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Background: Adolescent mental health appears to be in crisis, yet few studies have comprehensively charted the course of common mental disorders (CMDs; depression and anxiety) across this key life stage. We aimed to describe the course of CMD symptoms in adolescence by summarising annual prevalence, cumulative incidence, and course for depression and anxiety, both separately and as comorbid CMDs, by sex assigned at birth in a contemporary Australian cohort., Methods: The Child to Adult Transition Study (CATS) was established in 2012 to form a representative cohort of adolescents in Melbourne, VIC, Australia. 43 schools were recruited using a stratified sampling approach, and all 2289 students aged 8-9 years were invited to participate. 1239 (54·1%) students obtained parental written informed consent and were followed up annually from 2012 to 2019 for a total of ten waves. Data from waves 3-10 (ages 10 to 18 years) were used for the current study and analysed to describe the course of symptoms of CMDs across adolescence. Primary measures of interest were clinically relevant depressive symptoms, clinically relevant anxiety symptoms, and any CMD (clinically relevant depressive or anxiety symptoms) at waves 3-10. A secondary measure of interest was comorbid CMDs (concurrent reporting of clinically significant anxiety and depressive symptoms) at waves 3-10. Depressive symptoms in the past 2 weeks were self-reported using the 13-item validated Short Mood and Feelings Questionnaire (SMFQ) at each wave, with a threshold score of 12 or more indicating clinically relevant symptoms. Anxiety symptoms in the past two weeks were self-reported using an 8-item shortened version of the Spence Children's Anxiety Scale (SCAS) at each wave, with a threshold score of 11 or higher indicating clinically relevant symptoms. The course of CMDs was described using annual prevalence, cumulative incidence for depression and anxiety, separately and combined. Missing data were handled via multiple imputation. An author with lived experience was involved in the research and writing process., Findings: Of the 1239 adolescents who participated in the study, 667 (53·8%) were female and 572 (46·2%) were male. 769 (62·1%) of 1239 were classified as socioeconomically advantaged, 675 (66·4%) of the 1016 with available data had a mother whose highest level of education was vocational or tertiary, and 579 (70·7%) of the 819 participants with ethnicity data identified as Anglo-Celtic or European. Overall, incidence of any clinically significant CMD symptoms during adolescence was 74% (95% CI 70-77; 84% [81-88] for females and 61% [55-66] for males). Independently, incidences of clinically significant depressive symptoms and anxiety symptoms were 65% (62-68) and 58% (55-62), respectively. Incidence of comorbid CMD was 48% (45-52). The estimated mean ages of first report in adolescence for both sexes were 14·1 years (95% CI 13·9-14·4) and 13·6 years (3·3-13·9) for depressive and anxiety symptoms, respectively. Of those who reached the threshold score for any CMD between ages 10 and 18 years, over half had a chronic (three or more waves) course (depression 54% [49-60]; anxiety 52% [47-58]), and a third met criteria for full remission at any subsequent wave (depression 30% [25-35]; anxiety 33% [27-39]). Females were consistently estimated to have a worse course of adolescent CMDs compared with males (eg, 64% [58-70] of females had a chronic course of depressive symptoms vs 37% [26-48] of males)., Interpretation: In this contemporary multi-wave cohort study, almost three-quarters of adolescents reported CMD symptoms. The likelihood of chronicity of CMD symptoms (ie, recurrence) was high. Universal responses are urgently required to address this considerable public health problem., Funding: National Health and Medical Research Council of Australia and the Royal Children's Hospital Foundation., Competing Interests: Declaration of interests SMS and GCP were supported by the National Health and Medical Research Council of Australia (NHMRC) Investigator Grant (GNT1196999). SGD was supported by an NHMRC Investigator Grant (GNT202171). MM-B was supported by an NHMRC Investigator Grant (GNT 2009572). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Statins, such as lovastatin, have been known to inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Statins were reported to moderately suppress hepatitis C virus (HCV) replication in cultured cells harboring HCV RNA replicons. We report here using an HCV cell culture (HCVcc) system that high concentrations of lovastatin (5-20 μg/mL) markedly enhanced the release of HCV infectious particles (virion) in the culture supernatants by up to 40 times, without enhancing HCV RNA replication, HCV protein synthesis, or HCV virion assembly in the cells. We also found that lovastatin increased the phosphorylation (activation) level of extracellular-signal-regulated kinase 5 (ERK5) in both the infected and uninfected cells in a dose-dependent manner. The lovastatin-mediated increase of HCV virion release was partially reversed by selective ERK5 inhibitors, BIX02189 and XMD8-92, or by ERK5 knockdown using small interfering RNA (siRNA). Moreover, we demonstrated that other cholesterol-lowering statins, but not dehydrolovastatin that is incapable of inhibiting HMG-CoA reductase and activating ERK5, enhanced HCV virion release to the same extent as observed with lovastatin. These results collectively suggest that statins markedly enhance HCV virion release from infected cells through HMG-CoA reductase inhibition and ERK5 activation., (© 2024 The Societies and John Wiley & Sons Australia, Ltd.)

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a vital role in DNA damage repair and lymphocyte function, presenting a significant target in cancer and immune diseases. Current DNA-PKcs inhibitors are undergoing Phase I/II trials as adjuncts to radiotherapy and chemotherapy in cancer. Nevertheless, clinical utility is limited by suboptimal bioavailability. This study introduces DNA-PKcs inhibitors designed to enhance bioavailability. We demonstrate that a novel DNA-PKcs inhibitor, DA-143, surpasses NU7441 in aqueous solubility as well as other available inhibitors. In addition, DA-143 displayed an improvement in DNA-PKcs inhibition relative to NU7441 achieving an IC 50 of 2.5 nM. Consistent with current inhibitors, inhibition of DNA-PKcs by DA-143 resulted in increased tumor cell sensitivity to DNA-damage from chemotherapy and inhibition of human T cell function. The improved solubility of DA-143 is critical for enhanced efficacy at reduced doses and facilitates more effective evaluation of DNA-PKcs inhibition in both preclinical and clinical development., (© 2024. The Author(s).)

Previous studies have associated tumor size with metastasis and prognosis in lung carcinoma; however, a precise cut-off for predicting distant metastasis in lung adenocarcinoma remains unclear. The aim of this study was to determine the cut-off point for predicting distant metastasis in lung adenocarcinoma. A cross-sectional study was conducted at Dr. Moewardi Hospital, Surakarta, Indonesia, from January 2022 to September 2023. Total sampling was employed, involving patients over 18 years old with a confirmed diagnosis of lung adenocarcinoma based on lung computed tomography (CT) scan findings, who had not yet received chemotherapy and had confirmed metastasis outside the lung. The study's dependent variable was the incidence of distant metastasis, while the independent variable was lung adenocarcinoma size. Two experienced thoracic radiologists measured lung adenocarcinoma size by assessing the longest axis using chest multi-slice computed tomography (MSCT) in the lung window setting. Receiver operating characteristic (ROC) curve analysis determined the optimal tumor size cut-off for predicting distant metastasis. Of 956 thoracic cancer patients, 108 were diagnosed with lung adenocarcinoma. After applying the inclusion and exclusion criteria, 89 patients were eligible. In the present study, tumor size predicted 68.1% of distant metastasis cases, with a cut-off point of 7.25 cm, yielding a sensitivity of 61.9% and a specificity of 61.5%. Tumors >7.25 cm had a 2.60-fold higher risk of distant metastasis compared to smaller tumors, with larger tumors more likely to spread to various sites. In conclusion, lung adenocarcinomas larger than 7.25 cm have a 2.60-fold increased risk of distant metastasis, making tumor size a crucial predictive factor. The study provides valuable insights for radiologists and can improve diagnosis accuracy and treatment planning by emphasizing tumor size as a key factor in managing lung adenocarcinoma., Competing Interests: All the authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Background: Medical research productivity is globally increasing, with a lagging progress in third-world countries due to significant challenges, including inadequate training and brain drain. Syria had been showing a slow upward trend until the war broke out and severely hindered academic growth and productivity. A deeper understanding of the factors influencing research productivity in this context are fundamental to guide educational policies and resource allocation. Previous cross-sectional studies that evaluated the perspectives of Syrian academics on the issue were limited by the small sample size of published healthcare workers, making it difficult to identify the factors that enabled them to pursue research., Methods: To address this challenge, we employed a case-control design. We isolated published early-career Syrian healthcare workers and compared their characteristics and perceptions to unpublished matched controls. Authors in the fields of medicine, dentistry, and pharmacy affiliated with any Syrian University were identified through an extensive search of PubMed and Google Scholar.These authors were invited to complete a questionnaire that covered participants' research contributions, alongside their self-assessed knowledge, attitudes, and barriers towards research. The questionnaire was publicly published to recruit an equal sample of matching controls, with half consisting of unpublished researchers and the other half of participants without prior research contributions., Results: Six-hundred-sixteen participants were recruited. Their knowledge, attitudes, and perceived barriers explained 46% and 34% of the variability in research involvement and publication, respectively (P < 0.001). Getting involved in and publishing research studies associated with higher research-related knowledge and attitudes (P < 0.001). Respondents' assessment of research-related barriers and their academic scores did not differ between cases and controls. Superior research-related knowledge and attitudes were associated with male gender, higher English competency, and better internet connectivity. Meanwhile, extracurricular training and mentors' support were associated with more positive research-related attitudes and less perceived barriers., Conclusions: Research productivity of medical professionals in Syria exhibits a positive correlation with their knowledge and favorable attitudes towards medical research. Noteworthy, the demographic variations are linked to disparities in research-related knowledge and motivation. In conclusion, these results suggest a potential avenue for enhancement through concentrated efforts on improving extracurricular training interventions and mentors' support., (© 2024. The Author(s).)

