Effect of Strain Rate on Hydrogen Embrittlement of Ti6Al4V Alloy.

The phenomenon of hydrogen embrittlement (HE) in metals and alloys, which determines the performance of components in hydrogen environments, has recently been drawing considerable attention. This study explores the interplay between strain rates and solute hydrogen in inducing HE of Ti6Al4V alloy. For the hydrogen-charged sample, as the strain rate was decreased from 10-2/s to 10-5/s, the ductility decreased significantly, but the HE effect on mechanical strength was negligible. The low strain rate (LSR) conditions facilitated the development of high-angle grain boundaries, providing more pathways for hydrogen diffusion and accumulation. The presence of solute hydrogen intensified the formation of nano/micro-voids and intergranular cracking tendencies, with micro-crack occurrences observed exclusively in the LSR conditions. These factors expanded the brittle hydrogen-damaged region more deeply into the interior of the lattice. This, in turn, accelerated both crack initiation and intergranular crack propagation, finally resulting in a considerable HE effect and a reduction in ductility at the LSR. The current study underscores the influence of strain rate on HE, enhancing the predictability of longevity and improving the reliability of components operating in hydrogen-rich environments under various loading conditions.

Deciphering Hydrogen Embrittlement Mechanisms in Ti6Al4V Alloy: Role of Solute Hydrogen and Hydride Phase.

Ti6Al4V (Ti64) is a versatile material, finding applications in a wide range of industries due to its unique properties. However, hydrogen embrittlement (HE) poses a challenge in hydrogen-rich environments, leading to a notable reduction in strength and ductility. This study investigates the complex interplay of solute hydrogen (SH) and hydride phase (HP) formation in Ti64 by employing two different current densities during the charging process. Nanoindentation measurements reveal distinct micro-mechanical behavior in base metal, SH, and HP, providing crucial insights into HE mechanisms affecting macro-mechanical behavior. The fractography and microstructural analysis elucidate the role of SH and HP in hydrogen-assisted cracking behaviors. The presence of SH heightens intergranular cracking tendencies. In contrast, the increased volume of HP provides sites for crack initiation and propagation, resulting in a two-layer brittle fracture pattern. The current study contributes to a comprehensive understanding of HE in Ti6Al4V, essential for developing hydrogen-resistant materials.

Verticillium dahliae VdPBP1 Transcription Factor Is Required for Hyphal Growth, Virulence, and Microsclerotia Formation.

Verticillium dahliae, a fungal pathogen that affects more than 200 plant species, including tomatoes, requires specific proteins for its early steps in plant infection. One such crucial protein, VdPBP1, exhibits high expression in the presence of tomato roots. Its 313-amino acid C-terminal section restores adhesion in nonadhesive Saccharomyces cerevisiae strains. To uncover its role, we employed a combination of bioinformatics, genetics, and morphological analyses. Our findings underscore the importance of VdPBP1 in fungal growth and pathogenesis. Bioinformatic analysis revealed that the VdPBP1 gene consists of four exons and three introns, encoding a 952-codon reading frame. The protein features a 9aaTAD domain, LsmAD, and PAB1 DNA-binding sites, as well as potential nuclear localization and transmembrane helix signals. Notably, the deletion of a 1.1 kb fragment at the gene's third end impedes microsclerotia formation and reduces pathogenicity. Mutants exhibit reduced growth and slower aerial mycelial development compared to the wild type. The VdPBP1 deletion strain does not induce disease symptoms in tomato plants. Furthermore, VdPBP1 deletion correlates with downregulated microsclerotia formation-related genes, and promoter analysis reveals regulatory elements, including sites for Rfx1, Mig1, and Ste12 proteins. Understanding the regulation and target genes of VdPBP1 holds promise for managing Verticillium wilt disease and related fungal pathogens.

Spatial epidemiology of human anthrax in Son La province, Vietnam, 2003-2022.

