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irGSEA is an R package designed to assess the outcomes of various gene set scoring methods when applied to single-cell RNA sequencing data. This package incorporates six distinct scoring methods that rely on the expression ranks of genes, emphasizing relative expression levels over absolute values. The implemented methods include AUCell, UCell, singscore, ssGSEA, JASMINE and Viper. Previous studies have demonstrated the robustness of these methods to variations in dataset size and composition, generating enrichment scores based solely on the relative gene expression of individual cells. By employing the robust rank aggregation algorithm, irGSEA amalgamates results from all six methods to ascertain the statistical significance of target gene sets across diverse scoring methods. The package prioritizes user-friendliness, allowing direct input of expression matrices or seamless interaction with Seurat objects. Furthermore, it facilitates a comprehensive visualization of results. The irGSEA package and its accompanying documentation are accessible on GitHub (https://github.com/chuiqin/irGSEA).
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Algoritmos , Análise de Célula Única , Software , Análise de Célula Única/métodos , Humanos , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Análise de Sequência de RNA/métodosRESUMO
BACKGROUND: There is a great challenge to sedation for infants with cleft lip and palate undergoing CT scan, because there is the younger age and no consensus on the type, dosage, and route of drug administration. OBJECTIVE: This study aimed to evaluate the efficacy of intranasal administration of dexmedetomidine combined with midazolam as a sedative option for infants with cleft lip and palate under imaging procedures. METHODS: Infants scheduled for cleft lip and palate repair surgery were randomly assigned to the IND group (intranasal dexmedetomidine 2 µg/kg alone) and the INDM group (intranasal dexmedetomidine 2 µg/kg combined with midazolam 0.05 mg/kg). The primary outcome was the proportion of infants underwent successful computed tomography (CT) scans under intranasal sedation. The secondary outcomes included onset time and duration of sedation, recovery time, Ramsay sedation scale, hemodynamic parameters during sedation, and adverse events. Data analyses involved the unpaired t-test, the repeated-measures analysis of variance test, and the continuity correction χ2 test. RESULTS: One hundred five infants were included in the analysis. The proportion of infants underwent successful CT scans under sedation was significantly greater in the INDM group than in the IND group (47 [95.9%] vs. 45 [80.4%], p = 0.016). Additionally, the INDM group had a shorter onset time and a longer duration of sedation statistically (12 [8.5, 17] min vs. 16 [12, 20] min, p = 0.001; 80 [63.6, 92.5] min vs. 68.5 [38, 89] min, p = 0.014, respectively), and their recovery time was significantly longer (43 [30, 59.5] min vs. 31.5 [20.5, 53.5] min, p = 0.006). The difference in Ramsay sedation scale values 20 min after administration was statistically significant between the groups. No statistically significant difference was found between the groups in changes in heart rate and respiratory rate. CONCLUSION: Intranasal administration of dexmedetomidine in combination with midazolam resulted in higher sedation success in comparison with sole dexmedetomidine. However, it has a relatively prolonged duration of sedation and recovery time. TRIAL REGISTRATION: ChiCTR2100049122, Clinical trial first registration date: 21/07/2021.
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Fenda Labial , Fissura Palatina , Dexmedetomidina , Lactente , Humanos , Midazolam , Fenda Labial/cirurgia , Administração Intranasal , Fissura Palatina/cirurgia , Hipnóticos e Sedativos , Tomografia Computadorizada por Raios XRESUMO
The paper presented the treatment procedure of a 2-year-old patient with unrepaired bilateral cleft lip and palate (BCLP). Complicated situation included severely protruded premaxilla and constricted upper dental arch, possibly related to delayed treatment of cleft lip and palate. Orthodontic expansion lasted for 8 months, including using fan-type expander for 3 months. After that, premaxillary osteotomy was performed to reset the premaxilla, and 4 months later, simultaneous repair of cleft lip and palate was taken. Follow-up evaluation in 5.5 years revealed acceptable language development and craniofacial profile, and maxillary growth was satisfactory. The treatment procedure of this patient provided an exploratory protocol for those patients with unrepaired BCLP who suffered from deteriorated preaxillary protrusion and constricted upper arch.
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The U.S. Food and Drug Administration recently approved lonafarnib as the first treatment for Hutchinson-Gilford progeria syndrome (HGPS) and processing-deficient progeroid laminopathies. This approval was primarily based on a comparison of patients with HGPS treated with lonafarnib in 2 open-label trials with an untreated patient cohort. With up to 11 years of follow-up, it was found that the lonafarnib treated patients with HGPS had a survival benefit of 2.5 years compared with the untreated patients with HGPS. This large treatment effect on the objective endpoint of mortality using a well-matched comparator group mitigated potential sources of bias and together with other evidence, established compelling evidence of a drug effect with benefits that outweighed the risks. This approval is an example of U.S. Food and Drug Administration's regulatory flexibility for a rare disease while ensuring that standards for drug approval are met.
