The Identification of Enteric Fever-Specific Antigens for Population-Based Serosurveillance.

BACKGROUND: Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi A, is a major public health problem in low- and middle-income countries. Moderate sensitivity and scalability of current methods likely underestimate enteric fever burden. Determining the serological responses to organism-specific antigens may improve incidence measures. METHODS: Plasma samples were collected from blood culture-confirmed enteric fever patients, blood culture-negative febrile patients over the course of 3 months, and afebrile community controls. A panel of 17 Salmonella Typhi and Paratyphi A antigens was purified and used to determine antigen-specific antibody responses by indirect ELISAs. RESULTS: The antigen-specific longitudinal antibody responses were comparable between enteric fever patients, patients with blood culture-negative febrile controls, and afebrile community controls for most antigens. However, we found that IgG responses against STY1479 (YncE), STY1886 (CdtB), STY1498 (HlyE), and the serovar-specific O2 and O9 antigens were greatly elevated over a 3-month follow up period in S. Typhi/S. Paratyphi A patients compared to controls, suggesting seroconversion. CONCLUSIONS: We identified a set of antigens as good candidates to demonstrate enteric fever exposure. These targets can be used in combination to develop more sensitive and scalable approaches to enteric fever surveillance and generate invaluable epidemiological data for informing vaccine policies. CLINICAL TRIAL REGISTRATION: ISRCTN63006567.

The Germin-like protein OsGER4 is involved in promoting crown root development under exogenous jasmonic acid treatment in rice.

In rice (Oryza sativa L.), crown roots (CRs) have many important roles in processes such as root system expansion, water and mineral uptake, and adaptation to environmental stresses. Phytohormones such as auxin, cytokinin, and ethylene are known to control CR initiation and development in rice. However, the role of jasmonic acid (JA) in CR development remained elusive. Here, we report that JA promotes CR development by regulating OsGER4, a rice Germin-like protein. Root phenotyping analysis revealed that exogenous JA treatment induced an increase in CR number in a concentration-dependent manner. A subsequent genome-wide association study and gene expression analyses pinpointed a strong association between the Germin-like protein OsGER4 and the increase in CR number under exogenous JA treatment. The ProGER4::GUS reporter line showed that OsGER4 is a hormone-responsive gene involved in various stress responses, mainly confined to epidermal and vascular tissues during CR primordia development and to vascular bundles of mature crown and lateral roots. Notable changes in OsGER4 expression patterns caused by the polar auxin transport inhibitor NPA support its connection to auxin signaling. Phenotyping experiments with OsGER4 knockout mutants confirmed that this gene is required for CR development under exogenous JA treatment. Overall, our results provide important insights into JA-mediated regulation of CR development in rice.

Incommensurate Antiferromagnetic Order in Weakly Frustrated Two-Dimensional van der Waals Insulator CrPSe3.

Although magnetic order is suppressed by a strong frustration, it appears in complex forms such as a cycloid or spin density wave in weakly frustrated systems. Herein, we report a weakly magnetically frustrated two-dimensional (2D) van der Waals material CrPSe3. Polycrystalline CrPSe3 was synthesized at an optimized temperature of 700 °C to avoid the formation of any secondary phases (e.g., Cr2Se3). The antiferromagnetic transition appeared at TN ≈ 127 K with a large Curie-Weiss temperature θCW ≈ -301 K via magnetic susceptibility measurements, indicating weak frustration in CrPSe3 with a frustration factor of f (|θCW|/TN) ≈ 2.4. Evidently, the formation of a long-range incommensurate antiferromagnetic order was revealed by neutron diffraction measurements at low temperatures (below 120 K). The monoclinic crystal structure of the C2/m symmetry is preserved over the studied temperature range down to 20 K, as confirmed by Raman spectroscopy measurements. Our findings on the incommensurate antiferromagnetic order in 2D magnetic materials, not previously observed in the MPX3 family, are expected to enrich the physics of magnetism at the 2D limit, thereby opening opportunities for their practical applications in spintronics and quantum devices.

