Outcomes of 2-SSRS plus bevacizumab therapy strategy for brainstem metastases (BSM) over 2 cm3: a multi-center study.

Despite 2-staged stereotactic radiosurgery (2-SSRS) has been reported to provide patients with improved survival and limited toxicity, 2-SSRS for brainstem metastases (BSM) larger than 2 cm3 remains challenging. We tried to find out the effectiveness and safety of 2-SSRS plus bevacizumab therapy for BSMs over 2 cm3 and prognostic factors that related to the tumor local control. Patients that received 2-SSRS plus bevacizumab therapy from four gamma knife center were retrospectively studied from Jan 2014 to December 2023. Patients' domestic characteristics and the tumor features were evaluated before and after the treatment. Cox regression model was used to find out prognostic factors for tumor local control. 53 patients with 63 lesions received the therapy. The median peri-tumor edema volume greatly reduced at the end of therapy (P < 0.01), the median tumor volume dramatically reduced (P < 0.01) and patients' KPS score improved significantly (P < 0.05) 3 months after the therapy. Patients' median OS was 12.8 months. The tumor local control rate at 3, 6, and 12 months was 98.4%, 93.4%, and 85.2%. The incidence side effects were mainly oral and nasal hemorrhage (5.7%, 3/53), and radiation necrosis (13.2%, 7/53). Patients with primary lung adenocarcinoma, therapeutic dose over 12 Gy at second-stage SRS, primary peri-tumor edema volume less than 2.3 cm³, primary tumor volume less than 3.7 cm³ would enjoy longer tumor local control. These results suggested that 2-SSRS plus bevacizumab therapy was effective and safe for BSMs over 2 cm3. However, it is important for patients with BSM to receive early diagnosis and treatment to achieve good tumor local control.

Comparison of the RF-CL and CACS-CL models to estimate the pretest probability of obstructive coronary artery disease and predict prognosis in patients with stable chest pain and diabetes mellitus.

Background: The most appropriate tool for estimating the pretest probability (PTP) of obstructive coronary artery disease (CAD) in patients with diabetes mellitus (DM) and stable chest pain (SCP) remains unknown. Therefore, we aimed to validate and compare two recent models, namely, the risk factor-weighted clinical likelihood (RF-CL) model and coronary artery calcium score (CACS)-weighted clinical likelihood (CACS-CL) model, in these patient populations. Methods: A total of 1,245 symptomatic patients with DM, who underwent CACS and coronary computed tomographic angiography (CCTA) scan, were identified and followed up. PTP of obstructive CAD for each patient was estimated using the RF-CL model and CACS-CL model, respectively. Area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to assess the performance of models. The associations of major adverse cardiovascular events (MACE) with risk groups were evaluated using Cox proportional hazards regression. Results: Compared with the RF-CL model, the CACS-CL model revealed a larger AUC (0.856 vs. 0.782, p = 0.0016), positive IDI (12%, p < 0.0001) and NRI (34%, p < 0.0001), stronger association to MACE (hazard ratio: 0.26 vs. 0.38) and less discrepancy between observed and predicted probabilities, resulting in a more effective risk assessment to optimize downstream clinical management. Conclusion: Among patients with DM and SCP, the incorporation of CACS into the CACS-CL model resulted in a more accurate estimation for PTP and prediction of MACE. Utilizing the CACS-CL model, instead of the RF-CL model, might have greater potential to avoid unnecessary and omissive cardiovascular imaging testing with minimal cost.

A New Species of the Blind Cave Loach Genus Protocobitis (Cypriniformes: Cobitidae), Protocobitis longicostatus sp. nov., from Guangxi, China.

Protocobitis species are typical cave-dwelling fish, exhibiting distinctive morphological adaptations such as colorless body, lack of eyes, and reduced scales and ribs in response to their extreme cave habitats. Distinct from the recorded species, P. anteroventris, P. polylepis, and P. typhlops, a new species, Protocobitis longicostatus sp. nov., is described from Guangxi Zhuang Autonomous Region, China. Protocobitis longicostatus sp. nov. can easily be distinguished from all known congeners by the following characteristics: whole body covered by scales except head, 12 branched caudal fin rays, and long ribs. These species face threats from habitat degradation, hydrological changes, and environmental pollution. Thus, the conservation of cavefish in China has become an urgent issue.

