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ObjectivesTo identify and compare published models that use related factors to predict the risk of intracranial hemorrhage (ICH) in acute ischemic stroke patients receiving intravenous alteplase treatment.MethodsRisk prediction models for ICH in acute ischemic stroke patients receiving intravenous alteplase treatment were collected from PubMed, Embase, Web of Science, and the Cochrane Library up to April 7, 2023. A meta-analysis was performed using Stata 13.0, and the included models were evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST).ResultsA total of 656 references were screened, resulting in 13 studies being included. Among these, one was a prospective cohort study. Ten studies used internal validation; five studies used external validation, with two of them using both. The area under the receiver operating characteristic (ROC) curve for subjects reported in the models ranged from 0.68 to 0.985. Common predictors in the prediction models include National Institutes of Health Stroke Scale (NIHSS) (OR = 1.17, 95% CI 1.09–1.25, p

ObjectivesTo systematically evaluate the risk prediction models for postoperative delirium in older adult hip fracture patients.MethodsRisk prediction models for postoperative delirium in older adult hip fracture patients were collected from the Cochrane Library, PubMed, Web of Science, and Ovid via the internet, covering studies from the establishment of the databases to March 15, 2023. Two researchers independently screened the literature, extracted data, and used Stata 13.0 for meta-analysis of predictive factors and the Prediction Model Risk of Bias Assessment Tool (PROBAST) to evaluate the risk prediction models for postoperative delirium in older adult hip fracture patients, evaluated the predictive performance.ResultsThis analysis included eight studies. Six studies used internal validation to assess the predictive models, while one combined both internal and external validation. The Area Under Curve (AUC) for the models ranged from 0.67 to 0.79. The most common predictors were preoperative dementia or dementia history (OR = 3.123, 95% CI 2.108–4.626, p

BackgroundDespite the growing research on environment-physical activity (PA) relationships, field experimental studies are limited. Such studies offer opportunities to focus on real-world environmental exposure and related PA and health outcomes, allowing researchers to better isolate the causal effect of exposures/interventions. Focusing on the street/pedestrian environment as a routine setting for people's daily activities, this research aims to develop and test a field experiment protocol that integrates instantaneous assessments of the environment, PA, and health outcomes. The protocol involves the use of state-of-the-art environmental monitoring and biosensing techniques and focuses on physically active road users (pedestrians and bicyclists) who are more directly exposed to their surrounding environment than others such as drivers.Methods/DesignAn interdisciplinary research team first identified the target measurement domains for the health outcomes (e.g., stress, thermal comfort, PA) and the street-level environmental exposures (e.g., land use, greenery, infrastructure conditions, air quality, weather) guided by the previous literature which was primarily observational. Portable or wearable measurement instruments (e.g., GPS, accelerometer, biosensor, mini camera, smartphone app, weather station, air quality sensor) were identified, pilot tested, and selected for the identified measures. We ensured that these measures are readily linkable using the time stamp and include eye-level exposures as they impact the users' experiences more directly yet missing in most prior studies relying on secondary, aerial-level measures. A 50-min experimental route was then determined to include typical everyday environments in park and mixed-use settings and to engage participants in three common modes of transportation (walking, bicycling, and driving). Finally, a detailed staff protocol was developed, pilot-tested, and used in a 36-participant within-subject field experiment in College Station, TX. The experiment was successfully executed, showing its potential to support future field experiments that can provide more accurate real-time, real-environment, and multi-dimensional information.DiscussionOur study demonstrates the feasibility of capturing the multifold health benefits/harms related to walking and bicycling in varying urban environments by combining field experiments with environmental, behavioral, and physiological sensing. Our study protocol and reflections can be helpful for a broad spectrum of research addressing the complex and multi-level pathways between the environment, behavior, and health outcomes.

