Reliability, validity, usefulness, and sensitivity of a submaximal test of performing burpees in 3 minutes, in assessing and detecting changes in aerobic fitness of athletes during future prolonged self-isolation in a confined environment.

BACKGROUND: During a prolonged quarantine, there is a need to monitor aerobic fitness levels of trained individuals who are isolated with a simple fitness test that can be performed in confined space of their own homes. This study examined the reliability, validity, usefulness and sensitivity of a novel 3-min submaximal heart rate burpees test (or SubHR3-MBT) to assess and monitor changes in aerobic fitness, of trained athletes. In the SubHR3-MBT, male and female athletes performed 48 and 39 burpees respectively, within 3 min by following a constant beeping pace. The performance criterion of the SubHR3-MBT is the highest heart rate attained (or exercise HRpeak) at the end of 3-min (wherein a lower exercise HRpeak indicates a higher level of aerobic fitness). METHODS: A total of 40 male and female national athletes from various sports volunteered for the study. RESULTS: For reliability (Part 1), the SubHR3-MBT showed good relative and excellent reliability, with intraclass correlation coefficient 0.90 and coefficient of variation 2.6%, respectively. For validity (Part II), there was significant negative correlation between relative exercise HRpeak with respiratory gas-measured VO2max (r=-0.51, large; P<0.001). The test's technical error of measurement of 2.3 is slightly greater than its smallest worthwhile change of 1.5. For sensitivity (Part III), the athletes were tested twice for their SubHR3-MBT and VO2max, once at baseline and another at a followed-up test after >10 weeks. There was a significant correlation between the % change in relative exercise HRpeak with the % change in VO2max (r=-0.66, large; P<0.001). CONCLUSIONS: The SubHR3-MBT is a reliable, valid, marginally useful test and may be able to track changes in aerobic fitness in trained athletes with moderate levels of sensitivity, in case of future isolation due to pandemic occurrence.

Adolescents' motivation to use social network sites from a psychological needs perspective.

INTRODUCTION: Adolescents' social network sites (SNS) use is prominent during the developmental period. Various adolescents' motivations for using  SNS have been reported. However, there is a lack of psychological perspectives in understanding the reasons for adolescents to use SNS. This study explored adolescents' motivation to use SNS, and a comprehensive psychological framework was used to dismantle adolescents' reasons and purposes for using SNS. Adolescents' ways of using SNS were explored to contextualize teens' SNS use. METHODS: Semistructured interviews with 18 Malaysian adolescents (Mage = 15; 50% female; 10 Malay, 5 Chinese, 1 Indian, 1 Other Bumiputera) were conducted. The qualitative data were collected in 2021 in Malaysia through online video calls. Reflexive thematic analysis was the analytic approach. RESULTS: Six motivations for using SNS were identified: social interaction, content subscription and exploration, emotional support, participation, distraction, and self-expression. Each of the motivations was explicitly linked with different psychological needs. Adolescents were found to use SNS differently in three aspects: deliberate use (i.e., on purpose of use and time spent on SNS), content-selective, and audience-selective. CONCLUSION: This study demonstrates that psychological needs are the psychological reasons for adolescents' motivations for using SNS. Adolescence developmental tasks like strong peer identification and identity explorations are parts of the basic and compound psychological needs. Teens are pursuing a sense of self-coherence by using SNS. Adolescents demonstrated to use SNS differently at being deliberate and selective, which is speculated to be a result of the conflict between reflexive and reflective thought processes during SNS use.

Cognition following chimeric antigen receptor T-cell therapy: A systematic review.

