Working memory flips the direction of serial bias through memory-based decision.

Reported perception of a new stimulus is either attracted toward or repelled away from task-irrelevant prior stimuli. While prevailing theories propose that the opposing serial biases may stem from distinct stages of information processing, the exact role of working memory (WM) in the serial bias remains unclear despite its consistent involvement in nearly all pertinent studies. Additionally, it is not well understood whether this bias is primarily driven by the biased representation itself or by the decision-making process for the new stimulus. In the present study, we used an orientation delayed estimation paradigm with an attention-demanding intervening task, designed to disrupt the maintenance of stimulus information to investigate the role of WM in serial bias. In the analysis, we scrutinized the trajectory of mouse reports and response time to investigate how the response unfolds over time. Our findings indicate that the serial bias went from repulsive to attractive when WM maintenance was interrupted by the intervening task, and that the associated response trajectories and response time exhibited patterns that cannot be explained by the biased representation alone. These results demonstrate that the task-irrelevant prior stimulus influences the decision for the new stimulus, with the direction of the bias being determined by attentional demand during WM maintenance, thereby placing significant constraints on existing theories on the serial bias effect.

Nanoparticles for Augmenting Therapeutic Potential and Alleviating the Effect of Di(2-ethylhexyl) Phthalate on Gastric Cancer.

Changes in diet culture and modern lifestyle contributed to a higher incidence of gastrointestinal-related diseases, including gastritis, implicated in the pathogenesis of gastric cancer. This observation raised concerns regarding exposure to di(2-ethylhexyl) phthalate (DEHP), which is linked to adverse health effects, including reproductive and developmental problems, inflammatory response, and invasive adenocarcinoma. Research on the direct link between DEHP and gastric cancer is ongoing, and further studies are required to establish a conclusive association. In our study, extremely low concentrations of DEHP exerted significant effects on cell migration by promoting the epithelial-mesenchymal transition in gastric cancer cells. This effect was mediated by the modulation of the PI3K/AKT/mTOR and Smad2 signaling pathways. To address the DEHP challenges, our initial design of TPGS-conjugated fucoidan, delivered via pH-responsive nanoparticles, successfully demonstrated binding to the P-selectin protein. This achievement has not only enhanced the antigastric tumor efficacy but has also led to a significant reduction in the expression of malignant proteins associated with the condition. These findings underscore the promising clinical therapeutic potential of our approach.

Prevalence and clinical features of carotid artery web in patients undergoing endovascular thrombectomy for acute ischemic stroke.

PURPOSE: Carotid artery web (CaW) is a rare focal fibromuscular dysplasia that can lead to embolic strokes with large vessel occlusion. This condition can be effectively treated with endovascular thrombectomy (EVT). Our study aims to assess the prevalence of CaW among patients with acute ischemic stroke (AIS) who underwent EVT and to compare the clinical characteristics of CaW with other carotid artery pathologies. METHODS: We enrolled consecutive patients with AIS who underwent EVT at a single medical center and two regional teaching hospitals in Taiwan from September 2014 to December 2021. We compared CaW with carotid dissection (CaD) and carotid large artery atherosclerosis (CaLAA) in terms of patient demographics and thrombus histological findings. RESULTS: Of the 576 AIS patients who underwent EVT, four (mean age: 50 years) were diagnosed with CaW, resulting in a prevalence of 0.69%. Among these four patients, three experienced successful reperfusion after EVT and achieved functional independence (defined as a modified Rankin Scale score ≤2) three months post-stroke. Importantly, none of the CaW patients suffered a recurrent stroke within one year. Patients with CaW were younger than those with CaD or CaLAA, and exhibited fewer vascular risk factors. Additionally, CaW was associated with distal occlusion sites. The thrombus composition in CaW patients was similar to that in CaD patients. CONCLUSIONS: In conclusion, CaW is a rare finding among Asian patients with carotid artery disease who undergo for AIS. It is more prevalent in younger patients with a limited number of vascular risk factors.

Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion.

