Sub-Cluster Identification through Semi-Supervised Optimization of Rare-Cell Silhouettes (SCISSORS) in single-cell RNA-sequencing.

MOTIVATION: Single-cell RNA-sequencing (scRNA-seq) has enabled the molecular profiling of thousands to millions of cells simultaneously in biologically heterogenous samples. Currently, the common practice in scRNA-seq is to determine cell type labels through unsupervised clustering and the examination of cluster-specific genes. However, even small differences in analysis and parameter choosing can greatly alter clustering results and thus impose great influence on which cell types are identified. Existing methods largely focus on determining the optimal number of robust clusters, which can be problematic for identifying cells of extremely low abundance due to their subtle contributions toward overall patterns of gene expression. RESULTS: Here, we present a carefully designed framework, SCISSORS, which accurately profiles subclusters within broad cluster(s) for the identification of rare cell types in scRNA-seq data. SCISSORS employs silhouette scoring for the estimation of heterogeneity of clusters and reveals rare cells in heterogenous clusters by a multi-step semi-supervised reclustering process. Additionally, SCISSORS provides a method for the identification of marker genes of high specificity to the cell type. SCISSORS is wrapped around the popular Seurat R package and can be easily integrated into existing Seurat pipelines. AVAILABILITY AND IMPLEMENTATION: SCISSORS, including source code and vignettes, are freely available at https://github.com/jr-leary7/SCISSORS.

Prevalence and factors associated with fertility desires among HIV-positive MSM.

The National surveillance data showed that homosexual transmission played a considerable role in new HIV infections in China. The emphasis on antiretroviral therapy and prevention of mother-to-child transmission provided chances for reproduction among people living with HIV/AIDS. Issues of fertility desire have a paucity of data among HIV-positive men who have sex with men (MSM). This cross-sectional study has assessed fertility attitudes and associated factors, as well as the reproductive knowledge among HIV-positive MSM. Analysis was mainly based on the multinomial regression model. The study included 129 participants, and almost all of the participants (96.1%) were between 18 and 30 years old and 82.2% of them were single. About 35.6% expressed a fertility desire. MSM without siblings tended to have fertility desire (OR = 0.236, 95%CI: 0.078∼0.712, p = 0.010). Surrogacy (36.4%) was the most desired method among the 86 respondents who had the desire or did not make a decision. While the accuracy of the reproductive knowledge was only 69.6%. In summary, we recommend that providers offer much more professional information and develop assisted reproductive technology to meet the reproductive aspirations of HIV-positive MSM.

A retrospective review of sex differences of white matter hyperintensities in brain MRI of patients with migraine.

OBJECTIVES: The primary objective of this study was to evaluate the prevalence of white matter hyperintensities (WMHs) in patients who experience migraine and compare findings between adult male and female patients. Specific symptoms and comorbidities also were analyzed to determine whether they were associated with WMH prevalence or the sex of patients with migraine. We hypothesized that females would have a higher prevalence of WMHs, experience more frequent and more severe migraine headaches, and be more likely to have certain comorbidities associated with migraine than males. BACKGROUND: An increased prevalence of WMHs in patients with migraine has been proposed, although this relation is not well-supported by data from population-based MRI studies. The difference in brain morphology between males and females is of research interest, and females in the general population appear to have a higher prevalence of WMHs. Sex differences and various comorbidities in patients with migraine relative to the number of WMHs on brain imaging have not been fully investigated. METHODS: This was a cross-sectional study of 177 patients aged 18 years and older with a diagnosis of migraine who were seen in the Lehigh Valley Fleming Neuroscience Institute's Headache Center between January 1, 2000, and January 1, 2017. Patients' baseline characteristics were extracted from electronic medical records, including demographics, review of systems documentation, and brain imaging from MRI. Variables including headache severity, frequency of head pain, insomnia, and comorbidities (anxiety, depression, diabetes, hyperlipidemia, hypertension, and neck pain) also were analyzed for associations with the presence of WMHs. RESULTS: Females were found to have a significantly higher number of WMHs than males (median 3 [IQR: 0-7] vs. 0 [IQR: 0-3], p = 0.023). Patients with WMHs were significantly more likely than those without WMHs to have hypertension (39.8% of patients with WMHs vs. 20.3% without WMHs, p = 0.011), constipation (20.9% vs. 8.3%, p = 0.034), and sleep disorder (55.7% vs. 37.3%, p = 0.022). Females with migraine were significantly more likely to experience constipation than males (20.0% vs. 2.9%, p = 0.015). None of the migraine characteristics studied (frequency, severity, presence of aura) were different between sexes, nor were they significantly associated with the presence of WMHs. CONCLUSION: This study suggests that females with migraine may be more likely to have WMHs and experience constipation than males with migraine. Migraine frequency and severity were not different between sexes, nor were they significantly associated with the presence of WMHs. The findings of this study do not support a specific etiology of WMH development in individuals with migraine that differs from findings in the general population. Further studies are warranted.

