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Ensembl (https://www.ensembl.org) is a freely available genomic resource that has produced high-quality annotations, tools, and services for vertebrates and model organisms for more than two decades. In recent years, there has been a dramatic shift in the genomic landscape, with a large increase in the number and phylogenetic breadth of high-quality reference genomes, alongside major advances in the pan-genome representations of higher species. In order to support these efforts and accelerate downstream research, Ensembl continues to focus on scaling for the rapid annotation of new genome assemblies, developing new methods for comparative analysis, and expanding the depth and quality of our genome annotations. This year we have continued our expansion to support global biodiversity research, doubling the number of annotated genomes we support on our Rapid Release site to over 1700, driven by our close collaboration with biodiversity projects such as Darwin Tree of Life. We have also strengthened support for key agricultural species, including the first regulatory builds for farmed animals, and have updated key tools and resources that support the global scientific community, notably the Ensembl Variant Effect Predictor. Ensembl data, software, and tools are freely available.
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Bases de Dados Genéticas , Genômica , Animais , Genoma , Anotação de Sequência Molecular , Filogenia , Software , HumanosRESUMO
Neuropeptides regulate animal physiology and behavior, making them widely studied targets of functional genetics research. While the field often relies on differential -omics approaches to build hypotheses, no such method exists for neuropeptidomics. It would nonetheless be valuable for studying behaviors suspected to be regulated by neuropeptides, especially when little information is otherwise available. This includes nictation, a phoretic strategy of Caenorhabditis elegans dauers that parallels host-finding strategies of infective juveniles of many pathogenic nematodes. We here developed a targeted peptidomics method for the model organism C. elegans and show that 161 quantified neuropeptides are more abundant in its dauer stage compared with L3 juveniles. Many of these have orthologs in the commercially relevant pathogenic nematode Steinernema carpocapsae, in whose infective juveniles, we identified 126 neuropeptides in total. Through further behavioral genetics experiments, we identify flp-7 and flp-11 as novel regulators of nictation. Our work advances knowledge on the genetics of nictation behavior and adds comparative neuropeptidomics as a tool to functional genetics workflows.
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Proteínas de Caenorhabditis elegans , Nematoides , Neuropeptídeos , Animais , Caenorhabditis elegans , Nematoides/fisiologia , Espectrometria de MassasRESUMO
Ensembl (https://www.ensembl.org) has produced high-quality genomic resources for vertebrates and model organisms for more than twenty years. During that time, our resources, services and tools have continually evolved in line with both the publicly available genome data and the downstream research and applications that utilise the Ensembl platform. In recent years we have witnessed a dramatic shift in the genomic landscape. There has been a large increase in the number of high-quality reference genomes through global biodiversity initiatives. In parallel, there have been major advances towards pangenome representations of higher species, where many alternative genome assemblies representing different breeds, cultivars, strains and haplotypes are now available. In order to support these efforts and accelerate downstream research, it is our goal at Ensembl to create high-quality annotations, tools and services for species across the tree of life. Here, we report our resources for popular reference genomes, the dramatic growth of our annotations (including haplotypes from the first human pangenome graphs), updates to the Ensembl Variant Effect Predictor (VEP), interactive protein structure predictions from AlphaFold DB, and the beta release of our new website.
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Bases de Dados Genéticas , Software , Animais , Humanos , Anotação de Sequência Molecular , Genômica , GenomaRESUMO
BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.
