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Supplementary Table S1

All dose-response curves. Dose-response curves for all library compounds

Metabolic constraints in the tumor microenvironment constitute a barrier to effective antitumor immunity and similarities in the metabolic properties of T cells and cancer cells impede the specific therapeutic targeting of metabolism in either population. To identify distinct metabolic vulnerabilities of CD8+ T cells and cancer cells, we developed a high-throughput in vitro pharmacologic screening platform and used it to measure the cell type–specific sensitivities of activated CD8+ T cells and B16 melanoma cells to a wide array of metabolic perturbations during antigen-specific killing of cancer cells by CD8+ T cells. We illustrated the applicability of this screening platform by showing that CD8+ T cells were more sensitive to ferroptosis induction by inhibitors of glutathione peroxidase 4 (GPX4) than B16 and MC38 cancer cells. Overexpression of ferroptosis suppressor protein 1 (FSP1) or cytosolic GPX4 yielded ferroptosis-resistant CD8+ T cells without compromising their function, while genetic deletion of the ferroptosis sensitivity–promoting enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4) protected CD8+ T cells from ferroptosis but impaired antitumor CD8+ T-cell responses. Our screen also revealed high T cell–specific vulnerabilities for compounds targeting NAD+ metabolism or autophagy and endoplasmic reticulum (ER) stress pathways. We focused the current screening effort on metabolic agents. However, this in vitro screening platform may also be valuable for rapid testing of other types of compounds to identify regulators of antitumor CD8+ T-cell function and potential therapeutic targets.

Objectives We aimed to assess whether a pharmacist-led intervention enhances knowledge, medication adherence and glycemic control in patients with type 2 diabetes mellitus (T2DM). Methods We conducted a single-blinded randomized controlled trial in Vietnam. Individuals with T2DM were recruited from a general hospital and randomly allocated to intervention and routine care. The intervention group received routine care plus counselling intervention by a pharmacist, including providing drug information and answering individual patients’ queries relating to T2DM and medications, which had not been done in routine care. We assessed the outcomes: knowledge score as measured by the Diabetes Knowledge Questionnaire, self-reported adherence and fasting blood glucose (FBG) at the 1-month follow-up. Key findings A total of 165 patients (83 intervention, 82 control) completed the study; their mean age was 63.33 years, and 49.1% were males. The baseline characteristics of the patients were similar between the groups. At 1-month follow-up, the pharmacist’s intervention resulted in an improvement in all three outcomes: knowledge score [B = 5.527; 95% confidence intervals (CI): 3.982 to 7.072; P < 0.001], adherence [odds ratio (OR) = 9.813; 95% CI: 2.456 to 39.205; P = 0.001] and attainment of target FBG (OR = 1.979; 95% CI: 1.029 to 3.806; P = 0.041). Conclusions The pharmacist-led intervention enhanced disease knowledge, medication adherence and glycemic control in patients with T2DM. This study provides evidence of the benefits of pharmacist counselling in addition to routine care for T2DM outpatients in a Vietnam population.

BackgroundChronic obstructive pulmonary disease (COPD) and asthma rank among the leading causes of respiratory morbidity, particularly in low- and middle-income countries. This qualitative study aimed to explore the healthcare pathways of patients with chronic respiratory disease, and factors influencing their ability to access healthcare in Vietnam, where COPD and asthma are prevalent.MethodsWe conducted 41 in-depth interviews among patients, including 31 people with COPD, eight with asthma and two with asthma-COPD overlap syndrome. Participants were recruited at provincial- or national-level health facilities in two urban and two rural provinces in Vietnam. The interviews were audio-recorded, transcribed, and analysed using thematic analysis.ResultsPatients’ healthcare pathways were complex and involved visits to multiple health facilities before finally obtaining a definitive diagnosis at a provincial- or national-level hospital. Access to healthcare was affected considerably by participants’ limited knowledge of their respiratory conditions, the availability of social support, especially from family members, the costs of healthcare as well as health system factors (including the coverage of public health insurance, the distance to health facilities, and attitude of healthcare providers).ConclusionThe study demonstrated the need for improved access to timely diagnosis and treatment of chronic lung disease within the lower level of the health system. This can be achieved by enhancing the communication skills and diagnostic capacity of local healthcare workers. Health education programmes for patients and caregivers will contribute to improved control of lung disease.

Conductive inks commonly rely on oxidation-resistant metallic nanoparticles such as gold, silver, copper, and nickel. The criterion of air stability limits the scope of material properties attainable in printed electronic devices. Here we present an alternative approach based on air-stable nanoscale metal hydrides. Conductive patterns based on titanium hydride (TiH

