bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron Deficiency and Anemia 10 Years After Roux-en-Y Gastric Bypass for Severe Obesity
Authors: Sandvik Jorunn , Bjerkan Kirsti Kverndokk , Græslie Hallvard , Hoff Dag Arne Lihaug , Johnsen Gjermund , Klöckner Christian , Mårvik Ronald , Nymo Siren , Hyldmo Åsne Ask , Kulseng Bård Eirik
Published: September 2021

Iron deficiency with or without anemia is a well-known long-term complication after Roux-en-Y, gastric bypass (RYGB) as the procedure alters the gastrointestinal absorption of iron. Iron is essential for hemoglobin synthesis and a number of cellular processes in muscles, neurons, and other organs. Ferritin is the best marker of iron status, and in a patient without inflammation, iron deficiency occurs when ferritin levels are below 15 µg/L, while iron insufficiency occurs when ferritin levels are below 50 µg/L. Lifelong regular blood tests are recommended after RYGB, but the clinical relevance of iron deficiency and iron insufficiency might be misjudged as long as the hemoglobin levels are normal. The aim of this study was to explore the frequency of iron deficiency and iron deficiency anemia one decade or more after RYGB, the use of per oral iron supplements, and the frequency of intravenous iron treatment. Nine hundred and thirty patients who underwent RYGB for severe obesity at three public hospitals in Norway in the period 2003–2009 were invited to a follow-up visit 10–15 years later. Results from blood tests and survey data on the use of oral iron supplements and intravenous iron treatment were analyzed. Ferritin and hemoglobin levels more than 10 years after RYGB were available on 530 patients [423 (79.8%) women]. Median (IQR) ferritin was 33 (16–63) µg/L, and mean (SD) hemoglobin was 13.4 (1.3) g/dl. Iron deficiency (ferritin ≤ 15 µg/L) was seen in 125 (23.6%) patients; in addition, iron insufficiency (ferritin 16–50 µg/L) occurred in 233 (44%) patients. Mean (SD) hemoglobin levels were 12.5 (1.4) g/dl in patients with iron deficiency, 13.5 (1.2) g/dl in patients with iron insufficiency, 13.8 (1.3) g/dl in the 111 (21%) patients with ferritin 51–100 µg/L, and 13.8 (1.2) g/dl in the 55 (10%) patients with ferritin >100 µg/L. Two hundred and seventy-five (56%) patients reported taking oral iron supplements, and 138 (27.5%) had received intravenous iron treatment after the RYGB procedure. Iron deficiency or iron insufficiency occurred in two-thirds of the patients 10 years after RYGB, although more than half of them reported taking oral iron supplements.
Expression of Sex Hormone Receptor and Immune Response Genes in Peripheral Blood Mononuclear Cells During the Menstrual Cycle
Authors: Brundin Peik M. A. , Landgren Britt-Marie , Fjällström Peter , Shamekh Mohamed M. , Gustafsson Jan-Åke , Johansson Anders F. , Nalvarte Ivan
Published: September 2021

Sex hormones are known to interact with the immune system on multiple levels but information on the types of sex hormone receptors (SHR) and their expression levels in immune cells is scarce. Estrogen, testosterone and progesterone are all considered to interact with the immune system through their respective cell receptors (ERα and ERβ including the splice variant ERβ2, AR and PGR). In this study expression levels of SHR genes in peripheral blood mononuclear cells (PBMCs) and cell subsets (CD4+ and CD8+ T-cells, CD56+ NK-cells, CD14+ monocytes and CD19+ B-cells) were analyzed using standard manual qPCR or a qPCR array (TLDA). Nine healthy individuals including men (n = 2), premenopausal (Pre-MP, n = 5) and postmenopausal (post-MP, n = 2) women were sampled for PBMCs which were separated to cell subsets using FACS. Ten Pre-MP women were longitudinally sampled for total PBMCs at different phases of the menstrual cycle. We found that ERα was most abundant and, unexpectedly, that ERβ2 was the dominant ERβ variant in several FACS sorted cell subsets. In total PBMCs, SHR (ERα, ERβ1, ERβ2, and AR) expression did not fluctuate according to the phase of the menstrual cycle and PGR was not expressed. However, several immune response genes (GATA3, IFNG, IL1B, LTA, NFKB1, PDCD1, STAT3, STAT5A, TBX21, TGFB1, TNFA) were more expressed during the ovulatory and mid-luteal phases. Sex hormone levels did not correlate significantly with gene expression of SHR or immune response genes, but sex hormone-binding globulin (SHBG), a steroid hormone transporting protein, was positively correlated to expression of ERβ1 gene. This study provides new insights in the distribution of ERs in immune cells. Furthermore, expression patterns of several immune response genes differ significantly between phases of the menstrual cycle, supporting a role for sex hormones in the immune response.
Research on Detection Technology of 235U Enrichment and Loading Uniformity for Nuclear Fuel Rods
Authors: Gu Mingfei , Huang Dagui , Yu Dongbao , Tang Hui , Zhu Yongli
Published: September 2021

