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This paper reviews the current literature to examine what elements of osteopathic medicine can be used in psychiatry. The aim of this study was to use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct a systematic review of studies describing the efficacy of osteopathic manipulative medicine (OMM) in treating psychiatric problems directly and indirectly. The authors searched the databases PubMed, PsycINFO, and CINAHL (Cumulative Index to Nursing and Allied Health Literature), reviewing peer-reviewed articles from 1980 to April 2023. The literature demonstrates that OMM has a positive effect on psychiatric symptoms indirectly when treating certain medical conditions, such as chronic pain, fibromyalgia, and irritable bowel syndrome; however, there are many limitations on these studies, and further research is required prior to making firm recommendations. The evidence is lacking for osteopathic manual medicine being used directly to treat psychiatric conditions. This review demonstrates that in some populations, such as individuals with chronic pain, fibromyalgia, and irritable bowel syndrome, OMM could be considered by an osteopathic psychiatrist as an adjunct treatment. More research should be conducted in this area due to the many limitations in the available studies but current research suggests that the use of OMM by osteopathic psychiatrists could be beneficial for some patient populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Bowes et al.)

In this study, we present a validated Geant4 Monte Carlo simulation model of the Dingo thermal neutron imaging beamline at the Australian Centre for Neutron Scattering. The model, constructed using CAD drawings of the entire beam transport path and shielding structures, is designed to precisely predict the in-beam neutron field at the position at the sample irradiation stage. The model's performance was assessed by comparing simulation results to various experimental measurements, including planar thermal neutron distribution obtained in-beam using gold foil activation and [Formula: see text]B[Formula: see text]C-coated microdosimeters and the out-of-beam neutron spectra measured with Bonner spheres. The simulation results demonstrated that the predicted neutron fluence at the field's centre is within 8.1% and 2.1% of the gold foil and [Formula: see text]B[Formula: see text]C-coated microdosimeter measurements, respectively. The logarithms of the ratios of average simulated to experimental fluences in the thermal (E[Formula: see text] 0.414 eV), epithermal (0.414 eV < E[Formula: see text] 11.7 keV) and fast (E[Formula: see text] 11.7 keV) spectral regions were approximately - 0.03 to + 0.1, - 0.2 to + 0.15, and - 0.4 to + 0.2, respectively. Furthermore, the predicted thermal, epithermal and fast neutron components in-beam at the sample stage position constituted approximately 18%, 64% and 18% of the total neutron fluence., (© 2023. Springer Nature Limited.)

Background: RNA polymerase III-related or 4H leukodystrophy (POLR3-HLD) is an autosomal recessive hypomyelinating leukodystrophy characterized by neurological dysfunction, hypodontia and hypogonadotropic hypogonadism. The disease is caused by biallelic pathogenic variants in POLR3A , POLR3B , POLR1C or POLR3K . Craniofacial abnormalities reminiscent of Treacher Collins syndrome have been originally described in patients with POLR3-HLD caused by biallelic pathogenic variants in POLR1C . To date, no published studies have appraised in detail the craniofacial features of patients with POLR3-HLD. In this work, the specific craniofacial characteristics of patients with POLR3-HLD associated with biallelic pathogenic variants in POLR3A , POLR3B and POLR1C are described., Methods: The craniofacial features of 31 patients with POLR3-HLD were evaluated, and potential genotype-phenotype associations were evaluated., Results: Various craniofacial abnormalities were recognized in this patient cohort, with each individual presenting at least one craniofacial abnormality. The most frequently identified features included a flat midface (61.3%), a smooth philtrum (58.0%) and a pointed chin (51.6%). In patients with POLR3B biallelic variants, a thin upper lip was frequent. Craniofacial anomalies involving the forehead were most commonly associated with biallelic variants in POLR3A and POLR3B while a higher proportion of patients with POLR1C biallelic variants demonstrated bitemporal narrowing., Conclusion: Through this study, we demonstrated that craniofacial abnormalities are common in patients with POLR3-HLD. This report describes in detail the dysmorphic features of POLR3-HLD associated with biallelic variants in POLR3A , POLR3B and POLR1C ., Competing Interests: Competing interests: LTT currently manages sponsored clinical trials at the site level for Ionis Pharmaceuticals (Alexander disease clinical trial 2021–present), Passage Bio (Krabbe disease and GM1 gangliosidosis clinical trials, 2021–present) and Teva Pharmaceuticals (chronic and episodic migraine clinical trials, 2022–present). He also manages a GM1 gangliosidosis natural history study sponsored by the University of Pennsylvania with funding from Passage Bio. NIW is advisor and/or co-investigator for trials in Metachromatic Leukodystrophy (Shire/Takeda, Orchard, Evidera) and other leukodystrophies (Ionis, PassageBio, Vigil Neuro, Sana Biotech), without personal payment. AV receives research grants or in-kind research support without any personal compensation from Takeda, Passage Bio, Sanofi, Affynia, Orchard Therapeutics, Eli Lilly, ISD therapeutics, Illumina, Myrtelle, Homology, Sana and Ionis. She is a site investigator for the Ionis clinical trial in Alexander’s disease, SHP611 in Metachromatic leukodystrophy of Shire/Takeda and Passage Bio gene therapy in Krabbe. She serves on the scientific advisory board of the ELA foundation, the ULF Foundation and the Yaya Foundation Scientific and Clinical Advisory Council. She is a member of the Vanishing White Matter Consortium, the H-ABC Clinical Advisory Board. She receives grant funding from this RDCRN NCATS/NINDS (U01 NS106845, U54TR002823 and R21 NS123477. GB is/was a consultant for Passage Bio Inc (2020–2022) and Ionis (2019). She is/was a site investigator for the Alexander’s disease trial of Ionis (2021–present), Metachromatic leukodystrophy of Shire/Takeda (2020–2021), Krabbe and GM1 gene therapy trials of Passage Bio (2021–present), GM1 natural history study sponsored by the University of Pennsylvania with funding from Passage Bio (2021–present) and Adrenoleukodystrophy/Hematopoietic stem cell transplantation natural history study of Bluebird Bio (2019), a site sub-investigator for the MPS II gene therapy trial of Regenxbio (2021–present) and the MPS II clinical trial of Denali (2022–present). She has received an unrestricted educational grant from Takeda (2021–2022). She serves on the scientific advisory board of the Pelizaeus-Merzbacher Foundation, the Yaya Foundation Scientific and Clinical Advisory Council and is the Chair of the Medical and Scientific Advisory Board of the United Leukodystrophy Foundation. She is a member of the Vanishing White Matter Consortium, the H-ABC Clinical Advisory Board and the Chair of the POLR3-related (4H) Leukodystrophy Consortium. She is on the editorial boards of Neurology Genetics, Frontiers in Neurology – Neurogenetics and Journal of Medical Genetics., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Little is known about the prognostic ability of nCD64 in critically ill patients. This study aimed to assess the prognostic values of nCD64 in adult ICU patients with sepsis., Methods: A prospective cohort study was conducted at the ICU of Cho Ray Hospital in Vietnam between January 2019 to September 2020. All newly admitted 86 septic patients diagnosed based on sepsis-3 criteria were included. An evaluation of nCD64 was performed at admission (T0) and 48 h thereafter (T48). Delta nCD64 (nCD64 T48 - nCD64 T0), %delta nCD64 [(nCD64 T48 - nCD64 T0)/nCD64 T0 x 100%], APACHE II and SOFA scores were calculated and examined. Serum procalcitonin levels and white blood cell counts were documented. Spearman's rank correlation coefficient was used to test the correlation between nCD64 and severity scores. Receiver-operating characteristic (ROC) curve was performed to evaluate the predictive efficacy of the sepsis parameters., Results: Patients with septic shock had significantly higher nCD64 levels than septic patients [3,568 (2,589; 5,999) vs. 1,514 (1,416;2,542) molecules/cell, p  < 0.001]. nCD64 T0 and SOFA scores had a moderately positive linear correlation ( R  = 0.31, p  = 0.004). In the survivor group, nCD64 levels significantly decreased within the first 48 h of admission ( p  < 0.001), while this trend was not statistically significant in the non-survivor group ( p  = 0.866). The area under the ROC curve (AUC) value of %delta nCD64 combined with APACHE II score (0.81) was higher than that of any other parameter alone or in combination with each other., Conclusion: The nCD64 index may serve as a valuable biomarker for predicting the course of sepsis. Monitoring changes in nCD64 during the initial 48 h of admission can aid in predicting the prognosis of septic patients. The use of a combination of the trends of nCD64 index in the first 48 h with APACHE II score would further enhance the predictive accuracy. More studies with longer follow-ups are needed to fully understand the implications of serial trend and kinetics of nCD64 in septic 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 Pham, Nguyen, Duong, Phan, Tran, Trang and Pham.)

