bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Validation of TACE Refractoriness-Related Diagnostic and Prognostic Scores and Characterization of Tumor Microenvironment Infiltration in Hepatocellular Carcinoma
Authors: He Qifan , Yang Jian , Jin Yonghai
Published: April 2022

Background

Transcatheter arterial chemoembolization LIHC, Liver hepatocellular carcinoma; (TACE) is a valid therapeutic method for hepatocellular carcinoma (HCC). However, many patients respond poorly to TACE, thus leading to an adverse outcome. Therefore, finding new biomarkers for forecasting TACE refractoriness occurrence and prognosis becomes one of the current research priorities in the field of HCC treatment.

Materials and Methods

Based on microarray datasets and a high-throughput sequencing dataset, the TACE refractoriness–related genes (TRGs) were identified by differential expression analysis. LASSO and Cox regression were applied to construct TACE refractoriness diagnostic score (TRD score) and prognostic score (TRP score) and validated their accuracy in external datasets. Functional correlation of TRP score was analyzed by gene set variation analysis and Gene Ontology. CIBERSORT and IMMUNCELL AI algorithms were performed to understand the correlation between the two scores and immune activity. We further carried out the efficacy analysis of immunotherapy and targeted drugs in the different TRP score groups. Furthermore, a nomogram was built by integrating various independent prognostic factors and validated its effectiveness in different datasets.

Results

We identified 487 TRGs combined with GSE104580 and TCGA datasets. Then four novel TRGs (TTK, EPO, SLC7A11, and PON1) were screened out to construct TRD score and TRP score models, and both two scores had good predictive ability in external datasets. Tumors with high TRP score show an immunosuppressive phenotype with more infiltrations of regulatory T cells and macrophages. Immunotherapy and chemotherapy response evaluation revealed patients with a high TRP score demonstrated well reactions to immune checkpoint inhibitors (ICIs) and sorafenib. TRP score, TNM stage, and cancer type were brought into the combined nomogram with optimum prediction.

Conclusions

Our research provided dependable and simplified methods for patients with HCC to assess tumors’ susceptibility to TACE refractoriness and prognosis and guide patients’ clinical therapy choices.
A Competitive Study of the Static and Fatigue Performance of Flax, Glass, and Flax/Glass Hybrid Composites on the Structural Example of a Light Railway Axle Tie
Authors: Graupner Nina , Hohe Jörg , Schober Michael , Rohrmüller Benedikt , Weber David , Bruns Lisa , Bruns Albert , Müssig Jörg
Published: April 2022

The most common studies in the literature are those analyzing fatigue life under cyclic loading for flax fiber-reinforced composites. A novel type of staple fiber yarn made from flax tow with almost unidirectional fiber orientation and a quasi-unidirectional fabric was developed for composite applications. Additionally, a hybrid material made of flax and glass was produced for a demonstrator component (an axle tie of a narrow-gauge railway). For such an application, the investigation of fatigue strength is of particular importance. Therefore, the fatigue behavior of flax, glass, and hybrid flax/glass composites was investigated in the high cycle fatigue range. A total of 106 load cycles were carried out. From about 7³ to 8³ loading cycles, the flax laminate was found to have higher fatigue strength than the glass fiber-reinforced composite. The hybrid materials tend to show a higher fatigue strength than the glass type from approximately 2 × 105 load cycles. Results based on a finite element method also demonstrate better fatigue properties at an increased number of load cycles for flax-based composites than the glass fiber-reinforced component. The flax/glass component’s fatigue strength ranged between the flax values and the glass fiber-reinforced composites. Overall, the hybrid material shows significantly better static bending and impact characteristics than flax and considerably better fatigue properties than the glass fiber-reinforced composite making the hybrid material attractive for an application in an axle tie.
Recycling of Precast Concrete Waste Sludge With Paper Mill and Biomass Ashes for Lightweight Granulated Aggregate Production
Authors: Moukannaa Samira , Kursula Kalle , Perumal Priyadharshini , Ohenoja Katja , Illikainen Mirja
Published: April 2022

The construction and demolition waste generation is increasingly evolving with the rapid urbanization, with more than a quarter of the produced waste being landfilled without further treatment or recycling strategy. Hence, sustainable management and valorization methods such as recycling in construction materials is becoming increasingly essential to tackle the economic and environmental burdens of landfilling waste. Construction and demolition waste recycling has been intensively studied. However, the present study proposes a promising solution for recycling construction and demolition wastes (CDWs) from the precast concrete waste sludge and ashes from paper mill sludge and biomass. Artificial lightweight aggregates were designed and produced by alkali activating a mixture of 50–90 wt% of dried and milled CDW with 3–25 wt% of ash and 5–35 wt% of blast furnace slag. The properties of the produced aggregates were assessed via density, water absorption, porosity, and crushing tests, in addition to microstructural characterizations using XRD and scanning electron microscopy SEM analysis. The optimum NaOH concentration was 8M with the highest mechanical properties and lowest efflorescence. The produced aggregates revealed a high crushing force of 82 N at 28 days with 50 wt% CDW, 15 wt% biomass ash, and 25 wt% blast furnace slag presenting a possible recycling pathway for such side-stream materials.
Effect of Age on Mechanical Properties of Human Tooth Enamel
Authors: Jing Xia , Zhipeng Yang , Kaiyong Liu , Junjie Lu , Xinyuan He , Juan Zhang , Yujie Fan
Published: April 2022