BACKGROUND AND OBJECTIVES: Hydrocephalus is characterized by progressive enlargement of cerebral ventricles, resulting in impaired microvasculature and cerebral hypoperfusion. This study aimed to demonstrate the microvascular changes in hydrocephalic rats and the effects of cerebrospinal fluid (CSF) release on cerebral blood flow (CBF). METHODS: On postnatal day 21 (P21), male Wistar rats were intracisternally injected with either a kaolin suspension or saline. On P47, Evan's ratio (ER) was measured using MRI. On P49, the arteriolar diameter and vascular density of the pia were quantified using a capillary video microscope. The CBF was measured using laser Doppler flowmetry. The expressions of NeuN and glial fibrillary acidic protein determined by immunochemical staining were correlated with the ER. The CBF and rotarod test performance were recorded before and after CSF release. The expressions of 4-hydroxynonenal (4-HNE) and c-caspase-3 were studied on P56. RESULTS: Ventriculomegaly was induced to varying degrees, resulting in the stretching and abnormal narrowing of pial arterioles, which regressed with increasing ER. Quantitative analysis revealed significant decreases in the arteriolar diameter and vascular density in the hydrocephalic group compared with those in the control group. In addition, the CBF in the hydrocephalic group decreased to 30%-50% of that in the control group. In hydrocephalus, the neurons appear distorted, and the expression of 4-HNE and reactive astrogliosis increase in the cortex. After CSF was released, improvements in the CBF and rotarod test performance were inversely associated with the ER. In addition, the levels of 4-HNE and c-caspase-3 were further elevated. CONCLUSION: Rapid ventricular dilatation is associated with severe microvascular distortion, vascular regression, cortical hypoperfusion, and cellular changes that impair the recovery of CBF and motor function after CSF release. Moreover, CSF release may induce reperfusion injury. This pathophysiology should be taken into account when treating hydrocephalus.

Recombinant soluble form of receptor for advanced glycation end products ameliorates microcirculation impairment and neuroinflammation after subarachnoid hemorrhage.

Impaired cerebral microcirculation after subarachnoid hemorrhage (SAH) has been shown to be related to delayed ischemic neurological deficits (DIND). We previously demonstrated the involvement of the receptor for advanced glycation end products (RAGE) in the pathogenesis of SAH related neuronal death. In the present study, we aimed to investigate the therapeutic effects of a recombinant soluble form of RAGE (sRAGE) on microcirculation impairment following SAH. Intrathecal injection of autologous blood in rats, mixed primary astrocyte and microglia cultures exposed to hemolysates and endothelial cells â€‹(ECs) from human brain microvascular exposed to glia-conditioned medium or SAH patient's CSF were used as experimental SAH models in vivo and in vitro. The results indicated that intrathecal administration of recombinant sRAGE significantly ameliorated the vasoconstriction of cortical arterioles and associated perfusion impairment, brain edema, reduced cell death, endothelial dysfunction, and improved motor performance at 24 and 48 â€‹h after SAH induction in rats. The in vitro results further showed that recombinant sRAGE significantly reduced astrocyte swelling and microglia activation, in parallel with decreased mRNA expression levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in vitro. Moreover, the in vitro model of SAH-induced p-eNOS and eNOS suppression, along with stress fiber formation in brain microvascular ECs, was effectively reversed by sRAGE treatment and led to a decrease in cleaved-caspase 3 expression. In summary, recombinant sRAGE effectively lessened microcirculation impairment and vascular injury after SAH via the mechanism of anti-inflammation, which may provide a potential therapeutic strategy for SAH.

Nanoparticle-enhanced postbiotics: Revolutionizing cancer therapy through effective delivery.

