We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Statisticians typically estimate the parameters of latent class and latent profile models using the Expectation-Maximization algorithm. This paper proposes an alternative two-stage approach to model fitting. The first stage uses the modified k-means and hierarchical clustering algorithms to identify the latent classes that best satisfy the conditional independence assumption underlying the latent variable model. The second stage then uses mixture modeling treating the class membership as known. The proposed approach is theoretically justifiable, directly checks the conditional independence assumption, and converges much faster than the full likelihood approach when analyzing high-dimensional data. This paper also develops a new classification rule based on latent variable models. The proposed classification procedure reduces the dimensionality of measured data and explicitly recognizes the heterogeneous nature of the complex disease, which makes it perfect for analyzing high-throughput genomic data. Simulation studies and real data analysis demonstrate the advantages of the proposed method.
A Bayesian Model II approach to the estimation of proportions in m groups (discussed by Novick, Lewis, and Jackson) is extended to obtain posterior marginal distributions for the proportions. It is anticipated that these will be useful in applications (such as Individually Prescribed Instruction) where decisions are to be made separately for each proportion, rather than jointly for the set of proportions. In addition, the approach is extended to allow greater use of prior information than previously and the specification of this prior information is discussed.
A model for the analysis of paired comparison data is presented which combines features of the BTL-model with features of the Unfolding model. The model is metric, mathematically tractable, and has an exact algebraic solution. Since it is multidimensional and allows for individual differences, it is thought to be more realistic for some choice situations than either the Thurstone model or the BTL-model. No claim is made that the present model will be appropriate for all conceivable choice situations. Rather, it is argued that the fact that it is explicitly falsifiable is a point in its favor.
Some relations between maximum likelihood factor analysis and factor indeterminacy are discussed. Bounds are derived for the minimum average correlation between equivalent sets of correlated factors which depend on the latent roots of the factor intercorrelation matrix Ψ. Empirical examples are presented to illustrate some of the theory and indicate the extent to which it can be expected to be relevant in practice.
Investigations are conducted on the effect of wall proximity on the flow around a cylinder under an axial magnetic field, using the electrical potential probe technology to measure the velocity of liquid metal flow. The study focused on the impact of the inlet velocity of the fluid, the magnetic field and wall proximity on the characteristics of velocity fields, particularly on the vortex-shedding mode. Based on different magnitudes of the magnetic field and the distance from the cylinder to the duct wall, three types of vortex-shedding modes are identified, (I) shear layer oscillation state, (II) quasi-two-dimensional vortex-shedding states and (III) transition of the magnetohydrodynamic to hydrodynamic Kármán street. The transitions between these modes are analysed in detail. The experimental results show that the weak wall-proximity effect leads to the formation of the Kármán vortex street, while a reverse Kármán vortex street and secondary vortices emerge under a strong wall-proximity effect. It is noticed that the Kelvin–Helmholtz instability drives vortex shedding under regime I, leading to an increase in the Strouhal number (St) with stronger magnetic fields. Additionally, under a strong axial magnetic field, the wall-proximity effect (‘Shercliff layer effect’) promotes the instability of shear layers on both sides of the cylinder. These unique coupling effects are validated by variations in modal coefficients and energy proportions under different vortex-shedding regimes using the proper orthogonal decomposition method.
Fibrosis is a pathological condition that affects various organs by increasing fibrous connective tissue while reducing parenchymal cells. This imbalance can lead to compromised organ function and potential failure, posing significant health risks. The condition’s complexity necessitates the exploration of effective treatments to mitigate its progression and adverse outcomes.
Aims
This study aims to investigate the role of ghrelin, a peptide hormone known for its anti-inflammatory and anti-fibrotic properties, in modulating fibrosis across different organs. By binding to the growth hormone secretagogue receptor type 1a (GHSR-1a), ghrelin has shown potential in attenuating the fibrotic process, particularly through its interaction with the TGF-β signalling pathway.
Methods
An extensive review of clinical and animal model studies focusing on liver, kidney, lung, and myocardial fibrosis was conducted. The primary focus was on examining how ghrelin influences the TGF-β signalling pathway, with an emphasis on the regulation of TGF-β expression and the suppression of Smad signalling molecules. The methodology involved analysing data from various studies to understand ghrelin’s molecular mechanisms in combating fibrosis.