Dental health is closely related with people’s quality of life. Teeth are subject to different problems and risks over time. Therefore, studying the influence of age on mechanical properties of tooth enamel is of considerable importance. In this study, the collected human teeth were divided into four groups: deciduous (aged 6–12 years), juvenile permanent (aged 14–20 years), young adult permanent (aged 25–45 years), and older adult permanent (aged over 60 years) teeth. The mechanical properties of tooth enamel of all age groups were evaluated using a microhardness tester and laser confocal microscope. The results revealed that hardness of the deciduous teeth was much lower than that of permanent teeth. Hardness of young adult permanent teeth was the highest, followed by that of the older adult and juvenile permanent teeth. Deciduous teeth enamel had the highest fracture toughness, followed by that of young adult, juvenile, and older adult permanent teeth. The different chemical compositions and microstructures of enamel at different age groups resulted in the significant differences in mechanical properties. This research accords with the strategic requirement of improving peoples’ dental health, and its results are noteworthy in developing specific protocols for dental hygiene and clinical prevention.
Two-Year Visual Outcomes of Evolution Implantable Collamer Lens and Small Incision Lenticule Extraction for the Correction of Low Myopia
Authors: Fu Mengjun , Li Meiyan , Xian Yiyong , Yu Zhiqiang , Zhang Haorun , Choi Joanne , Niu Lingling , Wang Xiaoying , Zhou Xingtao
Published: April 2022

Purpose

To investigate the 2-year visual quality of Evolution Implantable Collamer Lens (EVO-ICL) and small incision lenticule extraction (SMILE) for the correction of low myopia.

Methods

In this prospective study, we included 25 eyes of 25 patients (7 men) who underwent EVO-ICL and 36 eyes of 36 patients (16 men) who underwent SMILE between January 2018 and December 2018. Subjective and objective visual outcomes were compared between ICL and SMILE. All patients were followed for 2 years.

Results

At the postoperative 2-year visit, the percentage of patients with uncorrected distance visual acuity (UDVA) greater than or equal to preoperative corrected distance visual acuity (CDVA) was comparable in the ICL group (80%, 20/25) and SMILE group (88.89%, 32/36). Spherical equivalent (SE) was within ± 0.50 D in 96% (24/25) of the ICL group and 94.44% (34/36) of the SMILE group. No eyes lost more than 2 lines of CDVA. Postoperative high-order aberrations (HOAs) were significantly increased in the ICL group (p < 0.01) and in the SMILE group (p < 0.01). The most common visual complaint was halo after ICL and starburst after SMILE. There was no correlation between HOAs and visual complaints (p > 0.05).

Conclusion

Evolution Implantable Collamer Lens provides comparable safety, efficacy, long-term visual stability, and high patient satisfaction when compared to SMILE in correcting low myopia. EVO-ICL could be a favorable alternative for low myopia.

Key messages What was known?

•

Visual outcomes of Evolution Implantable Collamer Lens (EVO-ICL) versus small incision lenticule extraction (SMILE) for correction of mild myopia remain unclear.

What this paper adds?

•

Evolution Implantable Collamer Lens (EVO-ICL) provides comparable safety, efficacy, long-term visual stability, and high patient satisfaction when compared to small incision lenticule extraction (SMILE) in correcting low myopia.

•

The most common visual complaint was halo after ICL and starburst after SMILE.
Updating Understanding of Macular Microvascular Abnormalities and Their Correlations With the Characteristics and Progression of Macular Edema or Exudation in Coats' Disease
Authors: Zhang Juan , Ruan Lu , Jiang Chen , Yang Qian , Ju Yuqiao , Chang Qing , Huang Xin
Published: April 2022

Objective

To investigate the associations of macular microvascular abnormalities with the characteristics and progression of macular edema or exudation in Coats' disease, toward an updated understanding of possible risk factors for macular edema or exudation.

Methods

Twenty-six eyes (26 patients) with Coats' disease and macular edema or exudation underwent multimodal imaging and were followed for 18 months. The eyes were classified according to their outcomes (refractory or improved). Macular capillary affections were assessed by optical coherence tomography angiography (OCTA) and fluorescein angiography (FA). Histopathological analysis of the macular region of an additional enucleated eye was performed.

Results

OCTA revealed telangiectasia in the deep capillary plexus (DCP) in 76.9% and the superficial capillary plexus (SCP) in 34.6% of 26 eyes with macular edema or exudation of Coats' disease, exceeding the rate detected by FA (21.4%). Eyes with intraretinal cystoid spaces/exudates of the macula presented higher presence of telangiectasia in the SCP (57.1% with vs. 8.3% without, X2 = 6.801, P = 0.009) and DCP (92.9 with vs. 58.3% without, X2 = 4.338, P = 0.037). The parafoveal vessel densities (VDs) and fractal dimension in the SCP and DCP were lower in affected eyes than in contralateral eyes (all P < 0.001). The VD in SCP (P = 0.009) and DCP (P = 0.010) were lower in refractory group than in improved group. Dilated capillaries with incomplete vessel walls and adjacent inflammatory cells were detected in the neuroretina of the macula in histopathological specimen.