AIM: Gastric cancer contributes to cancer-related fatalities. Conventional chemotherapy faces challenges due to severe adverse effects, prompting recent research to focus on postbiotics, which are safer biomolecules derived from nonviable probiotics. Despite promising in vitro results, efficient in vivo delivery systems remain a challenge. This study aimed to design a potential nanoparticle (NP) formulation encapsulating the Lacticaseibacillus paracasei GMNL-133 (SGMNL-133) isolate to enhance its therapeutic efficacy in treating gastric cancer. MAIN METHODS: We successfully isolated GMNL-133 (SGMNL-133) by optimizing the lysate extraction and column elution processes for L. paracasei GMNL-133, resulting in substantial enhancement of its capacity to inhibit the proliferation of gastric cancer cells. Additionally, we developed a potential NP utilizing arginine-chitosan and fucoidan encapsulating SGMNL-133. KEY FINDINGS: This innovative approach protected the SGMNL-133 from degradation by gastric acid, facilitated its penetration through the mucus layer, and enabled interaction with gastric cancer cells. Furthermore, in vivo experiments demonstrated that the encapsulation of SGMNL-133 in NPs significantly enhanced its efficacy in the treatment of orthotopic gastric tumors while simultaneously reducing tissue inflammation levels. SIGNIFICANCE: Recent research highlights postbiotics as a safe alternative, but in vivo delivery remains a challenge. Our study optimized the extraction of the lysate and column elution of GMNL-133, yielding SGMNL-133. We also developed NPs to protect SGMNL-133 from gastric acid, enhance mucus penetration, and improve the interaction with gastric cancer cells. This combination significantly enhanced drug delivery and anti-gastric tumor activity.

Association of temporalis muscle thickness with functional outcomes in patients undergoing endovascular thrombectomy.

INTRODUCTION: Temporalis muscle thickness (TMT) is a surrogate marker for sarcopenia. This study investigated the association of TMT with clinical outcomes in patients receiving endovascular thrombectomy (EVT) for stroke involving acute large vessel occlusion (LVO). MATERIAL AND METHODS: We enrolled consecutive patients who had undergone EVT between September 2014 and December 2021 at three thrombectomy-capable institutes. TMT was measured through preprocedural computerized tomography angiography. The clinical variables affecting TMT were investigated. The associations between TMT and clinical functional outcomes, defined using the modified Rankin scale, were also studied. RESULTS: A total of 657 patients were included (mean age: 72.0 ± 12.7 years; male: 52.1%). The mean TMT was 6.35 ± 1.84 mm. Younger age, male sex, higher body mass index, and premorbid functional independence were associated with larger TMT in both univariate and multivariate linear regression (P <.05). Ordinal logistic regression revealed that TMT was associated with better clinical outcomes at 90 days (Ptrend = 0.047); multivariate logistic regression indicated that larger TMT was an independent predictor (adjusted odds ratio: 1.14, 95% confidence interval: 1.03-1.27, P = 0.02) of favorable functional independence (modified Rankin scale score: 0-2). The effect was stronger in older patients (≥80 years) than younger patients, as revealed by interaction modeling analysis (Pinteraction = 0.06). CONCLUSION: TMT is associated with age, sex, body mass index, and premorbid functional status. Larger TMT is associated with better outcomes after EVT. The effects of TMT are more pronounced in older adults, indicating that sarcopenia may have influence on stroke outcomes.