SQuAPP-simple quantitative analysis of proteins and PTMs.

SUMMARY: The comprehensive analysis of the proteome and its modulation by post-translational modification (PTM) is increasingly used in biological and biomedical studies. As a result, proteomics data analysis is ever more carried out by scientists with limited expertise in this type of data. While excellent software solutions for comprehensive and rigorous analysis of quantitative proteomic data exist, most are complex and not well suited for non-proteomics scientists. Integrative analysis of multi-level proteomics data on protein and diverse PTMs, like phosphorylation or proteolytic processing, remains particularly challenging and inaccessible to most biologists. To fill this void, we developed SQuAPP, an R-Shiny web-based analysis pipeline for the quantitative analysis of proteomic data. SQuAPP uses a streamlined workflow model to guide expert and novice users through quality control, data pre-processing, statistical analysis and visualization steps. Processing the protein, peptide and PTM datasets in parallel and their quantitative integration enable rapid identification of protein-level-independent modulation of protein modifications and intuitive interpretation of dynamic dependencies between different protein modifications. AVAILABILITY AND IMPLEMENTATION: SQuAPP is available at http://squapp.langelab.org/. The source code and local setup instructions can be accessed from https://github.com/LangeLab/SQuAPP.

A novel proxy to examine interspecific phosphorus facilitation between plant species.

Resource complementarity can contribute to enhanced ecosystem functioning in diverse plant communities, but the role of facilitation in the enhanced complementarity is poorly understood. Here, we use leaf manganese concentration ([Mn]) as a proxy for rhizosheath carboxylate concentration to explore novel mechanisms of complementarity mediated by phosphorus (P) facilitation. In pot experiments, we showed that mixtures involving Carex korshinskyi, an efficient P-mobilizing species, exhibited greater biomass and relative complementarity effect than combinations without C. korshinskyi on P-deficient soils. Compared with monocultures, leaf [Mn] and [P] of species that are inefficient at P mobilization increased by 27% and 21% when grown with C. korshinskyi (i.e. interspecific P facilitation via carboxylates) rather than next to another inefficient P-mobilizing species. This experimental result was supported by a meta-analysis including a range of efficient P-mobilizing species. Phosphorus facilitation enhanced the relative complementarity effect in low-P environments, related to a greater change in several facilitated species of their root morphological traits relative to those in monoculture. Using leaf [Mn] as a proxy, we highlight a vital mechanism of interspecific P facilitation via belowground processes and provide evidence for the pivotal role of P facilitation mediated by the plasticity of root traits in biodiversity research.

A case study of HIV/AIDS services from community-based organizations during COVID-19 lockdown in China.