This study was conducted to determine the prevalence and determinants of medication adherence among patients with HIV/AIDS in southern Vietnam. Methods: A cross-sectional study was conducted in a hospital in southern Vietnam from June to December 2019 on patients who began antiretroviral therapy (ART) for at least 6 months. Using a designed questionnaire, patients were considered adherent if they took correct medicines with right doses, on time and properly with food and beverage and had follow-up visits as scheduled. Multivariable logistic regression was used to identify determinants of adherence. Key findings: A total of 350 patients (from 861 medical records) were eligible for the study. The majority of patients were male (62.9%), and the dominant age group (≥35 years old) accounted for 53.7% of patients. Sexual intercourse was the primary route of transmission of HIV (95.1%). The proportions of participants who took the correct medicine and at a proper dose were 98.3% and 86.3%, respectively. In total, 94.9% of participants took medicine appropriately in combination with food and beverage, and 75.7% of participants were strictly adherent to ART. The factors marital status (odds ratio (OR) = 2.54, 95%CI = 1.51–4.28), being away from home (OR = 1.7, 95%CI = 1.03–2.78), substance abuse (OR = 2.7, 95%CI = 1.44–5.05), general knowledge about ART (OR = 2.75, 95%CI = 1.67–4.53), stopping medication after improvement (OR = 4.16, 95%CI = 2.29–7.56) and self-assessment of therapy adherence (OR = 9.83, 95%CI = 5.44–17.77) were significantly associated with patients’ adherence. Conclusions: Three-quarters of patients were adherent to ART. Researchers should consider these determinants of adherence in developing interventions in further studies.

Metabolic constraints in the tumor microenvironment constitute a barrier to effective antitumor immunity and similarities in the metabolic properties of T cells and cancer cells impede the specific therapeutic targeting of metabolism in either population. To identify distinct metabolic vulnerabilities of CD8+ T cells and cancer cells, we developed a high-throughput in vitro pharmacologic screening platform and used it to measure the cell type–specific sensitivities of activated CD8+ T cells and B16 melanoma cells to a wide array of metabolic perturbations during antigen-specific killing of cancer cells by CD8+ T cells. We illustrated the applicability of this screening platform by showing that CD8+ T cells were more sensitive to ferroptosis induction by inhibitors of glutathione peroxidase 4 (GPX4) than B16 and MC38 cancer cells. Overexpression of ferroptosis suppressor protein 1 (FSP1) or cytosolic GPX4 yielded ferroptosis-resistant CD8+ T cells without compromising their function, while genetic deletion of the ferroptosis sensitivity–promoting enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4) protected CD8+ T cells from ferroptosis but impaired antitumor CD8+ T-cell responses. Our screen also revealed high T cell–specific vulnerabilities for compounds targeting NAD+ metabolism or autophagy and endoplasmic reticulum (ER) stress pathways. We focused the current screening effort on metabolic agents. However, this in vitro screening platform may also be valuable for rapid testing of other types of compounds to identify regulators of antitumor CD8+ T-cell function and potential therapeutic targets.

We aimed to determine the performance of the Global Registry of Acute Coronary Events (GRACE) risk score version 2.0, and the long-term follow up of antithrombotic management patterns in acute coronary syndrome patients (EPICOR) risk score for predicting 1-year postdischarge mortality in patients with acute coronary syndrome (ACS) in Vietnam. A prospective cohort study was conducted on 455 patients who were discharged with an ACS diagnosis from two hospitals in Can Tho, and one in Ho Chi Minh City. Online simplified EPICOR and GRACE 2.0 calculators were used to assess the expected risk of death. We compared the performance of predicting 1-year mortality between GRACE 2.0 and EPICOR risk scores by using the Hosmer-Lemeshow test, the area under the curve (AUC), and the De-Long test. The proportions of low-risk group, moderate-risk group, and high-risk group for GRACE were 31%, 42%, and 27%, respectively. Actual mortality rates for the low, medium and high-risk groups were 3.6%, 9.4%, and 19.4%. The proportions of low-risk and high-risk patients for EPICOR were 92.0% and 8.0%, respectively. The actual mortality rate of the high-risk group was 31.4%, and of the low-risk group 8.6%. Hosmer-Lemeshow test results of the GRACE 2.0 and EPICOR were 0.337 and 0.001, respectively. The AUC results of the GRACE 2.0 and EPICOR were 0.703 and 0.752 respectively, and the De-Long test with p = 0.0532. In conclusion, the GRACE 2.0 was better than EPICOR in predicting 1-year postdischarge mortality in Vietnamese patients with ACS.

Pneumonia is one of the most common infectious diseases and the fourth leading cause of death globally. According to US statistics in 2019, pneumonia is the most common cause of sepsis and septic shock. In the US, inpatient pneumonia hospitalizations account for the top 10 highest medical costs, totaling $9.5 billion for 960,000 hospital stays. The emergence of antibiotic resistance in the treatment of infectious diseases, including the treatment of pneumonia, is a globally alarming problem. Antibiotic resistance increases the risk of death and re-hospitalization, prolongs hospital stays, and increases treatment costs, and is one of the greatest threats in modern medicine. Drug-related problems (DRPs) in pneumonia - such as suboptimal antibiotic indications, prolonged treatment duration, and drug interactions - increase the rate of antibiotic resistance and adverse effects, thereby leading to an increased burden in treatment. In a context in which novel and effective antibiotics are scarce, mitigating DRPs in order to reduce antibiotic resistance is currently a prime concern. A variety of interventions proven useful in reducing DRPs are antibiotic stewardship programs, the use of biomarkers, computerized physician order entries and clinical decision support systems, and community-acquired pneumonia scores.