Awaji criteria for the diagnosis of amyotrophic lateral sclerosis in Hanoi, Vietnam.

The aim of the article was to evaluate the role of electromyography and the value of Awaji criteria for the diagnosis of ALS in the early stage. The study involves 48 patients (27 male and 21 females from 41 to 84 years old) who went to Bach Mai Hospital and Dong Do Clinic in Hanoi and were diagnosed with ALS according to Awaji criteria. All patients underwent clinical examination for ALS. The patients were examined for nerve conduction (motor and sensory conduction) using needle electromyography (EMG). Upper motor neuron (UMN) signs and lower motor neuron (LMN) signs were most common in the cervical region (89.58%), the lumbosacral region (70.83%), and the bulbar region (56.25%). The sensory nerve conduction was normal. The spontaneous activities (fasciculation, fibrillation, positive wave) accounted for more than 50% in all 4 regions: bulbar, cervical, thoracic, and lumbosacral regions. The abnormality of both clinical and electrodiagnosis was seen in the cervical region (87.5%) and lumbosacral one (70.83%) while the bulbar region and thoracic one usually had abnormal electrodiagnosis before clinical. There were 60.42% of patients with "definite ALS" by Awaji criteria. It allowed to make an earlier diagnosis cause the sensitivity of Awaji criteria (93.75%) was higher than the revised El Escorial criteria (85.42%) (p < 0.05). The needle EMG makes it possible to detect the early-stage symptoms of ALS in a situation where there are no clinical manifestations, especially in bulbar and thoracic regions.

Heterologous expression of the diazaquinomycin biosynthetic gene cluster.

Members of the diazaquinomycin class of natural products have shown potent and selective activity against Mycobacterium tuberculosis. However, poor aqueous solubility has prevented extensive studies in animal models thus far. Our long-term goal is to harness knowledge regarding diazaquinomycin biosynthesis towards the generation of derivatives for structure-activity relationship studies. We have previously sequenced the genomes of two diazaquinomycin-producing, actinomycete bacteria and identified putative daq biosynthetic gene clusters. Here, we report the heterologous expression of the daq gene cluster from the marine Streptomyces sp. F001 in S. coelicolor M1152. In addition to serving as functional proof for gene cluster assignment, the heterologous expression system reported here is expected to facilitate investigations aimed at elucidating diazaquinomycin biosynthesis.

Cost of Hospitalization for Foodborne Diarrhea: A Case Study from Vietnam.

Vietnam is undergoing a rapid social and economic developments resulting in speedy urbanization, changes in methods for animal production, food marketing systems, and food consumption habits. These changes will have major impacts on human exposures to food poisoning. The present case study aimed to estimate hospitalization costs of foodborne diarrhea cases in selected health facilities in Vietnam. This is a facility-based cost-of-illness study conducted in seven health facilities in Northern Vietnam. All suspect cases of foodborne diarrhea, as diagnosed by doctors, who admitted to the studied health facilities during June-August, 2013 were selected. Costs associated with hospitalization for foodborne diseases were estimated from societal perspective using retrospective approach. We included direct and indirect costs of hospitalization of foodborne diarrhea cases. During the study period, 87 foodborne diarrhea cases were included. On average, the costs per treatment episode and per hospitalization day for foodborne diarrhea case were US$ 106.9 and US$ 33.6 respectively. Indirect cost (costs of times to patient, their relatives due to the patient's illness) made up the largest share (51.3%). Direct medical costs accounted for 33.8%; direct non-medical costs (patient and their relatives) represented 14.9%. Cost levels and compositions varied by level of health facilities. More attentions should be paid on prevention, control of foodborne diarrhea cases in Vietnam. Ensuring safety of food depends on efforts of everyone involved in food chain continuum, from production, processing, and transport to consumption.

Patterns of Health Expenditures and Financial Protections in Vietnam 1992-2012.

