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1.
PLoS Biol ; 21(7): e3002168, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37410722

RESUMO

We know little about mammalian anemotaxis or wind sensing. Recently, however, Hartmann and colleagues showed whisker-based anemotaxis in rats. To investigate how whiskers sense airflow, we first tracked whisker tips in anesthetized rats under low (0.5 m/s) and high (1.5 m/s) airflow. Whisker tips showed increasing movement from low to high airflow conditions, with all whisker tips moving during high airflow. Low airflow conditions-most similar to naturally occurring wind stimuli-engaged whisker tips differentially. Most whiskers moved little, but the long supra-orbital (lSO) whisker showed maximal displacement, followed by the α, ß, and A1 whiskers. The lSO whisker differs from other whiskers in its exposed dorsal position, upward bending, length and thin diameter. Ex vivo extracted lSO whiskers also showed exceptional airflow displacement, suggesting whisker-intrinsic biomechanics mediate the unique airflow-sensitivity. Micro computed tomography (micro-CT) revealed that the ring-wulst-the follicle structure receiving the most sensitive afferents-was more complete/closed in the lSO, and other wind-sensitive whiskers, than in non-wind-sensitive whiskers, suggesting specialization of the supra-orbital for omni-directional sensing. We localized and targeted the cortical supra-orbital whisker representation in simultaneous Neuropixels recordings with D/E-row whisker barrels. Responses to wind-stimuli were stronger in the supra-orbital whisker representation than in D/E-row barrel cortex. We assessed the behavioral significance of whiskers in an airflow-sensing paradigm. We observed that rats spontaneously turn towards airflow stimuli in complete darkness. Selective trimming of wind-responsive whiskers diminished airflow turning responses more than trimming of non-wind-responsive whiskers. Lidocaine injections targeted to supra-orbital whisker follicles also diminished airflow turning responses compared to control injections. We conclude that supra-orbital whiskers act as wind antennae.


Assuntos
Córtex Somatossensorial , Vibrissas , Ratos , Animais , Vibrissas/fisiologia , Microtomografia por Raio-X , Córtex Somatossensorial/fisiologia , Estimulação Física , Movimento/fisiologia , Mamíferos
2.
J Gene Med ; 26(1): e3634, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37985132

RESUMO

BACKGROUND: Clopidogrel is an antiplatelet drug widely prescribed to prevent atherothrombotic events in coronary artery disease patients. However, there is evidence to suggest that the effectiveness of clopidogrel varies owing to genetic diversity in CYP2C19. This heterogeneity in South Asians, who are also known to have high risk of cardiac events than other population groups, highlights the importance of investigating CYP2C19 variants to estimate the risk proportion in the groups. METHODS: Given the high prevalence and genetic heterogeneity, the population-based case control was conducted in a cohort of 1191 subjects comprising 645 acute coronary syndrome (ACS) cases (unstable angina, ST-elevation myocardial infarction, and non-ST-elevation myocardial infarction) and 546 healthy controls of South Asian Indian origin. The metabolization status of CYP2C19 was assessed using *2, *3 and *17 variants in the stated cohorts to determine the prevalence of metabolization and its association with phenotypes. RESULTS: The results suggest a possible genetic association between studied CYP2C19 polymorphisms and ACS, since there was a higher proportion of intermediate and poor metabolizers present in the studied cohorts. The association analyses revealed that the *2 allele of CYP2C19 confers a significant risk for ACS, while the *17 allele provides protection. CONCLUSIONS: These findings contribute to the understanding of CYP2C19 genetic variants and their impact on clopidogrel response in South Asian Indians. Additionally, they underline the significance of assessing CYP2C19 variations in patients receiving clopidogrel therapy in order to improve therapeutic outcomes.


Assuntos
Síndrome Coronariana Aguda , Ticlopidina , Humanos , Clopidogrel/uso terapêutico , Alelos , Ticlopidina/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/genética , Farmacogenética , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/uso terapêutico , Genótipo , Resultado do Tratamento
3.
Brief Bioinform ; 23(4)2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35724564

