bluuebunny/crossref_metadata_2025 huggingface dataset:
Stable Water Isotope Assessment of Tundra Wetland Hydrology as a Potential Source of Arctic Riverine Dissolved Organic Carbon in the Indigirka River Lowland, Northeastern Siberia
Authors: Takano Shinya , Yamashita Youhei , Tei Shunsuke , Liang Maochang , Shingubara Ryo , Morozumi Tomoki , Maximov Trofim C. , Sugimoto Atsuko
Published: July 2021

Arctic tundra wetlands may be an important source of dissolved organic carbon (DOC) in Arctic rivers and the Arctic Ocean under global warming. We investigated stable water isotopes and DOC concentration in wetlands, tributaries, and the mainstream at the lower reaches of the Indigirka River in northeastern Siberia during the summers of 2010–2014 to assess the complex hydrology and role of wetlands as sources of riverine DOC. The wetlands had higher values of δ18O and DOC concentration than the tributaries and mainstream of the Indigirka River. A relationship between the two parameters was observed in the wetlands, tributaries, and mainstream, suggesting the wetlands can be a source of DOC for the mainstream through the tributaries. The combined temporal variations in riverine δ18O and DOC concentration indicate the mainstream water flowed into the tributaries during relatively high river-level periods in summer, whereas high DOC water in the downstream wetlands could be discharged to the mainstream through the tributaries during the low river-level periods. A minor fraction (7–13%) of riverine and wetland DOC was degraded during 40 days of dark incubation. Overall, the downstream wetlands potentially provide relatively less biodegradable DOC to the Arctic river and costal ecosystem during the low river-level periods—from late summer to autumn.
Monogenic Diabetes Modeling: In Vitro Pancreatic Differentiation From Human Pluripotent Stem Cells Gains Momentum
Authors: Burgos Juan Ignacio , Vallier Ludovic , Rodríguez-Seguí Santiago A.
Published: July 2021

The occurrence of diabetes mellitus is characterized by pancreatic β cell loss and chronic hyperglycemia. While Type 1 and Type 2 diabetes are the most common types, rarer forms involve mutations affecting a single gene. This characteristic has made monogenic diabetes an interesting disease group to model in vitro using human pluripotent stem cells (hPSCs). By altering the genotype of the original hPSCs or by deriving human induced pluripotent stem cells (hiPSCs) from patients with monogenic diabetes, changes in the outcome of the in vitro differentiation protocol can be analyzed in detail to infer the regulatory mechanisms affected by the disease-associated genes. This approach has been so far applied to a diversity of genes/diseases and uncovered new mechanisms. The focus of the present review is to discuss the latest findings obtained by modeling monogenic diabetes using hPSC-derived pancreatic cells generated in vitro. We will specifically focus on the interpretation of these studies, the advantages and limitations of the models used, and the future perspectives for improvement.
GAS1: A New β-Glucan Immunostimulant Candidate to Increase Rainbow Trout (Oncorhynchus mykiss) Resistance to Bacterial Infections With Aeromonas salmonicida achromogenes
Authors: Cornet Valérie , Khuyen Trinh Dinh , Mandiki Syaghalirwa. N. M. , Betoulle Stéphane , Bossier Peter , Reyes-López Felipe E. , Tort Lluis , Kestemont Patrick
Published: July 2021

β-glucans are prebiotic and/or food additives used by the aquaculture industry to enhance the immune response of fish. Their efficiency may vary according to their origin and structure. In this study, the immunostimulant effects of two β-glucan types extracted from wild-type baker’s yeast (Saccharomyces cerevisiae) and its null-mutant Gas1 were investigated. Gas1 has a beta-1,3-glucanosyltransferase activity necessary for cell wall assembly. Using a positive (commercial product MacroGard®) and a negative control (a diet without glucans), we evaluated the immune responses and disease resistance of rainbow trout juveniles (mean weight, ~44 g) fed control, low (0.2%) and high (0.5%) doses of Macrogard®, Gas1, and Wild type-β-glucan after a short-term (15 days, D15) or mid-term (36 days, D36) feeding periods. We found that β-glucan supplemented diets did not affect growth performance, mortality, splenic index, or leukocyte respiratory burst activity on D15 nor D36. However, each β-glucan triggered different immune effectors, depending of the doses or length of exposure compared to others and/or the negative control. Indeed, high dose of MacroGard® significantly increased lysozyme activities at D15 compared with the control and other diets (p<0.05). At D36, MacroGard β-glucan enhanced the production of lymphocytes in comparison with the control diet (p<0.05). Regarding WT β-glucan, at D36, WT-β-glucan, especially the high dose, provided the highest enzymatic activities (lysozyme and ACH50) and Ig level (p<0.01). Furthermore, on D36, Gas1 also increased lysozyme activity, Ig proportion, and some immune genes (mcsfra, hepcidin) compared with MacroGard® (p<0.05). Besides, both doses of Gas1-β-glucans increased the resistance of juveniles to bacterial infection highlighted by a higher survival rate at 14 days post-challenge compared with the control and other types and doses of β-glucans (p<0.05). In conclusion, our results suggest that Gas1-β-glucan could represent a promising immunostimulant that would help to prevent diseases in aquaculture even more efficiently than other β-glucans already in use. Mode of action and particular efficiency of this new Gas1 mutant are debated.
Long Non-Coding RNAs in the Tumor Immune Microenvironment: Biological Properties and Therapeutic Potential
Authors: Pi Ya-Nan , Qi Wen-Cai , Xia Bai-Rong , Lou Ge , Jin Wei-Lin
Published: July 2021