Health financing has been considered as an important building block of a health system and has a key role in promoting universal health coverage in the Vietnam. This paper aims to describe the pattern of health expenditure, including total health expenditure and composition of health expenditure, over the last two decades in Vietnam. The paper mainly uses the data from Vietnam National Health Account and Vietnam Living Standards Survey. We also included data from other relevant published literature, reports and statistics about health care expenditure in Vietnam. The per capita health expenditure in Vietnam increased from US$ 14 in 1995 to US$ 86 in 2012. The total health expenditure as a share of GDP also rose from 5.2% in 1995 to 6.9% in 2012. Public health expenditure as percentage of government expenditure rose from 7.4% in 1995 to nearly 10% in 2012. The coverage of health insurance went up from 10% in 1995 to 68.5% in 2012. However, health financing in Vietnam was depending on private expenditures (57.4% in 2012). As a result, the proportion of households with catastrophic expenditure in 2012 was 4.2%. The rate of impoverishment in 2012 was 2.5%. To ensure equity and efficient goal of health system, policy actions for containing the health care out-of-pocket payments and their poverty impacts are urgently needed in Vietnam.

Severe Pneumonia Caused by Respiratory Syncytial Virus and Adenovirus in Children from 2 to 24 Months at Children's Hospital 1 in Ho Chi Minh City, Vietnam.

In Vietnam, due to the lack of facilities to detect respiratory viruses from patients' specimens, there are only a few studies on the detection of viral pathogens causing pneumonia in children, especially respiratory syncytial virus (RSV) and adenovirus (Adv). Here, we performed a cross-sectional descriptive prospective study on 138 children patients from 2 to 24 months old diagnosed with severe pneumonia hospitalized at the Respiratory Department of Children's Hospital 1 from November 2021 to August 2022. The number of patients selected in this study was based on the formula n = ([Z(1 - α/2)]2 × P [1 - P])/d2, with α = 0.05, p = 0.5, and d = 9%, and the sampling technique was convenient sampling until the sample size was met. A rapid test was used to detect RSV and Adv from the nasopharyngeal swabs and was conducted immediately after the patient's hospitalization. Laboratory tests were performed, medical history interviews were conducted, and nasotracheal aspirates were collected for multiplex real-time PCR (MPL-rPCR) to detect viral and bacterial pathogens. The results of the rapid test and the MPL-rPCR in the detection of both pathogens were the same at 31.9% (44/138) for RSV and 8.7% (7/138) for Adv, respectively. Using MPL-rPCR, the detection rate was 21% (29/138) for bacterial pathogens, 68.8% (95/138) for bacterial-viral co-infections, and 6.5% (9/138) for viral pathogens. The results showed few distinctive traits between RSV-associated and Adv-associated groups, and the Adv group children were more prone to bacterial infection than those in the RSV group. In addition, the Adv group experienced a longer duration of treatment and a higher frequency of re-hospitalizations compared to the RSV group. A total of 100% of Adv infections were co-infected with bacteria, while 81.82% of RSV co-infected with bacterial pathogens (p = 0.000009). This study might be one of the few conducted in Vietnam aimed at identifying viral pathogens causing severe pneumonia in children.

Phenotypic variation in the lipopolysaccharide O-antigen of Salmonella Paratyphi A and implications for vaccine development.