AIMS: Anthrax is reported with frequency but poorly understood in Southeast Asian countries including Vietnam. In Vietnam, anthrax surveillance is national. However, case detection, prevention, and control are implemented locally at the provincial level. Here, we describe the epidemiological characteristics, identify spatial clusters of human anthrax, and compare the variation in livestock anthrax vaccine coverage to disease incidence in humans and livestock using historical data in Son La province, Vietnam (2003-2020). METHODS AND RESULTS: Most human cases occurred between April and September. Most of the patients were male, aged 15-54 years old. The human cases were mainly reported by public district hospitals. There was a delay between disease onset and hospitalization of ~5 days. We identified spatial clusters of high-high incidence communes in the northern communes of the province using the local Moran's I statistic. The vaccine coverage sharply decreased across the study period. The province reported sporadic human anthrax outbreaks, while animal cases were only reported in 2005 and 2022. CONCLUSIONS: These results suggest underreporting for human and livestock anthrax in the province. Intersectoral information sharing is needed to aid livestock vaccination planning, which currently relies on reported livestock cases. The spatial clusters identify areas for targeted surveillance and livestock vaccination, while the seasonal case data suggest prioritizing vaccination campaigns for February or early March ahead of the April peak. A regional approach for studying the role of livestock trading between Son La and neighbouring provinces in anthrax occurrence is recommended.

Drought stress-responsive abscisic acid and salicylic acid crosstalk with the phenylpropanoid pathway in soybean seeds.

Crosstalk between hormones and secondary metabolites regulates the interactions between plants and stress. However, little is known about the effects of hormone crosstalk on the concentration of flavonoids in seeds. In this study, we identified abscisic acid (ABA) as a negative regulator of flavonoid accumulation in soybean seeds under drought-stress conditions. Alterations in flavonoid accumulation at several intensities of water stress, followed by a recovery period, were measured during the soybean seed-filling stage. Low soil moisture (SM 10%) significantly decreased the total flavonoid content in seeds. The decline in flavonoid content was proportional to the severity of drought stress and was dependent on the activities of phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS), two key phenylpropanoid pathway enzymes. The expression of phenylalanine ammonia-lyase 1 (GmPAL1), chalcone isomerase 1A (GmCHI1A), and chalcone synthase 8 (GmCHS8) was associated with phenolic and flavonoid accumulation in soybean seeds of plants subjected to drought stress. Interestingly, the expression levels of GmCHS8 were highly correlated with flavonoid levels under drought stress and water recovery conditions. Cinnamic acid, which is a biosynthesis precursor shared by both phenylpropanoid metabolism and salicylic acid (SA) biosynthesis, decreased under drought stress conditions. Notably, exogenous ABA suppressed the expression of GmPAL1, which encodes the first rate-limiting enzyme in the phenylpropanoid biosynthesis pathway and affects downstream products such as SA and flavonoids. In conclusion, drought stress altered the phenylpropanoid-derived compounds, at least with regard to flavonoid and SA accumulation in seeds, which was regulated by antagonistic interactions with ABA.

Investigation on Methylene Blue Dye Adsorption in Aqueous by the Modified Mussel Shells: Optimization, Kinetic, Thermodynamic and Equilibrium Studies.

This study assessed the methylene blue adsorption using natural and modified mussel shell powders in the aqueous solution. The mussel shell samples were processed in a NaClO solution then modified with sodium dodecyl sulfate and ethylenediaminetetraacetic acid. The characteristics of mussel shell samples before and after modification were demonstrated using infared spectroscopy, thermogravimetric analysis, scanning electron microscopy, nitrogen adsorption/desorption, energy dispersive X-ray, water contact angle, and dynamic light scattering methods. Some factors such as the pH of the medium, adsorption temperature, and adsorption time had a significant effect on the methylene blue adsorption of mussel shell samples. The adsorption isotherm models and kinetics of methylene blue adsorption by mussel shell samples were also studied. A quadratic regression equation was selected with experimental planning following the Box-Behnken model combined with Design Expert 11.1.0.1 software to optimize the methylene blue adsorption process by mussel shell samples. These results open a promising direction for using naturally derived materials to remove organic pollutants from contaminated water.

Primary malignant melanoma of the male urethra: Case report and review of literature.