Conclusions

Macular capillary abnormalities, including telangiectasia and VD loss, were positively detected in eyes with macular edema or exudation of Coats' disease. Intraretinal cystoid spaces/exudates of the macula, rather than subretinal exudates, may be related to macular telangiectasia. VD losses in the SCP and DCP may be risk factors for refractory macular edema or exudation.
Effects of Electroacupuncture on Opioid-Induced Constipation in Patients With Cancer: Study Protocol for a Multicenter Randomized Controlled Trial
Authors: Wang Weiming , Wang Xinlu , Liu Yan , Sun Yuanjie , Liu Xiaoxu , Yan Yan , Liu Zhishun
Published: April 2022

Background

Opioid-induced constipation (OIC) is one of the most prevalent adverse events associated with cancer patients who receive opioid analgesics for moderate to severe pain. Acupuncture may be an effective treatment for OIC. We designed this trial to assess the efficacy and safety of electroacupuncture for OIC in cancer patients.

Methods

This is a multicenter, sham-controlled, parallel-group, subject- and assessor-blinded randomized trial. A total of 100 cancer patients with OIC will be randomly assigned to either the electroacupuncture group or the sham electroacupuncture group at a ratio of 1:1. Patients in each group will receive a total of 24-session treatment over 8 weeks, three sessions a week and 30 min each session. Thereafter, patients will be followed up for another 8 weeks. The primary outcome will be the proportion of responders, defined as a patient who has ≥3 spontaneous bowel movements (SBMs)/wk and ≥ increase of 1 SBM from baseline simultaneously for at least 6 out of 8 weeks of the treatment period. The secondary outcomes will include the mean weekly SBMs and complete spontaneous bowel movements, the mean Bristol Stool Form Scale score for stool consistency, the mean score for straining of SBM, the total and subscale scores of Patient Assessment of Constipation-Symptom questionnaires, and the total and subscale scores of Patient Assessment of Constipation-Quality of Life questionnaire. Patients' global assessment of treatment effectiveness, patients' expectation toward the effectiveness of acupuncture and safety of acupuncture will also be assessed. All efficacy analyses will be performed in the intention-to-treat population.

Discussion

To improve the adherence to intervention protocols, the majority of the participants will be recruited from an inpatient setting. The results will help to determine the clinical effects and safety of electroacupuncture for the treatment of OIC among patients with cancer.

Clinical Trial Registration

www.ClinicalTrials.gov, identifier: NCT03797586, registered on 4 January 2019, https://clinicaltrials.gov/ct2/show/NCT03797586.
Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Rocco Patricia R. M. , Silva Pedro L. , Cruz Fernanda F. , Tierno Paulo F. G. M. M. , Rabello Eucir , Junior Jéfiton Cordeiro , Haag Firmino , de Ávila Renata E. , da Silva Joana D. G. , Mamede Mariana M. S. , Buchele Konrad S. , Barbosa Luiz C. V. , Cabral Anna C. , Junqueira Antônio A. F. , Araújo-Filho João A. , da Costa Lucianna A. T. J. , Alvarenga Pedro P. M. , Moura Alexandre S. , Carajeleascow Ricardo , de Oliveira Mirella C. , Silva Roberta G. F. , Soares Cynthia R. P. , Fernandes Ana Paula S. M. , Fonseca Flavio Guimarães , Camargos Vidyleison Neves , Reis Julia de Souza , Franchini Kleber G. , Luiz Ronir R. , Morais Sirlei , Sverdloff Carlos , Martins Camila Marinelli , Felix Nathane S. , Mattos-Silva Paula , Nogueira Caroline M. B. , Caldeira Dayene A. F. , Pelosi Paolo , Lapa-e-Silva José R.
Published: April 2022

Background

Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain.

Methods

A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days.

Results

Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38–1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21–3.43], p < 0.0001), time to hospital discharge (1.37 [1.11–1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64–0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed.

Conclusions

Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia.

Clinical Trial Registration

Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.
Assessment of Reticulocyte and Erythrocyte Parameters From Automated Blood Counts in Vaso-Occlusive Crisis on Sickle Cell Disease
Authors: Feugray Guillaume , Kasonga Fiston , Grall Maximilien , Benhamou Ygal , Bobée-Schneider Victor , Buchonnet Gérard , Daliphard Sylvie , Le Cam Duchez Véronique , Lahary Agnès , Billoir Paul
Published: April 2022

Sickle cell disease is a complex genetic disease involving cell adhesion between red blood cells, white blood cells, platelets and endothelial cells, inducing painful vaso-occlusive crisis (VOC). We assessed reticulocyte and erythrocyte parameters in a cohort of confirmed SCD patients, and investigated whether a combination of these routine laboratory biomarkers of haemolysis could be used to predict VOC development. Reticulocyte and erythrocyte parameters were evaluated using the Sysmex XN-9000 analyser. A total of 98 patients with SCD were included, 72 in steady state and 26 in VOC. Among the 72 patients in steady state, 22 developed a VOC in the following year (median: 3 months [2–6]). The following parameters were increased in SCD patients with VOC development compared to SCD patients without VOC development in the following year: reticulocyte count (94.6 109/L [67.8–128] vs. 48.4 109/L [24.9–87.5]), immature reticulocyte count (259 109/L [181–334] vs. 152 109/L [129–208]) reticulocyte/immature reticulocyte fraction (IRF) ratio (6.63 109/(L*%) [4.67–9.56] vs. 4.94 109/(L*%) [3.96–6.61]), and medium fluorescence reticulocytes (MFR) (19.9% [17.4–20.7] vs. 17.1% [15.95–19.75]). The association of a reticulocyte count of >189.4 109/L and an MFR of >19.75% showed a sensitivity of 81.8% and a specificity of 88% to predict VOC development in the following year. Based on our findings, a combination of routine laboratory biomarkers, as reticulocyte count, immature reticulocyte count and fluorescent reticulocyte fraction at steady state, could be used to predict VOC development in SCD.
Chaperonin-Containing TCP1 Subunit 5 Protects Against the Effect of Mer Receptor Tyrosine Kinase Knockdown in Retinal Pigment Epithelial Cells by Interacting With Filamentous Actin and Activating the LIM-Kinase 1/Cofilin Pathway
Authors: Feng Lujia , Li Haichun , Du Yong , Zhang Ting , Zhu Yingting , Li Zhidong , Zhao Ling , Wang Xing , Wang Gongpei , Zhou Linbin , Jiang Zhaorong , Liu Zheng , Ou Zhancong , Wen Yuwen , Zhuo Yehong
Published: April 2022