Introduction: Ovarian metastatic squamous carcinoma of the cervix is rare, accounting for about 0.4%. This study reports a single case of metastatic recurrent cervical cancer in the ovary., Case Presentation: A 46-year-old patient with a history of cervical cancer T1b2N0M0 underwent a radical hysterectomy, bilateral pelvic lymph node dissection, and ovarian preservation. One year later, the patient was admitted to the hospital because of abdominal pain in the left iliac fossa; the abdominal computed tomography image showed a left ovarian tumour. The patient underwent laparoscopic left oophorectomy. Postoperative histopathology confirmed ovarian squamous cell carcinoma. From this case, we would like to review the literature on epidemiology, diagnosis, treatment, and prognosis., Clinical Discussion: Ovarian preservation during surgery in patients with cervical cancer offers many benefits, but careful patient selection is required. However, it should be selected carefully and closely monitored., Conclusions: Clinicians should be aware of this situation of ovarian metastasis in patients with early cervical cancer undergoing ovarian-conserving surgery., Competing Interests: None., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Studies often rely upon self-report and biological testing methods for measuring illicit drug use, although evidence for their agreement is limited to specific populations and self-report instruments. We aimed to examine comprehensively the evidence for agreement between self-reported and biologically measured illicit drug use among all major illicit drug classes, biological indicators, populations and settings., Methods: We systematically searched peer-reviewed databases (Medline, Embase and PsycINFO) and grey literature. Included studies reported 2 × 2 table counts or agreement estimates comparing self-reported and biologically measured use published up to March 2022. With biological results considered to be the reference standard and use of random-effect regression models, we evaluated pooled estimates for overall agreement (primary outcome), sensitivity, specificity, false omission rates (proportion reporting no use that test positive) and false discovery rates (proportion reporting use that test negative) by drug class, potential consequences attached to self-report (i.e. work, legal or treatment impacts) and time-frame of use. Heterogeneity was assessed by inspecting forest plots., Results: From 7924 studies, we extracted data from 207 eligible studies. Overall agreement ranged from good to excellent (> 0.79). False omission rates were generally low, while false discovery rates varied by setting. Specificity was generally high but sensitivity varied by drug, sample type and setting. Self-report in clinical trials and situations of no consequences was generally reliable. For urine, recent (i.e. past 1-4 days) self-report produced lower sensitivity and false discovery rates than past month. Agreement was higher in studies that informed participants biological testing would occur (diagnostic odds ratio = 2.91, 95% confidence interval = 1.25-6.78). The main source of bias was biological assessments (51% studies)., Conclusions: While there are limitations associated with self-report and biological testing to measure illicit drug use, overall agreement between the two methods is high, suggesting both provide good measures of illicit drug use. Recommended methods of biological testing are more likely to provide reliable measures of recent use if there are problems with self-disclosure., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

In health technology assessment (HTA), population-adjusted indirect comparisons (PAICs) are increasingly considered to adjust for the difference in the target population between studies. We aim to assess the conduct and reporting of PAICs in recent HTA practice, by performing, a methodological systematic review of studies implementing PAICs from PubMed, EMBASE Classic, Embase/Ovid Medline All, and Cochrane databases from January 1, 2010 to Feb 13, 2023. Four independent researchers screened the titles, abstracts, and full-texts of the identified records, then extracted data on methodological and reporting characteristics of 106 eligible articles. Most PAIC analyses (96.9%, n = 157) were conducted by (or received funding from) pharmaceutical companies. Prior to adjustment, 44.5% of analyses (n = 72) (partially) aligned the eligibility criteria of different studies to enhance the similarity of their target populations. In 37.0% of analyses (n = 60), the clinical and methodological heterogeneity across studies were extensively assessed. In 9.3% of analyses (n = 15), the quality (or bias) of individual studies was evaluated. Among 18 analyses using methods that required an outcome model specification, results of the model fitting procedure were adequately reported in three analyses (16.7%). These findings suggest that the conduct and reporting of PAICs are remarkably heterogeneous and suboptimal in current practice. More recommendations and guidelines on PAICs are thus warranted to enhance the quality of these analyses in the future., (© 2023 John Wiley & Sons Ltd.)

Background: Hemostatic dysfunction during extracorporeal membrane oxygenation (ECMO) due to blood-circuit interaction and the consequences of shear stress imposed by flow rates lead to rapid coagulation cascade and thrombus formation in the ECMO system and blood vessels. We aimed to identify the incidence and risk factors for cannula-associated arterial thrombosis (CaAT) post-decannulation., Methods: A retrospective study of patients undergoing arterial cannula removal following ECMO was performed. We evaluated the incidence of CaAT and compared the characteristics, ECMO machine parameters, cannula sizes, number of blood products transfused during ECMO, and daily hemostasis parameters in patients with and without CaAT. Multivariate analysis identified the risk factors for CaAT., Results: Forty-seven patients requiring venoarterial ECMO (VA-ECMO) or hybrid methods were recruited for thrombosis screening. The median Sequential Organ Failure Assessment score was 11 (interquartile range, 8-13). CaAT occurred in 29 patients (61.7%), with thrombosis in the superficial femoral artery accounting for 51.7% of cases. The rate of limb ischemia complications in the CaAT group was 17.2%. Multivariate analysis determined that the ECMO flow rate-body surface area (BSA) ratio (100 ml/min/m2) was an independent factor for CaAT, with an odds ratio of 0.79 (95% confidence interval, 0.66-0.95; P=0.014)., Conclusions: We found that the incidence of CaAT was 61.7% following successful decannulation from VA-ECMO or hybrid modes, and the ECMO flow rate-BSA ratio was an independent risk factor for CaAT. We suggest screening for arterial thrombosis following VA-ECMO, and further research is needed to determine the risks and benefits of such screening.

Cold storage is widely used to extend the postharvest life of most horticultural crops, including tomatoes, but this practice triggers cold stress and leads to the development of undesirable chilling injury (CI) symptoms. The underlying mechanisms of cold stress response and CI development in fruits remain unclear as they are often intermingled with fruit ripening changes. To gain insight into cold responses in fruits, we examined the effect of the potent ethylene signaling inhibitor 1-methylcyclopropene (1-MCP) on fruit ripening, CI occurrence and gene expression in mature green tomatoes during storage at 20°C and 5°C. 1-MCP treatments effectively inhibited ethylene production and peel color changes during storage at 20°C. Storage at 5°C also inhibited both ethylene production and peel color change; during rewarming at 20°C, 1-MCP treatments inhibited peel color change but failed to inhibit ethylene production. Furthermore, fruits stored at 5°C for 14 d developed CI symptoms (surface pitting and decay) during the rewarming period at 20°C regardless of 1-MCP treatment. Subsequent RNA-Seq analysis revealed that cold stress triggers a large-scale transcriptomic adjustment, as noticeably more genes were differentially expressed at 5°C (8,406) than at 20°C (4,814). More importantly, we have found some important divergences among genes involved in fruit ripening (up- or down-regulated at 20°C; inhibited by 1-MCP treatment) and those involved in cold stress (up- or down-regulated at 5°C; unaffected by 1-MCP treatment). Transcriptomic adjustments unique to cold stress response were associated with ribosome biogenesis, NcRNA metabolism, DNA methylation, chromatin formation/remodeling, and alternative splicing events. These data should foster further research into cold stress response mechanisms in fruits with the ultimate aim of improving tolerance to low temperature and reduction of CI symptoms during cold storage., 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 Mitalo, Kang, Tran, Kubo, Ariizumi and Ezura.)