RESUMO

In molecular biology, it is a general assumption that the ensemble of expressed molecules, their activities and interactions determine biological function, cellular states and phenotypes. Stable protein complexes-or macromolecular machines-are, in turn, the key functional entities mediating and modulating most biological processes. Although identifying protein complexes and their subunit composition can now be done inexpensively and at scale, determining their function remains challenging and labor intensive. This study describes Protein Complex Function predictor (PCfun), the first computational framework for the systematic annotation of protein complex functions using Gene Ontology (GO) terms. PCfun is built upon a word embedding using natural language processing techniques based on 1 million open access PubMed Central articles. Specifically, PCfun leverages two approaches for accurately identifying protein complex function, including: (i) an unsupervised approach that obtains the nearest neighbor (NN) GO term word vectors for a protein complex query vector and (ii) a supervised approach using Random Forest (RF) models trained specifically for recovering the GO terms of protein complex queries described in the CORUM protein complex database. PCfun consolidates both approaches by performing a hypergeometric statistical test to enrich the top NN GO terms within the child terms of the GO terms predicted by the RF models. The documentation and implementation of the PCfun package are available at https://github.com/sharmavaruns/PCfun. We anticipate that PCfun will serve as a useful tool and novel paradigm for the large-scale characterization of protein complex function.


Assuntos
Biologia Computacional , Proteínas , Biologia Computacional/métodos , Bases de Dados de Proteínas , Ontologia Genética , Humanos , Processamento de Linguagem Natural
4.
BJU Int ; 133 Suppl 4: 44-52, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38238965

RESUMO

OBJECTIVE: To evaluate near-infrared (NIR) spectroscopy in differentiating between benign and malignant bladder pathologies ex vivo immediately after resection, including the grade and stage of malignancy. PATIENTS AND METHODS: A total of 355 spectra were measured on 71 bladder specimens from patients undergoing transurethral resection of bladder tumour (TURBT) between April and August 2022. Scan time was 5 s, undertaken using a portable NIR spectrometer within 10 min from excision. Specimens were then sent for routine histopathological correlation. Machine learning models were applied to the spectral dataset to construct diagnostic algorithms; these were then tested for their ability to predict the histological diagnosis of each sample using its NIR spectrum. RESULTS: A two-group algorithm comparing low- vs high-grade urothelial cancer demonstrated 97% sensitivity, 99% specificity, and the area under the receiver operating characteristic curve (AUC) was 0.997. A three-group algorithm predicting stages Ta vs T1 vs T2 achieved 97% sensitivity, 92% specificity, and the AUC was 0.996. CONCLUSIONS: This first study evaluating the diagnostic potential of NIR spectroscopy in urothelial cancer shows that it can be accurately used to assess tissue in an ex vivo setting immediately after TURBT. This offers point-of-care assessment of bladder pathology, with potential to influence the extent of resection, reducing both the need for re-resection where invasive disease may be suspected, and also the potential for complications where extent of diagnostic resection can be limited. Further studies utilising fibre-optic probes offer the potential for in vivo assessment.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Bexiga Urinária/patologia , Espectroscopia de Luz Próxima ao Infravermelho , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos
5.
Popul Stud (Camb) ; 78(1): 63-77, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38032523

RESUMO

The practice of women eating after men is a common gender-inequitable food allocation mechanism among adults in Indian households and has been associated with poor health and nutritional outcomes for women. However, empirical evidence on whether a similar practice of girls eating after boys is prevalent among children is scarce. Using primary data from a household survey conducted in educationally backward areas of four Indian states, we provide new evidence of this practice among children. Almost 28 per cent of the sample households follow the mealtime custom of girls eating after boys. Scheduled Tribes and households with higher incomes are less likely to follow this practice. Other relevant factors include children's relative ages by sex and an interplay between family size and children's sex composition. While our findings may not be generalizable, they suggest an intersectionality between gender and other dimensions of inequality, namely social identity and economic class.


Assuntos
Características da Família , Equidade de Gênero , Criança , Masculino , Adulto , Humanos , Feminino , Índia , Renda
6.
Heart Lung Circ ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38871531