Increased frequency of CHD1 deletions in prostate cancers of African American men is associated with rapid disease progression without inducing homologous recombination deficiency.

We analyzed genomic data derived from the prostate cancer of African and European American men in order to identify differences that may contribute to racial disparity of outcome and that could also define novel therapeutic strategies. In addition to analyzing patient derived next generation sequencing data, we performed FISH based confirmatory studies of Chromodomain helicase DNA-binding protein 1 ( CHD1 ) loss on prostate cancer tissue microarrays. We created CRISPR edited, CHD1 deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. We found that subclonal deletion of CHD1 is nearly three times as frequent in prostate tumors of African American men than in men of European ancestry and it associates with rapid disease progression. We further showed that CHD1 deletion is not associated with homologous recombination deficiency associated mutational signatures in prostate cancer. In prostate cancer cell line models CHD1 deletion did not induce HR deficiency as detected by RAD51 foci formation assay or mutational signatures, which was consistent with the moderate increase of olaparib sensitivity. CHD1 deficient prostate cancer cells, however, showed higher sensitivity to talazoparib. CHD1 loss may contribute to worse outcome of prostate cancer in African American men. A deeper understanding of the interaction between CHD1 loss and PARP inhibitor sensitivity will be needed to determine the optimal use of targeted agents such as talazoparib in the context of castration resistant prostate cancer.

Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.

[Level and health evaluation of rare earth elements in human blood and hair in the mining areas in Northwest Hubei].

OBJECTIVE: To investigate the content of rare earth elements(REs)in blood and hair of residents in a RE mining area in Northwest Hubei, and evaluate the impact of REs on the health status of local residents. METHODS: A total of 191 residents from the core area of RE mining areas and 186 residents from non RE mining areas, aged 20-69, were selected. The content of REs in the blood and hair of the survey subjects was measured using inductively coupled plasma mass spectrometry, and compared with existing literature values. At the same time, blood tests and questionnaire surveys will be conducted on the health status of residents to examine whether human RE enrichment can lead to endemic diseases. RESULTS: The average total content of REs in the blood of residents in the mining area was 60.22 ng/mL, which was 3.35 times that of the control area; The average total content of REs in hair was 1197.91 ng/g, which was 6.32 times higher than the control area. As age increasing, the abundance of REs in the blood and hair of both men and women in mining areas increased. The proportion of Yttrium and Scandium in the blood and hair were much higher than that in the soil. Compared to hair, Yttrium and Scandium were more easily enriched in the blood. There was no significant difference in the probability of fatty liver, hepatitis B, hypoglycemia, hypotension, hypertension and heart disease and the average life span between residents in RE mining areas and those in the control area. CONCLUSION: The high daily average dietary intake of REs in residents leads to a relatively large accumulation of REs in human blood and hair, but no significant and substantial human health damage has been found at present.

Tandem Vinylogous Aldol and Intramolecular [2 + 2] Cycloaddition toward Benzocyclobutenes by UV Light Photocatalysis.

A facile and efficient radical tandem vinylogous aldol and intramolecular [2 + 2] cycloaddition reaction for direct synthesis of cyclobutane-containing benzocyclobutenes (BCBs) under extremely mild conditions without using any photocatalysts is reported. This approach exhibited definite compatibility with functional groups and afforded new BCBs with excellent regioselectivity and high yields. Moreover, detailed mechanism studies were carried out both experimentally and theoretically. The readily accessible, low-cost, and ecofriendly nature of the developed strategy will endow it with attractive applications in organic and medicinal chemistry.

Targeting EED as a key PRC2 complex mediator toward novel epigenetic therapeutics.

EED within the PRC2 complex is crucial for chromatin regulation, particularly in tumor development, such that its inhibition is a promising epigenetic therapeutic strategy. Significant advancement in PRC2 inhibitor development has been achieved with an approved EZH2 inhibitor in the market and with others in clinical trials. However, current EZH2 inhibitors are limited to specific blood cancers and encounter therapeutic resistance. EED stabilizes PRC2 and enhances its activity through unique allosteric mechanisms, thereby acting as both a scaffold protein and a recognizer of H3K27me3 making it an attractive drug target. This review provides an overview of epigenetic therapeutic strategies targeting EED, including allosteric inhibitors, PPI inhibitors, and PROTACs, together with brief discussions on the relevant challenges, opportunities, and future directions.