INTRODUCTION: We report a rare case of primary malignant melanoma with inguinal lymph node metastasis in the male urethra. CASE PRESENTATION: A 57-year-old male patient presented with a small tumor on the ventral surface of the penis, which was discovered 5 months ago and did not cause pain or discomfort. In the past month, the patient has developed symptoms of urinary incontinence. MRI and PET/CT scans revealed a primary tumor in the penile urethra, but no metastases were found. The patient underwent partial penectomy surgery and laparoscopic bilateral inguinal lymphadenectomy within one month. The pathological combined with immunohistochemical staining confirmed primary malignant melanoma in the urethra with right inguinal lymph node metastasis. Despite complying with surgical and immunotherapy treatment with Pembrolizumab for 18 cycles, the patient was diagnosed with recurrent cancer in the penile stump after 05 months and he passed away after 18 months. DISCUSSION: Urethral melanoma is a rare and highly invasive type of cancer. It was often diagnosed at a late stage because the initial symptoms were not obvious in the lower urinary tract. Additionally, cancer progressed very quickly, making it difficult to treat. CONCLUSION: Urethral melanoma, if detected at a late stage with lymph node metastasis, has a significantly poor prognosis irrespective of the treatment method employed. However, to our best knowledge, very few publications can be found on this disease, and the strategic treatment remained unknown.

To stay or re-migrate after the pandemic shock? Labor re-migration intention to the coastal areas of Thua Thiên Hue province in Vietnam.

This study applied the extended theory of planned behavior (ETPB) to explore factors that shape the behavioral intention of migrant laborers returning to the coastal region of Thua Thiên Hue province during the peak of the COVID-19 pandemic to remigrate. Data collection included 210 interviews with returned migrants aged 18 and above in 4 coastal communes of Thua Thiên Hue province, in-depth interviews (8 key informants) and a group discussion (5 persons). Exploratory factor analysis and a multivariate linear regression model were applied to analyze the data. Results showed that in addition to individual socio-demographic characteristics (i.e. level of education, age, income level and sex), attitudes, subjective norms, perceived behavioral control, and perceived risk were also determinant factors of migrants' intention to remigrate. This research suggested that in order to build resilience of rural migration workers, related departments should seriously consider the following recommendations: (i) raise awareness and encourage young rural people to complete their education and necessary skills; (ii) organize related psychological training programs for rural laborers; (iii) raise awareness about the necessity to participate in social insurance; (iv) promote rural job creation programs suitable for low education and low-skilled rural laborers; (v) raise awareness for local people, particularly school children, about the value and opportunities of being smart farmers in the context of 4.0 technology and social risks at the destination for low education and low-skilled laborers; (vi) digitalize migration labor management and provide digital information services regarding job opportunities for rural laborers.

Targeting Mitochondrial Metabolism to Save the Failing Heart.

Despite considerable progress in treating cardiac disorders, the prevalence of heart failure (HF) keeps growing, making it a global medical and economic burden. HF is characterized by profound metabolic remodeling, which mostly occurs in the mitochondria. Although it is well established that the failing heart is energy-deficient, the role of mitochondria in the pathophysiology of HF extends beyond the energetic aspects. Changes in substrate oxidation, tricarboxylic acid cycle and the respiratory chain have emerged as key players in regulating myocardial energy homeostasis, Ca2+ handling, oxidative stress and inflammation. This work aims to highlight metabolic alterations in the mitochondria and their far-reaching effects on the pathophysiology of HF. Based on this knowledge, we will also discuss potential metabolic approaches to improve cardiac function.

Estimation of the Acoustic Transducer Beam Aperture by Using the Geometric Backscattering Model for Side-Scan Sonar Systems.

In this paper, we propose an algorithm for estimating the beam aperture of the acoustic transducers by using the geometric backscattering model for side-scan sonar systems. The geometric backscattering model is developed to describe the propagation paths of the signal transmitted from the transducers towards the seabed and backscatters to the hydrophones. To evaluate our proposed algorithm, we have developed a side-scan sonar system. The side-scan sonar system uses two transducers, operating on two different frequencies and focusing on two different wave beams, to scan the images of the seabed. The proposed algorithm provides the estimated beam apertures of each transducer. Our obtained results agree quite well with the parameters provided by the manufacturers. Moreover, these results are used to calibrate the scanned images. We provide the scanned sonar 3D images of the Dong Do lakebed, Vietnam, to justify our proposal.