RESUMO

BACKGROUND: Although ultrasound (US) guidance for vascular access has been widely adopted, its use for transradial access (TRA) in the cardiac catheterisation laboratory is rare. There is a perception that US guidance does not offer a clinically relevant benefit over traditional palpation-guided TRA, amplified by inconsistent findings of individual studies. METHOD: A systematic review of MEDLINE, EMBASE and the Cochrane Library identified studies comparing US to palpation-guided TRA for cardiac catheterisation. Studies evaluating radial artery (RA) cannulation for any other reason were excluded. Event rates and risk ratios (RRs) were pooled for meta-analysis. Access failure was the primary outcome. A random-effects model was used for analysis. RESULTS: Of the 977 records screened, four studies with a total of 1,718 patients (861 US-guided and 864 palpation-guided procedures) were included in the meta-analysis. Most procedures were elective. The pooled analysis showed US guidance significantly lowered the risk of access failure (RR 0.45; 95% confidence interval [CI] 0.21-0.97; p=0.04). Heterogeneity was moderate (I2=51.2%; p=0.105). There was a strong trend to improved first-pass success with US (RR 1.29; 95% CI 1.00-1.66; p=0.05; I2=83.8%), although no differences were found in rates of difficult access (RR 0.29; 95% CI 0.07-1.18; p=0.09; I2=88.3%). Salvage US guidance was successful in 30/41 (73.2%) patients following failed palpation-guided TRA. No differences were found in already low complication rates including RA spasm (RR 1.18; 95% CI 0.70-1.99; p=0.53; I2=0.0%) and bleeding (RR 1.32; 95% CI 0.46-3.80; p=0.60; I2=0.0%). CONCLUSIONS: US guidance was found to improve TRA success in the cardiac catheterisation laboratory. Further investigation is necessary to determine whether routine, selective, or salvage use of US confers the most RA protection, patient satisfaction, and overall clinical benefit. (PROSPERO registration: CRD42022332238).

7.
Anal Chem ; 95(48): 17843-17850, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-37974413

RESUMO

Identifying and mapping steroids in tissues can provide opportunities for biomarker discovery, the interrogation of disease progression, and new therapeutics. Although separation coupled to mass spectrometry (MS) has emerged as a powerful tool for studying steroids, imaging and annotating steroid isomers remains challenging. Herein, we present a new method based on the fragmentation of silver-cationized steroids in tandem MS, which produces distinctive and consistent fragmentation patterns conferring confidence in steroid annotation at the regioisomeric level without using prior derivatization, separation, or instrumental modification. In addition to predicting the structure of the steroid with isomeric specificity, the method is simple, flexible, and inexpensive, suggesting that the wider community will easily adapt to it. We demonstrate the utility of our approach by visualizing steroids and steroid isomer distributions in mouse brain tissue using silver-doped pneumatically assisted nanospray desorption electrospray ionization mass spectrometry imaging.


Assuntos
Prata , Espectrometria de Massas por Ionização por Electrospray , Camundongos , Animais , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Esteroides/análise , Isomerismo
8.
J Asthma ; 60(2): 385-392, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35260034

RESUMO

OBJECTIVE: Type 2 (T2) inflammation offers a therapeutic target for biologics. Previous trials suggest obesity influences T2-biomarker levels in asthma, though have not accounted for key variables, e.g. inhaled (ICS)/oral corticosteroid (OCS) use. We hypothesized that body mass index (BMI) would affect T2-biomarker levels, after adjusting for covariates. METHODS: A retrospective analysis of data from two recent local trials of 153 participants with asthma (102 difficult-to-treat, 51 mild). Measurements included BMI, fractional exhaled nitric oxide (FeNO) and eosinophils. Correlation and regression analysis were performed for each biomarker to describe their relationship with BMI. Data was analyzed overall, and by asthma severity, T2-status and BMI tertile. RESULTS: Increasing BMI was associated with reduction in FeNO when stratified by BMI tertile (25 ppb lowest tertile, 18 ppb highest tertile; p = 0.014). Spearmans rank showed a negative correlation between BMI and FeNO in difficult-to-treat asthma (ρ= -0.309, p = 0.002). Linear regression adjusting for sex, age, smoking, atopy, allergic/perennial rhinitis, ICS and OCS confirmed BMI as a predictor of FeNO overall (ß= -2.848, p = 0.019). Eosinophils were reduced in the highest BMI tertile versus lowest in difficult-to-treat asthma (0.2x109/L, 0.3x109/L respectively; p = 0.02). CONCLUSIONS: Increasing BMI is associated with lower FeNO in asthma when adjusted for relevant covariates, including steroid use. There also appears to be an effect on eosinophil levels. Obesity, therefore, affects T2 biomarker levels with implications for disease endotyping and determination of eligibility for biologic therapy. Whether this is due to masking of underlying T2-high status or development of a truly T2-low endotype requires further research.