Cancer immunotherapy (CIT) is considered a revolutionary advance in the fight against cancer. The complexity of the immune microenvironment determines the success or failure of CIT. Long non-coding RNA (lncRNA) is an extremely versatile molecule that can interact with RNA, DNA, or proteins to promote or inhibit the expression of protein-coding genes. LncRNAs are expressed in many different types of immune cells and regulate both innate and adaptive immunity. Recent studies have shown that the discovery of lncRNAs provides a novel perspective for studying the regulation of the tumor immune microenvironment (TIME). Tumor cells and the associated microenvironment can change to escape recognition and elimination by the immune system. LncRNA induces the formation of an immunosuppressive microenvironment through related pathways, thereby controlling the escape of tumors from immune surveillance and promoting the development of metastasis and drug resistance. Using lncRNA as a therapeutic target provides a strategy for studying and improving the efficacy of immunotherapy.
m6A mRNA Methylation Regulates Epithelial Innate Antimicrobial Defense Against Cryptosporidial Infection
Authors: Xia Zijie , Xu Jihao , Lu Eugene , He Wei , Deng Silu , Gong Ai-Yu , Strass-Soukup Juliane , Martins Gislaine A. , Lu Guoqing , Chen Xian-Ming
Published: July 2021

Increasing evidence supports that N6-methyladenosine (m6A) mRNA modification may play an important role in regulating immune responses. Intestinal epithelial cells orchestrate gastrointestinal mucosal innate defense to microbial infection, but underlying mechanisms are still not fully understood. In this study, we present data demonstrating significant alterations in the topology of host m6A mRNA methylome in intestinal epithelial cells following infection by Cryptosporidium parvum, a coccidian parasite that infects the gastrointestinal epithelium and causes a self-limited disease in immunocompetent individuals but a life-threatening diarrheal disease in AIDS patients. Altered m6A methylation in mRNAs in intestinal epithelial cells following C. parvum infection is associated with downregulation of alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 and the fat mass and obesity-associated protein with the involvement of NF-кB signaling. Functionally, m6A methylation statuses influence intestinal epithelial innate defense against C. parvum infection. Specifically, expression levels of immune-related genes, such as the immunity-related GTPase family M member 2 and interferon gamma induced GTPase, are increased in infected cells with a decreased m6A mRNA methylation. Our data support that intestinal epithelial cells display significant alterations in the topology of their m6A mRNA methylome in response to C. parvum infection with the involvement of activation of the NF-кB signaling pathway, a process that modulates expression of specific immune-related genes and contributes to fine regulation of epithelial antimicrobial defense.
PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon Cancer
Authors: Lu Shuya , Gao Jianhui , Jia Huijie , Li Yang , Duan Yongbin , Song Fuyang , Liu Zhiang , Ma Shuai , Wang Mingyong , Zhao Tiesuo , Zhong Jiateng
Published: July 2021

The widespread appearance of drug tolerance and the low efficiency of single treatment have severely affected the survival time of the patients with colorectal cancer. Exploring new treatment options and combined treatment strategies have become the key to improving the prognosis. The combination of immunotherapy and chemotherapy have shown good clinical expectations. Here, we studied the cooperative effects of chloroquine, an anti-malarial drug that is now widely used in anti-tumor research, and RNA interference (RNAi) targeting the immune checkpoint molecule Programmed Death-1 (PD-1) delivered with attenuated Salmonella. Our results show that chloroquine can not only significantly inhibit the survival of colon cancer cells and induce apoptosis, but also effectively inhibit cell invasion and migration. The results of in vivo experiments show that chloroquine can increase the expression of PD-1 in tumor tissues. Combining chloroquine and PD-1 siRNA can further inhibit the growth and metastases of colon cancer and induce apoptosis. The mechanism underlying this phenomenon is the occurrence of chloroquine-induced apoptosis and the effective immune response caused by the attenuated Salmonella carrying PD-1 siRNA. This study suggests that the combined application of PD-1-based immunotherapy and anti-cancer drugs has become a new expectation for clinical treatment of colorectal cancer.
Opening a Marine Monument to Commercial Fishing Compromises Species Protections
Authors: Redfern Jessica V. , Kryc Kelly A. , Weiss Lena , Hodge Brooke C. , O’Brien Orfhlaith , Kraus Scott D. , Quintana-Rizzo Ester , Auster Peter J.
Published: July 2021

One of today’s greatest conservation challenges is balancing policies, laws, and management strategies established to achieve economic goals that depend on extracting ocean resources with those established to conserve marine biodiversity. We use the Northeast Canyons and Seamounts Marine National Monument (NCSM) as a case study to explore the consequences of changing from a policy that prevents fishing to a fisheries management policy. We found that opening the NCSM to commercial fishing reduces species protections. Fishing with pelagic and bottom tending fixed gear exposes species inhabiting the sea surface and midwater regions to entanglement and bycatch risk. Fishing with bottom tending fixed gear also exposes deep-sea coral habitat to gear known to have detrimental impacts. The NCSM was designated as a marine national monument due to the area’s unique ecological resources that are a subject of scientific interest. Our case study demonstrates that a fisheries management policy is insufficient to protect these ecological resources.
Variations in Seawater pCO2 Associated With Vertical Mixing During Tropical Cyclone Season in the Northwestern Subtropical Pacific Ocean
Authors: Ko Young Ho , Park Geun-Ha , Kim Dongseon , Kim Tae-Wook
Published: July 2021