To ensure that fuel rods operate in nuclear reactors safely and reliably, UO2 pellets with different enrichment levels of 235U in the same production line are manufactured in batches and divisionally managed to avoid confusion or the potential misloading of UO2 pellets with different enrichment levels. At the same time, nondestructive tests for their enrichment levels and loading uniformity and all UO2 pellets must be nondestructively tested during production. By studying the enrichment detection mechanism of the UO2 pellets of 235U, the design of an integral standard rod was carried out, and a single integral standard rod was used to achieve the calibration of the enrichment measurement curve, as well as the detection and calibration of abnormal pellets. This study undertook a comparison test of 235U enrichment between the neutron activation method and the array multi-probe passive method. The test results showed that the array multi-probe passive method had higher detection efficiency and equal accuracy.
Application of Machine Learning Algorithms for Geogenic Radon Potential Mapping in Danyang-Gun, South Korea
Authors: Rezaie Fatemeh , Kim Sung Won , Alizadeh Mohsen , Panahi Mahdi , Kim Hyesu , Kim Seonhong , Lee Jongchun , Lee Jungsub , Yoo Juhee , Lee Saro
Published: September 2021

Continuous generation of radon gas by soil and rocks rich in components of the uranium chain, along with prolonged inhalation of radon progeny in enclosed spaces, can lead to severe respiratory diseases. Detection of radon-prone areas and acquisition of detailed knowledge regarding relationships between indoor radon variations and geogenic factors can facilitate the implementation of more appropriate radon mitigation strategies in high-risk residential zones. In the present study, 10 factors (i.e., lithology; fault density; mean soil calcium oxide [CaO], copper [Cu], lead [Pb], and ferric oxide [Fe2O3] concentrations; elevation; slope; valley depth; and the topographic wetness index [TWI]) were selected to map radon potential areas based on measurements of indoor radon levels in 1,452 dwellings. Mapping was performed using three machine learning methods: long short-term memory (LSTM), extreme learning machine (ELM), and random vector functional link (RVFL). The results were validated in terms of the area under the receiver operating characteristic curve (AUROC), root mean square error (RMSE), and standard deviation (StD). The prediction abilities of all models were satisfactory; however, the ELM model had the best performance, with AUROC, RMSE, and StD values of 0.824, 0.209, and 0.207, respectively. Moreover, approximately 40% of the study area was covered by very high and high-risk radon potential zones that mainly included populated areas in Danyang-gun, South Korea. Therefore, the map can be used to establish more appropriate construction regulations in radon-priority areas, and identify more cost-effective remedial actions for existing buildings, thus reducing indoor radon levels and, by extension, radon exposure-associated effects on human health.
The Genomic Processes of Biological Invasions: From Invasive Species to Cancer Metastases and Back Again
Authors: Neinavaie Fargam , Ibrahim-Hashim Arig , Kramer Andrew M. , Brown Joel S. , Richards Christina L.
Published: September 2021

The concept of invasion is useful across a broad range of contexts, spanning from the fine scale landscape of cancer tumors up to the broader landscape of ecosystems. Invasion biology provides extraordinary opportunities for studying the mechanistic basis of contemporary evolution at the molecular level. Although the field of invasion genetics was established in ecology and evolution more than 50 years ago, there is still a limited understanding of how genomic level processes translate into invasive phenotypes across different taxa in response to complex environmental conditions. This is largely because the study of most invasive species is limited by information about complex genome level processes. We lack good reference genomes for most species. Rigorous studies to examine genomic processes are generally too costly. On the contrary, cancer studies are fortified with extensive resources for studying genome level dynamics and the interactions among genetic and non-genetic mechanisms. Extensive analysis of primary tumors and metastatic samples have revealed the importance of several genomic mechanisms including higher mutation rates, specific types of mutations, aneuploidy or whole genome doubling and non-genetic effects. Metastatic sites can be directly compared to primary tumor cell counterparts. At the same time, clonal dynamics shape the genomics and evolution of metastatic cancers. Clonal diversity varies by cancer type, and the tumors’ donor and recipient tissues. Still, the cancer research community has been unable to identify any common events that provide a universal predictor of “metastatic potential” which parallels findings in evolutionary ecology. Instead, invasion in cancer studies depends strongly on context, including order of events and clonal composition. The detailed studies of the behavior of a variety of human cancers promises to inform our understanding of genome level dynamics in the diversity of invasive species and provide novel insights for management.
hnRNPA2B1 Promotes Colon Cancer Progression via the MAPK Pathway
Authors: Tang Jingzhi , Chen Zhimin , Wang Qi , Hao Weijie , Gao Wei-Qiang , Xu Huiming
Published: September 2021

HNRNPA2B1, an RNA-binding protein, plays a key role in primary microRNA processing, alternative splicing, mRNA metabolism and transport. Interestingly, hnRNPA2B1 also works as an N6-methyladenosine (m6A) reader and is critical during tumorigenesis of various tissue types. However, its role in colon cancer is still unclear. In this study, we aimed to elucidate the biological functions of hnRNPA2B1 and to explore its underlying mechanisms in colon cancer. We examined the expression of hnRNPA2B1 in Oncomine and TCGA databases. Then verified the findings in colon cancer cells and clinical samples with western blotting and immunohistochemistry (IHC). We used CRISPR/Cas9 directed gene editing to knockout hnRNPA2B1 expression in human colon cancer cell line SW480 and HCT-116 and carried out both in vivo and in vitro experiments. The results were further confirmed by RNA-seq analyses. We found that hnRNPA2B1 significantly promoted colon cancer cell proliferation both in vitro and in vivo, while knockout of hnRNPA2B1 induced apoptosis and cell cycle arrest in SW480. RNA-seq analyses revealed that the ERK/MAPK pathway was activated by hnRNPA2B1 upregulation. In addition, both hnRNPA2B1 and MAPK pathway were activated in clinical colon cancer specimens and positively correlated. Mechanistically, hnRNPA2B1 appeared to be an upstream regulator of the ERK/MAPK pathway and inhibition of MAPK signaling blocked the effects of hnRNPA2B1. Taken together, our data demonstrated that the RNA-binding protein hnRNPA2B1 promotes cell proliferation and regulates cell cycle and apoptosis of human colon cancer by activating the ERK/MAPK signaling, which may provide a new insight into the development of hnRNPA2B1 as a potential therapeutic target for treatment of colon cancer.
Genetic and Environmental Determinants of T Helper 17 Pathogenicity in Spondyloarthropathies
Authors: Simone Davide , Stingo Alessia , Ciccia Francesco
Published: September 2021

