bluuebunny/crossref_metadata_2025 huggingface dataset:
Revealing Chronic Granulomatous Disease in a Patient With Williams-Beuren Syndrome Using Whole Exome Sequencing
Authors: Ripen Adiratna Mat , Chiow Mei Yee , Rama Rao Prakash Rao , Mohamad Saharuddin Bin
Published: November 2021

Blended phenotypes exhibited by a patient may present a challenge to the establishment of diagnosis. In this study, we report a seven-year-old Murut girl with unusual features of Williams-Beuren syndrome (WBS), including recurrent infections and skin abscesses. Considering the possibility of a second genetic disorder, a mutation screening for genes associated with inborn errors of immunity (IEI) was conducted using whole exome sequencing (WES). Analysis of copy number variations (CNVs) from the exome data revealed a 1.53Mb heterozygous deletion on chromosome 7q11.23, corresponding to the known WBS. We also identified a biallelic loss of NCF1, which indicated autosomal recessive chronic granulomatous disease (CGD). Dihydrorhodamine (DHR) flow cytometric assay demonstrated abnormally low neutrophil oxidative burst activity. Coamplification of NCF1 and its pseudogenes identified a GT-deletion (ΔGT) at the start of exon 2 in NCF1 (NM_000265.7: c.75_76delGT: p.Tyr26Hisfs*26). Estimation of NCF1-to-NCF1 pseudogenes ratio using ΔGT and 20-bp gene scans affirmed nil copies of NCF1 in the patient. While the father had a normal ratio of 2:4, the mother had a ratio of 1:5, implicating the carrier of ΔGT-containing NCF1. Discovery of a 7q11.23 deletion involving one NCF1 allele and a ΔGT in the second NCF1 allele explained the coexistence of WBS and CGD in our patient. This study highlights the capability of WES to establish a molecular diagnosis for a case with blended phenotypes, enabling the provision of appropriate prophylactic treatment.
Enhancing Natural Killer Cell Targeting of Pediatric Sarcoma
Authors: Omer Natacha , Nicholls Wayne , Ruegg Bronte , Souza-Fonseca-Guimaraes Fernando , Rossi Gustavo Rodrigues
Published: November 2021

Osteosarcoma, Ewing sarcoma (EWS), and rhabdomyosarcoma (RMS) are the most common pediatric sarcomas. Conventional therapy for these sarcomas comprises neoadjuvant and adjuvant chemotherapy, surgical resection of the primary tumor and/or radiation therapy. Patients with metastatic, relapsed, or refractory tumors have a dismal prognosis due to resistance to these conventional therapies. Therefore, innovative therapeutic interventions, such as immunotherapy, are urgently needed. Recently, cancer research has focused attention on natural killer (NK) cells due their innate ability to recognize and kill tumor cells. Osteosarcoma, EWS and RMS, are known to be sensitive to NK cell cytotoxicity in vitro. In the clinical setting however, NK cell cytotoxicity against sarcoma cells has been mainly studied in the context of allogeneic stem cell transplantation, where a rapid immune reconstitution of NK cells plays a key role in the control of the disease, known as graft-versus-tumor effect. In this review, we discuss the evidence for the current and future strategies to enhance the NK cell-versus-pediatric sarcoma effect, with a clinical focus. The different approaches encompass enhancing antibody-dependent NK cell cytotoxicity, counteracting the NK cell mechanisms of self-tolerance, and developing adoptive NK cell therapy including chimeric antigen receptor-expressing NK cells.
Comparison of Methods for Determining Erosion Threshold of Cohesive Sediments Using a Microcosm System
Authors: Ha Hun Jun , Ha Ho Kyung
Published: November 2021

Erosion of cohesive sediments is a ubiquitous phenomenon in estuarine and intertidal environments. Several methods have been proposed to determine the surface erosion threshold (τc0), which are still debatable because of the numerous and uncertain definitions. Based on erosion microcosm experiments, we have compared three different methods using (1) eroded mass (EM), (2) erosion rate (ER), and (3) suspended sediment concentration (SSC), and suggested a suitable method for revealing the variation of erodibility in intertidal sediments. Erosion experiments using a microcosm system were carried out in the Muuido tidal flat, west coast of South Korea. The mean values of τc0 for three methods were: 0.20 ± 0.08 Pa (EM); 0.18 ± 0.07 Pa (ER); and (3) 0.17 ± 0.09 Pa (SSC). The SSC method yielded the lowest τc0, due to the outflow of suspended sediment from the erosion chamber of the microcosm. This was because SSC gradually decreased with time after depleting the erodible sediment at a given bed shear stress (τb). Therefore, the regression between SSC and applied τb might skew an x-intercept, resulting in the underestimation (or “not-determined”) of τc0. The EM method yielded robust and accurate (within the range of τb step at which erosion begins) results. The EM method represents how the erodible depth thickens as τb increases and therefore seems better suited than the SSC and ER methods for representing depth-limited erosion of cohesive sediments. Furthermore, this study identified the spatiotemporal variations of τc0 by EM method in an intertidal flat. The τc0 in mud flat was about two times higher than that in mixed flat. Compared to the end of tidal emersion, the sediment was 10–40% more erodible at the beginning stage.
Marine Macrophytes as Carbon Sinks: Comparison Between Seagrasses and the Non-native Alga Halimeda incrassata in the Western Mediterranean (Mallorca)
Authors: Marx Lukas , Flecha Susana , Wesselmann Marlene , Morell Carlos , Hendriks Iris Eline
Published: November 2021