Background: We aimed to translate, cross-culturally adapt, and validate the General Medication Adherence Scale (GMAS) into Vietnamese. Methods: We followed the guidelines of Beaton et al. during the translation and adaptation process. In Stage I, two translators translated the GMAS to Vietnamese. Stage II involved synthesizing the two translations. Stage III featured a back translation. Stage IV included an expert committee review and the creation of the pre-final version of the GMAS, and in stage V, pilot testing was conducted on 42 Vietnamese patients with type 2 diabetes. The psychometric validation process evaluated the reliability and validity of the questionnaire. The internal consistency and test–retest reliability were assessed by Cronbach’s alpha and Spearman’s correlation coefficients. The construct validity was determined by an association examination between the levels of adherence and patient characteristics. The content validity was based on the opinion and assessment score by the expert committee. The Vietnamese version of the GMAS was created, including 11 items divided into three domains. There was a good equivalence between the English and the Vietnamese versions of the GMAS in all four criteria. Results: One hundred and seventy-seven patients were participating in the psychometric validation process. Cronbach’s alpha was acceptable for all questionnaire items (0.817). Spearman’s correlation coefficient of the test–retest reliability was acceptable for the GMAS (0.879). There are significant correlations between medication adherence levels and occupation, income, and the Beliefs about Medicines Questionnaire (BMQ) score regarding construct validity. Conclusions: The Vietnamese version of GMAS can be considered a reliable and valid tool for assessing medication adherence in Vietnamese patients.

To translate and cross-culturally adapt the Brief Illness Perception Questionnaire (BIPQ) and the Beliefs about Medicines Questionnaire (BMQ) into Vietnamese.We followed the guideline by Beaton et al. (20002007). Stage I: two translators (informed and uninformed) translated the questionnaires. Stage II: the translations were synthesised. Stage III: back translation was performed by two translators fluent in both Vietnamese and English but naïve to the outcome measurement. Stage IV: seven experts reached consensus on the pre-final Vietnamese version (BIPQ-V and BMQ-V). Stage V: field test of the questionnaires on 16 twelve-year-old students and 31 Vietnamese patients. In addition, we determined the internal consistency and test-retest reliability of the questionnaires in 34 Vietnamese patients with acute coronary syndrome.All experts agreed that there was semantic, idiomatic, experiential and conceptual equivalence between the original and pre-final Vietnamese versions of the BIPQ and BMQ. Cronbach's alpha coefficients of the internal consistency were acceptable for the BMQ-V Specific-Necessity (0.64), BMQ-V Specific-Concerns (0.62) and BMQ-V General-Harm (0.60), with the exception of BMQ-V General-Overuse (0.27). Intra-class correlation coefficients of the test-retest reliability were acceptable for the subscales of BMQ-V (range: 0.77-0.86), and BIPQ-V items (range: 0.62-0.85) with the exception of BIPQ-V 1 (0.44, 95% CI -014 to 0.72) and BIPQ-V 4 (0.57, 95% CI 0.22-0.81).The Vietnamese version of BIPQ and BMQ are reliable tools to assess illness perceptions and beliefs about medicines of patients with acute coronary syndrome. Psychometric properties of these questionnaires should be tested in different patient populations.Traduire en vietnamien et adapter culturellement le Bref Questionnaire sur la Perception de la Maladie (BIPQ) et le Questionnaire sur les Croyances relatives aux Médicaments (BMQ). MÉTHODES: Nous avons suivi les directives de Beaton et al. (2000 et 2007). Etape I: deux traducteurs (informés et non informés) ont traduit les questionnaires. Etape II: les traductions ont été synthétisées. Etape III: une re-traduction a été effectuée par deux traducteurs parlant couramment le vietnamien et l’anglais mais naïfs sur la mesure des résultats. Etape IV: sept experts sont parvenus à un consensus sur la version vietnamienne pré-finale (BIPQ-V et BMQ-V). Etape V: test sur le terrain des questionnaires sur 16 étudiants de 12 ans et 31 patients vietnamiens. En outre, nous avons déterminé la cohérence interne et la fiabilité du test/re-test des questionnaires chez 34 patients vietnamiens atteints de syndrome coronarien aigu. RÉSULTATS: Tous les experts ont convenu qu'il existait une équivalence sémantique, idiomatique, expérientielle et conceptuelle entre les versions originales et pré-finale vietnamiennes du BIPQ et du BMQ. Les coefficients alpha de cohérence interne de Cronbach étaient acceptables pour la nécessité spécifique du BMQ-V (0,64), les préoccupations spécifiques du BMQ-V (0,62) et la nocivité générale du BMQ-V (0,60), à l'exception de la qualité générale du BMQ-V (0,27). Les coefficients de corrélation intra-classe de la fiabilité du test/re-test étaient acceptables pour les sous-échelles de BMQ-V (plage: 0,77-0,86) et les éléments du BIPQ-V (plage: 0,62-0,85) à l'exception du BIPQ-V 1 (0,44; IC95%: −014-0,72) et du BIPQ-V 4 (0,57; IC95%: 0,22-0,81).Les versions vietnamiennes du BIPQ et du BMQ constituent des outils fiables pour évaluer les perceptions relatives à la maladie et les croyances concernant les médicaments destinés aux patients atteints du syndrome coronarien aigu. Les propriétés psychométriques de ces questionnaires doivent être testées dans différentes populations de patients.