BACKGROUND: This systematic review aimed to characterise the cognitive outcomes of patients who received chimeric antigen receptor T-cell therapy. METHODS: A systematic search of the literature was performed using PubMed, PsycINFO, SCOPUS, EMBASE, Medline, and CINAHL (February 2023). Risk of bias was assessed using the JBI Checklist for Case Reports and the Risk of Bias Assessment Tool for Non-randomised Studies. RESULTS: Twenty-two studies met inclusion criteria with a total of 1104 participants. There was considerable methodological heterogeneity with differing study designs (e.g., cohort studies, clinical trials, case studies, a qualitative interview, and a focus group), measures of cognition (e.g., self-report, neuropsychological measures, clinician assessed/neurological examinations), and longest follow-up time points (i.e., five days to five years). DISCUSSION: Results of the studies were heterogenous with studies demonstrating stable, improved, or reduced cognition across differing time points. Overall, cognitive symptoms are common particularly in the acute stage (<2 weeks) post-infusion. Most deficits that arise in the acute stage resolve within one to two weeks, however, there is a subset of patients who continue to experience and self-report persistent deficits in the subacute and chronic stages. Future studies are needed to comprehensively analyse cognition using a combination of self-report and psychometric measures following chimeric antigen receptor T-cell therapy in the acute, subacute, and chronic settings.

Synergistic effects of succession and microtopography of moraine on the fungal spatial diversity in a glacier forefield.

Primary succession and microtopography result in environmental changes and are important processes influencing the community assembly of soil fungi in the Arctic region. In glacier forefields that contain a series of moraine ridges, both processes contribute synchronously to fungal spatial diversity. To reveal the synergistic effects of succession and microtopography, we investigated the fungal community structure and environmental variables in the moraines of the Arklio Glacier, Ellesmere Island. The study sites were established at four locations from the top to the bottom of the ridge slope within each of the three moraine ridges of different post-glacial ages. The location-dependent community composition was equally diverse in both the initial and later stages of succession, suggesting that successional time could alter the effects of microtopography on the fungal community. Moreover, our results suggest that fungal communities at different locations follow different successional trajectories, even if they have passed through the same time lapse. Such a synergistic effect of succession and microtopography of moraines does not allow for parallel changes in fungal communities among moraines or among locations, suggesting that the moraine series contributes substantially to fungal spatial diversity in the glacier forefield.

Oral and Gut Microbiota Dysbiosis is Associated with Mucositis Severity in Autologous Hematopoietic Stem Cell Transplantation: Evidence from an Asian Population.

Mucositis is a debilitating complication of hematopoietic stem cell transplantation (HSCT). It is unclear how changes in the composition of microbiota, which are modulated by geographical location and ethnicity, may influence immune regulation leading to the development of mucositis, and the study of both oral and gut microbiota in a single population of autologous HSCT in the Asian region is lacking. The present study aimed to characterize the oral and gut microbiota changes, and the impact on both oral and lower gastrointestinal (GI) mucositis, with associated temporal changes in a population of adult recipients of autologous HSCT. Autologous HSCT recipients age ≥18 years were recruited from Hospital Ampang, Malaysia, between April 2019 and December 2020. Mucositis assessments were conducted daily, and blood, saliva, and fecal samples were collected prior to conditioning, on day 0, and at 7 days and 6 months post-transplantation. Longitudinal differences in alpha diversity and beta diversity were determined using the Wilcoxon signed-rank test and permutational multivariate analysis of variance, respectively. Changes in relative abundances of bacteria across time points were assessed using the microbiome multivariate analysis by linear models function. The combined longitudinal effects of clinical, inflammatory, and microbiota variables on mucositis severity were measured using the generalized estimating equation. Among the 96 patients analyzed, oral mucositis and diarrhea (representing lower GI mucositis) occurred in 58.3% and 95.8%, respectively. Alpha and beta diversities were significantly different between sample types (P < .001) and across time points, with alpha diversity reaching statistical significance at day 0 in fecal samples (P < .001) and at day +7 in saliva samples (P < .001). Diversities normalized to baseline by 6 months post-transplantation. Significant microbiota, clinical, and immunologic factors were associated with increasing mucositis grades. Increasing relative abundances of saliva Paludibacter, Leuconostoc, and Proteus were associated with higher oral mucositis grades, whereas increasing relative abundances of fecal Rothia and Parabacteroides were associated with higher GI mucositis grades. Meanwhile, increasing relative abundances of saliva Lactococcus and Acidaminococcus and fecal Bifidobacterium were associated with protective effects against worsening oral and GI mucositis grades, respectively. This study provides real-world evidence and insights into the dysbiosis of the microbiota in patients exposed to conditioning regimen during HSCT. Independent of clinical and immunologic factors, we demonstrated significant associations between relative bacteria abundances with the increasing severity of oral and lower GI mucositis. Our findings offer a potential rationale to consider the inclusion of preventive and restorative measures targeting oral and lower GI dysbiosis as interventional strategies to ameliorate mucositis outcome in HSCT recipients.