Growing research has found that exposing patients to forest landscapes through technology improves their health. However, studies on the effects of nature therapy sessions on particularly vulnerable groups that require frequent regular treatment such as patients of chronic kidney disease (CKD) is lacking. This study aims to understand the effects of watching panoramic videos of forest walks through virtual reality (VR) headsets on patients. We also examine the effects of the frequency of virtual exposure to forests on the physiological and psychological parameters of patients undergoing dialysis. Twenty-four dialysis patients with a mean age of 65.11 year underwent a virtual nature intervention over the course of 3 weeks. The intervention consists of 3 numbers of 6-min 360-degree nature videos delivered using VR headsets. We measured heart rate variability (HRV) and heart rate (HR) using continuous electrocardiographic (ECG) monitoring and assessed their emotional states using a questionnaire survey and in-depth interviews. The results showed that the initial 6 min of watching of the panoramic videos through VR headsets resulted in significantly reduced HR and sympathetic nerve activity and increased positive emotional responses. However, repeated VR exposure did not further improve the physiological health of the respondents. Considering these results, the use of VR headsets to watch 6-min nature videos indoors can be used to enhance the positive psychological responses among dialysis and bed-ridden patients. As this study is preliminary, future random controlled trials are needed to compare and determine the best dose, content, and delivery methods of such an intervention.

Prevalent methods for monitoring burn injuries and testing drug efficacies rely on fixed tissue sections. However, this may leave out cellular details in the living state. In vivo assessments of burn healing has been long sought after and are of scientific and clinical interest. Nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), collagen, and melanin are endogenous fluorescent molecules and their signals can be captured by two-photon microscopy (TPM), therefore providing information on epidermal histological features and collagen growth in real-time. In addition, TMP imaging on exogenous fluorescent substances provides a basis for detecting blood vessels. In this work, two-photon microscopy was used to capture the exogenous fluorescent substances and endogenous fluorescent molecules at different times to assess and track burn healing in vivo. Combining TPM imaging and morphological characteristics, proliferation and differentiation of the keratinocytes in different layers of skin, collagen contents, and angiogenesis were identified and quantified. The TPM monitoring method provides an effective tool to systemically evaluate skin healing of deep burns in vivo.

Staphylococcus aureus has been recognized as an important human pathogen and poses a serious health threat worldwide. With the advent of antibiotic resistance, such as the increased number of methicillin-resistant Staphylococcus aureus (MRSA), there is an urgent need to develop new therapeutical agents. In this study, Chinese traditional medicine Tanreqing (TRQ) has been used as an alternative treating agent against MRSA and we aim to unravel the mode of action of TRQ underlying MRSA inhibition. TRQ treatment affected numerous gene expression as revealed by RNA-seq analysis. Meanwhile, TRQ targeted cell division to inhibit cell growth as shown by illumination microscopy. Besides, we confirmed that TRQ downregulates the expression of virulence factors such as hemolysin and autolysin. Finally, we used a murine model to demonstrate that TRQ efficiently reduces bacterial virulence. Altogether, we have proved TRQ formula to be an effective agent against S. aureus infections.

BackgroundMany studies have demonstrated the positive clinical value of progestin-primed ovarian stimulation (PPOS) in patients with polycystic ovary syndrome (PCOS) who underwent assisted reproductive technology. However, the underlying factors contributing to this phenomenon remain unclear. We conducted a retrospective observational study to compare the clinical outcomes of women with PCOS who underwent PPOS or the short protocol to identify possible factors that influence the outcome.MethodsThis study included 304 patients who underwent PPOS and 152 patients who underwent short protocol from April 2014 to July 2019 after propensity-score matching. Human menopausal gonadotropin (hMG) dose, hormone profile, embryo development, and clinical outcomes of frozen-thawed embryo transfer (FET) cycles were compared. The primary outcome measure was the implantation rate. Logistic regression was performed to identify contributing factors, and receiver operating characteristic curve analysis was used to calculate the cutoff of luteinizing hormone (LH) difference ratio in clinical outcomes.ResultsCompared with the short protocol, PPOS resulted in a higher implantation rate (43.4% vs. 31.9%, P < 0.05), clinical pregnancy rate (61.8% vs. 47.4%, P < 0.05), and live birth rate (48.4% vs. 36.8%, P < 0.05). Similar fertilization, cleavage, and valid embryo rate per oocyte retrieved between groups were observed. The LH difference ratio was positively associated with implantation rate [P = 0.027, odds ratio (OR) = 1.861, 95% CI: 1.074–3.226]. The relationship between the LH difference ratio with clinical outcomes was confirmed by receiver operating characteristic curve analysis and comparisons among patients grouped by the LH difference ratio.ConclusionThe implantation rate was associated with the LH difference ratio during ovary stimulation in patients with PCOS. Our results provide the explanation why PPOS shows the positive clinical outcomes for patients with PCOS.

