Effect of the red uniform on the judgment of position or movement used in Wushu Routine, evaluated by practitioners of the modality

by Jinkun Li, Jingmin Zhang, Shuo Tao, Xiaoying Zeng, Rong Zou, Xiaobin Hong

In the artistic sports program, the referee’ scores directly determine the final results of the athletes. Wushu is a artistic sport that has a Chinese characteristic and has the potential to become an official competition at the Summer Olympic. In this study we tested whether a red uniform color affects Wushu Routine practitioners’ ratings of athletes’ position or movement of Wushu Routine. We also tested whether the effect varied depending on the gender of the athlete and the practitioner, and depending on whether female practitioners were in the ovulation phase of their menstrual cycle. Male (Experiment 1: N = 72) and female (Experiment 1: N = 72; Experiment 2: N = 52) participants who major in Wushu Routine were recruited to take a referee’s perspective and rate the movement quality of male and female athletes wearing red or blue uniforms. The results of Experiment 1 showed that both male and female athletes wearing red uniform (compared to blue uniform) received higher ratings (p = .002, η2 = .066; p = .014, η2 = .043), and the red effect was especially strong when male practitioners rated female athletes (p = .002, η2 = .069). The results of Experiment 2, in an all-female sample, showed that in most cases there was no difference in ratings made by women in the ovulation and non-ovulation phases of their menstrual cycle, with the exception of their ratings of male athletes wearing red; in this condition, women gave higher ratings when they were in the ovulation phase of their cycle (p = .026). The results suggest that there is a red effect in an artistic sport like Wushu Routine, in which gender and the female menstrual cycle play an important role.

Anxiety disorders among youth with substance use and associated factors in Northwest Ethiopia: A community-based study

by Mamaru Melkam, Demeke Demilew, Tilahun Kassew, Biruk Fanta, Sewbesew Yitayih, Kassahun Alemu, Yassin Muhammed, Berhanie Getnet, Eden Abetu, Gebrekidan Ewnetu Tarekeg, Mohammed Oumer, Goshu Nenko

Introduction

Anxiety disorder is an unpleasant emotional feeling with symptoms related to psychological and autonomic symptoms such as headache, perspiration, palpitations, dizziness, and stomach discomfort. The use of substances become a worldwide problem among youth which brings situation that leads to serious social and health-related problems. Anxiety disorders with substance use have a huge impact on their high prevalence, therapeutic issues, and poor prognosis on clinical effects. Although the prevalence of anxiety disorders is significant among young people who use substances, limited studies were conducted. Therefore, this study revealed the burden of anxiety disorders among youth with substance use and associated factors in Ethiopia.

Method

A community-based multi-stage with a simple random sampling technique was conducted. A total of 372 substance users study participants were recruited for this study. Alcohol, Smoking, and Substance Involvement Screening Tests, Depression Anxiety Stress Scales, and other tools were used to assess anxiety disorders with substance use and associated factors. Data were entered into Epi-data version 4.6, and exported to SPSS version 20 for further analysis. Bi-variables logistic regression analysis was employed to identify variables with a p-value of Results

From a total of 372 respondents the overall prevalence of anxiety disorders with substance use was 48.1%. Male sex [AOR = 1.99; 95% CI: (1.01–3.93)], low educational status of the father [AOR = 6.38 95%CI: (1.50–7.08)], and the presence of stress [AOR = 2.48; 95% CI: 2.48(2.43–4.40)] were significantly associated factors with anxiety disorders with substances use.

Conclusions and recommendations

The prevalence of anxiety disorders with substance use was 48.1% therefore; it is recommended that the zonal administration give collaborative work with the health bureau and facilitate awareness creation about the impact of substance abuse. Clinicians are recommended to mitigate anxiety disorders with substance use to get a good prognosis for clients with controlling their stress.

Chinese herbal medicine for post-viral fatigue: A systematic review of randomized controlled trials

by Le-Yan Hu, An-Qi Cai, Bo Li, Zheng Li, Jian-Ping Liu, Hui-Juan Cao

Background

Fatigue is a common symptom after viral infection. Chinese herbal medicine (CHM) is thought to be a potential effective intervention in relieving fatigue.

Purpose

To assess the effectiveness and safety of CHM for the treatment of post-viral fatigue.