Assuntos
Asma , Humanos , Asma/tratamento farmacológico , Estudos Retrospectivos , Óxido Nítrico/análise , Eosinófilos , Obesidade/complicações , Corticosteroides/uso terapêutico , Biomarcadores/análise , Testes Respiratórios , Expiração
9.
Can J Neurol Sci ; 50(3): 446-449, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35321778

RESUMO

We investigated the effects of transcranial alternating stimulation (tACS) in patients with insomnia. Nine patients with chronic insomnia underwent two in-laboratory polysomnography, 2 weeks apart, and were randomized to receive tACS either during the first or second study. The stimulation was applied simultaneously and bilaterally at F3/M1 and F4/M2 electrodes (0.75 mA, 0.75 Hz, 5-minute). Sleep onset latency and wake after sleep onset dropped on the stimulation night but they did not reach statistical significance; however, there were significant improvements in spontaneous and total arousals, sleep quality, quality of life, recall memory, sleep duration, sleep efficiency, and daytime sleepiness.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Estimulação Transcraniana por Corrente Contínua , Humanos , Distúrbios do Início e da Manutenção do Sono/terapia , Qualidade de Vida , Polissonografia
10.
Heart Vessels ; 38(12): 1476-1485, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37608153

RESUMO

To demonstrate that point-of-care multimodal spectroscopy using Near-Infrared (NIR) and Raman Spectroscopy (RS) can be used to diagnose human heart tissue. We generated 105 spectroscopic scans, which comprised 4 NIR and 3 RS scans per sample to generate a "multimodal spectroscopic scan" (MSS) for each heart, done across 15 patients, 5 each from the dilated cardiomyopathy (DCM), Ischaemic Heart Disease (IHD) and Normal pathologies. Each of the MSS scans was undertaken in 3 s. Data were entered into machine learning (ML) algorithms to assess accuracy of MSS in diagnosing tissue type. The median age was 50 years (IQR 49-52) for IHD, 47 (IQR 45-50) for DCM and 36 (IQR 33-52) for healthy patients (p = 0.35), 60% of which were male. MSS identified key differences in IHD, DCM and normal heart samples in regions typically associated with fibrosis and collagen (NIR wavenumbers: 1433, 1509, 1581, 1689 and 1725 nm; RS wavelengths: 1658, 1450 and 1330 cm-1). In principal component (PC) analyses, these differences explained 99.2% of the variation in 4 PCs for NIR, 81.6% in 10 PCs for Raman, and 99.0% in 26 PCs for multimodal spectroscopic signatures. Using a stack machine learning algorithm with combined NIR and Raman data, our model had a precision of 96.9%, recall of 96.6%, specificity of 98.2% and Area Under Curve (AUC) of 0.989 (Table 1). NIR and Raman modalities alone had similar levels of precision at 94.4% and 89.8% respectively (Table 1). MSS combined with ML showed accuracy of 90% for detecting dilated cardiomyopathy, 100% for ischaemic heart disease and 100% for diagnosing healthy tissue. Multimodal spectroscopic signatures, based on NIR and Raman spectroscopy, could provide cardiac tissue scans in 3-s to aid accurate diagnoses of fibrosis in IHD, DCM and normal hearts. Table 1 Machine learning performance metrics for validation data sets of (a) Near-Infrared (NIR), (b) Raman and (c and d) multimodal data using logistic regression (LR), stochastic gradient descent (SGD) and support vector machines (SVM), with combined "stack" (LR + SGD + SVM) AUC Precision Recall Specificity (a) NIR model  Logistic regression 0.980 0.944 0.933 0.967  SGD 0.550 0.281 0.400 0.700  SVM 0.840 0.806 0.800 0.900  Stack 0.933 0.794 0.800 0.900 (b) Raman model  Logistic regression 0.985 0.940 0.929 0.960  SGD 0.892 0.869 0.857 0.932  SVM 0.992 0.940 0.929 0.960  Stack 0.954 0.869 0.857 0.932 (c) MSS: multimodal (NIR + Raman) to detect DCM vs. IHD vs. normal patients  Logistic regression 0.975 0.841 0.828 0.917  SGD 0.847 0.803 0.793 0.899  SVM 0.971 0.853 0.828 0.917  Stack 0.961 0.853 0.828 0.917 (d) MSS: multimodal (NIR + Raman) to detect pathological vs. normal patients  Logistic regression 0.961 0.969 0.966 0.984  SGD 0.944 0.967 0.966 0.923  SVM 1.000 1.000 1.000 1.000  Stack 1.000 0.944 0.931 0.969 Bold values indicate values obtained from the stack algorithm and used for analyses.


