized by high clinical and genetic heterogeneity. Very few studies have reported the relationship between OTOF (Locus: DFNB9) and hereditary hearing loss in India. We aimed to decipher the genetic cause of prelingual NSHL in a large affected Muslim consanguineous families using whole-exome sequencing (WES). The study was performed following the guidelines and regulations of the Indian Council of Medical Research (ICMR), New Delhi. The population was identified from Jammu and Kashmir, the Northernmost part of India. Near about 100 individuals were born deaf-mute in the village of 3,000 inhabitants. A total of 103 individuals (with 52 cases and 51 controls) agreed to participate in this study. Our study revealed a rare non-sense homozygous mutation NC_000002.11:g.2:26702224G>A; NM_001287489.2:c.2122C>T; NP_001274418.1:p.(Arg708∗) in the 18th exon of the OTOF gene. Our study provides the first insight into this homozygous condition, which has not been previously reported in ExAC, 1,000 Genome and genomAD databases. Furthermore, the variant was confirmed in the population cohort (n = 103) using Sanger sequencing. In addition to the pathogenic OTOF variant, the WES data also revealed novel and recurrent mutations in CDH23, GJB2, MYO15A, OTOG, and SLC26A4 genes. The rare pathogenic and the novel variants observed in this study have been submitted to the ClinVar database and are publicly available online with the accessions SCV001448680.1, SCV001448682.1 and SCV001448681.1. We conclude that OTOF-related NSHL hearing loss is prevalent in the region due to successive inbreeding in its generations. We recommend premarital genetic testing and genetic counseling strategies to minimize and control the disease risk in future generations.
Knowledge and Information Exposure About Family Planning Among Women of Reproductive Age in Informal Settlements of Kira Municipality, Wakiso District, Uganda
Authors: Birabwa Catherine , Chemonges Dennis , Tetui Moses , Baroudi Mazen , Namatovu Fredinah , Akuze Joseph , Makumbi Fredrick , Ssekamatte Tonny , Atuyambe Lynn , Hernandez Alison , Sewe Maquins Odhiambo
Published: May 2021

Introduction: A high unmet need for family planning (FP) prevails in sub-Saharan Africa. Knowledge, awareness creation, and ensuring accessibility are frequently used to increase FP uptake. However, evidence on knowledge or information dissemination about FP among marginalized populations in urban settings in Africa is limited. This study explored the knowledge of FP methods, media exposure, and contact with FP providers among women from an informal settlement in Uganda.

Methods: Using a cross-sectional study design, we interviewed 626 women aged 15–49 years living in informal settlements of Kira municipality, selected through multistage sampling. Using a standard questionnaire, data was collected on socioeconomic characteristics, knowledge of FP methods, and access to media FP messages among others. Binomial log-linear regression was used to assess disparities in exposure to media FP messages or provider information. Data were analyzed using STATA version 14, at a 5% level of statistical significance.

Results: Nearly all women in the survey were aware of FP methods (99.7%). On average, each woman was aware of 10 FP methods. The most commonly known methods were male condoms (98.2%), injectables (97.4%), and the oral contraceptive pill (95.2%). Use of any contraceptive was found among 42.7% of respondents. Exposure to media was found in 70.6% of the respondents, mostly through television (58.5%) and radio (58.3%). Discussing FP with a provider was significantly associated with media exposure (aPR 1.4, 95% CI: 1.24–1.56). Less than 50% of women who were not using FP had contact with an FP provider. Women in union (aPR 1.6, 95% CI: 1.01–2.68) and those with access to media messages (aPR 2.5, 95% CI: 1.37–4.54) were more likely to have contact with a provider to discuss FP.

Conclusion: There is high general awareness about FP methods and media exposure, but method use was low. Further exploration of women's understanding of FP methods and the fit between existing education programs and FP knowledge needs in this urban setting should be conducted. The potential for mobile health solutions in this urban population should be explored. Future studies should focus on the knowledge and understanding of FP among unmarried and nulliparous women and those with no access to media information.
Non-Coated Rituximab Induces Highly Cytotoxic Natural Killer Cells From Peripheral Blood Mononuclear Cells via Autologous B Cells
Authors: Niu Chao , Chen Yongchong , Li Min , Zhu Shan , Zhou Lei , Xu Dongsheng , Li Zhaozhi , Xu Jianting , Li Wei , Wang Yufeng , Cui Jiuwei
Published: May 2021

Natural killer (NK) cells are becoming valuable tools for cancer therapy because of their cytotoxicity against tumor cells without prior sensitization and their involvement in graft-versus-host disease; however, it is difficult to obtain highly cytotoxic NK cells without adding extra feeder cells. In this study, we developed a new method for obtaining highly cytotoxic NK cells from peripheral blood mononuclear cells (PBMCs) independently of extra feeder cell addition using rituximab not coated on a flask (non-coated rituximab). We found that rituximab could promote both the activation and expansion of NK cells from PBMCs, irrespective of being coated on a flask or not. However, NK cells activated by non-coated rituximab had much greater antitumor activity against cancer cells, and these effects were dependent on autologous living B cells. The antibody-dependent cellular cytotoxicity effect of NK cells activated by non-coated rituximab was also more substantial. Furthermore, these cells expressed higher levels of CD107a, perforin, granzyme B, and IFN-γ. However, there was no difference in the percentage, apoptosis, and cell-cycle progression of NK cells induced by coated and non-coated rituximab. Non-coated rituximab activated NK cells by increasing AKT phosphorylation, further enhancing the abundance of XBP1s. In conclusion, we developed a new method for amplifying NK cells with higher antitumor functions with non-coated rituximab via autologous B cells from PBMCs, and this method more efficiently stimulated NK cell activation than by using coated rituximab.
Effects of Estradiol on Immunoglobulin G Glycosylation: Mapping of the Downstream Signaling Mechanism
Authors: Mijakovac Anika , Jurić Julija , Kohrt Wendy M. , Krištić Jasminka , Kifer Domagoj , Gavin Kathleen M. , Miškec Karlo , Frkatović Azra , Vučković Frano , Pezer Marija , Vojta Aleksandar , Nigrović Peter A. , Zoldoš Vlatka , Lauc Gordan
Published: May 2021