A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T-cell therapy.

CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy. These were compared with 124 consecutive T-ALL/LBL patients who received allo-HSCT in CR following chemotherapy. The study revealed that both the CAR-T and chemotherapy cohorts exhibited comparable 2-year overall survival (OS) (61.9% [95% CI, 44.1-78.1] vs. 67.6% [95% CI, 57.5-76.9], p = 0.210), leukaemia-free survival (LFS) (62.3% [95% CI, 44.6-78.4] vs. 62.0% [95% CI, 51.8-71.7], p = 0.548), non-relapse mortality (NRM) rates (32.0% [95% CI, 19.0-54.0] vs. 25.3% [95% CI, 17.9-35.8], p = 0.288) and relapse incidence rates (8.8% [95% CI, 3.0-26.0] vs. 15.8% [95% CI, 9.8-25.2], p = 0.557). Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.

IGSF8 is an innate immune checkpoint and cancer immunotherapy target.

Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival in vitro or in vivo. It is overexpressed and associated with low antigen presentation, low immune infiltration, and worse clinical outcomes in many tumors. An antibody that blocks IGSF8-NK receptor interaction enhances NK cell killing of malignant cells in vitro and upregulates antigen presentation, NK cell-mediated cytotoxicity, and T cell signaling in vivo. In syngeneic tumor models, anti-IGSF8 alone, or in combination with anti-PD1, inhibits tumor growth. Our results indicate that IGSF8 is an innate immune checkpoint that could be exploited as a therapeutic target.

Functionally selective dopamine D1 receptor endocytosis and signaling by catechol and non-catechol agonists.

The dopamine D1 receptor (D1R) has fundamental roles in voluntary movement and memory and is a validated drug target for neurodegenerative and neuropsychiatric disorders. However, previously developed D1R selective agonists possess a catechol moiety which displays poor pharmacokinetic properties. The first selective non-catechol D1R agonists were recently discovered and unexpectedly many of these ligands showed G protein biased signaling. Here, we investigate both catechol and non-catechol D1R agonists to validate potential biased signaling and examine if this impacts agonist-induced D1R endocytosis. We determined that most, but not all, non-catechol agonists display G protein biased signaling at the D1R and have reduced or absent Beta-arrestin recruitment. A notable exception was compound (Cmpd) 19, a non-catechol agonist with full efficacy at both D1R-G protein or D1R Beta-arrestin pathways. In addition, the catechol ligand A-77636 was a highly potent, super agonist for D1R Beta-arrestin activity. When examined for agonist-induced D1R endocytosis, balanced agonists SKF-81297 and Cmpd 19 induced robust D1R endocytosis while the G protein biased agonists did not. The Beta-arrestin super agonist, A-77636, showed significantly increased D1R endocytosis. Moreover, Beta-arrestin recruitment efficacy of tested agonists strongly correlated with total D1R endocytosis. Taken together, these results indicate the degree of D1R signaling functional selectivity profoundly impacts D1R endocytosis regardless of pharmacophore. The range of functional selectivity of these D1R agonists will provide valuable tools to further investigate D1R signaling, trafficking and therapeutic potential.

Chelerythrine induces apoptosis and ferroptosis through Nrf2 in ovarian cancer cells.

Ovarian cancer is a prevalent malignancy in the female reproductive system, representing a significantly fatal and incurable tumor. Chelerythrine (CHE), a natural benzopyridine alkaloid, has demonstrated a broad spectrum of anticancer activities. Nevertheless, the ovarian cancer inhibitory impact of CHE remains unclear. In this study, we investigated the cytotoxic mechanism and potential targets of CHE on in vitro cultures of A2780 and SKOV3 cells derived from ovarian cancer. Additionally, in vivo experiments were conducted to confirm the suppressive impact of CHE on tumor growth in nude mice. The findings revealed that CHE impeded the growth of A2780 and SKOV3 cells in a concentration-time-dependent manner and significantly suppressed the development of tumors in nude mice. CHE elevated the level of oxidative stress in tumor cells, prompted cell cycle halt in the S phase, and increased their mitochondrial membrane potential. Western blotting results demonstrated that CHE could modulate the expression of proteins associated with apoptotic and ferroptosis processes in A2780 and SKOV3 cells. Nrf2 was verified to be an upstream key target mediating the inhibitory impact of CHE on ovarian cancer cells. In summary, CHE exerts its anti-cancer effects on ovarian cancer by modulating Nrf2, inhibiting cellular proliferation, and promoting apoptosis and ferroptosis.