Study design

Systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods

The protocol of this systematic review was registered on PROSPERO (CRD42022380356). Trials reported changes of fatigue symptom, which compared CHM to no treatment, placebo or drugs, were included. Six electronic databases and three clinical trial registration platforms were searched from inception to November 2023. Literature screening, data extraction, and risk bias assessment were independently carried out by two reviewers. Quality of the included trials was evaluated using Cochrane risk of bias tool, and the certainty of the evidence was evaluated using GRADE. The meta-analysis was performed using Review Manager 5.4, mean difference (MD) and its 95% confidence interval (CI) was used for estimate effect of continuous data. Heterogeneity among trials was assessed through I² value.

Results

Overall, nineteen studies with 1921 patients were included. Results of individual trial or meta-analysis showed that CHM was better than no treatment (MD = -0.80 scores, 95%CI -1.43 to -0.17 scores, P = 0.01, 60 participants, 1 trial), placebo (MD = -1.90 scores, 95%CI -2.38 to -1.42 scores, P.00001, 184 participants, 1 trial), placebo on basis of rehabilitation therapy (MD = -14.90 scores, 95%CI -24.53 to -5.27 scores, P = 0.02, 118 participants, 1 trial) or drugs (MD = -0.38 scores, 95%CI -0.48 to -0.27 scores, I² = 0%, Pto drugs alone also showed better effect of combination therapy (average MD = -0.56 scores). In addition, CHM may improve the percentage of CD4 T lymphocytes and reduce the level of serum IL-6 (MD = -14.64 scores, 95%CI 18.36 to -10.91 scores, I² = 0%, P Conclusion

Current systematic review found that the participation of CHM can improve the symptoms of post-viral fatigue and some immune indicators. However, the safety of CHM remains unknown and large sample, high quality multicenter RCTs are still needed in the future.

Identification of the single and combined acute toxicity of Cr and Ni with <i>Heterocypris</i> sp. and the quantitative structure-activity relationship (QSAR) model

by Chi Su, Yilong Hua, Yi Liu, Shu Tao, Fei Jia, Wenhui Zhao, Wangyang Lin

Mining wastewater with heavy metals poses a serious threat to the ecological environment. However, the acute single and combined ecological effects of heavy metals, such as chromium (Cr) and nickel (Ni), on freshwater ostracods, and the development of relevant prediction models, remain poorly understood. In this study, Heterocypris sp. was chosen to investigate the single and combined acute toxicity of Cr and Ni. Then, the quantitative structure-activity relationship (QSAR) model was used to predict the combined toxicity of Cr and Ni. The single acute toxicity experiments revealed high toxicity for both Cr and Ni. In addition, Cr exhibited greater toxicity compared to Ni, as evidenced by its lower 96-hour half-lethal concentration (LC₅₀) of 1.07 mg/L compared to 4.7 mg/L for Ni. Furthermore, the combined acute toxicity experiments showed that the toxicity of Cr-Ni was higher than Ni but lower than Cr. Compared with the concentration addition (CA) and independent action (IA) models, the predicted results of the QSAR model were more consistent with the experimental results for the Cr-Ni combined acute toxicity. So, the high accuracy of QSAR model identified its feasibility to predict the toxicity of heavy metal pollutants in mining wastewater.

Retinoid orphan receptor gamma t (rorγt) promotes inflammatory eosinophilia but is dispensable for innate immune-mediated colitis

by Alvaro Torres-Huerta, Katelyn Ruley-Haase, Theodore Reed, Antonia Boger-May, Derek Rubadeux, Lauren Mayer, Arpitha Mysore Rajashekara, Morgan Hiller, Madeleine Frech, Connor Roncagli, Cameron Pedersen, Mary Catherine Camacho, Lauren Hollmer, Lauren English, Grace Kane, David L. Boone