A significant proportion of stroke patients in Malaysia are supported by informal caregivers who often lack sufficient training. This lack of preparation contributes to an escalation in caregiver burden. A cross-sectional study was conducted using Caregiving Knowledge Questionnaire (CKQ-my) and Zarit Burden Interview (ZBI) with convenient sampling. The findings revealed that caregivers had limited knowledge regarding proper positioning, and most of them reported experiencing mild burden. Multiple logistic regression analysis showed that informal caregivers who were also the primary caregivers for severe stroke patients experienced a higher burden. Recognising and understanding the factors that contribute to caregiver burden in stroke cases is essential for developing effective programs to improve the quality of life for both stroke survivors and their informal caregivers.

This study evaluated Aloe vera extract as a green inhibitor to prevent corrosion in seawater environments. A. vera extract was produced by maceration with methanol-water at room temperature. Electrochemical techniques were used to evaluate the corrosion inhibitor effectiveness of the A. vera extract. The morphology of the corrosion products was analyzed by FE-SEM equipped with EDS and AFM. FT-IR and LCMS characterized the functional and structural groups in this extract. The electrochemical measurements show that A. vera extract could effectively reduce the corrosion of API 5L steel in seawater environments. Inhibition efficiency (IE) increases with increasing concentration. Optimal corrosion inhibition efficiency of around 83.75% (PDP) and 88.60% (EIS) was obtained by adding 300 mg L -1 of extract at 310 K. Furthermore, the higher the concentration of A. vera extract, the greater the activation energy (E a ), with the highest activation energy being 48.24 kJ mol -1 for the concentration of 300 mg L -1 . Conversely, increasing the temperature and exposure duration reduces the corrosion inhibition efficiency (IE) values; the best exposure period was 30 min with 88.34% IE by a concentration of 300 mg L -1 at 300 K. This corrosion inhibition is achieved by the adsorption process of A. vera bioactive on metal surfaces with a mixed inhibitor through a physisorption-chemisorption mechanism. This finding was confirmed by the smoother surface morphology of the steel treated with A. vera extract than without. This unveiling investigation found that A. vera extract has the potential to be an environmentally friendly corrosion inhibitor in the seawater environment., (© 2024. The Author(s).)

Background: There is strong evidence showing the association between obesity, type 2 diabetes mellitus (T2DM), and knee pain resulting from osteoarthritis. Regular exercise has been reported as a foundational piece of the preventive therapy puzzle for knee osteoarthritis (KOA) patients. Nonetheless, evidence-based exercise protocols for people with comorbidities, such as obesity, T2DM, and KOA are limited. Therefore, the present trial aimed to assess the effectiveness of a 12-week home-based circuit training (HBCT) protocol on various indices related to cardiometabolic health, musculoskeletal fitness, and health-related quality of life (HRQoL) among overweight/obese older adult patients with KOA and T2DM during the COVID-19 lockdown., Methods: This is a randomized controlled trial study registered at the National Medical Research Register (ID: RSCH ID-21-01180-KGTNMRR ID-21-02367-FUM) and obtained approval on December 9, 2021. Seventy overweight or obese patients with KOA and T2DM (62.2 ± 6.1 years; 56% female) were randomly assigned to the intervention group (n = 35, HBCT) or the no-exercise control group (n = 35, CON). HBCT performed a 12-week progressive protocol (seven exercises; 15-30 repetitions per exercise, 1 min passive rest between exercises; 2-4 rounds per session; 20-60 min total session duration). Blood samples were collected, and assays were performed to assess the lipid profile, liver function, and fasting blood glucose (FBG). In addition, the 30-s Chair Stand Test (30CST) was used to evaluate lower body muscular strength and endurance while the Timed Up and Go (TUG) test was used to evaluate lower limb function, mobility, and the risk of falls for all the participants. HRQoL was assessed using the Osteoarthritis Knee and Hip Quality of Life (OAKHQoL). All the assessments were conducted at pre-, mid-, and post-training stages during the application or practice of the exercise protocol, rather than during the training sessions themselves., Results: HBCT significantly reduced total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aminotransferase, alanine aminotransferase, FBG and knee pain (p < 0.05). Furthermore, HBCT induced meaningful increases in high-density lipoprotein (HDL-C), lower body muscular strength, endurance, function, mobility, and HRQoL in overweight/obese older adults with T2DM and KOA (p < 0.05)., Conclusion: The present outcomes recommend that an injury-free HBCT program may improve various indicators related to cardiometabolic health, musculoskeletal fitness, and HRQoL in elderly with overweight/obesity, T2DM and KOA. These findings offer valuable insights for clinicians and practitioners seeking evidence-based exercise interventions tailored for patients managing substantial metabolic and musculoskeletal health challenges in clinical practice., (© 2024. The Author(s).)

Aberrant RET kinase signaling is activated in numerous cancers including lung, thyroid, breast, pancreatic, and prostate. Recent approvals of selective RET inhibitors, pralsetinib and selpercatinib, has shifted the focus of RET kinase drug discovery programs towards the development of selective inhibitors. However, selective inhibitors invariably lose efficacy as the selective nature of the inhibitor places Darwinian-like pressure on the tumor to bypass treatment through the selection of novel oncogenic drivers. Further, selective inhibitors are restricted for use in tumors with specific genetic backgrounds that do not encompass diverse patient classes. Here we report the identification of a pyrimido indole RET inhibitor found to also have activity against TRK. This selective dual RET/TRK inhibitor can be utilized in tumors with both RET and TRK genetic backgrounds and can also provide blockade of NTRK-fusions that are selected for from RET inhibitor treatments. Efforts towards developing dual RET/TRK inhibitors can be beneficial in terms of encompassing more diverse patient classes while also achieving blockade against emerging resistance mechanisms., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brendan Frett reports financial support was provided by National Institutes of Health. Katie Ryan reports financial support was provided by National Institutes of Health. If there are other authors, they 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 Ltd. All rights reserved.)

Aims: To examine the psychometric properties of the Diabetes Management Experiences Questionnaire (DME-Q). Adapted from the validated Glucose Monitoring Experiences Questionnaire, the DME-Q captures satisfaction with diabetes management irrespective of treatment modalities., Methods: The DME-Q was completed by adults with type 1 diabetes as part of a randomized controlled trial comparing hybrid closed loop (HCL) to standard therapy. Most psychometric properties were examined with pre-randomization data (n = 149); responsiveness was examined using baseline and 26-week follow-up data (n = 120)., Results: Pre-randomization, participants' mean age was 44 ± 12 years, 52% were women. HbA1c was 61 ± 11 mmol/mol (7.8 ± 1.0%), diabetes duration was 24 ± 12 years and 47% used an insulin pump prior to the trial. A forced three-factor analysis revealed three expected domains, that is, 'Convenience', 'Effectiveness' and 'Intrusiveness', and a forced one-factor solution was also satisfactory. Internal consistency reliability was strong for the three subscales ( α range = 0.74-0.84) and 'Total satisfaction' ( α  = 0.85). Convergent validity was demonstrated with moderate correlations between DME-Q 'Total satisfaction' and diabetes distress (PAID: r s  = -0.57) and treatment satisfaction (DTSQ; r s  = 0.58). Divergent validity was demonstrated with a weak correlation with prospective/retrospective memory (PRMQ: r s  = -0.16 and - 0.13 respectively). Responsiveness was demonstrated, as participants randomized to HCL had higher 'Effectiveness' and 'Total satisfaction' scores than those randomized to standard therapy., Conclusions: The 22-item DME-Q is a brief, acceptable, reliable measure with satisfactory structural and construct validity, which is responsive to intervention. The DME-Q is likely to be useful for evaluation of new pharmaceutical agents and technologies in research and clinical settings., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Autoimmune cytopenias are defined by autoantibodies' immune destruction of one or more blood elements. Most often it is autoimmune hemolytic anemia or immune thrombocytopenia or both that define Evans syndrome. It may be secondary to infection or to underlying pathology such as systemic autoimmune disease or primary immunodeficiency, especially when it becomes chronic over several years. Primary Immunodeficiencies or inborn errors of immunity (IEI) are no longer defined solely by infections: autoimmunity is part of the clinical features of several of these diseases. It is dominated by autoimmune cytopenias, in particular, immune thrombocytopenia (ITP) and autoimmune hemolytic anaemia (AIHA). The challenges for the clinician are the situations where autoimmune cytopenias are chronic, recurrent and/or refractory to the various long-term therapeutic options. Most of these therapies are similar in action and generally consist of non-mediated immune suppression or modulation. In these situations, primary Immunodeficiencies must be diagnosed as soon as possible to allow the initiation of a targeted treatment and to avoid several ineffective therapeutic lines.