In Spondyloarthropathies (SpA), a common group of immune-mediated diseases characterised by excessive inflammation of musculo-skeletal structures and extra-articular organs, T helper 17 (Th17) cells are widely considered the main drivers of the disease. Th17 are able to modulate their genes according to the immune environment: upon differentiation, they can adopt either housekeeping, anti-bacterial gene modules or inflammatory, pathogenic functions, and only the latter would mediate immune diseases, such as SpA. Experimental work aimed at characterising Th17 heterogeneity is largely performed on murine cells, for which the in vitro conditions conferring pathogenic potential have been identified and replicated. Interestingly, Th17 recognising different microorganisms are able to acquire specific cytokine signatures. An emerging area of research associates this heterogeneity to the preferential metabolic needs of the cell. In summary, the tissue environment could be determinant for the acquisition of pathogenetic features; this is particularly important at barrier sites, such as the intestine, considered one of the key target organs in SpA, and likely a site of immunological changes that initiate the disease. In this review, we briefly summarise genetic, environmental and metabolic factors that could explain how homeostatic, anti-microbial Th17 could turn into disease-causing cells in Spondyloarthritis.
Specific Deubiquitinating Enzymes Promote Host Restriction Factors Against HIV/SIV Viruses
Authors: Gao Wenying , Rui Yajuan , Li Guangquan , Zhai Chenyang , Su Jiaming , Liu Han , Zheng Wenwen , Zheng Baisong , Zhang Wenyan , Yang Yongjun , Hua Shucheng , Yu Xiaofang
Published: September 2021

Hijacking host ubiquitin pathways is essential for the replication of diverse viruses. However, the role of deubiquitinating enzymes (DUBs) in the interplay between viruses and the host is poorly characterized. Here, we demonstrate that specific DUBs are potent inhibitors of viral proteins from HIVs/simian immunodeficiency viruses (SIVs) that are involved in viral evasion of host restriction factors and viral replication. In particular, we discovered that T cell-functioning ubiquitin-specific protease 8 (USP8) is a potent and specific inhibitor of HIV-1 virion infectivity factor (Vif)-mediated apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3)G (A3G) degradation. Ectopic expression of USP8 inhibited Vif-induced A3G degradation and suppressed wild-type HIV-1 infectivity even in the presence of Vif. In addition, specific DUBs repressed Vpr-, Vpu-, and Vpx-triggered host restriction factor degradation. Our study has revealed a previously unrecognized interplay between the host’s DUBs and viral replication. Enhancing the antiviral activity of DUBs therefore represents an attractive strategy against HIVs/SIVs.
Effects of Short-Term Corticosteroid Use on Reactogenicity and Immunogenicity of the First Dose of ChAdOx1 nCoV-19 Vaccine
Authors: Yang Jinyoung , Ko Jae-Hoon , Baek Jin Yang , Hong Jinyeong , Ha Soyoung , Lee Beomki , Huh Kyungmin , Cho Sun Young , Kang Cheol-In , Chung Doo Ryeon , Kim Yae-Jean , Kang Eun-Suk , Peck Kyong Ran
Published: September 2021

The effects of corticosteroid use on the reactogenicity and immunogenicity of ChAdOx1 nCoV-19 (ChAd) vaccine were evaluated. Healthcare workers (HCWs) who took low-dose corticosteroid agents around the time of the first dose of ChAd (ChAdPd group) were recruited and the reactogenicity and immunogenicity were compared with those of ChAd (ChAd group) and BNT162b2 vaccination (BNT group) of HCWs without corticosteroid exposure. The immunogenicity was measured three weeks after vaccination using quantitative anti-SARS-CoV-2 spike protein (S) antibody electrochemiluminescence immunoassay and interferon gamma (IFN-γ) release assay. A total of 67 HCWs comprising 24 ChAd, 29 BNT, and 14 ChAdPd was included. The median total corticosteroid dose of the ChAdPd group was 30 mg prednisolone equivalents (interquartile range (IQR) 20–71.3 mg). HCWs in the ChAdPd group experienced significantly milder reactogenicity (median total score 7.5, IQR 4.0–18.0) compared to those in the ChAd group (median 23.0, IQR 8.0–43.0,P=0.012) but similar to that in the BNT group (median 5.0, IQR 3.0–9.0,P=0.067). The S antibody concentration of the ChAdPd group (62.4 ± 70.0 U/mL) was higher than that of the ChAd group, though without statistical significance (3.45 ± 57.6 U/mL,P=0.192). The cellular immune response was most robust in the ChAdPd group, with significantly higher IFN-γ concentration (5.363 ± 4.276 IU/mL), compared to the ChAd (0.978 ± 1.181 IU/mL,P=0.002) and BNT (1.656 ± 1.925 IU/mL,P=0.009) groups. This finding suggest that short-term corticosteroid reduces reactogenicity of the first dose of ChAd without hindering immunogenicity.
Fish Assemblages Associated With Oil and Gas Platforms in the Gulf of Thailand
Authors: Harvey Euan S. , Watts Stephanie L. , Saunders Benjamin J. , Driessen Damon , Fullwood Laura A. F. , Bunce Michael , Songploy Se , Kettratad Jes , Sitaworawet Paweena , Chaiyakul Sarin , Elsdon Travis S. , Marnane Michael J.
Published: September 2021