Does a negative correlation of heme oxygenase-1 with hematoma thickness in chronic subdural hematomas affect neovascularization and microvascular leakage? A retrospective study with preliminary validation.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a common neurological disease among elderly adults. The progression of CSDH is an angiogenic process, involving inflammatory mediators that affect vascular permeability, microvascular leakage, and hematoma thickness. The authors aimed to identify biomarkers associated with angiogenesis and vascular permeability that might influence midline shift and hematoma thickness. METHODS: Medical records and laboratory data of consecutive patients who underwent surgery for CSDH were analyzed. Collected data were basic demographic data, CSDH classification, CSDH thickness, midline shift, heme oxygenase-1 (HO-1) levels in hematomas, and common laboratory markers. Linear regression analysis was used to evaluate the relationship of CSDH thickness with characteristic variables. The chick chorioallantoic membrane (CAM) assay was used to test the angiogenic potency of identified variables in ex ovo culture of chick embryos. RESULTS: In total, 93 patients with CSDH (71.0% male) with a mean age of 71.0 years were included. The mean CSDH thickness and midline shift were 19.7 and 9.8 mm, respectively. The mean levels of HO-1, ferritin, total bilirubin, white blood cells, segmented neutrophils, lymphocytes, platelets, international normalized ratio, and partial thromboplastin time were 36 ng/mL, 14.8 µg/mL, 10.5 mg/dL, 10.3 × 103 cells/µL, 69%, 21.7%, 221.1 × 109 cells/µL, 1.0, and 27.8 seconds, respectively. Pearson correlation analysis revealed that CSDH thickness was positively correlated with midline shift distance (r = 0.218, p < 0.05) but negatively correlated with HO-1 concentration (r = -0.364, p < 0.01) and ferritin level (r = -0.222, p < 0.05). Multivariate linear regression analysis revealed that HO-1 was an independent predictor of CSDH thickness (ß = -0.084, p = 0.006). The angiogenic potency of HO-1 in hematoma fluid was tested with the chick CAM assay; topical addition of CSDH fluid with low HO-1 levels promoted neovascularization and microvascular leakage. Addition of HO-1 in a rescue experiment inhibited CSDH fluid-mediated angiogenesis and microvascular leakage. CONCLUSIONS: HO-1 is an independent risk factor in CSDH hematomas and is negatively correlated with CSDH thickness. HO-1 may play a role in the pathophysiology and development of CSDH, possibly by preventing neovascularization and reducing capillary fragility and hyperpermeability.

Reinforcement learning strategies in cancer chemotherapy treatments: A review.

BACKGROUND AND OBJECTIVE: Cancer is one of the major causes of death worldwide and chemotherapies are the most significant anti-cancer therapy, in spite of the emerging precision cancer medicines in the last 2 decades. The growing interest in developing the effective chemotherapy regimen with optimal drug dosing schedule to benefit the clinical cancer patients has spawned innovative solutions involving mathematical modeling since the chemotherapy regimens are administered cyclically until the futility or the occurrence of intolerable adverse events. Thus, in this present work, we reviewed the emerging trends involved in forming a computational solution from the aspect of reinforcement learning. METHODS: Initially, this survey in-depth focused on the details of the dynamic treatment regimens from a broad perspective and then narrowed down to inspirations from reinforcement learning that were advantageous to chemotherapy dosing, including both offline reinforcement learning and supervised reinforcement learning. RESULTS: The insights established in the chemotherapy-planning problem associated with the Reinforcement Learning (RL) has been discussed in this study. It showed that the researchers were able to widen their perspectives in comprehending the theoretical basis, dynamic treatment regimens (DTR), use of the adaptive control on DTR, and the associated RL techniques. CONCLUSIONS: This study reviewed the recent researches relevant to the topic, and highlighted the challenges, open questions, possible solutions, and future steps in inventing a realistic solution for the aforementioned problem.

Dental Pulp Stem Cell-Derived Conditioned Medium Alleviates Subarachnoid Hemorrhage-Induced Microcirculation Impairment by Promoting M2 Microglia Polarization and Reducing Astrocyte Swelling.