Acute Respiratory Distress Syndrome Associated with Multisystem Inflammatory Syndrome in a Child with Covid-19 and Diabetic Ketoacidosis: A Case Report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (Covid-19), has uncontrollable effects on many organs. A great number of previously published scientific reports have revealed that patients with diabetes mellitus face a more severe form of Covid-19 with a higher death rate. Here we present the case of a 13-year-old unvaccinated boy who was admitted to an intensive care unit (ICU) with a history of fever, cough, dyspnea, throat pain, nausea, and confusion that progressed to lethargy after 24 h. On clinical examination, he was in a coma with Kussmaul's breathing, and was anuric. His blood biochemical analysis demonstrated hyperglycemia, severe metabolic acidosis, kidney failure, electrolyte disturbances, and inflammation. Chest x-ray showed pneumonia and a pleural effusion. The results of the SARS-CoV-2 real-time polymerase chain reaction were positive. The patient was diagnosed with Covid-19-induced acute respiratory distress syndrome associated with multisystem inflammatory syndrome in children secondary to his acute respiratory failure, acute kidney injury, and new-onset type 1 diabetes mellitus with diabetic ketoacidosis. He was intubated for invasive mechanical ventilation and received a normal saline infusion and continuous insulin infusion (0.1 IU/kg/h) for the treatment of his diabetic ketoacidosis. He was also treated with methylprednisolone, aspirin, and heparin, and underwent continuous renal replacement therapy for acute renal failure for 9 days. The patient was discharged from ICU on day 16 and was followed up regularly as an outpatient with daily treatment, including subcutaneous insulin injection (30 IU/day) and a calcium channel blocker for hypertension (nifedipine 20 mg/day).

Bioglue endovascular treatment of fusiform aneurysm rupture of the distal anterior temporal artery of the middle cerebral artery: a case report.

The treatment of a ruptured fusiform distal anterior temporal artery aneurysm is a challenge for the stroke physician, however surgical closure and coil endovascular intervention are options. A total blockage can result in memory problems as well as object-related questions. We'd like to provide the clinical example of a 56-year-old woman with many underlying medical illnesses who was admitted to the hospital with a grade 7/10 headache and a Glasgow score of 15, but no focal neurological deficits, and was diagnosed with a ruptured distal temporal artery aneurysm. The aneurysm is positioned in the distal region, making endovascular intervention difficult to perform. As a result, we used an endovascular approach to repair with bioglue. When a patient develops fusiform aneurysms of the distal temporal artery, our findings provide an additional therapy option.

Steel slag quality control for road construction aggregates and its environmental impact: case study of Vietnamese steel industry-leaching of heavy metals from steel-making slag.

Steel slag is an industrial by product of steel manufacturing processes and has been widely utilized within civil and construction materials for road materials and environmental remediation in countries like Japan, USA, and European Union nations. However, the current utilization of steel slag in Vietnam is very low mainly because of lack of quality control of slag treatment and chances for reuse of treated steel slag. This paper presents the up to date steel slag production status in Vietnam through the extensive survey and sampling at seven large steel factories. The paper also highlights the environmental and quality control issues of these steel slags to use as road construction aggregates by assessing the heavy metals concentration in the leachate. The basic oxygen furnace (BOF) and electric arc furnace (EAF) slag samples were collected to evaluate leaching properties of metals leached from the slags. The two standardized batch leaching tests of steel slag roadbed material in Japan (JIS K 0058-1) and toxicity characteristics leaching procedure (TCLP-EPA method 1311) were performed to the evaluated the hazardous metals. The results of the leaching test show that almost all of the concentration of the metals in the leached solution does not exceed the National Standard for Industrial Wastewater Discharge (QCVN 40-2011). The pH and parameters such as total chromium, nickel, copper, lead, arsenic, and manganese differ from the two test methods. The acidic conditions employed in the EPA 1311 were not representative of condition excepted during slag reuse in road constructions because in the operation condition of the road, acidic liquid is absent. The leaching test results confirmed that JIS test which uses deionized water with gentle mixing prevents the slag sample from size degradation is suitable for the environmental assessment of steel slag use for roadbed material. This research suggests that the adjustment of pH value prior to disposal or reuse as base materials and official guideline should be promulgate by the authorities to ensure the leachate meet the surface water quality standard.

A giant fusiform middle cerebral artery treated by low-flow superficial temporal artery bypass: A case report.

