Computational pathology: A survey review and the way forward.

Computational Pathology (CPath) is an interdisciplinary science that augments developments of computational approaches to analyze and model medical histopathology images. The main objective for CPath is to develop infrastructure and workflows of digital diagnostics as an assistive CAD system for clinical pathology, facilitating transformational changes in the diagnosis and treatment of cancer that are mainly address by CPath tools. With evergrowing developments in deep learning and computer vision algorithms, and the ease of the data flow from digital pathology, currently CPath is witnessing a paradigm shift. Despite the sheer volume of engineering and scientific works being introduced for cancer image analysis, there is still a considerable gap of adopting and integrating these algorithms in clinical practice. This raises a significant question regarding the direction and trends that are undertaken in CPath. In this article we provide a comprehensive review of more than 800 papers to address the challenges faced in problem design all-the-way to the application and implementation viewpoints. We have catalogued each paper into a model-card by examining the key works and challenges faced to layout the current landscape in CPath. We hope this helps the community to locate relevant works and facilitate understanding of the field's future directions. In a nutshell, we oversee the CPath developments in cycle of stages which are required to be cohesively linked together to address the challenges associated with such multidisciplinary science. We overview this cycle from different perspectives of data-centric, model-centric, and application-centric problems. We finally sketch remaining challenges and provide directions for future technical developments and clinical integration of CPath. For updated information on this survey review paper and accessing to the original model cards repository, please refer to GitHub. Updated version of this draft can also be found from arXiv.

Sulfur-Promoted Oxidative Condensation of Chalcones with Unsubstituted Cyanoacetamide in DMSO: Access to 3-Cyanopyrid-2-ones.

Elemental sulfur and DABCO were found to be an excellent combination to promote a one-pot cascade of condensation-oxidative cyclization of chalcones and unsubstituted cyanoacetamide in DMSO to provide 3-cyanopyrid-2-ones.

Updated estimation of the burden of fungal disease in Vietnam.

BACKGROUND: Anecdotally, the burden of fungal diseases in Vietnam is rapidly rising, but there has been no updated estimate on this issue since a previous report in 2015. OBJECTIVES: In this study, we aimed at estimating the incidence and prevalence of serious fungal infections for the year 2020. METHODS: We made estimates with a previously described methodology, using reports on the incidence and prevalence of various established risk factors for fungal infections from local, regional or global sources. RESULTS: We estimated 2,389,661 cases of serious fungal infection occurred in Vietnam in 2020. The most common condition was recurrent vaginal candidiasis (4047/100,000 women annually). Among people living with HIV, we estimated 451 cases of cryptococcal meningitis, 1030 of pneumocystis pneumonia, 166 of histoplasmosis and 1612 of talaromycosis annually. Candidaemia incidence was estimated at 12/100,000 population each year. Owing to its high burden of tuberculosis and respiratory diseases, Vietnam had high rates of severe infections caused by Aspergillus species. Incidence of invasive aspergillosis is 24/100,000 population, allergic bronchopulmonary aspergillosis 78/100,000 and severe asthma with fungal sensitisation 102/100,000. Five-year period prevalence of chronic pulmonary aspergillosis is 120/100,000 population /5-year period. Mucormycosis, fungal keratitis and tinea capitis were estimated at 192, 14,431 and 201 episodes each year, respectively. CONCLUSIONS: The number of patients with mycoses in Vietnam is likely underestimated due to a lack of local data and limited diagnostic capacity, but at least 2.5% of the population might have some form of serious fungal disease.

Base-catalyzed multicomponent access to quinoxalin-2-thiones from o-phenylenediamines, aryl ketones and sulfur.

3-Arylquinoxaline-2-thiones were conveniently synthesized via three-component oxidative condensation of acetophenones with o-phenylenediamines and sulfur in DMSO in the presence of piperidine as a catalyst. The products could be readily isolated from the reaction mixture by simple precipitation and washing with methanol. This set of reaction conditions applied to higher homologs of acetophenones as well as benzyl phenyl ketones led to 2,3-di-C-substituted quinoxalines. Further functionalization of 3-phenylquinoxaline-2-thione via reaction on the thione group could be readily performed to provide quinoxaline derivatives in good yields.

Vinblastine loaded on graphene quantum dots and its anticancer applications.