Decommissioning of offshore oil and gas structures is either occurring, or imminent in most regions of the world. Most jurisdictions require that offshore structures be removed for onshore disposal. However, there is growing interest in understanding the ecological and socio-economic benefits of leaving structures in the water. Descriptions of how fish utilize the vertical structure created by wellhead platform jackets (platforms) will provide insights into possible outcomes of decommissioning alternatives, such as full removal, leave in situ, or translocation to a designated reefing site. We surveyed fish assemblages associated with seven platforms and five reference sites located ∼150 km offshore in the central Gulf of Thailand. The platforms spanned the entire water column (∼75 m) and were a mix of three and four legged structures. We used a Remotely Operated Vehicle (ROV) fitted with an underwater stereo video system to quantify the abundance, size, biomass, and economic value of fish associated with the platforms. We recorded 43 species of fish on the platforms and five reference sites with most fishes on platforms categorized as coral-reef or coral-reef-associated species. We observed a strong vertical zonation in the fish assemblage on the platforms. The Regal demoiselle (Neopomacentrus cyanomos) was numerically dominant (75% of all fish observed). We measured 3,933 kg of fish on the platforms with Caranx sexfasciatus accounting for 76.12% of that. We conservatively estimate each platform had a scaled mean biomass of ∼2,927 kg and the fished species had scaled mean economic value of 175,500 Thai Baht per platform. We estimated that the biomass of fish associated with the seven platforms was at least four times higher per unit area than some of the world’s most productive coral reefs.
Hyperuricemia in Psoriatic Arthritis: Epidemiology, Pathophysiology, and Clinical Implications
Authors: Tripolino Cesare , Ciaffi Jacopo , Ruscitti Piero , Giacomelli Roberto , Meliconi Riccardo , Ursini Francesco
Published: September 2021

Psoriatic arthritis (PsA) represents the articular component of the systemic psoriatic disease and the extra-cutaneous disorder most frequently found in patients with psoriasis. Besides the articular involvement, PsA is associated with several metabolic abnormalities such as insulin resistance, hypertension, diabetes and hyperuricemia. Uric acid is the final product of purine metabolism and the etiological substrate of gout. Accumulating evidence highlights the emerging role of hyperuricemia as a major cardiovascular risk factor. Moreover, different studies evaluated the interplay between hyperuricemia and psoriatic disease, suggesting that individuals affected by psoriasis or PsA might present higher serum levels of uric acid and that hyperuricemia might affect severity of clinical manifestations and degree of inflammation in PsA patients. In this review, we focus on the bidirectional relationship between uric acid and PsA, analyzing how uric acid may be involved in the pathogenesis of psoriasis/PsA and how clinical manifestations of PsA and inflammatory mediators are affected by uric acid concentrations. Finally, the effects of anti-rheumatic drugs on uric acid levels and the potential benefit of urate-lowering therapies on psoriasis and PsA were summarized.
Moniliophthora perniciosa, the Causal Agent of Cacao Witches’ Broom Disease Is Killed in vitro by Saccharomyces cerevisiae and Wickerhamomyces anomalus Yeasts
Authors: Ferraz Pedro , Brandão Rogelio Lopes , Cássio Fernanda , Lucas Cândida
Published: September 2021

Cacao plantations from South America have been afflicted with the severe fungal disease known as Witches’ Broom Disease (WBD), caused by the basidiomycete Moniliophthora perniciosa. Yeasts are increasingly recognized as good fungal biocides, although their application is still mostly restricted to the postharvest control of plant and fruit decay. Their possible utilization in the field, in a preharvest phase, is nevertheless promising, particularly if the strains are locally adapted and evolved and if they belong to species considered safe for man and the environment. In this work, a group of yeast strains originating from sugarcane-based fermentative processes in Brazil, the cacao-producing country where the disease is most severe, were tested for their ability to antagonize M. perniciosa in vitro. Wickerhamomyces anomalus LBCM1105 and Saccharomyces cerevisiae strains LBCM1112 from spontaneous fermentations used to produce cachaça, and PE2 widely used in Brazil in the industrial production of bioethanol, efficiently antagonized six strains of M. perniciosa, originating from several South American countries. The two fastest growing fungal strains, both originating from Brazil, were further used to assess the mechanisms underlying the yeasts’ antagonism. Yeasts were able to inhibit fungal growth and kill the fungus at three different temperatures, under starvation, at different culture stages, or using an inoculum from old yeast cultures. Moreover, SEM analysis revealed that W. anomalus and S. cerevisiae PE2 cluster and adhere to the hyphae, push their surface, and fuse to them, ultimately draining the cells. This behavior concurs with that classified as necrotrophic parasitism/mycoparasitism. In particular, W. anomalus within the adhered clusters appear to be ligated to each other through roundish groups of fimbriae-like structures filled with bundles of microtubule-sized formations, which appear to close after cells detach, leaving a scar. SEM also revealed the formation of tube-like structures apparently connecting yeast to hypha. This evidence suggests W. anomalus cells form a network of yeast cells connecting with each other and with hyphae, supporting a possible cooperative collective killing and feeding strategy. The present results provide an initial step toward the formulation of a new eco-friendly and effective alternative for controlling cacao WBD using live yeast biocides.
Transmission of Bacterial Symbionts With and Without Genome Erosion Between a Beetle Host and the Plant Environment
Authors: Wierz Jürgen C. , Gaube Paul , Klebsch Dagmar , Kaltenpoth Martin , Flórez Laura V.
Published: September 2021