CD8+ T cell exhaustion is a state of dysfunction acquired in chronic viral infection and cancer, characterized by the formation of Slamf6+ progenitor exhausted and Tim-3+ terminally exhausted subpopulations through unknown mechanisms. Here we establish the phosphatase PTPN2 as a new regulator of the differentiation of the terminally exhausted subpopulation that functions by attenuating type 1 interferon signaling. Deletion of Ptpn2 in CD8+ T cells increased the generation, proliferative capacity and cytotoxicity of Tim-3+ cells without altering Slamf6+ numbers during lymphocytic choriomeningitis virus clone 13 infection. Likewise, Ptpn2 deletion in CD8+ T cells enhanced Tim-3+ anti-tumor responses and improved tumor control. Deletion of Ptpn2 throughout the immune system resulted in MC38 tumor clearance and improved programmed cell death-1 checkpoint blockade responses to B16 tumors. Our results indicate that increasing the number of cytotoxic Tim-3+CD8+ T cells can promote effective anti-tumor immunity and implicate PTPN2 in immune cells as an attractive cancer immunotherapy target.

Background: Our study was conducted to determine the prevalence of drug-related problems (DRPs) in outpatient prescriptions, the impact of DRPs on treatment efficacy, safety, and cost, and the determinants of DRPs in prescribing for pediatric outpatients in Vietnam. Methods: A retrospective cross-sectional study was conducted on pediatric outpatients at a pediatric hospital in Can Tho, Vietnam. DRPs were classified according to the Pharmaceutical Care Network Europe classification (PCNE) of 2020. The study determined prevalence of DRPs and their impacts on efficacy, safety, and cost. Multivariate regression was used to identify the determinants of DRPs. Results: The study included 4339 patients (mean age 4.3, 55.8% male), with a total of 3994 DRPs, averaging 0.92 DRP/prescription. The proportion of prescriptions with at least one DRP was 65.7%. DRPs included inappropriate drug selection (35.6%), wrong time of dosing relative to meals (35.6%), inappropriate dosage form (9.3%), inappropriate indication (7.1%), and drug-drug interactions (0.3%). The consensus of experts was average when evaluating each aspect of efficiency reduction, safety reduction, and treatment cost increase, with Fleiss’ coefficients of 0.558, 0.511, and 0.541, respectively (p &lt, 0.001). Regarding prescriptions, 50.1% were assessed as reducing safety. The figures for increased costs and decreased treatment effectiveness were 29.0% and 23.9%, respectively. Patients who were ≤ 2 years old were more likely to have DRPs than patients aged 2 to 6 years old (OR = 0.696, 95% CI = 0.599–0.809) and patients aged over 6 years old (OR = 0.801, 95% CI = 0.672–0.955). Patients who had respiratory system disease were more likely to have DRPs than patients suffering from other diseases (OR = 0.715, 95% CI = 0.607–0.843). Patients with comorbidities were less likely to have DRPs than patients with no comorbidities (OR = 1.421, 95% CI = 1.219–1.655). Patients prescribed ≥ 5 drugs were more likely to have DRPs than patients who took fewer drugs (OR = 3.677, 95% CI = 2.907–4.650). Conclusion: The proportion of prescriptions in at least one DRP was quite high. Further studies should evaluate clinical significance and appropriate interventions, such as providing drug information and consulting doctors about DRPs.

Background Despite evidence that treatment reduces addiction-related harms, including crime and overdose, only a minority of addiction-affected individuals receive it. Linking individuals who committed an addiction-related crime to addiction treatment could improve outcomes. Methods The aim of this city-wide, pre-arrest diversion program, Madison Addiction Recovery Initiative (MARI) is to reduce crime and improve health (i.e., reduce the overdose deaths) among adults who committed a minor, non-violent, drug use-related offense by offering them a referral to treatment in lieu of arrest and prosecution of criminal charges. This manuscript outlines the protocol and methods for the MARI program development and implementation. MARI requires its participants to engage in the recommended treatment, without reoffending, during the six-month program, after which the initial criminal charges are “voided” by the law enforcement agency. The project, implemented in a mid-size U.S. city, has involved numerous partners, including law enforcement, criminal justice, public health, and academia. It includes training of the police officer workforce and collaboration with clinical partners for treatment need assessment, treatment placement, and peer support. Program evaluation includes formative, process, outcome (participant-level) and exploratory impact (community-level) assessments. For outcome evaluation, we will compare crime (primary outcome), overdose-related offenses, and incarceration-related data 12 months before and 12 months after the index crime between participants who completed (Group 1), started but not completed (Group 2), and were offered but did not start (Group 3) the program, and adults who would have been eligible should MARI existed (Historical Comparison, Group 4). Clinical characteristics will be compared at baseline between Groups 1–2, and pre-post the program within Group 1. Participant baseline data will be assessed as potential covariates. Surveys of police officers and program completers, and community-level indicators of crime and overdose pre- versus post-program will provide additional data on the program impact. Discussion By offering addiction treatment in lieu of arrest and prosecution of criminal charges, this pre-arrest diversion program has the potential to disrupt the cycle of crime, reduce the likelihood of future offenses, and promote public health and safety.