AIMS: The aim of our work is to load Vinblastine drugs loaded on graphene quantum dots to improve its cytotoxicity on cancer cells and reduce it on the normal cell in the composites. Moreover, the GQDs-Vin composite significantly inhibited tumour growth in animals. METHODS: GQDs-Vin composites were prepared by homogenisation of GQDs and Vin solutions. The loading of Vin on GQDs in the composites was characterised by FTIR, PL, UV-vis spectra, and TEM. The cytotoxicity of GQDs, Vin, and GQDs-Vin composites was investigated on the Hela, HGC-27, A549, MCF-7, CCF-STTG1 cells and Vero by in vitro and in vivo methods. The difference in cellular structure and organelles in mice's livers in comparison between the control group and GQDs-Vin (1:5) groups was characterised by TEM. RESULTS: The diameter of the nanoparticles of GQDs-Vin composites in weight ratios 1:1, 1:3 and 1:5 w/w of 50-70 nm, 100-150 nm and ∼500nm, respectively, is larger than that of GQDs of 10-50nm. The in vitro results showed that GQDs not only improved the cytotoxicity of Vin to cancer cells but also decreased its cytotoxicity towards normal cells in the composites. The GQDs-Vin (1:5) composite exhibited a stronger tumour inhibition effect than Vin alone. The morphology of mice's livers showed the absence GQDs-Vin nanoparticles in the mice livers suggesting the lack of storage and the leakage from the liver without any toxicity. CONCLUSIONS: Results of the improved cytotoxicity of GQDs-Vin composite on cancer cells, its reduced cytotoxicity on normal cells and the significant inhibition on tumour growth of GQDs-Vin composite compared with Vin and GQDs alone may indicate a synergistic effect of Vin and GQDs in their composites for anticancer application.

New oligomeric neolignans from the leaves of Magnolia officinalis var. biloba.

Six new oligomeric neolignans including two trimeric neolignans (1 and 2) and four dimeric neolignans (3-6) were isolated from the leaves of Magnolia officinalis var. biloba. Their structures were determined based on HR-ESIMS and NMR data, as well as electronic circular dichroism (ECD) calculations. Compound 1 is formed from two obovatol moieties directly linked to an aromatic ring of the remaining obovatol moiety, which is an unprecedented type of linkage between monomers. All isolates were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 1 and 3 showed significantly inhibitory activities with IC50 values of 6.04 and 3.26 µmol·L-1, respectively.

Azole-resistant Aspergillus fumigatus is highly prevalent in the environment of Vietnam, with marked variability by land use type.

Azole-resistant environmental Aspergillus fumigatus presents a threat to public health but the extent of this threat in Southeast Asia is poorly described. We conducted environmental surveillance in the Mekong Delta region of Vietnam, collecting air and ground samples across key land-use types, and determined antifungal susceptibilities of Aspergillus section Fumigati (ASF) isolates and azole concentrations in soils. Of 119 ASF isolates, 55% were resistant (or non-wild type) to itraconazole, 65% to posaconazole and 50% to voriconazole. Azole resistance was more frequent in A. fumigatus sensu stricto isolates (95%) than other ASF species (32%). Resistant isolates and agricultural azole residues were overrepresented in samples from cultivated land. cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus sensu stricto isolates carried known resistance mutations, with TR34 /L98H most frequent (34/38).

Psychological stress and associated factors among municipal solid waste collectors in Hanoi, Vietnam: A cross-sectional study.

INTRODUCTION: In low and middle-income countries, the manually operated municipal waste collection system prominently depended on the performance of waste collectors (WC). Most of the literature has focused on the impact of waste collection tasks on WCs' physical health, while little was known about the psychological effects of work-related stress. This study aimed to examine the prevalence of psychological stress and related factors among waste collectors in Hanoi, Vietnam. METHODS: A cross-sectional survey was conducted among 802 WCs in 2017. The questionnaire included the 7-item Stress component of the 21-item Depression, Anxiety and Stress Scale, and questions on demographics and work conditions. Descriptive and multivariate logistics regression analyses were conducted to examine the factors related to psychological stress among WCs. RESULTS: Results showed that 13.4% of WCs reported stress symptoms; among them, 3.3% of WCs experienced severe stress. Factors related to lower odds of self-reported psychological stress included self-perceived frequent exposure to high and low temperatures in the working environment (OR = 0.51 and 0.52, respectively). Factors associated with the increased likelihood of symptoms included frequent exposure to hot/flammable objects (OR = 2.41), working a night shift in the last three months (OR = 1.82), education lever lower than high school (OR = 1.82), and having an insufficient monthly income (OR = 1.99). CONCLUSION: The high percentage of workers with severe stress implies the need for mental health prevention and treatment for WCs who participated in this study.

