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INTRODUCTION: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is beneficial in acute ischaemic stroke (AIS). We aim to compare the realworld clinical outcomes and service efficiency of IVT in Malaysian primary stroke centres (PSCs) versus acute stroke ready hospitals (ASRHs). MATERIALS AND METHODS: We conducted a multi-centre cohort study involving 5 PSCs and 7 ASRHs in Malaysia. Through review of medical records of AIS patients who received IVT from 01 January 2014 to 30 June 2021, real-world data was extracted for analysis. Univariate and multivariate regression models were employed to evaluate the role of PSCs versus ASRHs in post-IVT outcomes and complications. Statistical significance was set at p<0.05. RESULTS: A total of 313 multi-ethnic Asians, namely 231 from PSCs and 82 from ASRHs, were included. Both groups were comparable in baseline demographic, clinical, and stroke characteristics. The efficiency of IVT delivery (door-toneedle time), functional outcomes (mRS at 3 months post- IVT), and rates of adverse events (intracranial haemorrhages and mortality) following IVT were comparable between the 2 groups. Notably, 46.8% and 48.8% of patients in PSCs and ASRHs group respectively (p=0.752) achieved favourable functional outcome (mRS≤1 at 3 months post-IVT). Regression analyses demonstrated that post-IVT functional outcomes and adverse events were independent of the role of PSCs or ASRHs. CONCLUSION: Our study provides real-world evidence which suggests that IVT can be equally safe, effective, and efficiently delivered in ASRHs. This may encourage the establishment of more ASRHs to extend the benefits of IVT to a greater proportion of stroke populations and enhance the regional stroke care.
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The reduced dielectric screening in atomically thin two-dimensional materials makes them very sensitive to the surrounding environment, which can be modulated to tune their optoelectronic properties. In this study, we significantly improved the optoelectronic properties of monolayer MoS2by varying the surrounding environment using different liquid dielectrics, each with a specific dielectric constant ranging from 1.89 to 18. Liquid mediums offer the possibility of environment tunability on the same device. For a back-gated field effect transistor, the field effect mobility exhibited more than two-order enhancement when exposed to a high dielectric constant medium. Further investigation into the effect of the dielectric environment on the optoelectronic properties demonstrated a variation in photoresponse relaxation time with the dielectric medium. The rise and decay times were observed to increase and decrease, respectively, with an increase in the dielectric constant of the medium. These results can be attributed to the dielectric screening provided by the surrounding medium, which strongly modifies the charged impurity scattering, the band gap, and defect levels of monolayer MoS2. These findings have important implications for the design of biological and chemical sensors, particularly those operating in a liquid environment. By leveraging the tunability of the dielectric medium, we can optimize the performance of such sensors and enhance their detection capabilities.
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Models of artificial intelligence (AI) that have billions of parameters can achieve high accuracy across a range of tasks1,2, but they exacerbate the poor energy efficiency of conventional general-purpose processors, such as graphics processing units or central processing units. Analog in-memory computing (analog-AI)3-7 can provide better energy efficiency by performing matrix-vector multiplications in parallel on 'memory tiles'. However, analog-AI has yet to demonstrate software-equivalent (SWeq) accuracy on models that require many such tiles and efficient communication of neural-network activations between the tiles. Here we present an analog-AI chip that combines 35 million phase-change memory devices across 34 tiles, massively parallel inter-tile communication and analog, low-power peripheral circuitry that can achieve up to 12.4 tera-operations per second per watt (TOPS/W) chip-sustained performance. We demonstrate fully end-to-end SWeq accuracy for a small keyword-spotting network and near-SWeq accuracy on the much larger MLPerf8 recurrent neural-network transducer (RNNT), with more than 45 million weights mapped onto more than 140 million phase-change memory devices across five chips.
