bluuebunny/crossref_metadata_2025 huggingface dataset:
Will the Inducing and Maintaining Remission of Non-biological Agents and Biological Agents Differ for Crohn's Disease? The Evidence From the Network Meta-Analysis
Authors: Rui Mingjun , Fei Zhengyang , Wang Yingcheng , Shi Fenghao , Meng Rui , Shang Ye , Ma Aixia , Li Hongchao
Published: September 2021

Background: Several drugs currently are available for the treatment of Crohn's disease, including non-biological agents such as anti-inflammatory agents, steroids, immunosuppressive agents, and biologic agents such as anti-tumor necrosis factor (TNF), anti-α4β7 integrin, anti-alpha-4 integrin and anti-interleukin 12/23. However, the choice of treatments for induction and maintenance is still a challenge. The relevant comparison between non-biologic agents and biologic agents is few. In our research, we aimed to help making decisions, as well as providing clinicians and patients with medication references.

Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of controlled trials for relevant randomized controlled trials published through to July 2020 and systematic reviews published from January 2011 to December 2020. Search results were screened by 2 independent reviewers first by title and abstract and then by full text. Disagreements were resolved through discussion with a third reviewer.

Results: 54 randomized controlled trials were included in our analysis. For induction of remission, azathioprine (OR, 3.5; 95% Crl, 1.4–8.9), infliximab (OR, 4.1; 95% Crl, 1.2–16.0), infliximab + azathioprine (OR, 7.0; 95% Crl, 1.2–41.0) and infliximab+ methotrexate (OR, 7.8; 95% Crl, 1.2–65.0) were more effective in first-line therapy than placebo. Adalimumab showed superiority to placebo in second-line therapy, but the range of SD was wide. For maintenance of remission, adalimumab (OR,2.24;95% Crl,1.17–4.76) and azathioprine (OR,2.05; 95% Crl,1.14–3.96) were more effective than placebo. Adalimumab (OR,0.56; 95%Crl,0.27–1.2), budesonide (OR,0.63; 95%Crl,0.26–1.6) and natalizumab (OR,0.65; 95%Crl,0.30–1.4) was associated with less risk of withdrawals when compared with placebo.

Conclusion: For induction of remission, azathioprine, infliximab, and infliximab + azathioprine were more effective in first-line therapy. In second-line therapy, adalimumab was more effective but should be interpreted carefully. For maintenance of remission, adalimumab and azathioprine were more effective. Besides, adalimumab, budesonide, natalizumab had lower withdrawals. Therefore, biological agents were not always better than non-biological agents and they have their own advantages in different treatment methods of Crohn's disease.
Systematic Review on the Efficacy and Safety of Oral Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis
Authors: Le Michelle , Berman-Rosa Melissa , Ghazawi Feras M. , Bourcier Marc , Fiorillo Loretta , Gooderham Melinda , Guenther Lyn , Hanna Sameh , Hong H. Chih-Ho , Landells Ian , Lansang Perla , Marcoux Danielle , Wiseman Marni C. , Yeung Jensen , Lynde Charles , Litvinov Ivan V.
Published: September 2021

Background: Atopic dermatitis is a chronic, relapsing and remitting disease that can be difficult to treat despite a recently approved biologic therapy targeting IL-4/IL-13 receptor. Oral janus kinase inhibitors (JAKi) represent a novel therapeutic class of targeted therapy to treat moderate-to-severe atopic dermatitis (AD).

Objective: To review the efficacy, safety, and pharmacokinetic characteristics of oral JAKi in the treatment of AD.

Methods: A PRISMA systematic review was conducted using MEDLINE, EMBASE (Ovid), and PubMed databases for studies assessing the efficacy, safety, and/or pharmacokinetic properties of oral forms of JAKi in the treatment of AD in pediatric or adult populations from inception to June 2021.

Results: 496 papers were reviewed. Of 28 articles that underwent full text screening, 11 met our inclusion criteria for final qualitative review. Four studies examined abrocitinib; three studies examined baricitinib; three examined upadacitinib and one examined gusacitinib (ASN002). Significant clinical efficacy and a reassuring safety profile was reported for all JAKi agents reviewed. Rapid symptom control was reported for abrocitinib, baricitinib and upadacitinib.

Limitations: Given the relatively limited evidence for each JAKi and the differences in patient eligibility criteria between studies, the data was not deemed suitable for a meta-analysis at this time.

Conclusion: Given their ability to achieve rapid symptom control with a reassuring safety profile, we recommend considering the use of JAKi as a reliable systemic treatment option for adult patients with moderate-to-severe AD, who are unresponsive to topical or skin directed treatments.
External Limiting Membrane Disruption Predicts Long-Term Outcome in Strict Treat-And-Extend Regimen in Neovascular Age-Related Macular Degeneration
Authors: Hoffmann Laura , Hatz Katja
Published: September 2021