Methods utilized for drug discovery and development within the kinome have rapidly evolved since the approval of imatinib, the first small molecule kinase inhibitor. Macrocycles have received increasing interest as a technique to improve kinase inhibitor drug properties evident by the FDA approvals of lorlatinib, pacritinib, and repotrectinib. Compared to their acyclic counterparts, macrocycles can possess improved pharmacodynamic and pharmacokinetic properties. This review highlights clinical success stories when implementing macrocycles in kinase-based drug discovery and showcases that macrocyclization is a clinically validated drug discovery strategy when targeting the kinome., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Curculigo latifolia (family Amaryllidaceae) is used empirically for medicinal purposes. It is distributed throughout Asian countries, especially Indonesia. This study aimed at standardizing the C. latifolia plant, analyzing its phytochemical profile, and evaluating its pharmacological effects. The powder from each organ (root, stem, and leaves) was standardized organoleptically and microscopically. Samples were extracted by graded maceration using hexane, ethyl acetate, and ethanol. The extracts were determined for total phenolic content (TPC) and total flavonoid content (TFC). Antioxidant (radical scavenging and metal ion reduction) and antityrosinase activities were determined by spectrophotometric methods. Extracts were analysed for phytochemical profiles by LC-ESI-MS. The highest TPC and TFC were found in the ethanolic extract of the root organ (68.63 ± 2.97 mg GAE/g) and the ethyl acetate extract of the stem (14.33 ± 0.71 mg QE/g extract). High antioxidant activities were found in the ethanolic root extract (20.42 ± 0.33  µ g/mL) and ethanolic stem extract (45.65 ± 0.77  µ g/mL) by DPPH• and NO• assays, respectively. The ion reduction activity (by CUPRAC assay) was most significant in the ethyl acetate stem extract (390.42 ± 14.49  µ mol GAEAC/g extract). Ethanolic root extract was the most active in inhibiting tyrosinase (IC 50 value of 108.5  µ g/mL). The correlation matrix between TPC and antioxidant activities showed a moderate to robust correlation, whereas the TPC and antityrosinase activity showed a robust correlation. The TFC and antioxidant or antityrosinase activities showed a weak to moderate correlation. The LC-ESI-MS data identified major phenols in the active extracts, including methyl 3-hydroxy-4-methoxy-benzoate, quercetin, 4-O-caffeoylquinic acid-1, and curculigoside. Overall, this study suggests that extracts from the C. latifolia plant offer potent antioxidant and antityrosinase activities, allowing them to be used as natural antioxidants and candidates for skin-lightening compounds., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Syamsu Nur et al.)

Pseudomonas aeruginosa is a bacterium that causes metal deterioration by forming biofilms on metal surfaces. This work was carried out to analyze the antibacterial activity and the phenolic and flavonoid contents of the Moringa oleifera leaf extract against Pseudomonas aeruginosa . M. oleifera leaves were extracted in a methanol solution at different concentrations. The M. oleifera leaf extract yields were 12.84%, 18.96%, and 19.64% for the 100%, 75%, and 50% methanol ratios, respectively. Extracts of M. oleifera leaves had a minimum inhibiting concentration (MIC) of approximately 6144  μ g/mL against P. aeruginosa for a ratio of 100% methanol. In addition, no antibacterial activity was found for the 75% and 50% methanol ratios. The total phenolic levels were 16.26%, 12.73%, and 12.33% for the 100%, 75%, and 50% methanol solvent ratios, respectively. The total amounts of flavonoids were 23.32%, 3.40%, and 0.64% for the 100%, 75%, and 50% methanol solvents, respectively. The chemical structure of M. oleifera consists of kaemferol-3-O-rutinoside, quercimeritrin, kaempferol-3-O- β -D-glucopyranoside, stearidonic acid, trichosanic acid, pyrophaeophorbide A, and stigmastan-3,6-dione. The concentration of the solvent is essential in the extraction of plant constituents. Different concentrations indicate differences in antibacterial activity, phenolic and flavonoid contents, and chemical structure., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Ahmad Royani et al.)

Tumorous cancer has been a widely known and well-studied medical phenomenon; however, rare diseases like Myeloproliferative Neoplasm (MPN) have received less attention, leading to delayed diagnosis. Despite the availability of advanced technology in diagnostic tools that can boost the procedure, the morphological assessment of bone marrow trephine (BMT) images remains critical to confirm and differentiate MPN subtypes. This paper reports a histopathological imagery dataset that was created to focus on the most common MPN from the Philadelphia Chromosome (Ph)-negative type, namely Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (MF). The dataset consisted of 300 BMT images that can be used to enable computer vision applications, such as image segmentation, disease classification, and object recognition, in assisting the classification of the MPN disease. Ethical approval was obtained from the Ministry of Health, Malaysia and the bone marrow trephine images were captured using a digital microscope from the Olympus model (BX41 Dual head microscope) with x10, x20, and x40 lens types. The development of comprehensive tools deployed from this dataset can assist medical practitioners in diagnosing diseases, thus overcoming the current challenges., 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. Published by Elsevier Inc.)

Fluorescence and photoacoustic imaging techniques offer valuable insights into cell- and tissue-level processes. However, these optical imaging modalities are limited by scattering and absorption in tissue, resulting in the low-depth penetration of imaging. Contrast-enhanced imaging in the near-infrared window improves imaging penetration by taking advantage of reduced autofluorescence and scattering effects. Current contrast agents for fluorescence and photoacoustic imaging face several limitations from photostability and targeting specificity, highlighting the need for a novel imaging probe development. This review covers a broad range of near-infrared fluorescent and photoacoustic contrast agents, including organic dyes, polymers, and metallic nanostructures, focusing on their optical properties and applications in cellular and animal imaging. Similarly, we explore encapsulation and functionalization technologies toward building targeted, nanoscale imaging probes. Bioimaging applications such as angiography, tumor imaging, and the tracking of specific cell types are discussed. This review sheds light on recent advancements in fluorescent and photoacoustic nanoprobes in the near-infrared window. It serves as a valuable resource for researchers working in fields of biomedical imaging and nanotechnology, facilitating the development of innovative nanoprobes for improved diagnostic approaches in preclinical healthcare.

Curculigo latifolia is a plant in the Hypoxidaceae family commonly used in herbal medicine. The study objective was to evaluate the antioxidant and anti-elastase properties of C. latifolia extracts in vitro and silico as a candidate for antiaging active ingredients. This study identified secondary metabolites of the hexane (HE), ethyl acetate (EAE), and ethanol extracts (EE) from the root (R), stem (S), and leaf (L) organs by LC-ESI-MS and evaluated in vitro antioxidant and inhibitor elastase activity. An antioxidant evaluation was performed using ABTS, Beta Carotene Bleaching (BCB), and Ferric Reduction Antioxidant Power (FRAP). Evaluation of anti-elastase was carried out using elastase and followed by an in silico study of molecular docking using the target protein elastase (1B0F). Fifteen C. latifolia metabolites were identified in C. latifolia extracts, most of which were phenolic compounds. In antioxidant testing, REE, REAE, SEE, and SEAE extracts showed potent antioxidant activity based on the ABTS, BCB, and FRAP methods. In anti-elastase testing, it was found that SEE, REE, REAE, and RHE extracts gave powerful inhibition of elastase activity (in the ranges of 16.89 to 27.91 µg/mL). The in-silico study demonstrated the potential of the identified metabolites to bind to the target protein 1B0F involved in remodeling the skin aging process. This research concludes that the extracts from C. latifolia have the potential to serve as an active antiaging source., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Berna Elya reports financial support, article publishing charges, equipment, drugs, or supplies, and statistical analysis were provided by the Indonesian Ministry of Higher Education and Culture. Muhammad Hanafi reports a relationship with the National Research and Innovation Agency Republic of Indonesia that includes: consulting or advisory., (© 2023 The Authors.)

