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Performance of the matrix-assisted laser desorption ionization time-of-flight mass spectrometry system for rapid identification of streptococci: a review
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been developed as a new type of soft ionization mass spectrometry in recent years. An increasing number of clinical microbiological laboratories consider it as an innovative approach for bacterial identification. This study was undertaken in order to evaluate the use of MALDI-TOF MS for rapid identification of the clinical streptococci. A systematic review was conducted based on a literature search of the Medline and Embase databases. Fixed-effects models based on the P-value and the I-square were used for meta-analysis while considering the possibility of heterogeneity between studies. Statistical analyses were performed by using STATA 11.0. Twenty-seven studies covering 3,540 streptococci were included in our meta-analysis. The MALDI-TOF MS correctly identified the species of 96% (I
2
= 92.8, P < 0.1) of the streptococci. The MALDI-TOF MS correctly identified the species of 99% of the
Streptococcus pneumoniae
(I
2
= 85.2%, P < 0.1), 100% of the
Streptococcus pyogenes
(I
2
= 32.8%, P > 0.1), and 100% of
Streptococcus agalactiae
(I
2
= 20.7%, P > 0.2). What’s more, it also had high confidence in other
Streptococcus
. But the accuracy of
bovis
needs to be improved. The overall performance of both MALDI-MS systems was different. Notably, the identifying accuracy rate of streptococci by VITEK MS was 98%, compared to 94% by the MALDI biotyper system. Interestingly, when analyzing the incorrect identification of MALDI-TOF MS, 36 out of the 38 strains of
Streptococcus mitis/oralis
were inaccurately identified as
Streptococcus pneumoniae
by the MALDI biotyper system. In conclusion, the results of this review indicated that MALDI-TOF MS could be a reliable and rapid method for identification of the streptococci.
Journal Article
STEM in the classroom: a scoping review of emerging research on the integration of STEM education within Australian schools
The paper presents a scoping review of research that has been conducted on integrated STEM programmes in Australian schools over a 10-year period (2012–2022). It aims to determine how integrated STEM is being practiced. A total of 17 papers were chosen for review. The review explored the major characteristics of research that has been conducted on integrated STEM programmes in Australian schools, the teaching strategies used to teach integrated STEM and the reported impacts of these programmes. In fifteen of the papers experts from outside the school such as scientists and engineers, usually academics, were involved. Cooperative learning, project/problem-based learning and authentic experiences were the most common teaching strategies in a field characterised by positive learner outcomes. It is evident that teaching strategies are significant in the integration of STEM. Future research should focus on addressing issues of ecological validity, sustainability and scalability to ensure as many students as possible reap the benefits of high-quality STEM education.
Journal Article
Association of the LRRK2 genetic polymorphisms with leprosy in Han Chinese from Southwest China
Leprosy is a chronic infectious and neurological disease that is caused by infection of
Mycobacterium leprae
(
M. leprae
). A recent genome-wide association study indicated a suggestive association of
LRRK2
genetic variant rs1873613 with leprosy in Chinese population. To validate this association and further identify potential causal variants of
LRRK2
with leprosy, we genotyped 13
LRRK2
variants in 548 leprosy patients and 1078 healthy individuals from Yunnan Province and (re-)analyzed 3225 Han Chinese across China. Variants rs1427267, rs3761863, rs1873613, rs732374 and rs7298930 were significantly associated with leprosy
per se
and/or paucibacillary leprosy (PB). Haplotype A-G-A-C-A was significantly associated with leprosy
per se
(
P
=0.018) and PB (
P
=0.020). Overexpression of the protective allele (Thr2397) of rs3761863 in HEK293 cells led to a significantly increased nuclear factor of activated T-cells’ activity compared with allele Met2397 after lipopolysaccharides stimulation. Allele Thr2397 could attenuate 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced autophagic activity in U251 cells. These data suggest that the protective effect of LRRK2 variant p.M2397T on leprosy might be mediated by increasing immune response and decreasing neurotoxicity after
M. leprae
loading. Our findings confirm that
LRRK2
is a susceptible gene to leprosy in Han Chinese population.