Inflammatory bowel diseases (IBD) result from uncontrolled inflammation in the intestinal mucosa leading to damage and loss of function. Both innate and adaptive immunity contribute to the inflammation of IBD and innate and adaptive immune cells reciprocally activate each other in a forward feedback loop. In order to better understand innate immune contributions to IBD, we developed a model of spontaneous 100% penetrant, early onset colitis that occurs in the absence of adaptive immunity by crossing villin-TNFAIP3 mice to RAG1^-/- mice (TRAG mice). This model is driven by microbes and features increased levels of innate lymphoid cells in the intestinal mucosa. To investigate the role of type 3 innate lymphoid cells (ILC3) in the innate colitis of TRAG mice, we crossed them to retinoid orphan receptor gamma t deficient (Rorγt^-/-) mice. Rorγt^-/- x TRAG mice exhibited markedly reduced eosinophilia in the colonic mucosa, but colitis persisted in these mice. Colitis in Rorγt^-/- x TRAG mice was characterized by increased infiltration of the intestinal mucosa by neutrophils, inflammatory monocytes, macrophages and other innate cells. RNA and cellular profiles of Rorγt^-/- x TRAG mice were consistent with a lack of ILC3 and ILC3 derived cytokines, reduced antimicrobial factors, increased activation oof epithelial repair processes and reduced activation of epithelial cell STAT3. The colitis in Rorγt^-/- x TRAG mice was ameliorated by antibiotic treatment indicating that microbes contribute to the ILC3-independent colitis of these mice. Together, these gene expression and cell signaling signatures reflect the double-edged sword of ILC3 in the intestine, inducing both proinflammatory and antimicrobial protective responses. Thus, Rorγt promotes eosinophilia but Rorγt and Rorγt-dependent ILC3 are dispensable for the innate colitis in TRAG mice.

Institutional capacity assessment in the lens of implementation research: Capacity of the local institutions in delivering WASH services at Cox’s Bazar district, Bangladesh

by Mahbubur Rahman, Mahbub-Ul Alam, Sharmin Khan Luies, Sharika Ferdous, Zahidul Mamun, Musarrat Jabeen Rahman, Debashish Biswas, Tazrina Ananya, Asadullah, Abul Kamal, Ritthick Chowdhury, Eheteshamul Russel Khan, Dara Johnston, Martin Worth, Umme Farwa Daisy, Tanvir Ahmed

Background

The influx of Forcibly Displaced Myanmar Nationals (FDMNs) has left the Southwest coastal district of Cox’s Bazar with one of the greatest contemporary humanitarian crises, stressing the existing water, sanitation, and hygiene (WASH) resources and services. This study aimed to assess the existing capacity of local institutions involved in delivering WASH services and identify relevant recommendations for intervention strategies.

Methods

We used a qualitative approach, including interviews and capacity assessment workshops with institutions engaged in WASH service delivery. We conducted five key informant interviews (KII) with sub-district level officials of the Department of Public Health Engineering (DPHE), Directorate General of Health Services (DGHS), Directorate of Primary Education (DPE) and Bangladesh Rural Advancement Committee (BRAC) to have a general idea of WASH service mechanisms. Seven capacity assessment workshops were organized with the relevant district and sub-district level stakeholders from August 2019 to September 2019. These workshops followed three key areas: i) knowledge of policy, organizational strategy, guidelines, and framework; ii) institutional arrangements for service delivery such as planning, implementation, coordination, monitoring, and reporting; and iii) availability and management of human, financial and infrastructural resources. Data were categorized using thematic content analysis.

Results

The majority of stakeholders lacked awareness of national WASH policies. Furthermore, the top-down planning approaches resulted in activities that were not context-specific, and lack of coordination between multiple institutions compromised the optimal WASH service delivery at the local level. Shortage of human resources in delivering sustainable WASH services, inadequate supervision, and inadequate evaluation of activities also required further improvement, as identified by WASH stakeholders.

Conclusion

Research evidence suggests that decision-makers, donors, and development partners should consider learning from the WASH implementers and stakeholders about their existing capacity, gaps, and opportunities before planning for any WASH intervention in any particular area.