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Afatinib , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Afatinib/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Vietnã/epidemiologiaRESUMO
PURPOSE: Androgen deprivation therapy (ADT) is the mainstay approach for prostate cancer (PCa) management. However, the most commonly used ADT modality, gonadotropin-releasing hormone (GnRH) agonists, has been associated with an increased risk of cardiovascular disease (CVD). METHODS: The PCa Cardiovascular (PCCV) Expert Network, consisting of multinational urologists, cardiologists and oncologists with expertise in managing PCa, convened to discuss challenges to routine cardiovascular risk assessment in PCa management, as well as how to mitigate such risks in the current treatment landscape. RESULTS: The experts identified several barriers, including lack of awareness, time constraints, challenges in implementing risk assessment tools and difficulties in establishing multidisciplinary teams that include cardiologists. The experts subsequently provided practical recommendations to improve cardio-oncology care for patients with PCa receiving ADT, such as simplifying cardiovascular risk assessment, individualising treatment based on CVD risk categories, establishing multidisciplinary teams and referral networks and fostering active patient engagement. A streamlined cardiovascular risk-stratification tool and a referral/management guide were developed for seamless integration into urologists' practices and presented herein. The PCCV Expert Network agreed that currently available evidence indicates that GnRH antagonists are associated with a lower risk of CVD than that of GnRH agonists and that GnRH antagonists are preferred for patients with PCa and a high CVD risk. CONCLUSION: In summary, this article provides insights and guidance to improve management for patients with PCa undergoing ADT.
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Doenças Cardiovasculares , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/induzido quimicamente , Antagonistas de Androgênios/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Medição de Risco , Hormônio Liberador de GonadotropinaRESUMO
INTRODUCTION: Dynamically titrated crystalloids are the standard of care for burn shock resuscitation. There are theoretical concerns that the adjunctive use of allogeneic plasma may perturb the patient's coagulation and inflammation status deleteriously. It was hypothesized that plasma-inclusive resuscitation (PIR) would not be associated with prothrombotic changes relative to baseline after thermal injury. METHODS: Patients admitted to a regional burn center who were treated with PIR as part of their burn resuscitation were enrolled. Whole blood samples were analyzed prospectively via rapid thromboelastography and rotational thromboelastometry to assess for coagulopathy at four time points throughout their acute burn resuscitation. The mixed-effect model for repeated measures followed by Tukey's post hoc test for comparisons was used to examine group differences. RESULTS: There were 35 patients in the analysis. Most were male (74.3%) with a median age of 43 y (32-55), concomitant inhalation injury of 28.6%, total body surface area burn size of 34% (27%-48.5%), and the overall mortality of the cohort was 28.6%. There were no transfusion reactions or thrombotic events. There were no differences in thromboelastography or rotational thromboelastometry parameters overall or when stratified by mortality, total body surface area burn, and inhalation injury. There were no significant differences between the fibrinolytic phenotypes over time. CONCLUSIONS: Data suggest that PIR was not associated with prothrombotic or lytic changes in burn patients relative to baseline. Further research is needed to confirm these findings and evaluate efficacy of PIR in acute burn resuscitation.
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In Vietnam, the public sector has largely been responsible for delivering methadone maintenance treatment (MMT) services. However, with foreign aid anticipated to decline in the coming years, the involvement of the private sector in delivering MMT services is critical to ensure the continued sustainability of MMT programs across Vietnam. This study aims to evaluate patient satisfaction and identify correlated factors among Vietnamese drug users undergoing MMT in both public and private methadone clinics. A cross-sectional study was conducted in one private and two public methadone facilities in Nam Dinh, a province in the North of Vietnam. A convenience sampling technique was applied to recruit 395 participants. Data was collected through 20-minute face-to-face interviews using a structured questionnaire. Multivariate Tobit regression was utilized to measure associated factors with patient satisfaction. Results showed that patients were highly satisfied with MMT services in both public and private; however, they expected a higher degree of comprehensive care services. Compared with public facilities, the satisfaction level of patients in private facilities was significantly lower in the following aspects: health administration and professional capacity of health workers. However, there were insignificant differences in regard to infrastructure, equipment, and availability of medical services resources, supporting a promising role of the private sector in supporting the expansion of the MMT programs in Vietnam. Integrating MMT with other physical and mental healthcare services, along with strategies for improving administrative procedures and health workers' capacity in private clinics, are critical implications of this study.