Enteric fever remains a major public health problem in South and Southeast Asia. The recent roll-out of the typhoid conjugate vaccine protecting against S. Typhi exhibits great promise for disease reduction in high burden areas. However, some endemic regions remain vulnerable to S. Paratyphi A due to a lack of licensed vaccines and inadequate WASH. Several developmental S. Paratyphi A vaccines exploit O-antigen as the target antigen. It has been hypothesised that O-antigen is under selective and environmental pressure, with mutations in O-antigen biosynthesis genes being reported, but their phenotypic effects are unknown. Here, we aimed to evaluate O-antigen variation in S. Paratyphi A originating from Nepal, and the potential effect of this variation on antibody binding. O-antigen variation was determined by measuring LPS laddering shift following electrophoresis; this analysis was complemented with genomic characterisation of the O-antigen region. We found structural O-antigen variation in <10 % of S. Paratyphi A organisms, but a direct underlying genetic cause could not be identified. High-content imaging was performed to determine antibody binding by commercial O2 monoclonal (mAb) and polyclonal antibodies, as well as polyclonal sera from convalescent patients naturally infected with S. Paratyphi A. Commercial mAbs detected only a fraction of an apparently "clonal" bacterial population, suggesting phase variation and nonuniform O-antigen composition. Notably, and despite visible subpopulation clusters, O-antigen structural changes did not appear to affect the binding ability of polyclonal human antibody considerably, which led to no obvious differences in the functionality of antibodies targeting organisms with different O-antigen conformations. Although these results need to be confirmed in organisms from alternative endemic areas, they are encouraging the use of O-antigen as the target antigen in S. Paratyphi A vaccines.

Combining machine learning with high-content imaging to infer ciprofloxacin susceptibility in isolates of Salmonella Typhimurium.

Antimicrobial resistance (AMR) is a growing public health crisis that requires innovative solutions. Current susceptibility testing approaches limit our ability to rapidly distinguish between antimicrobial-susceptible and -resistant organisms. Salmonella Typhimurium (S. Typhimurium) is an enteric pathogen responsible for severe gastrointestinal illness and invasive disease. Despite widespread resistance, ciprofloxacin remains a common treatment for Salmonella infections, particularly in lower-resource settings, where the drug is given empirically. Here, we exploit high-content imaging to generate deep phenotyping of S. Typhimurium isolates longitudinally exposed to increasing concentrations of ciprofloxacin. We apply machine learning algorithms to the imaging data and demonstrate that individual isolates display distinct growth and morphological characteristics that cluster by time point and susceptibility to ciprofloxacin, which occur independently of ciprofloxacin exposure. Using a further set of S. Typhimurium clinical isolates, we find that machine learning classifiers can accurately predict ciprofloxacin susceptibility without exposure to it or any prior knowledge of resistance phenotype. These results demonstrate the principle of using high-content imaging with machine learning algorithms to predict drug susceptibility of clinical bacterial isolates. This technique may be an important tool in understanding the morphological impact of antimicrobials on the bacterial cell to identify drugs with new modes of action.

Complete Genome Sequence of Soil Bacterium Burkholderia sp. Strain FERM BP-3421, a Producer of Spliceostatins.

Here, we report the complete genome sequence of Burkholderia sp. strain FERM BP-3421, a bacterium isolated previously from a soil sample in Japan. Strain FERM BP-3421 produces spliceostatins, which are splicing modulatory antitumor agents that advanced to preclinical development. The genome is composed of four circular replicons of 3.90, 3.0, 0.59, and 0.24 Mbp.

New C 2h phase of group III monochalcogenide monolayers AlX (X = S, Se, and Te) with anisotropic crystal structure: first-principles study.

In this paper, we introduce a new phase of two-dimensional aluminum monochalcogenide, namely C 2h-AlX (X = S, Se, and Te). With the C 2h space group, C 2h-AlX possesses a large unit cell containing 8 atoms. The C 2h phase of AlX monolayers is found to be dynamically and elastically stable based on the evaluation of its phonon dispersions and elastic constants. The anisotropic atomic structure of C 2h-AlX leads to a strong anisotropy in its mechanical properties with Young's modulus and Poisson's ratio strongly dependent on the directions examined in the two-dimensional plane. All three monolayers of C 2h-AlX are found to be direct band gap semiconductors, which are compared with the indirect band gap semiconductors of available D 3h-AlX. Particularly, the transition from direct to indirect band gap is observed in C 2h-AlX when a compressive biaxial strain is applied. Our calculated results indicate that C 2h-AlX exhibits anisotropic optical characteristics and its absorption coefficient is high. Our findings suggest that C 2h-AlX monolayers are suitable for applications in next-generation electro-mechanical and anisotropic opto-electronic nanodevices.