The use of anti-vascular-endothelial growth factor agents for neovascular age-related macular degeneration (nAMD) in different treatment schemes is widely common in clinical practice. However, there is currently limited data on the long-term outcomes of a strict treat-and-extend regimen (TER) and imaging biomarkers to predict both functional outcome and the potential for a TER exit due to success. In this retrospective study we followed treatment-naïve subjects with nAMD starting treatment with either ranibizumab or aflibercept in a TER without loading dose but with predefined exit criteria for up to 8 years. We evaluated both the functional outcome and several spectral-domain optical coherence tomography parameters in a follow-up mode using a standardized protocol. Within the 211 eyes followed for a mean of 60.3 ± 20.9 months, follow-up adherence was high with major part of discontinuations of TER being due to success. Mean best-corrected visual acuity (BCVA) increased from initially 63.9 ± 15.5 ETDRS letters to 70.0 ± 14.7 after 1 year (+6.1 letters, p < 0.001) and to 68.5 ± 18.1 (+4.6 letters, p = 0.028) at 5 years. A worse BCVA (p = 0.001) and a better external limiting membrane (ELM) disruption score at baseline predicted (p = 0.019) BCVA gain at 5 years. The probability of reaching the exit criteria was significantly associated with a better ELM disruption score (p = 0.044) and the absence of a central pigment epithelial detachment (PED) (p = 0.05) at baseline. Significant visual gains were sustained in a long-term TER in a real-world setting. Integrity of ELM at baseline predicted BCVA gain at 5 years and the potential for TER exit due to success.
Whole Genome Sequencing of SARS-CoV-2 Strains in COVID-19 Patients From Djibouti Shows Novel Mutations and Clades Replacing Over Time
Authors: Osman Ikram Omar , Levasseur Anthony , Brechard Ludivine , Abdillahi Hassan Iman , Salah Abdillahi Idil , Ali Waberi Zeinab , Delerce Jeremy , Bedotto Marielle , Houhamdi Linda , Fournier Pierre-Edouard , Colson Philippe , Aboubaker Mohamed Houmed , Raoult Didier , Devaux Christian A.
Published: September 2021

Since the start of COVID-19 pandemic the Republic of Djibouti, in the horn of Africa, has experienced two epidemic waves of the virus between April and August 2020 and between February and May 2021. By May 2021, COVID-19 had affected 1.18% of the Djiboutian population and caused 152 deaths. Djibouti hosts several foreign military bases which makes it a potential hot-spot for the introduction of different SARS-CoV-2 strains. We genotyped fifty three viruses that have spread during the two epidemic waves. Next, using spike sequencing of twenty-eight strains and whole genome sequencing of thirteen strains, we found that Nexstrain clades 20A and 20B with a typically European D614G substitution in the spike and a frequent P2633L substitution in nsp16 were the dominant viruses during the first epidemic wave, while the clade 20H South African variants spread during the second wave characterized by an increase in the number of severe forms of COVID-19.
Case Report: Pityriasis Rosea-Like Eruption Following COVID-19 Vaccination
Authors: Leerunyakul Kanchana , Pakornphadungsit Kallapan , Suchonwanit Poonkiat
Published: September 2021

Vaccination is one of the cornerstones in the efforts towards ending the coronavirus disease 2019 (COVID-19) pandemic. However, several adverse effects of COVID-19 vaccination have been identified. Pityriasis rosea (PR)-like eruption is a rare cutaneous complication of immunization. To the best of our knowledge, there have been no reports of PR-like eruptions following inoculation with Oxford/AstraZeneca ChAdOx1 nCoV-19 (AZD1222) vaccine. Here, we described a case of PR-like eruption that developed 14 days after Oxford/AstraZeneca vaccination in a 52-year-old Thai woman with glioblastoma. Treatment with topical 0.1% triamcinolone acetonide twice per day showed partial response after seven days. Despite this rare complication, our report highlights that the presence of PR-like eruption is not a contraindication for subsequent vaccinations.
Influence of Environmental Factors on the Variability of Archaeal Communities in a Karst Wetland
Authors: Chen Ying , Qiu Kairui , Zhong Ziyuan , Zhou Tao
Published: September 2021

Archaea are ubiquitous and play an important role in elemental cycles in Earth’s biosphere; but little is known about their diversity, distribution, abundance, and impact in karst environments. The present study investigated the effect of environmental factors on the variability of archaeal communities in the sediment of the Huixian karst wetland, the largest karst wetland in South China. Sediment cores were obtained from four sampling sites with different water depths and macrophyte inhabitants in both the winter of 2016 and the summer of 2018. The community analysis was based on PacBio sequencing and quantitative PCR of the archaeal 16S rRNA gene. The results showed that Euryarchaeota (57.4%) and Bathyarchaeota (38.7%) were dominant in all the samples. Methanogenic Methanosarcinales (25.1%) and Methanomicrobiales (13.7%), and methanotrophic archaea ANME-2d (9.0%) were the dominant Euryarchaeota; MCG-11 (16.5%), MCG-6 (9.1%), and MCG-5b (5.5%) were the dominant Bathyarchaeota. The community composition remained stable between summer and winter, and the vertical distributions of the archaeal phyla conformed to two patterns among the four sampling sites. In the winter samples, the archaeal 16S rRNA gene abundance was approximately 1.0E+10 copies/g of wet sediment and the Shannon index was 7.3±5, which were significantly higher than in the summer samples and in other karst environments. A correlation analysis showed that the moisture content and pH were the factors that mostly affected the archaeal communities. The prevalence of nitrate in the summer may be a key factor causing a significant decrease in archaeal abundance and diversity. Two features specific to karst environments, calcium-richness and weak alkalescence of the water supplies, may benefit the prevalence of bathyarchaeotal subgroups MCG-11, MCG-5b, and MCG-6. These results suggest that in karst wetlands, most of the archaea belong to clades that have significant roles in carbon turnover; their composition remains stable, but their abundance and diversity vary significantly from season to season.
The Conserved Colletotrichum spp. Effector Candidate CEC3 Induces Nuclear Expansion and Cell Death in Plants
Authors: Tsushima Ayako , Narusaka Mari , Gan Pamela , Kumakura Naoyoshi , Hiroyama Ryoko , Kato Naoki , Takahashi Shunji , Takano Yoshitaka , Narusaka Yoshihiro , Shirasu Ken
Published: September 2021