Glycans attached to immunoglobulin G (IgG) directly affect this antibody effector functions and regulate inflammation at several levels. The composition of IgG glycome changes significantly with age. In women, the most notable change coincides with the perimenopausal period. Aiming to investigate the effect of estrogen on IgG glycosylation, we analysed IgG and total serum glycomes in 36 healthy premenopausal women enrolled in a randomized controlled trial of the gonadotropin-releasing hormone analogue (GnRHAG) leuprolide acetate to lower gonadal steroids to postmenopausal levels and then randomized to transdermal placebo or estradiol (E2) patch. The suppression of gonadal hormones induced significant changes in the IgG glycome, while E2 supplementation was sufficient to prevent changes. The observed glycan changes suggest that depletion of E2 primarily affects B cell glycosylation, while liver glycosylation stays mostly unchanged. To determine whether previously identified IgG GWAS hits RUNX1, RUNX3, SPINK4, and ELL2 are involved in downstream signaling mechanisms, linking E2 with IgG glycosylation, we used the FreeStyle 293-F transient system expressing IgG antibodies with stably integrated CRISPR/dCas9 expression cassettes for gene up- and downregulation. RUNX3 and SPINK4 upregulation using dCas9-VPR resulted in a decreased IgG galactosylation and, in the case of RUNX3, a concomitant increase in IgG agalactosylation.
Fucoxanthin and Phenolic Contents of Six Dictyotales From the Tunisian Coasts With an Emphasis for a Green Extraction Using a Supercritical CO2 Method
Authors: Ktari Leila , Mdallel Cheima , Aoun Brahim , Chebil Ajjabi Leila , Sadok Saloua
Published: May 2021

Dictyotales, a common taxonomic group of brown seaweeds found in warm and temperate waters, are known for their richness in bioactive metabolites. In this study, six species of Dictyotales (Dictyopteris polypodioides, Dictyota dichotoma, Dictyota fasciola, Dictyota spiralis, Padina pavonica, and Taonia atomaria) collected from the Tunisian coasts were investigated for their antioxidant potentials, based on their contents of high added-value bioactive metabolites such as fucoxanthin and polyphenols. Fucoxanthin and polyphenols were analyzed quantitatively by high-performance liquid chromatography (HPLC) and UV spectrophotometer, respectively. The antioxidant property of extracts was also determined based on their ability to scavenge 2,2-Diphenyl-1-picrylhydrazyl (DPPH’s) free radical. Thus, the highest concentrations of fucoxanthin were obtained from T. atomaria and D. polypodioides (5.53 ± 1.2 and 3.43 ± 1.3 mg⋅g–1 dry weight, respectively), while the lowest amount was from D. spiralis (0.23 ± 0.1 m mg⋅g–1 dry weight). Dictyota dichotoma and T. atomaria gave the highest total phenol content (19.3 ± 0.4 and 15.2 ± 1.1 mg GAE⋅g–1 dry weight, respectively). In the second step, supercritical carbon dioxide (ScCO2) was used as a green and environmentally safe technique for the extraction of fucoxanthin from the most abundant species D. polypodioides. The extraction of fucoxanthin by ScCO2 allowed an extraction yield ranging from 0.50 ± 0.04% to 1.32 ± 0.02%, with 60°C temperature and 50-MPa pressure as the best extraction conditions. The maximum fucoxanthin and polyphenol recovery in the extract attained 15 and 64%, respectively. The results strengthen the possible use of Dictyotales from the Mediterranean Sea as a promising source of natural ingredients of health and economic interests contributing to Blue Growth in the region.
Membranous Nephropathy With Monoclonal IgM Lambda Deposits in a Patient With IgM Monoclonal Gammopathy: A Case Report
Authors: Hirose Go , Uchida Takahiro , Kojima Aki , Sugisaki Kentaro , Yamada Muneharu , Nagase Yoshihiro , Takaki Takashi , Nagahama Kiyotaka , Oda Takashi
Published: May 2021