Mulberry Leaf-Derived Morin Activates ß-Catenin by Binding to Frizzled7 to Promote Intestinal Stem Cell Expansion upon Heat-Stable Enterotoxin b Injury.

Intestinal stem cells (ISCs) sustain epithelial renewal by dynamically altering behaviors of proliferation and differentiation in response to various nutrition and stress inputs. However, how ISCs integrate bioactive substance morin cues to protect against heat-stable enterotoxin b (STb) produced by Escherichia coli remains an uncertain question with implications for treating bacterial diarrhea. Our recent work showed that oral mulberry leaf-derived morin improved the growth performance in STb-challenged mice. Furthermore, morin supplementation reinstated the impaired small-intestinal epithelial structure and barrier function by stimulating ISC proliferation and differentiation as well as supporting intestinal organoid expansion ex vivo. Importantly, the Wnt/ß-catenin pathway, an ISC fate commitment signal, was reactivated by morin to restore the jejunal crypt-villus architecture in response to STb stimulation. Mechanically, the extracellular morin-initiated ß-catenin axis is dependent or partially dependent on the Wnt membrane receptor Frizzled7 (FZD7). Our data reveal an unexpected role of leaf-derived morin, which represents molecular signaling targeting the FZD7 platform instrumental for controlling ISC regeneration upon STb injury.

Selective Sparse Sampling of Water Droplets in Oil with Acoustic Tweezers.

In microfluidics, water droplets are often used as independent biochemical microreactor units, enabling the implementation of massively parallel screening assays where only a few of the reacting water droplets yield a positive result. However, sampling the product of these few successful reactions is an unsolved challenge. One possible solution is to use acoustic tweezers, which are lab-free, easily miniaturized, and biocompatible manipulation tools, and existing acoustic tweezers manipulating particles or cells, and water droplet manipulation in oil with an acoustic tweezer is absent. The first challenge in attempting to recover a few water droplets from a large batch is the selective manipulation of water droplets in an oil system. In this paper, we trap and manipulate single water droplets in oil using integrated single-beam (focused beam/vortex beam) acoustic tweezers for the first time. We find that water droplets with a diameter smaller than half a wavelength are trapped by acoustic vortices, while larger ones are better captured by focused acoustic beams. It is the first step to extract the target water droplet microreactors (positive ones) in an oil system and analyze their content. Compared to previous techniques, such as fluorescence-activated cell sorting (FACS), our technique is sparse, meaning that the sampling time is proportional to the number of droplets required and very insensitive to the total number of microreactors, making it well suited for large-scale screening assays.

Alignment error modeling and control of a double-sided microlens array during precision glass molding.

Double-sided microlens arrays (DSMLAs) include combinations of two single-sided MLAs to overcome positioning errors and greatly improve light transmissivity compared to other types of lenses. Precision glass molding (PGM) is used to fabricate DSMLAs, but controlling alignment errors during this process is challenging. In this paper, a mold assembly was manufactured with a novel combination of materials to improve the alignment accuracy of mold cores during PGM by using the nonlinear thermal expansion characteristics of the various materials to improve the DSMLA alignment accuracy. By establishing a mathematical model of the DSMLA alignment error and a thermal expansion model of the mold-sleeve pair, the relationship between the maximum alignment error of the DSMLA and the mold-sleeve gap was determined. This research provides a method to optimize the mold-sleeve gap and minimize the alignment error of the DSMLA. The measured DSMLA alignment error was 10.56 µm, which is similar to the predicted maximum alignment error. Optical measurements showed that the uniformity of the homogenized beam spot was 97.81%, and the effective homogeneous area accounted for 91.66% of the total area. This proposed method provides a novel strategy to improve the performance of DSMLAs.

Association between sleep duration and metabolic syndrome: a population-based study in China.