Exerting forces on biomolecules inside living cells would allow us to probe their dynamic interactions in their native environment. Magnetic iron oxide nanoparticles represent a unique tool capable of pulling on biomolecules with the application of an external magnetic field gradient; however, their use has been restricted to biomolecules accessible from the extracellular medium. Targeting intracellular biomolecules represents an additional challenge due to potential nonspecific interactions with cytoplasmic or nuclear components. We present the synthesis of sulfobetaine-phosphonate block copolymer ligands, which provide magnetic nanoparticles that are stealthy and targetable in living cells. We demonstrate, for the first time, their efficient targeting in the nucleus and their use for magnetic micromanipulation of a specific genomic locus in living cells. We believe that these stable and sensitive magnetic nanoprobes represent a promising tool to manipulate specific biomolecules in living cells and probe the mechanical properties of living matter at the molecular scale.

Hepatitis B virus (HBV) is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Current therapeutic drugs for chronic HBV infection use IFN and nucleos(t)ide analogs; however, their efficacy is limited. Thus, there is an urgent need to develop new antivirals for HBV therapy. In this study, we identified a plant-derived polyphenolic bioflavonoid, amentoflavone, as a new anti-HBV compound. Amentoflavone treatment dose-dependently inhibited HBV infection in HBV-susceptible cells with HepG2-hNTCP-C4 and primary human hepatocyte PXB-cells. A mode-of-action study showed that amentoflavone inhibits the viral entry step, but not the viral internalization and early replication processes. Attachment of HBV particles as well as HBV preS1 peptide to HepG2-hNTCP-C4 cells was inhibited by amentoflavone. The transporter assay revealed that amentoflavone partly inhibits uptake of sodium taurocholate cotransporting polypeptide (NTCP)-mediated bile acid. Furthermore, effect of various amentoflavone analogs on HBs and HBe production from HBV-infected HepG2-hNTCP-C4 cells was examined. Robustaflavone exhibited comparable anti-HBV activity to that of amentoflavone and an amentoflavone-7,4', 4‴-trimethyl ether derivative (sciadopitysin) with moderate anti-HBV activity. Cupressuflavone or the monomeric flavonoid apigenin did not exhibit the antiviral activity. Amentoflavone and its structurally related biflavonoids may provide a potential drug scaffold in the design of a new anti-HBV drug inhibitor targeting NTCP., (© 2023 The Societies and John Wiley & Sons Australia, Ltd.)

Cochlear implantation (CI) has been successful in individuals with sensorineural hearing loss (SNHL) over the last few years. This study assessed the auditory and speech performance results of pediatrics with inner ear malformations (IEMs) following cochlear implantation at the Ahvaz cochlear implantation center and compared the outcomes of various malformations. All pediatrics with IEMs undergoing CI were included in the study. This retrospective study was performed on pediatrics with congenital IEMs who underwent cochlear implantation in Ahvaz cochlear implantation center between 2014 and 2019. The Category of Auditory Performance (CAP) and the Speech Intelligibility Rating (SIR) scores are two of the most frequently administered tests. The CAP with ranging from 0 (displays no awareness of environmental sounds) to 7 (can use the telephone with a familiar talker), was used to measure the speech perception performance of the implanted children. Furthermore, SIR consists of five performance categories ranging from "prerecognizable words in spoken language" to "connected speech is intelligible to all listeners". Finally, the study included 22 patients. The evaluation of the CT-Scan revealed three types of inner ear malformation: Incomplete Partition (IP)-I in 2 (9.1%), IP-II in 12 (54.5%), and common cavity in 8 (36.4%) individuals. The results were shown that the median CAP score preoperative was 0.5 (interquartile range (IQR): 0-2) and postoperative was 3.5 (IQR: 3-7). There were statistically significant differences in CAP scores between preoperative and second-year follow-up postoperative ( p value = 0.036). The results were shown that the median SIR score preoperative was 1 (IQR: 1-5) and postoperative was 2 (IQR: 1-5). There were statistically significant differences in SIR scores between preoperative and second-year follow-up postoperative ( p value = 0.001). Following a thorough preoperative screening, patients with specific IEMs can be candidates for CI and not a contraindication. There were statistically significant differences in CAP and SIR scores between preoperative and second-year follow-up postoperative in the common cavity and IP-II groups., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Otolaryngologists of India 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.)

Sigma 2 receptor (σ2R) is overexpressed in select cancers and is regarded as a biomarker for tumor proliferation. σ2R ligands are emerging as promising theranostics for cancer and neurodegenerative diseases. Herein, we describe the design and synthesis of a series of novel quinolyl pyrazinamides as selective and potent σ2R ligands that show sub-micromolar potency in pancreatic cancer cell lines. Compounds 14 (JR1-157) and 17 (JR2-298) bind σ2R with K i of 47 and 10 nM, respectively. Importantly, compound 14 has an oral bioavailability of 60% and shows significant in vivo efficacy without obvious toxicity in a syngeneic model of pancreatic cancer. The cytotoxicity of the quinolyl pyrazinamides significantly enhanced in the presence of copper and diminished in the presence of the copper-chelator tetrathiomolybdate. In conclusion, compound 14 is water-soluble, metabolically stable, orally active, and increases the expression of the autophagy marker LC3B and warrants further development for the treatment of pancreatic cancer.

Objectives: To evaluate the relationship between TGFBR3 rs284875 single nucleotide polymorphism (SNP) state and silent cerebral infarction (SCI) in asymptomatic patients with sickle cell disease (SCD)., Methods: A cross-sectional study was conducted on 50 children with SCD above 2 y of age followed up at the hematology outpatient clinic of Alexandria University Children's Hospital in Egypt. Twenty-four healthy children were included as a control group. All patients included in the study were subjected to complete history and clinical examination. Real-time polymerase chain reaction was performed on patients and controls for identification of SNP rs284875 of the TGFBR3 gene. A magnetic resonance imaging (MRI) of the brain were performed only on patients for detection of SCI., Results: Fifty SCD patients were enrolled (26 males and 24 females), with a median age of 10.9 y (2.3-17.8 y), and 24 children as healthy control for the studied SNP. Thirty-five (70%) patients had homozygous SCD, while 30% had sickle β-thalassemia. The brain MRI was normal in all the patients except for 2 patients who had features of SCI. The TGFBR3 rs284875 SNP was detected in 15 (30%) patients in the homozygous state (GG) versus only 1 (4.2%) child from the control group (p = 0.003). The prevalence of SCI was low in the study population and there was no statistically significant relationship between the TGFBR3 rs284875 SNP status and the presence of SCI in the brain MRI (p = 0.621)., Conclusions: This study confirmed a low prevalence of SCI in the SCD patient included in the study. The TGFBR3 rs284875 SNP did not significantly increase SCI among those patients., (© 2022. The Author(s).)

Chronic hepatitis C virus (HCV) infection can lead to liver cirrhosis and hepatocellular carcinoma. Although current medications using direct-acting antivirals (DAAs) are highly effective and well-tolerated for treating patients with chronic HCV, high prices and the existence of DAA-resistant variants hamper treatment. There is thus a need for easily accessible antivirals with different mechanisms of action. During the screening of Indonesian medicinal plants for anti-HCV activity, we found that a crude extract of Dryobalanops aromatica leaves possessed strong antiviral activity against HCV. Bioassay-guided purification identified an oligostilbene, vaticanol B, as an active compound responsible for the anti-HCV activity. Vaticanol B inhibited HCV infection in a dose-dependent manner with 50% effective and cytotoxic concentrations of 3.6 and 559.5 µg/mL, respectively (Selectivity Index: 155.4). A time-of-addition study revealed that the infectivity of HCV virions was largely lost upon vaticanol B pretreatment. Also, the addition of vaticanol B following viral entry slightly but significantly suppressed HCV replication and HCV protein expression in HCV-infected and a subgenomic HCV replicon cells. Thus, the results clearly demonstrated that vaticanol B acted mainly on the viral entry step, while acting weakly on the post-entry step as well. Furthermore, co-treatment of the HCV NS5A inhibitor daclatasvir with vaticanol B increased the anti-HCV effect. Collectively, the present study has identified a plant-derived oligostilbene, vaticanol B, as a novel anti-HCV compound.

Objective: Quran memorization is familiar in Indonesia since early childhood (EC) education level and it is reported to have a positive effect on children's emotional state. This study investigates how Quran memorization influences children's emotions in a certain condition using Frontal Alpha Asymmetry (FAA) index. Method : The participants were 4 children aged 5-7 years, studying at Islamic-based schools in Surakarta. The tasks included three methods of Quran learning: visual, by watching videos; auditory, by listening to murattal recitations of the Quran; and memory, by repeating rote. The FAA index measurement used absolute power data obtained from Electroencephalography (EEG) by calculating the natural logarithm (ln [right alpha power] - ln [left alpha power]) from channel F8 and channel F7 respectively. Results: The majority of participants showed a positive FAA index in almost all tasks. The FAA index of various tasks were not significantly different from each other, with P = 0.592 based on Kruskal-Wallis nonparametric test. The post hoc Mann-Whitney U test does not find any intervention that stands out among the others. Conclusion: Learning the Quran with methods that involve visual, auditory, and memory activities results in positive, happy, motivated and excited feelings in children's emotional state based on the FAA index assessment., Competing Interests: None., (Copyright © 2023 Tehran University of Medical Sciences.)