We report a case of membranous nephropathy with monoclonal immunoglobulin (Ig)M lambda deposits in a patient with IgM monoclonal gammopathy, in whom histological changes were observed on repeat renal biopsy. A 72-year-old Japanese woman was referred to our hospital because of massive proteinuria. A prominent increase in monoclonal IgM lambda level was identified, and she was diagnosed as having IgM monoclonal gammopathy of undetermined significance. Renal biopsy showed glomerular subepithelial electron-dense deposits that were found to be granular deposits of IgM lambda but not kappa or IgG by immunofluorescence staining, resulting in a diagnosis of membranous nephropathy with monoclonal IgM deposits. The second biopsy, which was performed 2 years later because of exacerbation of her nephrotic syndrome, demonstrated less immunofluorescence staining of IgM, and dominant IgG2 deposition without light chain restriction. Interestingly, immunostaining for thrombospondin-type-1-domain-containing-7A was positive in both renal biopsy tissues, although the second biopsy showed clearly stronger immunoreactivity. The effect of steroid therapy was limited; however, rituximab treatment improved both the hematological and renal abnormalities. Solitary deposition of IgM in membranous nephropathy is a quite rare condition. To our knowledge, this is the first case of monoclonal gammopathy of renal significance presenting as membranous nephropathy with monoclonal IgM deposits, in which chronological immunohistochemical changes were observed and rituximab therapy was effective.
An Adsorptive and Antioxidant Vaginal Gel Clears High-Risk HPV- and p16/Ki-67-Associated Abnormal Cytological Cervical Findings: A post-hoc Subgroup Analysis of a Prospective Randomized Controlled Trial on CIN2 and p16 Positive CIN1
Authors: Major Attila Louis , Skřivánek Ales , Grandjean Etienne Marc , Dvořák Vladimír , Malík Tomáš , Pluta Marek , Mayboroda Ivanna
Published: May 2021

Objective: To analyze the course of p16/Ki-67-positive abnormal cytological cervical findings and high risk (hr)-HPV- and p16/Ki-67-clearances in women treated with a vaginal gel.

Methods: 172 women with a histological diagnosis of CIN2 or p16-positive CIN1 lesions were selected based on a positive cytological p16/Ki-67 test. For 3 months, 75 patients in the active arm (AA) daily administered 5 ml of a vaginal gel. Ninety seven patients in the control arm (CA) underwent no treatment (“watchful waiting”). Endpoints were cytological evolution, p16/Ki-67- and hr-HPV-clearances.

Results: At 3 months, cytological regression was observed in 76% (57/75) of patients in the AA compared with 25% (24/97) in the CA. Progression occurred in 5% (4/75) of the AA compared with 15% (15/97) of the CA. The p16/Ki-67 status change was statistically significantly (p < 0.001) in favor of the AA: 77% (58/75) became negative compared to 21% (20/97) in the CA. hr-HPV prevalence decreased significantly (p < 0.001) in the AA from 87 to 44%, while increasing in the CA from 78 to 84%. Cytological regression and p16/Ki-67 changes persisted in the AA at 6 months.

Conclusions: The vaginal gel significantly cleared hr-HPV and p16/Ki-67 and was associated with improved cytological findings, thereby potentially offering an effective option against oncogenic risk.

Clinical Trial Registration: Identifier: [ISRCTN11009040].
The Efficacy of High-Dose Dexamethasone vs. Other Treatments for Newly Diagnosed Immune Thrombocytopenia: A Meta-Analysis
Authors: Xiao Qirong , Lin Bicun , Wang Hanyu , Zhan Weiwu , Chen Ping
Published: May 2021

Objective: To compare the therapeutic efficacies of high dose dexamethasone, prednisone and rituximab in combination with dexamethasone for newly diagnosed ITP (Immune Thrombocytopenia, ITP) patients.

Methods and results: Relevant publications for this study were obtained by searching PubMed, Embase, Cochrane, and CNKI (National Knowledge Infrastructure, CNKI) databases following the PRISMA guidelines. A total of, 15 publications were retrieved that contained sufficient data from 1,362 patients for high quality analysis of this study endpoints. Data analysis was carried out using Stata 11.0 software.

The primary outcomes were OR (Overall Response, OR) at 1 month after intervention and SR at 6 and 12 months. The secondary outcomes were AEs and relapse. There were no differences in the OR, while the SR was higher at 6 months (p = 0.001) as well as 12 months (p < 0.001) in the rituximab + dexamethasone group. In addition, the incidences of AEs (p = 0.008) were also higher in the rituximab + dexamethasone group. Dexamethasone was superior to prednisone based on OR (p = 0.006). We found no differences in SR at 6 months between dexamethasone and prednisone but SR at 12 months was higher in the dexamethasone group (p = 0.014). The relapse rate was higher in the high dose dexamethasone group compared to the rituximab + dexamethasone group (p = 0.042).

Conclusion: This demonstrated that new treatment options such as Rituximab + dexamethasone, could be a good alternative to traditional therapy in improving long-term response and reducing the rate of relapse. However, further studies are required on the increased risk of AEs associated with Rituximab + dexamethasone.
Development and Validation of a Predictive Model for Severe COVID-19: A Case-Control Study in China
Authors: Meng Zirui , Wang Minjin , Zhao Zhenzhen , Zhou Yongzhao , Wu Ying , Guo Shuo , Li Mengjiao , Zhou Yanbing , Yang Shuyu , Li Weimin , Ying Binwu
Published: May 2021

Background: Predicting the risk of progression to severe coronavirus disease 2019 (COVID-19) could facilitate personalized diagnosis and treatment options, thus optimizing the use of medical resources.