Journal Article
EP1028 Metastatic patterns do not provide additional prognostic information in patients with FIGO stage IV high-grade serous ovarian cancer
Introduction/BackgroundThe aim of our study was to investigate whether metastatic patterns were associated with prognosis in patients with FIGO stage IV high-grade serous ovarian cancer (HGSC).MethodologyWe retrospectively investigated FIGO stage IV HGSC patients who underwent primary staging or debulking surgery between April 2005 and June 2013 at our institution. None of these patients received neoadjuvant chemotherapy. Metastatic patterns were defined as pleural effusion (stage IVA), parenchymal metastases (stage IVB), and extra-abdominal lymph node metastases (stage IVB). Clinical characters and metastatic patterns were compared with chi-squared or Fisher’s exact tests as appropriate. Overall survival was analyzed using Kaplan-Meier method and Cox proportional hazards model.ResultsA total of 83 consecutive stage IV HGSC patients were identified. 42 (50.6%) patients were sub-classified into stage IVA with pleural effusion. Among the rest stage IVB patients, 19 (22.9%) patients had parenchymal metastases and 22 (26.5%) had extra-abdominal lymph node metastases. Five-year overall survival of stage IVA and IVB patients was 39.7% and 39.4%, respectively (p=0.711). Besides, there were no survival differences among three metastatic patterns (p=0.701).ConclusionOur study demonstrated that neither the sub-classification into FIGO IVA and IVB nor metastatic patterns of FIGO stage IV provided additional prognostic information.DisclosureNothing to disclose.
Journal Article
structural basis for activation of plant immunity by bacterial effector protein AvrPto
Pathogenic microbes use effectors to enhance susceptibility in host plants. However, plants have evolved a sophisticated immune system to detect these effectors using cognate disease resistance proteins, a recognition that is highly specific, often elicits rapid and localized cell death, known as a hypersensitive response, and thus potentially limits pathogen growth. Despite numerous genetic and biochemical studies on the interactions between pathogen effector proteins and plant resistance proteins, the structural bases for such interactions remain elusive. The direct interaction between the tomato protein kinase Pto and the Pseudomonas syringae effector protein AvrPto is known to trigger disease resistance and programmed cell death through the nucleotide-binding site/leucine-rich repeat (NBS-LRR) class of disease resistance protein Prf. Here we present the crystal structure of an AvrPto-Pto complex. Contrary to the widely held hypothesis that AvrPto activates Pto kinase activity, our structural and biochemical analyses demonstrated that AvrPto is an inhibitor of Pto kinase in vitro. The AvrPto-Pto interaction is mediated by the phosphorylation-stabilized P+1 loop and a second loop in Pto, both of which negatively regulate the Prf-mediated defences in the absence of AvrPto in tomato plants. Together, our results show that AvrPto derepresses host defences by interacting with the two defence-inhibition loops of Pto.
Journal Article
Novel mutations in quinolone resistance-determining regions of gyrA, gyrB, parC and parE in Shigella flexneri clinical isolates from eastern Chinese populations between 2001 and 2011
The aim of this study was to evaluate the prevalence of fluoroquinolone resistance and mechanisms of selected fluoroquinolone resistance in
Shigella flexneri
isolates. A total of 624
S. flexneri
strains isolated between 2001 and 2011 in Jiangsu Province of China were analysed for their fluoroquinolone susceptibility. The quinolone resistance-determining region of
gyrA
,
gyrB
,
parC
and
parE
were amplified and sequenced. In general, 90.5 % of
S. flexneri
exhibited resistance to nalidixic acid. The mean norfloxacin resistance rate was 22.4 % during the 11 years from 2001 to 2011 (6.4 % from 2001 to 2005 and 36.8 % from 2006 to 2011). Sequencing of
gyrA
,
gyrB
,
parC
and
parE
genes of all
S. flexneri
isolates showed that the mutation rate was as high as 93.9 %. In addition, 91.8 % and 92.3 % of
S. flexneri
harboured mutations in
gyrA
and
parC
, respectively. About 35.2 % of
S. flexneri
isolates susceptible to nalidixic acid contained mutations. Meanwhile, mutations were detected in 91.2 % of norfloxacin-susceptible strains, and almost all
S. flexneri
isolates resistant to fluoroquinolone contained mutations. To the best of our knowledge, this is the first study reporting the occurrence of point mutations Asn57Lys and His80Pro in
gyrA
and Ala85Thr, Asp111His and Ser129Pro in
parC
. Emerging fluoroquinolone resistance with a significantly high mutation rate of the
gyrA
and
parC
genes in
S. flexneri
in Jiangsu Province deserves attention, and monitoring antibiotic susceptibility is important for the effective management of
S. flexneri
infections.