Prospective longitudinal analysis of clinical and immunological risk factors associated with oral and gastrointestinal mucositis following autologous stem cell transplant in adults.

PURPOSE: The study aimed to characterize the incidence of both oral and gastrointestinal (GI) mucositis, its' associated temporal changes in local and systemic pro-inflammatory cytokines, and to explore predictive clinical and immunological factors associated with their occurrences in hematopoietic stem cell transplant (HSCT). METHODS: Autologous HSCT patients aged 18 years old and above were recruited from Hospital Ampang, Malaysia, between April 2019 to December 2020. Mucositis assessments were conducted daily, whilst blood and saliva were collected prior to conditioning regimen, on Day 0, Day+7 and 6-month. Baseline and inflammatory predictors in a repeated time measurement of moderate-severe mucositis were assessed by multiple logistic regression and generalized estimating equations, respectively. RESULTS: Of the 142 patients analyzed, oral mucositis and diarrhea (representing GI mucositis) were reported as 68.3% and 95.8%, respectively. Predictive factors for moderate-severe oral mucositis were BEAM or busulphan-based regimens (odds ratio (OR)=9.2, 95% confidence interval (CI)=1.16-72.9, p-value (p) = 0.005) and vomiting (OR=4.6, 95% CI 1.68-12.3, p = 0.004). Predictive factors for moderate-severe GI mucositis were BEAM or busulphan-based regimens (OR=3.9, 95% CI 1.05-14.5, p = 0.023), female sex (OR = 3.3, 95% CI 1.43-7.44, p = 0.004) and body mass index (OR=1.08, 95% CI 1.02-1.15, p = 0.010). Cytokines analyses were performed in 96 patients. Saliva and plasma interleukin-6 (OR=1.003, 95% CI 1.001-1.004, p < 0.001 and OR=1.01, 95% CI 1.001-1.015, p = 0.029), and plasma tumor necrosis factor-alpha (OR=0.91, 95% CI 0.85-0.99, p = 0.019) were predictive of moderate-severe oral mucositis in a time-dependent model. CONCLUSION: This study provides real-world evidence and insights into patient- and treatment-related factors affecting oral and GI mucositis in HSCT.

Vegetation as a key driver of the distribution of microbial generalists that in turn shapes the overall microbial community structure in the low Arctic tundra.

Understanding the variability of microbial niches and their interaction with abiotic and biotic factors in the Arctic can provide valuable insights into microbial adaptations to extreme environments. This study investigates the structure and diversity of soil bacterial communities obtained from sites with varying vegetation coverage and soil biogeochemical properties in the low Arctic tundra and explores how bacteria interact under different environmental parameters. Our findings reveal differences in bacterial composition and abundance among three bacterial niche breadths (specialists, common taxa, and generalists). Co-occurrence network analysis revealed Rhizobiales and Ktedonobacterales as keystone taxa that connect and support other microbes in the habitat. Low-elevation indicators, such as vascular plants and moisture content, were correlated with two out of three generalist modular hubs and were linked to a large proportion of generalists' distribution (18%). Structural equation modeling revealed that generalists' distribution, which influenced the remaining microbial communities, was mainly regulated by vegetation coverage as well as other abiotic and biotic factors. These results suggest that elevation-dependent environmental factors directly influence microbial community structure and module formation through the regulation of generalists' distribution. Furthermore, the distribution of generalists was mainly affected by macroenvironment filtering, whereas the distribution of specialists was mainly affected by microenvironment filtering (species-engineered microbial niche construction). In summary, our findings highlight the strong top-down control exerted by vegetation on generalists' distribution, which in turn shapes the overall microbial community structure in the low Arctic tundra.