INTRODUCTION: People living with HIV (PLHIV) relied on community-based organizations (CBOs) in accessing HIV care and support during the COVID-19 pandemic in China. However, little is known about the impact of, and challenges faced by Chinese CBOs supporting PLHIV during lockdowns. METHODS: A survey and interview study was conducted among 29 CBOs serving PLHIV in China between November 10 and November 23, 2020. Participants were asked to complete a 20-minute online survey on their routine operations, organizational capacity building, service provided, and challenges during the pandemic. A focus group interview was conducted with CBOs after the survey to gather CBOs' policy recommendations. Survey data analysis was conducted using STATA 17.0 while qualitative data was examined using thematic analysis. RESULTS: HIV-focused CBOs in China serve diverse clients including PLHIV, HIV high-risk groups, and the public. The scope of services provided is broad, ranging from HIV testing to peer support. All CBOs surveyed maintained their services during the pandemic, many by switching to online or hybrid mode. Many CBOs reported adding new clients and services, such as mailing medications. The top challenges faced by CBOs included service reduction due to staff shortage, lack of PPE for staff, and lack of operational funding during COVID-19 lockdowns in 2020. CBOs considered the ability to better network with other CBOs and other sectors (e.g., clinics, governments), a standard emergency response guideline, and ready strategies to help PLHIV build resilience to be critical for future emergency preparation. CONCLUSION: Chinese CBOs serving vulnerable populations affected by HIV/AIDS are instrumental in building resilience in their communities during the COVID-19 pandemic, and they can play significant roles in providing uninterrupted services during emergencies by mobilizing resources, creating new services and operation methods, and utilizing existing networks. Chinese CBOs' experiences, challenges, and their policy recommendations can inform policy makers on how to support future CBO capacity building to bridge service gaps during crises and reduce health inequalities in China and globally.

Prediction model based on 18F-FDG PET/CT radiomic features and clinical factors of EGFR mutations in lung adenocarcinoma.

The aim of this study was to build a prediction model for epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma. A retrospective analysis was performed on 88 patients with lung adenocarcinoma. All patients underwent an 18F-FDG PET/CT scan and genetic testing of EGFR before the treatment. In the training set, the radiomic features and clinical factors were screened out, and model-1 based on CT radiomic features, model-2 based on PET radiomic features, model-3 based on clinical factors, and model-4 based on radiomic features combined with clinical factors were established, respectively. The performance of the prediction model was assessed by area under the receiver operating characteristic (ROC) curve (AUC). The DeLong test was used to compare the performance of the models to screen out the optimal model, and then built the nomogram of the optimal model. The effect and clinical utility of the nomogram was verified in the validation cohort. In our analysis, model-4 was superior to the other prediction models in identifying EGFR mutations. The AUC was 0.864 (95% CI: 0.777-0.950), with a sensitivity of 0.714 and a specificity of 0.784. The nomogram of model-4 was established. In the validation cohort, the concordance index (C-index) value of the calibration curve of the nomogram model was 0.778 (95%CI: 0.585-0.970), and the nomogram had a good clinical utility. We demonstrated that the model based on 18F-FDG PET/CT radiomic features combined with clinical factors could predict EGFR mutations in lung adenocarcinoma, which was expected to be an important supplement to molecular diagnosis.

[Automatic detection model of hypertrophic cardiomyopathy based on deep convolutional neural network].

The diagnosis of hypertrophic cardiomyopathy (HCM) is of great significance for the early risk classification of sudden cardiac death and the screening of family genetic diseases. This research proposed a HCM automatic detection method based on convolution neural network (CNN) model, using single-lead electrocardiogram (ECG) signal as the research object. Firstly, the R-wave peak locations of single-lead ECG signal were determined, followed by the ECG signal segmentation and resample in units of heart beats, then a CNN model was built to automatically extract the deep features in the ECG signal and perform automatic classification and HCM detection. The experimental data is derived from 108 ECG records extracted from three public databases provided by PhysioNet, the database established in this research consists of 14,459 heartbeats, and each heartbeat contains 128 sampling points. The results revealed that the optimized CNN model could effectively detect HCM, the accuracy, sensitivity and specificity were 95.98%, 98.03% and 95.79% respectively. In this research, the deep learning method was introduced for the analysis of single-lead ECG of HCM patients, which could not only overcome the technical limitations of conventional detection methods based on multi-lead ECG, but also has important application value for assisting doctor in fast and convenient large-scale HCM preliminary screening.

MKNK2 enhances chemoresistance of ovarian cancer by suppressing autophagy via miR-125b.