Methods: In this prospective study, 206 patients with COVID-19 were enrolled from regional medical institutions between December 20, 2019, and April 10, 2020. We collated a range of data to derive and validate a predictive model for COVID-19 progression, including demographics, clinical characteristics, laboratory findings, and cytokine levels. Variation analysis, along with the least absolute shrinkage and selection operator (LASSO) and Boruta algorithms, was used for modeling. The performance of the derived models was evaluated by specificity, sensitivity, area under the receiver operating characteristic (ROC) curve (AUC), Akaike information criterion (AIC), calibration plots, decision curve analysis (DCA), and Hosmer–Lemeshow test.

Results: We used the LASSO algorithm and logistic regression to develop a model that can accurately predict the risk of progression to severe COVID-19. The model incorporated alanine aminotransferase (ALT), interleukin (IL)-6, expectoration, fatigue, lymphocyte ratio (LYMR), aspartate transaminase (AST), and creatinine (CREA). The model yielded a satisfactory predictive performance with an AUC of 0.9104 and 0.8792 in the derivation and validation cohorts, respectively. The final model was then used to create a nomogram that was packaged into an open-source and predictive calculator for clinical use. The model is freely available online at https://severeconid-19predction.shinyapps.io/SHINY/.

Conclusion: In this study, we developed an open-source and free predictive calculator for COVID-19 progression based on ALT, IL-6, expectoration, fatigue, LYMR, AST, and CREA. The validated model can effectively predict progression to severe COVID-19, thus providing an efficient option for early and personalized management and the allocation of appropriate medical resources.
Effect of a “Dual Trigger” Using a GnRH Agonist and hCG on the Cumulative Live-Birth Rate for Normal Responders in GnRH-Antagonist Cycles
Authors: Gao Fumei , Wang Yanbin , Fu Min , Zhang Qiuxiang , Ren Yumeng , Shen Huan , Han Hongjing
Published: May 2021

“Dual triggering” for final oocyte maturation using a combination of a gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) can improve clinical outcomes in high responders during in vitro fertilization–intracytoplasmic sperm injection (IVF–ICSI) GnRH-antagonist cycles. However, whether this dual trigger is also beneficial to normal responders is not known. We retrospectively analyzed the data generated from 469 normal responders from 1 January to 31 December 2017. The final oocyte maturation was undertaken with a dual trigger with a GnRHa combined with hCG (n = 270) or hCG alone (n = 199). Patients were followed up for 3 years. The cumulative live-birth rate was calculated as the first live birth achieved after all cycles having an embryo transfer (cycles using fresh embryos and frozen–thawed embryos) among both groups. Women in the dual-trigger group achieved a slightly higher number of oocytes retrieved (11.24 vs. 10.24), higher number of two-pronuclear (2PN) embryos (8.37 vs. 7.67) and a higher number of embryos available (4.45 vs. 4.03). However, the cumulative live-birth rate and the all-inclusive success rate for assisted reproductive technology was similar between the two groups (54.07 vs. 59.30%). We showed that a dual trigger was not superior to a hCG-alone trigger for normal responders in GnRH-antagonist cycles in terms of the cumulative live-birth rate.
Temporal Bacterial Community Diversity in the Nicotiana tabacum Rhizosphere Over Years of Continuous Monocropping
Authors: Yan Lang , Zhang Wenyou , Duan Wangjun , Zhang Yizheng , Zheng Wen , Lai Xianjun
Published: May 2021

Long-term continuous monocropping negatively influences the physicochemical and biological characteristics of cultivated soil, especially for the economically important crop of flue-cured tobacco that is intolerant to continuous monocropping. The underlying mechanism of soil sickness under continuous monoculture and the temporal dynamic changes over the tobacco life cycle among different monoculture time spans remain poorly characterized. In this study, high-throughput sequencing targeting the 16S rRNA gene phylogenetic marker was performed on 60 soil samples of rhizosphere soil from flue−cured tobacco in the replanting, growth and harvest period across 5, 10, and 20 years of a continuous monocropping system. Bacterial community diversity decreased with the increase in duration of continuous monocropping, and the rhizosphere microbiota was highly dynamic in the harvest period. The random forests algorithm identified 17 taxa as biomarkers and a model was established to correlate root microbiota with continuous monocropping time of flue-cured tobacco. Molecular ecological network analysis elaborated the differences and interactions in bacterial co-occurrence patterns under different monocropping systems. The co-occurrence microbial network was larger in size but there were fewer interactions among microbial communities with the increase in continuous monocropping duration. These results provide insights into the changes of flue−cured tobacco root microbiome diversity in response to continuous monocropping and suggest a model for successional dynamics of the root-associated microbiota over continuous monocropping time and development stage. This study may help elucidate the theoretical basis underlying obstacles to continuous monocropping and could contribute to improving guidance for tobacco production.
Association Between FSIP2 Mutation and an Improved Efficacy of Immune Checkpoint Inhibitors in Patients With Skin Cutaneous Melanoma
Authors: Ying Haoxuan , Lin Anqi , Liang Junyi , Zhang Jian , Luo Peng
Published: May 2021

Background

Immune checkpoint inhibitors (ICIs) have shown remarkable success in treating skin cutaneous melanoma (SKCM); however, the response to treatment varies greatly between patients. Considering that the efficacy of ICI treatment is influenced by many factors, we selected the Fibrosheath interacting protein 2 (FSIP2) gene and systematically analyzed its potential to predict the efficacy of ICI treatment.