Plant pathogens secrete proteins, known as effectors, that promote infection by manipulating host cells. Members of the phytopathogenic fungal genus Colletotrichum collectively have a broad host range and generally adopt a hemibiotrophic lifestyle that includes an initial biotrophic phase and a later necrotrophic phase. We hypothesized that Colletotrichum fungi use a set of conserved effectors during infection to support the two phases of their hemibiotrophic lifestyle. This study aimed to examine this hypothesis by identifying and characterizing conserved effectors among Colletotrichum fungi. Comparative genomic analyses using genomes of ascomycete fungi with different lifestyles identified seven effector candidates that are conserved across the genus Colletotrichum. Transient expression assays showed that one of these putative conserved effectors, CEC3, induces nuclear expansion and cell death in Nicotiana benthamiana, suggesting that CEC3 is involved in promoting host cell death during infection. Nuclear expansion and cell death induction were commonly observed in CEC3 homologs from four different Colletotrichum species that vary in host specificity. Thus, CEC3 proteins could represent a novel class of core effectors with functional conservation in the genus Colletotrichum.
Babesia microti: Pathogen Genomics, Genetic Variability, Immunodominant Antigens, and Pathogenesis
Authors: Puri Ankit , Bajpai Surabhi , Meredith Scott , Aravind L. , Krause Peter J. , Kumar Sanjai
Published: September 2021

More than 100 Babesia spp. tick-borne parasites are known to infect mammalian and avian hosts. Babesia belong to Order Piroplasmid ranked in the Phylum Apicomplexa. Recent phylogenetic studies have revealed that of the three genera that constitute Piroplasmida, Babesia and Theileria are polyphyletic while Cytauxzoon is nested within a clade of Theileria. Several Babesia spp. and sub-types have been found to cause human disease. Babesia microti, the most common species that infects humans, is endemic in the Northeastern and upper Midwestern United States and is sporadically reported elsewhere in the world. Most infections are transmitted by Ixodid (hard-bodied) ticks, although they occasionally can be spread through blood transfusion and rarely via perinatal transmission and organ transplantation. Babesiosis most often presents as a mild to moderate disease, however infection severity ranges from asymptomatic to lethal. Diagnosis is usually confirmed by blood smear or polymerase chain reaction (PCR). Treatment consists of atovaquone and azithromycin or clindamycin and quinine and usually is effective but may be problematic in immunocompromised hosts. There is no human Babesia vaccine. B. microti genomics studies have only recently been initiated, however they already have yielded important new insights regarding the pathogen, population structure, and pathogenesis. Continued genomic research holds great promise for improving the diagnosis, management, and prevention of human babesiosis, and in particular, the identification of lineage-specific families of cell-surface proteins with potential roles in cytoadherence, immune evasion and pathogenesis.
Impact of Tellurite on the Metabolism of Paenibacillus pabuli AL109b With Flagellin Production Explaining High Reduction Capacity
Authors: Farias Pedro , Francisco Romeu , Maccario Lorrie , Herschend Jakob , Piedade Ana Paula , Sørensen Søren , Morais Paula V.
Published: September 2021

Tellurium (Te) is a metalloid with scarce and scattered abundance but with an increased interest in human activity for its uses in emerging technologies. As is seen for other metals and metalloids, the result of mining activity and improper disposal of high-tech devices will lead to niches with increased abundance of Te. This metalloid will be more available to bacteria and represent an increasing selective pressure. This environmental problem may constitute an opportunity to search for microorganisms with genetic and molecular mechanisms of microbial resistance to Te toxic anions. Organisms from Te-contaminated niches could provide tools for Te remediation and fabrication of Te-containing structures with added value. The objective of this study was to determine the ability of a high metal-resistant Paenibacillus pabuli strain ALJ109b, isolated from high metal content mining residues, to reduce tellurite ion, and to evaluate the formation of metallic tellurium by cellular reduction, isolate the protein responsible, and determine the metabolic response to tellurite during growth. P. pabuli ALJ109b demonstrated to be resistant to Te (IV) at concentrations higher than reported for its genus. It can efficiently remove soluble Te (IV) from solution, over 20% in 8 h of growth, and reduce it to elemental Te, forming monodisperse nanostructures, verified by scattering electron microscopy. Cultivation of P. pabuli ALJ109b in the presence of Te (IV) affected the general protein expression pattern, and hence the metabolism, as demonstrated by high-throughput proteomic analysis. The Te (IV)-induced metabolic shift is characterized by an activation of ROS response. Flagellin from P. pabuli ALJ109b demonstrates high Te (0) forming activity in neutral to basic conditions in a range of temperatures from 20°C to 37°C. In conclusion, the first metabolic characterization of a strain of P. pabuli response to Te (IV) reveals a highly resistant strain with a unique Te (IV) proteomic response. This strain, and its flagellin, display, all the features of potential tools for Te nanoparticle production.
Emergence of mcr-1-Harboring Salmonella enterica Serovar Sinstorf Type ST155 Isolated From Patients With Diarrhea in Jiangsu, China
Authors: Liu Guoye , Qian Huimin , Lv Jingwen , Tian Benshun , Bao Changjun , Yan Hong , Gu Bing
Published: September 2021

Background:This study analyzed the antimicrobial resistance phenotypes and mechanisms of quinolone, cephalosporins, and colistin resistance in nontyphoidalSalmonellafrom patients with diarrhea in Jiangsu, China.