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BACKGROUND: Vestibular dysfunction in children is a debilitating condition that results in countless pernicious effects, such as motor development delay, poor academic performance and psychosocial impairment. Yet, research pertaining to vestibular and balance disorders amongst adolescents is still lacking and remains an enigma. METHODS: This paper outlines novel emerging aetiological factors contributing to vestibular dysfunction amongst adolescents by appraising published articles through a narrative review. RESULTS: Underlying aetiological factors of vestibular dysfunction can be identified among adolescents with thorough evaluation. Proper diagnostic evaluation of vestibular dysfunction is imperative in providing optimal care and guiding appropriate treatment strategies. The available literature demonstrated multifactorial aetiological factors that contribute to vestibular dysfunction in adolescents. CONCLUSION: Outlining the underlying aetiological factors of vestibular dysfunction is vital to ensure that patients receive appropriate care and treatment.
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Doenças Vestibulares , Vestíbulo do Labirinto , Criança , Humanos , Adolescente , Vertigem/diagnóstico , Tontura/etiologia , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/etiologiaRESUMO
The road to the delivery of high-quality cleft surgery into communities in the LMIC is beset with numerous hurdles. These include the availability of trained health care personnel, the availability of infrastructure in health care, parent awareness of the need for timely interventions in these children, presence of affordable treatment centres with adequate means of transport to and from these facilities for patients coming from the interior rural locations, but most importantly, the financial considerations that are the underlying limitations in most of these above mentioned considerations. We would like to approach this problem by describing the evolution of our own centre over several decades. Our centre, The Charles Pinto Centre for Cleft lip and palate at the Jubilee Mission Hospital is located in Thrissur, in the beautiful state of Kerala. In the late 1950s, Dr HS Adenwalla who had trained under experts in the art of Cleft Lip and Palate Surgery in Mumbai joined the hospital and transformed it through sheer dedication and meticulous clinical expertise into a major hub for treatment and also training in this speciality. In this endeavour he was greatly helped by non governmental organizations of which Smile Train deserves special mention in view of its model of functioning, empowering local partners by adequate funding for treatment, training and establishment of infrastructure, while ensuring strict adherence to safety standards. We believe that it is essential that there should be trained and dedicated health care personnel who are willing to treat such patients without an eye on the monetary benefits accrued, and also enough funding either from the government or from the NGOs to provide equipment and infrastructure for safe, high quality and accessible treatment and the establishment of multidisciplinary management. Lastly, the patients should also be made aware of the need for timely treatment and long-term follow- up.
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The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low inducible STAT3 activity was independently associated with inferior event-free survival in multivariate analyses. For inducible STAT5 activity, those with the lowest and highest responses had inferior event-free survival, compared to patients with intermediate STAT5 responses. Using existing RNA-sequencing data, we compared gene expression profiles for patients with low inducible STAT3/5 activation with those for patients with higher inducible STAT3/5 signaling. Genes encoding hematopoietic factors and mitochondrial respiratory chain subunits were overexpressed in the low STAT3/5 response groups, implicating inflammatory and metabolic pathways as potential mechanisms of chemotherapy resistance. We validated the prognostic relevance of individual genes from the low STAT3/5 response signature in a large independent cohort of pediatric AML patients. These findings provide novel insights into interactions between AML cells and the microenvironment that are associated with treatment failure and could be targeted for therapeutic interventions (AU)
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Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Regulação Neoplásica da Expressão Gênica , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT5/genética , Fator de Transcrição STAT5/metabolismo , Falha de TratamentoRESUMO
BACKGROUND: Despite the rapidly emerging reports of olfactory dysfunction amongst adult patients with coronavirus disease 2019, cases involving children and adolescents are scarcely reported. The literature was reviewed to elucidate olfactory dysfunction amongst children and adolescents with coronavirus disease 2019. METHODS: A search of the literature published from 1 December 2019 to 30 April 2021 was conducted using four databases, based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The search was performed over one month (May 2021). RESULTS: Only 9 articles were identified, with a total of 316 laboratory confirmed coronavirus disease 2019 positive children and adolescents, of whom 156 reported olfactory dysfunction. Four studies reported olfactory dysfunction based on subjective tests; four studies carried out objective assessment. Most studies reported on olfaction recovery. CONCLUSION: The literature review revealed an olfactory dysfunction rate of 49 per cent amongst children and adolescents with coronavirus disease 2019. Persistence of olfactory dysfunction was reported in 7.1 per cent of the patients. Further studies involving objective measures need to be carried out in children and adolescents with coronavirus disease 2019.