Retinitis pigmentosa (RP), characterized by the gradual loss of rod and cone photoreceptors that eventually leads to blindness, is the most common inherited retinal disorder, affecting more than 2.5 million people worldwide. However, the underlying pathogenesis of RP remains unclear and there is no effective cure for RP. Mutations in the Mer receptor tyrosine kinase (MERTK) gene induce the phagocytic dysfunction of retinal pigment epithelium (RPE) cells, leading to RP. Studies have indicated that filamentous actin (F-actin)—which is regulated by chaperonin-containing TCP1 subunit 5 (CCT5)—plays a vital role in phagocytosis in RPE cells. However, whether CCT5/F-actin signaling is involved in MERTK-associated RP remains largely unknown. In the present study, we specifically knocked down MERTK and CCT5 through siRNA transfection and examined the expression of CCT5 and F-actin in human primary RPE (HsRPE) cells. We found that MERTK downregulation inhibited cell proliferation, migration, and phagocytic function; significantly decreased the expression of F-actin; and disrupted the regular arrangement of F-actin. Importantly, our findings firstly indicate that CCT5 interacts with F-actin and is inhibited by MERTK siRNA in HsRPE cells. Upregulating CCT5 using CCT5-specific lentiviral vectors (CCT5-Le) rescued the cell proliferation, migration, and phagocytic function of HsRPE cells under the MERTK knockdown condition by increasing the expression of F-actin and restoring its regular arrangement via the LIMK1/cofilin, but not the SSH1/cofilin, pathway. In conclusion, CCT5 protects against the effect of MERTK knockdown in HsRPE cells and demonstrates the potential for effective treatment of MERTK-associated RP.
Forensic Application of Epidermal Ubiquitin Expression to Determination of Wound Vitality in Human Compressed Neck Skin
Authors: Zhang Siying , Ishida Yuko , Ishigami Akiko , Nosaka Mizuho , Kuninaka Yumi , Hata Satoshi , Yamamoto Hiroki , Hashizume Yumiko , Matsuki Jumpei , Yasuda Haruki , Kimura Akihiko , Furukawa Fukumi , Kondo Toshikazu
Published: April 2022

Ubiquitin is a member of the heat shock protein family and is rapidly induced by various types of stimuli, including ischemic and mechanical stress. However, its significance in determining wound vitality of neck compression skin in forensic pathology remains unclear. We immunohistochemically examined the expression of ubiquitin in the neck skin samples to understand its forensic applicability in determining wound vitality. Skin samples were obtained from 53 cases of neck compression (hanging, 42 cases; strangulation, 11 cases) during forensic autopsies. Intact skin from the same individual was used as the control. Ubiquitin expression was detected in 73.9% of keratinocytes in intact skin samples, but only in 21.2% of keratinocytes in the compression regions, with statistical differences between the control and compression groups. This depletion in the case of neck compression may be caused by the impaired conversion of conjugated to free ubiquitin and failure of de novo ubiquitin synthesis. From a forensic pathological perspective, immunohistochemical examination of ubiquitin expression in the skin of the neck can be regarded as a valuable marker for diagnosing traces of antemortem compression.
Oral Immune Priming Treatment Alters Microbiome Composition in the Red Flour Beetle Tribolium castaneum
Authors: Korša Ana , Lo Lai Ka , Gandhi Shrey , Bang Corinna , Kurtz Joachim
Published: April 2022

It is now well-established that the microbiome is relevant for many of an organism’s properties and that its composition reacts dynamically to various conditions. The microbiome interacts with host immunity and can play important roles in the defenses against pathogens. In invertebrates, immune priming, that is, improved survival upon secondary exposure to a previously encountered pathogen, can be dependent upon the presence of the gut microbiome. However, it is currently unknown whether the microbiome changes upon priming treatment. We here addressed this question in a well-established model for immune priming, the red flour beetle Tribolium castaneum exposed to the entomopathogenic bacterium Bacillus thuringiensis (Bt). After priming treatments, the microbiota composition of beetle larvae was assessed by deep sequencing of the V1-V2 region of the bacterial 16S rRNA gene. We compared the effect of two established routes of priming treatments in this system: injection priming with heat-killed Bt and oral priming via ingestion of filtered sterilized bacterial spore culture supernatants. For oral priming, we used several strains of Bt known to vary in their ability to induce priming. Our study revealed changes in microbiome composition following the oral priming treatment with two different strains of Bt, only one of which (Bt tenebrionis, Btt) is known to lead to improved survival. In contrast, injection priming treatment with the same bacterial strain did not result in microbiome changes. Combined with the previous results indicating that oral priming with Btt depends on the larval microbiome, this suggests that certain members of the microbiome could be involved in forming an oral priming response in the red flour beetle.
Genetic Diversity and Population Structure Reveal Cryptic Genetic Variation and Long Distance Migration of Puccinia graminis f. sp. tritici in the Indian Subcontinent
Authors: Prasad Pramod , Thakur Rajni Kant , Savadi Siddanna , Bhardwaj Subhash Chander , Gangwar Om Prakash , Lata Charu , Adhikari Sneha , Kumar Subodh
Published: April 2022