Seagrass species play a critical role in the mitigation of climate change by acting as valuable carbon sinks and storage sites. Another important ecosystem service of this coastal vegetation is nutrient removal. However, coastal ecosystems are under increasing pressure of global warming and associated establishment of invasive species. To elucidate the respective contributions of seagrass species Posidonia oceanica and Cymodocea nodosa and the non-native macroalga Halimeda incrassata as primary producers and nutrient sinks in coastal habitats we conducted in-situ incubations in the North-western Mediterranean Sea. Measured metabolic activity and nutrient removal as well as calcification rates in these habitats over a 24 h period in spring and summer confirmed that the endemic seagrass P. oceanica represents a valuable ecosystem with high O2 production and considerable carbon capture. The documented regression of P. oceanica meadows with higher temperatures and decline in autotrophy as measured here causes concern for the continuity of ecosystem services rendered by this habitat throughout the Mediterranean Sea with progressing climate warming. In contrast, the enhanced performance of C. nodosa and the calcifying alga H. incrassata with increasing temperatures, under expected rates of future warming is uncertain to mitigate loss of productivity in case of a potential shift in marine vegetation. This could ultimately lead to a decline in ecosystem services, decreased carbon storage and mitigation of climate change. Furthermore, this study provides a first estimate for the growth rate of H. incrassata in the Mediterranean Sea, supporting evidence for the mechanism of its rapid extension.
Trapping of Microplastics in Halocline and Turbidity Layers of the Semi-enclosed Baltic Sea
Authors: Zhou Qian , Tu Chen , Yang Jie , Fu Chuancheng , Li Yuan , Waniek Joanna J.
Published: November 2021

Microplastic pollution in semi-enclosed seas is gaining attention since microplastics are more likely to accumulate there. However, research on the vertical distribution of microplastics and impact factors is still limited. In this study, we focus on the Baltic Sea, which has distinguished salinity stratification, and we assume that the resulting strong density stratification (halocline) can influence the vertical distribution of microplastics in the water column. Therefore, we analyzed the vertical abundance distribution, the composition, and the sizes of microplastics (27.3–5,000.0 μm) in the Baltic Sea. The results showed that microplastics comprising fibers, fragments, and films occurred throughout the water column at an abundance of 1.1–27.7 items L−1. The abundance of microplastics (3.2–27.7 items L−1) at haloclines was significantly higher than those at other water depths except the near surfaces (p < 0.05), contributing 24.1–53.2% of the microplastics in the whole water column. Small microplastics (<100 μm) were more likely to accumulate in the water layers above halocline. Moreover, the current with high turbidity might be another carrier of microplastics in the near-bottom water layer due to its strong correlation with microplastics abundance. This study provides valuable evidence for the accumulation trend of microplastics in water columns and its influencing factors in the semi-enclosed marginal sea. Further research on the vertical distribution of microplastics under the control of multiple factors should be conducted in the future.
The Relative Early Decrease in Platelet Count Is Associated With Mortality in Post-cardiotomy Patients Undergoing Venoarterial Extracorporeal Membrane Oxygenation
Authors: Wang Liangshan , Shao Juanjuan , Shao Chengcheng , Wang Hong , Jia Ming , Hou Xiaotong
Published: November 2021

Background: The relationship between the magnitude of platelet count decrease and mortality in post-cardiotomy cardiogenic shock (PCS) patients undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO) has not been well-reported. This study was designed to evaluate the association between the relative decrease in platelet count (RelΔplatelet) at day 1 from VA-ECMO initiation and in-hospital mortality in PCS patients.

Methods: Patients (n = 178) who received VA-ECMO for refractory PCS between January 2016 and December 2018 at the Beijing Anzhen Hospital were reviewed retrospectively. Multivariable logistic regression analyses were performed to assess the association between RelΔplatelet and in-hospital mortality.

Results: One hundred and sixteen patients (65%) were weaned from VA-ECMO, and 84 patients (47%) survived to hospital discharge. The median [interquartile range (IQR)] time on VA-ECMO support was 5 (3–6) days. The median (IQR) RelΔ platelet was 41% (26–59%). Patients with a RelΔ platelet ≥ 50% had an increased mortality compared to those with a RelΔ platelet < 50% (57 vs. 37%; p < 0.001). A large RelΔplatelet (≥50%) was independently associated with in-hospital mortality after controlling for potential confounders (OR 8.93; 95% CI 4.22–18.89; p < 0.001). The area under the receiver operating characteristic curve for RelΔ platelet was 0.78 (95% CI, 0.71–0.85), which was better than that of platelet count at day 1 (0.69; 95% CI, 0.61–0.77).

Conclusions: In patients receiving VA-ECMO for post-cardiotomy cardiogenic shock, a large relative decrease in platelet count in the first day after ECMO initiation is independently associated with an increased in-hospital mortality.
Development of a Structured Query Language and Natural Language Processing Algorithm to Identify Lung Nodules in a Cancer Centre
Authors: Hunter Benjamin , Reis Sara , Campbell Des , Matharu Sheila , Ratnakumar Prashanthi , Mercuri Luca , Hindocha Sumeet , Kalsi Hardeep , Mayer Erik , Glampson Ben , Robinson Emily J. , Al-Lazikani Bisan , Scerri Lisa , Bloch Susannah , Lee Richard
Published: November 2021

Importance: The stratification of indeterminate lung nodules is a growing problem, but the burden of lung nodules on healthcare services is not well-described. Manual service evaluation and research cohort curation can be time-consuming and potentially improved by automation.