Chemoresistance is a major cause for high mortality and poor survival in patients with ovarian cancer. Changes of cellular autophagy is associated with tumor cell chemoresistance. MAP kinase interacting serine/threonine kinase 2 (MKNK2) belongs to the protein kinase superfamily mediating cell cycle, apoptosis and angiogenesis. However, its effects on chemoresistance during ovarian cancer development remain unclear. In this study, we found that MKNK2 expression levels were markedly up-regulated in chemoresistant ovarian cancer cells compared with the sensitive cells. In addition, significantly increased expression of MKNK2 was detected in clinical ovarian cancer tissues, particularly in tumor samples from patients with drug resistance, and high MKNK2 expression is closely associated with poor prognosis. Our in vitro experiments subsequently showed that MKNK2 knockdown markedly reduced the proliferation of chemoresistant ovarian cancer cells, which was confirmed in SKOV3/DDP xenograft mouse models. Importantly, MKNK2 knockdown considerably induced autophagy in ovarian cancer cells with drug resistance, which was involved in the suppression of cell proliferation. Of note, we showed that miR-125b directly targeted MKNK2, and a negative correlation was observed between the expression of them in clinical tumor tissues. MKNK2 silence also increased miR-125b expression levels in drug-resistant ovarian cancer cells. Intriguingly, MKNK2 knockdown-suppressed cell proliferation and -induced autophagy were almost abrogated by miR-125b inhibition in chemoresistant ovarian cancer cells. Together, these findings demonstrated that MNKN2 is responsible for chemoresistance in ovarian cancer through modulating autophagy by targeting miR-125b, which may be a promising therapeutic target to develop strategies against ovarian cancer with drug resistance.

Study on the time-effectiveness of exercise preconditioning on heart protection in exhausted rats.

To investigate the persistence time and the effectiveness of exercise preconditioning (EP) on myocardial protection in exhausted rats from myocardial enzymes, electrocardiogram (ECG), cardiac function, and mitochondrial respiratory function after cessation of exercise training. One hundred and twelve healthy male Sprague-Dawley rats were randomly divided into seven groups (n = 16): control group (CON), exhaustive exercise (EE) group, EP group, and EE after EP (EP + EE); furthermore, EP + EE group was randomly divided into 1D, 3D, 9D, and 18D groups (1D, 3D, 9D, and 18D) and performed exhaustive treadmill exercise at a speed of 30 m/min on the 1st, 3rd, 9th, and 18th days separately after EP exercise stopped. We detected the serum contents of N-terminal pro B type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) by the enzyme-linked immunosorbent assays method, recorded ECG, detected heart function by pressure volume catheter, measured the respiratory rates of rat myocardial mitochondria state 3 and 4 of complex I, complex II, and IV by high-resolution breathing apparatus. EP could decrease the serum content of NT-proBNP and cTnI, improved the electrical derangement and the left ventricular function in exhausted rats. Moreover, the protective effect was more obvious in the 9th day after EP stopped, whereas it would disappear when EP stopped for more than 18 days. Compared with EE group, the respiratory rate value of myocardial mitochondrial complex increased in 1D, 3D, and 9D groups. Therefore, the protective effect of EP on the heart of exhausted rats decreased with the prolongation of stopping training time, and the effect was significant within 3 days of discontinuing training, then decreased gradually, and completely disappeared in the 18th day. EP enhanced the cardiac function in exhausted rats through raising the nicotinamide adenine diphosphate hydride (NADH) electron transport chain and increased the respiration rates of mitochondrial respiratory complex I and IV state 3, thereby improved myocardial mitochondrial respiratory function and energy metabolism.

Persulfidation of Nitrate Reductase 2 Is Involved in l-Cysteine Desulfhydrase-Regulated Rice Drought Tolerance.

Hydrogen sulfide (H2S) is an important signaling molecule that regulates diverse cellular signaling pathways through persulfidation. Our previous study revealed that H2S is involved in the improvement of rice drought tolerance. However, the corresponding enzymatic sources of H2S and its regulatory mechanism in response to drought stress are not clear. Here, we cloned and characterized a putative l-cysteine desulfhydrase (LCD) gene in rice, which encodes a protein possessing H2S-producing activity and was named OsLCD1. Overexpression of OsLCD1 results in enhanced H2S production, persulfidation of total soluble protein, and confers rice drought tolerance. Further, we found that nitrate reductase (NR) activity was decreased under drought stress, and the inhibition of NR activity was controlled by endogenous H2S production. Persulfidation of NIA2, an NR isoform responsible for the main NR activity, led to a decrease in total NR activity in rice. Furthermore, drought stress-triggered inhibition of NR activity and persulfidation of NIA2 was intensified in the OsLCD1 overexpression line. Phenotypical and molecular analysis revealed that mutation of NIA2 enhanced rice drought tolerance by activating the expression of genes encoding antioxidant enzymes and ABA-responsive genes. Taken together, our results showed the role of OsLCD1 in modulating H2S production and provided insight into H2S-regulated persulfidation of NIA2 in the control of rice drought stress.