Stem rust caused by Puccinia graminis f. sp. tritici (Pgt) is a devastating disease of wheat worldwide since time immemorial. Several wheat stem rust outbreaks have been reported worldwide including India. Approximately 7 mha wheat area in central and peninsular India is highly vulnerable to stem rust epidemics. In this study, a repository of 29 single genotype uredospore pathotypes, representing five geographical regions, was characterized by investigating their virulence phenotype and simple sequence repeat (SSR) genotypes using 37 reproducible polymorphic SSR markers, 32 of which had ≥ 0.50 polymorphic information content (PIC) value. Virulence phenotypes were used to evaluate the virulence frequency (VF) and construct a hypothetical evolutionary hierarchy of these pathotypes. We projected seven lineages to explain the evolutionary pattern of the Pgt population. The VF of these pathotypes ranged between 0% and 100%. The virulence-based neighbor-joining (NJ) cluster analysis grouped Pgt pathotypes into five virulence groups. Likewise, five molecular groups were categorized using molecular genotypes. The molecular grouping was supported by principal coordinate analysis (PCoA), which revealed 25% of the cumulative variance contributed by the first two axes. Analysis of molecular variance (AMOVA) revealed 8 and 92% of the variation among and within the populations, respectively. The Mantel test confirmed a positive but weak correlation (R2 = 0.15) between virulence phenotypes and SSR genotypes. The highest and lowest values of different genetic diversity parameters (Na, Ne, I, He, uHe, and %P) revealed maximum and minimum variability in the Pgt population from Maharashtra and Uttar Pradesh, respectively. The population structure analysis clustered 29 Pgt pathotypes into two subpopulations and an admixture. Our results demonstrated that there was significant genetic diversity among Pgt pathotypes resulting from their long-distance dispersal ability complemented by gene flow. These findings provide insights into the virulence patterns, genetic variations, and possible evolution of Pgt pathotypes, which would support strategic stem rust resistance breeding.
Reclassification of 11 Members of the Family Rhodobacteraceae at Genus and Species Levels and Proposal of Pseudogemmobacter hezensis sp. nov.
Authors: Ma Tengfei , Xue Han , Piao Chungen , Liu Chengyi , Yang Mei , Bian Danran , Li Yong
Published: April 2022

A novel Gram-stain-negative, aerobic, motile bacterial strain, D13-10-4-6T, was isolated from the bark sample of Populus × euramericana. The strain could grow at 15–35°C, at pH 6–10 and in 0–4% (w/v) NaCl, and the strain tested positive for oxidase and catalase activities. The main polar lipids were phosphatidylmonomethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. The main respiratory quinone was Q-10, and the predominant fatty acid was C18:1 ω7c. The phylogenetic analyses showed that the strain belonged to the genus Pseudogemmobacter of the family Rhodobacteraceae. The family Rhodobacteraceae is an ecologically diverse group that includes bacteria from aquatic to terrestrial ecosystems. As a consequence, the classification of the family Rhodobacteraceae is difficult, not least when the early taxonomy work relied heavily on 16S rRNA gene analysis. Recently, the taxonomic status of many members of the family has been revised based on the genome analysis; however, there are still some classification conflicts due to the lack of genome sequences and parallel publication time. In this study, phylogenetic trees based on 16S rRNA gene, gyrB gene, and 120 concatenated proteins, the average amino acid identity (AAI) and percentage of conserved proteins (POCP) have been used for the analysis of strain D13-10-4-6T and other members of 15 genera within the family to further clarify their taxonomic relationships. For the data of phylogeny, AAI, and POCP, the taxonomic proposals are (1) reclassification of Rhodobacter tardus as the type species of a novel genus, Stagnihabitans gen. nov., as Stagnihabitans tardus comb. nov.; (2) reclassification of Tabrizicola alkalilacus, Tabrizicola sediminis, Tabrizicola algicola into a novel genus, Pseudotabrizicola gen. nov., as Pseudotabrizicola alkalilacus comb. nov., Pseudotabrizicola sediminis comb. nov., Pseudotabrizicola algicola comb. nov.; (3) reclassification of Rhodobacter sediminicola into the genus Cereibacter as Cereibacter sediminicola comb. nov.; (4) reclassification of Rhodobacter flagellatus, Rhodobacter thermarum, and Xinfangfangia soli into the genus Tabrizicola as Tabrizicola flagellatus comb. nov., Tabrizicola thermarum comb. Nov., and Tabrizicola soli comb. nov.; (5) reclassification of Xinfangfangia humi into the genus Pseudogemmobacter as Pseudogemmobacter humicola comb. nov.; (6) classification of strain D13-10-4-6T as a novel species of the genus Pseudogemmobacter, for which the name P. hezensis sp. nov. is proposed, the type strain is D13-10-4-6T (= CFCC 12033T = KCTC 82215T).
Optimized UV-Spectrophotometric Assay to Screen Bacterial Uricase Activity Using Whole Cell Suspension
Authors: Pugin Benoit , Plüss Serafina , Mujezinovic Denisa , Nielsen Rikke C. , Lacroix Christophe
Published: April 2022