Objective: To automate lung nodule identification in a tertiary cancer centre.

Methods: This retrospective cohort study used Electronic Healthcare Records to identify CT reports generated between 31st October 2011 and 24th July 2020. A structured query language/natural language processing tool was developed to classify reports according to lung nodule status. Performance was externally validated. Sentences were used to train machine-learning classifiers to predict concerning nodule features in 2,000 patients.

Results: 14,586 patients with lung nodules were identified. The cancer types most commonly associated with lung nodules were lung (39%), neuro-endocrine (38%), skin (35%), colorectal (33%) and sarcoma (33%). Lung nodule patients had a greater proportion of metastatic diagnoses (45 vs. 23%, p < 0.001), a higher mean post-baseline scan number (6.56 vs. 1.93, p < 0.001), and a shorter mean scan interval (4.1 vs. 5.9 months, p < 0.001) than those without nodules. Inter-observer agreement for sentence classification was 0.94 internally and 0.98 externally. Sensitivity and specificity for nodule identification were 93 and 99% internally, and 100 and 100% at external validation, respectively. A linear-support vector machine model predicted concerning sentence features with 94% accuracy.

Conclusion: We have developed and validated an accurate tool for automated lung nodule identification that is valuable for service evaluation and research data acquisition.
Rheumatic Manifestations and Diseases From Immune Checkpoint Inhibitors in Cancer Immunotherapy
Authors: Shen Pan , Deng Xuan , Hu Zhishuo , Chen Zhe , Huang Yao , Wang Ke , Qin Kai , Huang Ying , Ba Xin , Yan Jiahui , Han Liang , Tu Shenghao
Published: November 2021

Immune checkpoint inhibitors (ICIs), which can enhance antitumor immunity and inhibit cancer growth, have revolutionized the treatment of multiple cancers and dramatically decreased mortality. However, treatment with ICIs is directly associated with immune-related adverse events (irAEs) because of inflammation in off-target organs and autoimmunity resulting from non-specific immune activation. These irAEs can cause rheumatic diseases and manifestations such as inflammatory arthritis, polymyalgia rheumatica, myositis, vasculitis, Sicca and Sjogen's syndrome, and systemic lupus erythematosus. Early diagnosis and treatment of these adverse events will improve outcomes and quality of life for cancer patients. The treatment of rheumatic diseases induced by ICIs requires multidisciplinary cooperation among physicians. Furthermore, the underlying mechanisms are not fully understood and it is difficult to predict and evaluate these side effects precisely. In this review, we summarize available studies and findings about rheumatic irAEs, focusing mainly on the clinical manifestations, epidemiology, possible mechanisms, and guiding principles for treating these irAEs.
An Accurate Method for Studying Individual Microbial Lag: Experiments and Computations
Authors: Akkermans Simen , Van Impe Jan F. M.
Published: November 2021

Variability in the behavior of microbial foodborne pathogens and spoilers causes difficulties in predicting the safety and quality of food products during their shelf life. Therefore, the quantification of the individual microbial lag phase distribution is of high relevance to the field of quantitative microbial risk assessment. To construct models that predict the effect of changes in environmental conditions on the individual lag, an accurate determination of these distributions is required. Therefore, the current research focuses on the development of an experimental and computational method for accurate determination of individual lag phase distribution. The experimental method is unique in the sense that full liquid volumes are sampled without using dilutions to detect the final population, thereby minimizing experimental errors. Moreover, the method does not aim at the isolation of single cells but at a low number of cells. The fact that several cells can be present in the initial samples instead of having a single cell is considered by the computational method. This method relies on Monte Carlo simulation to predict the individual lag phase distribution for a given set of distribution parameters and maximum likelihood estimation to find the parameters that describe the experimental data best. The method was validated both through simulation and experiments and was found to deliver a desired accuracy.
Industrial Processing of Algerian Table Olive Cultivars Elaborated as Spanish Style
Authors: Sab Chafiaa , Romero Concepción , Brenes Manuel , Montaño Alfredo , Ouelhadj Akli , Medina Eduardo
Published: November 2021

Olives from the Sigoise, Verdale, and Sevillana cultivars were elaborated as Spanish-style table olives by four Algerian factories, and the quality and food safety of the industrial table olives have been studied by the analysis of physicochemical and microbiological parameters. Differences were observed between the treatments carried out by the different factories throughout the manufacturing process, especially during the washing stage, but no significant differences were found between the analyzed samples for the concentration of sugars and polyphenols. The final pH values reached at the end of fermentation ranged between 5.04 and 4.27, and the titratable acidity was above 0.4% for all samples. Lactic and acetic acids were produced in mean concentrations of 0.68% and 0.21% as a result of lactic acid bacteria (LAB) and yeast metabolism, respectively. However, the presence of butyric, isobutyric, and propionic acids was also detected, and was related to the growth of undesirable spoilage microorganisms, responsible for secondary fermentations. The high-throughput sequencing of bacterial DNA suggested the dominance of LAB species belonging to genera Lactiplantibacillus, Leuconostoc, Pediococcus, Oenococcus, or Enterococcus. The Enterobacteriaceae family was detected during the first days of brining and in only one sample after 120 days of fermentation. Other spoilage microorganisms were found, such as Lentilactobacillus buchneri or the Pectinatus and Acetobacter genera, capable of consuming lactic acid and these played an essential role in the onset of spoilage. The Clostridium and Enterobacter genera, producers of butyric and propionic acids, were responsible for the malodorous fermentation present in the industrial samples that were analyzed. The study concluded that the safety of the table olives analyzed was compromised by the presence of undesirable microorganisms and microbial stability was not guaranteed. The elaboration process can be improved by reducing the washing steps and the time should be reduced to avoid the loss of fermentable matter, with the goal of reaching a pH < 4.0 after the fermentation and preventing the possibility of the growth of spoilage microorganisms and foodborne pathogens.
Phylogenetic Analysis and Genome-Wide Association Study Applied to an Italian Listeria monocytogenes Outbreak
Authors: Chiaverini Alexandra , Guidi Fabrizia , Torresi Marina , Acciari Vicdalia Aniela , Centorotola Gabriella , Cornacchia Alessandra , Centorame Patrizia , Marfoglia Cristina , Blasi Giuliana , Di Domenico Marco , Migliorati Giacomo , Roussel Sophie , Pomilio Francesco , Sevellec Yann
Published: November 2021