What is known and objective: Coronary artery disease (CAD) is the leading cause of mortality worldwide. Patient education is an essential part of cardiac patients’ care targeting self-management behaviour to reduce risk factors and subsequent events. There has been no Vietnamese questionnaire to assess patient's knowledge about CAD; therefore, the purpose of this study was to translate, cross-culturally adapt and validate the Coronary Artery Disease Education Questionnaire—Short Version (CADE-Q SV) for use in Vietnam. Methods: Translation and cross-cultural adaption of the tool were carried out in five stages: (a) two independent translations from English into Vietnamese were produced; (b) these two translations were then synthesized; (c) two translators blinded to the outcome measurements independently created separate back translations into English; (d) nine experts reached consensus on all items of the Vietnamese version of the CADE-Q SV; and (e) a pilot study was conducted on 35 patients with acute coronary syndrome (ACS). The validity and reliability of the questionnaires were then evaluated in 117 Vietnamese patients with ACS. The internal consistency and test-retest reliability were assessed by Cronbach's alpha and Cohen's kappa coefficient, respectively. Construct validity was determined by examining the relationship between knowledge scores and patient characteristics. Results: The Vietnamese version of CADE-Q SV was created, including 20 items divided into two domains: medical and psychological condition, and nutrition and exercise. There was good equivalence between the original and the Vietnamese versions in all four areas: semantic, idiomatic, experiential and conceptual equivalence. Cronbach's alpha coefficients were acceptable for the questionnaire as a whole (0.78) and for the two domains: medical and psychological condition (0.71) and nutrition and exercise (0.52). All Cohen's kappa coefficients confirmed test-retest reliability (Kappa > 0.600; P

Metabolic constraints in the tumor microenvironment constitute a barrier to effective anti-tumor immunity and similarities in the metabolic properties of T cells and cancer cells impede the specific therapeutic targeting of metabolism in either population. To identify distinct metabolic vulnerabilities of CD8(+) T cells and cancer cells, we developed a high-throughput in vitro pharmacologic screening platform and used it to measure the cell type–specific sensitivities of activated CD8(+) T cells and B16 melanoma cells to a wide array of metabolic perturbations during antigen-specific killing of cancer cells by CD8(+) T cells. We illustrated the applicability of this screening platform by showing that CD8(+) T cells were more sensitive to ferroptosis than B16 and MC38 cancer cells. Overexpression of ferroptosis suppressor protein 1 (FSP1) or cytosolic GPX4 yielded ferroptosis-resistant CD8(+) T cells without compromising their function, while genetic deletion of the ferroptosis sensitivity–promoting enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4) protected CD8(+) T cells from ferroptosis, but impaired anti-tumor CD8(+) T cell responses. Our screen also revealed high T cell–specific vulnerabilities for compounds targeting NAD(+) metabolism or autophagy and ER stress pathways. We focused the current screening effort on metabolic agents. However, this in vitro screening platform may also be valuable for rapid testing of other types of compounds to identify regulators of anti-tumor CD8(+) T-cell function and potential therapeutic targets.

Background: Inappropriate antibiotic use among outpatients is recognized as the primary driver of antibiotic resistance. A proper understanding of appropriate antibiotic usage and associated factors helps to determine and limit inappropriateness. We aimed to identify the rate of appropriate use of antibiotics and identify factors associated with the inappropriate prescriptions. Methods: We conducted a cross-sectional descriptive study in outpatient antibiotic use at a hospital in Can Tho City, Vietnam, from August 1, 2019, to January 31, 2020. Data were extracted from all outpatient prescriptions at the Medical Examination Department and analyzed by SPSS 18 and Chi-squared tests, with 95% confidence intervals. The rationale for antibiotic use was evaluated through antibiotic selection, dose, dosing frequency, dosing time, interactions between antibiotics and other drugs, and general appropriate usage. Results: A total of 420 prescriptions were 51.7% for females, 61.7% with health insurance, and 44.0% for patients with one comorbid condition. The general appropriate antibiotic usage rate was 86.7%. Prescriptions showed that 11.0% and 9.5% had a higher dosing frequency and dose than recommended, respectively, 10.2% had an inappropriate dosing time, 3.1% had drug interactions, and only 1.7% had been prescribed inappropriate antibiotics. The risk of inappropriate antibiotic use increased in patients with comorbidities and antibiotic treatment lasting &gt, 7 days (p &lt, 0.05). Conclusions: The study indicated a need for more consideration when prescribing antibiotics to patients with comorbidities or using more than 7 days of treatment.

The Chemistry Science Investigation: Dognapping Workshop was designed to (i) target and inspire fourth grade students to view themselves as Junior Scientists before their career decisions are solidified; (ii) enable hands-on experience in fundamental scientific concepts; (iii) increase public interaction with science, technology, engineering, and mathematical personnel by providing face-to-face opportunities; (iv) give teachers a pathway forward for scientific resources; (v) meet the New Mexico K–5 Science Benchmark Performance Standards; (vi) most importantly, ensure everyone has fun! For this workshop, the students are told they will be going to see a Chemistry Magic Show, but the performance is stopped when the Chemistry Dog is reportedly stolen. The students first clear their names using a series of interactive stations and then apply a number of science experiments to solve the mystery. This report describes the workshop in detail, which is suitable for large (∼100 students per day) audiences but has...

Obesity is a major cancer risk factor, but how differences in systemic metabolism change the tumor microenvironment (TME) and impact anti-tumor immunity is not understood. Here, we demonstrate that high-fat diet (HFD)-induced obesity impairs CD8(+) T cell function in the murine TME, accelerating tumor growth. We generate a single-cell resolution atlas of cellular metabolism in the TME, detailing how it changes with diet-induced obesity. We find that tumor and CD8(+) T cells display distinct metabolic adaptations to obesity. Tumor cells increase fat uptake with HFD, whereas tumor-infiltrating CD8(+) T cells do not. These differential adaptations lead to altered fatty acid partitioning in HFD tumors, impairing CD8(+) T cell infiltration and function. Blocking metabolic reprogramming by tumor cells in obese mice improves anti-tumor immunity. Analysis of human cancers reveals similar transcriptional changes in CD8(+) T cell markers, suggesting interventions that exploit metabolism to improve cancer immunotherapy.