Psychometric evaluation of Oral Mucositis Daily Questionnaire: A cross-cultural adaptation of the Malay version in multiethnic adult autologous stem cell transplant.

Objective: Mucositis is one of the most feared side effects of cancer treatment. Psychometric analysis of a patient self-assessment score, the oral mucositis daily questionnaire in Malay (OMDQ-Mal) and its construct validity by means of confirmatory factor analysis (CFA) is lacking. This research aimed to test the validity and reliability of OMDQ-Mal. Methods: A total of 114 autologous stem-cell transplantation patients aged ≥ 18 years old at a national hematology center in Malaysia from April 2019 to December 2020 completed OMDQ-Mal concurrently with physician scores. Internal consistency and reproducibility were determined by Cronbach alpha and intraclass correlation coefficient, respectively. Correlations with physician scores were determined by Spearman correlation. Discriminative validity and construct validity were determined by Mann-Whitney U and CFA, respectively. Results: OMDQ-Mal demonstrated high internal consistency (α â€‹= â€‹0.874). Test-retest reliability between paired days were moderate to excellent (95% CI â€‹= â€‹0.676-0.953). Items in OMDQ-Mal had moderate to strong correlations with physician scores (ρ â€‹= â€‹0.503-0.721). Discriminative validity indicated that the scores of scales were significantly different between participants with severe and mild conditions. Construct validity results of loading factors 0.708-0.952; composite reliability 0.879-0.974; average variant extracted 0.710-0.841; and heterotrait-monotrait ratio 0.528 established the convergent and divergent validity. Conclusions: In conclusion, the OMDQ-Mal, which captured important quality of life responses, demonstrated adequate validity and reliability. This was supported by a two-component model CFA. The strong correlation of OMDQ-Mal with both physician scores indicated its potential as a comprehensive patient-reported outcome measure of mucositis of the entire alimentary tract.

Anticancer Mechanism of Flavonoids on High-Grade Adult-Type Diffuse Gliomas.

High-grade adult-type diffuse gliomas are the most common and deadliest malignant adult tumors of the central nervous system. Despite the advancements in the multimodality treatment of high-grade adult-type diffuse gliomas, the five-year survival rates still remain poor. The biggest challenge in treating high-grade adult-type diffuse gliomas is the intra-tumor heterogeneity feature of the glioma tumors. Introducing dietary flavonoids to the current high-grade adult-type diffuse glioma treatment strategies is crucial to overcome this challenge, as flavonoids can target several molecular targets. This review discusses the anticancer mechanism of flavonoids (quercetin, rutin, chrysin, apigenin, naringenin, silibinin, EGCG, genistein, biochanin A and C3G) through targeting molecules associated with high-grade adult-type diffuse glioma cell proliferation, apoptosis, oxidative stress, cell cycle arrest, migration, invasion, autophagy and DNA repair. In addition, the common molecules targeted by the flavonoids such as Bax, Bcl-2, MMP-2, MMP-9, caspase-8, caspase-3, p53, p38, Erk, JNK, p38, beclin-1 and LC3B were also discussed. Moreover, the clinical relevance of flavonoid molecular targets in high-grade adult-type diffuse gliomas is discussed with comparison to small molecules inhibitors: ralimetinib, AMG232, marimastat, hydroxychloroquine and chloroquine. Despite the positive pre-clinical results, further investigations in clinical studies are warranted to substantiate the efficacy and safety of the use of flavonoids on high-grade adult-type diffuse glioma patients.

Artificial intelligence in virtual reality simulation for interprofessional communication training: Mixed method study.