Lightweight high-precision SAR ship detection method based on YOLOv7-LDS

by Shiliang Zhu, Min Miao

The current challenges in Synthetic Aperture Radar (SAR) ship detection tasks revolve around handling significant variations in target sizes and managing high computational expenses, which hinder practical deployment on satellite or mobile airborne platforms. In response to these challenges, this research presents YOLOv7-LDS, a lightweight yet highly accurate SAR ship detection model built upon the YOLOv7 framework. In the core of YOLOv7-LDS’s architecture, we introduce a streamlined feature extraction network that strikes a delicate balance between detection precision and computational efficiency. This network is founded on Shufflenetv2 and incorporates Squeeze-and-Excitation (SE) attention mechanisms as its key elements. Additionally, in the Neck section, we introduce the Weighted Efficient Aggregation Network (DCW-ELAN), a fundamental feature extraction module that leverages Coordinate Attention (CA) and Depthwise Convolution (DWConv). This module efficiently aggregates features while preserving the ability to identify small-scale variations, ensuring top-quality feature extraction. Furthermore, we introduce a lightweight Spatial Pyramid Dilated Convolution Cross-Stage Partial Channel (LSPHDCCSPC) module. LSPHDCCSPC is a condensed version of the Spatial Pyramid Pooling Cross-Stage Partial Channel (SPPCSPC) module, incorporating Dilated Convolution (DConv) as a central component for extracting multi-scale information. The experimental results show that YOLOv7-LDS achieves a remarkable Mean Average Precision (mAP) of 99.1% and 95.8% on the SAR Ship Detection Dataset (SSDD) and the NWPU VHR-10 dataset with a parameter count (Params) of 3.4 million, a Giga Floating Point Operations Per Second (GFLOPs) of 6.1 and an Inference Time (IT) of 4.8 milliseconds. YOLOv7-LDS effectively strikes a fine balance between computational cost and detection performance, surpassing many of the current state-of-the-art object detection models. As a result, it offers a more resilient solution for maritime ship monitoring.

Downregulation of the CD151 protects the cardiac function by the crosstalk between the endothelial cells and cardiomyocytes via exosomes

by Luying Jiang, Jingbo Liu, Zhenjia Yang, Jianyu Wang, Wenkai Ke, Kaiyue Zhang, Chunran Zhang, Houjuan Zuo

Background

Heart failure (HF) is the last stage in the progression of various cardiovascular diseases. Although it is documented that CD151 contributes to regulate the myocardial infarction, the function of CD151 on HF and involved mechanisms are still unclear.

Method and results

In the present study, we found that the recombinant adeno-associated virus (rAAV)-mediated endothelial cell-specific knockdown of CD151-transfected mice improved transverse aortic constriction (TAC)-induced cardiac function, attenuated myocardial hypertrophy and fibrosis, and increased coronary perfusion, whereas overexpression of the CD151 protein aggravated cardiac dysfunction and showed the opposite effects. In vitro, the cardiomyocytes hypertrophy induced by PE were significantly improved, while the proliferation and migration of cardiac fibroblasts (CFs) were significantly reduced, when co-cultured with the CD151-silenced endothelial cells (ECs). To further explore the mechanisms, the exosomes from the CD151-silenced ECs were taken by cardiomyocyte (CMs) and CFs, verified the intercellular communication. And the protective effects of CD151-silenced ECs were inhibited when exosome inhibitor (GW4869) was added. Additionally, a quantitative proteomics method was used to identify potential proteins in CD151-silenced EC exosomes. We found that the suppression of CD151 could regulate the PPAR signaling pathway via exosomes.

Conclusion

Our observations suggest that the downregulation of CD151 is an important positive regulator of cardiac function of heart failure, which can regulate exosome-stored proteins to play a role in the cellular interaction on the CMs and CFs. Modulating the exosome levels of ECs by reducing CD151 expression may offer novel therapeutic strategies and targets for HF treatment.

The application of flipped learning to a gross anatomy dissection course

by Eun-Kyung Chung, Heoncheol Yun, Kwang-Il Nam, Young-Suk Cho, Eui-Ryoung Han

We implemented flipped learning for a gross anatomy dissection course and compared its effects on students’ motivation and academic achievement with those of traditional dissection methods. We invited 142 first-year medical students at Chonnam National University Medical School to participate in this study. All participants engaged in traditional dissection methods in the first part of the study and flipped learning in the latter part. Medical students’ motivation to learn anatomy by cadaveric dissection was measured using the ARCS (Attention, Relevance, Confidence, and Satisfaction) model. Thereafter, all students completed a written examination consisting of 96 multiple-choice questions. The students’ mean motivational score regarding attention was significantly higher in association with flipped learning than with traditional learning. However, the students’ mean motivational scores regarding relevance, confidence, and satisfaction were not significantly different between the methods. Additionally, the mean anatomy practice test score was significantly higher in association with flipped learning than with traditional learning. The students’ motivational scores and anatomy practice test scores associated with flipped learning positively correlated with the extent of learning material completion. The students’ responses indicated that flipped learning helped enhance the learning process, improve time management, reduce confusion during practice, and promote independent practice. The application of flipped learning to a cadaveric dissection course increased individual learning motivation, which improved learning activities both in and out of class, as well as academic achievement.