Methods

Patient data were collected from an ICI treatment cohort (n = 120) and a The Cancer Genome Atlas (TCGA)-SKCM cohort (n = 467). The data were divided into an FSIP2-mutant (MT) group and FSIP2-wild-type (WT) group according to FSIP2 mutation status. In this study, we analyzed the patients’ overall survival rate, tumor mutational burden (TMB), neoantigen load (NAL), copy number variation (CNV), cell infiltration data and immune-related genes. We used gene set enrichment analysis (GSEA) to delineate biological pathways and processes associated with the efficacy of immunotherapy.

Results

The efficacy of ICI treatment of SKCM patients with FSIP2 mutation was significantly better than that of patients without FSIP2 mutation. The patients in the FSIP2-MT group had higher tumor immunogenicity and lower regulatory T cell (Treg) infiltration. Results of GSEA showed that pathways related to tumor progression (MAPK and FGFR), immunomodulation, and IL-2 synthesis inhibition were significantly downregulated in the FSIP2-MT group.

Conclusion

Our research suggests that the FSIP2 gene has the potential to predict the efficacy of ICI treatment. The high tumor immunogenicity and low Treg levels observed may be closely related to the fact that patients with FSIP2-MT can benefit from ICI treatment.
Subarachnoid Hemorrhage in Mechanical Thrombectomy for Acute Ischemic Stroke: Analysis of the STRATIS Registry, Systematic Review, and Meta-Analysis
Authors: Lee Hubert , Qureshi Ayman M. , Mueller-Kronast Nils H. , Zaidat Osama O. , Froehler Michael T. , Liebeskind David S. , Pereira Vitor M.
Published: May 2021

Background: The indications for mechanical thrombectomy in acute ischemic stroke continue to broaden, leading neurointerventionalists to treat vessel occlusions at increasingly distal locations farther in time from stroke onset. Accessing these smaller vessels raises the concern of iatrogenic subarachnoid hemorrhage (SAH) owing to increasing complexity in device navigation and retrieval. This study aims to determine the prevalence of SAH following mechanical thrombectomy, associated predictors, and resulting functional outcomes using a multicenter registry and compare this with a systematic review and meta-analysis of the literature.

Methods: Data from STRATIS (The Systematic Evaluation of Patients Treated with Neurothrombectomy Devices for Acute Ischemic Stroke) registry were analyzed dichotomized by the presence or absence of SAH after thrombectomy. Only patients with 24-h post-procedural neuroimaging were included (n = 841). Multivariable logistic regression was performed to identify significant predictors of SAH. A systematic review and random-effects meta-analysis was also conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) protocol.

Results: The prevalence of post-thrombectomy SAH was 5.23% in STRATIS with 15.9% (1.84% overall) experiencing neurological decline. Distal location of vessel occlusion (OR 3.41 [95% CI: 1.75–6.63], p < 0.001) and more than 3 device passes (OR 1.34 [95% CI: 1.09–1.64], p = 0.01) were associated with a higher probability of SAH in contrast to a reduction with administration of intravenous tissue plasminogen activator (tPA) (OR 0.48 [95% CI: 0.26–0.89], p = 0.02). There was a trend toward a higher discharge NIHSS (8.3 ± 8.7 vs. 5.3 ± 6.6, p = 0.07) with a significantly reduced proportion achieving functional independence at 90 days (modified Rankin Score 0–2: 32.5% vs. 57.8%, p = 0.002) in SAH patients. Pooled analysis of 10,126 patients from 6 randomized controlled trials and 64 observational studies demonstrated a prevalence of 5.85% [95% CI: 4.51–7.34%, I2: 85.2%]. Only location of vessel occlusion was significant for increased odds of SAH at distal sites (OR 2.89 [95% CI: 1.14, 7.35]).

Conclusions: Iatrogenic SAH related to mechanical thrombectomy is more common with treatment of distally-situated occlusions and multiple device passes. While low in overall prevalence, its effect is not benign with fewer patients reaching post-procedural functional independence, particularly if symptomatic.
Prediction of Successful Memory Encoding Based on Lateral Temporal Cortical Gamma Power
Authors: Jun Soyeon , Kim June Sic , Chung Chun Kee
Published: May 2021

Prediction of successful memory encoding is important for learning. High-frequency activity (HFA), such as gamma frequency activity (30–150 Hz) of cortical oscillations, is induced during memory tasks and is thought to reflect underlying neuronal processes. Previous studies have demonstrated that medio-temporal electrophysiological characteristics are related to memory formation, but the effects of neocortical neural activity remain underexplored. The main aim of the present study was to evaluate the ability of gamma activity in human electrocorticography (ECoG) signals to differentiate memory processes into remembered and forgotten memories. A support vector machine (SVM) was employed, and ECoG recordings were collected from six subjects during verbal memory recognition task performance. Two-class classification using an SVM was performed to predict subsequently remembered vs. forgotten trials based on individually selected frequencies (low gamma, 30–60 Hz; high gamma, 60–150 Hz) at time points during pre- and during stimulus intervals. The SVM classifier distinguished memory performance between remembered and forgotten trials with a mean maximum accuracy of 87.5% using temporal cortical gamma activity during the 0- to 1-s interval. Our results support the functional relevance of ECoG for memory formation and suggest that lateral temporal cortical HFA may be utilized for memory prediction.
Creativity Is Optimal Novelty and Maximal Positive Affect: A New Definition Based on the Spreading Activation Model
Authors: Schubert Emery
Published: May 2021