This study examines interannual variations in the seawater CO2 partial pressure (pCO2) for months (August–October) with frequent tropical cyclone (TC) events in the northwestern subtropical Pacific Ocean (22°N–28°N, 135°E–145°E) between 2007 and 2017. The temperature-normalized pCO2 averaged over August–October showed a year-to-year variation ranging from 346 to 359 μatm over the 11 study years, which appeared to be related to the variation in vertical mixing that likely results from the TC activity in these months. Sea surface temperature and wind data consistently supported the association between mixing and TC intensity. Nonetheless, the pCO2 reduction caused by negative sea-surface temperature anomalies found over the TC season (July–October) shifted the study area from a CO2 source to a CO2 sink over these months. In the south (17°N–22°N) of the study area, mixing-driven variations in pCO2 were smaller during the same months, which appeared to be caused by the relatively deeper mixed layer depth and the more homogenous profile of CO2 in this tropical region. These results suggest that more extensive pCO2 measurements are required to fully resolve the effect of TCs on the carbonate system from the regional- to the basin-scale in the western Pacific Ocean, where TC intensity is expected to increase in the future.
First Insights Into the Horizontal Movements of Whale Sharks (Rhincodon typus) in the Northern Arabian Sea
Authors: Arrowsmith Lucy M. , Paidi Charan Kumar , Bloch Farukhkha Husenkha , John Sajan , Choudhury Binod Chandra , Kaul Rahul , Sequeira Ana M. M. , Pattiaratchi Charitha B. , Meekan Mark G.
Published: July 2021

Whale sharks off the western coast of India have suffered high levels of fishing pressure in the past, and today continue to be caught in small-scale fisheries as by-catch. Additionally, coastlines in this region host very large and growing human populations that are undergoing rapid development. This exacerbates ongoing anthropogenic threats to this species such as pollution, habitat loss, and ship traffic. For these reasons, there is an urgent need for data on movement patterns of whale sharks in this region of the Indian Ocean. Here, we address this issue by providing the first data on the horizontal movements of whale sharks tagged in the northern Arabian Sea off the western coast of the Indian state of Gujarat. From 2011 to 2017, eight individuals, ranging from 5.4 to 8 m were tagged and monitored using satellite telemetry. Tag retention varied from 1 to 137 days, with the sharks traveling distances of 34 – ∼2,230 km. Six of the eight individuals remained close to their tagging locations, although two sharks displayed wide ranging movements into the Arabian Sea, following frontal zones between water masses of different sea surface temperatures. We explore the relationship between the movement patterns of these whale sharks and the physical and biological processes of the region.
Investigation into Microstructure Evolution of Co–Ni–Cr–W–Based Superalloy During Hot Deformation
Authors: Zhang Wei , Zhu Baohong , Wu Shuaishuai , Tao Shutian
Published: July 2021

Hot compression tests were conducted using a Gleeble 3500 thermomechanical simulator at temperatures ranging from 1,000 to 1,200°C with the strain rate ranging from 0.1 to 10 s−1. Electron backscatter diffraction (EBSD) technique was employed by investigating the microstructure evolution during hot deformation. Microstructure observations reveal that deformation temperatures and strain rates have a significant effect on the DRX process. It is found that the fraction and grain size of DRX increase with the decreasing deformation temperature, along with the increasing high-angle grain boundaries (HAGBs). The fraction of DRX first decreases and then increases with the increase of strain rates. It is noted that there are both the nucleation mechanisms of discontinuous dynamic recrystallization (DDRX) and continuous dynamic recrystallization (CDRX) during the DRX process for Co–Ni–Cr–W–based superalloys. DDRX and CDRX are the primary and subsidiary nucleation mechanisms of DRX, respectively. It is also found that deformation temperatures and strain rates have almost no effect on the primary and subsidiary nucleation mechanisms of DRX. At the temperature above 1,150°C, the complete DRX occurred with the average grain sizes of about 25.32–29.01 μm. The homogeneity and refinement of microstructure can be obtained by selecting the suitable hot deformation parameters.
Molecular Testing on Cytology for Gene Fusion Detection
Authors: Schmitt Fernando , Di Lorito Alessia , Vielh Philippe
Published: July 2021

Cytology samples are suitable for the study of genotypic and phenotypic changes observed in different tumors. Being a minimally invasive technique, cytology sampling has been used as an acceptable alternative to track the alterations associated with tumor progression. Although the detection of gene mutations is well-established on cytology, in the last few years, gene fusion detections are becoming mandatory, especially in some tumor types such as lung cancer. Different technologies are available such as immunocytochemistry, fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and massive parallel sequencing approaches. Considering that many new drugs targeted fusion proteins, cytological samples can be of use to detect gene fusions in solid and lymphoproliferative tumor patients. In this article, we revised the use of several techniques utilized to check gene fusions in cytological material.
Kinetic Modeling of Slightly Acidic Electrolyzed Water Decay Characteristics in Fresh Cabbage Disinfection Against Human Norovirus
Authors: Kang Miran , Park Boyeon , Ha Ji-Hyoung
Published: July 2021

To consistently disinfect fresh vegetables efficiently, the decay of disinfectants such as chlorine, electrolyzed oxidizing water (EOW), ozonated water, and plasma-activated water during the disinfection maintenance stage needs to be understood. The aim of our study was to evaluate the changes in the inactivation kinetics of slightly acidic electrolyzed water (SAEW) against human norovirus (HuNoV), based on the cabbage-to-SAEW ratio. After disinfection of fresh cabbage with disinfected SAEW solution, SAEW samples were collected and analyzed for physicochemical properties such as pH, available chlorine concentrations (ACCs), and oxidation-reduction potential (ORP). SAEW virucidal effects were evaluated. We confirmed the decay of post-disinfection SAEW solution and demonstrated the different patterns of the decay kinetic model for HuNoV GI.6 and GII.4. In addition, the goodness of fit of the tested models based on a lower Akaike information criterion, root-mean-square error (RMSE), and residual sum of squares (RSS) was close to zero. In particular, the change in both the HuNoV GI.6 and GII.4 inactivation exhibited a strong correlation with the changes in the ACC of post-disinfection SAEW. These findings demonstrate that physicochemical parameters of SAEW play a key role in influencing the kinetic behavior of changes in the disinfection efficiency of SAEW during the disinfection process. Therefore, to optimize the efficiency of SAEW, it is necessary to optimize the produce-to-SAEW ratio in future studies.
Organic Acid Exposure Enhances Virulence in Some Listeria monocytogenes Strains Using the Galleria mellonella Infection Model
Authors: Li Minghao , Carpenter Charles E. , Broadbent Jeff R.
Published: July 2021