We propose here an electrochemical platform for multi-heavy metal ion detection in water based on MIL-88B(Fe)-NH 2 , an amine-functioned metal-organic framework (MOF) for modifying the surface of a glassy carbon electrode (GCE). Herein, MIL-88B(Fe)-NH 2 with abundant functionalized amine groups can play the role of capture sites for the enrichment of metal ions before electrochemical oxidation sensing. MIL-88B(Fe)-NH 2 was synthesized under optimized conditions through a solvothermal method and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transition electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. MIL-88B(Fe)-NH 2 was then drop-casted on GCE to electrochemically determine the Cd 2+ , Pb 2+ and Cu 2+ ion concentrations by differential pulse voltammetry (DPV). The electrochemical sensor exhibits excellent electrochemical performance toward Cd 2+ , Pb 2+ and Cu 2+ ions in the large linear ranges of 0.025-1.000 μM, 0.3-10.0 μM and 0.6-10.0 μM with limits of detection that are 2.0 × 10 -10 M, 1.92 × 10 -7 M and 3.81 × 10 -7 M, respectively. The fabricated sensor also shows high reliability and good selectivity. This MIL-88B(Fe)-NH 2 application strategy is promising for the evaluation of various heavy metal ions in water., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Hereby, we demonstrate that both systemic and intracerebroventricular (ICV) administrations of SHLP2 protected the male mice from high-fat diet (HFD)-induced obesity and improved insulin sensitivity. In addition, the activation of pro-opiomelanocortin (POMC) neurons by SHLP2 in the arcuate nucleus of the hypothalamus (ARC) is involved in the suppression of food intake and the promotion of thermogenesis. Through high-throughput structural complementation screening, we discovered that SHLP2 binds to and activates chemokine receptor 7 (CXCR7). Taken together, our study not only reveals the therapeutic potential of SHLP2 in metabolic disorders but also provides important mechanistic insights into how it exerts its effects on energy homeostasis., (© 2023. The Author(s).)

Background: Neurodegeneration due to cerebral folate transport deficiency is a rare autosomal recessive disorder caused by biallelic pathogenic variants in FOLR1. Onset typically occurs in late infancy and is characterized by psychomotor regression, epilepsy, and a hypomyelinating leukodystrophy on magnetic resonance imaging. If left untreated, progressive neurodegeneration occurs. However, early treatment with folinic acid has been shown to stabilize or reverse neurological features. Approximately thirty patients have been described worldwide. Here, we report the first two cases with genetically proven cerebral folate transport deficiency from South-Eastern Europe, describe the effect of oral folinic acid therapy on clinical and neuroradiological features and review the literature., Results: Two siblings presented in childhood with clinical and radiological findings consistent with a hypomyelinating leukodystrophy. Exome sequencing revealed a novel homozygous pathogenic variant in FOLR1 (c.465&#95;466delinsTG; p.W156G), confirming the diagnosis of neurodegeneration due to cerebral folate transport deficiency. Folinic acid treatment was promptly initiated in both patients. The younger sibling was treated early in disease course at 2 years of age, and demonstrated complete recovery in clinical and MRI features. The older sibling, who was 8 years of age at the time of diagnosis and treatment, demonstrated partial but substantial improvements., Conclusion: We present the first account in the literature that early treatment initiation with oral folinic acid alone can result in complete neurological recovery of both clinical and radiological abnormalities in neurodegeneration due to cerebral folate deficiency. Moreover, through the report of these patients along with review of the literature, we provide information about the natural history of the disease with comparison of treatment effects at different stages of disease progression. This report also reinforces the importance of universal access to genetic testing to ensure prompt diagnoses for treatable disorders., (© 2023. The Author(s).)

Purpose of Review: Cell-based therapies are an exciting new frontier in managing corneal diseases. The introduction of these novel therapies may provide new alternatives to corneal transplantation and decrease the dependence on donor corneal tissue. These changes have the potential to significantly impact eye banking in the future., Recent Findings: The current article reviews current research involving cell-based therapy for treating corneal disorders, including cultivated limbal stem cell transplantation, limbal mesenchymal stem cells for stromal regeneration, and the use of human-cultivated endothelial cells. We will look at barriers to the development and implementation of these therapies., Summary: As corneal surgery expands to include cell-based therapies; eye banks will need to redefine their role to support the everchanging landscape of corneal surgery and the decreased demand for corneal donor tissue., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Ganoderma multipileum , a wood decay mushroom, was initially discovered and classified in Taiwan through the analysis of its morphology and the internal transcribed spacer (ITS) region of nuclear ribosomal DNA. In this study, we identified a mushroom associated with the dieback of Delonix regia (Boj. ex Hook.) Raf., a woody ornamental street tree in Vietnam, as Ganoderma multipileum . This classification was based on phylogenetic analysis of ITS, RPB2, and TEF1 sequences, as well as morphology assessment and scanning electron microscope observation of basidiospores. The phylogenetic analysis revealed that the specimens collected in Vietnam formed a monophyletic group of Ganoderma multipileum with a high bootstrap value and posterior probability (100%/1.00). Furthermore, the morphological features consistent with laccate Ganoderma , including a thin pileipellis composed of enlarged and bulbous hyphae, and the basidiomes exhibited two different phenotypes. Notably, scanning electron microscopy of the basidiospores revealed ovoid spores with numerous echinules, providing the first documented evidence of this characteristic for Ganoderma multipileum . This research represents the first recorded instance of Ganoderma multipileum in Vietnam associated with the dieback of Delonix regia.

Discovery of pan-antagonist ligands for the melanocortin receptors will help identify the physiological activities controlled by these receptors. The previously reported MC3R/MC4R antagonist Ac-DPhe(pI)-Arg-Nal(2')-Arg-NH 2 was identified herein, for the first time, to possess MC1R and MC5R antagonist activity. Further structure-activity relationship studies probing the second and fourth positions were performed toward the goal of identifying potent melanocortin antagonists. Of the 21 tetrapeptides synthesized, 13 possessed MC1R, MC3R, MC4R, and MC5R antagonist activity. Three tetrapeptides were more than 10-fold selective for the mMC1R, including 8 (LTT1-44, Ac-DPhe(pI)-DArg-Nal(2')-Arg-NH 2 ) that possessed 80 nM mMC1R antagonist potency and was at least 40-fold selective over the mMC3R, mMC4R, and mMC5R. Nine tetrapeptides were selective for the mMC4R, including 14 [SSM1-8, Ac-DPhe(pI)-Arg-Nal(2')-Orn-NH 2 ] with an mMC4R antagonist potency of 1.6 nM. This compound was administered IT into mice, resulting in a dose-dependent increase in the food intake and demonstrating the in vivo utility of this compound series.

In flowering plants, pollination, pollen tube growth, and fertilization are regarded as the first hierarchical processes of producing offspring. However, their independent contributions to fruit set and development remain unclear. In this study, we examined the effect of three different types of pollen, intact pollen (IP), soft X-ray-treated pollen (XP) and dead pollen (DP), on pollen tube growth, fruit development and gene expression in "Micro-Tom" tomato. Normal germination and pollen tube growth were observed in flowers pollinated with IP; pollen tubes started to penetrate the ovary at 9 h after pollination, and full penetration was achieved after 24 h (IP24h), resulting in ~94% fruit set. At earlier time points (3 and 6 h after pollination; IP3h and IP6h, respectively), pollen tubes were still in the style, and no fruit set was observed. Flowers pollinated with XP followed by style removal after 24 h (XP24h) also demonstrated regular pollen tubes and produced parthenocarpic fruits with ~78% fruit set. As expected, DP could not germinate and failed to activate fruit formation. Histological analysis of the ovary at 2 days after anthesis (DAA) revealed that IP and XP comparably increased cell layers and cell size; however, mature fruits derived from XP were significantly smaller than those derived from IP. Furthermore, there was a high correlation between seed number and fruit size in fruit derived from IP, illustrating the crucial role of fertilization in the latter stages of fruit development. RNA-Seq analysis was carried out in ovaries derived from IP6h, IP24h, XP24h and DP24h in comparison with emasculated and unpollinated ovaries (E) at 2 DAA. The results revealed that 65 genes were differentially expressed (DE) in IP6h ovaries; these genes were closely associated with cell cycle dormancy release pathways. Conversely, 5062 and 4383 DE genes were obtained in IP24h and XP24h ovaries, respectively; top enriched terms were mostly associated with cell division and expansion in addition to the 'plant hormone signal transduction' pathway. These findings indicate that full penetration of pollen tubes can initiate fruit set and development independently of fertilization, most likely by activating the expression of genes regulating cell division and expansion., 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 Tran, Sugimoto, Kasozi, Mitalo and Ezura.)