BackgroundIt is unclear whether we should focus attention on cleavage-stage embryo quality and embryo development speed when transferring single particular grade vitrified-warmed blastocysts, especially poor-quality blastocysts (grade “C”).MethodThis retrospective study considered 3386 single vitrified-warmed blastocyst transfer cycles from January 2010 to December 2017. They were divided into group 1 (AA/AB/BA, n = 374), group 2 (BB, n = 1789), group 3 (BC, n = 901), and group 4 (CB, n = 322). The effects of cleavage-stage embryo quality and embryo development speed were measured in terms of clinical pregnancy and live birth rates in each group.ResultsPregnancy outcomes showed a worsening trend from groups 1 to 4; the proportion of embryos with better cleavage-stage quality and faster development speed decreased. In group 1, only the blastocyst expansion degree 3 was a negative factor in the clinical pregnancy rate (odds ratio (OR) [95% confidence interval (CI)]: 0.233 [0.091–0.595]) and live birth rate (0.280 [0.093–0.884]). In the other groups (BB, BC, and CB), blastocysts frozen on day 5 had significantly better clinical pregnancy outcomes than those frozen on day 6: 1.373 [1.095–1.722] for group 2, 1.523 [1.055–2.197] for group 3, and 3.627 [1.715–7.671] for group 4. The live birth rate was 1.342 [1.060–1.700] for group 2, 1.544 [1.058–2.253] in group 3, and 3.202 [1.509–6.795] in group 4, all Ps < 0.05). The degree of blastocoel expansion three for clinical pregnancy rate in group 2 (0.350 [0.135–0.906], P < 0.05) and day 3 blastomere number (>7) for live birth rate in group 4 (2.455 [1.190–5.063], P < 0.05) were two important factors.ConclusionWe should consider choosing BB/BC/CB grade blastocysts frozen on day 5, CB grade blastocysts with day 3 blastomere numbers (>7), and AA/AB/BA grade blastocysts with degrees of expansion (≥4) to obtain better pregnancy outcomes.

Physical activity brings multiple health benefits to seniors. Neighborhood parks provide seniors with accessible spaces and opportunities to engage in physical activity. This study investigated the associations between neighborhood park design characteristics and seniors' total walking step and energy expenditure during the park visit. Seniors' total step was measured by pedometer, and energy expenditure was calculated based on self-reported activities in the park. The study was conducted in 15 neighborhood parks with an area

The global coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV) has led to a huge health and economic crises. However, the research required to develop new drugs and vaccines is very expensive in terms of labor, money, and time. Owing to recent advances in data science, drug-repositioning technologies have become one of the most promising strategies available for developing effective treatment options. Using the previously reported human drug virus database (HDVD), we proposed a model to predict possible drug regimens based on a weighted reconstruction-based linear label propagation algorithm (WLLP). For the drug–virus association matrix, we used the weighted K-nearest known neighbors method for preprocessing and label propagation of the network based on the linear neighborhood similarity of drugs and viruses to obtain the final prediction results. In the framework of 10 times 10-fold cross-validated area under the receiver operating characteristic (ROC) curve (AUC), WLLP exhibited excellent performance with an AUC of 0.8828 ± 0.0037 and an area under the precision-recall curve of 0.5277 ± 0.0053, outperforming the other four models used for comparison. We also predicted effective drug regimens against SARS-CoV-2, and this case study showed that WLLP can be used to suggest potential drugs for the treatment of COVID-19.