From May 2015 to March 2016, a severe outbreak due toListeria monocytogenesST7 strain occurred in Central Italy and caused 24 confirmed clinical cases. The epidemic strain was deeply investigated using whole-genome sequencing (WGS) analysis. In the interested area, the foodborne outbreak investigation identified a meat food-producing plant contaminated by the outbreak strain, carried by pork-ready-to-eat products. In the same region, in March 2018, the epidemic strain reemerged causing one listeriosis case in a 10-month-old child. The aim of this study was to investigate the phylogeny of the epidemic and reemergent strains over time and to compare them with a closer ST7 clone, detected during the outbreak and with different pulsed-field gel electrophoresis (PFGE) profiles, in order to identify genomic features linked to the persistence and the reemergence of the outbreak. An approach combining phylogenetic analysis and genome-wide association study (GWAS) revealed that the epidemic and reemergent clones were genetically closer to the ST7 clone with different PFGE profiles and strictly associated with the pork production chain. The repeated detection of both clones was probably correlated with (i) the presence of truly persistent clones and the repeated introduction of new ones and (ii) the contribution of prophage genes in promoting the persistence of the epidemic clones. Despite that no significant genomic differences were detected between the outbreak and the reemergent strain, the two related clones detected during the outbreak can be differentiated by transcriptional factor and phage genes associated with the phage LP-114.
Small RNA Profiling in Mycobacterium Provides Insights Into Stress Adaptability
Authors: Chen Yingyu , Zhai Wenjun , Zhang Kailun , Liu Han , Zhu Tingting , Su Li , Bermudez Luiz , Chen Huanchun , Guo Aizhen
Published: November 2021

Mycobacteria encounter a number of environmental changes during infection and respond using different mechanisms. Small RNA (sRNA) is a post-transcriptionally regulatory system for gene functions and has been investigated in many other bacteria. This study used Mycobacterium tuberculosis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection models and sequenced whole bacterial RNAs before and after host cell infection. A comparison of differentially expressed sRNAs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and target prediction was carried out. Six pathogenically relevant stress conditions, growth rate, and morphology were used to screen and identify sRNAs. From these data, a subset of sRNAs was differentially expressed in multiple infection groups and stress conditions. Many were found associated with lipid metabolism. Among them, ncBCG427 was significantly downregulated when BCG entered into macrophages and was associated with increased biofilm formation. The reduction of virulence possibility depends on regulating lipid metabolism.
Evaluation of the OsTIR1 and AtAFB2 AID Systems for Genome Architectural Protein Degradation in Mammalian Cells
Authors: Yunusova Anastasia , Smirnov Alexander , Shnaider Tatiana , Lukyanchikova Varvara , Afonnikova Svetlana , Battulin Nariman
Published: November 2021

The auxin-inducible degron (AID) system is a promising tool for dynamic protein degradation. In mammalian cells, this approach has become indispensable to study fundamental molecular functions, such as replication, chromatin dynamics, or transcription, which are otherwise difficult to dissect. We present evaluation of the two prominent AID systems based on OsTIR1 and AtAFB2 auxin receptor F-box proteins (AFBs). We analyzed degradation dynamics of cohesin/condensin complex subunits in mouse embryonic stem cells (Rad21, Smc2, Ncaph, and Ncaph2) and human haploid HAP1 line (RAD21, SMC2). Double antibiotic selection helped achieve high homozygous AID tagging of an endogenous gene for all genes using CRISPR/Cas9. We found that the main challenge for successful protein degradation is obtaining cell clones with high and stable AFB expression levels due to the mosaic expression of AFBs. AFB expression from a transgene tends to decline with passages in the absence of constant antibiotic selection, preventing epigenetic silencing of a transgene, even at the AAVS1 safe-harbor locus. Comparing two AFBs, we found that the OsTIR1 system showed weak dynamics of protein degradation. At the same time, the AtAFB2 approach was very efficient even in random integration of AFB-expressed transgenes. Other factors such as degradation dynamics and low basal depletion were also in favor of the AtAFB2 system.
The VITAAL Stepping Exergame Prototype for Older Adults With Major Neurocognitive Disorder: A Usability Study
Authors: Swinnen Nathalie , de Bruin Eling D. , Dumoulin Chantal , Thalmann Melanie , Guimarães Vânia , De Jong Jacqueline , Vandenbulcke Mathieu , Vancampfort Davy
Published: November 2021

Purpose:This study investigates the usability of a stepping exergame in older adults with major neurocognitive disorder (MNCD) residing in a long-term care facility.