Loss of receptor interacting protein kinases 3 and caspase-8 augments intrinsic apoptosis in tubular epithelial cell and promote kidney ischaemia-reperfusion injury.

BACKGROUND: Ischaemia-reperfusion injury (IRI) is associated with programmed cell death that promotes inflammation and organ dysfunction. Necroptosis is mediated by members of receptor interacting protein kinases (RIPK1/3). Inhibition of RIPK1/3 provides a pro-survival benefit in kidney IRI. Caspase-8 initiates apoptosis and contributes to IRI. We studied whether inhibiting both RIPK3 and caspase-8 would provide an additional benefit in kidney IRI. METHODS: A clamp was applied to the left kidney pedicle for 45 min followed by right kidney nephrectomy. Kidney and serum from wild type, RIPK3-/- , and RIPK3-/- caspase-8-/- double knockout (DKO) mice were collected post-IRI for assessment of injury. Tubular epithelial cells (TEC) isolated from wild type, RIPK3-/- , and DKO mice were treated with interferons-γ and interleukin-1ß to induce apoptotic death. RESULTS: Kidney IRI of DKO mice did not show improvement over RIPK3-/- mice. We have found that DKO triggered 'intrinsic' apoptosis in TEC in response to interleukin-1ß and interferons-γ. Up-regulation of the B-cell lymphoma 2 (Bcl-2)-associated death promoter, the Bcl-2-homologous antagonist killer and Bcl-2-associated X protein and enhanced activation of caspase-3 and 9 were found in DKO TEC. TEC infected with Murine cytomegalovirus that encodes multiple cell death inhibitors resist to death. CONCLUSION: We show that the deletion of both RIPK3 and caspase-8 does not provide additive benefit in IRI or TEC death and may enhance injury by up-regulation of intrinsic apoptosis. This suggests blocking multiple death pathways may be required for the prevention of kidney IRI clinically.

Phosphorylation of ETS-1 is a critical event in DNA polymerase iota-induced invasion and metastasis of esophageal squamous cell carcinoma.

An aberrantly elevated expression of DNA polymerase ι (Pol ι) is significantly associated with poor prognosis of patients with esophageal squamous cell carcinoma (ESCC), yet the mechanisms behind this phenomenon remain obscure. Based on the RNA-Seq transcriptome and real-time PCR analysis, we identified ETS-1 as a candidate gene involved in Pol ι-mediated progression of ESCC. Wound-healing and transwell assay indicated that downregulation of ETS-1 attenuates Pol ι-mediated invasiveness of ESCC. Signaling pathway analysis showed that Pol ι enhances ETS-1 phosphorylation at threonine-38 through the Erk signaling pathway in ESCC cells. Kaplan-Meier analysis, based on 93 clinical tissue samples, revealed that ETS-1 phosphorylation at threonine-38 is associated with poor prognosis of ESCC patients. The present study thus demonstrates that phosphorylation of ETS-1 is a critical event in the Pol ι-induced invasion and metastasis of ESCC.

Brachytherapy in the treatment of breast cancer.

Brachytherapy is an important radio-therapeutic modality for a variety of malignancies, including prostate cancer, cervix cancer, breast cancer, vagina cancer, endometrium cancer, head and neck cancer, and many more. This technique has been shown to be an effective and safe non-pharmaceutical treatment with fewer serious complications and better outcome than other treatments for breast cancer. Every year, hundreds of thousands of patients around the world benefit from brachytherapy, which reliably delivers a relatively higher radiation dose to the intended target. However, the follow-up time, patient eligibility criteria, treatment strategy, and radiation doses used in published studies are somewhat inconsistent, making it difficult to strictly compare and evaluate the performance of the treatment. More rigorous studies are required to confirm the safety of this technique and to make outcome data more comparable. In this review, we focus on recent advances in breast brachytherapy techniques and provide an overview of outcomes, cosmetic outcome, toxicity, complications, and limitations of brachytherapy for the treatment of breast cancer. We also summarize the clinical outcomes and toxicity results in patients receiving or not receiving brachytherapy.