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COVID-19/complicações , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/virologia , SARS-CoV-2 , Adolescente , Criança , Feminino , Humanos , MasculinoRESUMO
The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low inducible STAT3 activity was independently associated with inferior event-free survival in multivariate analyses. For inducible STAT5 activity, those with the lowest and highest responses had inferior event-free survival, compared to patients with intermediate STAT5 responses. Using existing RNA-sequencing data, we compared gene expression profiles for patients with low inducible STAT3/5 activation with those for patients with higher inducible STAT3/5 signaling. Genes encoding hematopoietic factors and mitochondrial respiratory chain subunits were overexpressed in the low STAT3/5 response groups, implicating inflammatory and metabolic pathways as potential mechanisms of chemotherapy resistance. We validated the prognostic relevance of individual genes from the low STAT3/5 response signature in a large independent cohort of pediatric AML patients. These findings provide novel insights into interactions between AML cells and the microenvironment that are associated with treatment failure and could be targeted for therapeutic interventions.
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Fator Estimulador de Colônias de Granulócitos/farmacologia , Leucemia Mieloide Aguda/genética , Sistema de Sinalização das MAP Quinases , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT5/genética , Transcriptoma , Proteínas Supressoras de Tumor/genética , Adolescente , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Criança , Pré-Escolar , Criopreservação , Meios de Cultivo Condicionados/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Perfilação da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Interleucina-13/farmacologia , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Análise Multivariada , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Recidiva , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT5/metabolismo , Análise de Sequência de RNA , Ativação Transcricional , Microambiente Tumoral , Proteínas Supressoras de Tumor/metabolismo , Regulação para Cima , Adulto JovemRESUMO
Geographically, most tuberculosis (TB) cases in 2018 were reported from India. This TB burden is compounded by MDR-TB and XDR-TB. The strategies for the management and control of TB in the community depend on an understanding of the mode of spread of the different strains of TB isolates in the community. To determine the distribution and trends of M. tb strains over the time period in the community due to treatment, we carried out the present study on changes over two decades. Design/Methods. A total of 1218 M. tb isolates (year: 2001-2018) from Tiruvallur, India, were genotyped by spoligotyping after DNA extraction and subjected to anti-TB drug susceptibility testing for the first-line anti-TB drugs. Results. On analysis with the SpolDB4 database, majority (2001-2003: 53.32% and 2015-2018: 46.3%) of the isolates belonged to East African Indian (EAI) lineage, and the orphans designated in comparison to SpolDB4 stood 33% among 2001-2003 strain collection and 46.3% among 2015-2018 strain collection. 10.2% (2001-2003) and 9.26% (2015 to 2018) of isolates were monoresistant to isoniazid (H). MDR strains were less common among EAI strains (3.2%) compared to non-EAI strains (10.32%). Conclusions. EAI is the most predominant lineage in Tiruvallur, despite the presence of highly transmissible lineages like Beijing for the last two decades. The prevalence of MDR-TB is below the national average of 2-3% among the new TB cases in the last two decades. The reason can be attributed to the well-established nature of the locally circulating strains in this region which are not associated with drug resistance.
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BACKGROUND: Nasal lavage with mupirocin has the potential to reduce sinonasal morbidity in endoscopic endonasal approaches for skull base surgery. OBJECTIVE: To evaluate the effects of nasal lavage with and without mupirocin after endoscopic endonasal skull base surgery. METHODS: A pilot randomised, controlled trial was conducted on 20 adult patients who had undergone endoscopic endonasal approaches for skull base lesions. These patients were randomly assigned to cohorts using nasal lavages with mupirocin or without mupirocin. Patients were assessed in the out-patient clinic, one week and one month after surgery, using the 22-item Sino-Nasal Outcome Test questionnaire and nasal endoscopy. RESULTS: Patients in the mupirocin nasal lavage group had lower nasal endoscopy scores post-operatively, and a statistically significant larger difference in nasal endoscopy scores at one month compared to one week. The mupirocin nasal lavage group also showed better Sino-Nasal Outcome Test scores at one month compared to the group without mupirocin. CONCLUSION: Nasal lavage with mupirocin seems to yield better outcomes regarding patients' symptoms and endoscopic findings.