Methods:A total of 741 nontyphoidalSalmonellaisolates were collected from hospitals in major cities of Jiangsu Province, China between 2016 and 2017. Their susceptibility to commonly used antibiotics was evaluated by broth micro-dilution and sequencing analysis of resistance genes screened by a PCR method. Formcr-1positive isolates, genetic relationship study was carried out by pulsed-field gel electrophoresis and multiloci sequence typing analysis. The transferability of these plasmids was measured with conjugation experiments and the genetic locations ofmcr-1were analyzed by pulsed-field gel electrophoresis profiles of S1-digested genomic DNA and subsequent Southern blot hybridization.

Results:Among 741 nontyphoidalSalmonellaisolates, the most common serotypes identified wereS.Typhimurium (n=257, 34.7%) andS.Enteritidis (n=127, 17.1%), and the isolates showed 21.7, 20.6, and 5.0% resistance to cephalosporins, ciprofloxacin, and colistin, respectively. Among the 335 nalidixic acid-resistantSalmonella, 213 (63.6%) and 45 (13.4%) had at least one mutation ingyrAandparC. Among the plasmid-borne resistance,qnrS1(85; 41.9%) andaac(6')-Ib-cr4(75; 36.9%) were the most common quinolone resistance (PMQR) genes, whileblaCTX-M-14(n=35) andblaCTX-M-55(n=46) were found to be dominant extended-spectrum beta-lactamase (ESBL) genes in nontyphoidalSalmonella. In addition, eightmcr-1-harboring strains were detected since 2016 and they were predominate in children under the age of 7years. Conjugation assays showed the donorSalmonellastrain has functional and transferable colistin resistance and Southern blot hybridization revealed thatmcr-1was located in a high molecular weight plasmid.

Conclusion:In nontyphoidalSalmonella, there is a rapidly increasing trend of colistin resistance and this is the first report of patients harboringmcr-1-positiveSalmonellawith a new ST type ST155 and new serotypeS.Sinstorf. These findings demonstrate the necessity for cautious use and the continuous monitoring of colistin in clinical applications.
Peptides Targeting the Interaction Between Erb1 and Ytm1 Ribosome Assembly Factors
Authors: Orea-Ordóñez Lidia , Masiá Susana , Bravo Jerónimo
Published: September 2021

Ribosome biogenesis is an emerging therapeutic target. It has been proposed that cancer cells are addicted to ribosome production which is therefore considered a druggable pathway in cancer therapy. Cancer cells have been shown to be more sensitive to inhibition of the ribosome production than healthy cells. Initial attempts of inhibiting ribosome biogenesis have been focused on the inhibition of transcription by targeting RNA Pol I. Despite being a promising field of research, several limitations have been identified during the development of RNA Pol I inhibitors, like the lack of specificity or acquired resistance. Ribosome biogenesis is a multistep process and additional points of intervention, downstream the very initial stage, could be investigated. Eukaryotic ribosome maturation involves the participation of more than 200 essential assembly factors that will not be part of the final mature ribosome and frequently require protein–protein interactions to exert their biological action. Using mutagenesis, we have previously shown that alteration of the complex interface between assembly factors impairs proper ribosome maturation in yeast. As a first step toward the developing of ribosome biogenesis inhibitory tools, we have used our previously solved crystal structure of the Chaetomium thermophilum complex between the assembly factors Erb1 and Ytm1 to perform a structure-guided selection of interference peptides. The peptides have been assayed in vitro for their ability to bind their cellular partner using biophysical techniques.
Decoding the Structural Dynamics and Conformational Alternations of DNA Secondary Structures by Single-Molecule FRET Microspectroscopy
Authors: Bandyopadhyay Debolina , Mishra Padmaja P.
Published: September 2021

In addition to the canonical double helix form, DNA is known to be extrapolated into several other secondary structural patterns involving themselves in inter- and intramolecular type hydrogen bonding. The secondary structures of nucleic acids go through several stages of multiple, complex, and interconvertible heterogeneous conformations. The journey of DNA through these conformers has significant importance and has been monitored thoroughly to establish qualitative and quantitative information about the transition between the unfolded, folded, misfolded, and partially folded states. During this structural interconversion, there always exist specific populations of intermediates, which are short-lived or sometimes even do not accumulate within a heterogeneous population and are challenging to characterize using conventional ensemble techniques. The single-molecule FRET(sm-FRET) microspectroscopic method has the advantages to overcome these limitations and monitors biological phenomena transpiring at a measurable high rate and balanced stochastically over time. Thus, tracing the time trajectory of a particular molecule enables direct measurement of the rate constant of each transition step, including the intermediates that are hidden in the ensemble level due to their low concentrations. This review is focused on the advantages of the employment of single-molecule Forster’s resonance energy transfer (sm-FRET), which is worthwhile to access the dynamic architecture and structural transition of various secondary structures that DNA adopts, without letting the donor of one molecule to cross-talk with the acceptor of any other. We have emphasized the studies performed to explore the states of folding and unfolding of several nucleic acid secondary structures, for example, the DNA hairpin, Holliday junction, G-quadruplex, and i-motif.
Differential Modulation of the Voltage-Gated Na+ Channel 1.6 by Peptides Derived From Fibroblast Growth Factor 14
Authors: Singh Aditya K. , Dvorak Nolan M. , Tapia Cynthia M. , Mosebarger Angela , Ali Syed R. , Bullock Zaniqua , Chen Haiying , Zhou Jia , Laezza Fernanda
Published: September 2021