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Progéria , Estados Unidos , Humanos , Progéria/tratamento farmacológico , Progéria/genética , Lamina Tipo A/genética , Piperidinas/uso terapêutico , Piridinas/uso terapêuticoRESUMO
This study investigated the growth, SPAD value, chlorophyll fluorescence and transcriptome response of endophyte uninoculated and inoculated rice seedlings under Pb stress after treatment of 1 d and 5 d. Inoculation of endophytes significantly improved the plant height, SPAD value, Fv/F0, Fv/Fm and PIABS by 1.29, 1.73, 0.16, 1.25 and 1.90 times on the 1 d, by 1.07, 2.45, 0.11, 1.59 and 7.90 times on the 5 d, respectively, however, decreased the root length by 1.11 and 1.65 times on the 1 d and 5 d, respectively under Pb stress. Analysis of rice seedlings leaves by RNA-seq, there were 574 down-regulated and 918 up-regulated genes after treatment of 1 d, 205 down-regulated and 127 up-regulated genes after treatment of 5 d, of which 20 genes (11 up-regulated and 9 down-regulated) exhibited the same changing pattern after treatment of 1 d and 5 d. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to annotate these DEGs, and it was found that many of DEGs involved in photosynthesis, oxidative detoxification, hormone synthesis and signal transduction, protein phosphorylation/kinase and transcription factors. These findings provide new insights into the molecular mechanism of interaction between endophyte and plants under heavy metal stress, and contribute to agricultural production in limited environments.
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Oryza , Transcriptoma , Plântula/genética , Plântula/metabolismo , Endófitos/genética , Endófitos/metabolismo , Perfilação da Expressão Gênica , Oryza/metabolismo , Chumbo/toxicidade , Chumbo/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
On September 22, 2021, the Food and Drug Administration approved ruxolitinib for the treatment of chronic graft-versus-host disease (cGVHD) after the failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424-365 (REACH-3; CINC424D2301; NCT03112603), a randomized, open-label, multicenter trial of ruxolitinib in comparison to best available therapy (BAT) for the treatment of corticosteroid-refractory cGVHD occurring after the allogeneic hematopoietic stem cell transplantation. A total of 329 patients were randomized 1:1 to receive either ruxolitinib 10 mg twice daily (n = 165) or BAT (n = 164). BAT was selected by the investigator prior to randomization. The overall response rate through Cycle 7 Day 1 was 70% (95% CI, 63-77) in the ruxolitinib arm, and 57% (95% CI, 49-65) in the BAT arm. The median duration of response, calculated from first response to progression, death, or initiation of new systemic therapies for cGVHD, was 4.2 months (95% CI, 3.2-6.7) for the ruxolitinib arm and 2.1 months (95% CI, 1.6-3.2) for the BAT arm; and the median time from first response to death or initiation of new systemic therapies for cGVHD was 25 months (95% CI, 16.8-not estimable) for the ruxolitinib arm and 5.6 months (95% CI, 4.1-7.8) for the BAT arm. Common adverse reactions included anemia, thrombocytopenia, and infections. Given the observed response rate with durability, the clinical benefit of ruxolitinib appears to outweigh the risks of treatment for cGVHD after the failure of one or two lines of systemic therapy.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Criança , Doença Enxerto-Hospedeiro/induzido quimicamente , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Nitrilas/uso terapêutico , Pirazóis/efeitos adversos , Pirimidinas/uso terapêuticoRESUMO
On December 18, 2020, US Food and Drug Administration (FDA) approved a supplemental application for ponatinib extending the indication in patients with chronic-phase chronic myeloid leukemia (CP-CML) to patients with resistance or intolerance of at least 2 prior kinase inhibitors. Ponatinib was initially approved in December 2012 but was briefly voluntarily withdrawn due to serious safety concerns including the risk of arterial occlusive events (AOE). It returned to the market in December 2013 with an indication limited to patients with T315I mutation or for whom no other tyrosine kinase inhibitor (TKI) therapy was indicated with revised warnings and precautions. A post-marketing requirement was issued to identify the optimal safe and effective dose for CP-CML. Thus, the OPTIC trial was performed, which randomized patients to 1 of 3 doses, 45 mg, 30 mg, or 15 mg, with a dose reduction to 15 mg on achievement of MR2 (BCR-ABLIS ≤1%). Patients enrolled were treated with at least 2 prior TKIs or had a T315I mutation. Patients with a history of clinically significant, uncontrolled, or active cardiovascular disease were excluded. Efficacy was established on an interim analysis based on the rate of MR2 at 12 months in the modified intent-to-treat population of 261 patients, with 88, 86, and 87 patients in the 45, 30, and 15 mg cohorts, respectively. With a median follow-up of 28 months, the rate of achievement of MR2 at 12 months was 42%, 28%, and 24% in the respective cohorts. The safety profile was consistent with that observed in prior evaluations of ponatinib with notable adverse reactions including pancreatitis, hypertension, hyperlipidemia, liver dysfunction, and AOE. Of patients treated at the 45/15 mg dose, AOEs were seen in 13%, with a higher rate being observed in patients age 65 or older compared to younger patients. A readjudication of AOEs seen on the prior pivotal phase 2 study resulted in a rate of 26%. Overall, the results supported a modification of the recommended dose for patients with CP-CML to 45 mg until the achievement of MR2 followed by a reduction to 15 mg. The expansion of the indication to patients with exposure to 2 prior TKIs was approved given data showing that ponatinib could be successfully used for the treatment of this population with appropriate monitoring and screening for risk factors.