Materials and Methods:A mixed methods study was conducted. Participants played exergames for 30 min on one try-out session. During the exergames, the think aloud method was used, and field notes were taken by the facilitator. Following the exergames, participants completed the System Usability Scale (SUS) and a semi-structured in-depth interview about usability including their personal experiences. Audio files were transcribed and a thematic content analysis of the think aloud data, field notes and interviews were performed using NVivo 12.

Results:Twenty-two participants with MNCD were included [mean age = 84.3 ± 5.5 (70–95) years; 81.8% women; Short Physical Performance Battery score = 7.5 ± 3.2 (1–12), Montreal Cognitive Assessment score = 11.9 ± 4.4 (2–19)]. System usability was rated “ok to good” with a mean SUS score of 57.8 (SD= 12.3) with scores ranging from 37.5 to 90.0. Five main themes emerged from the thematic content analysis: (1) perceived user friendliness and acceptability of the exergames; (2) interactional experience; (3) motivational factors; (4) training modalities; and (5) risks. There were no adverse events nor dropouts.

Conclusion:Participants evaluated the usability of the exergames positively. The results indicate that the stepping exergame is usable in older adults with MNCD.
Age-Related Differences in Resting-State EEG and Allocentric Spatial Working Memory Performance
Authors: Jabès Adeline , Klencklen Giuliana , Ruggeri Paolo , Antonietti Jean-Philippe , Banta Lavenex Pamela , Lavenex Pierre
Published: November 2021

During normal aging resting-state brain activity changes and working memory performance declines as compared to young adulthood. Interestingly, previous studies reported that different electroencephalographic (EEG) measures of resting-state brain activity may correlate with working memory performance at different ages. Here, we recorded resting-state EEG activity and tested allocentric spatial working memory in healthy young (20–30 years) and older (65–75 years) adults. We adapted standard EEG methods to record brain activity in mobile participants in a non-shielded environment, in both eyes closed and eyes open conditions. Our study revealed some age-group differences in resting-state brain activity that were consistent with previous results obtained in different recording conditions. We confirmed that age-group differences in resting-state EEG activity depend on the recording conditions and the specific parameters considered. Nevertheless, lower theta-band and alpha-band frequencies and absolute powers, and higher beta-band and gamma-band relative powers were overall observed in healthy older adults, as compared to healthy young adults. In addition, using principal component and regression analyses, we found that the first extracted EEG component, which represented mainly theta, alpha and beta powers, correlated with spatial working memory performance in older adults, but not in young adults. These findings are consistent with the theory that the neurobiological bases of working memory performance may differ between young and older adults. However, individual measures of resting-state EEG activity could not be used as reliable biomarkers to predict individual allocentric spatial working memory performance in young or older adults.
Academic Publication of Neurodegenerative Diseases From a Bibliographic Perspective: A Comparative Scientometric Analysis
Authors: Liao Zhenxin , Wei Wei , Yang Mengling , Kuang Xuyuan , Shi Jian
Published: November 2021

Background: For measuring the impact in clinical and scientific research, the citation count of the articles is used in the bibliometric analysis, although there is no comprehensive summary of neurodegenerative disease research. This study intends to provide the neuroscientists and investigators with a practical reference guide to appraise the most important and influential articles written on this subject through a macroscopic view of the research activities on neurodegenerative diseases.

Materials and Methods: The Clarivate Analytics Web of Science was searched in July 2020. To ensure the breadth of the search scope, the search terms were confirmed as “multiple sclerosis” (MS) or “amyotrophic lateral sclerosis” (ALS) or “Parkinson's” or “Alzheimer's” or “Huntington's” or “neurodegenerative.” After excluding completely unrelated articles, the top-cited articles were collected and evaluated from special characteristics. The data analysis was performed using SPSS 18.0. The articles were characterized by citation number, publication year, topic, study type, authorship, journal, country, and institute of responding author and foundation.

Results: The query identified 593,050 articles. A total of 45% of the top-cited articles were published during 2000–2009, followed by 30 articles from 1990–1999. Diagnosis and pathology were the main research categories (n = 62). Alzheimer's disease (AD) was the main study topic (n = 43). Meanwhile, the United States confirmed the tremendous impact on the field of neurodegenerative diseases. Notably, 69 of 100 articles were studied in the United States, and the National Institutes of Health sponsored 49 articles. There were only 22 articles that can be divided by evidence level. No article was categorized as level 1 evidence. In the journal list with multiple articles, seven of 15 were general journals. The 58 authors, who contributed to more than one article, have been identified by VOSviewer, and the clusters of authors reveal the evolution of research focus in neurodegenerative diseases.

Conclusions: This study analyzed the bibliometric characteristics and connections of 100 top-cited articles in the field of neurodegenerative diseases in the Web of Science. Their main outcomes were as follows: First, the pathology and diagnostic researches took a major role in top-cited articles while the therapy articles are relatively less. Second, the United States confirmed the tremendous impact on the field of neurodegenerative diseases. Third, researchers also submitted their researches to general journals, not just focused on specialty journals.
The Potential Advantages of Tai Chi Chuan in Promoting Inhibitory Control and Spontaneous Neural Activity in Young Adults
Authors: Shen Qi-Qi , Yin Heng-Chan , Cui Lei , Zhang Jing-Yi , Wang Dong-Ling , Zhu Li-Na , Wang Yuan , Li Xiu-Juan
Published: November 2021