Journal Article
12 Genetic analysis of primary and recurrent adult granulosa cell tumors of the ovary
ObjectivesAdult granulosa cell tumors (aGCTs) are rare ovarian tumors underpinned by the FOXL2 p.C134W mutation, with a 10–30% risk of relapse. We sought to determine the genetic alterations underpinning primary and recurrent aGCTs.MethodsThirty-five aGCTs were subjected to massively parallel sequencing targeting 468 cancer-related genes (7 primary aGCTs that did not recur >4 years, 9 primary and matched recurrent aGCTs, 10 recurrent aGCTs). These cases and additional 12 aGCTs (n=3, primary aGCTs that did not recur; n=9, recurrent aGCTs) were subjected to Sanger sequencing analysis of the TERT promoter.ResultsAll aGCTs included harbored the FOXL2 p.C134W hotspot mutation. A significantly higher frequency of TERT promoter mutations was found in recurrent (64%) than in primary aGCTs (26%; p=0.017). Moreover, aGCT recurrences harbored a higher frequency of somatic KMT2D and TP53 mutations (16%, each) than primary aGCTs with subsequent recurrences (11% and 0%) and primary aGCTs without subsequent recurrences (14% and 0%). We identified a higher frequency of CDKN2A/B homozygous deletions in recurrent (16%) than in primary aGCTs (6%), and other gene alterations restricted to recurrent aGCTs. Pathway analysis revealed that aGCTs are underpinned by genetic alterations affecting the cell cycle pathway. Clonal decomposition of matched primary and recurrent aGCTs showed that aGCTs display multiple clones at diagnosis and relapse.ConclusionsOur findings suggest that although FOXL2 plays a crucial role in the tumorigenesis of aGCTs, recurrences might be associated with genetic alterations affecting TERT, cell cycle-related genes such as TP53 and CDKN2A/B, and other cancer-related genes, including KMT2D, TET2 and EPHA5.
Journal Article
Shortwave radiative closure experiment and direct forcing of dust aerosol over northwestern China
Modeled and observed solar diffuse fluxes at the surface usually have unacceptably large discrepancies. It is necessary to address and resolve these discrepancies in order to accurately calculate a reliable aerosol direct radiative forcing (DRF). We present and compare two methods of deriving dust aerosol optical properties from the MFRSR (Multi‐Filter Rotating Shadowband Radiometer) observations and the AERONET products. The single‐scattering albedo (SSA) values from MFRSR are found to be 10% less than those from the AERONET. This difference is mainly due to the different imaginary part of refractive index retrieved by the MFRSR compared to AERONET. These two sets of dust aerosol optical properties are used in the SBDART model to simulate the shortwave fluxes that are compared with the surface observations to perform the radiative closure experiment. The diffuse simulations using the AERONET‐derived aerosol SSA may have significant discrepancies compared with the observed diffuse irradiances. The DRFs at the top of atmosphere (TOA) simulated with the MFRSR‐derived aerosol optical properties are positive while the DRFs with the AERONET are negative. The sign of the DRFs at the surface and in the atmosphere using the MFRSR is the same as those using the AERONET while the magnitudes from the MFRSR are much larger. It indicates that dust aerosols with higher absorption as derived from the MFRSR heat the aerosol layer but cool the surface much more than those based on the AERONET, which may have an important impact on the boundary layer processes.
Journal Article
Modeling of Short Fiber Reinforced Polymer Composites Subjected to Multi‐block Loading
Short Fiber Reinforced Composite (SFRC) structures exhibit multiple microstructures (due to material flow during the process). They are generally subjected to variable amplitude loadings. In this context, a robust model is needed to predict fatigue life as a function of microstructure. In this paper, we propose a predictive micromechanical damage-based model allowing fatigue life prediction in the case of SFRC submitted to variable amplitude cyclic loading. An experimental study was firstly performed on Sheet Molding Compound (SMC) composite involving different microstructure configurations. Specimens were subjected to stress-controlled block loading. The influence of the order of the sequences was evaluated through Low-High amplitude (L-H) and High-Low amplitude (H-L) schemes. Damage accumulation is computed at the local scale to describe the evolution of the fiber-matrix interface damage until failure. A local failure criterion based on a critical damage state allowed predicting variable amplitude fatigue life as a function of microstructure. A good correlation was found between experimental and numerical results. Once the approach was validated, it has been used to model different useful variable amplitude loading schemes to emphasize the role of the loading sequence parameters and order.
Journal Article