BACKGROUND: Virtual reality simulations are shown to be an effective approach for interprofessional nurse-physician communication training. However, its scalability is constrained by unequal medical-nursing cohort size, rendering a great challenge for all nursing students to form an interprofessional team with medical students. With the evolution of artificial intelligence (AI), an AI medical team player can be integrated into virtual reality simulations for more nursing students to engage in interprofessional team training. OBJECTIVES: To describe the development of a novel AI-enabled virtual reality simulation (AI-enabled VRS) and to evaluate nursing students' competencies and experiences in communicating with an AI medical doctor. METHODS: A mixed-methods design using a one-group pretest-posttest design and focus group discussions were employed in the evaluation phase. Nursing students from a university were recruited to undertake the 2-hour AI-enabled VRS. Pre-test and post-tests were administered to evaluate the participants' communication knowledge and self-efficacy. Survey questionnaires were administered to examine their experiences with the virtual reality environment and the AI doctor. Five focus group discussions were conducted to gain deeper insight into their learning experiences. RESULTS: The participants demonstrated significant improvements in communication knowledge and interprofessional communication self-efficacy after the learning. They reported positively on the acceptability, feasibility and usability of the AI-enabled VRS. The subscale of "human-like" feature of the AI medical doctor was rated the lowest. Three themes surrounding participants' experiences of the virtual learning emerged: "relate to the real world", "artificial intelligence versus human intelligence" and "complement with face-to-face learning". CONCLUSIONS: This study demonstrates initial evidence on the potential of AI-enabled VRS in fostering nursing students' learning on interprofessional communication skills. The findings have also provided insights on how to improve the AI-enabled VRS, in particular, the expressiveness of the AI pedagogical agent and facilitating more dialogue trainings with learner-agent conversations.

Knowledge, attitudes, and practices towards COVID-19 among undergraduates during emergency remote learning.

Background: The coronavirus disease 2019 (COVID-19) pandemic paralyzes the education sector. To minimize the interruption of teaching and learning, most universities in Malaysia shifted to virtual mode during this unprecedented period of the pandemic. With an ever-increasing number of Malaysians fully vaccinated against COVID-19, the education system is expected to switch back to face-to-face mode this year. It is crucial to assess the knowledge, attitudes, and practices (KAP) of COVID-19 among emergency remote learning undergraduates before reverting to physical teaching and learning. Hence, a study was conducted with this aim in mind. Methods: A total of 299 Malaysian undergraduates were recruited through a snowball sampling approach. The online questionnaire encompassed three main segments: informed consent, sociodemographic information, and KAP questions on COVID-19. Results: The mean scores for knowledge, attitude, and practice were 4.05/6, 11.14/12, and 5.07/7, respectively. The results of the present study showed that year 1 respondents had significantly higher levels (p < 0.05) of KAP scores than year 4 respondents. In addition, the attitude score of science majors respondents was significantly greater (p < 0.05) than those of nonscience majors. The KAP scores showed no significant difference among groups with different sexes, ethnicities, and COVID-19 histories. Partial correlation analysis revealed that the overall knowledge score was positively correlated with attitude (r = 0.193, p = 0.001) and practice (r = 0.343, p < 0.001) scores whereas the total attitude score was positively correlated with the total practice score (r = 0.149, p = 0.010). Conclusion: Our current results suggest that COVID-19 workshops, seminars, or training programs for year 4 students could be conducted to enhance their KAP levels.

Assessing Physical Fitness of Athletes in a Confined Environment during Prolonged Self-Isolation: Potential Usefulness of the Test of Maximal Number of Burpees Performed in 3 Minutes.

Due to a prolonged period of quarantine during the COVID-19 pandemic, it is essential to monitor the physical condition of athletes isolated at home with a fitness tool that measures various aspects of physical fitness, which does not require any special equipment, and can be performed within a small space. This study assessed the reliability and validity of the test of performing the maximal number of burpees in 3 min (or 3-MBT) to monitor strength, power, and aerobic endurance in trained athletes. For Part I (reliability of the 3-MBT), 20 (10 male, 10 female) national athletes from various sports performed the 3-MBT on two separate test sessions. Athletes performed as many burpees as possible within 3 min and the primary performance criteria was the number of burpees completed (where a higher number reflected a better performance). The 3-MBT displayed excellent relative reliability in the athletes, with an intraclass correlation coefficient (ICC) and coefficient of variation (CV %) of >0.92, and <3.0%, respectively. For Part II (validity of the 3-MBT), 40 (20 M, 20 F) athletes performed the 3-MBT, and the countermovement jump (CMJ), isometric mid-thigh pull (IMTP), seated medicine ball throw (SMBT), isometric bench (IBP) and maximal aerobic power (VO2max) tests on separate sessions. When data of male and female athletes were pooled, there were significant correlations between relative 3-MBT and relative CMJ height (r = 0.65, large; p < 0.001), relative IMPT peak force (r = 0.50, large; p < 0.001), relative IBP peak force (r = 0.36, moderate, p = 0.02), and relative VO2max (r = 0.50, large; p < 0.001). In conclusion, the 3-MBT is a reliable and reasonably useful test and is a valid assessment of lower body power and strength, upper body strength and aerobic fitness in trained male and female athletes.