Tai Chi Chuan (TCC) is assumed to exert beneficial effects on functional brain activity and cognitive function in elders. Until now, empirical evidence of TCC induced intra-regional spontaneous neural activity and inhibitory control remains inconclusive. Whether the effect of TCC is better than that of other aerobic exercises is still unknown, and the role of TCC in younger adults is not yet fully understood. Here we used resting-state functional MRI (fMRI) to investigate the effects of 8-week TCC (n = 12) and brisk walking (BW, n = 12) on inhibitory control and fractional amplitude of low-frequency fluctuations (fALFF). The results found that TCC had significant effects on inhibitory control performance and spontaneous neural activity that were associated with significantly increased fALFF in the left medial superior frontal gyrus (Cohen’s d = 1.533) and the right fusiform gyrus (Cohen’s d = 1.436) and decreased fALFF in the right dorsolateral superior frontal gyrus (Cohen’s d = 1.405) and the right paracentral lobule (Cohen’s d = 1.132).TCC exhibited stronger effects on spontaneous neural activity than the BW condition, as reflected in significantly increased fALFF in the left medial superior frontal gyrus (Cohen’s d = 0.862). There was a significant positive correlation between the increase in fALFF in the left medial superior frontal gyrus and the enhancement in inhibitory control performance. The change in fALFF in the left medial superior frontal gyrus was able to explain the change in inhibitory control performance induced by TCC. In conclusion, our results indicated that 8 weeks of TCC intervention could improve processing efficiency related to inhibitory control and alter spontaneous neural activity in young adults, and TCC had potential advantages over BW intervention for optimizing spontaneous neural activity.
Oligodendrocyte Development and Implication in Perinatal White Matter Injury
Authors: Motavaf Mahsa , Piao Xianhua
Published: November 2021

Perinatal white matter injury (WMI) is the most common brain injury in premature infants and can lead to life-long neurological deficits such as cerebral palsy. Preterm birth is typically accompanied by inflammation and hypoxic-ischemic events. Such perinatal insults negatively impact maturation of oligodendrocytes (OLs) and cause myelination failure. At present, no treatment options are clinically available to prevent or cure WMI. Given that arrested OL maturation plays a central role in the etiology of perinatal WMI, an increased interest has emerged regarding the functional restoration of these cells as potential therapeutic strategy. Cell transplantation and promoting endogenous oligodendrocyte function are two potential options to address this major unmet need. In this review, we highlight the underlying pathophysiology of WMI with a specific focus on OL biology and their implication for the development of new therapeutic targets.
Incidence and Prevalence of Poststroke Shoulder Pain Among Different Regions of the World: A Systematic Review and Meta-Analysis
Authors: Zhang Qian , Chen Danna , Shen Yuxian , Bian Minjie , Wang Pu , Li Jun
Published: November 2021

Objectives: Poststroke shoulder pain (PSSP) is a common complication after stroke. This review aimed to provide updated information on the epidemiological characteristics of PSSP, reveal their trends over time and region.

Study Design and Setting: We searched the PubMed, Embase, Cochrane Library and Web of Science databases from inception until Dec 31, 2020. Data were extracted from the eligible studies, and their quality was assessed. The pooled incidence and prevalence estimates of PSSP and their 95% confidence intervals (CIs) were calculated. We analyzed the incidence and prevalence of PSSP by different geographical regions and countries and separately calculated the annual incidence and prevalence (and 95% CIs) of PSSP.

Results: A total of 21 studies were eligible for the meta-analysis. Eleven cohort studies were included to analyze the incidence of PSSP, and the estimated pooled incidence in 3,496 stroke patients was 0.29 (95% CI 0.21–0.36). Ten cross-sectional studies were included to analyze the prevalence of PSSP, and the pooled prevalence in 3,701 stroke patients was 0.33 (95% CI 0.22–0.43). In addition, we found that there were significant differences in the incidence and prevalence of PSSP between different geographical regions and different countries. Additionally, the incidence of PSSP fluctuated around 30%, and the prevalence had a downward trend over time.

Conclusions: Current evidence suggests that the incidence and prevalence of PSSP are high and may be influenced by geographical region and time.
Impact of Pituitary Stalk Preservation on Tumor Recurrence/Progression and Surgically Induced Endocrinopathy After Endoscopic Endonasal Resection of Suprasellar Craniopharyngiomas
Authors: Chen Zhengyuan , Ma Zengyi , He Wenqiang , Shou Xuefei , Ye Zhao , Zhang Yichao , Zhang Qilin , Qiao Nidan , Zhou Xiang , Cao Xiaoyun , He Min , Zhang Zhaoyun , Ye Hongying , Li Yiming , Li Shiqi , Zhao Yao , Shen Ming , Wang Yongfei
Published: November 2021

Objective: To investigate the factors associated with recurrence/progression after endoscopic endonasal resection of suprasellar craniopharyngiomas. Special attention was paid to assess the impact of pituitary stalk preservation on tumor recurrence/progression and endocrinological outcomes.

Methods: We retrospectively recruited 73 patients with suprasellar craniopharyngiomas undergone endoscopic endonasal approach (EEA) surgery from September 2014 to May 2019 and assessed their clinical characteristics, surgical outcomes, and recurrence/progression. Stalk preservation or sacrifice was determined by reviewing operative records, videos, and post-operative magnetic resonance imaging.

