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Xuan-Hai Do,1 Mai Thi Le,2,3 Thu Huyen Nguyen,2 Thanh Thien Le,2 Xuan-Hung Nguyen,2,4 Thanh Binh Mai,5 Thi My Nhung Hoang,3 Uyen Thi Trang Than2 1Department of Practical and Experimental Surgery, Vietnam Military Medical University, Hanoi, Vietnam; 2Center of Applied Sciences, Regenerative Medicine and Advance Technologies, Vinmec Healthcare System, Hanoi, Vietnam; 3Faculty of Biology, VNU University of Science, Vietnam National University, Hanoi, Vietnam; 4College of Health Sciences, VinUniversity, Hanoi, Vietnam; 5Department of Gastroenterology, 108 Military Central Hospital, Hanoi, VietnamCorrespondence: Uyen Thi Trang Than, 458 Minh Khai, Hai Ba Trung, Hanoi, Vietnam, Tel +84 85662355, Email v.uyenttt@vinmec.comPurpose: Hepatocellular carcinoma (HCC), a prevalent type of liver cancer, is mainly diagnosed in the advanced stage, leading to a high mortality rate. Recent advances have identified peripheral cytokines as a potential tool to predict disease outcomes and inform therapeutic decisions. Hence, in this study, we aim to build a predictive model for HCC based on serum levels of different cytokines.Patients and Methods: We used immunoassay to quantify the concentrations of IL-27, MIP-1β, Perforin, sCD137, sFas, and TNF-α in the serum of 38 HCC patients and 15 healthy controls. Logistic regression was then used to construct classification models detecting HCC based on these cytokines. A nomogram of the best-performing model was generated to visualize HCC prediction.Results: sFas and MIP-1β were found to be significantly higher in HCC patients compared to controls. Predictive models based on cytokine levels combining sFas, sCD137, and IL-27 performed the best in distinguishing HCC patients from healthy controls. This model has a bias-corrected area under the receiver operating characteristic (ROC) curve (AUC) of 0.948, a sensitivity of 92.11%, a specificity of 93.33%, and an accuracy of 0.925.Conclusion: Our findings suggest that serum cytokines have the potential to be utilized in HCC screening to improve detection rates.Keywords: hepatocellular carcinoma, cytokines, serum, biomarkers

Minh Tam Le,1,2 Nguyen Dac Nguyen,1,2 Nhu Quynh Thi Tran,1 Duong Dinh Le,3 Quoc Huy Vu Nguyen,2 Thanh Ngoc Cao1,2 1Center for Reproductive Endocrinology and Infertility, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam; 2Department of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam; 3Department of Public Health, Hue University of Medicine and Pharmacy, Hue University, Hue, VietnamCorrespondence: Minh Tam Le, Center for Reproductive Endocrinology and Infertility, Hue University of Medicine and Pharmacy, Hue University, 06 Ngo Quyen street, 53000, Vietnam, Email leminhtam@hueuni.edu.vnObjective: This study aimed to identify the factors that influence follicular output rate (FORT) and follicle-to-oocyte index (FOI) among infertile Vietnamese women, as described by the Poseidon classification of poor responders.Methods: This cross-sectional analysis includes women who received IVF/ICSI treatment at Hue University Hospital, Vietnam, between January 2017 and December 2019. The study population was divided into four groups: Group 1 (age < 35, AFC ≥ 5 and AMH ≥ 1.2 ng/mL, number of oocytes retrieved in the previous cycle ≤ 9), group 2 (age ≥ 35; AFC ≥ 5 and AMH ≥ 1.2 ng/mL, number of oocytes retrieved in the previous cycle ≤ 9), group 3 (age < 35; AFC < 5 and/or AMH < 1.2 ng/mL) and group 4 (age ≥ 35; AFC < 5 and/or AMH < 1.2 ng/mL). All of the patients underwent controlled ovarian stimulation utilizing GnRH antagonist.Results: A total of 243 cases were recruited into groups 1 (n = 44), 2 (n = 33), 3 (n = 54), and 4 (n = 112). There were statistically significant differences between the four groups in terms of age, infertility type, menstrual cycle, body mass index (BMI) and waist-hip ratio (WHR), endocrine tests, and total retrieved oocytes (p 0.05). The average number of oocytes per participant was 7.27, with the highest number occurring in group 1 (10.77) and the lowest occurring in group 4 (5.59). There was a relationship between FORT and BMI (ß: − 0.146, p=0.039), FSH starting dose (ß: 0.146, p=0.030), and AMH (ß:0.166, p=0.015). No statistically significant correlation was detected between FOI and other variables.Conclusion: The starting dose of FSH for ovarian stimulation and AMH concentration were positively associated with FORT in individuals with a poor prognosis, whereas BMI was negatively correlated with FORT; No other parameters were found to correlate with FOI.Keywords: follicular output rate, FORT, follicle-to-oocyte index, FOI, Poseidon, ovarian response

Nguyen Sa Viet Le,1,2 Minh Tam Le,2,3 Nguyen Dac Nguyen,2,3 Nhu Quynh Thi Tran,3 Quoc Huy Vu Nguyen,2 Thanh Ngoc Cao2,3 1Department of Assisted Reproduction, Hue Central Hospital, Hue, Vietnam; 2Department of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam; 3Center for Reproductive Endocrinology and Infertility, Hue University of Medicine and Pharmacy, Hue University, Hue, VietnamCorrespondence: Minh Tam Le Email leminhtam@huemed-univ.edu.vnPurpose: This study was designed to explore the value of ovarian volume (OV) measured by transvaginal ultrasound and its relationship with anthropometry and serum hormonal levels in a polycystic ovary syndrome (PCOS) population.Patients and Methods: A total of 119 women with PCOS from infertile couples were recruited in this cross-sectional study. On days 2– 4 of the menstrual cycle, transvaginal ultrasound examinations were performed, and hormonal profiles were measured. PCOS diagnosis was based on the Rotterdam 2003 criteria and classified into four phenotype groups. The PCOS group (study group) and the non-PCOS group (control group) were compared.Results: The mean age of the participants was 32.66± 4.10 years compared to 33.99± 4.78 years in 273 cases (69.6%) without PCOS. The mean OV was statistically larger in the PCOS group than in the non-PCOS group (7.65± 3.23 mL vs 6.08± 3.67 mL, p < 0.001) and positively correlated with serum anti-Mullerian (AMH) and luteinizing hormone (LH) levels (r=0.30; p < 0.001 and r=0.23; p < 0.001, respectively), and weakly and inversely correlated with age (− 0.182, p < 0.001). The area under the receiver operating characteristic (ROC) curve of OV in the diagnosis of PCOS was 0.613 (0.557– 0.670, 95% CI).Conclusion: The enlarged OV is remarkable in women with PCOS and is related to AMH and LH concentrations. Although the diagnostic potential of PCOS is substantially low, OV alone may contribute to predicting the severity of PCOS and better performance for the diagnosis of PCOS phenotypes.Keywords: ovarian volume, anti-Mullerian hormone, PCOS phenotypes, diagnose, infertility