Objectives: Adenomatous polyps are common, occurring in up to 25% of the population older than 50 years of age in the United States. Conflicting data are present in the literature about the impact of specific adenoma locations and the prediction on the number and advanced histology of adenomas elsewhere. With this study we aimed to review the association between cecal adenoma and the risk of discovering more and advanced adenomas in the remainder of the colon., Methods: We performed a retrospective study of 1880 patients who received outpatient colonoscopies between June 2012 and December 2014 at the Veterans Affairs Medical Center in Oklahoma City. The data collected included patient demographics, indications for colonoscopy, smoking history, alcohol use, family history of colon cancer, quality of bowel preparation, number of adenomas, location, size of adenomas, and the histology of adenomas and colon cancer., Results: The mean age of the study population was 61.6 ± 9.4 year, with 95% of the population being men. Cecal adenomas were found in 243 (12.9%) of patients. Patients with cecal adenoma tended to be older (65 ± 7 vs 61 ± 10, P < 0.0001), more likely to be men (97% vs 94%, P = 0.06) and less likely to have a colonoscopy done for screening indication (11% vs. 13%., P = 0.03). After adjusting for age, sex, indication, and quality of bowel preparation, patients with cecal adenoma were found to have a sixfold increase in finding ≥10 other adenomas elsewhere (4.5% vs 0.8% P = 0.0009) and a threefold increase in finding advanced adenomas (17.7% vs 9.9% P = 0.002) in the remainder of the colon. Stratifying by location, the increased risk was more pronounced in the right side (24.7% vs 8.9% P ≤ 0.0001) compared with the left side., Conclusions: Cecal adenoma is associated with an increased risk of finding more and advanced adenomas in the remainder of the colon, especially on the right side; therefore, the discovery of a cecal adenoma should prompt a more thorough evaluation of the entire colon, particularly the right colon.

Background:  The huge workload on doctors especially residents, who are the main health care providers in public hospitals, in addition to the vanishing incomes and lack of personal safety during the decade-long Syrian crisis, led to further hurdles in the focus on research. Postgraduate students in the medical and paramedical fields must conduct original research projects as part of their graduation requirements. However, this does not reflect on research publications coming from Syria. Methods:  This is a nation-wide cross-sectional study targeting medical, dental, and pharmacy postgraduate students who are at the phase of planning for their required projects. The questionnaire aimed to capture their attitudes toward research, perceived barriers, and previous research experiences in order to suggest evidence-based recommendations. Results:  The sample consisted of 429 residents representing about 22% of the target population. Nearly all the participants had positive opinion toward the important role of medical research and the significance of their participation. Agreement was also clear regarding perceived barriers, including the lack of adequate training and research facility. Seventy-one percent of the participants were not involved in any research before the time of their master theses, less than 13% of them had submitted an article for publication, and less than 5% had submitted more than one paper. Despite that, high-quality internet connectivity and rich English writing skills were associated with further research experiences. Additionally, mentors' support and self-paced learning of research skills had significant positive impact on students' research contributions with odds ratios of 2.04 [[95% Confidence Interval]: 1.02-4.06] and 2.68 [1.48-4.84], respectively. Conclusion:  Lack of training and mentorship, in addition to several common barriers to medical research, hampered residents' capacity of conducting and publishing research despite their positive attitudes toward it. Nevertheless, the variance within our sample exposed a promising window for implementing low-cost institutional and individual solutions such as peer-run self-paced training opportunities and long-distance mentoring., Competing Interests: Conflict of Interest None declared., (Syrian American Medical Society. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Acute myeloid leukemia (AML) is a heterogenous disease in which the initiation and maintenance of the malignant clone is blamed on a rare population of leukemia stem cells (LSCs). The persistence of such a malignant population is referred to as measurable/minimal residual disease (MRD). Evaluation of MRD is the gold standard for follow-up of therapy and constitutes an independent prognostic parameter. As LSCs are the main contributor to the persistence of MRD, then MRD should correlate with the bulk of LSCs at the individual case level. MRD is measured at defined time points during therapy. However, LSCs can be evaluated at diagnosis, which ensures the advantage of early prediction of high-risk patients and allows for early therapeutic decisions. Using two simple four-color monoclonal antibody combinations (CD38/CD123/CD34/CD45 and CD90/CD133/CD45/CD33) and the prism function of the Coulter Navios flow cytometer, the frequency of LSC subsets was evaluated in 84 newly diagnosed adult AML patients. For each panel, 16 possible combinations were detected. Our results showed that there was extreme variability in the percentage of the LSC fraction between different cases, as well as at the individual case level. For each LSC subset, the median value was used to divide cases into low and high expressors. LSC subsets that showed an impact on overall survival (OS) and disease-free survival (DFS) included CD123+, CD 123+/CD34-, CD34-/CD38+/CD123+, CD34+/CD38-/CD123+, CD133+, and CD133+/CD33-. On multivariate analysis, only CD123 (p ≤ 0.001, SE = 0.266, HR = 2.8, 95% CI = 1.74.7) and CD133+/CD33- (p = 0.017, SE = 0.263, HR = 1.9, 95% CI = 1.1-3.1) retained their significance for OS. Likewise, only CD34+/CD38-/CD123+ (p ≤ 0.001, HR 2.3, SE: 0.499, 95% CI: 2.4-17.4) and CD133 (p = 0.015, HR 2.3, SE 0.34, 95% CI: 1.2-4.4) retained their statistical significance for DFS. The LSC frequency at diagnosis showed a moderate to strong correlation with MRD status at day 14 and day 28. In conclusion, the level of LSCs at diagnosis correlated with MRD status at day 14 and day 28 in AML patients and had a deleterious impact on OS and DFS. It may be used as an early marker for high-risk patients allowing for early therapeutic decisions., 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 Kamel, Elsharkawy, Kandeel, Hanafi, Samra and Osman.)

Aims: Acceptable and accessible interventions are needed to address 'psychological insulin resistance', which is a common barrier to insulin uptake among adults with type 2 diabetes (T2D). Our aim was to test the feasibility of a randomised controlled trial (RCT) study design and acceptability of a theoretically grounded, psycho-educational, web-based resource to reduce negative insulin appraisals among adults with T2D., Methods: A double-blinded, parallel group, two-arm pilot RCT (1:1), comparing intervention with active control (existing online information about insulin). Eligible participants were Australian adults with T2D, taking oral diabetes medications., Exclusion Criteria: prior use of injectable medicines; being 'very willing' to commence insulin. Primary outcomes: study feasibility (recruitment ease, protocol fulfilment, attrition, data completeness); secondary outcomes: intervention acceptability (intervention engagement, user feedback) and likely efficacy (negative Insulin Treatment Appraisal Scale [ITAS] scores at follow-up). Online surveys completed at baseline and 2 weeks., Results: During 4-week recruitment, 76 people expressed interest: 51 eligible and 35 enrolled (intervention = 17, control = 18; median[interquartile range] age = 62[53, 69] years; 17 women). Protocol fulfilment achieved by 26 (74%) participants (n = 13 per arm), with low participant attrition (n = 6, 17%). Intervention acceptability was high (>80% endorsement, except format preference = 60%). ITAS negative scores differed between-groups at follow-up (M diff = -6.5, 95% confidence interval: -10.7 to -2.4), favouring the intervention., Conclusions: This novel web-based resource ("Is insulin right for me?") is acceptable and associated with a likely reduction in negative insulin appraisals, relative to existing resources. This pilot shows the study design is feasible and supports conduct of a fully powered RCT., (© 2021 Diabetes UK.)