Results
The findings from the reviewed studies indicate that ghrelin exerts significant anti-fibrotic effects across multiple organ systems. Specifically, ghrelin was found to downregulate TGF-β expression and suppress Smad signalling molecules, leading to a marked reduction in fibrous tissue accumulation and preservation of organ function. In liver fibrosis models, ghrelin reduced TGF-β1 levels and Smad3 phosphorylation, while in kidney and cardiac fibrosis, similar protective effects were observed. The data also suggest that ghrelin’s effects are mediated through both canonical and non-canonical TGF-β pathways.
Conclusions
Ghrelin presents a promising therapeutic agent in the management of fibrosis due to its potent anti-inflammatory and anti-fibrotic actions. Its ability to modulate the TGF-β signalling pathway underscores a vital molecular mechanism through which ghrelin can mitigate fibrotic progression in various organs. Future research should focus on further elucidating ghrelin’s molecular interactions and potential clinical applications in fibrosis treatment, offering new avenues for developing effective anti-fibrotic therapies.
Depression is highly prevalent in haemodialysis patients, and diet might play an important role. Therefore, we conducted this cross-sectional study to determine the association between dietary fatty acids (FA) consumption and the prevalence of depression in maintenance haemodialysis (MHD) patients. Dietary intake was assessed using a validated FFQ between December 2021 and January 2022. The daily intake of dietary FA was categorised into three groups, and the lowest tertile was used as the reference category. Depression was assessed using the Patient Health Questionnaire-9. Logistic regression and restricted cubic spline (RCS) models were applied to assess the relationship between dietary FA intake and the prevalence of depression. As a result, after adjustment for potential confounders, a higher intake of total FA [odds ratio (OR)T3 vs. T1 = 1·59, 95 % confidence interval (CI) = 1·04, 2·46] and saturated fatty acids (SFA) (ORT3 vs. T1 = 1·83, 95 % CI = 1·19, 2·84) was associated with a higher prevalence of depressive symptoms. Significant positive linear trends were also observed (P < 0·05) except for SFA intake. Similarly, the prevalence of depression in MHD patients increased by 20% (OR = 1.20, 95% CI = 1.01–1.43) for each standard deviation increment in SFA intake. RCS analysis indicated an inverse U-shaped correlation between SFA and depression (Pnonlinear > 0·05). Additionally, the sensitivity analysis produced similar results. Furthermore, no statistically significant association was observed in the subgroup analysis with significant interaction. In conclusion, higher total dietary FA and SFA were positively associated with depressive symptoms among MHD patients. These findings inform future research exploring potential mechanism underlying the association between dietary FA and depressive symptoms in MHD patients.
Systemic changes in multiple diseases may influence the onset of dementia. However, the specific temporality between exposure diseases and dementia remains uncertain.
Aims
By characterising the full spectrum of temporal disease trajectories before dementia, this study aims to yield a global picture of precursor diseases to dementia and to provide detailed instructions for risk management and primary prevention of dementia.
Method
Using the multicentre, community-based prospective UK Biobank, we constructed disease trajectories before dementia utilising the phenome-wide association analysis, paired directional test and association quantification. Stratified disease trajectories were constructed by dementia subtypes, gender, age of diagnosis and Apolipoprotein E (ApoE) status, respectively.
Results
Our study population comprised 434 266 participants without baseline dementia and 4638 individuals with all-cause dementia. In total, 1253 diseases were extracted as potential components of the disease trajectory before dementia. We identified three clusters of disease trajectories preceding all-cause dementia, initiated by circulatory, metabolic and respiratory diseases occurring approximately 5–15 years before dementia. Cerebral infarction or chronic renal failure following chronic ischaemic heart disease was the specific trajectory before vascular dementia. Apolipoprotein E (ApoE) ε4 non-carriers exhibited more complex trajectories compared with carriers. Lipid metabolism disorders remained in the trajectories regardless of dementia subtypes, gender, age of diagnosis and ApoE status.
Conclusions
This study provides a comprehensive view of the longitudinal disease trajectories before dementia and highlights the potential targets of midlife cardiometabolic dysfunction for dementia screening and prevention.
Despite extensive research into the neural basis of autism spectrum disorder (ASD), the presence of substantial biological and clinical heterogeneity among diagnosed individuals remains a major barrier. Commonly used case‒control designs assume homogeneity among subjects, which limits their ability to identify biological heterogeneity, while normative modeling pinpoints deviations from typical functional network development at individual level.
Methods
Using a world-wide multi-site database known as Autism Brain Imaging Data Exchange, we analyzed individuals with ASD and typically developed (TD) controls (total n = 1218) aged 5–40 years, generating individualized whole-brain network functional connectivity (FC) maps of age-related atypicality in ASD. We then used local polynomial regression to estimate a networkwise normative model of development and explored correlations between ASD symptoms and brain networks.