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Ensembl (https://www.ensembl.org) is unique in its flexible infrastructure for access to genomic data and annotation. It has been designed to efficiently deliver annotation at scale for all eukaryotic life, and it also provides deep comprehensive annotation for key species. Genomes representing a greater diversity of species are increasingly being sequenced. In response, we have focussed our recent efforts on expediting the annotation of new assemblies. Here, we report the release of the greatest annual number of newly annotated genomes in the history of Ensembl via our dedicated Ensembl Rapid Release platform (http://rapid.ensembl.org). We have also developed a new method to generate comparative analyses at scale for these assemblies and, for the first time, we have annotated non-vertebrate eukaryotes. Meanwhile, we continually improve, extend and update the annotation for our high-value reference vertebrate genomes and report the details here. We have a range of specific software tools for specific tasks, such as the Ensembl Variant Effect Predictor (VEP) and the newly developed interface for the Variant Recoder. All Ensembl data, software and tools are freely available for download and are accessible programmatically.
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Bases de Dados Genéticas , Genoma/genética , Anotação de Sequência Molecular , Software , Animais , Biologia Computacional/classificação , HumanosRESUMO
Ensembl Genomes (https://www.ensemblgenomes.org) provides access to non-vertebrate genomes and analysis complementing vertebrate resources developed by the Ensembl project (https://www.ensembl.org). The two resources collectively present genome annotation through a consistent set of interfaces spanning the tree of life presenting genome sequence, annotation, variation, transcriptomic data and comparative analysis. Here, we present our largest increase in plant, metazoan and fungal genomes since the project's inception creating one of the world's most comprehensive genomic resources and describe our efforts to reduce genome redundancy in our Bacteria portal. We detail our new efforts in gene annotation, our emerging support for pangenome analysis, our efforts to accelerate data dissemination through the Ensembl Rapid Release resource and our new AlphaFold visualization. Finally, we present details of our future plans including updates on our integration with Ensembl, and how we plan to improve our support for the microbial research community. Software and data are made available without restriction via our website, online tools platform and programmatic interfaces (available under an Apache 2.0 license). Data updates are synchronised with Ensembl's release cycle.
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Bases de Dados Genéticas , Genômica , Internet , Software , Animais , Biologia Computacional , Genoma Bacteriano/genética , Genoma Fúngico/genética , Genoma de Planta/genética , Plantas/classificação , Plantas/genética , Vertebrados/classificação , Vertebrados/genéticaRESUMO
Three new spirostan glycosides, dracochinosides A-C (1-3), and four known steroidal glycosides (4-7) were isolated from the aerial parts of Dracaena cochinchinensis (Lour.) S.C.Chen. Their chemical structures were determined by the IR, HR-ESI-MS, 1D-, and 2D-NMR spectra. Compounds 1-3, 6 and 7 inhibited nitric oxide production in LPS activated RAW 264.7 cells with IC50 values ranging from 57.5 to 92.8 µM. In addition, all the isolated compounds exhibited at least one of seven tested microbial strains with the MIC values ranging from 0.016 to 0.128 mg/mL. This is the first report of compounds 5-7 from the genus Dracaena.
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Phytochemical study on the methanol extract of the leaves of Phyllanthus reticulatus led to the isolation of two new compounds, phyllanretiosides A (1) and B (2) together with ten known ones (3-12). Their chemical structures were determined by HR-ESI-MS, NMR, and ECD spectra in comparison with the literature. Three ellagitannins, phyllanretioside A (1), corilagin (3), and phyllanthusiin C (4) inhibited lipopolysaccharide(LPS)-induced nitric oxide production in RAW 264.7 cells with IC50 values of 63.2, 83.2, and 5.6â µM, respectively. In addition, compounds 1, 3, and 4 exhibited significantly antimicrobial activity (MICs: 16-128â µg/mL) towards some of seven microbial strains.