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Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Idoso , Antineoplásicos/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Fusão bcr-abl/genética , Humanos , Imidazóis , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Inibidores de Proteínas Quinases/efeitos adversos , Piridazinas , Estados Unidos , United States Food and Drug AdministrationRESUMO
The regulation of gene expression plays an essential role in both the phenotype and adaptation of plants. Transcriptome sequencing enables simultaneous identification of exonic variants and quantification of gene expression. Here, we sequenced the leaf transcriptomes of 287 rice accessions from around the world and obtained a total of 177 853 high-quality single nucleotide polymorphisms after filtering. Genome-wide association study identified 44 354 expression quantitative trait loci (eQTLs), which regulate the expression of 13 201 genes, as well as 17 local eQTL hotspots and 96 distant eQTL hotspots. Furthermore, a transcriptome-wide association study screened 21 candidate genes for starch content in the flag leaves at the heading stage. HS002 was identified as a significant distant eQTL hotspot with five downstream genes enriched for diterpene antitoxin synthesis. Co-expression analysis, eQTL analysis, and linkage mapping together demonstrated that bHLH026 acts as a key regulator to activate the expression of downstream genes. The transgenic assay revealed that bHLH026 is an important regulator of diterpenoid antitoxin synthesis and enhances the disease resistance of rice. These findings improve our knowledge of the regulatory mechanisms of gene expression variation and complex regulatory networks of the rice genome and will facilitate genetic improvement of cultivated rice varieties.
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Antitoxinas , Oryza , Locos de Características Quantitativas/genética , Oryza/genética , Estudo de Associação Genômica Ampla , Transcriptoma , Polimorfismo de Nucleotídeo Único/genética , Antitoxinas/genética , Perfilação da Expressão GênicaRESUMO
A Gram-stain-negative and facultatively anaerobic bacterial strain designated as JM162201T was isolated from aquaculture water for farming Pacific white shrimp (Litopenaeus vannamei). The genome size of strain JM162201T was 4,436,316 bp, and the genomic DNA G + C content was 55.0%. Phylogenetic analysis based on 16S rRNA gene sequences and genomes showed that strain JM162201T belonged to the genus Shewanella and was closely related to Shewanella litorisediminis SMK1-12T (97.1%), Shewanella khirikhana TH2012T (97.0%), and Shewanella amazonensis SB2BT (96.0%). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain JM162201T and three reference type strains were below the recognized thresholds of 95.0-96.0% (for ANI) and 70.0% (for dDDH) for species delineation. Growth occurred at 10-40 °C (optimum, 30 °C), at pH 4.0-10.0 (optimum, 7.0-8.0), and in 0-6.0% NaCl (w/v, optimum, 0-0.1%). The major cellular fatty acids of strain JM162201T were summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C17:1 ω8c, iso-C15:0, C16:0, and C15:0. The predominant quinones were MK7, Q-7, and Q-8. The major polar lipids were phosphatidylethanolamine (PE) and phosphatidylglycerol (PG). Based on the polyphasic taxonomical analyses, strain JM162201T represents a novel species of the genus Shewanella, for which the name Shewanella jiangmenensis sp. nov. is proposed, with the type strain JM162201T (= GDMCC 1.2006T = KCTC 82340T).