There is an unmet need for effective therapies for treating diseases associated with the intestinal parasite Giardia lamblia. In this study, a library of chemically validated purified natural products and fungal extracts was screened for chemical scaffolds that can inhibit the growth of G. lamblia. The phenotypic screen led to the identification of several previously unreported classes of natural product inhibitors that block the growth of G. lamblia. Hits from phenotypic screens of these naturally derived compounds are likely to possess a variety of mechanisms of action not associated with clinically used nitroimidazole and thiazolide compounds. They may therefore be effective against current drug-resistant parasite strains. IMPORTANCE There is a direct link between widespread prevalence of clinical giardiasis and poverty. This may be one of the reasons why giardiasis is a significant contributor to diarrheal morbidity, stunting, and death of children in resource-limited communities around the world. FDA-approved treatments for giardiasis include metronidazole, related nitroimidazole drugs, and albendazole. However, a substantial number of clinical infections are resistant to these treatments. The depth of the challenge is partly exacerbated by a lack of investment in the discovery and development of novel agents for treatment of giardiasis. Applicable interventions must include new drug development strategies that will result in the identification of effective therapeutics, particularly those that are inexpensive and can be quickly advanced to clinical uses, such as products from nature. This study identified novel chemical scaffolds from fungi that can form the basis of future medicinal chemistry optimization of novel antigiardial agents., Competing Interests: The authors declare no conflict of interest.

Two styryl-lactone derivatives (1 and 2) were isolated from the aerial parts of Goniothalamus elegans . Compound 1 is a newly discovered natural product, and compound 2 is reported in this plant for the first time. The absolute configuration of 1 was determined based on the ECD spectrum. The two styryl-lactone derivatives were tested for cytotoxicity activity against five cancer cell lines and human embryonic kidney cells. The newly discovered compound demonstrated potent cytotoxicity, with IC 50 values ranging from 2.05 to 3.96 μM. Computational methods were also applied to investigate the mechanism of the cytotoxic activity of the two compounds. Density functional theory and molecular mechanisms were used to assess the interaction between protein targets to compound 1 and 2, respectively, through the EGF/EGFR signaling pathway. The results indicated that 1 showed a strong binding affinity for two proteins EGFR and HER-2. Finally, ADMET predictions were used to validate the pharmacokinetics and toxicity of these compounds. The results showed that both compounds are likely to be absorbed in the gastrointestinal tract and penetrate the blood-brain barrier. Based on our findings, these compounds may have potential for further studies to be developed into active ingredients for cancer treatment., Competing Interests: There is no conflict to declare., (This journal is © The Royal Society of Chemistry.)

International student mobility has traditionally witnessed a global South-North pattern. In recent years, a shift has occurred as the appeal of alternative geographies waxes, with Malaysia being an exemplar of inbound student mobility destination. To facilitate a deep probe of the under-researched global South-South student mobility, this study utilized a qualitative method to delve into 10 Chinese doctoral students' emic perceptions of their sojourn in Malaysia. Guided by a theoretical framework incorporating decolonization and recolonization, this study unpacks how these sociohistorical forces penetrate into and shape the students' preparation and navigation of a doctoral sojourn. Findings of the study reveal that while taking advantage of the Southern niche to yield commensurate benefits, thereby delegitimizing the Western supremacy, the students' make-do mentality and self-subjugating resistance inadvertently reinforce the Western dominance. Besides, these macro effects generate interlocking and conflicting affective consequences, instilling simultaneously positivity and inclusivity, inferiority, and anxiety. Altogether, decolonization and recolonization are concretely registered at the emotional level and bear a broader social significance. This article concludes with an alert and a call to address covert yet compelling inequalities in international student mobility., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Transitions of care (ToC) aim to provide continuity while preventing loss of information that may result in poor outcomes such as hospital readmission. Readmissions not only burden patients, they also increase costs. Given the high prevalence of coronary artery diseases (CAD) in the United States (US), patients with CAD often make up a significant portion of hospital readmissions. Objective: To conduct a systematic review evaluating the impact of pharmacist-driven ToC interventions on post-hospital outcomes for patients with CAD. Methods: MEDLINE, Scopus, and CINAHL were searched from database inception through 03/2020 using key words for CAD and pharmacists. Studies were included if they: (1) identified adults with CAD at US hospitals, (2) evaluated pharmacist-driven ToC interventions, and (3) assessed post-discharge outcomes. Outcomes were summarized qualitatively. Results: Of the 1612 citations identified, 11 met criteria for inclusion. Pharmacist-driven ToC interventions were multifaceted and frequently included medication reconciliation, medication counseling, post-discharge follow-up and initiatives to improve medication adherence. Hospital readmission and emergency room visits were numerically lower among patients receiving vs not receiving pharmacist-driven interventions, with statistically significant differences observed in 1 study. Secondary prevention measures and adherence tended to be more favorable in the pharmacist-driven intervention groups. Conclusion: Eleven studies of multifaceted, ToC interventions led by pharmacists were identified. Readmissions were numerically lower and secondary prevention measures and adherence were more favorable among patients receiving pharmacist-driven interventions. However, sufficiently powered studies are still required to confirm these benefits.

Background: People who inject drugs are exposed to various and changing risk environments and are at risk of multiple harms related to injecting drug use (IDU). We aimed to undertake a global systematic review of the prevalence of IDU, key IDU-related harms (including HIV, hepatitis C virus [HCV], and hepatitis B virus [HBV] infection and overdose), and key sociodemographic characteristics and risk exposures for people who inject drugs., Methods: We systematically searched for data published between Jan 1, 2017, and March 31, 2022, in databases of peer-reviewed literature (MEDLINE, Embase, and PsycINFO) and grey literature as well as various agency or organisational websites, and disseminated data requests to international experts and agencies. We searched for data on the prevalence, characteristics, and risks of people who inject drugs, including gender, age, sexuality, drug-use patterns, HIV, HCV, and HBV infections, non-fatal overdose, depression, anxiety, and injecting-related disease. Additional data were extracted from studies identified in our previous review. Meta-analyses were used to pool the data where multiple estimates were available for a country. We present country, regional, and global estimates for each variable examined., Findings: We screened 40 427 reports published between 2017 and 2022, and the 871 eligible reports identified were added to the 1147 documents from the previous review. Evidence of IDU was documented in 190 of 207 countries and territories, and 14·8 million people (95% uncertainty interval [UI] 10·0-21·7) aged 15-64 years globally were estimated to inject drugs. Existing evidence suggests that there might be 2·8 million (95% UI 2·4-3·2) women and 12·1 million (95% UI 11·0-13·3) men who inject drugs globally, and that 0·4% (95% CI 0·3-1·3) of people who inject drugs identify as transgender. The amount of available data on key health and social risks among people who inject drugs varied widely across countries and regions. We estimated that 24·8% (95% CI 19·5-31·6) of people who inject drugs globally had experienced recent homelessness or unstable housing, 58·4% (95% CI 52·0-64·8) had a lifetime history of incarceration, and 14·9% (95% CI 8·1-24·3) had recently engaged in sex work, with substantial geographical variation. Injecting and sexual risk behaviour varied considerably geographically, as did risks of harms. Globally, we estimated that 15·2% (95% CI 10·3-20·9) of people who inject drugs are living with HIV, 38·8% (95% CI 31·4-46·9) have current HCV infection, 18·5% (95% CI 13·9-24·1) have recently overdosed, and 31·7% (95% CI 23·6-40·5) have had a recent skin or soft tissue infection., Interpretation: IDU is being identified in a growing number of countries and territories that comprise more than 99% of the global population. IDU-related health harms are common, and people who inject drugs continue to be exposed to multiple adverse risk environments. However, quantification of many of these exposure and harms is inadequate and must be improved to allow for better targeting of harm-reduction interventions for these risks., Funding: Australian National Health and Medical Research Council., Competing Interests: Declaration of interests In the past 3 years, LD and MF have received investigator-initiated untied educational grants for studies of opioid medications in Australia from Indivior and Seqirus. AP has received investigator-initiated untied educational grants from Seqirus. JG is a consultant or advisor and has received research grants from AbbVie, bioLytical, Camurus, Cepheid, Gilead Sciences, Hologic, Indivior, and Merck or MSD. GJD has received research grants from AbbVie, Gilead Sciences, and Merck or MSD. EBC has received funding from the Canadian Network on Hepatitis C. These companies and organisations had no knowledge of or role in the design, conduct, interpretation, or publication of these findings. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Little is known about the role of neutrophil CD64 (nCD64) in detecting sepsis early in Asian populations. We examined the cut-off and predictive values of nCD64 for diagnosing sepsis in Vietnamese intensive care units (ICU) patients. A cross-sectional study was conducted at the ICU of Cho Ray Hospital between January 2019 and April 2020. All 104 newly admitted patients were included. Sensitivity (Sens), specificity (Spec), positive and negative predictive values (PPV and NPV), and receiver operating characteristic (ROC) curves were calculated to compare the diagnostic values of nCD64 with those of procalcitonin (PCT) and white blood cell (WBC) for sepsis. The median nCD64 value in sepsis patients was statistically higher than that of non-sepsis patients (3106 [1970-5200] vs. 745 [458-906] molecules/cell, p < 0.001). ROC analysis found that the AUC value of nCD64 was 0.92, which was higher than that of PCT (0.872), WBC (0.637), and nCD64 combined, with WBC (0.906) and nCD64 combined with WBC and PCT (0.919), but lower than that of nCD64 combined with PCT (0.924). With an AUC value of 0.92, the nCD64 index of 1311 molecules/cell-detected sepsis with 89.9% Sens, 85.7% Spec, 92.5% PPV, and 81.1% NPV. nCD64 can be a useful marker for early sepsis diagnosis in ICU patients. nCD64 combined with PCT may improve the diagnostic accuracy.