Glutamine is an amino acid that is mainly used for the treatment of gastrointestinal diseases in clinic, but there is a lack of such medicine in veterinary clinic, and its research in dogs has never been seen. This study aimed to investigate the pharmacokinetics of single and multiple administration of glutamine (Gln) tablets in Beagles. Twenty-four healthy Beagles were randomly selected for the pharmacokinetic study of a single dose of low (120 mg/kg), medium (240 mg/kg), and high (360 mg/kg) Gln tablets. After 7 days of washout period, six Beagles in the medium group were selected for a multiple-dose pharmacokinetic study, 240 mg/kg twice a day for 7 days. The Gln concentration in plasma was determined by a validated UPLC-MS/MS method. The results of single oral administration of different doses of Gln tablets showed that Cmax, AUC0→t, AUC0→∝ had a certain linear relationship with the dosage. T-tests were performed for single and multiple administration of Tmax, Cmax, t1/2λz, AUC0→t, and AUC0→∝, and the results showed no significant differences (p > 0.05). Therefore, Gln tablets were absorbed quickly by oral administration, and there was no accumulation in Beagles after 7 days of administration.

Great progress has been made in the treatment of driver gene-positive Non- Small Cell Lung Cancer (NSCLC) in recent years. RET fusion was seen in 0.7% to 2% of NSCLC and was associated with younger age and never-smoker status. The pralsetinib and selpercatinib for RET fusion NSCLC was recommended by the 2021 NSCLC treatment guidelines. This review outlines the research progress in the treatment of RET fusion NSCLC, identifies current challenges and describes proposals for improving the outlook for these patients.

Gastric cancer is an intractable malignant tumor that has the fifth highest morbidity and the third highest mortality in the world. Even though various treatment options did much to ameliorate the prognosis of advanced gastric cancer, the survival time remained unsatisfactory. It is significant to develop new therapeutic agents to improve the long-term outcome. Antibody–drug conjugate is an innovative and potent antineoplastic drug composed of a specifically targeted monoclonal antibody, a chemical linker, and a small molecule cytotoxic payload. Powerful therapeutic efficacy and moderate toxicity are its preponderant advantages, which imply the inevitable pharmaceutical developments to meet the demand for individualized precision therapy. Nevertheless, it is unavoidable that there is a phenomenon of drug resistance in this agent. This article systematically reviewed the recent progress of antibody–drug conjugates in advanced gastric cancer therapy.

Lung cancer is the leading cause of cancer deaths in the world. At present, immunotherapy has made a great breakthrough in lung cancer treatment. A variety of immune checkpoint inhibitors have been applied into clinical practice, including antibodies targeting the programmed cell death-1, programmed cell death-ligand 1, and cytotoxic T-lymphocyte antigen 4. However, in the actual clinical process, about 30%–50% of patients still do not receive long-term benefits. Abnormal antigen presentation, functional gene mutation, tumor microenvironment, and other factors can lead to primary or secondary resistance. In this paper, we reviewed the immune mechanism of immune checkpoint inhibitor resistance, various combination strategies, and prediction of biomarkers to overcome resistance in order to accurately screen out the advantageous population, expand the beneficiary population, and enable precise and individualized medicine.

Spatial distribution characteristics and origin of soil gasses were discussed in this study. We also examine the correlation between the spatial variation of soil gasses and fault activity, based on the measurements of Rn, Hg, H2, and CO2 concentrations in the eastern segment of the BLT fault zone in the southern Tianshan Mountains, Xinjiang, China. The results show that the Rn and CO2 concentrations on the hanging wall were higher than those near the fault zone and on the footwall of the fault. Moreover, the Hg and H2 concentrations on the footwall were also higher than those near the fault and on the hanging wall of the fault. The main factors affecting the variations in soil gas spatial distribution were gaseous origin structure of the crust, fault activity, fault fracture degree, stratigraphic lithology, and the cover layer. The results of active structural fault mapping show that the BLT fault has been active since the Late Quaternary and the thrust has broken the fault surface. Under the influence of tectonic compressive stress, the tension zone was formed on the hanging wall of the fault and fractures were developed. This result is consistent with the characteristics of soil gas concentrations measured in this study, indicating that the concentrations of Rn, Hg, H2, and CO2 are closely related to the fault activity. These findings can be applied to identify seismic precursors from gas monitoring data of the studied area.