Immunotherapy using checkpoint-blocking antibodies against PD-1 has produced impressive results in a wide range of cancers. However, the response remains heterogeneous among patients. We used noninvasive immuno-positron emission tomography (PET), using (89)Zr-labeled PEGylated single-domain antibody fragments (nanobodies or VHHs), to explore the dynamics and distribution of intratumoral CD8(+) T cells and CD11b(+) myeloid cells in response to anti–PD-1 treatment in the MC38 colorectal mouse adenocarcinoma model. Responding and nonresponding tumors showed consistent differences in the distribution of CD8(+) and CD11b(+) cells. Anti–PD-1 treatment mobilized CD8(+) T cells from the tumor periphery to a more central location. Only those tumors fully infiltrated by CD8(+) T cells went on to complete resolution. All tumors contained CD11b(+) myeloid cells from the outset of treatment, with later recruitment of additional CD11b(+) cells. As tumors grew, the distribution of intratumoral CD11b(+) cells became more heterogeneous. Shrinkage of tumors in responders correlated with an increase in the CD11b(+) population in the center of the tumors. The changes in distribution of CD8(+) and CD11b(+) cells, as assessed by PET, served as biomarkers to gauge the efficacy of anti–PD-1 treatment. Single-cell RNA sequencing of RNA from intratumoral CD45(+) cells showed that CD11b(+) cells in responders and nonresponders were markedly different. The responders exhibited a dominant population of macrophages with an M1-like signature, while the CD45(+) population in the nonresponders displayed an M2-like transcriptional signature. Thus, by using immuno-PET and single-cell RNA sequencing, we show that anti–PD-1 treatment not only affects interactions of CD8(+) T cells with the tumor but also impacts the intratumoral myeloid compartment.

CD8+ T cell exhaustion is a state of dysfunction acquired in chronic viral infection and cancer, characterized by the formation of Slamf6+ progenitor exhausted and Tim-3+ terminally exhausted subpopulations through unknown mechanisms. Here we establish the phosphatase PTPN2 as a novel regulator of the differentiation of the terminally exhausted subpopulation that functions by attenuating type 1 interferon signaling. Deletion of Ptpn2 in CD8+ T cells increased the generation, proliferative capacity, and cytotoxicity of Tim-3+ cells without altering Slamf6+ numbers during LCMV Clone 13 infection. Likewise, Ptpn2-deletion in CD8+ T cells enhanced Tim-3+ anti-tumor responses and improved tumor control. Deletion of Ptpn2 throughout the immune system resulted in MC38 tumor clearance and improved PD-1 checkpoint blockade responses to B16 tumors. Our results indicate that increasing the number of cytotoxic Tim-3+ CD8+ T cells can promote effective anti-tumor immunity and implicate PTPN2 in immune cells as an attractive cancer immunotherapy target.

This study aimed to assess the knowledge of antiretroviral (ARV) treatment and the associated factors in HIV-infected patients in Vietnam. We conducted a cross-sectional descriptive study of 350 human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients being treated with ARV at outpatient clinics at Soc Trang, Vietnam, from June 2019 to December 2019. Using an interview questionnaire, patients who answered at least eight out of nine questions correctly, including some required questions, were considered to have a general knowledge of ARV treatment. Using multivariate logistic regression to identify factors associated with knowledge of ARV treatment, we found that 62% of HIV-infected patients had a general knowledge of ARV treatment, with a mean score of 8.2 (SD 1.4) out of 9 correct. A higher education level (p &lt, 0.001), working away from home (p = 0.013), getting HIV transmitted by injecting drugs or from mother-to-child contact (p = 0.023), the presence of tension, anxiety, or stress (p = 0.005), self-reminding to take medication (p = 0.024), and a high self-evaluated adherence (p &lt, 0.001) were found to be significantly associated with an adequate knowledge of ARV treatment. In conclusion, education programs for patients, as well as the quality of medical services and support, should be strengthened.

SETTING Community-wide active case finding for tuberculosis (TB) using Xpert® MTB/RIF as the primary screening tool, Ca Mau Province, Viet Nam. OBJECTIVES To determine whether macroscopic sputum quality characteristics (sputum colour and volume) can be used to predict Xpert MTB-negative sputum and hence exclude sputum samples from testing. DESIGN Field staff conducted household visits to approximately 51,200 adults in 58 villages randomly selected from throughout the province. Sputum samples from all screened participants who were able to produce ⩾1 ml sputum underwent macroscopic sputum assessment and were tested with Xpert. RESULTS Of the 21,624 sputum samples tested, 159 (0.74%) were Xpert MTB-positive; 93% of the samples were 1-2 ml and nearly all were mucoid (93%) or mucopurulent (5.7%). One salivary sample was Xpert MTB-positive (2.0% of all salivary samples). The lowest positive predictive value for any sputum volume or colour characteristic was 0.66%. This was not substantially different from the overall prevalence of positive sputum Xpert MTB (0.74%). CONCLUSION Sputum colour and volume cannot be used to predict the presence or absence of M. tuberculosis in sputum detected using Xpert. These sputum quality parameters cannot therefore be used to exclude sputum samples from testing for TB.