Janus structures of the C 2h polymorph of gallium monochalcogenides: first-principles examination of Ga2XY (X/Y = S, Se, Te) monolayers.

Group III monochalcogenide compounds can exist in different polymorphs, including the conventional D 3h and C 2h phases. Since the bulk form of the C 2h-group III monochalcogenides has been successfully synthesized [Phys. Rev. B: Condens. Matter Mater. Phys. 73 (2006) 235202], prospects for research on their corresponding monolayers have also been opened. In this study, we design and systematically consider a series of Janus structures formed from the two-dimensional C 2h phase of gallium monochalcogenide Ga2XY (X/Y = S, Se, Te) using first-principles simulations. It is demonstrated that the Janus Ga2XY monolayers are structurally stable and energetically favorable. Ga2XY monolayers exhibit high anisotropic mechanical features due to their anisotropic lattice structure. All Janus Ga2XY are indirect semiconductors with energy gap values in the range from 1.93 to 2.67 eV. Due to the asymmetrical structure, we can observe distinct vacuum level differences between the two surfaces of the examined Janus structures. Ga2XY monolayers have high electron mobility and their carrier mobilities are also highly directionally anisotropic. It is worth noting that the Ga2SSe monolayer possesses superior electron mobility, up to 3.22 × 103 cm2 V-1 s-1, making it an excellent candidate for potential applications in nanoelectronics and nanooptoelectronics.

High Pressure-Driven Magnetic Disorder and Structural Transformation in Fe3 GeTe2 : Emergence of a Magnetic Quantum Critical Point.

Among the recently discovered 2D intrinsic van der Waals (vdW) magnets, Fe3 GeTe2 (FGT) has emerged as a strong candidate for spintronics applications, due to its high Curie temperature (130 - 220 K) and magnetic tunability in response to external stimuli (electrical field, light, strain). Theory predicts that the magnetism of FGT can be significantly modulated by an external strain. However, experimental evidence is needed to validate this prediction and understand the underlying mechanism of strain-mediated vdW magnetism in this system. Here, the effects of pressure (0 - 20 GPa) are elucidated on the magnetic and structural properties of Fe3 GeTe2 by means of synchrotron Mössbauer source spectroscopy, X-ray powder diffraction and Raman spectroscopy over a wide temperature range of 10 - 290 K. A strong suppression of ferromagnetic ordering is observed with increasing pressure, and a paramagnetic ground state emerges when pressure exceeds a critical value, PPM ≈ 15 GPa. The anomalous pressure dependence of structural parameters and vibrational modes is observed at PC ≈ 7 GPa and attributed to an isostructural phase transformation. Density functional theory calculations complement these experimental findings. This study highlights pressure as a driving force for magnetic quantum criticality in layered vdW magnetic systems.

Factors related to intracerebral haematoma in patients with aneurysmal subarachnoid haemorrhage in Vietnam: a multicentre prospective cohort study.