Minh Tam Le,1,2 Trung Van Nguyen,1 Thai Thanh Thi Nguyen,1 Hiep Tuyet Thi Nguyen,1 Duong Dinh Le,3 Vu Quoc Huy Nguyen2 1Center for Reproductive Endocrinology and Infertility, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam; 2Department of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam; 3Department of Public Health, Hue University of Medicine and Pharmacy, Hue University, Hue, VietnamCorrespondence: Minh Tam LeCenter for Reproductive Endocrinology and Infertility, Hue University of Medicine and Pharmacy, Hue University, 06 Ngo Quyen Street, Hue City, VietnamTel +84 989228779Email leminhtam@huemed-univ.edu.vnObjective: This study aimed to determine the role of sperm DNA fragmentation as a marker that could predict early pregnancy loss (EPL), either independently or in combination with another marker or markers, after intracytoplasmic sperm injection (ICSI) cycles.Methods: This prospective descriptive cohort study retrieved data from 162 couples who underwent their first ICSI cycles at the Center for Reproductive Endocrinology and Infertility of Hue University Hospital in Vietnam from May 2018 to December 2019. General characteristics, semen parameters, sperm DNA fragmentation index (DFI), fertilization, embryo development, pregnancy rates, and EPL were assessed. The receiver-operating characteristic (ROC) method was performed to identify the threshold of DFI in EPL. Multivariate analysis was used to demonstrate the relationship between the sperm DNA fragmentation level and EPL.Results: Of 162 ICSI cycles, 23 (14.2%) involved EPL. There was no significant difference between the sperm DNA fragmentation rate and the overall rate of pregnancy loss, although the negative pregnancy outcome group had a median DFI that was higher than that of the positive pregnancy outcome group (20% vs 17.8%). The ROC analysis indicated that a sperm DNA fragmentation rate of 16.6% was the priority cut-off that could be used to distinguish EPL with a sensitivity of 73.9% (95% confidence interval [CI], 67.15– 80.67) and specificity of 47.48% (95% CI, 39.79– 55.17). The multivariate analysis confirmed that in female factors such as age, body mass index (BMI), and sperm DNA fragmentation level affected the EPL rate. However, a combination of the sperm DNA fragmentation level and female age or female BMI could not sufficiently predict EPL.Conclusion: EPL can be affected by multiple factors including sperm DNA fragmentation; however, there is no sufficient evidence indicating that sperm DNA fragmentation, both as a single marker and combined with other markers, is a good predictor of EPL.Keywords: sperm DNA fragmentation, intracytoplasmic sperm injection, early pregnancy loss, infertility, assisted reproductive technology

Minh Tam Le,1,2 Nhu Quynh Thi Tran,1 Nguyen Dac Nguyen,1 Quoc Huy Vu Nguyen2 1Center for Reproductive Endocrinology and Infertility, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam; 2Department of OBGYN, Hue University of Medicine and Pharmacy, Hue University, Hue, VietnamCorrespondence: Minh Tam LeCenter for Reproductive Endocrinology and Infertility, Hue University of Medicine and Pharmacy, Hue University, 06 Ngo Quyen Street, Hue, VietnamTel +84 989 228 779Fax +84 234 3822 173Email leminhtam@huemed-univ.edu.vnPurpose: Metabolic syndrome (MetS) has been reported as a deleterious factor in male fertility potential, associated with hypogonadism, impaired spermatogenesis, decreased sperm concentration and motility, and increased sperm DNA damage. This study aimed to determine the prevalence of MetS in men from infertile couples and evaluate its effect on semen analysis (SA).Participants and Methods: A cross-sectional descriptive study was performed in men from infertile couples diagnosed based on the World Health Organization 2010 criteria and treated at the Hue Center for Reproductive Endocrinology and Infertility, Vietnam. General information included medical history, lifestyle, MetS factors, SA, and sperm DNA fragmentation test were collected. Based on the diagnostic criteria of the American Heart Association and the National Heart, Lung, and Blood Institute for Asian men, the study population was divided into two groups: MetS and non-MetS groups. The outcomes were analyzed for any relationship between MetS and the SA index and the DNA fragmentation index (DFI).Results: A total of 534 men from infertile couples were included in this study. The prevalence of MetS was 23.4%, and abnormal semen analysis accounted for 93.8%. Age, body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), hepatitis B and total cholesterol were related to the occurrence of MetS in infertile men (p < 0.05). MetS did not reveal any impact on the parameters of SA. There was a positive correlation between waist circumference (WC), WHR, WHtR, and systolic blood pressure (BP) with abnormal sperm head and DFI (p < 0.05).Conclusion: Although the prevalence of MetS was remarkable in men from infertile couples, there was no association between MetS and semen quality. However, WC, WHR, WHtR, and systolic BP were found to be significantly associated with abnormal sperm head and DFI.Keywords: prevalence, metabolic syndrome, infertility, sperm, semen analysis

Background. The pathogenesis of influenza A virus subtype H5N1 (hereafter, 'H5N1') infection in humans is not completely understood, although hypercytokinemia is thought to play a role. We previously reported that most H5N1 viruses induce high cytokine responses in human macrophages, whereas some H5N1 viruses induce only a low level of cytokine production similar to that induced by seasonal viruses. Methods. To identify the viral molecular determinants for cytokine induction of H5N1 viruses in human macrophages, we generated a series of reassortant viruses between the high cytokine inducer A/Vietnam/UT3028II/03 clone 2 (VN3028IIcl2) and the low inducer A/Indonesia/UT3006/05 (IDN3006) and evaluated cytokine expression in human macrophages. Results. Viruses possessing the acidic polymerase (PA) gene of VN3028IIcl2 exhibited high levels of hypercytokinemia-related cytokine expression in human macrophages, compared with IDN3006, but showed no substantial differences in viral growth in these cells. Further, the PA gene of VN3028IIcl2 conferred enhanced virulence in mice. Conclusions. These results demonstrate that the PA gene of VN3028IIcl2 affects cytokine production in human macrophages and virulence in mice. These findings provide new insights into the cytokine-mediated pathogenesis of H5N1 infection in humans. [ABSTRACT FROM AUTHOR]