Assuntos
Cardiomiopatia Dilatada , Isquemia Miocárdica , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cardiomiopatia Dilatada/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Algoritmos , Fibrose
11.
Cardiol Young ; 33(12): 2589-2596, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37066762

RESUMO

BACKGROUND: In single-ventricle patients undergoing staged-bidirectional Glenn, 36-59% have aorto-pulmonary collateral flow, but risk factors and clinical outcomes are unknown. We hypothesise that shunt type and catheter haemodynamics may predict pre-bidirectional Glenn aorto-pulmonary collateral burden, which may predict death/transplantation, pulmonary artery or aorto-pulmonary collateral intervention. METHODS: Retrospective cohort study of patients undergoing a Norwood procedure for single-ventricle anatomy. Covariates included clinical and haemodynamic characteristics up to/including pre-bidirectional Glenn catheterisation and aorto-pulmonary collateral burden at pre-bidirectional Glenn catheterisation. Multivariable models used to evaluate relationships between risk factors and outcomes. RESULTS: From January 2011 to March 2016, 104 patients underwent Norwood intervention. Male sex (odds ratio 3.36, 95% confidence interval 1.17-11.4), age at pre-bidirectional Glenn assessment (2.12, 1.33-3.39 per month), and pulmonary to systemic flow ratio (1.23, 1.08-1.41 per 0.1 unit) were associated with aorto-pulmonary collateral burden. Aorto-pulmonary collateral burden was not associated with death/transplantation (hazard ratio 1.19, 95% confidence interval 0.37-3.85), pulmonary artery (sub-hazard ratio 1.38, 0.32-2.61), or aorto-pulmonary collateral interventions (sub-hazard ratio 1.11, 0.21-5.76). Longer post-Norwood length of stay was associated with greater risk of death/transplantation (hazard ratio 1.22 per week, 95% confidence interval 1.08-1.38), but lower risk of aorto-pulmonary collateral intervention (sub-hazard ratio 0.86 per week, 95% confidence interval 0.75-0.98). Time to pre-bidirectional Glenn catheterisation was associated with lower risk of pulmonary artery (sub-hazard ratio 0.80 per month, 95% confidence interval 0.65-0.98) and aorto-pulmonary collateral intervention (sub-hazard ratio 0.79, 0.63-0.99). Probability of moderate/severe aorto-pulmonary collateral burden increased with left-to-right shunt (22.5% at <1.0, 57.6% at >1.4) and the age at pre-bidirectional Glenn catheterisation (10.6% at <2 months, 56.9% at >5 months). CONCLUSIONS: Aorto-pulmonary collateral burden is common after Norwood procedure and increases as age at bidirectional Glenn increases. As expected, higher pulmonary to systemic flow ratio is a marker for greater aorto-pulmonary collateral burden pre-bi-directional Glenn; aorto-pulmonary collateral burden does not confer risk of death/transplantation or pulmonary artery intervention.


Assuntos
Técnica de Fontan , Síndrome do Coração Esquerdo Hipoplásico , Procedimentos de Norwood , Coração Univentricular , Humanos , Masculino , Lactente , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Artéria Pulmonar/cirurgia , Ventrículos do Coração/cirurgia
12.
Perfusion ; 38(5): 983-992, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-35514051

RESUMO

INTRODUCTION: Cardiopulmonary bypass (CPB) machines have oxygenators with integrated filters and unique biocompatible coatings to combat systemic inflammatory response syndrome (SIRS) and mitigate coagulopathy. Contemporary oxygenators have undergone comparative studies; however, our study aimed to identify the most appropriate oxygenator for our regional Cardiothoracic unit in Australasia. METHODS: A prospective audit consecutively recruited one-hundred and fifty patients undergoing cardiac surgery at Waikato Hospital, New Zealand between the periods of 29th January 2018 and 31st July 2018. Fifty patients were recruited for each oxygenator arm: Sorin INSPIRE' (Group-S); Terumo CAPIOX'FX (Group-T); and Medtronic Affinity Fusion' (Group-M). The clinical outcomes were transfusions, chest drain output, reoperation and length of hospital stay (LOHS). Routine blood testing protocol included: haemoglobin, protein, albumin, white cell count (WCC), C-reactive protein (CRP), platelet count and coagulations tests including international normalized ratio (INR). RESULTS: Comparing Groups S, T and M there was no statistical difference in chest drain output (650 vs. 500 vs. 595 ml respectively, p = 0.45), transfusions (61 vs. 117 vs. 70 units, p = 0.67), reoperation (6 vs. 8 vs. 12%, p = 0.99) and LOHS (median 7.4 vs. 7.6 vs. 9.5 days, p = 0.42). Group-T had fewer SIRS cases but similar increase in CRP (p = 0.12) and WCC (p = 0.35). Group-M had a significant rise in post-op INR (p = 0.005) but no associated increase in chest drain output (p = 0.62). Group-S and -M required more 4%-albumin and Group-T had more transfusions. Only fresh frozen plasma (FFP) and red blood cell (RBC) transfusion had a significant relationship with LOHS (p < 0.05). CONCLUSION: Biochemically, there was slight difference among the oxygenators which did not translate into clinical difference in outcomes. The oxygenator design and perfusionist choice aided in our decision-making process.