Therapeutic Strategies against Ebola Virus Infection.

Since the 2014-2016 epidemic, Ebola virus (EBOV) has spread to several countries and has become a major threat to global health. EBOV is a risk group 4 pathogen, which imposes significant obstacles for the development of countermeasures against the virus. Efforts have been made to develop anti-EBOV immunization and therapeutics, with three vaccines and two antibody-based therapeutics approved in recent years. Nonetheless, the high fatality of Ebola virus disease highlights the need to continuously develop antiviral strategies for the future management of EBOV outbreaks in conjunction with vaccination programs. This review aims to highlight potential EBOV therapeutics and their target(s) of inhibition, serving as a summary of the literature to inform readers of the novel candidates available in the continued search for EBOV antivirals.

Dietary patterns of 5-year-old children and their correlates: findings from a multi-ethnic Asian cohort.

There is limited data on the dietary patterns of 5-year-old children in Asia. The study examined childhood dietary patterns and their maternal and child correlates in a multi-ethnic Asian cohort. Based on caregiver-reported 1-month quantitative FFQ of 777 children from the Growing Up in Singapore Towards healthy Outcomes cohort, cluster analysis identified two mutually exclusive clusters. Children in the 'Unhealthy' cluster (43·9 %) consumed more fries, processed meat, biscuits and ice cream, and less fish, fruits and vegetables compared with those in the 'Healthy' cluster (56·1 %). Children with mothers of lower educational attainment had twice the odds of being assigned to the 'Unhealthy' cluster (adjusted OR (95 % CI) = 2·19 (95 % CI 1·49-3·24)). Children of Malay and Indian ethnicities had higher odds of being assigned to the 'Unhealthy' cluster (adjusted OR = 25·46 (95 % CI 15·40, 42·10) and 4·03 (95 % CI 2·68-6·06), respectively), relative to Chinese ethnicity. In conclusion, this study identified two dietary patterns in children, labelled as the 'Unhealthy' and 'Healthy' clusters. Mothers' educational attainment and ethnicity were two correlates that were associated with the children's assignments to the clusters. These findings can assist in informing health promotion programmes targeted at Asian children.

Aquariibacter albus gen. nov., sp. nov., a new member of the order Burkholderiales, isolated from a freshwater aquarium.

A novel bacterium, strain SJAQ100T, was isolated from a freshwater aquarium and was characterized taxonomically and phylogenetically. Strain SJAQ100T was a Gram-stain-negative, aerobic, rod-shaped and non-motile bacterium. The strain grew optimally with 0 % NaCl and at 25-37 °C on Reasoner's 2A agar. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that the strain SJAQ100T clustered with members of Burkholderiales incertae sedis in the order Burkholderiales, but sequence similarities to known species were less than 96.5 %. The genomic DNA G+C content of strain SJAQ100T was 71.2 mol%. Genomic comparisons of strain SJAQ100T with species in the order Burkholderiales were made using the Genome-to-Genome Distance Calculator, average nucleotide identity and average amino acid identity analyses (values indicated ≤22.1, ≤78.1, and ≤68.1 % respectively). Strain SJAQ100T contained C16 : 0 and C16 : 1 ω7c/C16 : 1 ω6c as major fatty acids and Q-8 as the major quinone. The major polyamines were putrescine and cadaverine. Strain SJAQ100T contained phosphatidylethanolamine and diphosphatidylglycerol as major polar lipids. Based on the genotypic, chemotaxonomic and phenotypic results, strain SJAQ100T represents a novel genus and species, Aquariibacter albus gen. nov., sp. nov., which belongs to order Burkholderiales and the class Betaproteobacteria. The type strain is SJAQ100T (=KCTC 72203T=CGMCC 1.18869T=MCC 4385T).