Introduction: Rare neurodevelopmental disorders, including inherited white matter disorders or leukodystrophies, often present a diagnostic challenge on a genetic level given the large number of causal genes associated with a range of disease subtypes. This study aims to demonstrate the challenges and lessons learned in the genetic investigations of leukodystrophies through presentation of a series of cases solved using exome or genome sequencing., Methods: Each of the six patients had a leukodystrophy associated with hypomyelination or delayed myelination on MRI, and inconclusive clinical diagnostic genetic testing results. We performed next generation sequencing (case-based exome or genome sequencing) to further investigate the genetic cause of disease., Results: Following different lines of investigation, molecular diagnoses were obtained for each case, with patients harboring pathogenic variants in a range of genes including TMEM106B, GJA1, AGA, POLR3A , and TUBB4A . We describe the lessons learned in reaching the genetic diagnosis, including the importance of (a) utilizing proper multi-gene panels in clinical testing, (b) assessing the reliability of biochemical assays in supporting diagnoses, and (c) understanding the limitations of exome sequencing methods in regard to CNV detection and region coverage in GC-rich areas., Discussion: This study illustrates the importance of applying a collaborative diagnostic approach by combining detailed phenotyping data and metabolic results from the clinical environment with advanced next generation sequencing analysis techniques from the research environment to increase the diagnostic yield in patients with genetically unresolved leukodystrophies., Competing Interests: GB is a consultant for Passage Bio Inc. (2020-2022) and Ionis (2019). She is a site investigator for the Alexander's disease trial of Ionis Pharmaceuticals (2021-present), Metachromatic leukodystrophy of Shire/Takeda (2020-2021), Krabbe and GM1 gangliosidosis gene therapy trials of Passage Bio (2021-present), GM1 gangliosidosis natural history study sponsored by the University of Pennsylvania with funding from Passage Bio (2021-present) and Adrenoleukodystrophy/Hematopoietic stem cell transplantation natural history study of Bluebird Bio (2019), a site sub-investigator for the MPS II gene therapy trial of Regenxbio (2021-present) and the MPS II clinical trial of Denali (2022-present). She has received unrestricted educational grants from Takeda (2021-2022). She serves on the scientific advisory board of the Pelizaeus-Merzbacher Foundation, the Yaya Foundation Scientific and Clinical Advisory Council and is the Chair of the Medical and Scientific Advisory Board of the United Leukodystrophy Foundation. She is a member of the Vanishing White Matter Consortium, the H-ABC Clinical Advisory Board and the Chair of the POLR3-related (4H) Leukodystrophy Consortium. She is on the editorial boards of Neurology Genetics, Frontiers in Neurology – Neurogenetics, and Journal of Medical Genetics. LT currently manages sponsored clinical trials at the site level for Ionis Pharmaceuticals (Alexander disease clinical trial, 2021-present), Passage Bio (Krabbe disease and GM1 gangliosidosis clinical trials, 2021-present), and Teva Pharmaceuticals (chronic and episodic migraine clinical trials, 2022-present). He also manages a GM1 gangliosidosis natural history study sponsored by the University of Pennsylvania with funding from Passage Bio. MS has received honorarium from Takeda for speaking presentations. WK receives research support from Alexion, Bluebird Bio and MedDay, and is consultant and co-investigator for AMN disease trial of Minoryx. He also serves on scientific advisory boards of the United Leukodystrophy Foundation, the European Leukodystrophy Association and the Myelin Project Germany. The remaining 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 Perrier, Guerrero, Tran, Michell-Robinson, Legault, Brais, Sylvain, Dorman, Demos, Köhler, Pastinen, Thiffault and Bernard.)

Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. We sought to gain a better understanding of their experience with the public health care system in Quebec, Canada, to obtain suggestions for improving their services, and to identify modifiable factors to improve their quality of life. We conducted interviews with 13 parents. Data was analyzed thematically. Five themes were identified: challenges of the diagnostic odyssey, limited access to services, excessive parental responsibilities, positive relationships with health care professionals as a facilitator of care, and benefits of a specialized leukodystrophy clinic. Parents felt like waiting for the diagnosis was extremely stressful, and they expressed their need for transparency during this period. They identified multiple gaps and barriers in the health care system, which burdened them with many responsibilities. Parents emphasized the importance of a positive relationship with their child's health care professionals. They also felt grateful for being followed at a specialized clinic as it improved the quality of care received.

Background: In the context of COVID-19 pandemic, eHealth Literacy is important and essential for healthcare workers, especially medical students; eHealth Literacy Scale (eHEALS) was developed to measured eHealth literacy of individuals, with higher eHEALS scores indicated greater ehealth literacy., Objectives: The study evaluates the reliability and validity of Vietnamese version of eHEALS and analyzed some factors affecting on eHEALS score among Hanoi Medical University students in Vietnam., Methods: A cross-sectional study design was adopted, and data were elicited from 494 medical students. Exploratory Factor Analysis (EFA); Cronbach's alpha and correlation coefficients; split-half assessment; Poisson regression analysis were applied., Results: The total score of our subjects in the eHEALS was 30.34 ± 4.57. The results from Bartlett's test, Kaiser-Meyer-Olkin (KMO) test, calculated Cronbach's alpha coefficient and test-retest reliability were high. Poisson regression identified that eHEALS scores of participants was significantly associated with device, ongoing medical condition and trustworthiness of health information source (p < 0.05)., Discussion: Our study helps researchers who conduct studies in eHealth develop optimal applied and intervention researches in subjects with medical knowledge. Additional studies need to be required with numerous different groups of people in Vietnam., Conclusion: The Vietnamese version of eHEALS is a reliable and valid measure. Device, medical condition and trustworthiness of health information source are factors affecting on eHEALS score of students in Hanoi Medical University., 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 © 2022 Elsevier B.V. All rights reserved.)