Assuntos
Ponte Cardiopulmonar , Oxigenadores , Humanos , Testes de Coagulação Sanguínea , Ponte Cardiopulmonar/métodos , Contagem de Plaquetas , Proteína C-Reativa , Albuminas
13.
Mol Syst Biol ; 17(8): e10240, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34432947

RESUMO

Advancements in mass spectrometry-based proteomics have enabled experiments encompassing hundreds of samples. While these large sample sets deliver much-needed statistical power, handling them introduces technical variability known as batch effects. Here, we present a step-by-step protocol for the assessment, normalization, and batch correction of proteomic data. We review established methodologies from related fields and describe solutions specific to proteomic challenges, such as ion intensity drift and missing values in quantitative feature matrices. Finally, we compile a set of techniques that enable control of batch effect adjustment quality. We provide an R package, "proBatch", containing functions required for each step of the protocol. We demonstrate the utility of this methodology on five proteomic datasets each encompassing hundreds of samples and consisting of multiple experimental designs. In conclusion, we provide guidelines and tools to make the extraction of true biological signal from large proteomic studies more robust and transparent, ultimately facilitating reliable and reproducible research in clinical proteomics and systems biology.


Assuntos
Proteômica , Espectrometria de Massas
14.
Opt Express ; 30(2): 1195-1204, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35209284

RESUMO

We report the generation of tunable high-order optical vortices in the mid-infrared (mid-IR) using a picosecond optical parametric oscillator (OPO). The OPO is based on MgO:PPLN as the nonlinear gain medium and synchronously pumped by a mode-locked Yb-fiber laser at 1064 nm. Using a singly-resonant oscillator configuration for the OPO, we have achieved direct transfer of pump optical vortices to the non-resonant idler beam, with the resonant signal in the Gaussian cavity mode. We demonstrate the successful transfer of pump optical vortices of order, lp = 1 to 5, to the idler beam of the same order across the mid-IR, with an output power of 630 mW to 130 mW across 2538 nm to 4035 nm for the highest idler vortex order, li = 5. To the best of our knowledge, this is the first report of an OPO pumped by a vortex beam of order as high as lp = 5 and generating idler vortices of high order in the mid-IR.

15.
BMC Pulm Med ; 22(1): 363, 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36153525

RESUMO

BACKGROUND: Difficult-to-control asthma associated with elevated body mass index (BMI) is challenging with limited treatment options. The effects of pulmonary rehabilitation (PR) in this population are uncertain. METHODS: This is a randomised controlled trial of an eight-week asthma-tailored PR programme versus usual care (UC) in participants with difficult-to-control asthma and BMI ≥ 25 kg/m2. PR comprised two hours of education and supervised exercise per week, with encouragement for two individual exercise sessions. Primary outcome was difference in change in Asthma Quality of Life Questionnaire (AQLQ) in PR versus UC groups between visits. Secondary outcomes included difference in change in Asthma Control Questionnaire-6 (ACQ6), and a responder analysis comparing proportion reaching minimum clinically important difference for AQLQ and ACQ6. RESULTS: 95 participants were randomised 1:1 to PR or UC. Median age was 54 years, 60% were female and median BMI was 33.8 kg/m2. Mean  (SD) AQLQ was 3.9 (+/-1.2) and median (IQR) ACQ6 2.8(1.8-3.6). 77 participants attended a second visit and had results analysed. Median (IQR) change in AQLQ was not significantly different: 0.3 (- 0.2 to 0.6) in PR and - 0.1 (- 0.5 to 0.4) in UC, p = 0.139. Mean change in ACQ6 was significantly different: - 0.4 (95% CI - 0.6 to - 0.2) in PR and 0 (- 0.3 to + 0.3) in UC, p = 0.015, but below minimum clinically important difference. In ACQ6 responder analysis, minimum clinically important difference was reached by 18 PR participants (54.5%) versus 10 UC (22.7%), p = 0.009. Dropout rate was 31% between visits in PR group, and time to completion was significantly prolonged in PR group at 94 (70-107) days versus 63 (56-73) in UC, p < 0.001. CONCLUSIONS: PR improved asthma control and reduced perceived breathlessness in participants with difficult-to-control asthma and elevated BMI. However, this format appears to be suboptimal for this population with high drop-out rates and prolonged time to completion. Trial registration Clinicaltrials.gov. ID NCT03630432. Retrospectively registered, submitted May 26th 2017, posted August 14th 2018.