Kinetics and mechanical work done to move the body centre of mass along a curve

by Raphael M. Mesquita, Patrick A. Willems, Arthur H. Dewolf, Giovanna Catavitello

When running on a curve, the lower limbs interact with the ground to redirect the trajectory of the centre of mass of the body (CoM). The goal of this paper is to understand how the trajectory of the CoM and the work done to maintain its movements relative to the surroundings (W_com) are modified as a function of running speed and radius of curvature. Eleven participants ran at different speeds on a straight line and on circular curves with a 6 m and 18 m curvature. The trajectory of the CoM and W_com were calculated using force-platforms measuring the ground reaction forces and infrared cameras recording the movements of the pelvis. To follow a circular path, runners overcompensate the rotation of their trajectory during contact phases. The deviation from the circular path increases when the radius of curvature decreases and speed increases. Interestingly, an asymmetry between the inner and outer lower limbs emerges as speed increases. The method to evaluate W_com on a straight-line was adapted using a referential that rotates at heel strike and remains fixed during the whole step cycle. In an 18 m radius curve and at low speeds on a 6 m radius, W_com changes little compared to a straight-line run. Whereas at 6 m s^-1 on a 6 m radius, W_com increases by ~25%, due to an augmentation in the work to move the CoM laterally. Understanding these adaptations provides valuable insight for sports sciences, aiding in optimizing training and performance in sports with multidirectional movements.

Knowledge, attitudes, and practices regarding antibiotic use in Bangladesh: Findings from a cross-sectional study

by Md. Abu Raihan, Md. Saiful Islam, Shariful Islam, A. F. M. Mahmudul Islam, Khandaker Tanveer Ahmed, Tania Ahmed, Md. Nahidul Islam, Shamsunnahar Ahmed, Mysha Samiha Chowdhury, Dipto Kumar Sarker, Anika Bushra Lamisa

Background

Escalating antibiotic resistance presents a notable worldwide dilemma, pointing a large involvement of general population. The objective of this study was to assess knowledge, attitudes, and practices regarding the utilization of antibiotics among Bangladeshi residents.

Methods

A cross-sectional study, conducted from January 01 to April 25, 2022, included 1,947 Bangladeshi adults with a history of antibiotic use, via online surveys and face-to-face interviews using a pretested semi-structured questionnaire. Descriptive statistics, Chi-square tests, and multivariate linear regression models were employed.

Results

Mean scores for knowledge, attitudes, and practices were 6.59±1.20, 8.34±1.19, and 12.74±2.59, with correct rates of 73.22%, 92.67%, and 57.91%. Positive predictors for knowledge included being unmarried (β = 0.10, p = 0.001), higher education (College: β = 0.09, p = 0.025; Bachelor: β = 0.22, p Conclusions

Participants exhibited adequate knowledge and positive attitudes but lagged behind in proper practice of antibiotic use. Proper initiatives should be tailored to enhance prudent antibiotic use and mitigate the risk of antimicrobial resistance.

Hepatitis E virus infections among patients with acute febrile jaundice in two regions of Cameroon: First molecular characterization of hepatitis E virus genotype 4

by Abdou Fatawou Modiyinji, Lange Tchamba Amorgathe Tankeu, Chavely Gwladys Monamele, Moise Henri Yifomnjou Moumbeket, Paul Alain Tagnouokam Ngoupo, Huguette Tchetgna Simo, Abanda Njei Ngu, Kazanji Mirdad, Richard Njouom

Background

Febrile jaundice is a common indicator of certain infectious diseases, including hepatitis E. In Cameroon, the yellow fever virus is the only pathogen that is monitored in patients who present with this symptom. However, more than 90% of the samples received as part of this surveillance are negative for yellow fever. This study aimed to describe the prevalence and hepatitis E virus (HEV) genotype among yellow fever-negative patients in the Far North and West regions of Cameroon.

Methods

In a cross-sectional study, yellow fever surveillance-negative samples collected between January 2021 and January 2023 were retrospectively analyzed. Anti-HEV IgM and IgG antibodies were tested using commercially available ELISA kits. Anti-HEV IgM and/or IgG positive samples were tested for HEV RNA by real-time RT-PCR, followed by nested RT-PCR, sequencing and phylogenetic analysis.