Background: Headache disorders are among the leading causes of disability worldwide, especially in young adults. However, no data on the burden of these disorders in Vietnam have been published to date. This study is the first to assess the prevalence of headache disorders among Vietnamese medical students., Methods: This study was conducted in accordance with the recommended methodology of the Global Campaign. Data were collected through interviews using the HARDSHIP structured questionnaire, translated into Vietnamese, with diagnostic assessments based on ICHD-3 criteria. Participants were recruited from two medical universities in Vietnam. The 1-year prevalence rates of headache disorders of public health significance (migraine, tension-type headache [TTH], and probable medication-overuse headache [pMOH]) were estimated. Logistic regression analyses were performed to evaluate the associations between headache disorders and sociodemographic/anthropometric variables., Results: A total of 1,362 participants (42.7% males and 57.3% females) with a mean age of 21.1 ± 1.6 years were included. The overall 1-year prevalence of any headache was 82.6% [95% CI: 80.5-84.6], with a prevalence of 74.7% [71.0-78.2] among males and 88.5% [86.0-90.6] among females. The 1-year prevalences for specific headache types were as follows: migraine 21.8% [19.6-24.1], TTH 54.0% [51.3-56.7], pMOH 0.4% [0.2-1.0], and other headaches on ≥ 15 days/month 3.7% [2.7-4.8]. The one-day prevalence of any headache was 12.1%. Female gender (adjusted OR = 1.77 [1.32-2.36]; p < 0.001) was independently associated with a higher prevalence of migraine, while older age (aOR = 0.84 [0.77-0.91] per year increase) was associated with a lower prevalence. In contrast, TTH was more common among older participants (aOR = 1.07 [1.005-1.15] per year increase)., Conclusions: This study highlights the high prevalence of headache disorders, particularly migraine and TTH, among medical students in Vietnam. These findings underscore the critical need for public health initiatives to improve early diagnosis and effective management of headache disorders within this population., Competing Interests: Declarations Ethics and approvals The study was conducted in accordance with the Declaration of Helsinki, and informed consent was obtained from all subjects and their legal guardian(s). The protocol and questionnaire were reviewed and approved by the Institutional Review Board at the University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam. To protect privacy, any personal information that could be used to identify a specific individual has been removed. Data were collected anonymously and managed in compliance with data protection legislation. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Mesenchymal stem cell (MSC)-derived exosomes (EXs) have emerged as promising therapeutic agents for wound healing. However, the optimal conditions for manufacturing MSC-derived EXs that maximize their wound-healing potential have yet to be established. Hence, we compared the efficacy of five different MSC culture media, including three different serum-free, a platelet-supplemented, and a fetal bovine serum-supplemented media, in exosome manufacturing for wound healing applications. Although umbilical cord-derived MSCs (UCMSCs) cultured in these media exhibited similar proliferation, morphology, MSC surface marker expression, and stemness, EXs derived from UCMSCs cultured in different culture media displayed varying levels of growth factors and cytokines. Notably, EXs derived from platelet-supplemented media (DM-PLT&#95;EXs) exhibited significantly higher concentrations of keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF-A), platelet-derived growth factor (PDGF-BB), interleukin 6 (IL-6), interleukin 7 (IL-7), and interleukin 8 (IL-8) than EXs from other media. These differences correlated with the superior capability of DM-PLT&#95;EXs to promote human skin fibroblast proliferation and stimulate angiogenesis of human umbilical vein endothelial cells, making them a more suitable choice for wound healing applications. Our findings emphasize the significance of the culture medium selection in tailoring the therapeutic potential of UCMSC-derived EXs for wound healing., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: May-Thurner syndrome (MTS) is a continuous pathological change of the left common iliac vein intraluminal wall due to compression between the right common iliac artery and a lumbar vertebra, with clinical signs of compromised venous drainage of the left leg, which eventually leads to development of left-sided deep vein thrombosis (DVT)., Purpose: To analyze the correlation between iliac vessel geometry and probability of DVT in patients with MTS., Material and Methods: This study consists of two age-matched female groups: DVT (n = 21) and control (n = 28). Iliac vein geometry, including left common iliac vein (LCIV) diameter, percentage of stenosis, angle between LCIV and right common iliac vein (RCIV), tilt angle of each CIV with horizontal line, and crossing angle between right common iliac artery (RCIA) and LCIV, were measured on computed tomography venography (CTV) images. The probability of DVT development was assessed using logistic regression., Results: Comparing the DVT and control groups, the mean LCIV diameter was 2.4 mm and 3.7 mm ( P  = 0.001), and mean LCIV stenosis was 77.7% and 68.3% ( P  = 0.001), respectively. After age-adjustment, the odds of left DVT in patients with MTS correlated with LCIV diameter (odds ratio [OR]=0.25, P  < 0.001, 95% confidence interval [CI]=0.11-0.54), LCIV stenosis (%) (OR=1.12, P  = 0.003, 95% CI=1.04-1.21), LCIV tilt angle (OR=0.95, P  < 0.038, 95% CI=0.91-0.99), and angle between two CIVs (OR=1.04, P  < 0.039, 95% CI=1.00-1.09)., Conclusion: LCIV diameter and percentage of stenosis, LCIV tilt angle, and CIV angle were independent risk factors for the development of DVT in patients with MTS., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In the realm of cancer immunotherapy, the meticulous selection of neoantigens plays a fundamental role in enhancing personalized treatments. Traditionally, this selection process has heavily relied on predicting the binding of peptides to human leukocyte antigens (pHLA). Nevertheless, this approach often overlooks the dynamic interaction between tumor cells and the immune system. In response to this limitation, we have developed an innovative prediction algorithm rooted in machine learning, integrating T cell receptor β chain (TCRβ) profiling data from colorectal cancer (CRC) patients for a more precise neoantigen prioritization. TCRβ sequencing was conducted to profile the TCR repertoire of tumor-infiltrating lymphocytes (TILs) from 28 CRC patients. The data unveiled both intra-tumor and inter-patient heterogeneity in the TCRβ repertoires of CRC patients, likely resulting from the stochastic utilization of V and J segments in response to neoantigens. Our novel combined model integrates pHLA binding information with pHLA-TCR binding to prioritize neoantigens, resulting in heightened specificity and sensitivity compared to models using individual features alone. The efficacy of our proposed model was corroborated through ELISpot assays on long peptides, performed on four CRC patients. These assays demonstrated that neoantigen candidates prioritized by our combined model outperformed predictions made by the established tool NetMHCpan. This comprehensive assessment underscores the significance of integrating pHLA binding with pHLA-TCR binding analysis for more effective immunotherapeutic strategies., Competing Interests: TP, TN, BT, TD, ND, HP, TC, DL, HN, DT, TT, TP, ML, TV, MP, HG, HN, LT No competing interests declared, (© 2024, Pham et al.)

Background: Point-of-care ultrasound (POCUS) has emerged as an essential bedside tool for clinicians, but lack of access to ultrasound equipment has been a top barrier to POCUS use. Recently, several handheld ultrasound devices ("handhelds") have become available, and clinicians are seeking data to guide purchasing decisions. Few comparative studies of different handhelds have been done. We conducted a cross-sectional study comparing 6 handhelds readily available in the United States (Butterfly iQ +  ™ by Butterfly Network Inc.; Clarius ™ by Clarius Mobile Health; Kosmos ™ by EchoNous; TE Air ™ by Mindray; Vscan Air ™ SL and CL by General Electric; and Lumify ™ by Philips Healthcare). A multi-specialty group of physician POCUS experts (n = 35) acquired three standard ultrasound views (abdominal right upper quadrant, cardiac apical 4-chamber, and superficial neck and lung views) in random order on the same standardized patients and rated the image quality. Afterward, a final survey of the overall ease of use, image quality, and satisfaction of each handheld was completed., Results: Thirty-five POCUS experts specializing in internal medicine/hospital medicine, critical care, emergency medicine, and nephrology acquired and rated right upper quadrant, apical 4-chamber, and superficial neck and lung views with 6 different handhelds. For image quality, the highest-rated handhelds were Vscan Air ™ for the right upper quadrant view, Mindray TE Air ™ for the cardiac apical 4-chamber view, and Lumify ™ for superficial views of the neck and lung. Overall satisfaction with image quality was highest with Vscan Air ™ , Lumify ™ , and Mindray, while overall satisfaction with ease of use was highest with Vscan Air ™ . The 5 most desirable characteristics of handhelds were image quality, ease of use, portability, probe size, and battery life. Ultimately, all 6 handhelds had notable advantages and disadvantages, with no single device having all desired qualities or features., Conclusions: The overall satisfaction with image quality was rated highest with Vscan Air ™ , Lumify ™ , and Mindray TE Air ™ when acquiring right upper quadrant, apical 4-chamber, and superficial neck and lung views. No single handheld was perceived to be superior in image quality for all views. Vscan Air ™ was rated highest for overall ease of use and was the most preferred handheld for purchase by POCUS experts., (© 2024. The Author(s).)

Background and Objectives: The biofilm formation has been widely recognized as one of the main mechanisms of antimicrobial resistance development in microorganisms. However, few studies are focusing on this phenomenon in Candida spp. in clinical settings, especially on immuno-compromised patients., Materials and Methods: In this study, both the rate of biofilm formation in those patients and its drug susceptibility in initial and mature biofilm were assessed using crystal violet assay and dilution method., Results: The results demonstrated that the biofilm formation rate was similar between albicans and non-albicans Candida . However, the biofilm formation capacity was more pronounced in non-albicans Candida , especially, C. glabrata . As expected, there was a significant relationship between biofilm formation and drug resistance. In addition, our study reconfirmed that the age of high concentration of antifungal agents only affected Candida before its biofilm formation regardless of its biofilm formation capacity. In the contrary, once the biofilm was formed even elevated drug concentrations did not show sufficient efficacy, highlighting a need for high dosage at the early stage of treatment for those patients., Conclusion: The results of this study highlighted the importance of using appropriate antifungal agents for Candida treatment before the formation of biofilm., (Copyright© 2024 The Authors. Published by Tehran University of Medical Sciences.)

Objective: This study aimed to assess the diagnostic performance of the Risk of Ovarian Malignancy Algorithm (ROMA), Copenhagen Index (CPH-I), and Ovarian Adnexal Reporting and Data System (O-RADS) for the preoperative prediction of ovarian cancer (OC)., Methods: A prospective cohort study was conducted on 462 patients diagnosed with ovarian tumors admitted to the Departments of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy Hospital, and Hue Central Hospital from May 2020 to December 2022. ROMA and CPH-I were calculated using cancer antigen 125 (CA125), human epididymal protein 4 (HE4) levels, and patient characteristics (age and menopausal status). O-RADS criteria were applied to describe ovarian tumor characteristics from ultrasound findings. Compared with histopathological results, the predictive values of ROMA, CPH-I, and O-RADS alone or in combination with CA125/HE4 for OC were calculated., Results: Among 462 patients, 381 had benign tumors, 11 had borderline tumors, and 50 had OC. At optimal cut-off points, ROMA's and CPH-I's areas under the curves (AUCs) were 0.880 (95% confidence interval [CI]=0.846-0.909) and 0.890 (95% CI=0.857-0.918), respectively, and ROMA and CPH-I sensitivities/specificities (Se/Sp) were 68.85%/95.01% and 77.05%/91.08%, respectively. O-RADS ≥3 yielded an AUCs of 0.949 (95% CI=0.924-0.968), with Se/Sp of 88.52%/88.98% (p<0.001). Combining O-RADS with CA125 demonstrated the highest predictive value, with AUCs of 0.969 (95% CI=0.949-0.983) and Se/Sp of 98.36%/86.09% (p<0.001)., Conclusion: The ROMA, CPH-I, O-RADS, O-RADS + CA125, and O-RADS + HE4 models demonstrated good predictive values for OC; the combination of O-RADS and CA125 yielded the highest values., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