Results
We identified a subset exhibiting highly atypical individual-level FC, exceeding 2 standard deviation from the normative value. We also identified clinically relevant networks (mainly default mode network) at cohort level, since the outlier rates decreased with age in TD participants, but increased in those with autism. Moreover, deviations were linked to severity of repetitive behaviors and social communication symptoms.
Conclusions
Individuals with ASD exhibit distinct, highly individualized trajectories of brain functional network development. In addition, distinct developmental trajectories were observed among ASD and TD individuals, suggesting that it may be challenging to identify true differences in network characteristics by comparing young children with ASD to their TD peers. This study enhances understanding of the biological heterogeneity of the disorder and can inform precision medicine.
To meet the demands of laser-ion acceleration at a high repetition rate, we have developed a comprehensive diagnostic system for real-time and in situ monitoring of liquid sheet targets (LSTs). The spatially resolved rapid characterizations of an LST’s thickness, flatness, tilt angle and position are fulfilled by different subsystems with high accuracy. With the help of the diagnostic system, we reveal the dependence of thickness distribution on collision parameters and report the 238-nm liquid sheet generated by the collision of two liquid jets. Control methods for the flatness and tilt angle of LSTs have also been provided, which are essential for applications of laser-driven ion acceleration and others.
Here, we report the generation of MeV alpha-particles from H-11B fusion initiated by laser-accelerated boron ions. Boron ions with maximum energy of 6 MeV and fluence of 109/MeV/sr@5 MeV were generated from 60 nm-thick self-supporting boron nanofoils irradiated by 1 J femtosecond pulses at an intensity of 1019 W/cm2. By bombarding secondary hydrogenous targets with the boron ions, 3 × 105/sr alpha-particles from H-11B fusion were registered, which is consistent with the theoretical yield calculated from the measured boron energy spectra. Our results demonstrated an alternative way toward ultrashort MeV alpha-particle sources employing compact femtosecond lasers. The ion acceleration and product measurement scheme are referential for the studies on the ion stopping power and cross section of the H-11B reaction in solid or plasma.
National health insurance (NHI) Taiwan has provided additional markups on dental service fees for people with specific disabilities, and the expenditure has increased significantly from TWD473 million (USD15 million) in 2016 to TWD722 million (USD24 million) in 2022. The purpose of this study was to determine oral health risk and to develop a risk assessment model for capitation outpatient dental payments in children with Autism.
Methods
Based on the literature and expert opinion, we developed a level of oral health risk model from the claim records of 2019. The model uses oral outpatient claim data to analyze: (i) the degree of caries disease; (ii) the level of dental fear or cooperation; and (iii) the level of tooth structure. Each factor was given a score from zero to four and a total score was calculated. Low-, medium-, and high-risk groups were formed based on the total points. The oral health risk capitation models are estimated by ordinary least squares using an individual’s annual outpatient dental expenditure in 2019 as the dependent variable. For subgroups based on age group and level of disability, expenditures predicted by the models are compared with actual outpatient dental expenditures. Predictive R-squared and predictive ratios were used to evaluate the model’s predictability.
Results
The demographic variables, level of oral health risk, preventive dental care, and the type of dental health care predicted 30 percent of subsequent outpatient dental expenditure in children with autism. For subgroups (age group and disability level) of high-risk patients, the model substantially overpredicted the expenditure, whereas underprediction occurred in the low-risk group.
Conclusions
The risk-adjusted model based on principal oral health was more accurate in predicting an individual’s future expenditure than the relevant study in Taiwan. The finding provides insight into the important risk factor in the outpatient dental expenditure of children with autism and the fund planning of dental services for people with specific disabilities.
Blastocystis sp. is a prevalent protistan parasite found globally in the gastrointestinal tract of humans and various animals. This review aims to elucidate the advancements in research on axenic isolation techniques for Blastocystis sp. and their diverse applications. Axenic isolation, involving the culture and isolation of Blastocystis sp. free from any other organisms, necessitates the application of specific media and a series of axenic treatment methods. These methods encompass antibiotic treatment, monoclonal culture, differential centrifugation, density gradient separation, micromanipulation and the combined use of culture media. Critical factors influencing axenic isolation effectiveness include medium composition, culture temperature, medium characteristics, antibiotic type and dosage and the subtype (ST) of Blastocystis sp. Applications of axenic isolation encompass exploring pathogenicity, karyotype and ST analysis, immunoassay, characterization of surface chemical structure and lipid composition and understanding drug treatment effects. This review serves as a valuable reference for clinicians and scientists in selecting appropriate axenic isolation methods.