Prior research has suggested that the use of organic acids in the food industry may unintentionally enhance pathogenicity ofListeria monocytogenesstrain N1-227 and R2-499. This study explored the connection between habituation to L-lactic acid or acetic acid and virulence inL. monocytogenesstrains N1-227 and R2-499 using selected gene expression analysis and thein vivo Galleria mellonellawax worm model for infection. Expression of transcription factors (sigBandprfA) and genes related to acid resistance (gadD2, gadD3, andarcA) and bile resistance (bshandbilE) or to virulence (inlA, inlB, hly, plcA, plcB, uhpT, andactA) was investigated by quantitative real-time PCR (qRT-PCR), whilein vivovirulence was assessed by following the lethal time to 50% population mortality (LT50) ofG. mellonellalarvae after injection of untreated and habituatedL. monocytogenes.Twenty minutes of habituation to the organic acids at pH 6.0 significantly increased expression of key acid and bile stress response genes in both strains, while expression of virulence genes was strain-dependent. The expression of transcription factorsigBwas strain-dependent and there was no significant change in the expression of transcription factorprfAin both strains. Habituation to acid increased virulence of both strains as evidenced by decreased LT50ofG. mellonellalarvae injected withListeriahabituated to either acid. In summary, habituation of bothL. monocytogenesstrains to organic acids up-regulated expression of several stress and virulence genes and concurrently increased virulence as measured using theG. mellonellamodel.
HIV-1-Specific CAR-T Cells With Cell-Intrinsic PD-1 Checkpoint Blockade Enhance Anti-HIV Efficacy in vivo
Authors: Jiang Zhengtao , Liang Huitong , Pan Hanyu , Liang Yue , Wang Hua , Yang Xinyi , Lu Panpan , Zhang Xiao , Yang Jinlong , Zhang Dengji , Shen Xiaoting , Wang Jing , Liang Zhiming , Lin Qinru , Wang Yanan , Zhao Lin , Zhong Yangcheng , Lu Hongzhou , Zhu Huanzhang
Published: July 2021

Adoptive cellular immunotherapy therapy using broadly neutralizing antibody-based chimeric antigen receptor-T cells (bNAb-based CAR-T) has shown great potency and safety for the functional cure of HIV. The efficacy of bNAb-based CAR-T cells could be compromised by adaptive resistance during HIV chronic infection according to the phenomenon that cellular exhaustion was observed in endogenous cytotoxic T-lymphocytes (CTLs) along with upregulated expression of PD−1. Here, we created HIV-specific CAR-T cells using human peripheral blood mononuclear cells (PBMCs) and a 3BNC117-DNR CAR (3BD CAR) construct that enables the expression of PD-1 dominant negative receptor (DNR) and the single-chain variable fragment of the HIV-1-specific broadly neutralizing antibody 3BNC117 to target native HIV envelope glycoprotein (Env). Compared with HIV CAR expression alone, 3BD CAR-T cells displayed potent lytic and functional responses to Env-expressing cell lines and HIV-infected CD4+T cells. Moreover, 3BD CAR-T cells can kill HIV-latently-infected cell lines, which are reactivated by the secretory cytokines of effector cells followed by contact with initial HIV-expressing fraction. Furthermore, bioluminescence imaging indicated that 3BD CAR-T cells displayed superior anti-HIV function in an HIV NCG mouse model of transplanting Env+/PD-L1+cells (LEL6). These studies suggested that our proposed combinational strategy of HIV CAR-T therapy with PD-1 blockade therapy is feasible and potent, making it a promising therapeutic candidate for HIV functional cure.
Horizontal Transmission of Stress Resistance Genes Shape the Ecology of Beta- and Gamma-Proteobacteria
Authors: Kamal Shady Mansour , Simpson David J. , Wang Zhiying , Gänzle Michael , Römling Ute
Published: July 2021

The transmissible locus of stress tolerance (tLST) is found mainly in beta- and gamma-Proteobacteria and confers tolerance to elevated temperature, pressure, and chlorine. This genomic island, previously referred to as transmissible locus of protein quality control or locus of heat resistance likely originates from an environmental bacterium thriving in extreme habitats, but has been widely transmitted by lateral gene transfer. Although highly conserved, the gene content on the island is subject to evolution and gene products such as small heat shock proteins are present in several functionally distinct sequence variants. A number of these genes are xenologs of core genome genes with the gene products to widen the substrate spectrum and to be highly (complementary) expressed thus their functionality to become dominant over core genome genes. In this review, we will present current knowledge of the function of core tLST genes and discuss current knowledge on selection and counter-selection processes that favor maintenance of the tLST island, with frequent acquisition of gene products involved in cyclic di-GMP signaling, in different habitats from the environment to animals and plants, processed animal and plant products, man-made environments, and subsequently humans.
The Impact of Age on Mortality and Disability in Patients With Ischemic Stroke Who Underwent Cerebral Reperfusion Therapy: A Brazilian Cohort Study
Authors: Furlan Natália Eduarda , Luvizutto Gustavo José , Hamamoto Filho Pedro Tadao , Zanati Bazan Silméia Garcia , Modolo Gabriel Pinheiro , Ferreira Natalia Cristina , Miranda Luana Aparecida , de Souza Juli Thomaz , Winckler Fernanda Cristina , Vidal Edison Iglesias de Oliveira , de Freitas Carlos Clayton Macedo , Martin Luis Cuadrado , Bazan Rodrigo
Published: July 2021