OBJECTIVES: To investigate the impact of intracerebral haematoma (ICH) on the outcomes and the factors related to an ICH in patients with aneurysmal subarachnoid haemorrhage (aSAH) in a low- and middle-income country. DESIGN: A multicentre prospective cohort study. SETTING: Three central hospitals in Hanoi, Vietnam. PARTICIPANTS: This study included all patients (≥18 years) presenting with aSAH to the three central hospitals within 4 days of ictus, from August 2019 to June 2021, and excluded patients for whom the admission Glasgow Coma Scale was unable to be scored or patients who became lost at 90 days of follow-up during the study. OUTCOME MEASURES: The primary outcome was ICH after aneurysm rupture, defined as ICH detected on an admission head CT scan. The secondary outcomes were 90-day poor outcomes and 90-day death. RESULTS: Of 415 patients, 217 (52.3%) were females, and the median age was 57.0 years (IQR: 48.0-67.0). ICH was present in 20.5% (85/415) of patients with aSAH. There was a significant difference in the 90-day poor outcomes (43.5% (37/85) and 29.1% (96/330); p=0.011) and 90-day mortality (36.5% (31/85) and 20.0% (66/330); p=0.001) between patients who had ICH and patients who did not have ICH. The multivariable regression analysis showed that systolic blood pressure (SBP) ≥140 mm Hg (adjusted odds ratio (AOR): 2.674; 95% CI: 1.372 to 5.214; p=0.004), World Federation of Neurosurgical Societies (WFNS) grades II (AOR: 3.683; 95% CI: 1.250 to 10.858; p=0.018) to V (AOR: 6.912; 95% CI: 2.553 to 18.709; p<0.001) and a ruptured middle cerebral artery (MCA) aneurysm (AOR: 3.717; 95% CI: 1.848 to 7.477; p<0.001) were independently associated with ICH on admission. CONCLUSIONS: In this study, ICH was present in a substantial proportion of patients with aSAH and contributed significantly to a high rate of poor outcomes and death. Higher SBP, worse WFNS grades and ruptured MCA aneurysms were independently associated with ICH on admission.

Validation of the accuracy of the modified World Federation of Neurosurgical Societies subarachnoid hemorrhage grading scale for predicting the outcomes of patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Evaluating the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH) who may be at risk of poor outcomes using grading systems is one way to make a better decision on treatment for these patients. This study aimed to compare the accuracy of the modified World Federation of Neurosurgical Societies (WFNS), WFNS, and Hunt and Hess (H&H) Grading Scales in predicting the outcomes of patients with aSAH. METHODS: From August 2019 to June 2021, we conducted a multicenter prospective cohort study on adult patients with aSAH in three central hospitals in Hanoi, Vietnam. The primary outcome was the 90-day poor outcome, measured by a score of 4 (moderately severe disability) to 6 (death) on the modified Rankin Scale (mRS). We calculated the areas under the receiver operator characteristic (ROC) curve (AUROCs) to determine how well the grading scales could predict patient prognosis upon admission. We also used ROC curve analysis to find the best cut-off value for each scale. We compared AUROCs using Z-statistics and compared 90-day mean mRS scores among intergrades using the pairwise multiple-comparison test. Finally, we used logistic regression to identify factors associated with the 90-day poor outcome. RESULTS: Of 415 patients, 32% had a 90-day poor outcome. The modified WFNS (AUROC: 0.839 [95% confidence interval, CI: 0.795-0.883]; cut-off value≥2.50; PAUROC<0.001), WFNS (AUROC: 0.837 [95% CI: 0.793-0.881]; cut-off value≥3.5; PAUROC<0.001), and H&H scales (AUROC: 0.836 [95% CI: 0.791-0.881]; cut-off value≥3.5; PAUROC<0.001) were all good at predicting patient prognosis on day 90th after ictus. However, there were no significant differences between the AUROCs of these scales. Only grades IV and V of the modified WFNS (3.75 [standard deviation, SD: 2.46] vs 5.24 [SD: 1.68], p = 0.026, respectively), WFNS (3.75 [SD: 2.46] vs 5.24 [SD: 1.68], p = 0.026, respectively), and H&H scales (2.96 [SD: 2.60] vs 4.97 [SD: 1.87], p<0.001, respectively) showed a significant difference in the 90-day mean mRS scores. In multivariable models, with the same set of confounding variables, the modified WFNS grade of III to V (adjusted odds ratio, AOR: 9.090; 95% CI: 3.494-23.648; P<0.001) was more strongly associated with the increased risk of the 90-day poor outcome compared to the WFNS grade of IV to V (AOR: 6.383; 95% CI: 2.661-15.310; P<0.001) or the H&H grade of IV to V (AOR: 6.146; 95% CI: 2.584-14.620; P<0.001). CONCLUSIONS: In this study, the modified WFNS, WFNS, and H&H scales all had good discriminatory abilities for the prognosis of patients with aSAH. Because of the better effect size in predicting poor outcomes, the modified WFNS scale seems preferable to the WFNS and H&H scales.