Deacylative Carbon-Carbon Bond Cleavage of Ketone Equivalents: Applications to Radical Carbon-Carbon Bond Formation Reactions.

This article describes the synthetic application of ketone-derived oxaziridines as alkyl radical precursors in copper-catalyzed Carbon-Carbon bond formation reactions. Experimental and computational studies indicate a free radical mechanism, where alkyl radicals are efficiently generated via cleavage of a Carbon-Carbon bond of oxaziridines. Acyclic and unstrained cyclic oxaziridines are applicable to the present radical process, allowing for the generation of various alkyl radicals with good functional group compatibility.

Drug-Resistant Aspergillus flavus Is Highly Prevalent in the Environment of Vietnam: A New Challenge for the Management of Aspergillosis?

The burden of aspergillosis, especially Chronic Pulmonary Aspergillosis, is increasingly recognized, and the increasing presence of azole-resistant environmental Aspergillus fumigatus has been highlighted as a health risk. However, a sizable minority of aspergillosis is caused by Aspergillus flavus, which is assumed to be sensitive to azoles but is infrequently included in surveillance. We conducted environmental sampling at 150 locations in a rural province of southern Vietnam. A. flavus isolates were identified morphologically, their identity was confirmed by sequencing of the beta-tubulin gene, and then they were tested for susceptibility to azoles and amphotericin B according to EUCAST methodologies. We found that over 85% of A. flavus isolates were resistant to at least one azole, and half of them were resistant to itraconazole. This unexpectedly high prevalence of resistance demands further investigation to determine whether it is linked to agricultural azole use, as has been described for A. fumigatus. Clinical correlation is required, so that guidelines can be adjusted to take this information into account.

Patulignans A-C, three structurally unique lignans from the leaves of Melicope patulinervia.

(±)-Patulignans A-C (1-3), three unique pairs of lignan enantiomers were isolated from the leaves of Melicope patulinervia. Patulignan A (1) possesses an unprecedented dimethyloxonane moiety in nature, meanwhile patulignans B (2) and C (3) are epimers carrying a novel dimethyl-1,6-dioxaspiro[4.5]decane skeleton. Their structures were established by spectroscopy methods and electronic circular dichroism (ECD) calculations. Compounds 1-3 showed significant inhibitory activity against α-glucosidase.

Assessing the efficacy and safety of magnesium sulfate for management of autonomic nervous system dysregulation in Vietnamese children with severe hand foot and mouth disease.

BACKGROUND: Brainstem encephalitis is a serious complication of hand foot and mouth disease (HFMD) in children. Autonomic nervous system (ANS) dysregulation and hypertension may occur, sometimes progressing to cardiopulmonary failure and death. Vietnamese national guidelines recommend use of milrinone if ANS dysregulation with Stage 2 hypertension develops. We wished to investigate whether magnesium sulfate (MgSO4) improved outcomes in children with HFMD if used earlier in the evolution of the ANS dysregulation (Stage 1 hypertension). METHODS: During a regional epidemic we conducted a randomized, double-blind, placebo-controlled trial of MgSO4 in children with HFMD, ANS dysregulation and Stage 1 hypertension, at the Hospital for Tropical Diseases in Ho Chi Minh city. Study participants received an infusion of MgSO4 or matched placebo for 72 h. We also reviewed data from non-trial HFMD patients in whom milrinone failed to control hypertension, some of whom received MgSO4 as second line therapy. The primary outcome for both analyses was a composite of disease progression within 72 h - addition of milrinone (trial participants only), need for ventilation, shock, or death. RESULTS: Between June 2014 and September 2016, 14 and 12 participants received MgSO4 or placebo respectively, before the trial was stopped due to futility. Among 45 non-trial cases with poorly controlled hypertension despite high-dose milrinone, 33 received MgSO4 while 12 did not. There were no statistically significant differences in the composite outcome between the MgSO4 and the placebo/control groups in either study (adjusted relative risk (95%CI) of [6/14 (43%) vs. 6/12 (50%)], 0.84 (0.37, 1.92), p = 0.682 in the trial and [1/33 (3%) vs. 2/12 (17%)], 0.16 (0.01, 1.79), p = 0.132 in the observational cohort). The incidence of adverse events was similar between the groups. Potentially toxic magnesium levels occurred very rarely with the infusion regime used. CONCLUSION: Although we could not demonstrate efficacy in these studies, there were no safety signals associated with use of 30-50 mg/kg/hr. MgSO4 in severe HFMD. Intermittent outbreaks of HFMD are likely to continue across the region, and an adequately powered trial is still needed to evaluate use of MgSO4 in controlling hypertension in severe HFMD, potentially involving a higher dose regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 AUG 2013). Trial sponsor: University of Oxford.