Uricase catalyzes the conversion of uric acid into allantoin with concomitant reduction of molecular oxygen to hydrogen peroxide. In humans, uricase is not functional, thereby predisposing individuals to hyperuricemia, a metabolic disturbance associated with gout, chronic kidney disorders, and cardiovascular diseases. The efficacy of current therapies to treat hyperuricemia is limited, and novel approaches are therefore desired, for instance using uricase-expressing probiotic strains. Here, we evaluated UV-spectrophotometric and H2O2-based fluorescent assays to enable the rapid identification of uricase activity in a broad panel of lactobacilli, Bacillus, and Bifidobacterium species. We highlighted abiotic (medium composition and mode of sterilization) and biotic (H2O2-producing strains) factors impacting the measurements’ accuracy, and reported on the stepwise optimization of a simple, fast, and robust high-throughput UV-spectrophotometric method to screen uricase activity using whole bacterial suspension, thereby assessing both cell-associated and extracellular activity. The validity of the optimized assay, based on the monitoring of uric acid degradation at 300 nm, was confirmed via liquid chromatography. Finally, a panel of 319 Qualified Presumption of Safety (QPS) strains of lactobacilli (18 species covering nine genera), Bacillus (three species), and Bifidobacterium (four species) were screened for uricase activity using the optimized method. All 319 strains, but the positive control Bacillus sp. DSM 1306, were uricase-negative, indicating that this activity is rare among these genera, especially in isolates from food or feces. Altogether, the UV-spectrophotometric high-throughput assay based on whole bacterial suspension reported here can be used to rapidly screen large microbial collections, by simultaneously detecting cell-associated and extracellular uricase activity, thereby accelerating the identification of uricolytic strains with therapeutic potential to treat hyperuricemia.
Bradykinin-Induced Sensitization of Transient Receptor Potential Channel Melastatin 3 Calcium Responses in Mouse Nociceptive Neurons
Authors: Behrendt Marc , Solinski Hans Jürgen , Schmelz Martin , Carr Richard
Published: April 2022

TRPM3 is a calcium-permeable cation channel expressed in a range of sensory neurons that can be activated by heat and the endogenous steroid pregnenolone sulfate (PS). During inflammation, the expression and function of TRPM3 are both augmented in somatosensory nociceptors. However, in isolated dorsal root ganglion (DRG) neurons application of inflammatory mediators like prostaglandins and bradykinin (BK) inhibit TRPM3. Therefore, the aim of this study was to examine the effect of preceding activation of cultured 1 day old mouse DRG neurons by the inflammatory mediator BK on TRPM3-mediated calcium responses. Calcium signals were recorded using the intensity-based dye Fluo-8. We found that TRPM3-mediated calcium responses to PS were enhanced by preceding application of BK in cells that responded to BK with a calcium signal, indicating BK receptor (BKR) expression. The majority of cells that co-expressed TRPM3 and BKRs also expressed TRPV1, however, only a small fraction co-expressed TRPA1, identified by calcium responses to capsaicin and supercinnamaldehyde, respectively. Signaling and trafficking pathways responsible for sensitization of TRPM3 following BK were characterized using inhibitors of second messenger signaling cascades and exocytosis. Pharmacological blockade of protein kinase C, calcium–calmodulin-dependent protein kinase II and diacylglycerol (DAG) lipase did not affect BK-induced sensitization, but inhibition of DAG kinase did. In addition, release of calcium from intracellular stores using thapsigargin also resulted in TRPM3 sensitization. Finally, BK did not sensitize TRPM3 in the presence of exocytosis inhibitors. Collectively, we show that preceding activation of DRG neurons by BK sensitized TRPM3-mediated calcium responses to PS. Our results indicate that BKR-mediated activation of intracellular signaling pathways comprising DAG kinase, calcium and exocytosis may contribute to TRPM3 sensitization during inflammation.
Comparison of Efficacy of Lokomat and Wearable Exoskeleton-Assisted Gait Training in People With Spinal Cord Injury: A Systematic Review and Network Meta-Analysis
Authors: Zhang Lingjie , Lin Fabin , Sun Lei , Chen Chunmei
Published: April 2022

Objective

Lokomat and wearable exoskeleton-assisted walking (EAW) have not been directly compared previously. To conduct a network meta-analysis of randomized and non-randomized controlled trials to assess locomotor abilities achieved with two different types of robotic-assisted gait training (RAGT) program in persons with spinal cord injury (SCI).

Methods

Three electronic databases, namely, PubMed, Embase, and the Cochrane Library, were systematically searched for randomized and non-randomized controlled trials published before August 2021, which assessed locomotor abilities after RAGT.

Results

Of 319 studies identified for this review, 12 studies were eligible and included in our analysis. Studies from 2013 to 2021 were covered and contained 353 valid data points (N-353) on patients with SCI receiving wearable EWA and Lokomat training. In the case of wearable EAW, the 10-m walk test (10-MWT) distance and speed scores significantly increased [distance: 0.85 (95% CI = 0.35, 1.34); speed: −1.76 (95% CI = −2.79, −0.73)]. The 6-min walk test (6-MWT) distance [−1.39 (95% CI = −2.01, −0.77)] and the timed up and go (TUG) test significantly increased [(1.19 (95% CI = 0.74, 1.64)], but no significant difference was observed in the walking index for spinal cord injury (WISCI-II) [−0.33 (95% CI = −0.79, 0.13)]. Among the patients using Lokomat, the 10-MWT-distance score significantly increased [−0.08 (95% CI = −0.14, −0.03)] and a significant increase in the WISCI-II was found [1.77 (95% CI = 0.23, 3.31)]. The result of network meta-analysis showed that the probability of wearable EAW to rank first and that of Lokomat to rank second was 89 and 47%, respectively, in the 10-MWT speed score, while that of Lokomat to rank first and wearable EAW to rank second was 73 and 63% in the WISCI-II scores.