Many phytophagous insects harbor symbiotic bacteria that can be transmitted vertically from parents to offspring, or acquired horizontally from unrelated hosts or the environment. In the latter case, plants are a potential route for symbiont transfer and can thus foster a tripartite interaction between microbe, insect, and plant. Here, we focus on two bacterial symbionts of the darkling beetle Lagria villosa that belong to the genus Burkholderia; the culturable strain B. gladioli Lv-StA and the reduced-genome strain Burkholderia Lv-StB. The strains can be transmitted vertically and confer protection to the beetle’s eggs, but Lv-StA can also proliferate in plants, and both symbiont strains have presumably evolved from plant pathogens. Notably, little is known about the role of the environment for the transmission dynamics and the maintenance of the symbionts. Through manipulative assays, we demonstrate the transfer of the symbionts from the beetle to wheat, rice and soybean plants, as well as leaf litter. In addition, we confirm that aposymbiotic larvae can pick up Lv-StA from dry leaves and the symbiont can successfully establish in the beetle’s symbiotic organs. Also, we show that the presence of plants and soil in the environment improves symbiont maintenance. These results indicate that the symbionts of L. villosa beetles are still capable of interacting with plants despite signatures of genome erosion and suggest that a mixed-mode of bacterial transmission is likely key for the persistence of the symbiosis.
RNA Therapeutics - Research and Clinical Advancements
Authors: Feng Rundong , Patil Suryaji , Zhao Xin , Miao Zhiping , Qian Airong
Published: September 2021

RNA therapeutics involve the use of coding RNA such as mRNA as well as non-coding RNAs such as small interfering RNAs (siRNA), antisense oligonucleotides (ASO) to target mRNA, aptamers, ribozymes, and clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR/Cas) endonuclease to target proteins and DNA. Due to their diverse targeting ability and research in RNA modification and delivery systems, RNA-based formulations have emerged as suitable treatment options for many diseases. Therefore, in this article, we have summarized different RNA therapeutics, their targeting strategies, and clinical progress for various diseases as well as limitations; so that it might help researchers formulate new and advanced RNA therapeutics for various diseases. Additionally, U.S. Food and Drug Administration (USFDA)-approved RNA-based therapeutics have also been discussed.
Detection of Cerebrospinal Fluid Neurofilament Light Chain as a Marker for Alpha-Synucleinopathies
Authors: Canaslan Sezgi , Schmitz Matthias , Villar-Piqué Anna , Maass Fabian , Gmitterová Karin , Varges Daniela , Lingor Paul , Llorens Franc , Hermann Peter , Zerr Inga
Published: September 2021

Alpha-synucleinopathies, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are a class of neurodegenerative diseases. A diagnosis may be challenging because clinical symptoms partially overlap, and there is currently no reliable diagnostic test available. Therefore, we aimed to identify a suitable marker protein in cerebrospinal fluid (CSF) to distinguish either between different types of alpha-synucleinopathies or between alpha-synucleinopathies and controls. In this study, the regulation of different marker protein candidates, such as alpha-synuclein (a-Syn), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and total tau (tau) in different types of alpha-synucleinopathies, had been analyzed by using an ultrasensitive test system called single-molecule array (SIMOA). Interestingly, we observed that CSF-NfL was significantly elevated in patients with DLB and MSA compared to patients with PD or control donors. To differentiate between groups, receiver operating characteristic (ROC) curve analysis resulted in a very good diagnostic accuracy as indicated by the area under the curve (AUC) values of 0.87–0.92 for CSF-NfL. Furthermore, we observed that GFAP and tau were slightly increased either in DLB or MSA, while a-Syn levels remained unregulated. Our study suggests NfL as a promising marker to discriminate between different types of alpha-synucleinopathies or between DLB/MSA and controls.
What Is the Role of Thalamostriatal Circuits in Learning Vocal Sequences?
Authors: Xiao Lei , Roberts Todd F.
Published: September 2021

Basal ganglia (BG) circuits integrate sensory and motor-related information from the cortex, thalamus, and midbrain to guide learning and production of motor sequences. Birdsong, like speech, is comprised of precisely sequenced vocal elements. Learning song sequences during development relies on Area X, a vocalization related region in the medial striatum of the songbird BG. Area X receives inputs from cortical-like pallial song circuits and midbrain dopaminergic circuits and sends projections to the thalamus. It has recently been shown that thalamic circuits also send substantial projections back to Area X. Here, we outline a gated-reinforcement learning model for how Area X may use signals conveyed by thalamostriatal inputs to direct song learning. Integrating conceptual advances from recent mammalian and songbird literature, we hypothesize that thalamostriatal pathways convey signals linked to song syllable onsets and offsets and influence striatal circuit plasticityviaregulation of cholinergic interneurons (ChIs). We suggest that syllable sequence associated vocal-motor information from the thalamus drive precisely timed pauses in ChIs activity in Area X. When integrated with concurrent corticostriatal and dopaminergic input, this circuit helps regulate plasticity on medium spiny neurons (MSNs) and the learning of syllable sequences. We discuss new approaches that can be applied to test core ideas of this model and how associated insights may provide a framework for understanding the function of BG circuits in learning motor sequences.
Early Treatment of Ruptured Blood Blister-Like Aneurysms of the Internal Carotid Artery With Flow Diverters Using Single Antiplatelet Therapy: A Single-Center Experience With Long-Term Follow-Up
Authors: Tanburoglu Anil , Andic Cagatay
Published: September 2021

Background and Purpose: Blood Blister-like aneurysms (BBAs) of the internal carotid artery (ICA) are rare entities of cerebral aneurysms. FD use in acutely ruptured aneurysms, timing of treatment and antiplatelet regimen are main debate topics in clinical practice when the treatment decision is flow diversion. The aim of this study is to report the safety and efficacy of a single-center FD treatment for ruptured BBAs in the early phase of SAH using the SAPT regimen.