The voltage-gated Na+ (Nav) channel is a primary molecular determinant of the initiation and propagation of the action potential. Despite the central role of the pore-forming α subunit in conferring this functionality, protein:protein interactions (PPI) between the α subunit and auxiliary proteins are necessary for the full physiological activity of Nav channels. In the central nervous system (CNS), one such PPI occurs between the C-terminal domain of the Nav1.6 channel and fibroblast growth factor 14 (FGF14). Given the primacy of this PPI in regulating the excitability of neurons in clinically relevant brain regions, peptides targeting the FGF14:Nav1.6 PPI interface could be of pre-clinical value. In this work, we pharmacologically evaluated peptides derived from FGF14 that correspond to residues that are at FGF14’s PPI interface with the CTD of Nav1.6. These peptides, Pro-Leu-Glu-Val (PLEV) and Glu-Tyr-Tyr-Val (EYYV), which correspond to residues of the β12 sheet and β8-β9 loop of FGF14, respectively, were shown to inhibit FGF14:Nav1.6 complex assembly. In functional studies using whole-cell patch-clamp electrophysiology, PLEV and EYYV were shown to confer differential modulation of Nav1.6-mediated currents through mechanisms dependent upon the presence of FGF14. Crucially, these FGF14-dependent effects of PLEV and EYYV on Nav1.6-mediated currents were further shown to be dependent on the N-terminal domain of FGF14. Overall, these data suggest that the PLEV and EYYV peptides represent scaffolds to interrogate the Nav1.6 channel macromolecular complex in an effort to develop targeted pharmacological modulators.
Intake of Products Containing Anthocyanins, Flavanols, and Flavanones, and Cognitive Function: A Narrative Review
Authors: Gardener Samantha L. , Rainey-Smith Stephanie R. , Weinborn Michael , Bondonno Catherine P. , Martins Ralph N.
Published: September 2021

The purpose of this review is to examine human research studies published within the past 6 years which evaluate the role of anthocyanin, flavanol, and flavanone consumption in cognitive function, and to discuss potential mechanisms of action underlying any observed benefits. Evidence to date suggests the consumption of flavonoid-rich foods, such as berries and cocoa, may have the potential to limit, or even reverse, age-related declines in cognition. Over the last 6 years, the flavonoid subgroups of anthocyanins, flavanols, and flavanones have been shown to be beneficial in terms of conferring neuroprotection. The mechanisms by which flavonoids positively modulate cognitive function are yet to be fully elucidated. Postulated mechanisms include both direct actions such as receptor activation, neurotrophin release and intracellular signaling pathway modulation, and indirect actions such as enhancement of cerebral blood flow. Further intervention studies conducted in diverse populations with sufficient sample sizes and long durations are required to examine the effect of consumption of flavonoid groups on clinically relevant cognitive outcomes. As populations continue to focus on adopting healthy aging strategies, dietary interventions with flavonoids remains a promising avenue for future research. However, many questions are still to be answered, including identifying appropriate dosage, timeframes for intake, as well as the best form of flavonoids, before definitive conclusions can be drawn about the extent to which their consumption can protect the aging brain.
Reduced Insulin-Like Growth Factor-I Effects in the Basal Forebrain of Aging Mouse
Authors: Zegarra-Valdivia Jonathan A. , Chaves-Coira Irene , Fernandez de Sevilla Maria Estrella , Martinez-Rachadell Laura , Esparza Julio , Torres-Aleman Ignacio , Nuñez Angel
Published: September 2021

It is known that aging is frequently accompanied by a decline in cognition. Furthermore, aging is associated with lower serum IGF-I levels that may contribute to this deterioration. We studied the effect of IGF-I in neurons of the horizontal diagonal band of Broca (HDB) of young (≤6 months old) and old (≥20-month-old) mice to determine if changes in the response of these neurons to IGF-I occur along with aging. Local injection of IGF-I in the HDB nucleus increased their neuronal activity and induced fast oscillatory activity in the electrocorticogram (ECoG). Furthermore, IGF-I facilitated tactile responses in the primary somatosensory cortex elicited by air-puffs delivered in the whiskers. These excitatory effects decreased in old mice. Immunohistochemistry showed that cholinergic HDB neurons express IGF-I receptors and that IGF-I injection increased the expression of c-fos in young, but not in old animals. IGF-I increased the activity of optogenetically-identified cholinergic neurons in young animals, suggesting that most of the IGF-I-induced excitatory effects were mediated by activation of these neurons. Effects of aging were partially ameliorated by chronic IGF-I treatment in old mice. The present findings suggest that reduced IGF-I activity in old animals participates in age-associated changes in cortical activity.
Research on a Segmentation Algorithm for the Tujia Brocade Images Based on Unsupervised Gaussian Mixture Clustering
Authors: He Shuqi
Published: September 2021