Silver and gold nanoparticles biosynthesized by aqueous extract of burdock root, Arctium lappa as antimicrobial agent and catalyst for degradation of pollutants.

This study presents an efficient and facile method for biosynthesis of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) using aqueous extract of burdock root (BR), A. lappa, and their applications. The nanoparticles were characterized by ultraviolet-visible spectrophotometry, X-ray diffraction, transmission electron microscopy, energy dispersive X-ray, thermogravimetry, and differential thermal analysis. AgNPs capped the BR extract (BR-AgNPs) possessed roughly spherical geometry with an average diameter of 21.3 nm while uneven geometry of AuNPs capped the BR extract (BR-AuNPs) showed multi shapes in average size of 24.7 nm. The BR-AgNPs strongly inhibited five tested microorganism strains. In particular, the nanoparticles showed excellent catalytic activity for the conversion of pollutants within wastewater. Pseudo-first-order rate constants for the degradation of 4-nitrophenol, methyl orange, and rhodamine B were respectively found 6.77 × 10-3, 3.70 × 10-3, and 6.07 × 10-3 s-1 for BR-AgNPs and 6.87 × 10-3, 6.07 × 10-3, and 7.07 × 10-3 s-1 for BR-AuNPs. Graphical abstract ᅟ.

Streptococcus suis, an important cause of adult bacterial meningitis in northern Vietnam.

BACKGROUND: Streptococcus suis can cause severe systemic infection in adults exposed to infected pigs or after consumption of undercooked pig products. S. suis is often misdiagnosed, due to lack of awareness and improper testing. Here we report the first fifty cases diagnosed with S. suis infection in northern Viet Nam. METHODOLOGY/PRINCIPAL FINDINGS: In 2007, diagnostics for S. suis were set up at a national hospital in Hanoi. That year there were 43 S. suis positive cerebrospinal fluid samples, of which S. suis could be cultured in 32 cases and 11 cases were only positive by PCR. Seven patients were blood culture positive for S. suis but CSF culture and PCR negative; making a total of 50 patients with laboratory confirmed S. suis infection in 2007. The number of S. suis cases peaked during the warmer months. CONCLUSIONS/SIGNIFICANCE: S. suis was commonly diagnosed as a cause of bacterial meningitis in adults in northern Viet Nam. In countries where there is intense and widespread exposure of humans to pigs, S. suis can be an important human pathogen.

Assessment of fatigue in patients with chronic hepatitis C using the Fatigue Impact Scale.

The aim of this study was to assess the impact of fatigue on the quality of life of patients with chronic hepatitis C (CHC) and to examine its relationship with various parameters of the disease, including viral load. The Fatigue Impact Scale (FIS), a self-report questionnaire, was applied to 92 patients with CHC, and the results were compared to those of an age-matched cohort of 213 healthy blood donors. Fatigue was frequent and disabling, being present in 67% of CHC patients, and the FIS was significantly increased in CHC patients compared to the healthy controls. Fatigue severity was not correlated with the activity of the disease or with the level of viremia. The FIS proved to be a valuable tool to assess this symptom. It should be of help for better evaluation of the clinical spectrum of the disease and should be included in trials assessing the efficacy of therapeutic interventions.