The interleukin (IL)-1 family is a major proinflammatory cytokine family, ranging from the well-studied IL-1s to the most recently discovered IL-33. As a new focus, IL-33 has attracted extensive research for its crucial immunoregulatory roles, leading to the development of notable monoclonal antibodies as clinical candidates. Efforts to develop small molecules disrupting IL-33/ST2 interaction remain highly desired but encounter challenges due to the shallow and featureless interfaces. The information from relative cytokines has shown that traditional binding site identification methods still struggle in mapping cryptic sites, necessitating dynamic approaches to uncover druggable pockets on IL-33. Here, we employed mixed-solvent molecular dynamics (MixMD) simulations with diverse-property probes to map the hotspots of IL-33 and identify potential binding sites. The protocol was first validated using the known binding sites of two IL-1 family members and then applied to the structure of IL-33. Our simulations revealed several binding sites and proposed side-chain rearrangements essential for the binding of a known inhibitor, aligning well with experimental NMR findings. Further microsecond-time scale simulations of this IL-33-protein complex unveiled distinct binding modes with varying occurrences. These results could facilitate future efforts in developing ligands to target challenging flexible pockets of IL-33 and IL-1 family cytokines in general.

Research Question: What is the diagnostic accuracy of hysterosalpingo-foam sonography (HyFoSy), using two-dimensional ultrasound in tubal patency assessment in infertile women compared with laparoscopy with dye chromotubation?, Design: This prospective study was conducted at My Duc Hospital, Vietnam. Infertile women aged 18 years or older, who were scheduled for laparoscopy, were included. Visual Analogue Scale (VAS) score for perception of pain during HyFoSy was used. Laparoscopy was carried out on the same day. Clinicians undertaking laparoscopy were blinded to HyFoSy results. Sensitivity, specificity, negative and positive predictive value, and 95% confidence intervals were calculated. A sample size of 455 women (n = 910 fallopian tubes) was needed to demonstrate a fluctuation hypothesis, not exceeding 6%, for sensitivity and specificity (power 0.80, two-sided alpha 5%, loss to follow-up 5%)., Results: Between 2019 and 2022, 455 participants were recruited. Hysterosalpingo-foam sonography was unsuccessfully carried out in six participants. Two withdrew their consent. Data analysis was conducted on the remaining 447 participants (n = 868 fallopian tubes). The sensitivity and specificity of hysterosalpingo-foam sonography compared with laparoscopy were 0.75 (95% CI 0.71 to 0.79) and 0.70 (95% CI 0.65 to 0.74), respectively. Hysterosalpingo-foam sonography gave a positive predictive value of 0.76 (95% CI 0.73 to 0.80) and negative predictive value of 0.68 (95% CI 0.64 to 0.73). A total of 42.8% of women reported a VAS score of no pain. No adverse event was reported., Conclusion: Compared with laparoscopy with dye chromotubation, two-dimensional HyFoSy is a well-tolerated, reliable technique for assessing tubal patency., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Ovarian clear cell carcinoma (CCC) has an East Asian preponderance. It is associated with endometriosis, a benign condition where endometrial (inner lining of the uterus) tissue is found outside the uterus and on the peritoneal surface, in the abdominal or pelvic space. CCC is relatively more resistant to conventional chemotherapy compared to other ovarian cancer subtypes and is associated with a poorer prognosis. In this study, we recruited and obtained tumour tissues from seven patients across the four stages of CCC. The tumour and the tumour microenvironment (TME) from 7 CCC patients spanning clinical stages 1-4 were transcriptionally profiled using high-resolution scRNA-seq to gain insight into CCC's biological mechanisms. Firstly, we built a scRNA-seq resource for the CCC tumour microenvironment (TME). Secondly, we identified the different cell type proportions and found high levels of immune infiltration in CCC. Thirdly, since CCC is associated with endometriosis, we compared CCC with two publicly available endometriosis scRNA-seq datasets. The CCC malignant cells showed similarities with glandular secretory and ciliated epithelial cells found in endometriosis. Finally, we determined the differences in cell-cell communication between various cell types present in CCC TME and endometriosis conditions to gain insights into the transformations in CCC., Competing Interests: Conflict of interest statement None declared.

Severe acute malnutrition (SAM) remains a major global public health problem. SAM cases are treated using ready-to-use therapeutic food (RUTF) at a dosage of ∼200 kcal/kg/day per the standard treatment protocol (STD). Emerging evidence on simplifications to the standard protocol, which among other adaptations, includes reducing the daily RUTF dosage, indicates that it is effective and safe for treating children with SAM. In response to a foreseen stock shortage of RUTF, the government of Afghanistan endorsed the temporary use of a modified treatment protocol in which the daily RUTF dosage was prescribed at 1000 kcal/day (irrespective of body weight) until the child achieved moderate acute malnutrition status (weight-for-height z-score ≥ -3 or mid-upper arm circumference [MUAC] ≥ 115 mm), at which point 500 kcal/day was prescribed until cured (modified treatment protocol [MTP]). In this paper, we report the results of this nonweight-based daily RUTF dosage experience. Data of 2042 children with SAM, treated using either the STD protocol (n = 269) or the MTP protocol (n = 1773) from August 2019 to March 2021 in five provinces, were analyzed. The per-protocol analyses confirmed noninferiority of MTP protocol when compared to STD protocol for recovery rate [93.3% vs. 90.2%; ∆ (95% confidence interval, CI) = 3.1 (-0.9; 7.2) %] and length-of-stay [82.6 vs. 75.6 days; ∆ (95% CI) = 6.9 (3.3; 10.5) days], considering the margin of noninferiority of -10% and +14 days, respectively. Weight gain velocity was smaller in the MTP protocol group than in the STD protocol group [3.7 (1.7) vs. 5.2 (2.9) g/kg/day; ∆ (95% CI) = -1.5 (-1.8, -1.2); p < 0.001]. The STD group had a significantly higher mean than the MTP group for absolute MUAC gain [∆ (95% CI) = 1.7 (1.0; 2.3) mm; p < 0.001] and the MUAC velocity [∆ (95% CI) = 0.29 (0.20; 0.37) mm/week; p < 0.001]. Our results confirm the noninferiority of a nonweight-based daily dosage and support the endorsement of this modification as an alternative to the standard protocol in resource-constrained contexts., (© 2024 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

BACKGROUND Monostotic fibrous dysplasia is a benign proliferation of fibrous and osseous tissues that expand medullary bone to cause symptoms due to compression of adjacent organs and anatomical structures. Focal seizures are rarely the first sign of this kind of lesion. This report describes a young female patient with left-sided focal motor seizures associated with fibrous dysplasia presenting as a mass in the right parietal bone. CASE REPORT An 18-year-old female student with left-sided focal motor seizures presented with a mass in the right parietal bone. Computed tomography revealed an expansile mixed-density lesion on the right parietal bone, a relatively homogeneous ground-glass appearance in the outer circumferential portion, and a lucent eccentric area with thinned but sclerotic borders. Magnetic resonance imaging revealed a homogeneously hypointense signal on T1WI, a small hyperintense signal on T2WI, and avid enhancement signal intensity on post-contrast T1. Electroencephalogram showed inter-ictal epileptiform activities derived from the right fronto-central lobe. Surgical en bloc resection with a margin of normal bone and cranioplasty were performed. Histopathology showed features indicative of fibrous dysplasia, including osteoid trabeculae arranged haphazardly in a dense fibroblastic stroma, irregular trabeculae lacking conspicuous osteoblastic rimming, and intervening fibrous stroma containing cytologically bland spindle cells. The patient achieved seizure control and has remained neurologically intact. CONCLUSIONS This report has highlighted the importance of early diagnosis of fibrous dysplasia of bone to exclude primary bone malignancy or bone metastasis, to ensure rapid management and symptom control.