Introduction: Psychological barriers to insulin therapy are associated with the delay of clinically indicated treatment intensification for people with type 2 diabetes (T2D), yet few evidence-based interventions exist to address these barriers. We describe the protocol for a randomised controlled trial (RCT) examining the efficacy of a novel, theoretically grounded, psychoeducational, web-based resource designed to reduce psychological barriers to insulin among adults with non-insulin treated T2D: ' Is insulin right for me?' ., Methods and Analysis: Double-blind, parallel group RCT. A target sample of N=392 participants (n=196/arm) will be randomised (1:1) to ' Is insulin right for me?' (intervention) or widely available online resources (control). Eligible participants include adults (18-75 years), residing in Australia, currently taking oral hypoglycaemic agents to manage T2D. They will be primarily recruited via invitations and reminders from the national diabetes registry (from a purposefully selected sample of N≥12 000)., Exclusion Criteria: experience of self-administered injectable; previously enrolled in pilot RCT; 'very willing' to start insulin as baseline. Outcomes will be assessed via online survey at 2 weeks and 6 months. Primary outcome between-group: difference in mean negative Insulin Treatment Appraisal Scores (ITAS negative) at 2-week and 6-month follow-up., Secondary Outcomes: between-group differences in mean positive insulin appraisals (ITAS positive) and percentage difference in intention to commence insulin at follow-up time points. All data analyses will be conducted according to the intention-to-treat principle., Ethics and Dissemination: Deakin University Human Research Ethics Committee (2020-073). Dissemination via peer-reviewed journals, conferences and a plain-language summary., Trial Registration Number: ACTRN12621000191897; Australian and New Zealand Clinical Trials Registry., Competing Interests: Competing interests: EH-T has undertaken research funded by an unrestricted educational grant from Abbott Diabetes Care, AstraZeneca, and Sanofi; received speaker fees from Novo Nordisk and Roche to Australian Centre for Behavioural Research in Diabetes (ACBRD); and served on an advisory board for AstraZeneca. EEH has no conflicts of interest to disclose. JF has received unrestricted educational grants for research support from Roche, Sanofi, and Medtronic. TS serves on advisory boards for Novo Nordisk and Liva Health Care and is currently on a EIT Health research grant held jointly with Roche Diagnostics. JS has served on advisory boards for Janssen, Medtronic, Roche Diabetes Care, and Sanofi Diabetes; her research group (Australian Centre for Behavioural Research in Diabetes [(ACBRD])) has received honoraria for this advisory board participation and has also received unrestricted educational grants and in-kind support from Abbott Diabetes Care, AstraZeneca, Medtronic, Roche Diabetes Care, and Sanofi Diabetes. JS has also received sponsorship to attend educational meetings from Medtronic, Roche Diabetes Care, and Sanofi Diabetes, and consultancy income or speaker fees from Abbott Diabetes Care, AstraZeneca, Medtronic, Novo Nordisk, Roche Diabetes Care, and Sanofi Diabetes. All other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The banana mild mosaic virus (BanMMV) (Betaflexiviridae, Quinvirinae, unassigned species) is a filamentous virus that infects Musa spp. and has a very wide geographical distribution. The current BanMMV indexing process for an accession requires the testing of no less than four plants cultivated in a greenhouse for at least 6 months and causes a significant delay for the distribution of the germplasm. We evaluated the sensitivity of different protocols for BanMMV detection from in vitro plants to accelerate the testing process. We first used corm tissues from 137 in vitro plants and obtained a diagnostic sensitivity (DSE) of only 61% when testing four plants per accession. After thermotherapy was carried out to eliminate BanMMV infection, the meristem was recovered and further grown in vitro. The same protocol was evaluated in parallel on the corm tissue surrounding the meristem, as a rapid screening to evaluate virus therapy success, and was compared to the results obtained following the standard protocol. The obtained results showed 28% false negatives when conducting testing from corm tissues, making this protocol unsuitable in routine processes. Furthermore, RT-PCR and high-throughput sequencing (HTS) tests were applied on tissues from the base ( n = 39) and the leaves ( n = 36). For RT-PCR, the average DSE per sample reached 65% from either the base or leaves. HTS was applied on 36 samples and yielded 100% diagnostic specificity (DSP) and 100% DSE, whatever the sampled tissue, allowing the identification of a new Betaflexiviridae species infecting Musa . These results suggest that a reliable diagnostic of BanMMV from in vitro plants using RT-PCR or HTS technologies might represent an efficient alternative for testing after greenhouse cultivation.

Isolation and determination of antibacterial compounds from plants are essential to obtain a new antibacterial as a substitute for conventional resistant antibiotics. This study aims to isolate and identify a new robustaflavone as antibacterial activity from Garcinia latissima Miq. leave. In this study, the isolation process was carried out using column chromatography followed by preparative thin layer chromatography (TLC) based on the TLC profile. The fraction D was tested for anti-bacterial Bacillus subtilis using the TLC bioautography method. The isolates obtained were then identified using 1H-NMR, 13C-NMR, distortionless enhancement by polarization transfer, heteronuclear single quantum coherence, and heteronuclear multiple bond coherence. The Activity assay of the isolate was performed using the microdilution method. A pure compound obtained the result of the separation process with eluent n-hexane: Ethyl acetate (3:2) with R f 0.6. This spot follows the spot in the contact bioautographic result of fraction D, the spot with R f 0.6 gives an inhibition zone. After identifying and purifying the isolate were known as Robustaflavone, this compound has activity against B. subtilis with a (minimum inhibitory concentration) value of 2500 ppm. Robustaflavone successfully isolated and identified from G. latissima leave and its antibacterial activity., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Advanced Pharmaceutical Technology & Research.)

Flavonoids and phenols have an arginase inhibitory and antioxidant activity. The Sterculia genus has phenols and flavonoids content. This study aimed to investigate the arginase inhibitory and antioxidant activity of the chemical constituent of Sterculia comosa (wall) Roxb and also their binding affinities to arginase. The most active extract was methanol extract. This active extract was determined for its arginase inhibitory and antioxidant activity, determined the total phenols and total flavonoids, and identified chemical compound. The methanol extract has IC 50 2.787 μg/ml for arginase inhibitory activity and IC 50 4,199 μg/ml for DPPH scavenging activity. The total phenols 723.61 mg GAE/gr, total flavonoids content 28.96 mg QE/gr extract. The chemical constituent: KC4.4.6 ((-)-2-(E)-caffeoyl-D-glyceric acid) and KC4.4.5.1 (trans-isoferulic acid) have an arginase inhibitory activity KC4.4.6: 98,03 μg/ml and KC4.4.5.1: 292,58 μg/ml. Antioxidant activity with DPPH methods KC4.4.6: 48,77 μg/ml and KC4.4.5.1: 88,08 μg/ml. Antioxidant by FRAP methods KC4.4.6: 16,4 FeEAC mol/g and KC4.4.5.1: 15,79 FeEAC mol/g. The isolate trans-isoferulic acid predicted has good interaction to arginase. Isolate KC4.4.6. Predicted has good interaction to PLPro of SARS CoV-2 PLpro. However, both isolates did not show good interaction to 3CLPro, nsp12, and Spike protein of SARS CoV-2., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Numerous therapeutic compounds have been isolated from naturally abundant organic resources, which may offer economical and sustainable sources of compounds with safe and efficacious biological activities. In the cosmetics industry, natural compounds with anti-aging activities are eagerly sought. Thus, we prepared various extracts from Rubus fraxinifolius leaves and used enzyme inhibition assays to isolate compounds with protective effects against skin aging. Two triterpenoids were isolated from Rubus fraxinifolius Poir. leaves. The structures were characterized by spectroscopic analyses (LC-ESI-MS, 1D/2D NMR) and comparison to reported data. Compound 1 and 2 were determined as 2,3-O-ethyleneglycol, 19-hydroxyurs-12-en-23,28-dioic acid and 2,3-O-propanediol,19-hydroxyurs-12-en-28-oic acid. Methanol extract and isolates were assessed for their inhibitory effects on elastase and tyrosinase. Compounds 1 and 2 inhibited elastase with IC 50 122.199 µg/mL and 98.22 µg/mL, and also inhibited tyrosinase with IC 50 207.79 µg/mL and 221.51 µg/mL, respectively. The molecular docking proved that both compounds have affinities toward the enzymes., (© 2021. The Author(s).)

The aim of this study was to investigate the impact of oral impairment on chewing behaviour, food bolus properties and food comfortability during elderly consumption of model cheeses. Seventy-two elderly persons (aged 66 to 88) was recruited and classified into two groups according to dental status (poor vs. satisfactory). They showed a wide range of salivary flow rates whatever their dental status (stimulated: 0.2-3.8 mL min -1 , resting: 0.1-0.8 mL min -1 ). Standardized bites of four model cheeses with an identical composition but different textures (soft, hard, processed and whipped) were tested. The time and number of chewing cycles required to form a bolus were measured. The rheological properties of the bolus were studied, as was saliva moistening. Food comfortability was assessed by means of a questionnaire composed of 5 sections (1-oral comfort, 2-bolus formation, 3-pain, 4-texture and 5-flavour perception). The chewing parameters measured were not modified by the oral health. However, elderly with poor dentition formed harder boluses than elderly with satisfactory dentition. Moreover, for elderly with poor dentition, the quantity of saliva incorporated into the bolus was correlated with the stimulated salivary flow rate, which was not the case for elderly with satisfactory dentition. General oral comfort and its different attributes were poorly associated with the oral health of the elderly. A multifactorial analysis performed on an average cheese showed that food comfortability is independent of changes in the hardness and moistening of the bolus, regardless of dental status. In particular, poor dental status increases the hardness of the bolus without modifying its comfortability.

