Changes in atherosclerotic cardiovascular disease risk over time among people living with HIV.

OBJECTIVE: To describe changes in atherosclerotic cardiovascular disease (ASCVD) risk over time among people living with HIV (PLHIV). METHODS: We used data from the TREAT Asia HIV Observational Database (TAHOD) and the Australian HIV Observational Database (AHOD). Five-year ASCVD risk was calculated using the D:A:D equation. Individuals were eligible for inclusion if they were aged ≥18 years, had started ART, had no previous history of ASCVD and had complete ASCVD risk factor data available within the first 5 years of ART initiation. RESULTS: A total of 3368 adults contributed data, 3221 were from TAHOD and 147 were from AHOD. The median age at ART initiation was 36 [IQR 31-43] years for TAHOD participants, and 42 [IQR 35-50] years for AHOD participants. Most TAHOD (70.4%) and AHOD (91.8%) participants were male. Overall, ASCVD risk increased from 0.84% (95% CI 0.81%-0.87%) at ART initiation to 1.34% (95% CI 1.29%-1.39%) after 5 years on ART. After adjusting for traditional and HIV-associated ASCVD risk factors, ASCVD risk increased at a similar rate among sub-populations defined by HIV exposure (heterosexuals, men who have sex with men, people who inject drugs), race/ethnicity (Caucasian and Asian) and nadir CD4 at ART initiation (<200 and ≥200 cells/mm3). CONCLUSIONS: These findings emphasize the growing burden of ASCVD risk among PLHIV and the need to develop interventions that are effective across a broad range of HIV sub-populations.

Comparison of diagnostic efficiency of detecting IgG and IgE with immunoassay method in diagnosing ABPA: a meta-analysis.

BACKGROUND: Hitherto, the bulk of diagnostic criteria regards Aspergillus-specific immunoglobulin E as a key item, and regard IgG as an auxiliary method in diagnose. Nevertheless, there is no conclusive study in summarize the performance of IgG and IgE diagnosing ABPA. METHODS: We conducted a systematic review to identify studies report results of IgE and IgG detection in diagnosing ABPA. QUADAS-2 tool was used to evaluate included studies, and we applied the HSROC model to calculate the pooled sensitivity and specificity. Deeks' funnel was derived to evaluated the public bias of included studies, and Cochrane Q test and I2 statistic were used to test the heterogeneity. RESULTS: Eleven studies were included in this study (1127 subjects and 215 for IgE and IgG). Deeks's test for IgE and IgG were 0.10 and 0.19. The pooled sensitivity and specificity for IgE were 0.83 (95%CI: 0.77, 0.90) and 0.89 (0.83, 0.94), and for IgG were 0.93 (0.87, 0.97) and 0.73 (0.62,0.82), with P value < 0.001. The PLR and NLR for IgE were 7.80 (5.03,12.10) and 0.19 (0.13,0.27), while for IgG were 3.45 (2.40,4.96) and 0.09 (0.05,0.17). The combined diagnostic odds ratio and diagnostic score were 41.49 (26.74,64.36) and3.73 (3.29,4.16) for IgE, respectively, and were 38.42 (19.23,76.79) and 3.65 (2.96,4.34) for IgG. CONCLUSION: The sensitivity for IgG diagnosing ABPA is higher than IgE, while the specificity for IgE is higher. IgG might be able to play a more important role in filtering ABPA patients.

MYB57 transcriptionally regulates MAPK11 to interact with PAL2;3 and modulate rice allelopathy.

Rice allelopathy is a natural method of weed control that is regarded as an eco-friendly practice in agroecology. The allelopathic potential of rice is regulated by various genes, including those that encode transcription factors. Our study characterized a MYB transcription factor, OsMYB57, to explore its role in the regulation of rice allelopathy. Increasing the expression of OsMYB57 in rice using the transcription activator VP64 resulted in increased inhibitory ratios against barnyardgrass. The gene expression levels of OsPAL, OsC4H, OsOMT, and OsCAD from the phenylpropanoid pathway were also up-regulated, and the content of l-phenylalanine increased. Chromatin immunoprecipitation incorporated with HiSeq demonstrated that OsMYB57 transcriptionally regulated a mitogen-activated protein kinase (OsMAPK11); in addition, OsMAPK11 interacted with OsPAL2;3. The expression of OsPAL2;3was higher in the allelopathic rice PI312777 than in the non-allelopathic rice Lemont, and OsPAL2;3 was negatively regulated by Whirly transcription factors. Moreover, microbes with weed-suppression potential, including Penicillium spp. and Bacillus spp., were assembled in the rhizosphere of the rice accession Kitaake with increased expression of OsMYB57, and were responsible for phenolic acid induction. Our findings suggest that OsMYB57 positively regulates rice allelopathy, providing an option for the improvement of rice allelopathic traits through genetic modification.