Creativity is commonly defined as a process that leads to a novel and useful outcome (an idea, product, or expression). However, two dilemmas about this definition remain unresolved: (1) A strict application of usefulness is difficult to apply to artistic works: who decides what artwork is useful, and how it is useful? (2) The implied boundary conditions of novelty are problematic: The default perspective is that novelty has a monotonic increasing relationship with creativity, or it is categorical—i.e., novel or not. To address these dilemmas, this paper proposes a spreading activation model of creativity (SAMOC), a model built on a brain-architecture-inspired vast interconnected network of nodes, each node representing information, and assigned meanings through interaction with the environment. Nodes are linked to each other according to principles of temporal contiguity (linking objects/events in time) and similarity (linking objects/events by shared features). A node activated by attention spreads through the network through previously linked nodes. Nodes that are well connected activate each other easily, while those that are weakly connected do not. Net total activation corresponds to positive affect (e.g., pleasure), and this is proposed as an essential criteria for a creative work of art, instead of usefulness. SAMOC also predicts that creativity will be optimized at an intermediate, not extreme, level of novelty. Too much activation will occur with the activation of preexisting ideas (hence reproduction rather than creativity), and too much novelty will not produce spread of activation. The two functions (spreading activation and the novelty curve) are superposed to demonstrate this optimal novelty hypothesis. Early evidence of the hypothesis comes from the data that some great works of art were critically rejected at premiers (suggesting excessive novelty), but after sufficient repetition (and therefore linking) became suitably associated and commenced generating activation. The hypothesis has important implications for future empirical research programs on creativity, and for the definition of creativity itself.
Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU
Authors: Bachmann Sarah , Bell Michael , Klimek Jennifer , Zempel Hans
Published: May 2021

In the adult human brain, six isoforms of the microtubule-associated protein TAU are expressed, which result from alternative splicing of exons 2, 3, and 10 of the MAPT gene. These isoforms differ in the number of N-terminal inserts (0N, 1N, 2N) and C-terminal repeat domains (3R or 4R) and are differentially expressed depending on the brain region and developmental stage. Although all TAU isoforms can aggregate and form neurofibrillary tangles, some tauopathies, such as Pick’s disease and progressive supranuclear palsy, are characterized by the accumulation of specific TAU isoforms. The influence of the individual TAU isoforms in a cellular context, however, is understudied. In this report, we investigated the subcellular localization of the human-specific TAU isoforms in primary mouse neurons and analyzed TAU isoform-specific effects on cell area and microtubule dynamics in human SH-SY5Y neuroblastoma cells. Our results show that 2N-TAU isoforms are particularly retained from axonal sorting and that axonal enrichment is independent of the number of repeat domains, but that the additional repeat domain of 4R-TAU isoforms results in a general reduction of cell size and an increase of microtubule counts in cells expressing these specific isoforms. Our study points out that individual TAU isoforms may influence microtubule dynamics differentially both by different sorting patterns and by direct effects on microtubule dynamics.
Insight Into Spinocerebellar Ataxia Type 31 (SCA31) From Drosophila Model
Authors: Ishiguro Taro , Nagai Yoshitaka , Ishikawa Kinya
Published: May 2021

Spinocerebellar ataxia type 31 (SCA31) is a progressive neurodegenerative disease characterized by degeneration of Purkinje cells in the cerebellum. Its genetic cause is a 2.5- to 3.8-kb-long complex pentanucleotide repeat insertion containing (TGGAA)n, (TAGAA)n, (TAAAA)n, and (TAAAATAGAA)n located in an intron shared by two different genes: brain expressed associated with NEDD4-1 (BEAN1) and thymidine kinase 2 (TK2). Among these repeat sequences, (TGGAA)n repeat was the only sequence segregating with SCA31, which strongly suggests its pathogenicity. In SCA31 patient brains, the mutant BEAN1 transcript containing expanded UGGAA repeats (UGGAAexp) was found to form abnormal RNA structures called RNA foci in cerebellar Purkinje cell nuclei. In addition, the deposition of pentapeptide repeat (PPR) proteins, poly(Trp-Asn-Gly-Met-Glu), translated from UGGAAexp RNA, was detected in the cytoplasm of Purkinje cells. To uncover the pathogenesis of UGGAAexp in SCA31, we generated Drosophila models of SCA31 expressing UGGAAexp RNA. The toxicity of UGGAAexp depended on its length and expression level, which was accompanied by the accumulation of RNA foci and translation of repeat-associated PPR proteins in Drosophila, consistent with the observation in SCA31 patient brains. We also revealed that TDP-43, FUS, and hnRNPA2B1, motor neuron disease–linked RNA-binding proteins bound to UGGAAexp RNA, act as RNA chaperones to regulate the formation of RNA foci and repeat-associated translation. Further research on the role of RNA-binding proteins as RNA chaperones may also provide a novel therapeutic strategy for other microsatellite repeat expansion diseases besides SCA31.
Oxytocin-Trust Link in Oxytocin-Sensitive Participants and Those Without Autistic Traits
Authors: Kurokawa Hirofumi , Kinari Yusuke , Okudaira Hiroko , Tsubouchi Kiyotaka , Sai Yoshimichi , Kikuchi Mitsuru , Higashida Haruhiro , Ohtake Fumio
Published: May 2021