Introduction: The main driver for increased stroke prevalence is the aging of the population; however, the best evidenced-based strategies for stroke treatment and prevention are not always followed for older patients. Therefore, the aim was studying the association of age with clinical outcomes (mortality and functional disability) in stroke patients who underwent cerebral reperfusion therapy at hospital discharge and 90 days after ictus.

Methods: This was a retrospective (stroke databank analysis) cohort study of participants who had been diagnosed with ischemic stroke and undergone intravenous cerebral reperfusion therapy or mechanical thrombectomy. The variable of interest was patient age, which was categorized into four groups: (1) up to 59 years; (2) 60 to 69 years; (3) 70 to 79 years old; and (4) above 79 years. The primary outcome was mortality at hospital discharge and 90 days after stroke, and the secondary outcome was functional capacity at hospital discharge and 90 days after stroke.

Results: A total of 281 patients was included in the study (235 treated by thrombolysis alone, and 46 treated with mechanical thrombectomy). The mean age of the total sample was 67 ± 13.1 years. The oldest patients had the most unfavorable outcomes, except for mortality rate, at hospital discharge (mRS > 2; OR: 1.028; 95% CI 1.005 to 1.051; p = 0.017; mRS > 3; OR: 1.043, 95% CI 1.018 to 1.069; p = 0.001) and 90 days after stroke (mRS > 2; OR: 1.028; 95% CI 1.005 to 1.051; p = 0.017; mRS > 3; OR: 1.043, 95% CI 1.018 to 1.069; p = 0.001).

Conclusion: Cerebral reperfusion was a viable treatment for ischemic stroke in both elderly and very elderly patients, as it did not increase mortality. However, it was observed that older individuals had worse functional outcomes at hospital discharge and 90 days after stroke.
Load Auditory Feedback Boosts Crutch Usage in Subjects With Central Nervous System Lesions: A Pilot Study
Authors: Tamburella Federica , Lorusso Matteo , Tagliamonte Nevio Luigi , Bentivoglio Francesca , Bigioni Alessandra , Pisotta Iolanda , Lancini Matteo , Pasinetti Simone , Ghidelli Marco , Masciullo Marcella , Saraceni Vincenzo Maria , Molinari Marco
Published: July 2021

Background:Crutches are the most common walking aids prescribed to improve mobility in subjects with central nervous system (CNS) lesions. To increase adherence to the appropriate level of crutch usage, providing load-related auditory feedback (aFB) may be a useful approach. We sensorized forearm crutches and developed a custom software to provide aFB information to both user and physical therapist (PhT).

Aim:Evaluate aFB effects on load control during gait by a self-controlled case series trial.

Methods:A single experimental session was conducted enrolling 12 CNS lesioned participants. Load on crutch was recorded during 10 Meter Walk Test performed with and without aFB. In both cases, crutch load data, and gait speed were recorded. Usability and satisfaction questionnaires were administered to participants and PhTs involved.

Results:Reliable data were obtained from eight participants. Results showed that compared to the no FB condition, aFB yielded a significant reduction in the mean load on the crutches during gait (p= 0.001). The FB did not influence gait speed or fatigue (p> 0.05). The experience questionnaire data indicated a positive experience regarding the use of aFB from both participants' and PhTs' perspectives.

Conclusion:aFB significantly improves compliance with crutch use and does not affect gait speed or fatigue by improving the load placed on crutches. The FB is perceived by users as helpful, safe, and easy to learn, and does not interfere with attention or concentration while walking. Furthermore, the PhTs consider the system to be useful, easy to learn and reliable.
Previous History of Migraine Is Associated With Fatigue, but Not Headache, as Long-Term Post-COVID Symptom After Severe Acute Respiratory SARS-CoV-2 Infection: A Case-Control Study
Authors: Fernández-de-las-Peñas César , Gómez-Mayordomo Víctor , García-Azorín David , Palacios-Ceña Domingo , Florencio Lidiane L. , Guerrero Angel L. , Hernández-Barrera Valentín , Cuadrado María L.
Published: July 2021

Objective

To investigate the association of pre-existing migraine in patients hospitalised and who recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the presence of post-coronavirus disease (COVID) symptoms.

Background

No study has investigated the role of migraine as a risk factor for development of post-COVID symptoms.

Methods

A case-control study including individuals hospitalised during the first wave of the pandemic (from February 20 to May 31, 2020) was conducted. Patients with confirmed previous diagnosis of migraine were considered cases. Two age- and sex-matched individuals without a history of headache per case were also recruited as controls. Hospitalisation/clinical data were collected from hospital medical records. Patients were scheduled for a telephone interview. A list of post-COVID symptoms was systematically evaluated, but participants were invited to freely report any symptom. The Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index were used to assess anxiety/depressive symptoms and sleep quality. Multivariable conditional logistic regression models were constructed.