A giant fusiform aneurysm of the middle cerebral artery is a disease that causes many difficulties for endovascular intervention as well as surgery. No 1 solution is optimal for all cases, however for post-bifurcation aneurysms, trapping the aneurysms with a reanastomosis reimplantation, an in situ side to side bypass is feasible and has good results. We reported a 28-year-old male patient, admitted to the hospital because of severe headache, Glasgow Coma Scale 13 points, left hemiplegia, was diagnosed with subarachnoid hemorrhage due to rupture of a giant fusiform aneurysm of the middle cerebral artery in the M2 segment, Hunt and Hess grade 4. The patient underwent microsurgery with clipping aneurysm combined with a low-flow technique connecting the superficial temporal artery to the middle cerebral artery. Our findings suggest that surgery to connect the superficial temporal artery to the M2 segment and at the same time obstructing the parent artery occlusion of selected giant MCA aneurysm is an option to consider.

Convergence of Bar and Cry1Ac Mutant Genes in Soybean Confers Synergistic Resistance to Herbicide and Lepidopteran Insects.

Soybean is a globally important crop species, which is subject to pressure by insects and weeds causing severe substantially reduce yield and quality. Despite the success of transgenic soybean in terms of Bacillus thuringiensis (Bt) and herbicide tolerance, unforeseen mitigated performances have still been inspected due to climate changes that favor the emergence of insect resistance. Therefore, there is a need to develop a biotech soybean with elaborated gene stacking to improve insect and herbicide tolerance in the field. In this study, new gene stacking soybean events, such as bialaphos resistance (bar) and pesticidal crystal protein (cry)1Ac mutant 2 (M#2), are being developed in Vietnamese soybean under field condition. Five transgenic plants were extensively studied in the herbicide effects, gene expression patterns, and insect mortality across generations. The increase in the expression of the bar gene by 100% in the leaves of putative transgenic plants was a determinant of herbicide tolerance. In an insect bioassay, the cry1Ac-M#2 protein tested yielded higher than expected larval mortality (86%), reflecting larval weight gain and weight of leaf consumed were less in the T1 generation. Similarly, in the field tests, the expression of cry1Ac-M#2 in the transgenic soybean lines was relatively stable from T0 to T3 generations that corresponded to a large reduction in the rate of leaves and pods damage caused by Lamprosema indicata and Helicoverpa armigera. The transgenic lines converged two genes, producing a soybean phenotype that was resistant to herbicide and lepidopteran insects. Furthermore, the expression of cry1Ac-M#2 was dominant in the T1 generation leading to the exhibit of better phenotypic traits. These results underscored the great potential of combining bar and cry1Ac mutation genes in transgenic soybean as pursuant of ensuring resistance to herbicide and lepidopteran insects.

Acute myocarditis after COVID-19 vaccination with mRNA-1273 in a patient with former SARS-CoV-2 infection.

We describe a case of a 20-year-old healthy man developing chest pain and classical symptoms of vaccine reactogenicity 12 h after receiving the first dose of mRNA-1273 (Moderna). Cardiac troponin T was increased, and subepicardial inflammation and focal contractile dysfunction were detected by cardiac magnetic resonance imaging and echocardiography. We confirmed the diagnosis of acute myocarditis by endomyocardial biopsy demonstrating significant infiltration of monocytes and T lymphocytes. Although we detected IgG against nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) indicating prior infection, the patient repeatedly tested negative for SARS-CoV-2 and had been asymptomatic for several months. Furthermore, viral genome analysis of endomyocardial biopsy samples was negative for SARS-CoV-2 and other potential cardiotropic viruses. These findings and the strong temporal relation between the vaccination and the symptom onset imply a potential side effect of mRNA-1273.

On the Inhibitability of Natural Products Isolated from Tetradium ruticarpum towards Tyrosine Phosphatase 1B (PTP1B) and α-Glucosidase (3W37): An In Vitro and In Silico Study.