There have been numerous studies in which the biological role of oxytocin in trusting behavior has been investigated. However, a link between oxytocin and trust in humans was discovered only in one early study. We hypothesized that there is a large interindividual variation in oxytocin sensitivity, and that such variation is one reason for the doubt surrounding the role of oxytocin in trusting behavior. Here, in a double-blind, prospective, case-control study, we administered intranasal oxytocin to participants of trust and risk games. We measured salivary oxytocin concentration, relating it to the amount of money transferred among participants (a proxy for trust) and the autism-spectrum quotient (AQ). A one-sided Fisher’s exact test was performed to detect differences between the oxytocin and placebo groups in the proportions of investors who transferred the maximum amount of money. We discovered a tendency for participants who received oxytocin to transfer higher amounts of money to co-participants than those who received a placebo (P = 0.04). We also revealed a high degree of interindividual variation in salivary oxytocin concentrations after oxytocin administration. After stratifying the samples with respect to oxytocin sensitivity, oxytocin-sensitive participants in the oxytocin group also transferred higher amounts of money than those in the placebo group (P = 0.03), while such a tendency was not observed for oxytocin-insensitive participants (P = 0.34). Participants with lower AQ scores (less severe autistic traits) exhibited a greater tendency toward trusting behavior after oxytocin administration than did those with higher AQ scores (P = 0.02). A two-sample t-test that was performed to detect significant differences in the mean transfers between the oxytocin and placebo groups indicated no significant between-group difference in the mean transfers (P = 0.08). There are two possible interpretations of these results: First, there is no effect of oxytocin on trust in humans; second, the effects of oxytocin on trust in humans is person-dependent. However, the results should be interpreted with caution as the effect size was not larger than the minimal detectable effect size and the results were not statistically significant (P > 0.05) after Bonferroni corrections.
The Prognostic Value of New Index (LANR) Composed of Pre-operative Lymphocytes, Albumin, and Neutrophils in Patients With Resectable Colorectal Cancer
Authors: Liang Xinjun , Yao Shuang , Lu Ping , Ma Yifei , Xu Hongli , Yin Zhucheng , Hu Junjie , Liu Yanyan , Wei Shaozhong
Published: May 2021

Background: Inflammatory factors and nutritional status are critical to the prognosis of colorectal cancer patients. This study aimed to investigate the prognostic value of the combination of preoperative lymphocytes, albumin, and neutrophils (LANR) in patients with resectable colorectal cancer.

Methods: A total of 753 patients with pathologically diagnosed primary colorectal cancer were included in the study. The value of LANR was defined as follows: LANR, lymphocyte × albumin/neutrophil. The ROC curve, subgroup analysis and Cox proportional hazard regression analysis were used to assess the prognostic value of LANR in overall survival and progression-free survival.

Results: The median age of the patients was 60 years (range 52–67 years). In overall survival, the area under the curve of LANR was 0.6276, and the HR (95% CI) was 0.551 (0.393–0.772). And in progression-free survival, the area under the curve of LANR was 0.5963, and the HR (95% CI) was 0.697 (0.550–0.884). The results indicate that preoperative LANR may be a reliable predictor of overall and progression-free survival in resectable colorectal cancer patients.

Conclusions: LANR is an important prognostic indicator for patients with resectable colorectal cancer, and it can also provide a reference for clinicians and patients to choose a treatment plan.
Optimal Range of Lymphadenectomy in Pathological Stage T1 and T2 Esophageal Squamous Cell Carcinoma
Authors: Wu Hansheng , Zhuang Weitao , Huang Shujie , Guan Xueting , Zheng Yuju , Xie Zefeng , Chen Gang , Tang Jiming , Zhou Haiyu , Xie Liang , Ben Xiaosong , Zhou Zihao , Li Zijun , Chen Rixin , Qiao Guibin
Published: May 2021

Background

Lymph node metastasis is a primary contributor to tumor progression in esophageal squamous cell carcinoma (ESCC), and the optimal extent of lymphadenectomy during esophagectomy remains controversial. This study aimed to investigate the appropriate number of lymph nodes to be dissected in pT1-2Nany stage ESCC to achieve the best prognosis and avoid missing positive lymph nodes (PLNs).

Methods

A total of 497 patients with pT1 to pT2 esophageal cancer from two institutions were retrospectively analyzed and their surgical and pathological records were critically reviewed. Stepwise analyses were conducted by calculating a serial of hazard ratios and odd ratios to determine the optimal range of lymphadenectomy for overall survival (OS).

Results

The best survival outcome can be obtained when the number of lymph node examined (NLNE) is 10–18 in pT1N0 ESCC, while the NLNE should exceed 24 in pT2N0 diseases. In patients with pT1-2Nany and pT2Nany ESCC, resection of 15–25 and 24–37 lymph nodes, respectively, could provide significant added value for identifying positive nodal metastasis. When the NLNE exceeds this appropriate range, resection of extra lymph node is not helpful to improve the probability of finding PLNs.