Synthesis and biological evaluation of novel oxazolo[5,4-d]pyrimidines as potent VEGFR-2 inhibitors.

Tumor angiogenesis is mediated by vascular endothelial growth factor receptor (VEGFR) and other protein kinases. Inhibition of these kinases presents an attractive approach for developing anticancer therapeutics. In this work, a series of 2,5,7-trisubstituted oxazolo[5,4-d]pyrimidines were synthesized, and their inhibitory activities were investigated against VEGFR-2 and human umbilical vein endothelial cells (HUVEC) in vitro. Compound 9n exhibited the most potent inhibitory activity with IC50 values of 0.33 and 0.29 µM for VEGFR-2 kinase and HUVEC, respectively. A further kinase selectivity assay revealed that these compounds exhibit good VEGFR and moderate EGFR inhibitory activities. Docking analysis suggested a common mode of interaction at the ATP-binding site of VEGFR-2.

Double negative Treg cells promote nonmyeloablative bone marrow chimerism by inducing T-cell clonal deletion and suppressing NK cell function.

The establishment of immune tolerance and prevention of chronic rejection remain major goals in clinical transplantation. In bone marrow (BM) transplantation, T cells and NK cells play important roles for graft rejection. In addition, graft-versus-host-disease (GVHD) remains a major obstacle for BM transplantation. In this study, we aimed to establish mixed chimerism in an irradiation-free condition. Our data indicate that adoptive transfer of donor-derived T-cell receptor (TCR) αß(+) CD3(+) CD4(-) CD8(-) NK1.1(-) (double negative, DN) Treg cells prior to C57BL/6 to BALB/c BM transplantation, in combination with cyclophosphamide, induced a stable-mixed chimerism and acceptance of C57BL/6 skin allografts but rejection of third-party C3H (H-2k) skin grafts. Adoptive transfer of CD4(+) and CD8(+) T cells, but not DN Treg cells, induced GVHD in this regimen. The recipient T-cell alloreactive responsiveness was reduced in the DN Treg cell-treated group and clonal deletions of TCRVß2, 7, 8.1/2, and 8.3 were observed in both CD4(+) and CD8(+) T cells. Furthermore, DN Treg-cell treatment suppressed NK cell-mediated BM rejection in a perforin-dependent manner. Taken together, our results suggest that adoptive transfer of DN Treg cells can control both adoptive and innate immunities and promote stable-mixed chimerism and donor-specific tolerance in the irradiation-free regimen.

Prediction of tide level based on variable weight combination of LightGBM and CNN-BiGRU model.

Accurate tide level prediction is crucial to human activities in coastal areas. Many practical applications show that compared with traditional harmonic analysis, long short-term memory (LSTM), gated recurrent units (GRUs) and other neural networks, along with ensemble learning models, such as light gradient boosting machine (LightGBM) and eXtreme gradient boosting (XGBoost), can achieve extremely high prediction accuracy in relatively stationary time series. Therefore, this paper proposes a variable weight combination model based on LightGBM and CNN-BiGRU with relevant research. It uses the variable weight combination method to weight and synthesize the prediction results of the two base models so that the combination model has a stronger ability to capture time series features and fits the data well. The experimental results show that in contrast to the base model LightGBM, the RMSE value and MAE value of the combination model are reduced by 43.2% and 44.7%, respectively; in contrast to the base model CNN-BiGRU, the RMSE value and MAE value of the combination model are reduced by 35.3% and 39.1%, respectively. This means that the variable weight combination model can greatly improve the accuracy of tide level prediction. In addition, we use tidal data from different geographical environments to further verify the good universality of the model. This study provides a new idea and method for tide prediction.

Evaluation of the relationship between left atrial strain and exercise tolerance in patients with hypertrophic cardiomyopathy by treadmill stress echocardiography.