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This first study investigated the presence of dioxins and furans in river sediments around a craft village in Vietnam, focusing on Secondary Steel Recycling. Sediment samples were collected from various locations along the riverbed near the Da Hoi Secondary Steel Recycling village in Bac Ninh province. The analysis was conducted using a HRGC/HRMS-DFS device, detecting a total of 17 dioxin/furan isomers in all samples, with an average total concentration of 288.86 ng/kg d.w. The concentrations of dioxin/furan congeners showed minimal variation among sediment samples, ranging from 253.9 to 344.2 ng/kg d.w. The predominant compounds in the dioxin group were OCDD, while in the furan group, they were 1,2,3,4,6,7,8-HpCDF and OCDF. The chlorine content in the molecule appeared to be closely related to the concentration of dioxins and their percentage distribution. However, the levels of furan isomers did not vary significantly. The distribution of these compounds was not dependent on the flow direction, as they were mainly found in solid waste and are not water-soluble. Although the hepta and octa congeners had high concentrations, when converted to TEQ values, the tetra and penta groups (for dioxins) and the penta and hexa groups (for furans) contributed more to toxicity. Furthermore, the source of dioxins in sediments at Da Hoi does not only originate from steel recycling production activities but also from other combustion sites. The average total toxicity was 10.92 ng TEQ/kg d.w, ranging from 4.99 to 17.88 ng TEQ/kg d.w, which did not exceed the threshold specified in QCVN 43:2017/BTNMT, the National Technical Regulation on Sediment Quality. Nonetheless, these levels are still concerning. The presence of these toxic substances not only impacts aquatic organisms in the sampled water environment but also poses potential health risks to residents living nearby.
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Dioxinas , Monitoramento Ambiental , Furanos , Sedimentos Geológicos , Rios , Aço , Poluentes Químicos da Água , Rios/química , Vietnã , Sedimentos Geológicos/química , Sedimentos Geológicos/análise , Dioxinas/análise , Aço/química , Poluentes Químicos da Água/análise , Furanos/análise , Furanos/química , Monitoramento Ambiental/métodos , ReciclagemRESUMO
Traumatic brain injury (TBI) causes diffuse axonal injury which can produce chronic white matter pathology and subsequent post-traumatic neurodegeneration with poor patient outcomes. Tau modulates axon cytoskeletal functions and undergoes phosphorylation and mis-localization in neurodegenerative disorders. The effects of tau pathology on neurodegeneration after TBI are unclear. We used mice with neuronal expression of human mutant tau to examine effects of pathological tau on white matter pathology after TBI. Adult male and female hTau.P301S (Tg2541) transgenic and wild-type (Wt) mice received either moderate single TBI (s-TBI) or repetitive mild TBI (r-mTBI; once daily × 5), or sham procedures. Acutely, s-TBI produced more extensive axon damage in the corpus callosum (CC) as compared to r-mTBI. After s-TBI, significant CC thinning was present at 6 weeks and 4 months post-injury in Wt and transgenic mice, with homozygous tau expression producing additional pathology of late demyelination. In contrast, r-mTBI did not produce significant CC thinning except at the chronic time point of 4 months in homozygous mice, which exhibited significant CC atrophy (- 29.7%) with increased microgliosis. Serum neurofilament light quantification detected traumatic axonal injury at 1 day post-TBI in Wt and homozygous mice. At 4 months, high tau and neurofilament in homozygous mice implicated tau in chronic axon pathology. These findings did not have sex differences detected. Conclusions: Neuronal tau pathology differentially exacerbated CC pathology based on injury severity and chronicity. Ongoing CC atrophy from s-TBI became accompanied by late demyelination. Pathological tau significantly worsened CC atrophy during the chronic phase after r-mTBI.
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Lesões Encefálicas Traumáticas , Doenças Desmielinizantes , Tauopatias , Substância Branca , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Atrofia/patologia , Lesões Encefálicas Traumáticas/patologia , Doenças Desmielinizantes/patologia , Camundongos Transgênicos , Proteínas tau/genética , Proteínas tau/metabolismo , Substância Branca/patologiaRESUMO
Movement disorders are a major cause of disability worldwide and their increasing prevalence predicts a substantial future burden of care. Impactful patient care requires availability of, and accessibility to, effective medications, knowledge, and disease awareness among both medical professionals and patients, driven by skilled personnel to harness and manage resources. The highest burden of movement disorders is in low-to-middle income countries where resources are often limited and infrastructure is insufficient to meet growing demands. This article focuses on the specific challenges faced in the management and delivery of care for movement disorders in Indochina, the mainland region of Southeast Asia comprising the neighboring countries of Cambodia, Laos, Malaysia, Myanmar, Thailand, and Vietnam. The first Indochina Movement Disorders Conference was held in August 2022 in Ho Chi Minh City, Vietnam, to provide a platform to better understand the situation in the region. Future management of movement disorders in Indochina will require progressive adaptation of existing practices to reflect modern approaches to care delivery. Digital technologies offer an opportunity to strengthen these processes and address the challenges identified in the region. Ultimately, a long-term collaborative approach by regional healthcare providers is key.