Conclusion

Lokomat and wearable EAW had effects on the performance of locomotion abilities, namely, distance, speed, and function. Wearable EAW might lead to better outcomes in walking speed compared with that in the case of Lokomat.
Metacognitive Ability and the Precision of Confidence
Authors: Somatori Keita , Kunisato Yoshihiko
Published: April 2022

In prior research, signal detection theory (SDT) has been widely utilized to assess metacognitive ability. However, the SDT metacognitive model requires the use of a two-alternative forced-choice task, while confidence must also be measured discretely. In our model, participants’ cognitive ability and their confidence in the cognitive task were used to estimate their metacognitive abilities. Therefore, in this study, a metacognitive model that can be applied to various cognitive tasks was developed. This model implements the item response theory (IRT) and Q-learning models to estimate cognitive ability; participants’ metacognitive ability is defined as the discrepancy between their confidence in their cognitive ability and their actual cognitive ability. The entire procedure was divided into two experiments. In experiment 1, two different cognitive tasks were used to estimate metacognitive ability and to examine overall discriminative and convergent validity. Notably, the parameters representing metacognitive ability did not correlate with cognitive ability but were positively correlated between the two tasks. In experiment 2, we performed a similar analysis using a different task to test the replicability of experiment 1. The results for experiment 2 were replicated for discriminative and convergent validity, albeit with weak results. Our metacognitive model exhibited high interpretability and versatility.
Positron Emission Tomography in the Neuroimaging of Autism Spectrum Disorder: A Review
Authors: Tan Zhiqiang , Wei Huiyi , Song Xiubao , Mai Wangxiang , Yan Jiajian , Ye Weijian , Ling Xueying , Hou Lu , Zhang Shaojuan , Yan Sen , Xu Hao , Wang Lu
Published: April 2022

Autism spectrum disorder (ASD) is a basket term for neurodevelopmental disorders characterized by marked impairments in social interactions, repetitive and stereotypical behaviors, and restricted interests and activities. Subtypes include (A) disorders with known genetic abnormalities including fragile X syndrome, Rett syndrome, and tuberous sclerosis and (B) idiopathic ASD, conditions with unknown etiologies. Positron emission tomography (PET) is a molecular imaging technology that can be utilizedin vivofor dynamic and quantitative research, and is a valuable tool for exploring pathophysiological mechanisms, evaluating therapeutic efficacy, and accelerating drug development in ASD. Recently, several imaging studies on ASD have been published and physiological changes during ASD progression was disclosed by PET. This paper reviews the specific radioligands for PET imaging of critical biomarkers in ASD, and summarizes and discusses the similar and different discoveries in outcomes of previous studies. It is of great importance to identify general physiological changes in cerebral glucose metabolism, cerebral blood flow perfusion, abnormalities in neurotransmitter systems, and inflammation in the central nervous system in ASD, which may provide excellent points for further ASD research.
Role of Extracellular Vesicles in Glia-Neuron Intercellular Communication
Authors: Ahmad Shahzad , Srivastava Rohit K. , Singh Pratibha , Naik Ulhas P. , Srivastava Amit K.
Published: April 2022

Cross talk between glia and neurons is crucial for a variety of biological functions, ranging from nervous system development, axonal conduction, synaptic transmission, neural circuit maturation, to homeostasis maintenance. Extracellular vesicles (EVs), which were initially described as cellular debris and were devoid of biological function, are now recognized as key components in cell-cell communication and play a critical role in glia-neuron communication. EVs transport the proteins, lipids, and nucleic acid cargo in intercellular communication, which alters target cells structurally and functionally. A better understanding of the roles of EVs in glia-neuron communication, both in physiological and pathological conditions, can aid in the discovery of novel therapeutic targets and the development of new biomarkers. This review aims to demonstrate that different types of glia and neuronal cells secrete various types of EVs, resulting in specific functions in intercellular communications.
Individualized Nutritional Support for Hospitalized Patients With Oropharyngeal Dysphagia After Stroke: A Randomized Controlled Trial
Authors: Yan Xiu-Li , Liu Zhuo , Sun Ye , Zhang Peng , Lu Xue-Yan , Mu Fei , Du Juan , Yang Yi , Guo Zhen-Ni
Published: April 2022

Objectives

Post-stroke dysphagia may cause aspiration pneumonia, malnutrition, dehydration, and other complications. However, data on the effects of nutritional supplementation and its value after stroke are insufficient. We aimed to evaluate the effect of an individualized 1-week nutrition intervention program on swallowing function and nutritional status in stroke patients with oropharyngeal dysphagia.

Methods

This study comprised the control group receiving oral nutritional support and continuous nasogastric tube feeding according to the results of the water swallow test (WST). The intervention group additionally underwent a volume-viscosity swallowing test (V-VST) and intermittent oroesophageal tube feeding based on WST. The outcomes were measured after 7 days of intervention, including the improvement of swallowing function assessment by WST, biochemical parameters, such as total serum protein, serum albumin, hemoglobin levels and body composition. This trial was registered with the Chinese Clinical Trial Registry, identifier ChiCTR 2100054054.