Material and Method: This study involved a retrospective analysis of a prospectively collected database. Records of patients admitted to our clinic and treated by endovascular route on ruptured BBA between January 2013 and December 2020 were reviewed. Ruptured supraclinoid ICA BBAs treated with FD devices with SAPT within 48 h from ictus of SAH are included. BBA of atypical anatomic locations, other endovascular techniques performed, and delayed admissions (>48 h) were excluded from the study. Demographic, clinical and angiographic features of patients and aneurysms, FD types and numbers, periprocedural complications, immediate and follow-up angiographic and clinical outcomes were recorded.

Results: A total of six patients with ruptured BBAs treated via FDs within 48 h and used SAPT were included in the study. The mean age was 41.6 years (range from 34 to 45 years), and four of six patients were female. All patients were treated within 48 h after ictus, and the mean treatment day was 1.33 days. One patient received ticagrelor, and five patients received prasugrel as SAPT for one year after treatment. No procedure-related death and rebleeding were recorded. One (16.7 %) treatment responsive procedure-related complication occurred (transient ischemia). Overall good outcome rate was 83.3%. One patient died due to pneumonia. The immediate control angiograms showed complete occlusions of BBAs in one patient (16.6%). The complete occlusion rate was 100 % for five survivors at the control angiogram. The median follow-up was 49.5 months.

Conclusion: This single-center experience suggests that early treatment (<2 days) within SAH of ruptured BBAs with FDs using SAPT is safe and effective in terms of clinical and radiological long-term outcomes.
Superficial Macula Capillary Complexity Changes Are Associated With Disability in Neuromyelitis Optica Spectrum Disorders
Authors: Wei Ruili , Xie Jianyang , Wu Huihui , He Fangping , Meng Fangxia , Liu Jiang , Liang Hui , Zhao Yitian
Published: September 2021

Purpose: We examined the macular microvascular changes of the macula in neuromyelitis optica spectrum disorder (NMOSD) patients and its association with their disability and other clinical variables.

Methods: Thirty-four NMOSD (13 patients without optic neuritis, NMOSD-NON, and 21 patients with a history of optic neuritis, NMOSD-ON) and 44 healthy controls (HCs) were included in the study. Optical coherence tomographic angiography (OCTA) was used to image the superficial (SCP), deep (DCP), and whole capillary plexus (WCP) in a 2.5-mm-diameter concentric circle [excluding the foveal avascular zone (FAZ)]. An algorithm (Dbox) was used to quantify the complexity of the three capillary layers by fractal analysis. We also evaluated the expanded disability scale status (EDSS).

Results: Dbox values were significantly reduced in SCP (p < 0.001), DCP (p < 0.001), and WCP (p = 0.003) of NMOSD when compared with HCs. Dbox values were significantly reduced in NMOSD eyes with optic neuritis when compared with healthy controls (p < 0.001) and eyes without optic neuritis (p = 0.004) in the SCP. In the DCP, eyes with optic neuritis showed significantly reduced Dbox values when compared with eyes without optic neuritis (p = 0.016) and healthy controls (p < 0.001); eyes without optic neuritis showed significantly reduced Dbox values (p = 0.007) in the DCP when compared with healthy controls. A significant negative correlation (Rho = −0.475, p = 0.005) was shown between the superficial macula Dbox values and the EDSS in NMOSD patients. Additionally, a negative correlation (Rho = −0.715, p = 0.006) was seen in the superficial Dbox values in [e]eyes without optic neuritis and EDSS.

Conclusions: Macular microvascular damage in the superficial plexus is associated with disability in NMOSD. Macular microvascular alterations arise independently of the occurrence of ON in NMOSD.
Cognitive and Emotional Appraisal of Motivational Interviewing Statements: An Event-Related Potential Study
Authors: Hui Karen Y. L. , Wong Clive H. Y. , Siu Andrew M. H. , Lee Tatia M. C. , Chan Chetwyn C. H.
Published: September 2021

The counseling process involves attention, emotional perception, cognitive appraisal, and decision-making. This study aimed to investigate cognitive appraisal and the associated emotional processes when reading short therapists' statements of motivational interviewing (MI). Thirty participants with work injuries were classified into the pre-contemplation (PC,n= 15) or readiness stage of the change group (RD,n= 15). The participants viewed MI congruent (MI-C), MI incongruent (MI-INC), or control phrases during which their electroencephalograms were captured. The results indicated significant Group × Condition effects in the frontally oriented late positive complex (P600/LPC). The P600/LPC's amplitudes were more positive-going in the PC than in the RD group for the MI congruent statements. Within the PC group, the amplitudes of the N400 were significantly correlated (r= 0.607–0.649) with the participants' level of negative affect. Our findings suggest that the brief contents of MI statements alone can elicit late cognitive and emotional appraisal processes beyond semantic processing.
Retinal Vasculopathy in Alzheimer’s Disease
Authors: Shi Haoshen , Koronyo Yosef , Rentsendorj Altan , Fuchs Dieu-Trang , Sheyn Julia , Black Keith L. , Mirzaei Nazanin , Koronyo-Hamaoui Maya
Published: September 2021