Tujia brocades are important carriers of Chinese Tujia national culture and art. It records the most detailed and real cultural history of Tujia nationality and is one of the National Intangible Cultural Heritage. Classic graphic elements are separated from Tujia brocade patterns to establish the Tujia brocade graphic element database, which is used for the protection and inheritance of traditional national culture. Tujia brocade dataset collected a total of more than 200 clear Tujia brocade patterns and was divided into seven categories, according to traditional meanings. The weave texture of a Tujia brocade is coarse, and the textural features of the background are obvious, so classical segmentation algorithms cannot achieve good segmentation effects. At the same time, deep learning technology cannot be used because there is no standard Tujia brocade dataset. Based on the above problems, this study proposes a method based on an unsupervised clustering algorithm for the segmentation of Tujia brocades. First, the cluster number K is calculated by fusing local binary patterns (LBP) and gray-level co-occurrence matrix (GLCM) characteristic values. Second, clustering and segmentation are conducted on each input Tujia brocade image by adopting a Gaussian mixture model (GMM) to obtain a preliminary segmentation image, wherein the image yielded after preliminary segmentation is rough. Then, a method based on voting optimization and dense conditional random field (DenseCRF) (CRF denotes conditional random filtering) is adopted to optimize the image after preliminary segmentation and obtain the image segmentation results. Finally, the desired graphic element contour is extracted through interactive cutting. The contributions of this study include: (1) a calculation method for the cluster number K wherein the experimental results show that the effect of the clustering number K chosen in this paper is ideal; (2) an optimization method for the noise points of Tujia brocade patterns based on voting, which can effectively eliminate isolated noise points from brocade patterns.
The Impact of β-1,4-Galactosyltransferase V on Microglial Function
Authors: Wang Xiaoyu , Shi Naiqi , Hui Meiqi , Jin Hui , Gao Shumei , Zhou Qiao , Zhang Li , Yan Meijuan , Shen Hongmei
Published: September 2021

β-1,4 Galactosyltransferase V (β-1,4-GalT V) belongs to the β-1,4 galactosyltransferase family, which modifies proteins and plays a vital role in biological function. Our previous study revealed that β-1,4-GalT V was expressed in the cortex and hippocampus and participated in the recovery of spatial learning and memory in rats with traumatic brain injury. However, the expression of β-1,4-GalT V in microglia, resident immune cells in the central nervous system, and its impact on microglia in resting and lipopolysaccharide-triggered activated stages are elusive. In this study, we clarified that β-1,4-GalT V expresses in microglia, and it regulates microglial migration, proliferation, and release of the inflammatory factors. We also observed that β-1,4-GalT V affects the expression level of tumor necrosis factor receptor (TNFR)2 instead of TNFR1. These results strongly support the fact that β-1,4-GalT V is involved in microglial function.
Alternation of Neuronal Feature Selectivity Induced by Paired Optogenetic-Mechanical Stimulation in the Barrel Cortex
Authors: Cheng Yu-Po , Huang Jian-Jia , Yeh Chun-I , Pei Yu-Cheng
Published: September 2021

Paired stimulation has been applied to modulate neuronal functions in the primary somatosensory cortex but its utility in the alternation of tuning function, such as direction tuning for whisker stimuli, remains unclear. In the present study, we attempted to manipulate feature preferences in barrel cortical neurons using repetitive paired whisker deflection combined with optogenetic stimulation and to obtain optimal parameters that can induce neuroplasticity. We found no significant response changes across stimulus parameters, such as onset asynchronies and paired directions. Only when paired stimulation was applied in the nonpreferred direction of the principal whisker of a neuron, were the neuron’s responses enhanced in that direction. Importantly, this effect was only observed when the optogenetic stimulus preceded the mechanical stimulus. Our findings indicate that repetitive paired optogenetic-mechanical stimulation can induce in vivo neuroplasticity of feature selectivity in limited situations.
An Approach for Stabilizing Abnormal Neural Activity in ADHD Using Chaotic Resonance
Authors: Nobukawa Sou , Wagatsuma Nobuhiko , Nishimura Haruhiko , Doho Hirotaka , Takahashi Tetsuya
Published: September 2021

Reduced integrity of neural pathways from frontal to sensory cortices has been suggested as a potential neurobiological basis of attention-deficit hyperactivity disorder. Neurofeedback has been widely applied to enhance reduced neural pathways in attention-deficit hyperactivity disorder by repeated training on a daily temporal scale. Clinical and model-based studies have demonstrated that fluctuations in neural activity underpin sustained attention deficits in attention-deficit hyperactivity disorder. These aberrant neural fluctuations may be caused by the chaos–chaos intermittency state in frontal-sensory neural systems. Therefore, shifting the neural state from an aberrant chaos–chaos intermittency state to a normal stable state with an optimal external sensory stimulus, termed chaotic resonance, may be applied in neurofeedback for attention-deficit hyperactivity disorder. In this study, we applied a neurofeedback method based on chaotic resonance induced by “reduced region of orbit” feedback signals in the Baghdadi model for attention-deficit hyperactivity disorder. We evaluated the stabilizing effect of reduced region of orbit feedback and its robustness against noise from errors in estimation of neural activity. The effect of chaotic resonance successfully shifted the abnormal chaos-chaos intermittency of neural activity to the intended stable activity. Additionally, evaluation of the influence of noise due to measurement errors revealed that the efficiency of chaotic resonance induced by reduced region of orbit feedback signals was maintained over a range of certain noise strengths. In conclusion, applying chaotic resonance induced by reduced region of orbit feedback signals to neurofeedback methods may provide a promising treatment option for attention-deficit hyperactivity disorder.
Changes in the Care of Neurological Diseases During the First Wave of the COVID-19 Pandemic: A Single Private Center Study in Argentina
Authors: Calandri Ismael L. , Hawkes Maximiliano A. , Marrodan Mariano , Ameriso Sebastián F. , Correale Jorge , Allegri Ricardo F.
Published: September 2021

Introduction: Healthcare systems are struggling to cope with the rapid evolution of the COVID-19 pandemic. In Argentina, the pandemic is advancing despite prolonged lockdown measures. We aim to analyze the impact of the easing of lockdown measures in the number of visits to the emergency department (ED), and outpatient consultations (OC) to a tertiary neurological center.