Results

Overall, 57 patients with confirmed diagnosis of migraine and 144 non-migraine controls who had recovered from COVID-19 were assessed at 7.3 months (SD 0.6) after hospital discharge. The number of post-COVID symptoms in the migraine group was significantly greater (OR 1.70, 95% CI 1.29–2.25, P < 0.001) than in the non-migraine group. Fatigue was significantly more prevalent (OR 2.89, 95% CI 1.32–6.32, P = 0.008) in the migraine group. However, no between-groups difference in the prevalence of headache as a post-COVID symptom was detected.

Conclusion

Patients with a history of migraine who recovered from COVID-19 exhibited more long-term fatigue as post-COVID sequelae than those without migraine. Some of the pathophysiological changes associated with migraine could predispose to the occurrence of post-COVID symptoms.
A Novel Cognition-Guided Neurofeedback BCI Dataset on Nicotine Addiction
Authors: Bu Junjie , Liu Chang , Gou Huixing , Gan Hefan , Cheng Yan , Liu Mengyuan , Ni Rui , Liang Zhen , Cui Guanbao , Zeng Ginger Qinghong , Zhang Xiaochu
Published: July 2021

Compared with the traditional neurofeedback paradigm, the cognition-guided neurofeedback brain–computer interface (BCI) is a novel paradigm with significant effect on nicotine addiction. However, the cognition-guided neurofeedback BCI dataset is extremely lacking at present. This paper provides a BCI dataset based on a novel cognition-guided neurofeedback on nicotine addiction. Twenty-eight participants are recruited and involved in two visits of neurofeedback training. This cognition-guided neurofeedback includes two phases: an offline classifier construction and a real-time neurofeedback training. The original electroencephalogram (EEG) raw data of two phases are provided and evaluated in this paper. The event-related potential (ERP) amplitude and channel waveform suggest that our BCI dataset is of good quality and consistency. During neurofeedback training, the participants’ smoking cue reactivity patterns have a significant reduction. The mean accuracy of the multivariate pattern analysis (MVPA) classifier can reach approximately 70%. This novel cognition-guided neurofeedback BCI dataset can be used to develop comparisons with other neurofeedback systems and provide a reference for the development of other BCI algorithms and neurofeedback paradigms on addiction.
Diet Data Collected Using 48-h Dietary Recall: Within—and Between-Person Variation
Authors: Rossato Sinara Laurini , Fuchs Sandra Costa
Published: July 2021

Background and Aims: Forty-eight-hour dietary recall is a valuable source of information regarding food consumption in a population-based sample. This method covers 2 consecutive days in a single interview. Nevertheless, the number of assessments and the sample size necessary to estimate usual intake are unknown. We aimed to assess sources of variation, sample sizes, and numbers of days necessary to estimate usual nutrient intake using the 48-h dietary recall.

Methods: This was a population-based cross-sectional study including 237 participants, 11–90 years old, selected using multistage probabilistic sampling to obtain data using 48-h dietary recall. Analysis of variance was used to calculate within- and between-person variation and determine the statistical parameters necessary to calculate sample size and the number of days required to calculate the usual energy and nutrient intake.

Results: Within-person variation was generally lower than between-person variation, except for calcium (CVw2 = 40.8; CVb2 = 38.4%), magnesium (CVw2 = 27.4; CVb2 = 18.7%), and monounsaturated fat (CVw2 = 20.0; CVb2 = 17.3%) for the entire group and magnesium for women (CVw2 = 28.3; CVb2 = 91.8%). The number of days and sample size required to determine usual energy and nutrient intake varied substantially with gender and age (e.g., vitamin C in women N = 9, in men N = 1,641).

Conclusions: Energy and nutrient intake assessment using the 48-h dietary recall misrepresents within-person variation but can generate acceptable results for between-person variation. The calculation of sample size and number of days required to determine usual energy and nutrient intake might have been affected by inadequate assessment of the within-person variation.
Development and Validation of a Radiomic Nomogram for Predicting the Prognosis of Kidney Renal Clear Cell Carcinoma
Authors: Gao Ruizhi , Qin Hui , Lin Peng , Ma Chenjun , Li Chengyang , Wen Rong , Huang Jing , Wan Da , Wen Dongyue , Liang Yiqiong , Huang Jiang , Li Xin , Wang Xinrong , Chen Gang , He Yun , Yang Hong
Published: July 2021

Purpose

The present study aims to comprehensively investigate the prognostic value of a radiomic nomogram that integrates contrast-enhanced computed tomography (CECT) radiomic signature and clinicopathological parameters in kidney renal clear cell carcinoma (KIRC).

Methods

A total of 136 and 78 KIRC patients from the training and validation cohorts were included in the retrospective study. The intraclass correlation coefficient (ICC) was used to assess reproducibility of radiomic feature extraction. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) as well as multivariate Cox analysis were utilized to construct radiomic signature and clinical signature in the training cohort. A prognostic nomogram was established containing a radiomic signature and clinicopathological parameters by using a multivariate Cox analysis. The predictive ability of the nomogram [relative operating characteristic curve (ROC), concordance index (C-index), Hosmer–Lemeshow test, and calibration curve] was evaluated in the training cohort and validated in the validation cohort. Patients were split into high- and low-risk groups, and the Kaplan–Meier (KM) method was conducted to identify the forecasting ability of the established models. In addition, genes related with the radiomic risk score were determined by weighted correlation network analysis (WGCNA) and were used to conduct functional analysis.

Results

A total of 2,944 radiomic features were acquired from the tumor volumes of interest (VOIs) of CECT images. The radiomic signature, including ten selected features, and the clinical signature, including three selected clinical variables, showed good performance in the training and validation cohorts [area under the curve (AUC), 0.897 and 0.712 for the radiomic signature; 0.827 and 0.822 for the clinical signature, respectively]. The radiomic prognostic nomogram showed favorable performance and calibration in the training cohort (AUC, 0.896, C-index, 0.846), which was verified in the validation cohort (AUC, 0.768). KM curves indicated that the progression-free interval (PFI) time was dramatically shorter in the high-risk group than in the low-risk group. The functional analysis indicated that radiomic signature was significantly associated with T cell activation.