An automatic glaucoma grading method based on attention mechanism and EfficientNet-B3 network.

Glaucoma infection is rapidly spreading globally and the number of glaucoma patients is expected to exceed 110 million by 2040. Early identification and detection of glaucoma is particularly important as it can easily lead to irreversible vision damage or even blindness if not treated with intervention in the early stages. Deep learning has attracted much attention in the field of computer vision and has been widely studied especially in the recognition and diagnosis of ophthalmic diseases. It is challenging to efficiently extract effective features for accurate grading of glaucoma in a limited dataset. Currently, in glaucoma recognition algorithms, 2D fundus images are mainly used to automatically identify the disease or not, but do not distinguish between early or late stages; however, in clinical practice, the treatment of early and late glaucoma is not the same, so it is more important to proceed to achieve accurate grading of glaucoma. This study uses a private dataset containing modal data, 2D fundus images, and 3D-OCT scanner images, to extract the effective features therein to achieve an accurate triple classification (normal, early, and moderately advanced) for optimal performance on various measures. In view of this, this paper proposes an automatic glaucoma classification method based on the attention mechanism and EfficientNetB3 network. The EfficientNetB3 network and ResNet34 network are built to extract and fuse 2D fundus images and 3D-OCT scanner images, respectively, to achieve accurate classification. The proposed auto-classification method minimizes feature redundancy while improving classification accuracy, and incorporates an attention mechanism in the two-branch model, which enables the convolutional neural network to focus its attention on the main features of the eye and discard the meaningless black background region in the image to improve the performance of the model. The auto-classification method combined with the cross-entropy function achieves the highest accuracy up to 97.83%. Since the proposed automatic grading method is effective and ensures reliable decision-making for glaucoma screening, it can be used as a second opinion tool by doctors, which can greatly reduce missed diagnosis and misdiagnosis by doctors, and buy more time for patient's treatment.

Improving speech depression detection using transfer learning with wav2vec 2.0 in low-resource environments.

Depression, a pervasive global mental disorder, profoundly impacts daily lives. Despite numerous deep learning studies focused on depression detection through speech analysis, the shortage of annotated bulk samples hampers the development of effective models. In response to this challenge, our research introduces a transfer learning approach for detecting depression in speech, aiming to overcome constraints imposed by limited resources. In the context of feature representation, we obtain depression-related features by fine-tuning wav2vec 2.0. By integrating 1D-CNN and attention pooling structures, we generate advanced features at the segment level, thereby enhancing the model's capability to capture temporal relationships within audio frames. In the realm of prediction results, we integrate LSTM and self-attention mechanisms. This incorporation assigns greater weights to segments associated with depression, thereby augmenting the model's discernment of depression-related information. The experimental results indicate that our model has achieved impressive F1 scores, reaching 79% on the DAIC-WOZ dataset and 90.53% on the CMDC dataset. It outperforms recent baseline models in the field of speech-based depression detection. This provides a promising solution for effective depression detection in low-resource environments.

Antidementia and Psychotropic Drug Use in Older People with Dementia in Australia: A National Data Linkage Study.

OBJECTIVES: To estimate the national prevalence of antidementia and psychotropic medication use, and sociodemographic factors associated with their use, in Australians living with dementia. DESIGN: Retrospective cross-sectional study. SETTING AND PARTICIPANTS: Nationwide data linkage study using 2021 Census and Pharmaceutical Benefits Scheme (PBS) data. All people aged 65 or older with dementia (self-reported in the Census or dispensed an antidementia drug subsidized by the PBS) were included. METHODS: Medication use was defined as at least 1 dispensing during the 3-month period following the Census (August-October 2021). Prevalence of antidementia and psychotropic medication use, including antipsychotics, benzodiazepines and Z-drugs, antiepileptics, opioids, and psychostimulants, was calculated. Sociodemographic factors associated with medication use were explored using multivariable logistic regression models. RESULTS: Of the 177,809 older people living with dementia included, 58.6% were using at least 1 psychotropic medication. Antidepressants were the most commonly used psychotropics (41%), followed by opioids (20%) and antipsychotics (13%). Antidementia medications were used by a quarter of people with dementia (26%). People with dementia living in the highest socioeconomic area were more likely to use antidementia medications [adjusted odds ratio (OR), 1.22; 95% CI, 1.17-1.28] and less likely to use psychotropics (OR, 0.91; 95% CI, 0.88-0.95) compared with people living in the lowest socioeconomic area. Conversely, those living in inner regional areas were more likely to use psychotropics (OR, 1.06; 95% CI, 1.03-1.10) and less likely to use antidementia medications (OR, 0.79; 95% CI, 0.77-0.82) compared with people living in metropolitan areas. CONCLUSIONS AND IMPLICATIONS: Psychotropics were commonly used in people with dementia in Australia. Disparities in access to health care due to socioeconomic status or remoteness may have influenced the use of antidementia and psychotropic medications. Further strategies to allow more equitable access to resources and medications are needed.