Introduction: There has already been a rising demand in utilising phantom for hybrid Positron Emission Tomography/ Computed Tomography (PET/CT) scanner of nuclear imaging. This review further clarifies this topic and investigates how the previous research phantoms operated with the need for quantitative hybrid nuclear imaging of PET/CT while providing a relatively high image quality when it was performed. In this article, the necessity of previous and current phantom studies in hybrid nuclear imaging of PET/CT scanners is reviewed., Methods: PubMed and Google Scholar were systematically searched for the relevant studies by following the PRISMA 2009 checklist. A past decade literature search was conducted from 2010 until November 2020 to secure the relevance of the phantom study. Databases were recruited using keywords such as phantom, quantification, standardisation, harmonisation, image quality, standardised uptake value and multicentre study. However, all keywords were related to PET/CT. All abstracts and eligible full-text articles were screened independently, and finally, the quality assessments of this review were performed., Results: From the 200 retrieved articles, 80 were rejected after the screening of the abstracts and 35 after reading the full-text. The 20 accepted articles addressed the distribution of phantom types used in selected articles studies which were NEMA (67%), ACR (8%) and others (25%). The articles showed the various experimental studies, either phantom studies (35%) or phantom plus clinical studies (65%). For clinical studies (n = 829), the distribution of prospective studies was (n = 674) and retrospective studies was (n =155). The distribution of phantom pathway application showed the studies focused on 40% of reconstruction protocol studies, 30% of the multicentre and standardisation of accreditation program studies, and 30% of the quantification of uptake values studies., Conclusions: According to this review, the phantom study have a pivotal role in hybrid nuclear imaging of PET/CT either in technical aspects of the scanners (such as data acquisition and reconstruction protocol) or clinical characteristics of patients. In addition to this, the necessity to identify the suitable system phantoms to use within PET/CT scans by considering the continuous development of new phantom studies are needed. Researchers are encouraged to adopt efforts on phantom quantitative validation, including verification with clinical data of patients.

Motivation: Complex data structures composed of different groups of observations and blocks of variables are increasingly collected in many domains, including metabolomics. Analysing these high-dimensional data constitutes a challenge, and the objective of this article is to present an original multivariate method capable of explicitly taking into account links between data tables when they involve the same observations and/or variables. For that purpose, an extension of standard principal component analysis called NetPCA was developed., Results: The proposed algorithm was illustrated as an efficient solution for addressing complex multigroup and multiblock datasets. A case study involving the analysis of metabolomic data with different annotation levels and originating from a chronic kidney disease (CKD) study was used to highlight the different aspects and the additional outputs of the method compared to standard PCA. On the one hand, the model parameters allowed an efficient evaluation of each group's influence to be performed. On the other hand, the relative relevance of each block of variables to the model provided decisive information for an objective interpretation of the different metabolic annotation levels., Availability and Implementation: NetPCA is available as a Python package with NumPy dependencies., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Because of its ability to generate biological hypotheses, metabolomics offers an innovative and promising approach in many fields, including clinical research. However, collecting specimens in this setting can be difficult to standardize, especially when groups of patients with different degrees of disease severity are considered. In addition, despite major technological advances, it remains challenging to measure all the compounds defining the metabolic network of a biological system. In this context, the characterization of samples based on several analytical setups is now recognized as an efficient strategy to improve the coverage of metabolic complexity. For this purpose, chemometrics proposes efficient methods to reduce the dimensionality of these complex datasets spread over several matrices, allowing the integration of different sources or structures of metabolic information. Bioinformatics databases and query tools designed to describe and explore metabolic network models offer extremely useful solutions for the contextualization of potential biomarker subsets, enabling mechanistic hypotheses to be considered rather than simple associations. In this study, network principal component analysis was used to investigate samples collected from three cohorts of patients including multiple stages of chronic kidney disease. Metabolic profiles were measured using a combination of four analytical setups involving different separation modes in liquid chromatography coupled to high resolution mass spectrometry. Based on the chemometric model, specific patterns of metabolites, such as N-acetyl amino acids, could be associated with the different subgroups of patients. Further investigation of the metabolic signatures carried out using genome-scale network modeling confirmed both tryptophan metabolism and nucleotide interconversion as relevant pathways potentially associated with disease severity. Metabolic modules composed of chemically adjacent or close compounds of biological relevance were further investigated using carbon transfer reaction paths. Overall, the proposed integrative data analysis strategy allowed deeper insights into the metabolic routes associated with different groups of patients to be gained. Because of their complementary role in the knowledge discovery process, the association of chemometrics and bioinformatics in a common workflow is therefore shown as an efficient methodology to gain meaningful insights in a clinical context., Competing Interests: The authors declare that this study received indirect partial funding from AstraZeneca. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication., (Copyright © 2021 Boccard, Schvartz, Codesido, Hanafi, Gagnebin, Ponte, Jourdan and Rudaz.)

Introduction: Faculty of medicine plays a role to support the students' success in passing national exit exam through mentorship. Peer-reflection evaluates the students' learning process. We aimed to analyze the impact of peer-reflection to change the students' learning attitude and improve national exam score., Methods: Nine test-retaker students participated in mentorship program for three months. They took two parts of faculty-level examination. After the 1st and the 2nd part of faculty exam, there were peer-reflections I and II that argued about the characters, strengths and weaknesses, suggestions. Then, they did self-reflection to conduct responses about the mentorship including the impact of peers' input and finally took national exam. The examination score before and after peer-reflection were compared. We analyzed the statement of reflection by documents and content analysis. The progress of examination score was analyzed descriptively., Results: The students objectively understood the strengths and weaknesses of their way of learning, and then implemented the peers' advices. Peer-reflection method provided a feeling of same purpose, then developed ways of learning that promoted them to be higher motivated. Finally, 6 of 9 students passed the exam., Discussion: Suggestions given by peers would be memorable and powerfully changed motivation. Peer-reflection explored non-academic problems that determined the pattern and the way of how students learned., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Hanafi et al.)

Napabucasin, undergoing multiple clinical trials, was reported to inhibit the signal transducer and transcription factor 3 (STAT3). To better elucidate its mechanism of action, we designed a napabucasin-based proteolysis targeting chimera (PROTAC), XD2-149 that resulted in inhibition of STAT3 signaling in pancreatic cancer cell lines without inducing proteasome-dependent degradation of STAT3. Proteomics analysis of XD2-149 revealed the downregulation of the E3 ubiquitin-protein ligase ZFP91. XD2-149 degrades ZFP91 with DC 50 values in the nanomolar range. The cytotoxicity of XD2-149 was significantly, but not fully, reduced with ZFP91 knockdown providing evidence for its multi-targeted mechanism of action. The NQO1 inhibitor, dicoumarol, rescued the cytotoxicity of XD2-149 but not ZFP91 degradation, suggesting that the NQO1-induced cell death is independent of ZFP91. ZFP91 plays a role in tumorigenesis and is involved in multiple oncogenic pathways including NF-κB and HIF-1α.

Banana mild mosaic virus (BanMMV) (Betaflexiviridae, Quinvirinae, unassigned species) is a filamentous virus belonging to the Betaflexiviridae family. It infects Musa spp. with a very wide geographic distribution. The genome variability of plant viruses, including the members of the Betaflexiviridae family, makes their molecular detection by specific primers particularly challenging. During routine indexing of the Musa germplasm accessions, a discrepancy was observed between electron microscopy and immunocapture (IC) reverse transcription (RT) polymerase chain reaction (PCR) test results for one asymptomatic accession. Filamentous viral particles were observed while molecular tests failed to amplify any fragment. The accession underwent high-throughput sequencing and two complete genomes of BanMMV with 75.3% of identity were assembled. Based on these sequences and on the 54 coat protein sequences available from GenBank, a new forward primer, named BanMMV CP9, compatible with Poty1, an oligodT reverse primer already used in diagnostics, was designed. A retrospective analysis of 110 different germplasm accessions from diverse origins was conducted, comparing BanMMCP2 and BanMMV CP9 primers. Of these 110 accessions, 16 tested positive with both BanMMCP2 and BanMMV CP9, 3 were positive with only BanMMCP2 and 2 tested positive with only BanMMV CP9. Otherwise, 89 were negative with the two primers and free of flexuous virions. Sanger sequencing was performed from purified PCR products in order to confirm the amplification of the BanMMV sequence for the five accessions with contrasting results. It is highly recommended to use the two primers successively to improve the inclusiveness of the protocol.

Objective: Elastases are protease enzymes, which mainly hydrolyze proteins of the connective tissue, so they have a significant impact on human disease. Rubus rosifolius is one of the Rubus species found in Indonesian mountains, and it has potential as an elastase inhibitor. The objective of this research was to examine the in vitro elastase inhibitor activity of R. rosifolius leaves and to dock different ligands of its constituents against target protein of Porcine Pancreatic Elastase (PPE) receptor., Method: Dried leaves powder of R. rosifolius was extracted using Soxhlet apparatus with n -hexane, ethyl acetate, and methanol. The extract was evaporated, and in vitro elastase inhibitor activity was determined using PPE with the quercetin used as control positive. Selected nine constituents of R. rosifolius were evaluated on the docking behavior of elastase receptor using Protein-Ligand ANT System (PLANTS) computational software with PPE enzyme with Protein Data Bank (PDB) file 1BRU., Result: The methanol extract showed significantly inhibited elastase with IC50 186.13 μg/mL, but ethyl acetate extract showed weak activity, and n -hexane extract did not show any activity. Docking studies and binding free energy calculations and hydrogen bonding with some amino acids revealed that ellagic acid showed the least binding energy for the target enzyme., Conclusion: This research has opened new insights into understanding that constituents of R. rosifolius methanol extract are potential inhibitors against elastase, and suggested the active compound is ellagic acid., Competing Interests: There are no conflicts of interest., (© 2020 Journal of Pharmacy and Bioallied Sciences.)