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Shewanella , Água , Aquicultura , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Shewanella/genéticaRESUMO
In January 2021, the U.S. Food and Drug Administration (FDA) approved crizotinib for pediatric patients 1 year and older and young adults with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). This is the first approval for pediatric sALCL. Approval was based on a single-arm trial of crizotinib monotherapy that included 26 patients, aged 1-20 years, with previously treated sALCL. Efficacy was based on centrally assessed objective response rate (88%) and duration of response. Herein, we highlight unique aspects of the regulatory review, including extension of the indication to young adults, postmarketing safety, and dose optimization strategies.
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Imunoconjugados , Linfoma Anaplásico de Células Grandes , Criança , Crizotinibe/uso terapêutico , Humanos , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Estados Unidos , United States Food and Drug Administration , Adulto JovemRESUMO
PURPOSE: To investigate the effects of ICU quality control indicators on the VAP incidence rate and mortality in China throughout 2019. METHODS: This was a retrospective study. A total of 1267 ICUs from 30 provinces in mainland China were included. Data were collected using the National Clinical Improvement System Data that report ICU information. Ten related quality control indicators were analyzed, including 5 structural factors (patient-to-bed ratio, physician-to-bed ratio, nurse-to-bed ratio, patient-to-physician ratio, and patient-to-nurse ratio), 3 process factors (unplanned endotracheal extubation rate, reintubation rate within 48 h, and microbiology detection rate before antibiotic use), and 2 outcome factors (VAP incidence rate and mortality). The information on the most common infectious pathogens and the most commonly used antibiotics in ICU was also collected. The Poisson regression model was used to identify the impact of factors on the incidence rate and mortality of VAP. RESULTS: The incidence rate of VAP in these hospitals in 2019 was 5.03 (2.38, 10.25) per 1000 ventilator days, and the mortality of VAP was 11.11 (0.32, 26.00) %. The most common causative pathogen was Acinetobacter baumannii (in 39.98% of hospitals), followed by Klebsiella pneumoniae (38.26%), Pseudomonas aeruginosa, and Escherichia coli. In 26.90% of hospitals, third-generation cephalosporin was the most used antibiotic, followed by carbapenem (24.22%), penicillin and beta-lactamase inhibitor combination (20.09%), cephalosporin with beta-lactamase inhibitor (17.93%). All the structural factors were significantly associated with VAP incidence rate, but not with the mortality, although the trend was inconsistent. Process factors including unplanned endotracheal extubation rate, reintubation rate in 48 h, and microbiology detection rate before antibiotic use were associated with higher VAP mortality, while unplanned endotracheal extubation rate and reintubation rate in 48 h were associated with higher VAP mortality. Furthermore, K. pneumoniae as the most common pathogen was associated with higher VAP mortality, and carbapenems as the most used antibiotics were associated with lower VAP mortality. CONCLUSION: This study highlights the association between the ICU quality control (QC) factors and VAP incidence rate and mortality. The process factors rather than the structural factors need to be further improved for the QC of VAP in the ICU.
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Pneumonia Associada à Ventilação Mecânica , Humanos , Estudos Retrospectivos , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Inibidores de beta-Lactamases , Incidência , Unidades de Terapia Intensiva , Hospitais , Antibacterianos/uso terapêutico , Carbapenêmicos , Klebsiella pneumoniae , CefalosporinasRESUMO
There is nearly 5,800 ha of Sanhua plum (Prunus salicina Linn) planted in Babu district in Hezhou, Guangxi, with over 67,000 tons of annual output. In August 2021, anthracnose symptoms were observed on Sanhua plum leaves in three different cultivated towns in Babu district in Hezhou, Guangxi (N23°49' - 24°48', E111°12' - 112°03'). The plant disease incidence was over 50% with approximately 20 to 30% of leaves on a plant being symptomatic. The disease outbreak occurred in the warm and damp climate (June to August) in Hezhou. Initially, small chlorotic spots developed on the leaves which gradually enlarged to larger irregular dark brown sunken lesions with yellowish halos, necrotic lesions abscised and formed holes at a later stage. In severe cases, the whole leaf withered and defoliated. Three symptomatic leaf samples were collected from three different cultivated towns in Hezhou. Margins of infected tissues were cut into 3×3 mm pieces, surface disinfected with 