Results: Gross total resection (GTR) was achieved in 51 cases (69.9%). Tumor recurrence was seen in 5 cases (9.8%) and progression was seen in 8 cases (36.4%), respectively. GTR (OR = 0.248 CI 0.081–0.759; p = 0.015) was the only independent factor influencing recurrence/progression. Kaplan-Meier survival analysis showed that the mean recurrence/progression-free survival were 53 (95% CI 48–59) and 39 (95% CI 28–50) months, respectively, in patients with and without GTR (p = 0.011). Pituitary stalk preservation was more common in cases with peripheral type tumors (83% vs. 30%, p < 0.01). Preserving the pituitary stalk does not appear to decrease the percentage of GTR (75.5% vs. 55.0%, p = 0.089), or increase the rate of tumor recurrence (12.5% vs. 0%, p = 0.508) or progression (46.2% vs. 22.2%, p = 0.486). However, surgically induced hypothyroidism (60.5% vs. 100%, p = 0.041) and diabetes insipidus (35.1% vs. 81.8%, p = 0.017) were significantly lower in patients with stalk preservation. For patients who had hypopituitarism before EEA, there was no difference between those with and without stalk preservation regarding post-operative hypopituitarism (p > 0.05).

Conclusion: GTR is the only independent predictor of recurrence/progression after EEA surgery for suprasellar craniopharyngiomas. Preserving the pituitary stalk does not appear to increase the risk of non-GTR and tumor recurrence/progression and might help reduce the risk of surgically induced hypothyroidism and diabetes insipidus. We recommend preserving the pituitary stalk in peripheral type suprasellar craniopharyngiomas with normal pituitary function, especially in cases without hypothyroidism or diabetes insipidus. On the other hand, stalk sacrifice could be considered in central type tumors with severe pre-operative endocrinopathy.
Galvanic Vestibular Stimulation Effects on EEG Biomarkers of Motor Vigor in Parkinson's Disease
Authors: Kazemi Alireza , Mirian Maryam S. , Lee Soojin , McKeown Martin J.
Published: November 2021

Background: Impaired motor vigor (MV) is a critical aspect of Parkinson's disease (PD) pathophysiology. While MV is predominantly encoded in the basal ganglia, deriving (cortical) EEG measures of MV may provide valuable targets for modulation via galvanic vestibular stimulation (GVS).

Objective: To find EEG features predictive of MV and examine the effects of high-frequency GVS.

Methods: Data were collected from 20 healthy control (HC) and 18 PD adults performing 30 trials total of a squeeze bulb task with sham or multi-sine (50–100 Hz “GVS1” or 100–150 Hz “GVS2”) stimuli. For each trial, we determined the time to reach maximum force after a “Go” signal, defined MV as the inverse of this time, and used the EEG data 1-sec prior to this time for prediction. We utilized 53 standard EEG features, including relative spectral power, harmonic parameters, and amplitude and phase of bispectrum corresponding to standard EEG bands from each of 27 EEG channels. We then used LASSO regression to select a sparse set of features to predict MV. The regression weights were examined, and separate band-specific models were developed by including only band-specific features (Delta, Theta, Alpha-low, Alpha-high, Beta, Gamma). The correlation between MV prediction and measured MV was used to assess model performance.

Results: Models utilizing broadband EEG features were capable of accurately predicting MV (controls: 75%, PD: 81% of the variance). In controls, all EEG bands performed roughly equally in predicting MV, while in the PD group, the model using only beta band features did not predict MV well compared to other bands. Despite having minimal effects on the EEG feature values themselves, both GVS stimuli had significant effects on MV and profound effects on MV predictability via the EEG. With the GVS1 stimulus, beta-band activity in PD subjects became more closely associated with MV compared to the sham condition. With GVS2 stimulus, MV could no longer be accurately predicted from the EEG.

Conclusions: EEG features can be a proxy for MV. However, GVS stimuli have profound effects on the relationship between EEG and MV, possibly via direct vestibulo-basal ganglia connections not measurable by the EEG.
Acute Psychosis Due to Anti-N-Methyl D-Aspartate Receptor Encephalitis Following COVID-19 Vaccination: A Case Report
Authors: Flannery Patrick , Yang Ingrid , Keyvani Madjid , Sakoulas George
Published: November 2021

Anti-N-methyl D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis has been reported after SARS-CoV-2 infection, but not after SARS-CoV-2 vaccination. We report the first known case of anti-NMDAR encephalitis after SARS-CoV-2 immunization in a young female presenting with acute psychosis, highlighting a rare potential immunological complication of vaccination against SARS-CoV-2 that is currently being distributed worldwide. The patient presented initially with anxiety and hypochondriacal delusions which progressed to psychosis and catatonia but returned to baseline with aggressive immunomodulatory therapy consisting of intravenous immunoglobulin, high-dose glucocorticoids, and rituximab. This study highlights that the workup of acute psychosis should include establishing a history of recent vaccination followed by a thorough neurological assessment, including for anti-NMDAR antibodies in blood and cerebrospinal fluid.
Morphometry Difference of the Hippocampal Formation Between Blind and Sighted Individuals
Authors: Pan Ningning , Zheng Ke , Zhao Yanna , Zhang Dan , Dong Changxu , Xu Junhai , Li Xianglin , Zheng Yuanjie
Published: November 2021