Aneurysmal subarachnoid hemorrhage (SAH) can cause severe neurological deficits and high mortality. Early brain edema following SAH contributes to the initiation of microcirculation impairment and may further lead to delayed ischemic neurologic deficit (DIND). This study aimed to investigate whether dental pulp stem cell conditioned medium (DPSC-CM) ameliorates SAH-induced microcirculation impairment and the underlying mechanisms. SAH was induced via intrathecal injection of fresh autologous blood in Wistar male adult rat. DPSC-CM or DPSC-CM + insulin growth factor-1 (IGF-1) antibody was randomly administered by intrathecal route 5 min after SAH induction. To evaluate the underlying mechanisms of DPSC-CM in the treatment of SAH, primary rat astrocyte and microglia co-cultures were challenged with hemolysate or SAH-patient CSF in the presence or absence of DPSC-CM. The results showed that in vivo, DPSC-CM treatment decreased the brain water content, improved microcirculation impairment and enhanced functional recovery at 24 h post-SAH. DPSC-CM treatment also alleviated the expressions of water channel protein aquaporin-4 (AQP4) and pro-inflammatory cytokines, and enhanced the expressions of anti-inflammatory factors in the cortical region. However, all the beneficial effects of DPSC-CM were abrogated after treatment with IGF-1 neutralizing antibody. The in vitro results further showed that DPSC-CM treatment reduced hemolysate/SAH-patient CSF-induced astrocyte swelling and promoted M2 microglia polarization, partially through IGF-1/AKT signaling. The data suggested that DPSC-CM significantly reduced brain edema and rescued microcirculation impairment with concomitant anti-inflammatory benefits after SAH, and may potentially be developed into a novel therapeutic strategy for SAH.

Outcome of endovascular thrombectomy in patients with end-stage renal disease undergoing dialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) are often excluded from clinical trials of endovascular thrombectomy (EVT). This study investigated the outcome in these patients. METHODS: From September 2014 to July 2021, all patients undergoing EVT for anterior circulation stroke in two stroke centers in Taiwan were included. They were divided into no renal dysfunction (non-RD, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2), RD (eGFR <60 mL/min/1.73 m2 but no dialysis), and ESRD undergoing dialysis (ESRD-dialysis). The clinical features and outcomes were compared. RESULTS: Of 482 patients included, there were 20 ESRD-dialysis, 110 RD, and 352 non-RD patients. The Alberta Stroke Program Early CT Score (ASPECTS), National Institutes of Health Stroke Scale (NIHSS), use of intravenous thrombolysis, EVT-related time metrics, and successful recanalization rates were comparable among the three groups. However, the ESRD-dialysis patients had more symptomatic intracerebral hemorrhage (ICH, 15% vs 3.6% vs 3.7%), more contrast-induced encephalopathy (15% vs 1.8% vs 0.9%), and a higher mortality at 90 days (35% vs 18% vs 11%) than the other groups. Multivariable analysis revealed that ESRD-dialysis was associated with a less favorable outcome (OR 0.21, 95% CI 0.04 to 0.77) and more severe disability or mortality (modified Rankin Scale 5 or 6; OR 13.1, 95% CI 3.93 to 48.1) at 90 days. In the ESRD-dialysis group, the patients with premorbid functional dependence had a significantly higher mortality than those without (75% vs 8.3%; P=0.004). CONCLUSION: ESRD-dialysis patients were associated with symptomatic ICH and less favorable outcome at 90 days. Patients with premorbid functional dependency had an excessively high mortality.

Targeting nanoparticle-conjugated microbubbles combined with ultrasound-mediated microbubble destruction for enhanced tumor therapy.

The stress of the abnormal stromal matrix of solid tumors is a major limiting factor that prevents drug penetration. Controlled, accurate, and efficient delivery of theranostic agents into tumor cells is crucial. Combining ultrasound with nanocarrierbased drug delivery systems have become a promising approach for targeted drug delivery in preclinical cancer therapy. In this study, to ensure effective tumor barrier penetration, access to the tumor microenvironment, and local drug release, we designed targeted nanoparticle (NP)-conjugated microbubbles (MBs); ultrasound could then help deliver acoustic energy to release the NPs from the MBs. The ultrasound-targeted MB destruction (UTMD) system of negatively charged NPs was conjugated with positively charged MBs using an ionic gelation method. We demonstrated the transfer of targeted NPs and their entry into gastric cancer cells through ligand-specific recognition, followed by enhanced cell growth inhibition owing to drug delivery-induced apoptosis. Moreover, the UTMD system combining therapeutic and ultrasound image properties can effectively target gastric cancer, thus significantly enhancing antitumor activity, as evident by tumor localization in an orthotopic mouse model of gastric cancer. The combination of ultrasound and NP-based drug delivery systems has become a promising approach for targeted drug delivery in preclinical cancer therapy.