Assuntos
Asma , Qualidade de Vida , Asma/reabilitação , Índice de Massa Corporal , Dispneia/reabilitação , Terapia por Exercício/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Heart Lung Circ ; 31(7): 916-923, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35339371

RESUMO

OBJECTIVES: Our objective is to assess whether the presence of myocardial viability is a predictor of mortality among patients undergoing coronary artery bypasss grafting (CABG) through a systematic review meta-analysis. METHODS: Comprehensive review of EMBASE and PubMed in accordance with PRISMA guidelines, including studies of patients undergoing CABG with assessment of myocardial viability and recorded long-term mortality, age and sex. Studies were restricted to the last decade, and data were stratified by imaging modality (magnetic resonance imaging [MRI] or nuclear medicine). Random-effects model for assessing pooled effect, heterogeneity assessment using Chi-square and I2 statistics, publication bias assessed by funnel plots and Egger's test. RESULTS: Meta-analysis of contemporary data (January 2010 to October 2020) yielded 3,621 manuscripts of which 92 were relevant, and 6 appropriate for inclusion with 993 patients. Pooled analysis showed that patients with non-viable myocardium undergoing CABG are at 1.34 times the risk of mortality compared to those with viable myocardium (95% CI 1.01-1.79, p=0.05). Subgroup analysis of the MRI or nuclear medicine modalities was not statistically significant and there was no confounding by age or sex in meta-regression. There was significant heterogeneity in imaging modality and diagnostic criteria, but heterogeneity between study findings was low with an I2 statistic of 29%. The risk of publication bias was moderate on the Newcastle-Ottawa Scale), but not statistically significant (Egger's Test coefficient=1.3, 95%CI -0.35-2.61, p=0.10). CONCLUSIONS: There is a multitude of methods for assessing cardiac viability for coronary revascularisation surgery, making meta-analyses fraught with limitations. Our meta-analysis demonstrates that the finding of non-viable myocardium can not be used draw conclusions for risk assessment in coronary surgery.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/cirurgia , Humanos , Miocárdio , Medição de Risco
17.
Heart Lung Circ ; 31(8): 1126-1133, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35597706

RESUMO

OBJECTIVES: Type A aortic dissection (ATAAD) is hypothesised as a progression of aneurysmal dilation, but 60% of patients in the International Registry of Acute Aortic Dissection (iRAD) registry had a maximum aortic diameter (MAD)<55 mm. We aim to demonstrate that size ratios and aortic wall stress, assessed using a simplified markers, are unique to aortic patients who have had adverse events (ATAAD) compared to those who have not (thoracic aortic aneurysm [TAA]). METHODS: A retrospective cohort analysis of patients who underwent aortic intervention at Waikato Hospital, New Zealand between 2015-2020, comparing dissection (ATAAD) to TAA patients. MAD; ratio of MAD to standardised-points within the aorta; and MAD-to-height collected from computed tomography (CT)-scans of all patients was undertaken. Receiver operating characteristic (ROC)-analysis to determine cut-off point for each marker was undertaken together with multivariable logistic regression comparing both cohorts, cross-validated by propensity-score matched analysis. RESULTS: Cohort of 215 patients, 78 (36.3%) ATAAD and 137 (63.7%) TAA; median age at intervention 63.3 years, 52 (24.2%) females, both cohorts matched for size. Using the entire cohort, the MAD: sinus of Valsalva (SoV) ratio>1.06 (cut-off value) had 4.5-times greater association with ATAAD (95%CI 1.46-13.8) and a 0.1-unit increased conferred 1.45-times greater association with ATAAD (95%CI 1.00-2.08). MAD>55 mm only seen in 33.3% of ATAAD (n=26/78), and not associated with ATAAD (OR 1.88, 95%CI 0.64-5.51). Compared to MAD, MAD:SoV ratio had greater sensitivity (33% vs 73%), lower number-needed-to-treat (17.9 vs 2.7) and superior discrimination (area under the curve [AUC] 0.54 vs 0.71). Findings were consistent with propensity score matched analysis. CONCLUSIONS: MAD:SoV ratio significantly correlates with ATAAD (4.5 times), with superior sensitivity, discrimination, and attributable-risk-percentage compared to MAD alone.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Doença Aguda , Dissecção Aórtica/diagnóstico , Aorta/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
18.
Hosp Pharm ; 57(1): 52-60, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35521024