The detailed morphometry alterations of the human hippocampal formation (HF) for blind individuals are still understudied. 50 subjects were recruited from Yantai Affiliated Hospital of Binzhou Medical University, including 16 congenital blindness, 14 late blindness, and 20 sighted controls. Volume and shape analysis were conducted between the blind (congenital or late) and sighted groups to observe the (sub)regional alterations of the HF. No significant difference of the hippocampal volume was observed between the blind and sighted subjects. Rightward asymmetry of the hippocampal volume was found for both congenital and late blind individuals, while no significant hemispheric difference was observed for the sighted controls. Shape analysis showed that the superior and inferior parts of both the hippocampal head and tail expanded, while the medial and lateral parts constrained for the blind individuals as compared to the sighted controls. The morphometry alterations for the congenital blind and late blind individuals are nearly the same. Significant expansion of the superior part of the hippocampal tail for both congenital and late blind groups were observed for the left hippocampi after FDR correction. Current results suggest that the cross-model plastic may occur in both hemispheres of the HF to improve the navigation ability without the stimuli of visual cues, and the alteration is more prominent for the left hemisphere.
Plaque-Associated Oligomeric Amyloid-Beta Drives Early Synaptotoxicity in APP/PS1 Mice Hippocampus: Ultrastructural Pathology Analysis
Authors: Sanchez-Varo Raquel , Sanchez-Mejias Elisabeth , Fernandez-Valenzuela Juan Jose , De Castro Vanessa , Mejias-Ortega Marina , Gomez-Arboledas Angela , Jimenez Sebastian , Sanchez-Mico Maria Virtudes , Trujillo-Estrada Laura , Moreno-Gonzalez Ines , Baglietto-Vargas David , Vizuete Marisa , Davila Jose Carlos , Vitorica Javier , Gutierrez Antonia
Published: November 2021

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by initial memory impairments that progress to dementia. In this sense, synaptic dysfunction and loss have been established as the pathological features that best correlate with the typical early cognitive decline in this disease. At the histopathological level, post mortem AD brains typically exhibit intraneuronal neurofibrillary tangles (NFTs) along with the accumulation of amyloid-beta (Abeta) peptides in the form of extracellular deposits. Specifically, the oligomeric soluble forms of Abeta are considered the most synaptotoxic species. In addition, neuritic plaques are Abeta deposits surrounded by activated microglia and astroglia cells together with abnormal swellings of neuronal processes named dystrophic neurites. These periplaque aberrant neurites are mostly presynaptic elements and represent the first pathological indicator of synaptic dysfunction. In terms of losing synaptic proteins, the hippocampus is one of the brain regions most affected in AD patients. In this work, we report an early decline in spatial memory, along with hippocampal synaptic changes, in an amyloidogenic APP/PS1 transgenic model. Quantitative electron microscopy revealed a spatial synaptotoxic pattern around neuritic plaques with significant loss of periplaque synaptic terminals, showing rising synapse loss close to the border, especially in larger plaques. Moreover, dystrophic presynapses were filled with autophagic vesicles in detriment of the presynaptic vesicular density, probably interfering with synaptic function at very early synaptopathological disease stages. Electron immunogold labeling showed that the periphery of amyloid plaques, and the associated dystrophic neurites, was enriched in Abeta oligomers supporting an extracellular location of the synaptotoxins. Finally, the incubation of primary neurons with soluble fractions derived from 6-month-old APP/PS1 hippocampus induced significant loss of synaptic proteins, but not neuronal death. Indeed, this preclinical transgenic model could serve to investigate therapies targeted at initial stages of synaptic dysfunction relevant to the prodromal and early AD.
Molecular Strategies for Intensity-Dependent Olfactory Processing in Caenorhabditis elegans
Authors: Cheng Hankui , Liu Yu , Xue Yadan , Shao Jiajie , Tan Zhibing , Liu Siyan , Duan Shumin , Kang Lijun
Published: November 2021

Various odorants trigger complex animal behaviors across species in both quality- and quantity-dependent manners. However, how the intensity of olfactory input is encoded remains largely unknown. Here we report that isoamyl alcohol (IAA) induces bi-directional currents through a Gα- guanylate cyclase (GC)- cGMP signaling pathway inCaenorhabditis elegansolfactory neuron amphid wing “C” cell (AWC), while two opposite cGMP signaling pathways are responsible for odor-sensing in olfactory neuron amphid wing “B” cell (AWB): (1) a depolarizing Gα (GPA-3)- phosphodiesterase (PDE) – cGMP pathway which can be activated by low concentrations of isoamyl alcohol (IAA), and (2) a hyperpolarizing Gα (ODR-3)- GC- cGMP pathway sensing high concentrations of IAA. Besides, IAA induces Gα (ODR-3)-TRPV(OSM-9)-dependent currents in amphid wing “A” cell (AWA) and amphid neuron “H” cell with single ciliated sensory ending (ASH) neurons with different thresholds. Our results demonstrate that an elaborate combination of multiple signaling machineries encode the intensity of olfactory input, shedding light on understanding the molecular strategies on sensory transduction.
Extramammary Paget’s Disease in the Genital Area of a Male: A Case Report and Review of the Literature
Authors: Zhao Dan , Wen Bo-ping , Xu Sen-yin
Published: November 2021

Extramammary Paget’s disease (EMPD) is an uncommon intraepithelial malignancy that is rarely found in the male. Currently, there is very little knowledge pertaining to EMPD imaging, particularly in cases that involve the scrotum. Here, a 67-year-old man with lichenification on his left scrotum confirmed to be EMPD was reviewed. Bloodwork did not return a positive result, but syphilis-specific antibodies were found. Conventional high-frequency ultrasound (US) and contrast-enhanced ultrasound (CEUS) imaging were utilized to determine the lesion size and blood perfusion. In the present case, the lesion’s size and involvement were vividly depicted by CEUS, while results obtained by conventional US were grossly underestimated. Consequently, multimodal imaging assessment is likely to provide more accurate diagnoses for uncommon diseases, such as EMPD, and to aid in clinical decision-making.