We took advantage of pseudopartial wetting to promote the spreading of precursor films whose surface density smoothly decays to zero away from a sessile droplet. By following the spreading dynamics of semidilute precursor films of polybutadiene melts on silicon wafers, we measure molecular diffusion coefficients for different molar masses and temperatures. For homopolymers, chains follow a thermally activated 2D Rouse diffusion mechanism, with an activation energy revealing polymer segment interactions with the surface. This Rouse model is generalized to chains with specific terminal groups.

Background: Acute myeloid leukemia (AML) evolves from neoplastic transformation of stem cell disease termed "leukemia stem cells" (LSCs). An unsatisfactory response to AML therapy is determined by the presence of minimal residual disease (MRD). The predominance of LSCs might anticipate sustained MRD results. The present study aimed to demonstrate the effect of LSCs on MRD at induction days 14 and 28 on overall survival (OS) and disease-free survival (DFS) and to compare LSC expression with MRD status., Patients and Methods: A total of 84 patients with de novo adult AML underwent testing using LSC panels for CD38/CD123/CD34/CD45 and CD90/CD133/CD45/CD33 and different regular MRD panels., Results: At day 14 after induction, the high expression of CD123 and CD133 had adverse effects on both OS and DFS (P = .004 and P ≤ .001 and P ≤ .001 and P ≤ .001, respectively). Greater expression of CD34 + /CD38 - /CD123 + resulted in unfavorable OS and DFS (P ≤ .001 for both). Both CD34 + /CD38 - /CD123 + and CD34 - /CD38 + /CD123 + expression at day 14 after induction had an adverse effect on DFS only (P < .001 and P = .029, respectively). On multivariate analysis, CD133 expression and MRD status were independent prognostic parameters (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.2-4.4; P = .015; and HR, 2.9; 95% CI, 1.0-7.9; P = .041). At day 28 after induction, MRD and increased CD123 + /CD34 - , CD34 + /CD38 - /CD123 + , CD133 + /CD33 - expression were associated with inferior OS (P = .016, P = .0035, P = .0.002, and P = .002, respectively). MRD and high expression of CD34 + CD123 + , CD133 + /CD33 - , CD34 + /CD38 - /CD123 + were associated with inferior DFS (P < .001, P = .002, P < .001, P < .001, respectively). On multivariate analysis, only CD133 + /CD33 - expression was the independent prognostic factor (HR, 3.1; 95% CI, 1.5-6.7; P = .003)., Conclusions: Estimation of LSC expression is a sensitive indicator of the response to therapy in adult patients with AML and might be a better prognosticator than the findings from regular MRD panels., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Extinction of natural resources builds up pressure on governments to invest in research to find more sustainable resources within the construction sector. Earlier studies on mortar and concrete show that bottom ash and basalt fiber are independently alternative binders in the concrete sector. This study aims to use bottom ash and basalt fiber blends as alternative novel-based composites in pure cement paste. The strength and durability properties of two different percentages of bottom ash (40% and 50%) and three volume fractions of basalt fiber (0.3%, 0.75%, and 1.5%) were used at three curing periods (7, 28, and 56 days). In order to measure the physical properties of the basalt-reinforced bottom ash cement paste composites flowability, dry unit weight, porosity, and water absorption measurements at 7, 28, and 56 days of curing were performed. Furthermore, the mechanical properties of composites were determined by unconfined compressive strength and flexural strength tests. Finally, to assess the durability, sulfate-resistance and seawater-resistance tests have been performed on composites at 28 and 56 days of curing. Results showed that the addition of basalt fiber improves the physical, mechanical, and chemical stability properties of paste up to a limiting basalt fiber addition (0.3% volume fraction) where, above, an adverse effect has been monitored. It is clear that observed results can lead to the development of sustainability strategies in the concrete industry by utilizing bottom ash and basalt fiber as an alternative binder.

The liquid crystal state is an ordered physical state between a solid and a liquid. Previous research, in gas chromatography, proved that it provides a geometric selectivity, which allows the separation of geometric position isomers and cis-trans isomers that are difficult to separate on conventional gas chromatography stationary phases (polydimethyl siloxane derived and polyethylene glycol stationary phases). However, their use was generally very limited by the rather high temperature at which they must be operated, normally above the solid-liquid crystal transition temperature. In the present study we are interested in a new synthesized material, 1,4- bis (4-bromohexyloxy benzoate) phenyl (BHOBP). The first characterizations of BHOBP were carried out by thermogravimetric analysis, hot-stage optical microscopy and differential scanning calorimetry to control the thermal stability of the BHOBP as well as the nematic texture of the mesophase highlighted in a well-defined temperature range (120 °C-200 °C). When heated, the solid compound led to a stable liquid crystal state. Its cooling has revealed "a new metastable physical state, which is the supercooled liquid crystal phase". After these first characterizations, the new material was used as a stationary phase for gas chromatography. The BHOBP was deposited in a capillary column by the dynamic method. The inverse gas chromatography study of the column revealed a solid-stable nematic phase transition temperature, in agreement with the first characterization methods. The stable liquid crystal phase showed good resolutions in the analysis of some geometric isomers of low volatility as PAHs. The presence of the supercooled liquid crystal state in the chromatographic column has also been confirmed. This new metastable state is particularly interesting because it enlarged the scope of this material by improving the resolution of several mixtures. Thus, the separation of highly volatile mixtures of geometric isomers (e.g. cis and trans-decalin) was achieved only through this metastable mesophase confirming its unique selectivity. The metastable liquid crystal, used at 80 °C, has also exhibited an original behavior by its stability after several weeks of use at the same temperature, maintaining constant retention factors and selectivity., 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 © 2019. Published by Elsevier B.V.)

Background and Objectives: Endophytic actinomycetes have been known as a promising source for new antibiotics discovery against susceptible and resistant forms of pathogenic microorganisms. This study was aimed at determining antibacterial compound from Streptomyces sp. strain B-92 isolated from a medicinal plant Neesia altissima ., Materials and Methods: Streptomyces sp. strain UICC B-92 was endophytic actinomycetes of N. altissima that obtained from Universitas Indonesia Culture Collection (UICC). Isolation and determination of bioactive compound were carried out using thin layer chromatography (TLC), nuclear magnetic resonance spectroscopy (NMR), and liquid chromatography mass spectrometry (LC-MS) analyses. An in vitro antibacterial assay of pure bioactive compound from the endophytic actinomycetes strain was performed against Bacillus cereus strain ATCC 10876, Escherichia coli strain ATCC 25922, Salmonella typhimurium strain ATCC 25241, Shigella flexneri strain ATCC 12022 and Staphylococcus aureus strain ATCC 25923., Results: The bioactive compound was identified as 4-((3S,4R,5S)-3,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-2-yloxy) phenazine-1-carboxylic acid. In vitro antimicrobial assay showed that bioactive compound of Streptomyces sp. strain UICC B-92 exhibited antagonistic activities against two Gram-positive bacteria, viz, B. cereus strain ATCC 10876 and S. aureus strain ATCC 25923., Conclusion: The findings of this research showed that, bioactive compound of Streptomyces sp. strain UICC B-92 is suggested a new compound based on glycoside structure and its position., (Copyright© 2020 Iranian Neuroscience Society.)

The purpose of this study was to perform a discrimination and classification of diesel samples from the four major suppliers of petroleum products in Morocco using Fourier Transform Infrared Spectroscopy (FTIR), Gas Chromatography coupled with Mass Spectrometry (GC-MS) and chemometrics tools. Eighty diesel samples were collected from different gas stations owned by the four biggest brands in the Moroccan market. Principal Component Analysis (PCA) was performed to depict the similarities between the samples and check the presence of outliers. Partial Least Squares Discriminant Analysis (PLS-DA) models were set up for the discrimination and the classification of the four groups of samples (i.e., diesel suppliers). The models proposed in this study, were characterized by good prediction abilities, especially the FTIR-PLSDA model that was characterized by 100% of accurate discrimination of the four groups. The approach of analysis showed that the FTIR spectra can provide a cheap and rapid means for the determination of the diesel origin and to ensure the traceability of diesel products marketed in Morocco with respect for the rules of the green chemistry., (Copyright © 2019 Elsevier B.V. All rights reserved.)