Predictive validity of the prognosis on admission aneurysmal subarachnoid haemorrhage scale for the outcome of patients with aneurysmal subarachnoid haemorrhage.

This multicentre prospective cohort study aimed to compare the accuracy of the PAASH, WFNS, and Hunt and Hess (H&H) scales in predicting the outcomes of adult patients with aneurysmal SAH presented to three central hospitals in Hanoi, Vietnam, from August 2019 to June 2021. Of 415 eligible patients, 32.0% had a 90-day poor outcome, defined as an mRS score of 4 (moderately severe disability) to 6 (death). The PAASH, WFNS and H&H scales all have good discriminatory abilities for predicting the 90-day poor outcome. There were significant differences in the 90-day mean mRS scores between grades I and II (p = 0.001) and grades II and III (p = 0.001) of the PAASH scale, between grades IV and V (p = 0.026) of the WFNS scale, and between grades IV and V (p < 0.001) of the H&H scale. In contrast to a WFNS grade of IV-V and an H&H grade of IV-V, a PAASH grade of III-V was an independent predictor of the 90-day poor outcome. Because of the more clearly significant difference between the outcomes of the adjacent grades and the more strong effect size for predicting poor outcomes, the PAASH scale was preferable to the WFNS and H&H scales.

3D Printing of Cellulase-Laden Cellulose Nanofiber/Chitosan Hydrogel Composites: Towards Tissue Engineering Functional Biomaterials with Enzyme-Mediated Biodegradation.

The 3D printing of a multifunctional hydrogel biomaterial with bioactivity for tissue engineering, good mechanical properties and a biodegradability mediated by free and encapsulated cellulase was proposed. Bioinks of cellulase-laden and cellulose nanofiber filled chitosan viscous suspensions were used to 3D print enzymatic biodegradable and biocompatible cellulose nanofiber (CNF) reinforced chitosan (CHI) hydrogels. The study of the kinetics of CNF enzymatic degradation was studied in situ in fibroblast cell culture. To preserve enzyme stability as well as to guarantee its sustained release, the cellulase was preliminarily encapsulated in chitosan-caseinate nanoparticles, which were further incorporated in the CNF/CHI viscous suspension before the 3D printing of the ink. The incorporation of the enzyme within the CHI/CNF hydrogel contributed to control the decrease of the CNF mechanical reinforcement in the long term while keeping the cell growth-promoting property of chitosan. The hydrolysis kinetics of cellulose in the 3D printed scaffolds showed a slow but sustained degradation of the CNFs with enzyme, with approximately 65% and 55% relative activities still obtained after 14 days of incubation for the encapsulated and free enzyme, respectively. The 3D printed composite hydrogels showed excellent cytocompatibility supporting fibroblast cell attachment, proliferation and growth. Ultimately, the concomitant cell growth and biodegradation of CNFs within the 3D printed CHI/CNF scaffolds highlights the remarkable potential of CHI/CNF composites in the design of tissue models for the development of 3D constructs with tailored in vitro/in vivo degradability for biomedical applications.

Tumor genomic profiling and personalized tracking of circulating tumor DNA in Vietnamese colorectal cancer patients.