Results

In total, 173 participants completed the study between September 1, 2020, and April 30, 2021. Patients receiving individualized nutritional support showed a more significant improvement in the total effective rate of swallowing function (95.3% vs. 85.1%, P < 0.05). After the intervention, the total serum protein level (0.97 ± 0.41 vs. −0.83 ± 0.47 g/L; P < 0.05), serum albumin level (0.33 ± 0.28 vs. −1.39 ± 0.36 g/L; P < 0.001) and lean tissue mass (0.13 ± 0.35 vs. −1.00 ± 0.40 g/L; P < 0.05) increased in the intervention group. The decrease of hemoglobin levels in the control group was more evident (−6.17 ± 1.63 vs. −0.64 ± 1.40 g/L; 95%CI, −9.78 to −1.28; P = 0.001). The difference of phase angle between the two groups was statistically significant (5.93 ± 0.88° vs. 5.77 ± 0.78°; P = 0.035), but not in body fat mass.

Conclusions

In stroke patients with oropharyngeal dysphagia, the use of individualized nutritional support based on V-VST and intermittent oroesophageal tube feeding during the first week of hospitalization improved swallowing function and maintained nutritional status.

Clinical Trial Registration

https://clinicaltrials.gov/, identifier: ChiCTR 2100054054.
Association of Dietary Energy Intake With Constipation Among Men and Women: Results From the National Health and Nutrition Examination Survey
Authors: Yang Shuai , Wu Xiao-Li , Wang Shou-Qing , Guo Xiang-Ling , Guo Fu-Zheng , Sun Xiao-Feng
Published: April 2022

Background

Previous studies supported that dietary factor was associated with constipation, but the relationship between dietary energy intake and constipation has not been well-studied. Therefore, we aimed to evaluate the prevalence and correlation between energy intake and constipation among men and women.

Methods

These observational analyses included 12,587 adults (≥20 years) from the 2005–2010 cycles of the National Health and Nutrition Examination Surveys (NHANES). Constipation was defined as Bristol Stool Scale Type 1 (separate hard lumps, like nuts) or Type 2 (sausage-like but lumpy). Total energy intake was obtained from the two 24-h dietary recalls and averaged. We used the logistic regression model in Generalized Linear Model (GLM) function, controlling demographic, lifestyle, and dietary factors, to estimate the association between energy intake and constipation among men and women.

Results

The overall weighted incidence of constipation in this research was 7.4%, the incidence in women and men was 10.4 and 4.3%, respectively. After multivariable adjustment, middle energy consumption correlated with decreased risk of constipation in men (OR:0.5, 95% CI:0.29–0.84), and lower-middle energy intake increased the constipation risk in women (OR: 1.56, 95% CI: 1.15–2.13). High energy consumption was not associated with increased or decreased constipation risk.

Conclusions

To our knowledge, this is the first research to investigate the association between energy intake and constipation; the study demonstrates that appropriate energy consumption can help reduce the risk of constipation in men, and relatively low energy intake is associated with increased constipation risk in women.
De novo Creation and Assessment of a Prognostic Fat-Age-Inflammation Index “FAIN” in Patients With Cancer: A Multicenter Cohort Study
Authors: Yin Liangyu , Song Chunhua , Cui Jiuwei , Lin Xin , Li Na , Fan Yang , Zhang Ling , Liu Jie , Chong Feifei , Wang Chang , Liang Tingting , Liu Xiangliang , Deng Li , Yang Mei , Yu Jiami , Wang Xiaojie , Liu Xing , Yang Shoumei , Zuo Zheng , Yuan Kaitao , Yu Miao , Cong Minghua , Li Zengning , Weng Min , Yao Qinghua , Jia Pingping , Li Suyi , Guo Zengqing , Li Wei , Shi Hanping , Xu Hongxia
Published: April 2022

Background and Aims

Malnutrition is highly prevalent and is related to multiple impaired clinical outcomes in cancer patients. This study aimed to de novo create an objective, nutrition-related index specially for prognostic purposes in oncology populations.

Methods

We performed a multicenter cohort study including 14,134 cancer patients. The prognostic impact for each baseline characteristic was estimated by calculating Harrell's C-index. The optimal parameters reflecting the nutritional and inflammatory impact on patients' overall survival were selected to develop the fat-age-inflammation (FAIN) index. The associations of the FAIN with the nutritional status, physical performance, quality of life, short-term outcomes and mortality of patients were comprehensively evaluated. Independent external validation was performed to further assess the prognostic value of the FAIN.

Results

The study enrolled 7,468 men and 6,666 women with a median age of 57 years and a median follow-up of 42 months. The FAIN index was defined as: (triceps skinfold thickness + albumin) / [age + 5 × (neutrophil count/lymphocyte count)]. There were significant associations of the FAIN with the nutritional status, physical performance, quality of life and short-term outcomes. The FAIN also showed better discrimination performance than the Nutritional Risk Index, the Prognostic Nutritional Index and the Controlling Nutritional Status index (all P < 0.05). In multivariable-adjusted models, the FAIN was independently associated with a reduced death hazard both as a continuous variable (HR = 0.57, 95%CI = 0.47–0.68) and per one standard deviation (HR = 0.83, 95%CI = 0.78–0.88). External validation in a multicenter lung cancer cohort (n = 227) further confirmed the prognostic value of the FAIN.

Conclusions

This study created and assessed the prognostic FAIN index, which might act as a feasible option to monitor the nutritional status and help develop intervention strategies to optimize the survival outcomes of cancer patients.