Supervised Optimal Chemotherapy Regimen Based on Offline Reinforcement Learning.

In recent years, reinforcement learning (RL) has achieved a remarkable achievement and it has attracted researchers' attention in modeling real-life scenarios by expanding its research beyond conventional complex games. Prediction of optimal treatment regimens from observational real clinical data is being popularized, and more advanced versions of RL algorithms are being implemented in the literature. However, RL-generated medications still need careful supervision of expertise parties or doctors in healthcare. Hence, in this paper, a Supervised Optimal Chemotherapy Regimen (SOCR) approach to investigate optimal chemotherapy-dosing schedule for cancer patients was presented by using Offline Reinforcement Learning. The optimal policy suggested by the RL approach was supervised by incorporating previous treatment decisions of oncologists, which could add clinical expertise knowledge on algorithmic results. Presented SOCR approach followed a model-based architecture using conservative Q-Learning (CQL) algorithm. The developed model was tested using a manually constructed database of forty Stage-IV colon cancer patients, receiving line-1 chemotherapy treatments, who were clinically classified as 'Bevacizumab based patient' and 'Cetuximab based patient'. Experimental results revealed that the supervision from the oncologists has considered the effect to stabilize chemotherapy regimen and it was suggested that the proposed framework could be successfully used as a supportive model for oncologists in deciding their treatment decisions.

Online flipped learning methods for teaching hospitality skills and management practices in an epidemic situation: A study on learning attitude and effectiveness.

Starting in 2019, the ongoing COVID-19 pandemic has lasted 3 years and will likely continue to affect the lives of people all over the world. According to a United Nations Educational, Scientific and Cultural Organization (UNESCO) survey, more than 91% of students from all over the world have been affected by the spread of COVID-19. The application of technological networks can help solve problems related to being unable to attend school in person, as online teaching can effectively help reduce learning loss in the short term. In Taiwan, the higher education system has been using online learning, but now faces a new and huge crisis, as some courses do not readily translate to this setting. In professional courses run by hospitality departments, it is essentially impossible to accurately convey the practical skills required, for example, aspects of color, aroma, and taste through online teaching. Moreover, the learning level of each student varies greatly. During the online teaching process, instructors teach professional skills and movements through a single teaching video, which may not meet the needs of all students. In response, this study explores using the flipped teaching method, to not only enable students to master and control their learning and effectively adjust their self- adaptive learning progress but also to help teachers solve problems and impart professional skills using a two-way, interactive, online teaching method. This approach, flipping a class in an online learning environment, could effectively make up for the one-way teaching sometimes created by video content, and address the problem of gaps in learning professional practical skills. It can also induce students with poor learning attitudes to actively participate in learning. This study involved 55 bachelor students from a university of science and technology in Taiwan. The research results are as follows: (1) Students who participated in the flipped teaching mode, which involved two-way interaction showed better professional understanding of the course and improved willingness to learn, thereby improving the learning effect. (2) Awareness of these poor practical catering professional skills in students, assisted in laying the professional foundation for students to gradually improve their learning attitude and their advanced skills. This indicates that students with poor academic performance in an online environment might benefit from two-way interactive teaching. Teachers should clarify detailed descriptions of professional practical actions that confuse students. (3) In flipped learning, the grouping of "game/toy-based e-learning" can not only improve the performance of students who actively study to achieve good grades but also help and motivate other students to learn together. These results indicate that in flipped classrooms that use an online learning environment, the active learning and learning attitudes of students were positive and that their interest in learning and learning efficiency was also significantly improved. At the same time, this approach stimulated the innovation, creativity, and creative development of students in using professional technology in the hospitality industry. It transformed the passive learning situation of online one-way teaching into an active two-way teaching environment.

Prevalence of Vitamin D Deficiency and Associated Factors in Critically Ill Patients: A Multicenter Observational Study.