75% alcohol for 10 s, 2% NaOCl for 2 min followed by three washes in sterile distilled water and transferred to potato dextrose agar (PDA) plates. In total, forty-one isolates were obtained after 4 days of incubation at 25â on PDA, and thirty-one of them were Colletotrichum (average isolation frequency 76%). Three representative isolates (HZ18-1, HZ22-3, and HZ46-3) were selected for further study. After 7 days on PDA at 25â, isolates had white to light grey cottony aerial mycelium on the obverse and revealed dark grey on the reverse. Conidia were hyaline, cylindroid, tapering slightly near both ends, measuring 16.3 ± 1.2 µm × 5.6 ± 0.4 µm, 16.1 ± 1.4 µm × 6.4 ± 0.7 µm, 16.2 ± 1.1 µm × 6.0 ± 0.4 µm (n=90) for HZ18-1, HZ22-3, and HZ46-3, respectively. Appressoria were brown, elliptic or fusoid, deeply lobed, measuring 10.2 ± 1.6 µm × 6.8 ± 1.0 µm, 10.7 ± 1.3 µm × 6.6 ± 0.8 µm, 9.3± 1.3 µm × 6.9 ± 0.9 µm (n=90) for HZ18-1, HZ22-3, and HZ46-3, respectively. These characteristics were consistent with the descriptions of Colletotrichum aeschynomenes B. Weir & P. R. Johnst (Weir et al. 2012). The internal transcribed spacer (ITS) region and the intergenic region and flanking regions of Apn2 and MAT1-2-1 (ApMAT) were amplified using ITS1/ITS4 and AM-F/AM-R primers, respectively (White et al. 1990; Silva et al. 2012). BLASTn analysis of the sequences showed over 99% identity with the corresponding loci from the culture collection C. aeschynomenes ICMP 17673 (ex-type). Sequences from the three isolates were deposited in GenBank (Accession Nos.: ITS, OM838335, OM838339, OM838370; ApMAT, OM816771, OM816775, OM816806). Phylogenetic maximum likelihood analysis with RAxML version 8.2.10 based on the concatenated sequences of ITS and ApMAT showed that the three isolates clustered with the ex-type specimen of C. aeschynomenes ICMP 17673. Pathogenicity was confirmed on leaves with and without wounds of 24 two-year-old Sanhua plum plants in a greenhouse. The wound was made with a sterilized toothpick. Wounded and unwounded leaves were inoculated with 20 µL of conidial suspension (106 conidia/mL) of the three isolates and control plants were inoculated with sterile distilled water (20 leaves/plant, 3 plants/treatment). All plants were covered with plastic bags to maintain high humidity. After 8 days of incubation at 25â with constant light, necrotic lesions were observed on inoculated leaves, whereas control plants showed no symptoms. To fulfill Koch's postulates, all fungi were successfully reisolated from symptomatic leaves. This species has been reported on Aeschynomene virginica in the United States (Weir et al. 2012), Manihot esculenta in Thailand (Sangpueak et al. 2018), Theobroma cacao (Nascimento et al. 2019) and Myrciaria dubia (Matos et al. 2020) in Brazil. To our knowledge, this is the first report of C. aeschynomenes causing Sanhua plum leaf anthracnose in China. The results will provide valuable information for management of anthracnose associated with Sanhua plum.
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Plum (Prunus salicina Lindl.) is widely cultivated for its rich nutrients and flavor in China. In August 2020, leaf blight symptoms were observed on plum in Meishan, Sichuan, China (N29°24', E104°30'). Irregular brown spots initially appeared on the edge or tip of the leaf, then extended to larger taupe lesions that were surrounded by a chlorotic halo. In the late stage, grey-brown blighted tissue covered the entire leaf causing leaves to wither, curl and abscise. The leaves with blight were collected from three different towns in Meishan where the disease incidence was found on 15-30% of plum plants. The margin of diseased leaves was cut into small pieces (3×3 mm), surface disinfected with 75% ethanol solution for 10 s, 2% NaOCl for 1 min, and rinsed in sterile distilled water three times. Tissue pieces were plated on potato dextrose agar (PDA) and incubated at 25°C. Forty-nine morphologically similar colonies were observed on PDA plates after 3-5 days and three of these (TEY9-1, TEY12-1, TEY15A-1) were selected for intensive study. The colonies produced abundant whitish to yellowish aerial mycelium after 7 days incubation at 25°C in the dark. Macroconidia on carnation leaf agar (CLA) were falcate, hyaline, straight to slightly curved, smooth to slightly rough with 3 to 6 septa, the apical cell was blunt or hooked, and the basal cell was barely notched, 31.6 ± 2.4 µm × 4.7 ± 0.4 µm, 28.9 ± 3.0 µm × 4.5 ± 0.5 µm, 32.5 ± 3.4 µm × 4.5 ± 0.5 for TEY9-1, TEY12-1, TEY15A-1, respectively. Microconidia were hyaline, fusoid or ovoid, nonseptate or one-septate, 14.4 ± 3.9 µm × 4.3 ± 0.6 µm, 13.0 ± 3.0 µm × 4.0 ± 0.4 µm, 11.0 ± 2.4 µm × 3.7 ± 0.5 for TEY9-1, TEY12-1, TEY15A-1, respectively. Genomic DNA was extracted from 7-day-old aerial mycelia of these isolates. The internal transcribed spacer (ITS), translation elongation factor (TEF1), calmodulin (CAM) and partial RNA polymerase second largest subunit (RPB2) were amplified using primers ITS4/ITS1, EF1/EF2, CL1/CL2A, and 5f2/7cr, respectively (White et al. 1990; O'Donnell et al. 2000, 2010). Sequences were deposited in GenBank (ITS: OK315638-OK315640; TEF1: OK338756-OK338758; CAM: OK338759-OK338761; RPB2: OK338762-OK338764). A maximum Likelihood (ML) phylogenetic tree was constructed with RAxML version 8.2.10 based on the concatenated sequences (ITS, TEF1, CAM, RPB2). According to morphology and phylogenetic analysis, TEY9-1 and TEY15A-1 were identified as Fusarium pernambucanum, and TEY12-1 was identified as Fusarium sulawesiense. Pathogenicity tests were conducted on young healthy leaves of 12 two-year-old plum plants in a 28°C greenhouse in Nanning, Guangxi, China. The epidermis of tested leaves was slightly scratched with sterile toothpick-tips forming a 3-mm-diameter cross-shaped wound, followed by inoculation with a 10 µl conidial suspension (106 spores /ml in 0.1% sterile Tween 20). Control leaves were wounded in the same way and treated with 0.1% sterile Tween 20. Plants were covered with polythene bags to maintain high humidity for 5 days. Inoculated leaves showed light brown to dark brown lesions, whereas control leaves were symptomless. Both species were re-isolated from symptomatic leaves, completing Koch's postulates. To our knowledge, this is the first report of F. pernambucanum and F. sulawesiense causing leaf blight on plum trees in China. These results will provide valuable information for prevention and management of leaf blight on plum trees.
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Submucous cleft palate, presenting as varying degrees of palatal bony defect, can be difficult to detect in its early stage. The connection between submucous cleft palate and cleft lip has been noticed by clinicians but are rarely reported in literature. AIMS: To investigate the correlation between the degree of deformity of palatal bony defect and that of cleft lip. PATIENTS AND METHODS: Thirty-four patients with unilateral (n = 23) or bilateral (n = 11) cleft lip presenting with submucous cleft palate were included. Patients were divided into 3 groups according to the degree of malformation of cleft lip (microform, incomplete, and complete). The length and width of palatal bony defect was then measured from the palatal computer tomography. RESULTS: In patients with unilateral cleft lip, the proportions of microform cleft lip, incomplete cleft lip, and complete cleft lip were 17.4%, 60.9%, and 21.7%, respectively. In patients with bilateral cleft lip, there were 3 cases with microform and 1 case with incomplete cleft lip on both sides. No correlation was found between the length or relative width of palatal bony defect with the side ( P length = 1.000; P relative width = 0.262) or the severity ( P length = 0.605; P relative width = 0.254) of cleft lip. CONCLUSIONS: The form of cleft lip presenting with submucous cleft palate varies, and there was no correlation with the length or relative width of palatal bony defect. Advanced imaging techniques for children with cleft lip may assist the early diagnosis of submucous cleft palate.
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Fenda Labial , Fissura Palatina , Criança , Fenda Labial/diagnóstico por imagem , Fenda Labial/cirurgia , Fissura Palatina/complicações , Fissura Palatina/diagnóstico por imagem , Fissura Palatina/cirurgia , Humanos , Idioma , Tomografia Computadorizada por Raios XRESUMO
Effective noise reduction and abnormal feature extraction are important for abnormal sound detection occurring in urban traffic operations. However, to improve the detection accuracy of continuous traffic flow and even overlapping vehicle bodies, effective methods capable to achieve accurate signal-to-noise ratio and appropriate characteristic parameters should be explored. In view of the disadvantages of traditional traffic detection methods, such as Short-Time Energy (STE) and Mel Frequency Cepstral Coefficients (MFCC), this study adopts an improved spectral subtraction method to analyze traffic noise. Through the feature fusion of STE and MFCC coefficients, an innovative feature parameter, E-MFCC, is obtained, assisting to propose a traffic noise detection solution based on Triangular Wave Analysis (TWA). APP Designer in MATLAB was used to establish a traffic detection simulation platform. The experimental results showed that compared with the accuracies of traffic detection using the traditional STE and MFCC methods as 67.77% and 76.01%, respectively, the detection accuracy of the proposed TWA is significantly improved, attaining 91%. The results demonstrated the effectiveness of the traffic detection method proposed in solving the overlapping problem, thus achieving accurate detection of road traffic volume and improving the efficiency of road operation.