A Comparison of an Australian Observational Longitudinal Alzheimer's Disease Cohort to Community-Based Australian Data.

Background: Observational Alzheimer's disease (AD) cohorts including the Australian, Biomarkers, Imaging and Lifestyle (AIBL) Study have enhanced our understanding of AD. The generalizability of findings from AIBL to the general population has yet to be studied. Objective: We aimed to compare characteristics of people with AD dementia in AIBL to 1) the general population of older Australians using pharmacological treatment for AD dementia, and to 2) the general population of older Australians who self-reported a diagnosis of dementia. Methods: Descriptive study comparing people aged 65 years of over (1) in AIBL that had a diagnosis of AD dementia, (2) dispensed with pharmacological treatment for AD in Australia in 2021 linked to the Australian census in 2021 (refer to as PBS/census), (3) self-reported a diagnosis of dementia in the 2021 Australian census (refer to as dementia/census). Baseline characteristics included age, sex, highest education attainment, primary language, and medical co-morbidities. Results: Participants in AIBL were younger, had more years of education, and had a lower culturally and linguistically diverse (CALD) population compared to the PBS/census cohort and dementia/census cohort (mean age±standard deviation - AIBL 79±7 years, PBS/census 81±7, p < 0.001, dementia/census 83±8, p < 0.001; greater than 12 years of education AIBL 40%, PBS/census 35%, p = 0.020, dementia/census 29%, p < 0.001; CALD - AIBL 3%, PBS/census 20%, p < 0.001, dementia/census 22%, p < 0.001). Conclusions: Our findings suggest that care should be taken regarding the generalizability of AIBL in CALD populations and the interpretation of results on the natural history of AD.

The healing effect of hydrogen-rich water on acute radiation-induced skin injury in rats.

This study aimed to determine the healing effect of hydrogen-rich water (HRW) on radiotherapy-induced skin injury. Rats were irradiated with a 6 MeV electron beam from a Varian linear accelerator. After skin wound formation, rats were individually administrated with distilled water, HRW (1.0 ppm) or HRW (2.0 ppm). We measured the healing time and observed the healing rate of the wounded surface. After irradiation, the malondialdehyde (MDA) content and the superoxide dismutase (SOD) activity in the wounded tissues were evaluated, as determined using an MDA and SOD assay kit. Interleukin-6 (IL-6) and epidermal growth factor (EGF) levels were assessed by enzyme-linked immunosorbent assay (ELISA). Models of skin damage were successfully established using a 44 Gy electronic beam. The healing time was shortened in the two HRW-treated groups (P < 0.05). Furthermore, interventions of HRW resulted in a marked reduction in the MDA (P < 0.05) and IL-6 levels (P < 0.01). Additionally, the SOD activity in the two HRW-treated groups was higher than that in the distilled water group at the end of the 1st, 2nd and 3rd weeks (P < 0.001). The EGF level was also significantly increased at the end of the 1st and 2nd weeks (P < 0.05). Compared with the HRW (1.0 ppm) group, the healing rate was higher and the healing time was reduced in the HRW (2.0 ppm) group. A significant decrease was observed in the IL-6 level at the end of the 1st, 3rd and 4th weeks (P < 0.05) and in the EGF content at the end of the 1 week after the HRW administration (P < 0.01). Collectively, our data indicate that HRW accelerates wound healing of radiation-induced skin lesions through anti-oxidative and anti-inflammatory effects, suggesting that HRW has a healing effect on acute radiation-mediated skin injury, and that this is dependent on the concentration of the hydrogen.

Breast cancer cells alter the dynamics of stromal fibronectin-collagen interactions.

Breast cancer cells recruit surrounding stromal cells, such as cancer-associated fibroblasts (CAFs), to remodel their extracellular matrix (ECM) and promote invasive tumor growth. Two major ECM components, fibronectin (Fn) and collagen I (Col I), are known to interact with each other to regulate cellular behavior. In this study, we seek to understand how Fn and Col I interplay and promote a dysregulated signaling pathway to facilitate tumor progression. Specifically, we investigated the evolution of tumor-conditioned stromal ECM composition, structure, and relaxation. Furthermore, we assessed how evolving Fn-Col I interactions gradually affected pro-angiogenic signaling. Our data first indicate that CAFs initially assembled a strained, viscous, and unfolded Fn matrix. This early altered Fn matrix was later remodeled into a thick Col I-rich matrix that was characteristic of a dense tumor mass. Next, our results suggest that this ECM remodeling was primarily mediated by matrix metalloproteinases (MMPs). This MMP activity caused profound structural and mechanical changes in the developing ECM, which then modified vascular endothelial growth factor (VEGF) secretion by CAFs and matrix sequestration. Collectively, these findings enhance our understanding of the mechanisms by which Fn and Col I synergistically interplay in promoting a sustained altered signaling cascade to remodel the breast tumor stroma for invasive breast tumor growth.