Background: Vitamin D deficiency is common in the general population worldwide, and the prevalence and severity of vitamin D deficiency increase in critically ill patients. The prevalence of vitamin D deficiency in a community-based cohort in Northern Taiwan was 22.4%. This multicenter cohort study investigated the prevalence of vitamin D deficiency and associated factors in critically ill patients in Northern Taiwan. Methods: Critically ill patients were enrolled and divided into five groups according to their length of stay at intensive care units (ICUs) during enrolment as follows: group 1, <2 days with expected short ICU stay; group 2, <2 days with expected long ICU stay; group 3, 3-7 days; group 4, 8-14 days; and group 5, 15-28 days. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25(OH)D) level < 20 ng/ml, and severe vitamin D deficiency was defined as a 25(OH)D level < 12 ng/ml. The primary analysis was the prevalence of vitamin D deficiency. The exploratory analyses were serial follow-up vitamin D levels in group 2, associated factors for vitamin D deficiency, and the effect of vitamin D deficiency on clinical outcomes in critically ill patients. Results: The prevalence of vitamin D deficiency was 59% [95% confidence interval (CI) 55-62%], and the prevalence of severe vitamin D deficiency was 18% (95% CI 15-21%). The median vitamin D level for all enrolled critically ill patients was 18.3 (13.7-23.9) ng/ml. In group 2, the median vitamin D levels were <20 ng/ml during the serial follow-up. According to the multivariable analysis, young age, female gender, low albumin level, high parathyroid hormone (PTH) level, and high sequential organ failure assessment (SOFA) score were significantly associated risk factors for vitamin D deficiency. Patients with vitamin D deficiency had longer ventilator use duration and length of ICU stay. However, the 28- and 90-day mortality rate were not associated with vitamin D deficiency. Conclusions: This study demonstrated that the prevalence of vitamin D deficiency is high in critically ill patients. Age, gender, albumin level, PTH level, and SOFA score were significantly associated with vitamin D deficiency in these patients.

A Study on Flipped Learning Concerning Learning Motivation and Learning Attitude in Language Learning.

From the popularity of flipped teaching in United States primary and high schools, it is thought that students have more learning control to adjust to the learning progress and are assisted in problem solving and learning guidance during class period. It is believed that flipped teaching could prompt underachieving learners' active learning and thereby enhance learning effectiveness. A total of 386 high school students in Chungli, Taiwan, were part of an experimental study and the research results are summarized below: (1) Students who participated in the flipped teaching models demonstrated better comprehension levels with the teaching content due to this change in learning style and attitude, which in turn, enhanced learning effectiveness. (2) To eliminate poor language performance of underachieving students, it is necessary to lay solid foundations to gradually enhance language learning effectiveness regarding this particular group of students. Films suitable for students' individual ability could be combined with new language learned in the unit to genuinely assist underachieving learners' language learning effectiveness. (3) For students who care about their performance, a "system of play" style grouping should be determined in order to enable the tracking of group performance and term performance. According to the results, further developments regarding active learning ability, boosts in learning interests, enhanced learning effectiveness, and the prompting of creativity resulting in a shift from passive learner to active learner have been proposed.

Mangiferin induces immune responses and evaluates the survival rate in WEHI-3 cell generated mouse leukemia in vivo.