Folk experiences suggest natural products in Tetradium ruticarpum can be effective inhibitors towards diabetes-related enzymes. The compounds were experimentally isolated, structurally elucidated, and tested in vitro for their inhibition effects on tyrosine phosphatase 1B (PTP1B) and α-glucosidase (3W37). Density functional theory and molecular docking techniques were utilized as computational methods to predict the stability of the ligands and simulate interaction between the studied inhibitory agents and the targeted proteins. Structural elucidation identifies two natural products: 2-heptyl-1-methylquinolin-4-one (1) and 3-[4-(4-methylhydroxy-2-butenyloxy)-phenyl]-2-propenol (2). In vitro study shows that the compounds (1 and 2) possess high potentiality for the inhibition of PTP1B (IC50 values of 24.3 ± 0.8, and 47.7 ± 1.1 µM) and α-glucosidase (IC50 values of 92.1 ± 0.8, and 167.4 ± 0.4 µM). DS values and the number of interactions obtained from docking simulation highly correlate with the experimental results yielded. Furthermore, in-depth analyses of the structure-activity relationship suggest significant contributions of amino acids Arg254 and Arg676 to the conformational distortion of PTP1B and 3W37 structures overall, thus leading to the deterioration of their enzymatic activity observed in assay-based experiments. This study encourages further investigations either to develop appropriate alternatives for diabetes treatment or to verify the role of amino acids Arg254 and Arg676.

Vertical financial disparity, energy prices and emission reduction: Empirical insights from Pakistan.

The economic and environmental aspects of energy production have become important due to the increasing complexity energy sector and envoirnmental pollution, warranting to test the connection between financial imbalances, energy prices and carbon emission. The study aims to test the impact of vertical fiscal imbalances (VFI) on energy prices and carbon emission trends by considering the dual-perspectives of environmental regulation and industrial structure. The empirical outcomes indicated that vertical fiscal imbalances limited the environmental quality of Pakistan. Furthermore, VFI also caused environmental degradation by affecting industrial structure. VFI inhibits the intensity of environmental regulation, promotes the upgrade of industrial structures, both of which cause additional carbon emissions. The study suggest to energy ministries and energy regulation offices to revisit the machinism of energy prices determination and revised machanisim should provide a user-friendly assessment to understand the actual costs associated with the rising concern of environmental pollution. By this, envoirnmental protection maximization and optimal energy conservation is expacted to increase. Based on empirical findings, the study extends the suggestion that vertical fiscal imbalances should be considered an active indicator by the key policy makers and other stakeholders for energy prices determination and environmental quality upgradation.

Low-Dose vs. Standard-Dose Intravenous Alteplase in Bridging Therapy Among Patients With Acute Ischemic Stroke: Experience From a Stroke Center in Vietnam.

Background: To date, the role of bridging intravenous thrombolysis before mechanical thrombectomy (MTE) is controversial but still recommended in eligible patients. Different doses of intravenous alteplase have been used for treating patients with acute ischemic stroke from large-vessel occlusion (LVO-AIS) in Asia, largely due to variations in the risks for intracerebral hemorrhage (ICH) and treatment affordability. Uncertainty exists over the potential benefits of treating low-dose alteplase, as opposed to standard-dose alteplase, prior to MTE among patients with LVO-AIS. Aim: The aim of the study was to compare outcomes of low- vs. standard-dose of bridging intravenous alteplase before MTE among LVO-AIS patients. Methods: We performed a retrospective analysis of LVO-AIS patients who were treated with either 0.6 mg/kg or 0.9 mg/kg alteplase prior to MTE at a stroke center in Northern Vietnam. Multivariable logistic regression models, accounting for potential confounding factors including comorbidities and clinical factors (e.g., stroke severity), were used to compare the outcomes between the two groups. Our primary outcome was functional independence at 90 days following stroke (modified Rankin score; mRS ≤ 2). Secondary outcomes included any ICH incidence, early neurological improvement, recanalization rate, and 90-day mortality. Results: We analyzed data of 107 patients receiving bridging therapy, including 73 with low-dose and 34 with standard-dose alteplase before MTE. There were no statistically significant differences between the two groups in functional independence at 90 days (adjusted OR 1.02, 95% CI 0.29-3.52) after accounting for potential confounding factors. Compared to the standard-dose group, patients with low-dose alteplase before MTE had similar rates of successful recanalization, early neurological improvement, 90-day mortality, and ICH complications. Conclusion: In the present study, patients with low-dose alteplase before MTE were found to achieve comparable clinical outcomes compared to those receiving standard-dose alteplase bridging with MTE. The findings suggest potential benefits of low-dose alteplase in bridging therapy for Asian populations, but this needs to be confirmed by further clinical trials.