Introduction: The identification of a new adverse event (AE) caused by a drug product is one of the key activities in the pharmaceutical industry to ensure the safety profile of a drug product. Machine learning (ML) has the potential to assist with signal detection and supplement traditional pharmacovigilance (PV) surveillance methods. This pilot ML modeling study was designed to detect potential safety signals for two AbbVie products and test the model's capability of detecting safety signals earlier than humans., Methods: Drug X, a mature product with post-marketing data, and Drug Y, a recently approved drug in another therapeutic area, were selected. Gradient boosting-based ML approaches (e.g., XGBoost) were applied as the main modeling strategy., Results: For Drug X, eight true signals were present in the test set. Among 12 potential new signals generated, four were true signals with a 50.0% sensitivity rate and a 33.3% positive predictive value (PPV) rate. Among the remaining eight potential new signals, one was confirmed as a signal and detected six months earlier than humans. For Drug Y, nine true signals were present in the test set. Among 13 potential new signals generated, five were true signals with a 55.6% sensitivity rate and a 38.5% PPV rate. Among the remaining eight potential new signals, none were confirmed as true signals upon human review., Conclusion: This model demonstrated acceptable accuracy for safety signal detection and potential for earlier detection when compared to humans. Expert judgment, flexibility, and critical thinking are essential human skills required for the final, accurate assessment of adverse event cases., (© 2024. The Author(s).)

Small auxin-up RNA (SAUR) proteins were known as a large family that supposedly participated in various biological processes in higher plant species. However, the SAUR family has been still not explored in cacao (Theobroma cacao L.), one of the most important industrial trees. The present work, as an in silico study, revealed comprehensive aspects of the structure, phylogeny, and expression of TcSAUR gene family in cacao. A total of 90 members of the TcSAUR gene family have been identified and annotated in the cacao genome. According to the physic-chemical features analysis, all TcSAUR proteins exhibited slightly similar characteristics. Phylogenetic analysis showed that these TcSAUR proteins could be categorized into seven distinct groups, with 10 sub-groups. Our results suggested that tandemly duplication events, segmental duplication events, and whole genome duplication events might be important in the growth of the TcSAUR gene family in cacao. By re-analyzing the available transcriptome databases, we found that a number of TcSAUR genes were exclusively expressed during the zygotic embryogenesis and somatic embryogenesis. Taken together, our study will be valuable to further functional characterizations of candidate TcSAUR genes for the genetic engineering of cacao., (© 2024. The Author(s).)

Cu-doping contents in the TiO 2 lattice structure were studied to show the effects on the crystal structure, morphology, and photocatalytic activity of TiO 2 nanoparticles and thus composite cellulosic nanofibrous membranes. Pristine and copper-doped TiO 2 nanoparticles were synthesized using the sol-gel technique, a wet chemical method with the advantages of low synthesizing temperature, uniform nanosize distribution, and purity. The as-synthesized semiconductor nanoparticles were first tested with the dye removal process and then impregnated onto electrospun cellulose nanofibers (CL nanofibers) to acquire modified nanofibers with self-cleaning properties. The as-prepared composite CL nanofibers consisting of doped and undoped TiO 2 nanoparticles were characterized by various techniques, such as field emission scanning electron microscopy, transmission electron microscopy, UV-vis, X-ray diffraction, Fourier transform infrared spectroscopy, and tensile tests. The copper-doped TiO 2 molar ratio in the nanocomposite was found to possess a pronounced impact on the dye removal and self-cleaning effects under the visible light spectrum, whereas TiO 2 is highly effective under specific UV-light irradiation. Optical measurements and dye decomposition showed that the Cu-doped TiO 2 nanocomposite was optimized at a 1% molar ratio by the copper-doping concentration regarding dye removal and self-cleaning applications under the visible light range., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objectives: This study aimed to translate and validate the Vietnamese version of the Epilepsy Self-Management Scale (V-ESMS)., Methods: The translation and cross-cultural adaptation of the original version of the ESMS into Vietnamese followed the Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes Measures guideline with "forward-backward" translation and culturally adapted. The participants were recruited consecutively at neurology clinics at Nguyen Tri Phuong Hospital and University Medical Center, Ho Chi Minh City, from January 2022 to July 2022 and required to complete the V-ESMS. The validity was assessed by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Cronbach's alpha and intraclass correlation coefficient (ICC) were used to evaluate internal and temporal reliability, respectively., Results: A total of 200 participants were recruited for analysis. The V-ESMS included 36 items and five domains. The factor loading ranged between 0.313 and 0.927; most items loaded in their hypothesized factors proved in the original scale. Using the CFA, theCMIN/DF, comparative fit index, and root mean square error of approximation were 2.883, 0.80, and 0.097, respectively. The Cronbach's alpha in each domain was 0.79-0.907; the scale was 0.936. The ICC from 0.94 to 0.98 showed excellent test-retest reliability., Conclusion: The 36-item V-ESMS with five domains presented good validity and reliability. This instrument could be used to assess self-management in people with epilepsy in Vietnam., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The anatomical parameters of the acetabulum vary among races and geographical regions. Multislice Computed Tomography (CT) has proven to be a practical approach to assess morphological parameters of the acetabulum. The purpose of this study was to explore morphological characteristics of the acetabulum measured by CT scans in Vietnamese adults., Methods: Thirty-five consecutive patients aged 18 years and older received indications and eligibility for total hip replacement surgery. Sixty-three acetabulum were examined with multislice computed tomographic system (CT) with multiplanar reconstruction (MPR). Measured morphometric parameters of acetabulum included acetabular inclination angle (AIA), acetabular anteversion angle (AAA), acetabular angle of sharp (AAS), sagittal acetabular angle (SAA), acetabular horizontal offset (AHO), transverse acetabular ligament anteversion (TALA), transverse acetabular ligament inclination (TALI), acetabular depth (ADe), acetabular depth ratio (ADr) and acetabular diameter (ADi)., Results: The mean values of acetabular diameter, femoral head diameter, AIA, AAA, AAS, SAA, TALA, TALI, AHO, ADe, ADr were 50.22±3.56 mm, 43.54±3.68 mm, 40.27±5.09 mm, 13.30±5.54 mm, 39.46±5.41 mm, 26.38±9.01 mm, 9.49±3.92 mm, 47.70±6.73 mm, 3.06±0.37 mm, 18.62±2.95 mm and 309.60±41.87 mm., Conclusion: Our initial data has showed morphological characteristics of the acetabulum in Vietnamese adults, different from the populations from other parts of world. Also, significant correlation between the orientation of the acetabulum and the transverse acetabular ligament was documented., Competing Interests: The authors declare no conflict of interest.

Bacterial cells tightly regulate the intracellular concentrations of essential transition metal ions by deploying a panel of metal-regulated transcriptional repressors and activators that bind to operator-promoter regions upstream of regulated genes. Like other zinc uptake regulator (Zur) proteins, Acinetobacter baumannii Zur represses transcription of its regulon when Zn II is replete and binds more weakly to DNA when Zn II is limiting. Previous studies established that Zur proteins are homodimeric and harbor at least two metal sites per protomer or four per dimer. Cd II X-ray absorption spectroscopy (XAS) of the Cd 2 Zn 2 Ab Zur metalloderivative with Cd II bound to the allosteric sites reveals a S(N/O) 3 first coordination shell. Site-directed mutagenesis suggests that H89 and C100 from the N-terminal DNA binding domain and H107 and E122 from the C-terminal dimerization domain comprise the regulatory metal site. K Zn for this allosteric site is 6.0 (±2.2) × 10 12 M -1 with a functional "division of labor" among the four metal ligands. N-terminal domain ligands H89 and C100 contribute far more to K Zn than H107 and E122, while C100S Ab Zur uniquely fails to bind to DNA tightly as measured by an in vitro transcription assay. The heterotropic allosteric coupling free energy, Δ G c , is negative, consistent with a higher K Zn for the Ab Zur-DNA complex and defining a bioavailable Zn II set-point of ≈6 × 10 -14 M. Small-angle X-ray scattering (SAXS) experiments reveal that only the wild-type Zn homodimer undergoes allosteric switching, while the C100S Ab Zur fails to switch. These data collectively suggest that switching to a high affinity DNA-binding conformation involves a rotation/translation of one protomer relative to the other in a way that is dependent on the integrity of C100. We place these findings in the context of other Zur proteins and Fur family repressors more broadly.