Overexpression of Lsi1 in cold-sensitive rice mediates transcriptional regulatory networks and enhances resistance to chilling stress.

Frequent cold spells in late spring can damage early rice seedlings. However, overexpression of the silicon-uptake gene Lsi1 (Lsi1-OX) in cold-sensitive rice (Oryza sativa L., accession: Dular) notably enhances its chilling resistance. In this study, we found that continual chilling led to chlorophyll and RNA degradation in wild-type Dular leaves, whereas leaves from a Lsi1-OX line exhibited no obvious changes. A comparison of the global mRNA expression between the two rice lines showed that genes encoding photosynthesis-antenna proteins were downregulated and those encoding the proteasome were upregulated in the wild-type organism. Moreover, the differential responses of the two rice lines to chilling stress were found to correlate with the transcription factor OsWRKY53, which was predicted target of the respective microRNA (miRNA) novel-m0586-5p. In addition, miRNAs that targeted genes involved in the process of reactive oxygen species (ROS) metabolism were differentially expressed in the two rice lines after chilling stress, when comparative analysis of the outcomes of RNA sequencing on the two rice lines. Our results suggest that when overexpressed Lsi1 in cold-sensitive rice, it possibility regulates the transcription factor OsWRKY53 in addition to the genes involved in the ROS metabolism, thus mediating resistance to chilling stress.

Protein-crystal interface mediates cell adhesion and proangiogenic secretion.

The nanoscale materials properties of bone apatite crystals have been implicated in breast cancer bone metastasis and their interactions with extracellular matrix proteins are likely involved. In this study, we used geologic hydroxyapatite (HAP, Ca10(PO4)6(OH)2), closely related to bone apatite, to investigate how HAP surface chemistry and nano/microscale topography individually influence the crystal-protein interface, and how the altered protein deposition impacts subsequent breast cancer cell activities. We first utilized Förster resonance energy transfer (FRET) to assess the molecular conformation of fibronectin (Fn), a major extracellular matrix protein upregulated in cancer, when it adsorbed onto HAP facets. Our analysis reveals that both low surface charge density and nanoscale roughness of HAP facets individually contributed to molecular unfolding of Fn. We next quantified cell adhesion and secretion on Fn-coated HAP facets using MDA-MB-231 breast cancer cells. Our data show elevated proangiogenic and proinflammatory secretions associated with more unfolded Fn adsorbed onto nano-rough HAP facets with low surface charge density. These findings not only deconvolute the roles of crystal surface chemistry and topography in interfacial protein deposition but also enhance our knowledge of protein-mediated breast cancer cell interactions with apatite, which may be implicated in tumor growth and bone metastasis.

Methyl-CpG binding domain protein acts to regulate the repair of cyclobutane pyrimidine dimers on rice DNA.

UVB radiation causes cyclobutane pyrimidine dimers (CPDs) to form on the DNA of living organisms. This study found that overexpression of the silicon absorbance gene Lsi1 reduced the accumulation of CPDs in rice, which profited from the reactivation by photolyase. The transcript abundance of deoxyribodipyrimidine photolyase (Os10g0167600) was generally correlated with the silicon content of the rice, and the up-regulation of Os10g0167600 was found to be highest in the UVB-treated Lsi1-overexpressed (Lsi1-OX) rice. A trans-acting factor, methyl-CpG binding domain protein (OsMeCP), was found to interact with the cis-element of Os10g0167600. The nucleic location of OsMeCP effectively enabled the transcriptional regulation. Compared with the WT, the level of OsMeCP was lower in the Lsi1-OX rice but higher in the Lsi1-RNAi line. Rice cultured in a high silicate-concentration solution also exhibited less OsMeCP abundance. Overexpression of OsMeCP led to lower Os10g0167600 transcript levels and a higher CPD content than in the WT, but the reverse was true in the OsMeCP-RNAi line. These findings indicate that OsMeCP acts as a negative regulator of silicon, and can mediate the repression of the transcription from Os10g0167600, which inhibits the photoreactivation of the photolyase involved in the repair of CPDs.