Incorporating Domain Knowledge and Structure-Based Descriptors for Machine Learning: A Case Study of Pd-Catalyzed Sonogashira Reactions.

Machine learning has revolutionized information processing for large datasets across various fields. However, its limited interpretability poses a significant challenge when applied to chemistry. In this study, we developed a set of simple molecular representations to capture the structural information of ligands in palladium-catalyzed Sonogashira coupling reactions of aryl bromides. Drawing inspiration from human understanding of catalytic cycles, we used a graph neural network to extract structural details of the phosphine ligand, a major contributor to the overall activation energy. We combined these simple molecular representations with an electronic descriptor of aryl bromide as inputs for a fully connected neural network unit. The results allowed us to predict rate constants and gain mechanistic insights into the rate-limiting oxidative addition process using a relatively small dataset. This study highlights the importance of incorporating domain knowledge in machine learning and presents an alternative approach to data analysis.

The incidence of primary antibiotic resistance of Helicobacter pylori in Vietnam.

GOALS: To determine the susceptibility of Helicobacter pylori strains isolated from a Vietnamese population to 5 antibiotics. BACKGROUND: The incidence of antibiotic resistance in H. pylori infection is increasing worldwide and has become a leading cause for failure of treatment. Antibiotic susceptibility testing is very important to provide optimal regimens in a clinical setting. STUDY: We isolated 103 H. pylori strains from the gastric mucosa of H. pylori-infected patients from 2 areas in Vietnam (Ho Chi Minh and Hanoi) in 2008. Epsilometer test was used to determine the minimum inhibitory concentrations of amoxicillin, clarithromycin (CLR), metronidazole (MNZ), levofloxacin, and tetracycline. RESULTS: Among the 103 strains, the resistance rates were 0% (amoxicillin), 33% (CLR), 69.9% (MNZ), 18.4% (levofloxacin), and 5.8% (tetracycline). The resistant strains showed a high-level of resistance (≥ 256 µg/mL) to CLR, 23.5% (8/34), and MNZ, 29.1% (21/72). The resistance rate for CLR was significantly higher in Ho Chi Minh than in Hanoi (49% vs. 18.5%, P=0.001). Resistance to both CLR and MNZ was most commonly observed (24.3%). Two strains (1.9%) were resistant to 4 of the 5 antibiotics. No significant association was observed between antibiotic resistance rates and age, sex, or clinical outcomes of the patients. CONCLUSIONS: High incidence of resistance to CLR and MNZ suggests that standard triple therapies may not be useful as first-line treatment in Vietnam. Alternative strategies such as bismuth-based quadruple therapies or sequential therapy may be more effective in Vietnam.

Vietnam Association of Gastroenterology (VNAGE) consensus on the management of Helicobacter pylori infection.

Helicobacter pylori (H. pylori) infection is prevalent and has a rapidly increasing antibiotic resistance rate in Vietnam. Reinfection is quite common, and gastric carcinoma remains one of the most common malignancies, which is not uncommon to develop after successful eradication. The purpose of this consensus is to provide updated recommendations on the management of H. pylori infection in the country. The consensus panel consisted of 32 experts from 14 major universities and institutions in Vietnam who were invited to review the evidence and develop the statements using the Delphi method. The process followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The consensus level was defined as ≥80% for agreement on the proposed statements. Due to the limited availability of high-quality local evidence, this consensus was also based on high-quality evidence from international studies, especially those conducted in other populations in the Asia-Pacific region. The panel finally reached a consensus on 27 statements after two voting rounds, which consisted of four sections (1) indications for testing and selection of diagnostic tests (2), treatment regimens, (3) post-treatment confirmation of H. pylori status, and (4) reinfection prevention methods and follow-up after eradication. Important issues that require further evidence include studies on third-line regimens, strategies to prevent H. pylori reinfection, and post-eradication follow-up for precancerous gastric lesions. We hope this consensus will help guide the current clinical practice in Vietnam and promote multicenter studies in the country and international collaborations.

Helicobacter pylori infection and gastroduodenal diseases in Vietnam: a cross-sectional, hospital-based study.