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Condução de Veículo , Simulação por Computador , Ruído , Razão Sinal-RuídoRESUMO
In June 2020, the U.S. Food and Drug Administration granted accelerated approval to selinexor for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. Approval was based on SADAL, a multicenter trial of selinexor monotherapy in patients with DLBCL after two to five systemic regimens. Efficacy was based on independent review committee-assessed objective response rate (ORR) and duration of response using Lugano criteria. In 134 patients treated with the approved dosage (60 mg orally on days 1 and 3 of each week), the ORR was 29% (95% confidence interval, 22-38), with complete response in 13% and with 38% of responses lasting at least 6 months. Gastrointestinal toxicity developed in 80% of patients, hyponatremia in 61%, central neurological toxicity (such as dizziness and mental status changes) in 25%, and ocular toxicity in 18%. New or worsening grade 3 or 4 thrombocytopenia, lymphopenia, neutropenia, anemia, or hyponatremia developed in ≥15%. Adverse reactions led to selinexor dose interruption in 61% of patients, dose reduction in 49%, and permanent discontinuation in 17%, with thrombocytopenia being the leading cause of dose modifications. Postmarketing studies will evaluate reduced dosages of selinexor and further evaluate clinical benefit in patients with relapsed or refractory DLBCL. IMPLICATIONS FOR PRACTICE: Selinexor is a new potential option for adults with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, in the third-line setting or beyond. Toxicities are typically manageable but can be difficult to tolerate and necessitate close monitoring and supportive care.
Assuntos
Linfoma Difuso de Grandes Células B , Neutropenia , Humanos , Hidrazinas , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Estudos Multicêntricos como Assunto , Resultado do Tratamento , TriazóisRESUMO
BACKGROUND: Pediatric anticancer drug development has numerous challenges. The Pediatric Research Equity Act (PREA) and the Best Pharmaceuticals for Children Act (BPCA) were passed to address pediatric drug development deficiencies in general. Until recently, the requirements for pediatric evaluation of most oncology products developed for adult cancers have been waived. Because children typically do not have the same type of cancers, which occur commonly in adults, or the indication or drug had been granted an orphan designation, PREA therefore has had no impact. Pediatric studies for labeling updates are largely done through BPCA by a written request (WR) issued by the Food and Drug Administration (FDA). Because the cancers that occur in pediatric and adult populations do not share the same etiology or natural history, there are limited opportunities to extrapolate adult efficacy and safety to the pediatric population. The characteristics of individual pediatric studies included in WRs have varied greatly over time. PROCEDURE: In this study, we searched WRs that were issued by the FDA since 2001. We found 40 such requests issued for oncology drugs and biologics, which had been accepted by sponsors. RESULTS: Clinical trials included in 23 of the WRs have been concluded, 19 have resulted in exclusivity, and three drugs that were studied have been approved for use in pediatric populations. Herein, we present the spectrum of WRs from a regulatory, study design, dosing, formulation, analysis plan, evidentiary standard of efficacy, and safety perspective. CONCLUSIONS: This provides information on requests issued in the past nearly 20 years and studies that are completed. As WRs have provided the only regulatory mechanism to assure pediatric cancer drug development, this can potentially provide insight on how pediatric cancer drug development may change in the future.
Assuntos
Antineoplásicos/uso terapêutico , Aprovação de Drogas/legislação & jurisprudência , Avaliação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Criança , Ensaios Clínicos como Assunto/estatística & dados numéricos , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMO
A Gram staining-negative, halophilic, aerobic, non-motile bacteria, designated strain WN018T, were isolated from the natural saline-alkali wetland soil of Binhai new district, Tianjin, China (38°46'N, 117°13'E). Cells of strain WN018T were short rod-shaped, 0.3-0.4 µm wide and 0.5-1.9 µm long, and growth occurred optimally at 30-33 °C, pH 7.5-8.0, and in the presence of 4-8% (w/v) NaCl. Based on 16S rRNA gene sequence analysis, the isolates could be affiliated to the genus Halomonas, exhibiting highest sequence similarity of 97.50% to Halomonas venusta DSM 4743T. The DNA G+C content of the strain was 63.8%. The distinct phylogenetic position and phenotypic traits distinguished the novel isolate from its nearest neighbors. The major respiratory quinone of strain WN018T was Q-9 (91.0%) and Q-8 (9.0%), and the dominant fatty acids were C16:0, C14:0, C10:0, C12:0 3-OH. The major polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), three phospholipids (PL), aminolipid (AL), and two unidentified lipids (L). The average nucleotide identity (ANI) based on whole-genome sequences of strain WN018T and Halomonas hydrothermalis DSM 15725T was 93.02%, and the dDDH value between these two strains was determined to be 49.7%. Therefore, we propose a novel species in the genus Halomonas to accommodate the novel isolate: Halomonas humidisoli sp. nov. (type strain WN018T = ACCC 19975T = KCTC 52854T).