The retina has been increasingly investigated as a site of Alzheimer’s disease (AD) manifestation for over a decade. Early reports documented degeneration of retinal ganglion cells and their axonal projections. Our group provided the first evidence of the key pathological hallmarks of AD, amyloid β-protein (Aβ) plaques including vascular Aβ deposits, in the retina of AD and mild cognitively impaired (MCI) patients. Subsequent studies validated these findings and further identified electroretinography and vision deficits, retinal (p)tau and inflammation, intracellular Aβ accumulation, and retinal ganglion cell-subtype degeneration surrounding Aβ plaques in these patients. Our data suggest that the brain and retina follow a similar trajectory during AD progression, probably due to their common embryonic origin and anatomical proximity. However, the retina is the only CNS organ feasible for direct, repeated, and non-invasive ophthalmic examination with ultra-high spatial resolution and sensitivity. Neurovascular unit integrity is key to maintaining normal CNS function and cerebral vascular abnormalities are increasingly recognized as early and pivotal factors driving cognitive impairment in AD. Likewise, retinal vascular abnormalities such as changes in vessel density and fractal dimensions, blood flow, foveal avascular zone, curvature tortuosity, and arteriole-to-venule ratio were described in AD patients including early-stage cases. A rapidly growing number of reports have suggested that cerebral and retinal vasculopathy are tightly associated with cognitive deficits in AD patients and animal models. Importantly, we recently identified early and progressive deficiency in retinal vascular platelet-derived growth factor receptor-β (PDGFRβ) expression and pericyte loss that were associated with retinal vascular amyloidosis and cerebral amyloid angiopathy in MCI and AD patients. Other studies utilizing optical coherence tomography (OCT), retinal amyloid-fluorescence imaging and retinal hyperspectral imaging have made significant progress in visualizing and quantifying AD pathology through the retina. With new advances in OCT angiography, OCT leakage, scanning laser microscopy, fluorescein angiography and adaptive optics imaging, future studies focusing on retinal vascular AD pathologies could transform non-invasive pre-clinical AD diagnosis and monitoring.
Impact of Branched Chain Amino Acid on Muscle Mass, Muscle Strength, Physical Performance, Combined Survival, and Maintenance of Liver Function Changes in Laboratory and Prognostic Markers on Sarcopenic Patients With Liver Cirrhosis (BCAAS Study): A Randomized Clinical Trial
Authors: Singh Tejavath Arun , Mathur Amit , Nathiya Deepak , Singh Pratima , Raj Preeti , Suman Supriya , Mundada Payal Ramakant , Atif Sheikh , Rai Ramesh Roop , Tomar Balvir Singh
Published: September 2021

Background: This study aimed to investigate the long-term effects of branched-chain amino acids (BCAAs) supplementations on the parameters associated with improved prognosis in sarcopenic patients with liver cirrhosis (LC) and evaluate its impact on cirrhotic-related events.

Methods: A 24-week, single-center, randomized, open-label, controlled, two cohort parallel-group intervention study was carried out by comparing the efficacy of BCAAs against lactoalbumin (L-ALB) on 106 sarcopenic patients with LC. The BCAA (intervention) group was treated with 7.2 g BCAA per dose, whereas the L-ALB group was treated with 6.3 g of L-ALB. The primary outcome was to assess the effect of BCAA on the parameters of sarcopenia, such as muscle mass, muscle strength, and physical performance. The secondary outcomes were to study the combined survival and maintenance of liver function changes in laboratory and prognostic markers over the duration of 6 months.

Results: The treatment with BCAA leads to the significant improvement in sarcopenic parameters, such as muscle strength, muscle function, and muscle mass. The total cirrhotic-related complications and cumulative event-free survival occurred fewer in the BCAA group than in the L-ALB group. In addition, prognostic markers improved significantly in the study.

Conclusion: The current study demonstrated that long-term BCAAs supplementation improved sarcopenia and prognostic markers in patients with advanced LC.
Profiles of Odd- and Branched-Chain Fatty Acids and Their Correlations With Rumen Fermentation Parameters, Microbial Protein Synthesis, and Bacterial Populations Based on Pure Carbohydrate Incubation in vitro
Authors: Xin Hangshu , Khan Nazir Ahmad , Liu Xin , Jiang Xin , Sun Fang , Zhang Shuzhi , Sun Yukun , Zhang Yonggen , Li Xiang
Published: September 2021

The objectives of this study were to evaluate changes in profiles of odd- and branched-chain fatty acids (OBCFA), including pentadecanoic acid (C15:0), 13-methyltetradecanoic acid (iso-C15:0), 12-methyltetradecanoic acid (anteiso-C15:0), 14-methylpentadecanoic acid (iso-C16:0), heptadecanoic acid (C17:0), 15-methylhexadecanoic acid (iso-C17:0), and 14-methylhexadecanoic acid (anteiso-C17:0) during in vitro fermentation of pure carbohydrates mixtures in the buffer-rumen fluid. The second objective was to correlate the changes in the OBCFA profile to the corresponding changes in ruminal fermentation parameters, microbial crude protein (MCP) synthesis, and bacterial populations. Five pure carbohydrates mixtures containing different cellulose: starch (C:S) ratios, i.e., 0:100, 25:75, 50:50, 75:25, and 100:0, were incubated for 6, 12, 18, and 24 h in vitro. The results showed that there was significant interaction (P < 0.05) between C:S and incubation time for changes in all OBCFA profiles, except iso-C17:0. The highest concentration of total OBCFA (3.94 mg/g dry matter; DM) was observed in the residues after 24 h of fermentation when the C:S was 0:100, while the lowest concentration of OBCFA (1.65 mg/g DM) was produced after 6 h of incubation when the C:S was 50:50. The correlation analysis revealed that the concentration of iso-C16:0 might be a potential marker for the estimation of total volatile fatty acids (ρ = 0.78) and MCP synthesis (ρ = 0.82) in the rumen. Compared to starch degrading bacteria, cellulolytic bacteria had stronger correlations with OBCFA concentrations, and the strongest correlation was found between the population of Ruminococcus flavefaciens with C15:0 concentration (ρ = 0.70). Notably, this is the first paper reporting relationship between OBCFA with rumen fermentation products and microbial protein synthesis based on fermentation of pure carbohydrates mixtures in vitro, and thus avoid confounding interference from dietary protein and fat presence in the in vivo studies. However, more in-depth experiments are needed to substantiate the current findings.
Role of 18F-FDG-PET/CT in Combination With Neutrophil–Lymphocyte Ratio in the Diagnosis of Upper Urinary Tract Lesion: Can We Accurately Predict Malignant Tumor?
Authors: Ke Zhi-Bin , Lin Xiao-Dan , Chen Ye-Hui , Lin Yun-Zhi , Chen Shao-Hao , Chen Shao-Ming , Chen Yu , Wei Yong , Zheng Qing-Shui , Xue Xue-Yi , Li Xiao-Dong , Xu Ning
Published: September 2021