Candida nivariensis is emerging as a highly resistant species of the Candida glabrata complex causing invasive and mucocutaneous infections. In this study, three cases of vulvovaginal candidiasis caused by C. nivariensis are described and identified by Internal Transcribed Spacer 1-2 sequencing. All isolates were susceptible in vitro to anidulafungin, micafungin, caspofungin, 5-flucytosine, posaconazole, voriconazole, itraconazole, amphotericin B, and showed dose-dependent susceptibility to fluconazole. In two patients, three doses of oral fluconazole were effective, while one patient developed clinical fluconazole resistance with a new relapse after 6 months. Increasing the weekly dose of fluconazole showed to be effective in this patient., Competing Interests: The authors have no conflict of interest., (© 2024 The Authors.)

Biopolymer analysis, including proteomics and glycomics, relies heavily on the use of mass spectrometry for structural elucidation, including sequence determination. Novel methods to improve sample workup, instrument performance, and data analysis continue to be developed to address shortcomings associated with sample preparation, analysis time, data quality, and data interpretation. Here, we present a new method that couples in-source collision-induced dissociation (IS-CID) with two-dimensional tandem mass spectrometry (2D MS/MS) as a way to simplify proteomics and glycomics workflows while also providing additional insight into analyte structures over traditional MS/MS experiments. Specifically, IS-CID is employed as a gas-phase digestion method, i.e., to break down intact full-length polysaccharide or peptide ions prior to mass analysis. The resulting mixtures of oligomeric ions are analyzed by 2D-MS/MS, a technique that allows association of product ions with their precursor ions without isolation of the latter. A novel data analysis strategy is introduced to leverage the second dimension of 2D MS/MS spectra, in which stairstep patterns, representing outputs of a molecule's MS n scans, are extracted for structural interconnectivity information on the oligomer. The results demonstrate the potential applicability of 2D MS/MS strategies to the modern omics workflow and structural analysis of various classes of biopolymers., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Houttuynia cordata Thunb. has long been widely used as a daily vegetable and traditional medicine. The flavonoid component of H. cordata has plenty of pharmacological effects, such as antibacterial, anti-inflammatory, and antioxidant. In this study, we applied the aqueous two-phase system (ATPS) combined with ultrasonic extraction for extracting H. cordata leaves., Methods: We optimized the extraction process to improve the extraction efficiency of the two flavonoids, hyperin and quercitrin, by Surface Method Response - Central Composite Design (RSM-CCD). Next, we investigated the antibacterial ability of H. cordata ATPS extract from optimal conditions against two bacterial strains, Cutibacterium acnes and Staphylococcus epidermidis ., Results: The results showed that using 10% (NH 4 ) 2 SO 4 and 35% ethanol for ATPS extraction resulted in the highest hyperin and quercitrin contents. From the RSM-CCD results, the optimal extraction conditions were determined to be ultrasonic extraction at 50 °C for 30 min, giving results consistent with the predicted model and obtaining hyperin and quercitrin contents at 1.5681 ± 0.0114 and 4.6225 ± 0.0327 mg/g, respectively.Furthermore, ATPS extract has excellent antibacterial activity with a minimum inhibitory concentration (MIC) value of 250 μg/mL on both C. acnes and S. epidermidis . This MIC is significantly lower than the H. cordata ultrasound-assisted (UA) extract, with MICs of 1500.00 and 156.25 μg/mL on C. acnes and S. epidermidis , respectively. In addition, the results from the disk diffusion assay also showed that ATPS extraction has superior internal antibacterial activity with a zone of inhibition diameter at 250 μg/mL of 8.67 ± 1.15 and 5.00 ± 2.00 mm. Meanwhile, those of UA extract on C. acnes is 5.67 ± 1.53 mm (at 1500 μg/mL), and on S. epidermidis is 1.34 ± 0.58 mm (at 156.25 μg/mL)., Conclusion: To sum up, our research highlights the potential of H. cordata ATPS extracts as the starting material for topical preparations for effectively treating acne., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Objectives: This study aimed to determine (1) the needsof Vietnamese people with epilepsy (PWE) and their caregivers for self-management mobile health applications and (2) the self-management features expected to be included in an application., Methods: The survey consisted of an anonymous self-administered questionnaire that was distributed to PWE and caregivers from the age of 18 in Vietnam through online platforms and onsite at Nguyen Tri Phuong Hospital and University Medical Center, Ho Chi Minh City, from February 2022 to May 2022. The questionnaire assessed the participants' attitudes toward epilepsy self-management mobile applications, their willingness to use applications, and their expectations of the contents of an application., Results: Responses from 103 participants were submitted. Eighty-one participants (78.6%) reported using a smartphone, but only 50.6% of those claimed to know about self-management applications. Most respondents (70.9%) thought the applications would be useful for disease self-management, and 68.9% were willing to use epilepsy self-management applications. In addition, the most expected features to be included in self-management applications were epilepsy information, seizure first aid, connecting with medical professionals, and a seizure diary., Conclusion: Most Vietnamese PWE and caregivers had a willingness to use epilepsy self-management applications.The expected features are related to all aspects of self-management, including information, seizure, medication, and safety management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lichens produce secondary metabolites that have many pharmaceutical activities such as antimicrobial, antioxidant, antiviral, anticancer, antigenotoxic, anti-inflammatory, analgesic and antipyretic activities. However, there is limited research on their efflux pump inhibitory activities. Twelve phytochemicals were isolated from Usnea aciculifera , and their activity of AcrAB-TolC efflux pump inhibition was evaluated. Four potential compounds, which are diffractaic acid (2) , 8' - O - methylstictic acid (5) , 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 2,4-dimethoxy-3,6-dimethylbenzoate ( 8) and 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 2-hydroxy-4-methoxy-3,6-dimethylbenzoate (9) , were found by virtual screening using pharmacophore and 2D-QSAR model. Compound 8 exhibited AcrB inhibition activity in vitro with an accumulation H33342 percentage compared with untreated control of 202% at a concentration of 50 µM and increased the antibacterial activity of levofloxacin by four-fold at a concentration of 200 µM. By molecular docking and molecular dynamics (MD) simulation, the binding affinity of depside and depsidone derivatives to AcrB was also clarified. Despite the poor docking score to the AcrB binding site, compound 8 was the most stable among the four complexes at 20 ns of MD simulation. The analysis of long MD at 100 ns indicated that compound 8 interacts strongly with the residues in the distal pocket, creating a stable complex with ΔG bind of -31.51  kcal.mol-1. According to the ADMETlab 2.0 web server's predictions of pharmacokinetics and toxicities, compound 8 has the potential for drug development.Communicated by Ramaswamy H. Sarma.

In the nature, Candida species are normal inhabitants and can be observed in a wide variety of vertebrates. In humans, especially for cancer patients who fall prey to opportunistic pathogens, this group of susceptible multi-drug resistant and biofilm-forming yeasts, are among the commonest ones. In this study, Candida species in 76 oral lesion samples from Vietnamese nasopharyngeal-cancer patients were isolated, morphologically identified using CHROMagar™, germ tube formation, and chlamydospore formation tests, and molecularly confirmed by PCR-RFLP. The drug susceptibility of these isolates was then tested, and the gene ERG11 was DNA sequenced to investigate the mechanism of resistance. The results showed that Candida albicans remained the most prevalent species (63.16% of the cases), followed by Candida glabrata , Candida tropicalis , and Candida krusei . The rates of resistance of non-albicans Candida for tested drugs were 85.71%, 53.57%, and 57.14% to fluconazole, clotrimazole, and miconazole, respectively. Although the drug-resistance rate of Candida albicans was lower than that of non-albicans Candida , it was higher than expected, suggesting an emerging drug-resistance phenomenon. Furthermore, ERG11 DNA sequencing revealed different mutations (especially K128T), implying the presence of multiple resistance mechanisms. Altogether, the results indicate an alarming drug-resistance situation in Candida species in Vietnamese cancer patients and emphasize the importance of species identification and their drug susceptibility prior to treatment., Competing Interests: The authors declare no conflicts of interest. All the experiments undertaken in this study comply with the current laws of the country where they were performed., (© 2023 The Authors. Published by Elsevier B.V.)