Background: Radiofrequency catheter ablation is the preferred treatment choice for ventricular arrhythmias (VAs) originating from right ventricular outflow tract (RVOT) in symptomatic patients and is usually performed under fluoroscopy guidance. Zero-fluoroscopy (ZF) ablations using 3D mapping system applied for treatment of various types of arrhythmias are trending and practiced in many centers around the world, but rarely done in Vietnam. The objective of this study was to evaluate the efficacy and safety of zero-fluoroscopy ablation of RVOT VAs, compared with fluoroscopy-guided ablation without a 3D electroanatomic mapping (EAM) system., Methods and Results: We conducted a nonrandomized, prospective single-center study including 114 patients with RVOT VAs that had electrocardiographic features of typical left bundle branch block, inferior axis QRS morphology, and a precordial transition ≥ V 3 , from May 2020 to July 2022. The patients were assigned (without randomization) to two different approaches of either zero-fluoroscopy ablation under the guidance of the Ensite system (ZF group) or fluoroscopy-guided ablation without a 3D EAM (fluoroscopy group) in a 1:1 ratio. After a follow-up time of 5.0 ± 4.9 months and 6.9 ± 9.3 months in the ZF and fluoroscopy groups, respectively, the results showed a higher success rate in the fluoroscopy group than in the complete ZF group (87.3% vs 86.8%), although the difference was not statistically significant. No major complication was noted in both the groups., Conclusion: ZF ablation for RVOT VAs can be done safely and effectively using the 3D electroanatomic mapping system. The results of ZF approach are comparable to that of the fluoroscopy-guided approach without a 3D EAM system., Competing Interests: No author has conflict of interest., (© 2023 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Academic probation at universities has become a matter of pressing concern in recent years, as many students face severe consequences of academic probation. We carried out research to find solutions to decrease the situation mentioned above. Our research used the power of massive data sources from the education sector and the modernity of machine learning techniques to build an academic warning system. Our system is based on academic performance that directly reflects students' academic probation status at the university. Through the research process, we provided a dataset that has been extracted and developed from raw data sources, including a wealth of information about students, subjects, and scores. We build a dataset with many features that are extremely useful in predicting students' academic warning status via feature generation techniques and feature selection strategies. Remarkably, the dataset contributed is flexible and scalable because we provided detailed calculation formulas that its materials are found in any university or college in Vietnam. That allows any university to reuse or reconstruct another similar dataset based on their raw academic database. Moreover, we variously combined data, unbalanced data handling techniques, model selection techniques, and research to propose suitable machine learning algorithms to build the best possible warning system. As a result, a two-stage academic performance warning system for higher education was proposed, with the F2-score measure of more than 74% at the beginning of the semester using the algorithm Support Vector Machine and more than 92% before the final examination using the algorithm LightGBM., Competing Interests: Conflicts of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Cancer is currently a global health challenge, characterized by dysfunction of organs due to the uncontrolled growth of cells exponentially. The therapies used to treat cancer in patients so far are widely used. However, there are also some problems, such as the high cost of surgery and chemotherapy. Thus, there are many barriers to care for patients with cancer, especially in low and middle-income countries. In addition, the many risks and adverse effects of radiation treatment. Therefore, to reduce mortality in patients with the disease, we need a newer therapy with more targeted treatment, fewer side effects, and cheaper cost. The application of bacteria in cancer treatment was first developed in 1983. Currently, this therapy is attracting the attention of scientists due to its great potential in cancer treatment. This chapter discusses the successful research on the bacteriophage for cancer, the mechanism and its potential. In addition, some types of bacteria that are most important for cancer treatment and limitations on the widespread application of this therapy were also mentioned. Reviewing all the researches on bacteriotherapy in cancer are essential to increase the knowledge in this area and make this therapy more optimal in the future., (Copyright © 2023. Published by Elsevier Inc.)

The Squaretail mullet Ellochelon vaigiensis is widely found from marine to brackish and freshwater, including the Vietnamese Mekong Delta (VMD). Data on the length-weight relationships (LWRs), growth pattern, and condition factor (CF) play an essential role in fisheries assessment but are limited to E. vaigiensis - a commercial fish in VMD. To better understand the growth pattern of this fish, the study collected samples at four sites, including Thanh Phu, Ben Tre (BT); Duyen Hai, Tra Vinh (TV); Tran De, Soc Trang (ST); and Dong Hai, Bac Lieu (BL). Each month, fish samples were collected using bottom nets at each sampling site during high tide in both the dry season (January to May 2021) and the wet season (November to December 2020 and June to October 2021). This study qualified whether LWRs, growth pattern, and CF of E. vaigiensis vary with sexual, intraspecific, and spatiotemporal variables. The analysis results of 942 specimens showed that fish total length (TL = 17.86 ± 0.13 cm) and weight (W = 54.29 ± 1.05 g) changed with sex, season, month and site. The W could be appraised from a given TL due to high coefficients ( r 2 ) of LWRs that were regulated by fish size and season but not sex. The species showed negative allometry as its slope value of LWRs (b = 2.34 ± 0.30) was <3. The growth pattern did not change with sex and site but varied fish size, season, and months ranging from negative allometry to isometry. The CF of females (1.08 ± 0.01) was higher than males (0.99 ± 0.01). Albeit this fish showed spatiotemporal variation in CF, ranging from 0.81 ± 0.01 to 1.25 ± 0.02, the CF (1.02 ± 0.01) was significantly higher than the one threshold, indicating that E. vaigiensis lived a favorable condition. Research results show that this fish species has a dominant growth pattern in terms of length ( b < 3) and is well adapted to the environment ( CF ≈ 1). These data have an important role in suggesting the future aquaculture of this fish., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

This study delves into emic perceptions of Chinese international doctoral students' navigation of a disrupted study trajectory during the 2019 coronavirus pandemic. Drawing on semi-structured interviews with students and the conceptual framework of bioecological systems theory and needs-response agency, the article reveals a nuanced picture of how activities, relations and roles nested in a PhD study trajectory are impacted by and respond to the crisis. Specifically, the pandemic has instigated a ripple effect upon PhD study that is embedded within a complex system of person-environment factors in the microsystem, mesosystem, exosystem and macrosystem. Confronting these changes and challenges, the students enact needs-response agency to cope with these impacts so as to restore stability. The study concludes with some practical implications for related stakeholders in the bioecological system to generate conditions and support for students to harness possibilities for growth amidst and beyond the health crisis., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 European Association for International Education.)

Objective. Ion radiotherapy with protons or carbon ions is one of the most advanced clinical methods for cancer treatment. To further improve the local tumor control, ion radiotherapy using multiple ion species has been investigated. Due to complexity of dose distributions delivered by multi-ion therapy in a tumor, a validation strategy for the planned treatment efficacy must be established that can be potentially used in the quality assurance (QA) protocol for the multi-ion treatment plans. In previous work, we demonstrated that the microdosimetric approach using the silicon on insulator (SOI) microdosimeter is practical for validating cell surviving fraction (SF) of MIA PaCa-2 cells in the independent fields of helium, carbon, oxygen, and neon ion beams. Approach. This paper extends the previous study, and we demonstrate a microdosimetry based approach as a pilot study to build the QA protocol in the multi-ion therapy predicting the cell SF along the spread-out Bragg peak obtained by combined irradiations of He+O and C+Ne ions. Across the study, the SOI microdosimeter system MicroPlus was used for measurement of the lineal energy in individual ion fields followed by deriving the lineal energy of combined ion fields delivered by a pencil beam scanning system at HIMAC. Main results. The predicted cell SF based on derived lineal energy and dose in the combined fields was in good agreement with the planned cell SF by our in-house treatment planning system. Significance. The presented results indicated the potential benefit of the SOI microdosimeter system MicroPlus as the QA system in the multi-ion radiotherapy., (© 2022 Institute of Physics and Engineering in Medicine.)