Assuntos
Halomonas , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/genética , Ácidos Graxos/análise , Halomonas/genética , Hibridização de Ácido Nucleico , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , SoloRESUMO
A Gram-staining-negative, halophilic, aerobic, oval-shaped or vibrio-shaped, motile by a polar flagellum strain, designated YL5-2T, was isolated from natural saline-alkaline wetland soil of Binhai new district, Tianjin, China. Strain YL5-2T grew optimally at 35 °C, pH 7.5-8.0, and in the presence of 10-25% (w/v) NaCl on MA medium. Phylogenetic analyses based on 16S rRNA gene sequences showed that the isolate belonged to the genus Halovibrio and exhibited high sequence similarity of 97.7% to Halovibrio variabilis DSM 3050T. The sole respiratory ubiquinone of strain YL5-2T is Q-9, and the dominant fatty acids were C18:1ω9c, C16:0, C19:0 cycloω8c, and Summed Feature 8. The major polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC), and lipid (L). The DNA G+C content of the strain was 62.1 mol%. The average nucleotide identity (ANI) based on whole genome sequences of strain YL5-2T and Halovibrio variabilis DSM 3050T was 93.85%, and the dDDH value between these two strains was determined to be 52.0%. Phenotypic, chemotaxonomic, phylogenetic, and genomic analyses suggested that strain YL5-2T represent a novel species of the genus Halovibrio, for which the name Halovibrio salipaludis sp. nov. is proposed. The type strain is YL5-2T (=KCTC 52852T=ACCC 19971T).
Assuntos
Microbiologia do Solo , Solo , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/genética , Ácidos Graxos , Halomonadaceae , Hibridização de Ácido Nucleico , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
BACKGROUND: Primitive electronic waste (e-waste) recycling is ongoing in Guiyu, so toxic heavy metals may continue to threaten the health of children in the area. OBJECTIVE: This study primarily aimed to evaluate the effect of e-waste exposure on haemoglobin (Hb) synthesis in preschool children. METHODS: Medical examinations were conducted with the permission of children's guardians and the approval of the Ethics Committee of the Medical College of Shantou University. This study recruited 224 children (aged 3-6 years, exposed group) who lived in Guiyu and 204 children (aged 3-6 years, control group) who lived in a town free of e-waste pollution. Blood levels of lead, Hb, ferritin, folate and vitamin B12 were tested in all children. Furthermore, all children were assessed for thalassemia, and their parents were asked to fill in questionnaires. RESULTS: There were no significant differences in the level of ferritin, folate, or vitamin B12 between the exposed and control groups (P > 0.05). No children were identified as having thalassemia in all study participants. Blood lead level (BLL) and the risk of children with BLL ≥ 10 µg/dL in the exposed group were significantly higher than those in the control group (all P < 0.01). Three subgroups of each group were created according to BLL (Group A: < 5.0 µg/dL; Group B: 5.0-9.9 µg/dL; Group C: ≥ 10.0 µg/dL). Hb level decreased with elevated BLL in the exposed group (P = 0.03), but not in the control group (P = 0.14). Hb levels in group B and group C were also significantly lower in the exposed group than in the control group (Group B: 122.6 ± 9.5 g/L versus 125.8 ± 8.2 g/L, P = 0.01; Group C: 120.3 ± 7.3 g/L versus 123.6 ± 8.3 g/L, P = 0.03). In addition, the prevalence of anaemia associated with BLLs above 10 µg/dL and between 5.0 and 9.9 µg/dL were both significantly higher in the exposed group than in the control group (4.0% vs. 0.5%, 5.4% vs. 1.5%, respectively, both P < 0.05). CONCLUSION: Lead exposure more significantly inhibits Hb synthesis in children who live in e-waste dismantling areas than in those who live in non-e-waste dismantling areas. Other toxins released from e-waste may also contribute to the inhibition of Hb synthesis and may lead to anaemia in local children. Further investigations are needed to provide evidence for the development of relevant protective measures.