Results

Overall, 121 of the 543 samples (22.3%, 95% CI: 19.0% - 26.0%) were positive for at least one anti-HEV marker. Amongst these, 8.1% (44/543) were positive for anti-HEV IgM, 5.9% (32/543) for anti-HEV IgG, and 8.3% (45/544) for both markers. A total of 15.2% (12/79) samples were positive for HEV RNA real-time RT-PCR and 8 samples were positive for HEV RNA by nested RT-PCR. Phylogenetic analysis showed that the retrieved sequences clustered within HEV genotypes/subtypes 1/1e, 3/3f and 4/4b.

Conclusion

Our results showed that HEV is one of the causes of acute febrile jaundice in patients enrolled in the yellow fever surveillance program in two regions of Cameroon. We described the circulation of three HEV genotypes, including two zoonotic genotypes. Further studies will be important to elucidate the transmission routes of these zoonotic HEV genotypes to humans in Cameroon.

Comprehensive analysis of single cell and bulk data develops a promising prognostic signature for improving immunotherapy responses in ovarian cancer

by Huanfei Ding, Bowen Hu, Ruixia Guo

The tumor heterogeneity is an important cause of clinical therapy failure and yields distinct prognosis in ovarian cancer (OV). Using the advantages of integrated single cell RNA sequencing (scRNA-seq) and bulk data to decode tumor heterogeneity remains largely unexplored. Four public datasets were enrolled in this study, including E-MTAB-8107, TCGA-OV, GSE63885, and GSE26193 cohorts. Random forest algorithm was employed to construct a multi-gene prognostic panel and further evaluated by receiver operator characteristic (ROC), calibration curve, and Cox regression. Subsequently, molecular characteristics were deciphered, and treatments strategies were explored to deliver precise therapy. The landscape of cell subpopulations and functional characteristics, as well as the dynamic of macrophage cells were detailly depicted at single cell level, and then screened prognostic candidate genes. Based on the expression of candidate genes, a stable and robust cell characterized gene associated prognosis signature (CCIS) was developed, which harbored excellent performance at prognosis assessment and patient stratification. The ROC and calibration curves, and Cox regression analysis elucidated CCIS could serve as serve as an independent factor for predicting prognosis. Moreover, a promising clinical tool nomogram was also constructed according to stage and CCIS. Through comprehensive investigations, patients in low-risk group were charactered by favorable prognosis, elevated genomic variations, higher immune cell infiltrations, and superior antigen presentation. For individualized treatment, patients in low-risk group were inclined to better immunotherapy responses. This study dissected tumor heterogeneity and afforded a promising prognostic signature, which was conducive to facilitating clinical outcomes for patients with OV.

Infiltration of CD3+ and CD8+ lymphocytes in association with inflammation and survival in pancreatic cancer

by Gerik W. Tushoski-Alemán, Kelly M. Herremans, Patrick W. Underwood, Ashwin Akki, Andrea N. Riner, Jose G. Trevino, Song Han, Steven J. Hughes

Background

Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins.

Methods

Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples.

Results

Our findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC.

Conclusion

In this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.

Therapeutic interventions on human breast cancer xenografts promote systemic dissemination of oncogenes

by Gorantla V. Raghuram, Kavita Pal, Gaurav Sriram, Afzal Khan, Ruchi Joshi, Vishalkumar Jadhav, Sushma Shinde, Alfina Shaikh, Bhagyeshri Rane, Harshada Kangne, Indraneel Mittra

Metastatic dissemination following successful treatment of the primary tumour remains a common cause of death. There is mounting evidence that therapeutic interventions themselves may promote development of metastatic disease. We earlier reported that cell-free chromatin particles (cfChPs) released from dying cancer cells are potentially oncogenic. Based on this observation we hypothesized that therapeutic interventions may lead to the release of cfChPs from therapy induced dying cancer cells which could be carried via the blood stream to distant organs to transform healthy cells into new cancers that would masquerade as metastasis. To test this hypothesis, we generated xenografts of MDA-MB-231 human breast cancer cells in severe combined immune-deficient mice, and using immuno-fluorescence and FISH analysis looked for cfChPs in their brain cells. We detected multiple human DNA signals representing cfChPs in nuclei of brain cells of mice which co-localized with eight human onco-proteins. No intact MDA-MB-231 cells were detected. The number of co-localizing human DNA and human c-Myc signals increased dramatically following treatment with chemotherapy, localized radiotherapy or surgery, which could be prevented by concurrent treatment with three different cfChPs deactivating agents. These results suggest that therapeutic interventions lead to the release cfChPs from therapy induced dying cancer cells carrying oncogenes and are transported via the blood stream to brain cells to potentially transform them to generate new cancers that would appear as metastases. cfChPs induced metastatic spread of cancer is preventable by concurrent treatment with agents that deactivate cfChPs.

Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis

by Hong Duo, Mengying Jin, Yanwei Yang, Rewaan Baheti, Yujia Feng, Zirui Fu, Yuyue Jiang, Lanzhuoying Zheng, Jing Wan, Huaqin Pan

Background

Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations.

Methods

Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI.

Results

Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83–1.05, P = 0.26, I² = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09–3.00, P = 0.02, I² = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83–1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments.

Conclusion

According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Cost-effectiveness analysis of olaparib maintenance therapy for BRCA mutation ovarian cancer in the public sector in Malaysia

by Chee Meng Yong, Prathepamalar A. P. Yehgambaram, Shaun Wen Huey Lee

Introduction

Ovarian cancer is one of the most common cancer among women in Malaysia. Patients with ovarian cancer are often diagnosed at an advanced stage. Despite initial response to surgery and chemotherapy, most patients will experience a relapse. Olaparib has been reported have promising effects among BRCA mutated ovarian cancer patients. This study aimed to evaluate the cost–effectiveness of olaparib as a maintenance therapy for BRCA ovarian cancer in Malaysia.

Methods

We developed a four-state partitioned survival model which compared treatment with olaparib versus routine surveillance (RS) from a Malaysian healthcare perspective. Mature overall survival (OS) data from the SOLO-1 study were used and extrapolated using parametric models. Medication costs and healthcare resource usage costs were derived from local inputs and publications. Deterministic and probabilistic sensitivity analyses (PSA) were performed to explore uncertainties.

Results

In Malaysia, treating patients with olaparib was found to be more costly compared to RS, with an incremental cost of RM149,858 (USD 33,213). Patients treated with olaparib increased life years by 3.05 years and increased quality adjusted life years (QALY) by 2.76 (9.45 years vs 6.40 years; 7.62 vs 4.86 QALY). This translated to an incremental cost-effectiveness ratio (ICER) of RM 49,159 (USD10,895) per life year gained and RM54,357 (USD 12,047) per QALY gained, respectively. ICERs were most sensitive to time horizon of treatment, discount rate for outcomes, cost of treatment and health state costs, but was above the RM53,770/QALY threshold.

Conclusion

The use of olaparib is currently not a cost-effective strategy compared to routine surveillance based upon the current price in Malaysia for people with ovarian cancer with BRCA mutation, despite the improvement in overall survival.

Pharmacogenomics of poor drug metabolism in greyhounds: Canine P450 oxidoreductase genetic variation, breed heterogeneity, and functional characterization

by Stephanie E. Martinez, Amit V. Pandey, Tania E. Perez Jimenez, Zhaohui Zhu, Michael H. Court

Greyhounds metabolize cytochrome P450 (CYP) 2B11 substrates more slowly than other dog breeds. However, CYP2B11 gene variants associated with decreased CYP2B11 expression do not fully explain reduced CYP2B11 activity in this breed. P450 oxidoreductase (POR) is an essential redox partner for all CYPs. POR protein variants can enhance or repress CYP enzyme function in a CYP isoform and substrate dependent manner. The study objectives were to identify POR protein variants in greyhounds and determine their effect on coexpressed CYP2B11 and CYP2D15 enzyme function. Gene sequencing identified two missense variants (Glu315Gln and Asp570Glu) forming four alleles, POR-H1 (reference), POR-H2 (570Glu), POR-H3 (315Gln, 570Glu) and POR-H4 (315Gln). Out of 68 dog breeds surveyed, POR-H2 was widely distributed across multiple breeds, while POR-H3 was largely restricted to greyhounds and Scottish deerhounds (35% allele frequencies), and POR-H4 was rare. Three-dimensional protein structure modelling indicated significant effects of Glu315Gln (but not Asp570Glu) on protein flexibility through loss of a salt bridge between Glu315 and Arg519. Recombinant POR-H1 (reference) and each POR variant (H2-H4) were expressed alone or with CYP2B11 or CYP2D15 in insect cells. No substantial effects on POR protein expression or enzyme activity (cytochrome c reduction) were observed for any POR variant (versus POR-H1) when expressed alone or with CYP2B11 or CYP2D15. Furthermore, there were no effects on CYP2B11 or CYP2D15 protein expression, or on CYP2D15 enzyme kinetics by any POR variant (versus POR-H1). However, V_max values for 7-benzyloxyresorufin, propofol and bupropion oxidation by CYP2B11 were significantly reduced by coexpression with POR-H3 (by 34–37%) and POR-H4 (by 65–72%) compared with POR-H1. K_m values were unaffected. Our results indicate that the Glu315Gln mutation (common to POR-H3 and POR-H4) reduces CYP2B11 enzyme function without affecting at least one other major canine hepatic P450 (CYP2D15). Additional in vivo studies are warranted to confirm these findings.