RESUMO

Background: Adverse drug events (ADEs) result in excess hospitalizations. Thorough admission medication histories (AMHs) may prevent ADEs; however, the resources required oftentimes outweigh what is available in large hospital settings. Previous risk prediction models embedded into the Electronic Medical Record (EMR) have been used at hospitals to aid in targeting delivery of scarce resources. Objective: To determine if an AMH scoring tool used to allocate resources can decrease 30-day hospital readmissions. Design Setting and Participants: Propensity-matched cohort study, Medicine/Surgery patients in large academic safety-net hospital. Intervention or Exposure: Pharmacy-conducted AMHs identified by risk model versus standard of care AMH. Main Outcomes and Measures: A total of 30-day hospital readmissions and inpatient ADE prevention. Results: The model screened 87 240 hospitalizations between June 2017 and June 2019 and 4027 patients per group were included. There were significantly less 30 day readmissions among high-risk identified patients that received a pharmacy-conducted AMH compared to controls (11% vs 15%; P = 0.004) and no significant difference in readmission rates for low-risk patients. While there was significantly higher documentation of major ADE prevention in the pharmacy-led AMH group versus control (1656 vs 12; P < 0.001), there was no difference in electronically-detected inpatient ADEs between groups. Conclusions: A risk tool embedded into the EMR can be used to identify patients whom pharmacy teams can easily target for AMHs. This study showed significant reductions in readmissions for patients identified as high-risk. However, the same benefit in readmissions was not seen in those identified at low-risk, which supports allocating resources to those that will benefit the most.

19.
Biophys J ; 120(4): 586-597, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33460597

RESUMO

Single giant unilamellar vesicles (GUVs) rupture spontaneously from their salt-laden suspension onto solid surfaces. At hydrophobic surfaces, the GUVs rupture via a recurrent, bouncing ball rhythm. During each contact, the GUVs, rendered tense by the substrate interactions, porate, and spread a molecularly transformed motif of a monomolecular layer on the hydrophobic surface from the point of contact in a symmetric manner. The competition from pore closure, however, limits the spreading and produces a daughter vesicle, which re-engages with the substrate. At solid hydrophilic surfaces, by contrast, GUVs rupture via a distinctly different recurrent burst-heal dynamics; during burst, single pores nucleate at the contact boundary of the adhering vesicles, facilitating asymmetric spreading and producing a "heart"-shaped membrane patch. During the healing phase, the competing pore closure produces a daughter vesicle. In both cases, the pattern of burst-reseal events repeats multiple times, splashing and spreading the vesicular fragments as bilayer patches at the solid surface in a pulsatory manner. These remarkable recurrent dynamics arise, not because of the elastic properties of the solid surface, but because the competition between membrane spreading and pore healing, prompted by the surface-energy-dependent adhesion, determine the course of the topological transition.


Assuntos
Lipídeos , Lipossomas Unilamelares , Fenômenos Biofísicos , Interações Hidrofóbicas e Hidrofílicas , Bicamadas Lipídicas
20.
Opt Lett ; 46(13): 3235-3238, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197424

RESUMO

We report a high-average-power picosecond optical vortex source tunable in the near-infrared, using an antiresonant-ring (ARR) interferometer internal to an optical parametric oscillator (OPO) in combination with an external cylindrical lens for astigmatic mode conversion. The ARR OPO is tunable in the signal across 1457-1647 nm with a vortex intensity profile and up to 1 W of average power at 1602 nm. The corresponding idler is tunable over 3006-3945 nm in a Gaussian intensity profile with as much as 1.6 W at 3168 nm. The vortex signal and the Gaussian idler exhibit passive power stability better than 1.7% rms and 1.3% rms, respectively, over >1h. The signal pulses have a Gaussian duration of <19ps with a time-bandwidth product of ΔτΔν<3.6 across the tuning range.

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