INTRODUCTION: The relationship between sleep duration and metabolic syndrome (MetS) remains debatable. In the present study, we analysed the link between total sleep duration (including nighttime sleep and nap duration) and MetS as well as its components among the Chinese population. MATERIAL AND METHODS: This was a cross-sectional study from a prospective population cohort including 8616 participants over 40 years in Guangxi, China, evaluated from April 2011 to January 2012. MetS was diagnosed using modified criteria from the National Cholesterol Education Program's Adult Treatment Panel III. Sleep information was obtained through a standard self-report-based questionnaire. The connection between sleep duration and MetS prevalence as well as its components was evaluated using a logistic regression model. RESULTS: After adjusting for potential confoundings, the longer daily sleep duration (≥ 10 hours) group was observed to have the higher odds of having MetS than the reference group with ≥ 7 and < 8 hours of sleep [odds ratio (OR): 1.25, 95% confidence interval (CI): 1.03-1.52, p = 0.023], as well as the highest odds of having elevated triglycerides (OR: 1.25, 95% CI: 1.03-1.52) and fasting blood glucose (OR: 1.21, 95% CI: 1.01-1.45). Further analysis demonstrated that sleeping > 9 hours per night was correlated to MetS in females (OR: 1.27, 95% CI: 1.02-1.58), while napping ≥ 90 minutes was correlated to MetS (OR: 1.44, 95% CI: 1.11-1.87) in males. CONCLUSION: Both longer nighttime sleep duration and longer naps may be associated with the development of MetS.

Novel Oridonin Analog CYD0682 Inhibits Hepatic Stellate Cell Activation via the Heat Shock Protein 90-Dependent STAT3 Pathway.

INTRODUCTION: Activated hepatic stellate cells (HSCs) are the primary effector cells in hepatic fibrosis, over depositing extracellular matrix (ECM) proteins. Our previous work found oridonin analog CYD0682 attenuates proliferation, Transforming Growth Factor ß (TGFß)-induced signaling, and ECM production in immortalized HSCs. The underlying mechanism behind these reductions is unclear. The Signal Transduction and Activator of Transcription 3 (STAT3) pathway plays a central role in HSC activation and has been found to be overexpressed in models of hepatic injury. In this study, we will examine the effect of CYD0682 on STAT3 signaling. METHODS: Immortalized human (LX-2) and rat (HSC-T6) HSC lines were treated with CYD0682 or Tanespimycin (17-AAG) with or without TGF-ß. Nuclear and cytosolic proteins were extracted. Protein expression was analyzed with Western blot. DNA binding activity was assessed with STAT3 DNA Binding ELISA. Cell viability was assessed with Alamar blue assay. RESULTS: CYD0682 treatment inhibited STAT3 phosphorylation at tyrosine 705 in a dose-dependent manner in LX-2 and HSC-T6 cells. STAT3 DNA binding activity and STAT3 regulated protein c-myc were significantly decreased by CYD0682. Notably, TGFß-induced STAT3 phosphorylation and ECM protein expression were inhibited by CYD0682. STAT3 is reported to be a Heat Shock Protein 90 (HSP90) client protein. Notably, CYD0682 attenuated the expression of endogenous STAT3 and other HSP90 client proteins FAK, IKKα, AKT and CDK9. HSP90 specific inhibitor 17-AAG suppressed endogenous and TGFß-induced STAT3 phosphorylation and ECM protein production. CONCLUSIONS: CYD0682 attenuates endogenous and TGFß-induced STAT3 activation and ECM production via an HSP90 dependent pathway in HSCs. Further study of this pathway may present new targets for therapeutic intervention in hepatic fibrosis.

Clinical and CT Quantitative Features for Predicting Liver Metastases in Patients with Pancreatic Neuroendocrine Tumors: A Study with Prospective/External Validation.