Background: Currently, intramedullary nailing for tibial fractures has very good postoperative treatment results. Combining the advantages of traditional medicine and modern medicine is a comprehensive treatment method that brings the best benefits to the patient., Methods: The study method was a controlled clinical trial. The study included 60 patients with a definitive diagnosis of tibial fracture who underwent intramedullary nailing surgery. These patients were divided into 2 groups: with and without electroacupuncture treatment., Results: Electro-acupuncture had a significant analgesic effect in 24-48 h after surgery: After 24 h or electro-acupuncture, the pain difference in the study group and the control groups was 3.03 ± 1.25 and 2.46 ± 1.33, respectively (p < 0.05). The VAS score difference between day 1 and day 2 in the study group and the control group was 0.61 ± 0.71 and 0.59 ± 0.67, respectively (p < 0.05). At 48 h postoperatively, the circumference of the calf on the fractured side in the study group and the control group was 36.1 ± 2.1 and 37.3 ± 2.2 cm, respectively (p < 0.05). At 72 h postoperatively, the circumference of the calf in the study group and the control group was 35.9 ± 2.6 and 37.6 ± 2.8 cm, respectively (p < 0.05). The effect of electro-acupuncture on bone healing did not differ between the study group and the control group (p > 0.05). During 7 days of using the treatment regimen, there were 3.3 % of patients with dizziness, 3.3 % of patients with vomiting/nausea, 3.3 % of patients with bleeding at the injection site. There was no difference in blood pressure, pulse rate, hematological indexes and biochemical indexes of patients before and after using the treatment regimen., Conclusion: Electro-acupuncture has a significant analgesic effect 24 h-48 h after surgery. The effect of electroacupuncture on bone healing was not different between the two groups. Electroacupuncture is a safe, effective method with few side effects., Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships with anyone that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cockayne syndrome is a rare inherited DNA repair multisystemic disorder. Here, we aim to raise awareness of the phenotypic resemblances between Cockayne syndrome and the neurodevelopmental disorder caused by pathogenic variants in MORC2, a gene also involved in DNA repair. Using exome sequencing, we identified a de novo pathogenic variant in MORC2 in our patient. Our patient's phenotype was characterized by multiple features evocative of Cockayne syndrome. Based on our patient's phenotype, in addition to the phenotypic description of patients with pathogenic variants in MORC2 reported in the literature, we suggest that pathogenic variants in this gene are associated with a Cockayne-like phenotype., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Neuronal primary cilia are known to be a required organelle for energy balance and leptin action. However, whether primary cilia directly mediate adaptive responses during starvation is yet unknown. Therefore, we investigated the counterregulatory roles of primary cilia, and their related leptin action in energy-depleted condition., Method: We generated leptin receptor (LepR) neuron-specific primary cilia knockout (Ift88 KO LepR ) mice. Leptin-mediated electrophysiological properties of the neurons in fasting condition were assessed using patch-clamp technique. Adaptive responses and neuroendocrine reflexes were measured by monitoring counterregulatory hormones., Results: In fasting state, the leptin-induced neuronal excitability and leptin homeostasis were impaired in Ift88 KO LepR . In addition, the Ift88 KO LepR exhibited aberrant fasting responses including lesser body weight loss, decreased energy expenditure, and lower heat generation compared to wild-type littermates. Furthermore, the primary cilia in LepR neurons are necessary for counterregulatory responses and leptin-mediated neuroendocrine adaptation to starvation., Conclusion: Our results demonstrated that the neuronal primary cilia are crucial neuronal components mediating the adaptive counterregulatory responses to starvation., Competing Interests: Declaration of competing interest All authors declare no competing financial or other interests in relation to this study., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Opioid use disorder (OUD) and mental disorders are major public health issues and comorbidity is common. Among people with OUD, comorbid mental disorders are associated with poorer health outcomes. To our knowledge, this is the first systematic review and meta-analysis to estimate prevalence of specific mental disorders among people with OUD., Methods: We searched Embase, MEDLINE, and PsycInfo from 1990 to 2021 for observational studies of depression, anxiety, post-traumatic stress disorder (PTSD), bipolar, personality, and other pre-specified mental disorders among people with OUD. We pooled current and lifetime estimates of each disorder using random-effects meta-analyses with 95% Confidence Intervals (CIs). Meta-regressions and stratified analyses were used to assess heterogeneity of prevalence estimates by methodological factors and sample characteristics., Findings: Of the 36,971 publications identified, we included data from 345 studies and 104,135 people with OUD in at least one pooled estimate. Among people with OUD, the prevalence of current depression was 36.1% (95%CI 32.4-39.7%), anxiety was 29.1% (95%CI 24.0-33.3%), attention-deficit/hyperactivity disorder was 20.9% (95%CI 15.7-26.2%), PTSD was 18.1% (95%CI 15.4-20.9%), and bipolar disorder was 8.7% (95%CI 6.7-10.7%). Lifetime prevalence of anti-social personality disorder was 33.6% (95%CI 29.1-38.0%) and borderline personality disorder was 18.2% (95% CI 13.4-23.1%). Sample characteristics and methodological factors, including sex, were associated with variance of multiple prevalence estimates., Interpretation: Our findings emphasise the need for access to mental disorder treatment among people with OUD. Specific mental disorder estimates may inform clinical guidelines, treatment services, and future research for people with OUD, including subpopulations with distinct treatment needs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Charting the emergence of eukaryotic traits is important for understanding the characteristics of organisms that contributed to eukaryogenesis. Asgard archaea and eukaryotes are the only organisms known to possess regulated actin cytoskeletons. Here, we determined that gelsolins (2DGels) from Lokiarchaeota (Loki) and Heimdallarchaeota (Heim) are capable of regulating eukaryotic actin dynamics in vitro and when expressed in eukaryotic cells. The actin filament severing and capping, and actin monomer sequestering, functionalities of 2DGels are strictly calcium controlled. We determined the X-ray structures of Heim and Loki 2DGels bound actin monomers. Each structure possesses common and distinct calcium-binding sites. Loki2DGel has an unusual WH2-like motif (LVDV) between its two gelsolin domains, in which the aspartic acid coordinates a calcium ion at the interface with actin. We conclude that the calcium-regulated actin cytoskeleton predates eukaryogenesis and emerged in the predecessors of the last common ancestor of Loki, Heim and Thorarchaeota., (© 2022. The Author(s).)

Background Relatively greater increases in hypertension prevalence among US rural residents may contribute to geographic disparities in recurrent stroke. There is limited US information on poststroke antihypertensive medication use by rural/urban residence. We assessed antihypertensive use and lifestyle characteristics for US rural compared with urban stroke survivors and residence-based trends in use between 2005 and 2019. Methods and Results US stroke survivors with hypertension were identified in the 2005 to 2019 national Behavioral Risk Factor Surveillance System surveys. We ascertained the survey-weighted prevalence of reported antihypertensive use and lifestyle characteristics (ie, physical activity, diabetes, cholesterol, body mass index, and smoking) among respondents with hypertension in odd years over this period by rural/urban residence. Separate trend analyses were used to detect changes in use over time. Survey-weighted logistic regression was used to calculate unadjusted and adjusted (sociodemographic and lifestyle factors) odds ratios for antihypertensive use by year. Our study included 82 175 individuals (36.4% rural residents). Lifestyle characteristics were similar between rural and urban residents except for higher smoking prevalence among rural residents. Antihypertensive use was similar between rural and urban stroke survivors in unadjusted and adjusted analyses (>90% in both populations). Trend analyses showed a small but significant increase in antihypertensive use over time among urban ( P =0.033) but not rural stroke survivors ( P =0.587). Conclusions Our findings indicate that poststroke antihypertensive use is comparable in rural and urban residents with a reported history of hypertension, but additional work is merited to identify reasons for a trend for increased use of these drugs among urban residents.

Background: Major host countries of international students such as Australia, Canada, New Zealand, the UK, and the US have introduced post-study work rights as a strategic policy to both enhance their destination attraction and support international students' post-graduation work experiences. While this policy is generally welcomed by both host institutions and international students, little is known about the support mechanism for the growing cohort of international student graduates who stay in their countries of study on temporary graduate visas, especially in relation to major concerns such as post-graduation work, visa application, and migration pathways. Objective: This article fills an important gap in the existing literature. It aims to assess the role of universities in supporting their international alumni on temporary visas. Research Design: It is derived from a study that includes 50 interviews with university staff, agents, and international graduates. It uses positioning theory as a conceptual framework. Results: The findings of the study raise concerns about the scope of university advice. It reports loopholes which legitimize the practices of migration agents to the conditions that enable them to exercise their exclusive rights in providing work-migration nexus advice to international students and graduates, making this cohort vulnerable to exploitation of unethical agents. The study provides the evidence base to develop recommendations for related stakeholders in improving the post-graduation experiences of international student graduates who remain in the host countries on temporary visas.

Information about the occurrence of polybrominated diphenyl ethers (PBDEs) in indoor dusts from various industrial sectors in Southeast Asia is still scarce. In this study, concentrations and congener-specific profiles of PBDEs were determined in indoor dusts from industrial factories, offices, and houses in northern Vietnam. Levels of Σ8PBDEs were higher in the office dusts (median 270; range 230-300 ng/g) and factory dusts (170; 89-510 ng/g) than in the house dusts (61; 25-140 ng/g). BDE-209 was the most dominant congener, accounting for 27-98% (average 62%) of Σ8PBDEs, suggesting the abundance of products treated with deca-BDE mixtures. Residential, commercial, and industrial activities in the studied locations of this survey were not significant sources of PBDEs as compared to those of informal waste processing activities in Vietnam. Relatively low PBDE concentrations detected in our dust samples partially reflect effectiveness of the global PBDE phase-out. Human exposure and health risk associated with dust-bound PBDEs were estimated, indicating acceptable levels of risk (i.e., neurobehavioral effects). The contributions of workplace dusts in total daily intake doses of PBDEs via dust ingestion were more important for local workers in informal recycling areas than factory workers and general population, raising the need of appropriate labor protection measures., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Pseudomonas aeruginosa is a non-fermentative Gram-negative opportunistic pathogen, frequently encountered in difficult-to-treat hospital-acquired infections and also wastewaters. The natural resistance of this pathogen, together with the frequent occurrence of multidrug-resistant strains, make current antibiotic therapy inefficient in treating P. aeruginosa infections. Antibiotic therapy creates a huge pressure to select resistant strains in clinical settings but also in the environment, since high amounts of antibiotics are released in waters and soil. Essential oils (EOs) and plant-derived compounds are efficient, ecologic, and sustainable alternatives in the management of various diseases, including infections. In this study, we evaluated the antibacterial effects of four commercial essential oils, namely, tea tree, thyme, sage, and eucalyptus, on 36 P. aeruginosa strains isolated from hospital infections and wastewaters. Bacterial strains were characterized in terms of virulence and antimicrobial resistance. The results show that most strains expressed soluble pore toxin virulence factors such as lecithinase (89-100%) and lipase (72-86%). All P. aeruginosa strains were positive for alginate encoding gene and 94.44% for protease IV; most of the strains were exotoxin producers (i.e., 80.56% for the ExoS gene, 77.78% for the ExoT gene, while the ExoU gene was present in 38.98% of the strains). Phospholipase-encoding genes (plc) were identified in 91.67/86.11% of the cases (plcH/plcN genes). A high antibiotic resistance level was identified, most of the strains being resistant to cabapenems and cephalosporins. Cabapenem resistance was higher in hospital and hospital wastewater strains (55.56-100%) as compared to those in urban wastewater. The most frequently encountered encoding genes were for extended spectrum β-lactamases (ESBLs), namely, bla CTX-M (83.33% of the strains), bla SHV (80.56%), bla GES (52.78%), and bla VEB (13.89%), followed by carbapenemase-encoding genes ( bla VIM , 8.33%). Statistical comparison of the EOs' antimicrobial results showed that thyme gave the lowest minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentrations (MBEC) in P. aeruginosa -resistant isolates, making this EO a competitive candidate for the development of efficient and ecologic antimicrobial alternatives.