Objective

To explore whether preoperative 18Fluorine-Fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) in combination with neutrophil–lymphocyte ratio (NLR) could accurately predict malignant lesions of upper urinary tract (UUT).

Methods and Materials

The clinicopathologic data of a total of 252 patients with UUT lesions receiving surgical treatment at our center from January 2012 to November 2019 were retrospectively analyzed. All patients performed routine preoperative hematological examination, urine cytology, computed tomography urography (CTU), and 18F-FDG-PET/CT. Clinicopathologic data between 179 cases with malignancy (Group 1) and 73 cases with benign lesions (Group 2) were compared. Multivariate logistic regression analysis was used to explore the independent predictors of malignant UUT lesions. Receiver operating characteristic (ROC) curve was used to evaluate the predictive ability.

Results

Among all patients, univariate analysis showed that NLR, hydronephrosis, CTU indicating malignancy, and PET/CT indicating malignancy were significantly associated with malignant UUT lesions; multivariate analysis revealed that NLR, CTU indicating malignancy, and PET/CT indicating malignancy were independent predictors of malignant UUT lesions; the area under ROC curve (AUC) of NLR, CTU, PET/CT, combining CTU and NLR, combining PET/CT and NLR, and combining PET/CT and CTU were 0.735, 0.788, 0.857, 0.863, 0.913, and 0.919, respectively, for postoperative pathological malignancy. Among 68 patients undergoing ureteroscopy biopsy, univariate analysis suggested that NLR, positive urine exfoliation cytology, CTU indicating malignancy, and PET/CT indicating malignancy were significantly associated with malignant UUT lesions; multivariate analysis demonstrated that positive urine cytology, PET/CT indicating malignancy, and NLR were independent predictors of malignant UUT lesions; the AUC of NLR, ureteroscopy biopsy, and combining PET/CT and NLR were 0.768, 0.853, and 0.839, respectively, for postoperative pathological malignancy.

Conclusions

Combining preoperative NLR and PET/CT performed well in differentiating benign from malignant UUT lesions, which could not be identified by traditional imaging or urine cytology. Combining preoperative NLR and PET/CT could be used to reduce unnecessary ureteroscopy biopsy, which might result in tumor cell dissemination and risk of associated complications.
Comparative Study of Pulmonary Combined Large-Cell Neuroendocrine Carcinoma and Combined Small-Cell Carcinoma in Surgically Resected High-Grade Neuroendocrine Tumors of the Lung
Authors: Wang Yanan , Qian Fangfei , Chen Ya , Yang Zhengyu , Hu Minjuan , Lu Jun , Zhang Yanwei , Zhang Wei , Cheng Lei , Han Baohui
Published: September 2021

Objectives

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) are both classified as pure and combined subtypes. Due to the low incidence and difficult diagnosis of combined LCNEC (C-LCNEC) and combined SCLC (C-SCLC), few studies have compared their clinical features and prognosis.

Materials and Methods

We compared the clinical features, mutation status of driver genes (EGFR, ALK, ROS1, KRAS, and BRAF), and prognosis between C-LCNEC and C-SCLC. Univariate and multivariate Cox regression analyses were applied for survival analysis.

Results

We included a total of 116 patients with C-LCNEC and 76 patients with C-SCLC in the present study. There were significant differences in distribution of smoking history, tumor location, pT stage, pN stage, pTNM stage, visceral pleural invasion (VPI), and combined components between C-LCNEC and C-SCLC (P<0.05 for all). C-SCLC was more advanced at diagnosis as compared to C-LCNEC. The incidence of EGFR mutations in C-LCNEC patients was higher than C-SCLC patients (25.7 vs. 5%, P=0.004). We found that tumor size, pN stage, peripheral CEA level, and adjuvant chemotherapy were independently prognostic factors for DFS and OS in C-LCNEC patients, while peripheral NSE level, pT stage, pN stage, VPI and adjuvant chemotherapy were independently associated with DFS and OS for C-SCLC patients (P<0.05 for all). Propensity score matching with adjustment for the confounders confirmed a more favorable DFS (P=0.032) and OS (P=0.019) in patients with C-LCNEC in comparison with C-SCLC patients upon survival analysis.

Conclusions

The mutation landscape of driver genes seemed to act in different way between C-SCLC and C-LCNEC, likely by which result in clinical phenotype difference as well as better outcome in C-LCNEC.