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Transtornos dos Movimentos , Humanos , Indochina , Sudeste Asiático/epidemiologia , Vietnã/epidemiologia , TailândiaRESUMO
Community health workers (CHW) can play an active role in providing integrated HIV and harm reduction services. We used social media to create a virtual network among Vietnamese CHW. This paper reports CHW's social media engagement and the relationships with other work-related indicators. Sixty CHW participated in an intervention for integrated HIV/drug use service delivery. Following two in-person sessions, Facebook groups were established for CHW to share information, seek consultation, and refer patients. CHW's levels of online engagements were tracked for six months and linked to their service provision confidence, interaction with patients and other providers, and job satisfaction. The CHW made 181 posts, which received 557 comments and 1,607 reactions during the six months. Among the 60 CHW, 22 (36.6%) had three or more posts, 19 (31.7%) had one or two posts, and 19 (31.7%) had no post. Comparing the baseline and 6-month follow-up data, we observed that those who posted three or more times showed better service provision confidence (p = 0.0081), more interaction with providers in other settings (p = 0.0071), and higher job satisfaction (p = 0.0268). Our study suggests using social media to engage CHW in virtual communications to improve service provision in communities.
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Infecções por HIV , Mídias Sociais , Humanos , Agentes Comunitários de Saúde , Vietnã , ComunicaçãoRESUMO
Herein, dual-emission carbon dots (DE-CDs) were synthesized using a one-pot hydrothermal method. DE-CDs exhibited two well-separated peaks at 433 and 513 nm under ultraviolet excitation. The prepared DE-CDs offer selective detection of Fe3+ ions via inner filter effect (IFE) and Pb2+ ions via aggregation-induced enhancement (AIE). The obtained DE-CDs showed a good affinity for both Fe3+ and Pb2+ ions in the presence of various interfering ions. The limits of detection were 0.797 ppm and 4.739 ppm for Pb2+ and Fe3+, respectively. The finding reveals the huge potential of DE-CDs for the selective detection of multiple targets in one solution.
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Combination of high quality cavity such as glass microsphere and emitting nano-particle coating layers can create novel strongly emitting devices. Herein, we demonstrate an erbium-doped silica microsphere coated by dual-emission carbon quantum dots, which have the sizes of 3-5 nm, emitting green up-conversion with narrow line-width green light at wavelength of 537 nm. The dual-emission carbon quantum dots fabricated by hydrothermal process and have luminescent emission wavelengths in the range of 410-550 nm. The carbon quantum dot coated erbium silica microsphere is pumped at wavelength of 976 nm through the optical fibre on which microsphere attached on the tip. The dual-emission carbon quantum dot layers attributed to the strong green up-conversion light enhancement similar coated noble metallic thin films, however the light enhancement from dual-emission carbon quantum dot coated erbium silica microsphere depended on the thickness of coating layers. This result is useful for making visible emitting micro-devices and photonic integrated circuits.
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The Ensembl project (https://www.ensembl.org) annotates genomes and disseminates genomic data for vertebrate species. We create detailed and comprehensive annotation of gene structures, regulatory elements and variants, and enable comparative genomics by inferring the evolutionary history of genes and genomes. Our integrated genomic data are made available in a variety of ways, including genome browsers, search interfaces, specialist tools such as the Ensembl Variant Effect Predictor, download files and programmatic interfaces. Here, we present recent Ensembl developments including two new website portals. Ensembl Rapid Release (http://rapid.ensembl.org) is designed to provide core tools and services for genomes as soon as possible and has been deployed to support large biodiversity sequencing projects. Our SARS-CoV-2 genome browser (https://covid-19.ensembl.org) integrates our own annotation with publicly available genomic data from numerous sources to facilitate the use of genomics in the international scientific response to the COVID-19 pandemic. We also report on other updates to our annotation resources, tools and services. All Ensembl data and software are freely available without restriction.