Small molecules baicalein and cinnamaldehyde are potentiators of measles virus-induced breast cancer oncolysis.

BACKGROUND: Although the breast cancer mortality has slowed down from 2008 to 2017, breast cancer incidence rate continues to rise and thus, new and/or improved treatments are highly needed. Among them, oncolytic virotherapy which has the ability of facilitating the antitumor adaptive immunity, appears as a promising anticancer therapy. Oncolytic measles virus (MV) is particularly suitable for targeting breast cancer due to the upregulation of MV's receptor nectin-4. Nonetheless, with limited clinical success currently, ways of boosting MV-induced breast cancer oncolysis are therefore necessary. Oncolytic virotherapy alone and combined with chemotherapeutic drugs are two strategic areas with intensive development for the search of anticancer drugs. Considering that baicalein (BAI) and cinnamaldehyde (CIN) have demonstrated antitumor properties against multiple cancers including breast cancer, they could be good partners for MV-based oncolytic virotherapy. PURPOSE: To assess the in vitro effect of BAI and CIN with MV and assess their combination effects. METHODS: We examined the combinatorial cytotoxic effect of oncolytic MV and BAI or CIN on MCF-7 breast cancer cells. Potential anti-MV activities of the phytochemicals were first investigated in vitro to determine the optimal combination model. Synergism of MV and BAI or CIN was then evaluated in vitro by calculating the combination indices. Finally, cell cycle analysis and apoptosis assays were performed to confirm the mechanism of synergism. RESULTS: Overall, the viral sensitization combination modality using oncolytic MV to first infect MCF-7 breast cancer cells followed by drug treatment with BAI or CIN was found to produce significantly enhanced tumor killing. Further mechanistic studies showed that the combinations 'MV-BAI' and 'MV-CIN' display synergistic anti-breast cancer effect, mediated by elevated apoptosis. CONCLUSION: We demonstrated, for the first time, effective combination of oncolytic MV with BAI or CIN that could be further explored and potentially developed into novel therapeutic strategies targeting nectin-4-marked breast cancer cells.

Anticancer Mechanism of Curcumin on Human Glioblastoma.

Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin's anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.

Red blood cell transfusion in patients with anti-Yta.

BACKGROUND: Yta is a high frequency red blood cell (RBC) antigen, present in 99.7% of studied populations. It is extremely immunogenic, and when anti-Yta is present, provision of Yt(a-) blood is often challenging. The objectives of our study were to assess the incidence and severity of acute hemolytic transfusion reactions to Yt(a+) donor RBCs in recipients with preformed anti-Yta and to identify any patient factors associated with severe hemolytic reactions. STUDY DESIGN AND METHODS: Patients with anti-Yta identified by the Red Cell Reference Laboratories of the Australian Red Cross Lifeblood over the past 20 years were included. Their transfusion records were collected via the referring laboratory to ascertain if any patients received RBC transfusion and if there was any evidence of transfusion reactions. RESULTS: Fifty-two patients with anti-Yta were identified; only 12 were confirmed to have received a RBC transfusion. Nine received Yt(a+) or untyped allogeneic RBCs, including four patients who received a total of 16 indirect antiglobulin test (IAT) crossmatch incompatible, likely Yt(a+) RBCs. None of the nine patients had documented acute hemolytic reactions. CONCLUSION: There are limited published data describing the clinical significance of anti-Yta . Based on our data, it appears that transfusing patients with anti-Yta using incompatible crossmatched RBCs does not pose a significant risk of an acute hemolytic transfusion reaction when the antibody reaction strength is weak ≤2+ (0-4) by IAT crossmatch. For strong examples of the antibody, in the absence of other assay data, such as the monocyte monolayer assay, Yt(a-) blood should continue to be sourced where possible.