Despite the significant clinical responses observed with checkpoint blockade, there is an urgent need to identify new therapeutic targets in immune cells for combination therapies. However, the use of functional genomic approaches in immune cells to discover immunotherapy targets is limited by inefficient vector delivery or perturbation of cell states. To circumvent these limitations, we developed CHIME: CHimeric IMmune Editing, a bone marrow chimeric CRISPR-Cas9 delivery system, to rapidly evaluate gene function in innate and adaptive immune cells in vivo without prior ex vivo manipulation. This approach enables efficient deletion of genes of interest in major immune lineages without altering immune development or function. To discover novel immunotherapy targets we performed an in vivo pooled genetic screen for negative regulators of CD8+ T-cell responses to LCMV Clone 13 viral infection. We found that deletion of the phosphatase Ptpn2 enhances CD8+ T-cell responses to chronic pathogens and cancer. In models of both chronic viral infection and transplantable tumors, Ptpn2 null CD8+ T cells expand more and show increased expression of effector genes compared to wild-type cells. Consistent with this, in the LCMV Clone 13 model, Ptpn2 deletion in CD8+ T cells affects the differentiation and expansion of exhausted subpopulations by increasing IFN-I signaling. Furthermore, deletion of Ptpn2 in the immune system induces a CD8+ T cell-dependent clearance of tumors and synergizes with PD-1 immune checkpoint blockade. Our results suggest that therapeutic inhibition of Ptpn2 in immune cells may enhance CD8+ T-cell effector function and mediate antitumor immunity to improve tumor control. More generally, these findings suggest that this genetic platform can enable rapid target discovery through pooled loss-of-function screening in immune cell lineages in vivo and presents a novel target for potential immune based therapies. Citation Format: Martin LaFleur, Thao Nguyen, Matthew Coxe, Brian Miller, Kathleen Yates, Jacob Gillis, Debattama Sen, John Doench, Nicholas Haining, Arlene Sharpe. CHIME screening identifies PTPN2 as a novel regulator of antitumor immunity [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B47.

Background: Patient adherence to cardioprotective medications improves outcomes of acute coronary syndrome (ACS), but few adherence-enhancing interventions have been tested in low-income and middle-income countries.Objectives: We aimed to assess whether a pharmacist-led intervention enhances medication adherence in patients with ACS and reduces mortality and hospital readmission.Methods: We conducted a randomized controlled trial in Vietnam. Patients with ACS were recruited, randomized to the intervention or usual care prior to discharge, and followed 3 months after discharge. Intervention patients received educational and behavioral interventions by a pharmacist. Primary outcome was the proportion of adherent patients 1 month after discharge. Adherence was a combined measure of self-reported adherence (the 8-item Morisky Medication Adherence Scale) and obtaining repeat prescriptions on time. Secondary outcomes were (1) the proportion of patients adherent to medication; (2) rates of mortality and hospital readmission; and (3) change in quality of life from baseline assessed with the European Quality of Life Questionnaire - 5 Dimensions - 3 Levels at 3 months after discharge. Logistic regression was used to analyze data. Registration: ClinicalTrials.gov (NCT02787941).Results: Overall, 166 patients (87 control, 79 intervention) were included (mean age 61.2 years, 73% male). In the analysis excluding patients from the intervention group who did not receive the intervention and excluding all patients who withdrew, were lost to follow-up, died or were readmitted to hospital, a greater proportion of patients were adherent in the intervention compared with the control at 1 month (90.0% vs. 76.5%; adjusted OR = 2.77; 95% CI, 1.01-7.62) and at 3 months after discharge (90.2% vs. 77.0%; adjusted OR = 3.68; 95% CI, 1.14-11.88). There was no significant difference in median change of EQ-5D-3L index values between intervention and control [0.000 (0.000; 0.275) vs. 0.234 (0.000; 0.379); p = 0.081]. Rates of mortality, readmission, or both were 0.8, 10.3, or 11.1%, respectively; with no significant differences between the 2 groups.Conclusion: Pharmacist-led interventions increased patient adherence to medication regimens by over 13% in the first 3 months after ACS hospital discharge, but not quality of life, mortality and readmission. These results are promising but should be tested in other settings prior to broader dissemination.

OBJECTIVES: To determine the extent of physicians' adherence to prescribing guidelines for acute coronary syndrome in Vietnamese hospitals.METHODS: Retrospective cross-sectional study of medical records of all patients with ACS admitted to two public hospitals in Ho Chi Minh City, Vietnam, from January to December 2013. Percentages of eligible patients receiving guideline-recommended medications were determined. Factors associated with non-adherence were identified using multivariate logistic regression.RESULTS: Overall, 711 medical records were reviewed and 284 patients fulfilled inclusion criteria (mean age 64 years; 69.4% male). Of those patients eligible for treatment, aspirin was prescribed for 97.9% at arrival and 96.3% at discharge; dual antiplatelet therapy was prescribed for 92.3% at arrival and 91.7% at discharge; loading doses were prescribed for 79.5% (aspirin) and 55.8% (clopidogrel); beta blockers were prescribed for 58.7% at arrival and 76.7% at discharge; angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) were prescribed for 89.1% at arrival and discharge; and statins were prescribed for 94.1% at arrival and 90.7% at discharge. Patients undergoing an invasive procedure were more likely to receive guideline-recommended medications at discharge: dual antiplatelet therapy (OR 3.77; 95% CI 1.23-11.52), beta blocker (OR 3.95; 95% CI 1.86-8.40), and ACEI/ARB (OR 4.01; 95% CI 1.30-12.41). Ninety of the excluded patients were discharged without completing treatment.CONCLUSIONS: In general, physicians closely adhered to ACS prescribing guidelines in Vietnamese hospital practice. Prescribing of beta blockers and clopidogrel loading doses was probably suboptimal. Why patients do not complete treatment needs to be investigated. This article is protected by copyright. All rights reserved.