The COVID-19 pandemic has resulted in a large number of fatalities and, at present, lacks a readily available curative treatment for patients. Here, we demonstrate that unmodified red blood cell-derived extracellular vesicles (RBCEVs) can inhibit SARS-CoV-2 infection in a phosphatidylserine (PS) dependent manner. Using T cell immunoglobulin mucin domain-1 (TIM-1) as an example, we demonstrate that PS receptors on cells can significantly increase the adsorption and infection of authentic and pseudotyped SARS-CoV-2 viruses. RBCEVs competitively inhibit this interaction and block TIM-1-mediated viral entry into cells. We further extend the therapeutic efficacy of this antiviral treatment by loading antisense oligonucleotides (ASOs) designed to target conserved regions of key SARS-CoV-2 genes into RBCEVs. We establish that ASO-loaded RBCEVs are efficiently taken up by cells in vitro and in vivo to suppress SARS-CoV-2 replication. Our findings indicate that this RBCEV-based SARS-CoV-2 therapeutic displays promise as a potential treatment capable of inhibiting SARS-CoV-2 entry and replication.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 80%-85% of total cases and leading to millions of deaths worldwide. Drug resistance is the primary cause of treatment failure in NSCLC, which urges scientists to develop advanced approaches for NSCLC treatment. Among novel approaches, the miRNA-based method has emerged as a potential approach as it allows researchers to modulate target gene expression. Subsequently, cell behaviors are altered, which leads to the death and the depletion of cancer cells. It has been reported that miRNAs possess the capacity to regulate multiple genes that are involved in various signaling pathways, including the phosphoinositide 3-kinase, receptor tyrosine kinase/rat sarcoma virus/mitogen-activated protein kinase, wingless/integrated, retinoblastoma, p53, transforming growth factor β, and nuclear factor-kappa B pathways. Dysregulation of these signaling pathways in NSCLC results in abnormal cell proliferation, tissue invasion, and drug resistance while inhibiting apoptosis. Thus, understanding the roles of miRNAs in regulating these signaling pathways may enable the development of novel NSCLC treatment therapies. However, a comprehensive review of potential miRNAs in NSCLC treatment has been lacking. Therefore, this review aims to fill the gap by summarizing the up-to-date information on miRNAs regarding their targets, impact on cancer-associated pathways, and prospective outcomes in treating NSCLC. We also discuss current technologies for delivering miRNAs to the target cells, including virus-based, non-viral, and emerging extracellular vesicle-based delivery systems. This knowledge will support future studies to develop an innovative miRNA-based therapy and select a suitable carrier to treat NSCLC effectively., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Efflux pumps have been reported as one of the significant mechanisms by which bacteria evade the effects of multiple antibiotics. The tripartite efflux pump MexAB-OprM in Pseudomonas aeruginosa is one of the most significant multidrug efflux systems due to its broad resistance to antibiotics such as chloramphenicol, fluoroquinolones, lipophilic β-lactam antibiotics, nalidixic acid, novobiocin, rifampicin, and tetracycline. A promising strategy to overcome this resistance mechanism is to combine antibiotics with efflux pump inhibitors (EPIs), which can increase their intracellular concentration to enhance their biological activities. Based on 143 EPIs with chemically diverse skeletons, the 3D pharmacophore and 2D-QSAR modelings were developed and used for the virtual screening on 9.2 million compounds including ZINC15, DrugBank, and Traditional Chinese Medicine databases to identify new EPIs. The molecular docking was also performed to evaluate the binding affinity of potential EPIs to the distal-binding pocket of MexB and resulted in 611 potential EPIs. The structure-activity relationship analyses suggested that nitrogen heterocyclic compounds, piperazine and pyridine scaffolds, and amide derivatives are the most favorable chemically features for MexAB inhibitory activities. The results from molecular dynamics analysis in 100 ns indicated that ZINC009296881 and ZINC009200074 were the most potential MexB inhibitors with strong binding affinity to the distal pocket and MM/GBSA ∆G bind values of - 38.97 and - 30.19 kcal mol -1 , respectively. The predicted pharmacokinetic properties and toxicity of these compounds indicated their potential oral drugs. Multistep virtual screening of EPIs for MexAB-OprM, efflux pump multidrug resistant of P. aeruginosa., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: This study aimed to evaluate the value of anti-Müllerian hormone (AMH) in predicting ovulation induced by aromatase inhibitors (AI) and pregnancy outcomes in women with polycystic ovary syndrome (PCOS)., Methods: From January 2018 to December 2020, this prospective cohort study enrolled women with PCOS aged between 18 and 45 years who underwent ovulation induction using AI protocol and intrauterine insemination (IUI) for infertility at a Center for Reproductive Endocrinology and Infertility, University Hospital. Receiver operating characteristic curves were used to estimate the chance of ovulation responses and pregnancy outcomes., Results: In total, 64% of 65 women with PCOS were recruited following AI treatment, and the clinical pregnancy rate was 19.4% following IUI. Patients who experienced ovulation had a lower mean serum AMH concentration than non-responders (7.11 ng/mL vs. 8.95 ng/mL, respectively), but the difference was not statistically significant. Between the pregnancy and non-pregnancy groups, statistically significant differences in AMH concentrations were observed (8.71 ng/mL vs. 6.73 ng/mL, respectively, P = 0.040). The area under the curve of the receiver operating characteristic for non-ovulation prediction was 0.445, 95% CI (0.284-0.606) with P = 0.467, and for clinical pregnancy was 0.735, 95% CI (0.561-0.910) with P = 0.104., Conclusions: In women with PCOS, the AMH level does not predict ovarian responsiveness to AI treatment, but it does predict the success of IUI cycles., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening., Competing Interests: VN VTCN is affiliated with Gene Solutions. The author has no other competing interests to declare, TN HTN is affiliated with Gene Solutions. The author has no other competing interests to declare, ND NNTD is affiliated with Gene Solutions. The author has no other competing interests to declare, TP TMQP is affiliated with Gene Solutions. The author has no other competing interests to declare, GN GTHN is affiliated with Gene Solutions. The author has no other competing interests to declare, TN TDN is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TTTT is affiliated with Gene Solutions. The author has no other competing interests to declare, DV, TP, TJ, VN, HN, TN, QD, TD, AT, VN, VN, LH, QT, TP, TH, BN, TN, TN, DP, BP, TV, TN, TT, MT, NT, TL, TT, MD, HB, VK, TP, DT, TL, TP, ML, VC, TD No competing interests declared, TN THHN is affiliated with Gene Solutions. The author has no other competing interests to declare, LH LAKH is affiliated with Gene Solutions. The author has no other competing interests to declare, TT THT is affiliated with Gene Solutions. The author has no other competing interests to declare, DV DHV is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TMTT is affiliated with Gene Solutions. The author has no other competing interests to declare, MN MNN is affiliated with Gene Solutions. The author has no other competing interests to declare, TV TTVV is affiliated with Gene Solutions. The author has no other competing interests to declare, AN ANN is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TTT is affiliated with Gene Solutions. The author has no other competing interests to declare, VT VUT is affiliated with Gene Solutions. The author has no other competing interests to declare, ML MPL is affiliated with Gene Solutions. The author has no other competing interests to declare, TD TTD is affiliated with Gene Solutions. The author has no other competing interests to declare, TP TVP is affiliated with Gene Solutions. The author has no other competing interests to declare, HN HDN is affiliated with Gene Solutions. The author has no other competing interests to declare, DN DSN holds equity in Gene Solutions.DSN is affiliated with Gene Solutions. The author has no other competing interests to declare, DT DKT is affiliated with Gene Solutions. The author has no other competing interests to declare, HT HST is affiliated with Gene Solutions. The author has no other competing interests to declare, HG HG holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for HG who is inventor on the patent application (USPTO 17930705).HG is affiliated with Gene Solutions. The author has no other competing interests to declare, HN HNN holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for HNN who is inventor on the patent application (USPTO 17930705).HNN is affiliated with Gene Solutions. The author has no other competing interests to declare, MP MDP holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for MDP who is inventor on the patent application (USPTO 17930705).MDP is affiliated with Gene Solutions. The author has no other competing interests to declare, LT LST holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for LST who is inventor on the patent application (USPTO 17930705).LST is affiliated with Gene Solutions. The author has no other competing interests to declare, (© 2023, Nguyen, Nguyen et al.)