Mangiferin is a naturally occurring polyphenol, widely distributed in Thymeraceae families, and presents pharmacological activity, including anti-cancer activities in many human cancer cell lines. Mangiferin has also been reported to affect immune responses; however, no available information concerning the effects of mangiferin on immune reactions in leukemia mice in vivo. In the present study, we investigated the effects of mangiferin on leukemia WEHI-3 cell generated leukemia BLAB/c mice. Overall, the experiments were divided into two parts, one part was immune responses experiment and the other was the survival rate experiment. The immune responses and survival rate study, 40 mice for each part, were randomly separated into five groups (N = 8): Group I was normal animals and groups II-V WEHI-3 cell generated leukemia mice. Group II mice were fed normal diet as a positive control; group III, IV, and V mice received mangiferin at 40, 80, and 120 mg/kg, respectively, by intraperitoneal injection every 2 days for 20 days. Leukocytes cell population, macrophage phagocytosis, and NK cell activities were analyzed by flow cytometry. Isolated splenocytes stimulated with lipopolysaccharide (LPS) and concanavalin A (Con A) were used to determine the proliferation of B and T cells, respectively, and subsequently were analyzed by flow cytometry. Results indicated that mangiferin significantly increased body weight, decreased the liver and spleen weights of leukemia mice. Mangiferin also increased CD3 T-cell and CD19 B cell population but decreased Mac-3 macrophage and CD11b monocyte. Furthermore, mangiferin decreased phagocytosis of macrophages from PBMC and peritoneal cavity at 40, 80, and 120 mg/kg treatment. However, it also increased NK cell activity at 40 and 120 mg/kg treatment. There were no effects on T and B cell proliferation at three examined doses. In survival rate studies, mangiferin significantly elevated survival rate at 40 and 120 mg/kg treatment of leukemia mice in vivo.

Casticin Inhibits In Vivo Growth of Xenograft Tumors of Human Oral Cancer SCC-4 Cells.

BACKGROUND/AIM: Casticin, one of the active components of Vitex rotundifolia L., presents biological and pharmacological activities including inhibition of migration, invasion and induction of apoptosis in numerous human cancer cells in vitro. This study aimed to assess the effects of casticin on tumor growth in a human oral cancer SCC-4 cell xenograft mouse model in vivo. MATERIALS AND METHODS: Twenty-four nude mice were injected subcutaneously with SCC-4 cells and when palpable tumors reached a volume of 100-120 mm3 the mice were randomly divided into three groups. The control (0.1% dimethyl sulfoxide), casticin (0.2 mg/kg), and casticin (0.4 mg/kg) groups were intraperitoneally injected every two days for 18 days. Tumor volume and body weights were measured every two days. RESULTS: Casticin significantly decreased tumor volume and weight in SCC-4 cell xenograft mice but there was no statistically significant difference between the body weights of control mice and mice treated with 0.2 mg/kg or 0.4 mg/kg casticin. Therefore, the growth of SCC-4 cells in athymic nude mice can be inhibited by casticin in vivo. CONCLUSION: These findings support further investigations in the potential use of casticin as an oral anti-cancer drug in the future.

Endovascular Treatment Outcome and CT Angiography Findings in Acute Basilar Artery Occlusion with and without Underlying Intracranial Atherosclerotic Stenosis.

PURPOSE: To compare clinical characteristics and treatment outcomes of intra-arterial thrombectomy (IAT) in acute basilar artery occlusion (BAO) with and without underlying intracranial atherosclerotic stenosis (ICAS) and to investigate the usefulness of preprocedural CT angiography findings in the diagnosis of ICAS. MATERIALS AND METHODS: Twenty patients who received IAT for acute BAO between September 2014 and March 2019 were included. Additional therapies such as angioplasty, stent placement, and tirofiban infusion were provided while treating ICAS. Clinical and angiographic results of treatment were recorded. Preprocedural CT angiography findings in ICAS and non-ICAS groups were compared to assess (i) basilar tip opacification, (ii) partial occlusion, (iii) presence of convex border, (iv) occlusion segment longer than two thirds of the basilar artery or 20 mm, (v) dense basilar artery, and (vi) wall calcification in the occluded segment. RESULTS: Among the 20 patients (mean age, 71.3 y; mean stroke score, 24.8), optimal recanalization was achieved in 19 (95%). Three patients had good clinical outcomes. There were 6 patients with underlying ICAS. No difference was observed between ICAS and non-ICAS groups in terms of optimal angiographic recanalization and good outcome. On CT angiography, basilar tip occlusion (100% vs 29%), partial occlusion (100% vs 83%), and long occlusion length (100% vs 14%) significantly differed between the groups (P ≤ .01). CONCLUSIONS: In acute BAO, underlying ICAS does not affect optimal recanalization rate or clinical outcome. Preprocedural CT angiography is a potentially useful tool to detect it.