The N100, an early auditory event-related potential, has been found to be altered in patients with psychosis. However, it is unclear if the N100 is a psychosis endophenotype that is also altered in the relatives of patients.
Methods
We conducted a family study using the auditory oddball paradigm to compare the N100 amplitude and latency across 243 patients with psychosis, 86 unaffected relatives, and 194 controls. We then conducted a systematic review and a random-effects meta-analysis pooling our results and 14 previously published family studies. We compared data from a total of 999 patients, 1192 relatives, and 1253 controls in order to investigate the evidence and degree of N100 differences.
Results
In our family study, patients showed reduced N100 amplitudes and prolonged N100 latencies compared to controls, but no significant differences were found between unaffected relatives and controls. The meta-analysis revealed a significant reduction of the N100 amplitude and delay of the N100 latency in both patients with psychosis (standardized mean difference [s.m.d.] = −0.48 for N100 amplitude and s.m.d. = 0.43 for N100 latency) and their relatives (s.m.d. = − 0.19 for N100 amplitude and s.m.d. = 0.33 for N100 latency). However, only the N100 latency changes in relatives remained significant when excluding studies with affected relatives.
Conclusions
N100 changes, especially prolonged N100 latencies, are present in both patients with psychosis and their relatives, making the N100 a promising endophenotype for psychosis. Such changes in the N100 may reflect changes in early auditory processing underlying the etiology of psychosis.
Non-suicidal self-injury (NSSI) is prevalent in major depressive disorder (MDD) during adolescence, but the underlying neural mechanisms are unclear. This study aimed to investigate microstructural abnormalities in the cingulum bundle associated with NSSI and its clinical characteristics.
Methods
130 individuals completed the study, including 35 healthy controls, 47 MDD patients with NSSI, and 48 MDD patients without NSSI. We used tract-based spatial statistics (TBSS) with a region of interest (ROI) analysis to compare the fractional anisotropy (FA) of the cingulum bundle across the three groups. receiver-operating characteristics (ROC) analysis was employed to evaluate the ability of the difficulties with emotion regulation (DERS) score and mean FA of the cingulum to differentiate between the groups.
Results
MDD patients with NSSI showed reduced cingulum integrity in the left dorsal cingulum compared to MDD patients without NSSI and healthy controls. The severity of NSSI was negatively associated with cingulum integrity (r = −0.344, p = 0.005). Combining cingulum integrity and DERS scores allowed for successful differentiation between MDD patients with and without NSSI, achieving a sensitivity of 70% and specificity of 83%.
Conclusions
Our study highlights the role of the cingulum bundle in the development of NSSI in adolescents with MDD. The findings support a frontolimbic theory of emotion regulation and suggest that cingulum integrity and DERS scores may serve as potential early diagnostic tools for identifying MDD patients with NSSI.
Blastocystis sp. is a common parasite in the intestinal tract of humans and animals. The clinical diagnosis of Blastocystis sp. mainly depends on the microscopic observation of parasite, which can lead to false-negative results. An accurate and convenient diagnostic approach for Blastocystis sp. infection is crucial for effectively preventing and controlling blastocystosis. Herein, we developed a recombinase polymerase amplification (RPA) method for detecting Blastocystis sp. The results showed that the DNA amplification by RPA established in this study could be performed within 5 min at 37°C, with maximum band intensity observed at 30 min. The minimum detection limit of RPA was 100 fg μL−1, consistent with conventional polymerase chain reaction (cPCR). Furthermore, the RPA method exhibited no cross-reactivity with 7 other non-target pathogens in the intestinal tract. Next, the newly established RPA method was used to analyse 40 fecal samples collected clinically, and the detection results were consistent with cPCR. These results corroborate that the newly developed RPA method has good sensitivity and specificity and offers the advantage of short detection times, which can be harnessed for differential diagnosis and rapid detection of Blastocystis sp.