RATIONALE AND OBJECTIVES: We aimed to evaluate clinical characteristics and quantitative CT imaging features for the prediction of liver metastases (LMs) in patients with pancreatic neuroendocrine tumors (PNETs). METHODS: Patients diagnosed with pathologically confirmed PNETs were included, 133 patients were in the training group, 22 patients in the prospective internal validation group, and 28 patients in the external validation group. Clinical information and quantitative features were collected. The independent variables for predicting LMs were confirmed through the implementation of univariate and multivariate logistic analyses. The diagnostic performance was evaluated by conducting receiver operating characteristic curves for predicting LMs in the training and validation groups. RESULTS: PNETs with LMs demonstrated significantly larger diameter and lower arterial/portal tumor-parenchymal enhancement ratio, arterial/portal absolute enhancement value (AAE/PAE value) (p < 0.05). After multivariate analyses, A high level of tumor marker (odds ratio (OR): 5.32; 95% CI, 1.54-18.35), maximum diameter larger than 24.6 mm (OR: 7.46; 95% CI, 1.70-32.72), and AAE value ≤ 51 HU (OR: 4.99; 95% CI, 0.93-26.95) were independent positive predictors of LMs in patients with PNETs, with area under curve (AUC) of 0.852 (95%CI, 0.781-0.907). The AUCs for prospective internal and external validation groups were 0.883 (95% CI, 0.686-0.977) and 0.789 (95% CI, 0.602-0.916), respectively. CONCLUSION: Tumor marker, maximum diameter and absolute enhancement value in arterial phase were independent predictors with good predictive performance for the prediction of LMs in patients with PNETs. Combining clinical and quantitative features may facilitate the attainment of good predictive precision in predicting LMs.

Reducing younger and older adults' spatial disorientation during indoor-outdoor transitions: Effects of route alignment and visual access on wayfinding.

Getting lost could lead to frustration, anxiety, and even fatal accidents. Previous research primarily focused on disorientation in indoor or outdoor environments separately. The indoor-outdoor transition received little attention, yet it is in this complex transition that individuals often lose their way. Therefore, the effects of indoor-outdoor route alignment, visual access, and age on wayfinding performance and spatial cognition were examined. Twenty older adults (aged 18-25) and twenty young adults (aged 65-82) participated in an experiment through desktop Virtual Reality (VR). They traversed indoor-outdoor environments and were informed within a building to quickly navigate an item inside another building. They also drew the route map. Participants repeated tasks in four different environments. Their spatial cognition and wayfinding performance were analyzed. Four main findings were derived. Firstly, the accuracy of global representation of the routes in the indoor-outdoor route alignment environment was higher than that in the non-aligned environment. Secondly, in environments with higher visual access, the accuracy of global representation of the routes for older adults was higher than that with lower visual access. Thirdly, enhancing visual access attenuated the negative impact of the non-aligned route on global representation of the routes. This effect is particularly beneficial for older adults. Fourthly, the younger adults outperformed the older adults in both wayfinding performance and global representation of the routes in indoor-outdoor environments. This difference could potentially be attributed to variations in education level, mental rotation ability, and digital experience. These findings provide valuable implications for urban design and wayfinding strategies.

Effect of Placental Transfusion on Long-Term Neurodevelopmental Outcomes in Premature Infants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The pathophysiology and the potential risks of placental transfusion (PT) differ substantially in preterm infants, necessitating specific studies in this population. This study aimed to evaluate the safety and efficacy of PT in preterm infants from the perspective of long-term neurodevelopmental outcomes. METHODS: We conducted a systematic literature search using placental transfusion, preterm infant, and its synonyms as search terms. Cochrane Central Register of Controlled Trials, Medline, and Embase were searched until March 07, 2023. Two reviewers independently identified, extracted relevant randomized controlled trials, and appraised the risk of bias. The extracted studies were included in the meta-analysis of long-term neurodevelopmental clinical outcomes using fixed-effects models. RESULTS: A total of 5612 articles were identified, and seven randomized controlled trials involving 2551 infants were included in our meta-analysis. Compared with immediate cord clamping (ICC), PT may not impact adverse neurodevelopment events. No clear evidence was found of a difference in the risk of neurodevelopmental impairment (risk ratio [RR]: 0.89, 95% confidence interval [CI]: 0.76 to 1.03, P = 0.13, I2 = 0). PT was not associated with the incidence of cerebral palsy (RR: 1.23, 95% CI: 0.59 to 2.57, P = 0.79, I2 = 0). Analyses showed no differences between the two interventions in cognitive, language, and motor domains of neurodevelopment. CONCLUSIONS: From the perspective of long-term neurodevelopment, PT at preterm birth may be as safe as ICC. Future studies should focus on standardized, high-quality clinical trials and individual participant data to optimize cord management strategies for preterm infants after birth.