Conclusions

For ESCC patients undergoing radical esophagectomy, the optimal extent of lymphadenectomy is 15–25 for pT1Nany disease and 24–37 for pT2Nany disease.
Involved Site Radiotherapy Extends Time to Premature Menopause in Infra-Diaphragmatic Female Hodgkin Lymphoma Patients – An Analysis of GHSG HD14- and HD17-Patients
Authors: Rosenbrock Johannes , Vásquez-Torres Andrés , Mueller Horst , Behringer Karolin , Zerth Matthias , Celik Eren , Fan Jiaqi , Trommer Maike , Linde Philipp , Fuchs Michael , Borchmann Peter , Engert Andreas , Marnitz Simone , Baues Christian
Published: May 2021

Introduction

Consolidation radiotherapy in intermediate stage Hodgkin´s lymphoma (HL) has been the standard of care for many years as involved field radiotherapy (IFRT) after chemotherapy. It included initially involved region(s). Based on randomized studies, radiation volumes could be reduced and involved site radiation therapy (ISRT) became the new standard. ISRT includes the initially affected lymph nodes. In young adults suffering from HL, infertility and hypogonadism are major concerns. With regard to these questions, we analyzed the influence of modern radiotherapy concepts such as consolidating ISRT in infradiaphragmatic involvement of HL after polychemotherapy.

Patients and Methods

Five hundred twelve patients treated within German Hodgkin Study Group (GHSG) HD14 and HD17 trials were evaluated. We analyzed log-adjusted follicle-stimulating-hormone (FSH)- and luteinizing-hormone (LH)-levels of HD14-patients with infradiaphragmatic radiotherapy (IDRT) in comparison with HD14-patients, who had a supradiaphragmatic radiotherapy (SDRT). In a second step, we compared IFRT with ISRT of female HD17 patients regarding the effects on ovarian function and premature menopause.

Results

We analyzed FSH- and LH-levels of 258 female and 241 male patients, all treated with IFRT. Of these 499 patients, 478 patients had SDRT and 21 patients had IDRT. In a multiple regression model, we could show that log-adjusted FSH (p=0.0006) and LH values (p=0.0127) were significantly higher after IDRT than after SDRT. The effect of IDRT on gonadal function was comparable to two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc). We compared the effect of IFRT with ISRT in thirteen female HD17 patients with infradiaphragmatic (ID) involvement. The mean ovarian dose after ISRT was significantly lower than after IFRT. The calculated proportion of surviving non-growing follicles (NGFs) increased significantly from 11.87% to 24.48% in ISRT compared to IFRT, resulting in a significantly longer calculated time to menopause. The younger the age at therapy, the greater the absolute time gain until menopause.

Conclusion

Infradiaphragmatic IFRT impairs gonadal function to a similar extent as two cycles of BEACOPPesc. In comparison, the use of ISRT target volume definition significantly reduced radiation dose to the ovaries and significantly extends the time interval from treatment to premature menopause.
TTSurv: Exploring the Multi-Gene Prognosis in Thousands of Tumors
Authors: Qi Yue , Xin Mengyu , Zhang Yuanfu , Hao Yangyang , Liu Qian , Wang Peng , Guo Qiuyan
Published: May 2021

Thoracic malignancies are a common type of cancer and area major global health problem. These complex diseases, including lung cancer, esophageal cancer, and breast cancer, etc. have attracted considerable attention from researchers. Potential gene-cancer associations can be explored by demonstrating the association between clinical data and gene expression data. Emerging evidence suggests that the transcriptome plays a particularly critical role as a diagnostic biomarker in pathology and histology studies. Thus, there is an urgent need to develop a platform that allows users to perform a comprehensive prognostic analysis of thoracic cancers. Here, we developed TTSurv, which aims to correlate coding and noncoding genes with cancers by combining high-throughput data with clinical prognosis. TTSurv focuses on the application of high-throughput data to detect ncRNAs, such as lncRNAs and microRNAs, as novel diagnostic and prognostic biomarkers. For a more comprehensive analysis, a large amount of public expression profile data with clinical follow-up information have been integrated into TTSurv. TTSurv also provides flexible methods such as a minimum p-value algorithm and unsupervised clustering methods that can classify thoracic cancer samples into different risk groups. TTSurv will expand our understanding of ncRNAs in thoracic malignancies and provide new insights into their application as potential prognostic/diagnostic biomarkers.
Epidemiology of Kawasaki Disease in Europe
Authors: Piram Maryam
Published: May 2021

Aim of the review: To review major epidemiological aspects of Kawasaki disease (KD) in Europe, describing demographic characteristics, revising its incidence along with time trends and geographic variations, and describing migration studies to provide clues about its etiology.

Recent findings: The annual incidence of KD in Europe is about 10–15 per 100,000 children under 5 years old and seems to be relatively stable over time and space. Demographic characteristics are in line with those in other countries of the world, with a higher incidence in children from Asia and possibly North African origin. All studies performed across Europe found a coherent seasonal distribution of KD onset peaking from winter to early spring. This seasonal distribution was consistent over the years and suggests a climate-related environmental trigger. The occurrence of peaks during pandemics, microbiological findings and a possible link with southerly winds support the hypothesis of an airborne infectious agent. Neither other airborne agents such as pollutants or pollens nor urbanization and industrialization seem to have major effect on the etiology.

Conclusion: Discrepancies in KD incidence rates across studies were due more to methodological differences, variation in definitions and awareness of the disease than a real increase in incidence. Genetic predisposition is undeniable in KD, but environmental factors seem to play a pivotal role. Several lines of evidence support a non-exclusive airborne infectious agent with a protective immune response by the host as a key factor in inducing the inflammatory cascade responsible for symptoms and complications.