ObjectiveWe aimed to determine the association between physician adherence to prescribing guideline-recommended medications during hospitalisation and 6-month major adverse outcomes of patients with acute coronary syndrome in Vietnam.DesignProspective cohort study.SettingThe study was carried out in two public hospitals in Vietnam between January and October 2015. Patients were followed for 6 months after discharge.ParticipantsPatients who survived during hospitalisation with a discharge diagnosis of acute coronary syndrome and who were eligible for receiving at least one of the four guideline-recommended medications.ExposuresGuideline adherence was defined as prescribing all guideline-recommended medications at both hospital admission and discharge for eligible patients. Medications were antiplatelet agents, beta-blockers, ACE inhibitors or angiotensin II receptor blockers and statins.Main outcome measureSix-month major adverse outcomes were defined as all-cause mortality or hospital readmission due to cardiovascular causes occurring during 6 months after discharge. Cox regression models were used to estimate the association between guideline adherence and 6-month major adverse outcomes.ResultsOverall, 512 patients were included. Of those, there were 242 patients (47.3%) in the guideline adherence group and 270 patients (52.3%) in the non-adherence group. The rate of 6-month major adverse outcomes was 30.5%. A 29% reduction in major adverse outcomes at 6 months after discharge was found for patients of the guideline adherence group compared with the non-adherence group (adjusted HR, 0.71; 95% CI, 0.51 to 0.98; p=0.039). Covariates significantly associated with the major adverse outcomes were percutaneous coronary intervention, prior heart failure and renal insufficiency.ConclusionsIn-hospital guideline adherence was associated with a significant decrease in major adverse outcomes up to 6 months after discharge. It supports the need for improving adherence to guidelines in hospital practice in low-income and middle-income countries like Vietnam.

Health-related quality of life (HRQL) is a good indicator to monitor and evaluate healthcare services for adults with HIV/AIDS. This study described HRQL of adults with HIV and its determinants, and compared it with HRQL for the general population. A cross-sectional study with a national multistage sampling of households with and without HIV-positive people was conducted in 2008. Six provinces were purposively selected to represent areas of the country and progressions of HIV epidemics. Households were sampled with probability-proportional-to-size, following the selection of rural and urban districts. A total of 820 HIV-positive and HIV-negative adults (mean age: 32.5; 38.7% female) were interviewed. Among 400 HIV-positive people, 52.3% had a history of injecting drugs, and 56.3% were at AIDS stage and receiving antiretroviral treatment (ART). HRQL was measured using the EuroQOL five-dimension questionnaire (EQ-5D). Multiple regression models were purposefully constructed to examine the determinants of HRQL. The EQ-5D index and visual analog scale (VAS) score in less advanced HIV people (0.90, 69.3) and AIDS patients (0.88, 65.2) were significantly lower than those of the general population (0.96, 81.6) (p

Objectives Ischaemic heart diseases (IHDs) are a leading cause of death worldwide. Although prescribing according to guidelines improves health outcomes, it remains suboptimal. We determined whether interventions targeted at healthcare professionals are effective to enhance prescribing and health outcomes in patients with IHDs. Methods We systematically searched PubMed and EMBASE for studies published between 1 January 2000 and 31 August 2017. We included original studies of interventions targeted at healthcare professionals to enhance prescribing guideline-recommended medications for IHDs. We only included randomised controlled trials (RCTs). Main outcomes were the proportion of eligible patients receiving guideline-recommended medications, the proportion of patients achieving target blood pressure and target low-density lipoprotein-cholesterol (LDL-C)/cholesterol level and mortality rate. Meta-analyses were performed using the inverse-variance method and the random effects model. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results We included 13 studies, 4 RCTs (1869 patients) and 9 cluster RCTs (15 224 patients). 11 out of 13 studies were performed in North America and Europe. Interventions were of organisational or professional nature. The interventions significantly enhanced prescribing of statins/lipid-lowering agents (OR 1.23; 95% CI 1.07 to 1.42, P=0.004), but not other medications (aspirin/antiplatelet agents, beta-blockers, ACE inhibitors/angiotensin II receptor blockers and the composite of medications). There was no significant association between the interventions and improved health outcomes (target LDL-C and mortality) except for target blood pressure (OR 1.46; 95% CI 1.11 to 1.93; P=0.008). The evidence was of moderate or high quality for all outcomes. Conclusions Organisational and professional interventions improved prescribing of statins/lipid-lowering agents and target blood pressure in patients with IHDs but there was little evidence of change in other outcomes. PROSPERO registration number CRD42016039188.