Characterization and comparison of human and mouse milk cells

by Rose Doerfler, Saigopalakrishna Yerneni, Alexandra Newby, Namit Chaudhary, Ashley Shu, Katherine Fein, Juliana Hofstatter Azambuja, Kathryn A. Whitehead

Recent data has characterized human milk cells with unprecedented detail and provided insight into cell populations. While such analysis of freshly expressed human milk has been possible, studies of cell functionality within the infant have been limited to animal models. One commonly used animal model for milk research is the mouse; however, limited data are available describing the composition of mouse milk. In particular, the maternal cells of mouse milk have not been previously characterized in detail, in part due to the difficulty in collecting sufficient volumes of mouse milk. In this study, we have established a method to collect high volumes of mouse milk, isolate cells, and compare the cell counts and types to human milk. Surprisingly, we found that mouse milk cell density is three orders of magnitude higher than human milk. The cell types present in the milk of mice and humans are similar, broadly consisting of mammary epithelial cells and immune cells. These results provide a basis of comparison for mouse and human milk cells and will inform the most appropriate uses of mouse models for the study of human phenomena.

Maternal and perinatal outcomes of hypertensive disorders in pregnancy: Insights from the National Hospital of Obstetrics and Gynecology in Vietnam

by Nguyen Thi Huyen Anh, Nguyen Manh Thang, Truong Thanh Huong

Introduction

Hypertension is the common disorder encountered during pregnancy, complicating 5% to 10% of all pregnancies. Hypertensive disorders in pregnancy (HDP) are also a leading cause of maternal and perinatal morbidity and mortality. The majority of feto-maternal complications due to HPD have occurred in the low- and middle-income countries. However, few studies have been done to assess the feto-maternal outcomes and the predictors of adverse perinatal outcome among women with HDP in these countries.

Methods

A prospective cohort study was conducted on women with HDP who were delivered at National Hospital of Obstetrics and Gynecology, Vietnam from March 2023 to July 2023. Socio-demographic and obstetrics characteristics, and feto-maternal outcomes were obtained by trained study staff from interviews and medical records. Statistical analysis was performed using SPSS version 26.0. Bivariate and multiple logistic regressions were done to determine factors associated with adverse perinatal outcome. A 95% confidence interval not including 1 was considered statically significant.

Results

A total of 255 women with HDP were enrolled. Regarding adverse maternal outcomes, HELLP syndrome (3.9%), placental abruption (1.6%), and eclampsia (1.2%) were three most common complications. There was no maternal death associated with HDP. The most common perinatal complication was preterm delivery developed in 160 (62.7%) of neonates. Eight stillbirths (3.1%) were recorded whereas the perinatal mortality was 6.3%. On bivariate logistic regression, variables such as residence, type of HDP, highest systolic BP, highest diastolic BP, platelet count, severity symptoms, and birth weight were found to be associated with adverse perinatal outcome. On multiple logistic regression, highest diastolic BP, severity symptoms, and birth weight were found to be independent predictors of adverse perinatal outcome.

Conclusion

Our study showed lower prevalence of stillbirth, perinatal mortality, and maternal complication compared to some previous studies. Regular antenatal care and early detection of abnormal signs during pregnancy help to devise an appropriate monitoring and treatment strategies for each women with HDP.