Conclusions

The nomogram combined with CECT radiomic and clinicopathological signatures exhibits excellent power in predicting the PFI of KIRC patients, which may aid in clinical management and prognostic evaluation of cancer patients.
A Novel Post-Operative ALRI Model Accurately Predicts Clinical Outcomes of Resected Hepatocellular Carcinoma Patients
Authors: Liao Minjun , Sun Jiarun , Zhang Qifan , Tang Cuirong , Zhou Yuchen , Cao Mingrong , Chen Tao , Hu Chengguang , Yu Junxiong , Song Yangda , Li Meng , Liao Weijia , Zhou Yuanping
Published: July 2021

Background

Hepatocellular carcinoma (HCC) is one of the leading malignant tumors worldwide. Prognosis and long-term survival of HCC remain unsatisfactory, even after radical resection, and many non-invasive predictors have been explored for post-operative patients. Most prognostic prediction models were based on preoperative clinical characteristics and pathological findings. This study aimed to investigate the prognostic value of a newly constructed nomogram, which incorporated post-operative aspartate aminotransferase to lymphocyte ratio index (ALRI).

Methods

A total of 771 HCC patients underwent radical resection from three medical centers were enrolled and grouped into the training cohort (n = 416) and validation cohort (n = 355). Prognostic prediction potential of ALRI was assessed by receiver operating curve (ROC) analysis. The Cox regression model was used to identify independent prognostic factors. Nomograms for overall survival (OS) and disease-free survival (DFS) were constructed and further validated externally.

Results

The ROC analysis ranked ALRI as the most effective prediction marker for resected HCC patients, with the cut-off value determined at 22.6. Higher ALRI level positively correlated with larger tumor size, higher tumor node metastasis (TNM) stage, and inversely with lower albumin level and shorter OS and DFS. Nomograms for OS and DFS were capable of discriminating HCC patients into different risk-groups.

Conclusions

Post-operative ALRI was of prediction value for HCC prognosis. This novel nomogram may categorize HCC patients into different risk groups, and offer individualized surveillance reference for post-operative patients.
Assessment of Vascular Network Connectivity of Hepatocellular Carcinoma Using Graph-Based Approach
Authors: Liu Qiaoyu , Zhang Boyu , Wang Luna , Zheng Rencheng , Qiang Jinwei , Wang He , Yan Fuhua , Li Ruokun
Published: July 2021

Background

The angiogenesis of liver cancer is a key condition for its growth, invasion, and metastasis. This study aims to investigate vascular network connectivity of hepatocellular carcinoma (HCC) using graph-based approach.

Methods

Orthotopic HCC xenograft models (n=10) and the healthy controls (n=10) were established. After 21 days of modeling, hepatic vascular casting and Micro-CT scanning were performed for angiography, followed by blood vessels automatic segmentation and vascular network modeling. The topologic parameters of vascular network, including clustering coefficient (CC), network structure entropy (NSE), and average path length (APL) were quantified. Topologic parameters of the tumor region, as well as the background liver were compared between HCC group and normal control group.

Results

Compared with normal control group, the tumor region of HCC group showed significantly decreased CC [(0.046 ± 0.005) vs. (0.052 ± 0.006), P=0.026], and NSE [(0.9894 ± 0.0015) vs. (0.9927 ± 0.0010), P<0.001], and increased APL [(0.433 ± 0.138) vs. (0.188 ± 0.049), P<0.001]. Compared with normal control group, the background liver of HCC group showed significantly decreased CC [(0.047 ± 0.004) vs. (0.052 ± 0.006), P=0.041] and increased NSE [0.9938 (0.9936~0.9940) vs. (0.9927 ± 0.0010), P=0.035]. No significant difference was identified for APL between the two groups.

Conclusion

Graph-based approach allows quantification of vascular connectivity of HCC. Disrupted vascular topological connectivity exists in the tumor region, as well as the background liver of HCC.
Balloon Test Occlusion of Internal Carotid Artery in Recurrent Nasopharyngeal Carcinoma Before Endoscopic Nasopharyngectomy: A Single Center Experience
Authors: Yang Renhao , Wu Hui , Chen Binghong , Sun Wenhua , Hu Xiang , Wang Tianwei , Guo Yubin , Qiu Yongming , Dai Jiong
Published: July 2021

Objectives

Endoscopic nasopharyngectomy (ENPG) is a promising way in treating recurrent nasopharyngeal carcinoma (rNPC), but sometimes may require therapeutic internal carotid artery (ICA) occlusion beforehand. Balloon test occlusion (BTO) is performed to evaluate cerebral ischemic tolerance for ICA sacrifice. However, absence of neurological deficits during BTO does not preclude occur of delayed cerebral ischemia after permanent ICA occlusion. In this study, we evaluate the utility of near-infrared spectroscopy (NIRS) regional cerebral oxygen saturation (rSO2) monitoring during ICA BTO to quantify cerebral ischemic tolerance and to identify the valid cut-off values for safe carotid artery occlusion. This study also aims to find out angiographic findings of cerebral collateral circulation to predict ICA BTO results simultaneously.

Material and Methods

87 BTO of ICA were performed from November 2018 to November 2020 at authors’ institution. 79 angiographies of collateral flow were performed in time during BTO and classified into several Subgroups and Types according to their anatomic and collateral flow configurations. 62 of 87 cases accepted monitoring of cerebral rSO2. Categorical variables were compared by using Fisher exact tests and Mann–Whitney U tests. Receiver operating characteristic curve analysis was used to determine the most suitable cut-off value.