IL(interleukin)-6 is a multifunctional cytokine crucial for immunological, hematopoiesis, inflammation, and bone metabolism. Strikingly, IL-6 has been shown to significantly contribute to the initiation of cytokine storm-an acute systemic inflammatory syndrome in Covid-19 patients. Recent study has showed that blocking the IL-6 signaling pathway with an anti-IL-6 receptor monoclonal antibody (mAb) can reduce the severity of COVID-19 symptoms and enhance patient survival. However, the mAb has several drawbacks, such as high cost, potential immunogenicity, and invasive administration due to the large-molecule protein product. Instead, these issues could be mitigated using small molecule IL-6 inhibitors, but none are currently available. This study aimed to discover IL-6 inhibitors based on the PPI with a novel camelid Fab fragment, namely 68F2, in a crystal protein complex structure (PDB ID: 4ZS7). The pharmacophore models and molecular docking were used to screen compounds from DrugBank databases. The oral bioavailability of the top 24 ligands from the screening was predicted by the SwissAMDE tool. Subsequently, the selected molecules from docking and MD simulation illustrated a promising binding affinity in the formation of stable complexes at the active binding pocket of IL-6. Binding energies using the MM-PBSA technique were applied to the top 4 hit compounds. The result indicated that DB08402 and DB12903 could form strong interactions and build stable protein-ligand complexes with IL-6. These potential compounds may serve as a basis for further developing small molecule IL-6 inhibitors in the future., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This randomized controlled trial investigates the efficacy of thread-embedding acupuncture (TEA) compared to sham TEA in treating drug-resistant epilepsy (DRE). Fifty-four DRE outpatients were randomly divided into two groups: TEA (27 patients) and sham TEA (27 patients). Both groups received four sessions of TEA or sham TEA, spaced four weeks apart, targeting GV20, GV14, BL15, BL18, ST40, and GB34 acupoints. Antiseizure medications were maintained at consistent doses throughout the study. Outcome measures included satisfactory seizure control, seizure freedom, and heart rate (HR) and heart rate variability (HRV) measurements. TEA demonstrated a significantly higher rate of satisfactory seizure control at follow-up compared to the sham TEA group (37% vs. 3.7%, p = 0.003). While no significant intergroup differences were observed in HR, HRV, and HRV components at each stage, the TEA group experienced a significant decrease in HR and a significant increase in HRV posttreatment. This study demonstrates TEA's effectiveness in managing DRE and suggests its impact may relate to heightened parasympathetic nerve activity. Further research with extended follow-up periods is necessary to validate these findings., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Van-Dan Nguyen et al.)

Background: Spermatogenesis and sperm quality may be negatively impacted by an increase in reactive oxygen species. This study investigates the efficacy of combined antioxidant therapy for treating male infertility, as measured by semen analyses and the sperm DNA fragmentation index (DFI). Infertile men with a high sperm DNA fragmentation index were instructed to take two oral micronutrient capsules daily for three months. Each antioxidant formulation contained 60 mg vitamin E, 400 µg folic acid, 30 mg selenium, 125 mg L-arginine, 220 mg L-carnitine, 7.5 mg coenzyme Q10, 40 mg L-glutathione, and 20 mg zinc citrate. At entry and post-treatment, the general characteristics, semen analysis, and sperm chromatin dispersion assays were recorded and compared., Results: After three months of treatment with antioxidant compounds, the quality of spermatozoa improved significantly, as indicated by a decrease in the mean DNA fragmentation index from 45.6 ± 17.2% to 34.8 ± 20.3%; an increase in sperm concentration from 29.7 × 10 6 /mL to 35.7 × 10 6 /mL (p < 0.001), an increase in a total number of spermatozoa from 72.1 × 10 6 to 95.5 × 10 6 (p = 0.012), and an increase in the vitality from 75.5 ± 17.1 to 81.1 ± 14.4% viable forms (p < 0.001)., Conclusions: Micronutrient supplementation can improve sperm quality and DNA integrity in infertile men. Men with infertility and significant sperm DNA fragmentation who take antioxidants for three months experience a reduction in DNA fragmentation index and an increase in sperm quality as measured by the semen analysis., Trial Registration: NCT04509583 . Registered 12 August 2020, Hue University of Medicine and Pharmacy Ethics Committee-Retrospectively registered., (© 2023. The Author(s).)

Introduction: Neoantigen-based immunotherapy has emerged as a promising strategy for improving the life expectancy of cancer patients. This therapeutic approach heavily relies on accurate identification of cancer mutations using DNA sequencing (DNAseq) data. However, current workflows tend to provide a large number of neoantigen candidates, of which only a limited number elicit efficient and immunogenic T-cell responses suitable for downstream clinical evaluation. To overcome this limitation and increase the number of high-quality immunogenic neoantigens, we propose integrating RNA sequencing (RNAseq) data into the mutation identification step in the neoantigen prediction workflow., Methods: In this study, we characterize the mutation profiles identified from DNAseq and/or RNAseq data in tumor tissues of 25 patients with colorectal cancer (CRC). Immunogenicity was then validated by ELISpot assay using long synthesis peptides (sLP)., Results: We detected only 22.4% of variants shared between the two methods. In contrast, RNAseq-derived variants displayed unique features of affinity and immunogenicity. We further established that neoantigen candidates identified by RNAseq data significantly increased the number of highly immunogenic neoantigens (confirmed by ELISpot) that would otherwise be overlooked if relying solely on DNAseq data., Discussion: This integrative approach holds great potential for improving the selection of neoantigens for personalized cancer immunotherapy, ultimately leading to enhanced treatment outcomes and improved survival rates for cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nguyen, Tran, Nguyen, Nguyen, Pham, Nguyen, Tran, Nguyen, Tran, Pham, Le, Phan, Giang, Nguyen and Tran.)

Chemical profiling for quality monitoring and evaluation of medicinal plants is gaining attention. This study aims to develop an HPLC method followed by multivariate analysis to obtain HPLC profiles of five specific flavonoids, including rutin (1), hyperin (2), isoquercitrin (3), quercitrin (4), and quercetin (5) from Houttuynia cordata leaves and powder products and assess the quality of H. cordata samples. Eventually, we successfully established HPLC-based flavonoid profiles and quantified the contents of 32 H. cordata fresh leave samples and four powder products. The study also quantified the contents of those five essential flavonoids using an optimized RP-HPLC method. Peak areas of samples were then investigated with principal component analysis (PCA) and hierarchical cluster analysis (HCA) to evaluate the similarity and variance. Principal components in PCA strongly influenced by hyperin and quercetin showed that the samples were clustered into subgroups, demonstrating H. cordata samples' quality. The results of HCA showed the similarity and divided the samples into seven subgroups. In conclusion, we have successfully developed a practical methodology that combined the HPLC-based flavonoid profiling and multivariate analysis for the quantification and quality control of H. cordata samples from fresh leaves and powder products. For further studies, we will consider various environmental factors, including climate and soil factors, to investigate their effects on the flavonoid contents of H. cordata .

Objectives: This study aimed to determine the relationship between oxidative stress (OS) measured by the oxidation-reduction potential (ORP) and the results of semen analysis among men from infertile couples., Methods: This cross-sectional study included 166 men from infertile couples, determined according to the World Health Organization guidelines. The general characteristics, semen analysis, sperm chromatin dispersion assay, and ORP of all subjects were evaluated and analyzed statistically., Results: Among 166 men from infertile couples, individuals with OS had a significantly higher DNA fragmentation index (DFI) than men without OS (22.37% ± 11.67% vs. 17.98% ± 8.98%). The sperm concentration, total sperm count, motility rate, and normal morphology were negatively correlated, while and an abnormal head and neck-tail were positively correlated with ORP. There was also a positive association between the DFI and OS level. The optimal ORP threshold for determining sperm quality was 0.77 mV/10 6 sperm/mL (sensitivity, 50.4%; specificity, 93.5%; positive predictive value, 52.9%; negative predictive value, 32.3%)., Conclusions: Determining the ORP suggests that OS has an adverse effect on the total sperm count, sperm motility, sperm concentration, morphology, vitality, and DNA fragmentation index.