Objective: The aim of this study is to evaluate the left atrial strain (LAS) in patients with hypertrophic cardiomyopathy (HCM) by treadmill exercise stress echocardiography, combined with three-dimensional speckle tracking technology, for predicting exercise tolerance. Methods: A total of 97 patients with HCM who underwent treadmill exercise stress echocardiography were recruited in Sichuan Provincial People's Hospital between January 2018 and January 2021, and 30 control subjects were selected to be included in the normal group. HCM patients with their metabolic equivalents (METS) ≤ 6.0 were included in the HCM-1 group, while those with METS > 6.0 were included in the HCM-2 group. The LAS and exercise tolerance were analyzed. The ultrasound parameters that could predict a decrease in exercise tolerance were screened, and a predictive model was constructed. Results: It was found that METS, Rest-LASr, Rest-LAScd, and Rest-LASct were significantly lower in HCM patients than those in normal controls. There was a significant difference in age, Target_HR, LVMI, LAVI, E/e'-Rest, E/e'-Peak, Rest-LASr, Rest-LAScd, and Rest-LASct between the HCM-1 and the HCM-2 groups. LASr is an independent resting echocardiographic predictor of METS ≤ 6.0. LASr remained significant for predicting different subtypes (AHCM, asymmetric HCM, and obstructive HCM). Rest-LASr (AUC 0.990) was better at predicting METS ≤ 6.0 than Peak-E/e' (AUC 0.753). A multivariate model (LASr + Age + Target_HR) was established for METS prediction. Conclusion: Left atrial reservoir strain (LASr) has the strongest association with METS ≤ 6.0. The LASr is an independent resting predictor of METS ≤ 6.0 and has a good performance record in predicting different subtypes of HCM. Compared with the traditional parameters, Peak-E/e' and Rest-E/e', Rest-LASr is the best predictor. Rest-LASr can serve as a reliable method for HCM patients who are unable to undergo exercise testing but require an urgent evaluation of their METS, which provides a basis for clinical treatment decision-making and treatment effect evaluation.

A Treatable Cause of Pulsatile Tinnitus: A Case of Sigmoid Sinus Dehiscence.

Tinnitus is a symptom of an underlying condition that can be neurological, ontological, or infectious in origin. This case report describes a patient with pulsatile tinnitus caused by sigmoid sinus dehiscence, which was successfully treated by sigmoid sinus dehiscence repair. We recommend computed tomography angiography/magnetic resonance angiography or digital subtraction angiography to rule out vascular malformation, such as arteriovenous fistula, prior to surgical intervention. In addition, we recommend imaging of the brain and formal evaluation by an ophthalmologist and lumbar puncture prior to surgical intervention to rule out idiopathic intracranial hypertension if suspected.

Effectiveness of online HIV treatment services in the context of the COVID-19 pandemic.

Background: The COVID-19 pandemic has created challenges with respect to HIV care services. Remote online services might provide an effective method for health service delivery to people living with HIV (PLHIV). Few studies have focused on the efficacy of telemedical services for PLHIV and the effect of antiretroviral treatment via online services in China. Methods: We developed a platform called the "No. 8 Health" for online antiretroviral drug collection and delivery services in Beijing from January 21 to June 30, 2022. We evaluated the online treatment service according to viral load suppression rates and compared differences in social characteristics between PLHIV who received antiretroviral drugs through online or offline treatment services. Results: By June 2022, 9528 PLHIV had received outpatient treatment services, among which 44.6% (4031/9528) used the online treatment and drug delivery services for a total of 5590 person-times. The satisfaction rate was 100%. Rates of viral load suppression among PLHIV who initiated antiretroviral therapy (ART) in 2020 and 2021 were 96.4% and 93.1%, respectively. Results showed that the viral load suppression rate was 97.9%. Regarding HIV rapid self-testing, 4513 men who have sex with men used the online HIV rapid testing service. The number of users was approximately the same as in 2021, but both were slightly lower than those in 2020. Conclusion: This study was the first to evaluate the effect of online drug collection and delivery services and virologic outcomes among PLHIV in China. The online service helped with maintenance of ART services, but the COVID-19 pandemic still had some impacts on viral load suppression.