Methods: We compared the number of ED visits with the social mobility overtime. We also compared the number of OC, and the geographic distribution of patients' addresses between 2019 and 2020.

Results: ED visits decreased 48.33% (n = 14,697 in 2019 vs. n = 7,595 in 2020). At the beginning of the lockdown, the social mobility decreased in pharmacies/groceries, and workplaces, along with a reduction in the number of ED visits. With the easing of lockdown restrictions, the social mobility decreased in residential places, slightly increased in workplaces and almost return to normal in pharmacies/groceries. Variations in ED visits correlate better with social mobility in workplaces (coef. =0.75, p < 0.001) than in groceries/pharmacies (coef. =0.68, p < 0.001). OC decreased 43%. Fourteen percent of OC were tele consults. This was associated with an increase of the geographical area of influence of our center (standard distance of 109 km in 2019 and 127 km in 2020).

Conclusions: Despite an increase in social mobility, the number of ED visits and OC to an Argentinian tertiary neurological center remain worrisomely low. The pandemic catalyzed the introduction of telemedicine in our country. This has also allowed patients from distant zones to gain access to specialized neurological care.
The Maryland Acute Stroke Emergency Medical Services Routing Pilot: Expediting Access to Thrombectomy for Stroke
Authors: Haight Taylor , Tabaac Burton , Patrice Kelly-Ann , Phipps Michael S. , Butler Jaime , Johnson Brenda , Aycock Anna , Toral Linda , Yarbrough Karen L. , Schrier Chad , Lawrence Erin , Goldszmidt Adrian , Marsh Elisabeth B. , Urrutia Victor C.
Published: September 2021

Background: Mechanical thrombectomy (MT) is the standard of care for acute ischemic stroke caused by large vessel occlusion, but is not available at all stroke centers. Transfers between hospitals lead to treatment delays. Transport directly to a facility capable of MT based on a prehospital stroke severity scale score has been recommended, if transportation time is less than 30 min.

Aims: We hypothesized that an Emergency Medical Services (EMS) routing algorithm for stroke, using the Los Angeles Motor Scale (LAMS) in the field, would improve time from last known well to MT, without causing patients to miss the IV Thrombolysis (IVT) window.

Methods: An EMS algorithm in the Baltimore metro area using the LAMS was implemented. Patients suspected of having an acute stroke were assessed by EMS using the LAMS. Patients scoring 4 or higher and within 20 h from last known well, were transported directly to a Thrombectomy Center, if transport could be completed within 30 min. The algorithm was evaluated retrospectively with prospectively collected data at the Thrombectomy Centers. The primary outcome variables were proportion of patients with suspected stroke rerouted by EMS, proportion of rerouted ischemic stroke patients receiving MT, time to treatment, and whether the IVT window was missed.

Results: A total of 303 patients were rerouted out of 2459 suspected stroke patients over a period of 6 months. Of diverted patients, 47% had acute ischemic stroke. Of these, 48% received an acute stroke treatment: 16.8% IVT, 17.5% MT, and 14% MT+IVT. Thrombectomy occurred 119 min earlier in diverted patients compared to patients transferred from other hospitals (P = 0.006). 55.3% of diverted patients undergoing MT and 38.2% of patients transferred from hospital to hospital were independent at 90 days (modified Rankin score 0–2) (P = 0.148). No patient missed the time window for IVT due to the extra travel time.

Conclusions: In this retrospective analysis of prospectively acquired data, implementation of a pre-hospital clinical screening score to detect patients with suspected acute ischemic stroke due to large vessel occlusion was feasible. Rerouting patients directly to a Thrombectomy Center, based on the EMS algorithm, led to a shorter time to thrombectomy.
Identification of Circular RNAs Related to Vascular Endothelial Proliferation, Migration, and Angiogenesis After Spinal Cord Injury Using Microarray Analysis in Female Mice
Authors: Ye Xin , Chen Yilei , Wang Jiasheng , Chen Jian , Yao Ying , Wang Lin-lin , Zhao Fengdong
Published: September 2021

Background: Traumatic spinal cord injury (SCI) can result in severe disability and causes a considerable socio-economic burden worldwide. Circular RNAs (circRNAs) are important regulators of gene expression and pathological processes, and may represent therapeutic targets for SCI. To further evaluate the role of circRNAs in SCI, we elucidated circRNA expression profiles related to vascular endothelial proliferation, migration, and angiogenesis during the early stages of secondary injury in a mouse model of SCI.

Methods: Microarray analysis was performed to investigate the circRNA expression patterns in the spinal cord 3 days after SCI in female mice. Bioinformatic analyses, including GO enrichment analysis, KEGG pathway analysis, and circRNA-miRNA-mRNA network construction, were conducted to explore the role of circRNA dysregulation in vascular endothelial proliferation, migration, and angiogenesis following SCI.

Results: The expression of 1,288 circRNAs was altered (>2-fold change, p < 0.05) in the spinal cord after SCI, consisting of 991 upregulated and 297 downregulated circRNAs. We constructed a circRNA-mRNA network to predict whether these circRNAs could act as “miRNA sponges.” We next assessed the association of altered circRNAs with vascular endothelial proliferation, migration, and angiogenesis using GO and KEGG analyses. Using this analysis, we found that a total of 121 circRNAs were correlated with vascular endothelial proliferation, migration, and angiogenesis in the spinal cord after SCI.