Background: Colorectal cancer (CRC) is the fifth most common cancer with rising prevalence in Vietnam. However, there is no data about the mutational landscape and actionable alterations in the Vietnamese patients. During post-operative surveillance, clinical tools are limited to stratify risk of recurrence and detect residual disease. Method: In this prospective multi-center study, 103 CRC patients eligible for curative-intent surgery were recruited. Genomic DNA from tumor tissue and paired white blood cells were sequenced to profile all tumor-derived somatic mutations in 95 cancer-associated genes. Our bioinformatic algorithm identified top mutations unique for individual patient, which were then used to monitor the presence of circulating tumor DNA (ctDNA) in serial plasma samples. Results: The top mutated genes in our cohort were APC, TP53 and KRAS. 41.7% of the patients harbored KRAS and NRAS mutations predictive of resistance to Cetuximab and Panitumumab respectively; 41.7% had mutations targeted by either approved or experimental drugs. Using a personalized subset of top ranked mutations, we detected ctDNA in 90.5% of the pre-operative plasma samples, whereas carcinoembryonic antigen (CEA) was elevated in only 41.3% of them. Interim analysis after 16-month follow-up revealed post-operative detection of ctDNA in two patients that had recurrence, with the lead time of 4-10.5 months ahead of clinical diagnosis. CEA failed to predict recurrence in both cases. Conclusion: Our assay showed promising dual clinical utilities in residual cancer surveillance and actionable mutation profiling for targeted therapies in CRC patients. This could lay foundation to empower precision cancer medicine in Vietnam and other developing countries.

Dosimetric impact of image artifact from a wide-bore CT scanner in radiotherapy treatment planning.

PURPOSE: Traditional computed tomography (CT) units provide a maximum scan field-of-view (sFOV) diameter of 50 cm and a limited bore size, which cannot accommodate a large patient habitus or an extended simulation setup in radiation therapy (RT). Wide-bore CT scanners with increased bore size were developed to address these needs. Some scanners have the capacity to reconstruct the CT images at an extended FOV (eFOV), through data interpolation or extrapolation, using projection data acquired with a conventional sFOV. Objects that extend past the sFOV for eFOV reconstruction may generate image artifacts resulting from truncated projection data; this may distort CT numbers and structure contours in the region beyond the sFOV. The purpose of this study was to evaluate the dosimetric impact of image artifacts from eFOV reconstruction with a wide-bore CT scanner in radiotherapy (RT) treatment planning. METHODS: Testing phantoms (i.e., a mini CT phantom with equivalent tissue inserts, a set of CT normal phantoms and anthropomorphic phantoms of the thorax and the pelvis) were used to evaluate eFOV artifacts. Reference baseline images of these phantoms were acquired with the phantom centrally positioned within the sFOV. For comparison, the phantoms were then shifted laterally and scanned partially outside the sFOV, but still within the eFOV. Treatment plans were generated for the thoracic and pelvic anthropomorphic phantoms utilizing the Eclipse treatment planning system (TPS) to study the potential effects of eFOV artifacts on dose calculations. All dose calculations of baseline and test treatment plans were carried out using the same MU. RESULTS: Results show that both body contour and CT numbers are altered by image artifacts in eFOV reconstruction. CT number distortions of up to -356 HU for bone tissue and up to 323 HU for lung tissue were observed in the mini CT phantom. Results from the large body normal phantom, which is close to a clinical patient size, show average CT number changes of up to -49 HU. Wider distribution (i.e., standard deviation) of the HU values was seen when the phantom was placed at more than 2.8 cm beyond the 50 cm sFOV. Anthropomorphic phantom studies with several standard beam configurations show that body contour distortion causes tumor dose calculation reduction of 3.0 and 1.9% for 6 and 23 MV x-rays, respectively, when not accounting for tissue heterogeneities during dose computation. When heterogeneity correction is used in planning, the competing effects of the body contour distortion and the CT number distortion cause a smaller error in tumor dose calculation. Less than 0.9% error in calculated dose was observed in volumetric modulated are therapy (VMAT) treatment plans. CONCLUSIONS: The image artifacts from eFOV reconstruction alter the CT numbers and body contours of the imaged objects, which has the potential to produce inaccuracies in dose calculations during radiotherapy treatment planning. The radiation therapy team should be aware of these image artifacts and their effects on target dose calculations during CT simulation as well as treatment planning.