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Biologia Computacional/métodos , Bases de Dados de Ácidos Nucleicos , Genômica/métodos , SARS-CoV-2/genética , Vertebrados/genética , Animais , COVID-19/epidemiologia , COVID-19/virologia , Humanos , Internet , Anotação de Sequência Molecular/métodos , Pandemias , Vertebrados/classificaçãoRESUMO
Delmopinol hydrochloride (delmopinol) is a cationic surfactant that is effective for treating and preventing gingivitis and periodontitis. This study evaluated the effectiveness of delmopinol for reducing attachment of Campylobacter jejuni to chicken meat, stainless steel, and high-density polyethylene (HDPE). These test materials were spot-inoculated with a C. jejuni culture. After 10 min, samples were sprayed with 0.5% or 1.0% delmopinol, 0.01% sodium hypochlorite, or distilled water. After a 1, 10, or 20 min contact time, samples were rinsed, which were serially diluted onto Campy-Cefex Agar. For additional samples, solutions were applied before inoculation with C. jejuni. Cultures remained undisturbed for 1, 10, or 20 min. Samples were then rinsed and plated as above. When C. jejuni was inoculated before treatments, 1% delmopinol application led to mean log reductions of 1.26, 3.70, and 3.72 log cfu ml-1, greater than distilled water alone, for chicken, steel and HDPE, respectively. When C. jejuni was inoculated after spray treatments, 1% delmopinol reduced C. jejuni by 2.72, 3.20, and 3.99 mean log cfu ml-1 more than distilled water for chicken, steel and HDPE, respectively. Application of 1% delmopinol, resulted in a significantly (P < .05) greater log reduction than a 0.01% sodium hypochlorite or distilled water application.
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Campylobacter jejuni , Animais , Polietileno , Aço Inoxidável , Aves Domésticas , Hipoclorito de Sódio/farmacologia , Carne , Microbiologia de Alimentos , Galinhas , Água , Contagem de Colônia MicrobianaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is the fastest increasing cause of cancer death in Australia. A recent Australian consensus guidelines recommended HCC surveillance for cirrhotic patients and non-cirrhotic chronic hepatitis B (CHB) patients at gender and age specific cut-offs. A cost-effectiveness model was then developed to assess surveillance strategies in Australia. METHODS: A microsimulation model was used to evaluate three strategies: biannual ultrasound, biannual ultrasound with alpha-fetoprotein (AFP) and no formal surveillance for patients having one of the conditions: non-cirrhotic CHB, compensated cirrhosis or decompensated cirrhosis. One-way and probabilistic sensitivity analyses as well as scenario and threshold analyses were conducted to account for uncertainties: including exclusive surveillance of CHB, compensated cirrhosis or decompensated cirrhosis populations; impact of obesity on ultrasound sensitivity; real-world adherence rate; and different cohort's ranges of ages. RESULTS: Sixty HCC surveillance scenarios were considered for the baseline population. The ultrasound + AFP strategy was the most cost-effective with incremental cost-effectiveness ratios (ICER) compared to no surveillance falling below the willingness-to-pay threshold of A$50,000 per quality-adjusted life year (QALY) at all age ranges. Ultrasound alone was also cost-effective, but the strategy was dominated by ultrasound + AFP. Surveillance was cost-effective in the compensated and decompensated cirrhosis populations alone (ICERs < $30,000), but not cost-effective in the CHB population (ICERs > $100,000). Obesity could decrease the diagnostic performance of ultrasound, which in turn, reduce the cost-effectiveness of ultrasound ± AFP, but the strategies remained cost-effective. CONCLUSIONS: HCC surveillance based on Australian recommendations using biannual ultrasound ± AFP was cost-effective.