BACKGROUND: The rate of H. pylori infection in Vietnam is reportedly high, but the spectrum of H. pylori-associated gastroduodenal diseases has not been systematically investigated. Moreover, despite the similarities of ethnicity and diet, the age-standardized incidence rate of gastric cancer in the northern city of Hanoi is higher than that in the southern city of Ho Chi Minh, but the reason for this phenomenon is unknown. The virulence of Vietnamese H. pylori has also not been investigated in detail. METHODS: Individuals undergoing esophagogastroduodenoscopy were randomly recruited. H. pylori infection status was determined based on the combined results of culture, histology, immunohistochemistry, rapid urine test and serum ELISA. Peptic ulcer (PU) and gastroesophageal reflux disease was diagnosed by endoscopy, and chronic gastritis was determined histologically. H. pylori virulence factors were investigated by PCR and sequencing. RESULTS: Among the examined patients, 65.6% were infected with H. pylori. The prevalence of infection was significantly higher in those over 40 years of age than in those aged ≤40. Chronic gastritis was present in all H. pylori-infected individuals, 83.1% of whom had active gastritis, and 85.3% and 14.7% had atrophy and intestinal metaplasia, respectively. PU was present in 21% of infected patients, whereas its incidence was very low in non-infected individuals. The prevalence of PU was significantly higher in Hanoi than in Ho Chi Minh. The prevalence of vacA m1, which has been identified as an independent risk factor for PU in Vietnam, was significantly higher among H. pylori isolates from Hanoi than among those from Ho Chi Minh. CONCLUSIONS: H. pylori infection is common in Vietnam and is strongly associated with PU, active gastritis, atrophy and intestinal metaplasia. vacA m1 is associated with an increased risk for PU and might contribute to the difference in the prevalence of PU and gastric cancer between Hanoi and Ho Chi Minh.

Evaluation of rapid urine test for the detection of Helicobacter pylori infection in the Vietnamese population.

PURPOSE: This study attempted to assess the value of the RAPIRUN test for the diagnosis of Helicobacter pylori infection in the Vietnamese population. METHODS: We recruited 148 Vietnamese patients undergoing upper gastrointestinal endoscopy during which five gastric biopsies were taken; blood and urine samples were collected from each patient. Helicobacter pylori infection status was determined by a combination of three different methods, including culture, immunohistochemistry, and serum ELISA. RAPIRUN tests were performed using urine samples. RESULTS: The sensitivity, specificity, and accuracy of the RAPIRUN test in these Vietnamese patients were 79.5, 90.7, and 84.5%, respectively. CONCLUSIONS: The RAPIRUN test is useful for the diagnosis of H. pylori infection in the Vietnamese population, showing high specificity, acceptable sensitivity, non-invasiveness, convenience, and rapidity.

Analysis of virulence factors of Helicobacter pylori isolated from a Vietnamese population.

BACKGROUND: The incidence of gastric cancer differs among countries in Asia, and it has been suggested that virulence factors associated with Helicobacter pylori are partly responsible. The aim of this study was to investigate several genetic factors regarded as virulence or molecular epidemiologic markers in H. pylori isolates from Vietnamese subjects. RESULTS: The cagA, vacA and cag right-end junction genotypes of 103 H. pylori strains from Vietnam (54 from Hanoi and 49 from Ho Chi Minh) were determined by PCR and sequencing. Three types of deletion in the region located upstream of the cagA Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region were identified: the 39-bp deletion type, the 18-bp deletion type, and the no-deletion type. The majority of strains studied (77%; 80/103) had the 18-bp deletion irrespective of geographical location in the country or clinical outcome. All of the 39-bp and 18-bp deletion-type strains possessed the East Asian type cagA repeat region. The type II cag right-end junction genotype was predominant (84%). The vacA m1 genotype was significantly more common in strains isolated in Hanoi, where the incidence of gastric cancer is higher, than in strains from Ho Chi Minh. CONCLUSION: Pre-EPIYA-region typing of the cagA gene could provide a new genetic marker of H. pylori genomic diversity. Our data support the hypothesis that vacA m1 is closely associated with gastric carcinogenesis.

Evaluation of the anti-East Asian CagA-specific antibody for CagA phenotyping.

The determination of the cagA genotype is generally based on sequencing the variable 3' region of the cagA gene. In a previous study, we successfully generated an anti-East Asian CagA-specific antibody (anti-EAS Ab) immunoreactive only with the East Asian CagA and not with the Western CagA. In a small number of Japanese patients, anti-EAS Ab appeared to be a useful tool for phenotyping CagA immunohistochemically. The present study was conducted to validate the anti-EAS Ab immunohistochemistry method in a larger number of patients from Vietnam and Thailand. A total of 385 Vietnamese and Thais were recruited. Helicobacter pylori status was determined by a combination of three methods, including culture, histology, and immunohistochemistry with anti-H. pylori antibody. The sensitivity, specificity, and accuracy of the anti-EAS Ab immunohistochemistry method for the diagnosis of CagA phenotype were calculated based on the results of the cagA sequencing as the gold standard. The sensitivity, specificity, and accuracy of our immunohistochemistry method were 96.7%, 97.9%, and 97.1%, respectively. Moreover, anti-EAS Ab was not cross-reactive with noninfected gastric mucosa. In conclusion, immunohistochemistry with anti-EAS Ab appears to be a good method for determination of CagA phenotype.