Conclusions: Our study provides circRNA expression profiles during the early stages of SCI. circRNA.7079, circRNA.7078, and circRNA.6777 were found to play key roles in the vascular endothelial proliferation, migration, and angiogenesis, and may represent therapeutic targets for SCI.
Social Behavior Observer Checklist: Patterns of Spontaneous Behaviors Differentiate Patients With Neurodegenerative Disease From Healthy Older Adults
Authors: Rankin Katherine P. , Toller Gianina , Gavron Lauren , La Joie Renaud , Wu Teresa , Shany-Ur Tal , Callahan Patrick , Krassner Maggie , Kramer Joel H. , Miller Bruce L.
Published: September 2021

Neurodegenerative disease syndromes often affect personality and interpersonal behavior in addition to cognition, but there are few structured observational measures of altered social demeanor validated for this population. We developed the Social Behavior Observer Checklist (SBOCL), a 3-min checklist tool, to facilitate identification of patterns of interpersonal behavior that are diagnostically relevant to different neurodegenerative syndromes. Research assistants without formal clinical training in dementia used the SBOCL to describe participants' behavior, including 125 healthy older adults and 357 patients diagnosed with one of five neurodegenerative disease syndromes: 135 behavioral variant frontotemporal dementia (bvFTD), 57 semantic variant primary progressive aphasia (svPPA), 51 non-fluent variant PPA (nfvPPA), 65 progressive supranuclear palsy (PSP), and 49 amyloid-positive Alzheimer's disease syndrome (AD), all of whom had concurrent 3D T1 MRI scans available for voxel-based morphometry analysis. SBOCL item interrater reliability ranged from moderate to very high, and score elevations showed syndrome-specific patterns. Subscale scores derived from a degree*frequency product of the items had excellent positive predictive value for identifying patients. Specifically, scores above 2 on the Disorganized subscale, and above 3 on the Reactive and Insensitive subscales, were not seen in any healthy controls but were found in many patients with bvFTD, svPPA, nfvPPA, PSP, and AD syndromes. Both the Disorganized and Reactive subscale scores showed significant linear relationships with frontal and temporal gray matter volume that generalized across syndromes. With these initial psychometric characteristics, the SBOCL may be a useful measure to help non-experts identify patients who are appropriate for additional specialized dementia evaluation, without adding time to patient encounters or requiring the presence of an informant.
Case Report: The Use of Rituximab in Antibody-Negative Autoimmune Encephalitis
Authors: Park Soo-Hyun , Kim Yong-Chan
Published: September 2021

Antibody-negative autoimmune encephalitis (AE) is challenging to diagnose because clinically suspected antibody-negative AE cases are difficult to confirm. If not treated properly, like antibody-positive AE, antibody-negative AE can cause irreparable damage to patients. Previously, immunotherapy was effective in treating patients with antibody-negative AE. We present the case of a 63-year-old man who was admitted to our hospital with altered cognition. He was diagnosed with antibody-negative AE based on CSF, brain MRI, and B-cell counts; autoimmune diseases with similar clinical symptoms were ruled out. He was treated with immunotherapy, especially rituximab, for antibody-negative AE. After 3 weeks of treatment, his mental state and brain MRI results, concomitant with a decrease in CD19+/CD20+ B-cell counts. This case report shows that patients with antibody-negative AE may respond to rituximab, similar to those with antibody-positive AE. Thus, potentially undetected antibodies could be responsible for the treatment outcome.
Needs Assessment of Safe Medicines Management for Older People With Cognitive Disorders in Home Care: An Integrative Systematic Review
Authors: Vaismoradi Mojtaba , Behboudi-Gandevani Samira , Lorenzl Stefan , Weck Christiane , Paal Piret
Published: September 2021

Background and Objectives:The global trend of healthcare is to improve the quality and safety of care for older people with cognitive disorders in their own home. There is a need to identify how medicines management for these older people who are cared by their family caregivers can be safeguarded. This integrative systematic review aimed to perform the needs assessment of medicines management for older people with cognitive disorders who receive care from their family caregivers in their own home.

Methods:An integrative systematic review of the international literature was conducted to retrieve all original qualitative and quantitative studies that involved the family caregivers of older people with cognitive disorders in medicines management in their own home. MeSH terms and relevant keywords were used to search four online databases of PubMed (including Medline), Scopus, CINAHL, and Web of Science and to retrieve studies published up to March 2021. Data were extracted by two independent researchers, and the review process was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Given that selected studies were heterogeneous in terms of the methodological structure and research outcomes, a meta-analysis could not be performed. Therefore, narrative data analysis and knowledge synthesis were performed to report the review results.

Results:The search process led to retrieving 1,241 studies, of which 12 studies were selected for data analysis and knowledge synthesis. They involved 3,890 older people with cognitive disorders and 3,465 family caregivers. Their methodologies varied and included cohort, randomised controlled trial, cross-sectional studies, grounded theory, qualitative framework analysis, and thematic analysis. The pillars that supported safe medicines management with the participation of family caregivers in home care consisted of the interconnection between older people's needs, family caregivers' role, and collaboration of multidisciplinary healthcare professionals.

Conclusion:Medicines management for older people with cognitive disorders is complex and multidimensional. This systematic review provides a comprehensive image of the interconnection between factors influencing the safety of medicines management in home care. Considering that home-based medicines management is accompanied with stress and burden in family caregivers, multidisciplinary collaboration between healthcare professionals is essential along with the empowerment of family caregivers through education and support.