Environment-induced epigenetics are involved in diapause regulation, but the molecular mechanism that epigenetically couples nutrient metabolism to diapause regulation remains unclear. In this study, we paid special attention to the significant differences in the level of N6-adenosine methylation (m6A) of dihydroxyacetone phosphate acyltransferase (DHAPAT) and phosphatidate phosphatase (PAP) genes in the lipid metabolism pathway of the bivoltine silkworm (Bombyx mori) strain Qiufeng developed from eggs incubated at a normal temperature (QFHT, diapause egg producer) compared to those from eggs incubated at a low temperature (QFLT, non-diapause egg producer). We knocked down DHAPAT in the pupal stage of the QFLT group, resulting in the non-diapause destined eggs becoming diapausing eggs. In the PAP knockdown group, the colour of the non-diapause destined eggs changed from light yellow to pink 3 days after oviposition, but they hatched as normal. Moreover, we validated that YTHDF3 binds to m6A-modified DHAPAT and PAP mRNAs to promote their stability and translation. These results suggest that RNA m6A methylation participates in the diapause regulation of silkworm by changing the expression levels of DHAPAT and PAP and reveal that m6A epigenetic modification can be combined with a lipid metabolism signal pathway to participate in the regulation of insect diapause traits, which provides a clearer image for exploring the physiological basis of insect diapause.
Placental trophoblastic cells play important roles in placental development and fetal health. However, the mechanism of trophoblastic cell fusion is still not entirely clear. The level of Tspan5 in the embryo culture medium was detected using enzyme-linked immunosorbent assay (ELISA). Fusion of BeWo cells was observed by immunofluorescence. Cell fusion-related factors and EMT-related factors were identified by qRT-PCR and western blotting. Notch protein repressor DAPT was used to verify the role of Tspan5 in BeWo cells. The expression of Tspan5 was significantly increased in embryo culture medium. The fusion of BeWo cells was observed after treatment with forskolin (FSK). Cell fusion-related factors (i.e. β-hCG and syncytin 1/2) and Tspan5 were significantly increased after FSK treatment. In addition, FSK treatment promoted EMT-related protein expression in BeWo cells. Knockdown of Tspan5 inhibited cell fusion and EMT-related protein levels. Notch-1 and Jagged-1 protein levels were significantly upregulated, and the EMT process was activated by overexpression of Tspan5 in FSK-treated BeWo cells. Interestingly, blocking the Notch pathway by the repressor DAPT had the opposite results. These results indicated that Tspan5 could promote the EMT process by activating the Notch pathway, thereby causing cell fusion. These findings contribute to a better understanding of trophoblast cell syncytialization and embryonic development. Tspan5 may be used as a therapeutic target for normal placental development.
Major depressive disorder (MDD) is a serious psychiatric disorder marked by low mood and anhedonia. Understanding the neural mechanism of MDD is essential for the treatment of depression. White matter fibres, connecting different computational units in the brain, have an important effect on brain function; however, the mechanism of white matter fibre abnormality in MDD is still unclear.
Aims
Our study expected to find white matter abnormalities associated with the frontal lobe and hippocampus in individuals with MDD.
Method
Using diffusion tensor imaging data and tract-based spatial statistics, we investigated the microstructural differences in white matter fibre tracts between 30 adults with MDD compared with 31 healthy controls, and calculated the association between MDD-related microstructural changes and illness duration.
Results
It was found that patients with MDD showed reduced fractional anisotropy in the genu and body of the corpus callosum, right corona radiata and part of the thalamic radiations, suggesting lower fibrous myelination levels in these regions; the decreased fractional anisotropy in these regions was associated with longer illness duration.
Conclusions
Our results suggest that MDD may be associated with microstructural damage of key fibre tracts, which could provide insights into the understanding and treatment of MDD.
This study aims to understand the epidemiological characteristics of SARS-CoV-2 infection in the paediatric population during the outbreak of the Omicron variant in Shanghai. We retrospectively analysed the population-based epidemiological characteristics and clinical outcome of SARS-CoV-2 Omicron variant infection in children in Minhang District, Shanghai, based on the citywide surveillance system during the outbreak period in 2022 (March to May). During this time, a total of 63,969 cases of SARS-CoV-2 infection were notified in Minhang District, out of which 4,652 (7.3%) were children and adolescents <18 years. The incidence rate of SARS-CoV-2 infections in children was 153 per 10,000. Of all paediatric cases, 50% reported to be clinically symptomatic within 1–3 days after PCR confirmation by parents or themselves, with 36.3% and 18.9% of paediatric cases reporting fever and cough. Also, 58.4% of paediatric cases had received at least one dose of the COVID-19 vaccine and 52.1% had received two doses of the COVID-19 vaccination. Our findings are informative for the implementation of appropriate measures to protect children from the threat of SARS-CoV-2 infection.