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Antibioticoprofilaxia/métodos , Endoscopia/efeitos adversos , Mupirocina/uso terapêutico , Lavagem Nasal/métodos , Procedimentos Cirúrgicos Nasais/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Neoplasias da Base do Crânio/cirurgia , Adulto , Idoso , Endoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Nasais/métodos , Projetos Piloto , Complicações Pós-Operatórias/microbiologia , Base do Crânio/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
The title mol-ecular salts, C16H16NO+·PF6 -, (I), and C21H21N2 +·PF6 -, (II), are pyridine derivatives. In compound (I), the cation comprises a methyl N-substituted pyridine ring and a meth-oxy-substituted benzene ring connected by a C=C double bond. The F atoms of the PF6 - anion are disordered over two sets of sites with refined occupancy factors of 0.614â (7):0.386â (7). In compound (II), the cation comprises a pyridine ring attached to unsubstituted phenyl ring and a di-methyl-aniline ring, which are connected by a C=C double bond. The anion is PF6 -. In both salts, the cation adopts an E configuration with respect to the C=C bond. The pyridine ring makes a dihedral angle of 9.86â (12)° with the meth-oxy-substituted benzene ring in compound (I) and 11.2â (3)° with the di-methyl-amine-substituted benzene ring in compound (II). In compound (I), the crystal packing is stabilized by weak C-Hâ¯F inter-molecular inter-actions which result in R 4 3(14) ring motifs, forming mol-ecular sheets running parallel to (03). These are further stabilized by weak P-Fâ¯π interactions. In compound (II), the crystal packing is stabilized by C-Hâ¯F inter-actions, which result in R 6 6(40) ring motifs, forming mol-ecular sheets running parallel to (101) and these are further connected by π-π inter-actions.
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In the title 1-oxo-1,2-di-hydro-naphthalene derivatives, C28H24O6, (I), C34H22O5S, (II), and C27H20O3S2, (III), the cyclo-hexa-1,3-diene rings of the 1,2-di-hydro-naphthalene ring systems adopt half-chair, boat and half-chair conformations, respectively. The carbonyl O atoms attached to the di-hydro-naphthalene ring systems are each significantly deviated from the mean plane of the 1,2-di-hydro-naphthalene ring system, by 0.6162â (12)â Å in (I), 0.6016â (16)â Å in (II) and 0.515â (3)â Å in (III). The mean planes of the 1,2-di-hydro-naphthalene ring systems make dihedral angles of 85.83â (3), 88.19â (3) and 81.67â (8)°, respectively, with the methyl-phenyl ring in (I), the pyrene ring in (II) and the phenyl ring in (III). In (I), the mol-ecular structure is stabilized by an intra-molecular C-Hâ¯O hydrogen bond, generating an S(6) ring motif. In the crystal of (I), mol-ecules are linked by an inter-molecular C-Hâ¯O hydrogen bond, which generates a C(8) zigzag chain running along [100]. Adjacent chains are further connected by C-Hâ¯π and offset π-π inter-actions [centroid-centroid distance = 3.6572â (9)â Å], forming a double-chain structure. In the crystals of (II) and (III), mol-ecules are linked into chain structures by offset π-π inter-actions with centroid-centroid distances of 3.5349â (12) and 3.8845â (13)â Å for (II) and 3.588â (2)â Å for (III). In (II) and (III), the thio-phene rings are orientationally disordered over two sites, with occupancy ratios of 0.69:0.31 for (II), and 0.528â (4):0.472â (4) and 0.632â (5):0.368â (5) for (III).