This article examines how graduate employability is viewed by employers in six economically disadvantaged mountainous provinces in Vietnam. The study reported in this article identified continuous self-learning, resilience, adaptability, devotion and empathy for the local people and local community to be among the main employability attributes expected of graduates in regional Vietnam. The findings of the study raise the importance of context situatedness in looking at employability and show how employability is characterised by the local structural conditions, demographic features and socio-cultural norms. The study provides significant implications for career guidance and graduate employability development, especially in relation to regional areas., (© The Author(s) 2022.)

A phenotypic screen of the ReFRAME compound library was performed to identify cell-active inhibitors that could be developed as therapeutics for giardiasis. A primary screen against Giardia lamblia GS clone H7 identified 85 cell-active compounds at a hit rate of 0.72%. A cytotoxicity counterscreen against HEK293T cells was carried out to assess hit compound selectivity for further prioritization. Mavelertinib (PF-06747775), a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), was identified as a potential new therapeutic based on indication, activity, and availability after reconfirmation. Mavelertinib has in vitro efficacy against metronidazole-resistant 713-M3 strains. Other EGFR-TKIs screened in follow-up assays exhibited insignificant inhibition of G. lamblia at 5 μM, suggesting that the primary molecular target of mavelertinib may have a different mechanistic binding mode from human EGFR-tyrosine kinase. Mavelertinib, dosed as low as 5 mg/kg of body weight or as high as 50 mg/kg, was efficacious in the acute murine Giardia infection model. These results suggest that mavelertinib merits consideration for repurposing and advancement to giardiasis clinical trials while its analogues are further developed.

Glioblastoma (GBM) is still one of the most commonly diagnosed advanced stage primary brain tumors. Current treatments for patients with primary GBM (pGBM) are often not effective and a significant proportion of the patients with pGBM recur. The effective treatment options for recurrent GBM (rGBM) are limited and survival outcomes are poor. This retrospective multicenter pilot study aims to determine potential cell-free microRNAs (cfmiRs) that identify patients with pGBM and rGBM tumors. 2,083 miRs were assessed using the HTG miRNA whole transcriptome assay (WTA). CfmiRs detection was compared in pre-operative plasma samples from patients with pGBM (n = 32) and rGBM (n = 13) to control plasma samples from normal healthy donors (n = 73). 265 cfmiRs were found differentially expressed in plasma samples from pGBM patients compared to normal healthy donors (FDR < 0.05). Of those 193 miRs were also detected in pGBM tumor tissues (n = 15). Additionally, we found 179 cfmiRs differentially expressed in rGBM, of which 68 cfmiRs were commonly differentially expressed in pGBM. Using Random Forest algorithm, specific cfmiR classifiers were found in the plasma of pGBM, rGBM, and both pGBM and rGBM combined. Two common cfmiR classifiers, miR-3180-3p and miR-5739, were found in all the comparisons. In receiving operating characteristic (ROC) curves analysis for rGBM miR-3180-3p showed a specificity of 87.7% and a sensitivity of 100% (AUC = 98.5%); while miR-5739 had a specificity of 79.5% and sensitivity of 92.3% (AUC = 90.2%). This study demonstrated that plasma samples from pGBM and rGBM patients have specific miR signatures. CfmiR-3180-3p and cfmiR-5739 have potential utility in diagnosing patients with pGBM and rGBM tumors using a minimally invasive blood assay., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

In the present work, a three-dimensional electrode reactor (3Der) using pallet activated carbon (PAC), as particle electrodes, was investigated to degrade non-biodegradable organic pollutants in pharmaceutical wastewater and steel industry wastewater. The effect of operating parameters, such as pH, electrode distance, O 2 flow rate, and current density was investigated. The TOC removal efficiency in 3Der was achieved at the highest mineralization yield of 94.1% after 180 min electrolysis, which was 10-19% higher than the two-dimensional electrode reactor (2Der). The higher performance of the 3Der can be attributed to the indirect and direct oxidation mechanisms. The impact of supporting electrolytes was decreased in order as chloride > nitrate > sulfate. The morphology of sludge and the presence of Fe(OH) 3 after Fenton-oxidation were investigated. 3Der system improved biodegradability of pharmaceutical wastewater after electro-Fenton treatment at a PW/SIW ratio of 3:1 (BOD 5 /COD = 0.6). Hence, the mechanism of 3Der/PAC, as particle electrodes was also proposed. 3Der with PAC particle electrodes using steel industry wastewater as a catalyst is an exciting technique for remediation of organic contaminated pharmaceutical wastewater., (Copyright © 2022. Published by Elsevier Ltd.)

A series of lupane-, oleanane- and dammarane-based triterpenoids with 3β-amino, A-ring azepano- and 3,4-seco-fragments has been synthesized and evaluated for antiviral activity against influenza A(H1N1) virus. It was found that azepanodipterocarpol 8 and 3β-amino-28-oxoallobetulin 11 showed antiviral activity with IC 50 1.1 and 2.6 μg ml -1 , and selectivity index of 19 and 10, respectively., (© 2022. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Aim: Healthcare workers have directly provided care for COVID-19 patients, and have faced many additional sources leading to poor mental health. The study aimed to investigate the mental health problems and related factors among healthcare staff in Vietnam., Methods: A descriptive cross-sectional mixed methods study, combining quantitative and qualitative research methods, was performed among 400 healthcare workers working at the National Hospital for Tropical Diseases and Ninh Binh General Hospital from the first day of treatment for COVID-19 patients to May 01, 2020., Results: The results showed that 8.0% of participants had stress, 17.5% of participants had anxiety, and 14.8% of participants had depression. Approximately 50% of participants reported that they had at least one of these symptoms. The findings illustrated that stress, anxiety, and depression were associated with the position in a hospital, health status during the COVID-19 pandemic, family members/relatives infected with COVID-19, physical and mental support from friends, family, and community, department, years of working, and the average work hours per day of healthcare workers exposed to COVID-19., Conclusion: During the COVID-19 pandemic, healthcare workers who worked in the hospital providing treatment and care for COVID-19 patients dealt with mental health problems such as stress, anxiety, and depression. It is necessary to promote mental health among healthcare workers, to contribute to the fight against the COVID-19 outbreak in Vietnam., 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 © 2022 Nguyen, Tran, Bui, Tran, Tran, Do, Nguyen and Tran.)

Pogostemon Desf . includes a wide range of taxa found in subtropical and tropical areas. Few works, however, have studied microanatomical characteristics of Pogostemon species and as yet identified features of Pogostemon auricularius (L.) Hassk. Thus, in this paper, we examined the taxonomic implications of root, stem and leaf morphology for species P. auricularius collected from Quang Tri Province. Light microscopy was mainly used in our study. Qualitative characters like stem quadrangular, hirsute; leaves opposite, ovate, margin serrulate; calyx campanulate; corolla small with separate equal lobes have been found in P. auricularius. Epidermal anatomy on the aerial parts of the species like epidermal cell shape, anticlinal walls, trichomes types, stomata types and calcium oxalate crystals types were examined as well. Quantitative characters like the length and width of leaf blade and inflorescence; the size of oil droplet, stomata and calcium oxalate crystals measured provided taxonomic significance. Based on identifying morphological characteristics of P. auricularius , we aimed to contribute to the taxonomic investigation into the genus Pogostemon and give relative morphological and microanatomical features compared with other taxa.