Results

The most suitable cut-off △rSO2 value for detecting BTO-positive group obtained through ROC curve analysis was 5% (sensitivity: 100%, specificity: 86%). NIRS rSO2 monitoring wasn’t able to detect BTO false‐negative results (p = 0.310). The anterior Circle was functionally much more important than the posterior Circle among the primary collateral pathways. The presence of secondary collateral pathways was considered as a sign of deteriorated cerebral hemodynamic condition during ICA BTO. In Types 5 and 6, reverse blood flow to the ICA during BTO protected patients from delayed cerebral ischemia after therapeutic ICA occlusion (p = 0.0357). In Subgroup IV, absence of the posterior Circle was significantly associated with BTO-positive results (p = 0.0426).

Conclusion

Angiography of cerebral collateral circulation during ICA BTO is significantly correlated with ICA BTO results. Angiographic ICA BTO can be performed in conjunction with NIRS cerebral oximeter for its advantage of being noninvasive, real-time, cost-effective, simple for operation and most importantly for its correct prediction of most rSO2 outcomes of ICA sacrifice. However, in order to ensure a safe carotid artery occlusion, more quantitative adjunctive blood flow measurements are recommended when angiography of cerebral collateral circulation doesn’t fully support rSO2 outcome among clinically ICA BTO-negative cases.
The RNA-Binding Protein NELFE Promotes Gastric Cancer Growth and Metastasis Through E2F2
Authors: Chen Changyu , Zheng Qiang , Pan Shubo , Chen Wenzheng , Huang Jianfeng , Cao Yi , Tu Yi , Li Zhengrong , Yu Changjun , Jie Zhigang
Published: July 2021

Worldwide, the incidence rate of gastric cancer ranks fifth, and the mortality rate of gastric cancer ranks third among all malignant tumors. However, the pathogenesis of gastric cancer remains poorly understood. In this study, we demonstrated that the expression level of NELFE is higher in human gastric cancer tissues than in adjacent nontumor tissues. A high level of NELFE is associated with worse postoperative overall survival (OS) and relapse-free survival (RFS) rates in patients with gastric cancer. Moreover, the expression of NELFE is correlated with high tumor grade and lymph node metastasis in gastric cancer patients. Knockdown of NELFE dramatically inhibits the cell proliferation and metastasis of gastric cancer xenografts in vivo. Furthermore, we found that NELFE binding to the 3’UTR of E2F2 affects the mRNA stability of E2F2 to regulate the expression level of E2F2. In gastric cancer, E2F2 also acts as an oncogene to inhibit the proliferation and migration of gastric cancer cells by knocking down the expression level of E2F2. However, overexpressing E2F2 in cells with NELFE knockdown significantly reverses the inhibition of cell proliferation and migration induced by NELFE knockdown. Therefore, NELFE at least partially functions as an oncogene through E2F2. Moreover, CIBERSORTx analysis of the proportion of tumor-infiltrating immune cells (TICs) revealed that immune cells are correlated with NELFE and E2F2 expression, suggesting that NELFE and E2F2 might be responsible for the preservation of the immunodominant status for gastric cancer. In conclusion, NELFE acts as an oncogene in gastric cancer and can be used as a potential therapeutic target.
m6A Regulator-Mediated Methylation Modification Model Predicts Prognosis, Tumor Microenvironment Characterizations and Response to Immunotherapies of Clear Cell Renal Cell Carcinoma
Authors: Xu Wenhao , Tian Xi , Liu Wangrui , Anwaier Aihetaimujiang , Su Jiaqi , Zhu Wenkai , Wan Fangning , Shi Guohai , Wei Gaomeng , Qu Yuanyuan , Zhang Hailiang , Ye Dingwei
Published: July 2021

Background

This study aims to establish an N6-methyladenosine (m6A) RNA methylation regulators-mediated methylation model and explore its role in predicting prognostic accuracy of immune contexture and characterizations of clear cell renal cell carcinoma (ccRCC).

Methods

The m6A modification subclasses (m6AMS) were identified by unsupervised cluster analysis and three clusters were determined by consensus clustering algorithm in a discovering cohort. Testing and real-world validation cohorts were used to identify predictive responses for immune checkpoint therapies (ICTs) of m6AMS.

Results

Prognostic implications landscape of m6A regulators in cancers and its differential expression levels in ccRCC patients were identified. Based on discovering cohort, ccRCC were automatically divided into three m6AMS, and cluster 3 showed significant worse survival than cluster 1/2. Importantly, it was found that the immune checkpoint molecules expression was significantly elevated in cluster 3. Besides, m6A scoreLow group (cluster 1&2) have significantly elevated TIDE score compared with m6A scoreHigh group (cluster 3). There was conspicuous tertiary lymphoid tissue, aggressive phenotype, elevated glycolysis, expression of PD-L1, abundance of CD8+ T cells, CD4+ FOXP3+ Treg cells and TCRn immune cells infiltration in the high m6A score group. Interestingly, there are significantly increased patients with clinical benefit in m6A scoreHigh group in 368 patients receiving ICTs from testing IMvigor210 (n = 292) and validation FUSCC (n = 55) cohorts.

Conclusion

Our discovery highlights the relationship between tumor epigenetic heterogeneity and immune contexture. Immune-rejection cluster 3 has pro-tumorigenic immune infiltration, and shows significant clinical benefits for ccRCC patients receiving ICTs, enabling patient selection for future clinical treatment.