US Food and Drug Administration Approval Summary: Talazoparib in Combination With Enzalutamide for Treatment of Patients With Homologous Recombination Repair Gene-Mutated Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: The US Food and Drug Administration (FDA) approved talazoparib with enzalutamide for first-line treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: The approval was based on the HRR gene-mutated (HRRm) population of TALAPRO-2, a randomized, double-blind trial that randomly assigned 1,035 patients with mCRPC to receive enzalutamide with either talazoparib or placebo. Two cohorts enrolled sequentially: an all-comer population (Cohort 1), followed by an HRRm-only population (Cohort 2). The independent primary end points were radiographic progression-free survival (rPFS) per blinded independent central review (BICR) in Cohort 1 (all-comers) and in the combined HRRm population (all HRRm patients from Cohorts 1 and 2). Overall survival (OS) was a key secondary end point. RESULTS: A statistically significant improvement in rPFS by BICR was demonstrated in both the all-comers cohort and the combined HRRm population, with hazard ratio (HR) of 0.63 (95% CI, 0.51 to 0.78; P < .0001) and 0.45 (95% CI, 0.33 to 0.61; P < .0001), respectively. In an exploratory analysis of the 155 patients with BRCA-mutated (BRCAm) mCRPC, rPFS HR was 0.20 (95% CI, 0.11 to 0.36). In the non-HRRm/unknown stratum of Cohort 1 (n = 636), the rPFS HR was 0.70 (95% CI, 0.54 to 0.89). OS was immature. CONCLUSION: Despite a statistically significant rPFS improvement in the all-comer cohort, FDA did not consider the magnitude of rPFS clinically meaningful in the context of the broad indication, combination treatment, and safety profile. Approval was therefore limited to patients with HRRm mCRPC, for whom there was a statistically significant and clinically meaningful improvement in rPFS and favorable OS results. This represents the first approval for the first-line treatment of patients with HRRm mCRPC.

Multifocal fatty liver nodules mimicking a metastatic disease: A case report.

Multifocal fatty liver nodules can present a diagnostic challenge due to their resemblance to metastatic liver disease. This case report illustrates the complexity of such scenarios through the presentation of a middle-aged male patient. Despite the common nature of fatty liver disease, characterized by hepatocyte fat accumulation leading to diffuse and uniform liver lesions, rare instances exhibit heterogeneous appearances. The case underlines the potential confusion arising from imaging modalities when multiple small nodules disperse throughout the liver, mimicking multifocal tumors or metastases. The report emphasizes the critical role of comprehensive diagnostic procedures in preventing misdiagnosis and unwarranted interventions. Effective management hinges on multidisciplinary collaboration among specialists, ensuring accurate differentiation and appropriate treatment. This study serves as a reminder of the intricacies involved in interpreting multifocal fatty liver nodules that may masquerade as metastatic disease, highlighting the need for precision in clinical practice.

Exploration of 1,2,3-triazolo fused triterpenoids as inhibitors of human coronavirus 229E targeting the viral nsp15 protein.

The coronavirus disease-19 (COVID-19) pandemic has raised major interest in innovative drug concepts to suppress human coronavirus (HCoV) infections. We previously reported on a class of 1,2,3-triazolo fused betulonic acid derivatives causing strong inhibition of HCoV-229E replication via the viral nsp15 protein, which is proposedly related to compound binding at an intermonomer interface in hexameric nsp15. In the present study, we further explored the structure-activity relationship (SAR), by varying the substituent at the 1,2,3-triazolo ring as well as the triterpenoid skeleton. The 1,2,3-triazolo fused triterpenoids were synthesized by a multicomponent triazolization reaction, which has been developed in-house. Several analogs possessing a betulin, oleanolic acid, or ursolic acid core displayed favorable activity and selectivity (EC50 values for HCoV-229E: 1.6-3.5 µM), but neither of them proved as effective as the lead compound containing betulonic acid. The 18ß-glycyrrhetinic acid-containing analogs had low selectivity. The antiviral findings were rationalized by in silico docking in the available structure of the HCoV-229E nsp15 protein. The new SAR insights will aid the further development of these 1,2,3-triazolo fused triterpenoid compounds as a unique type of coronavirus inhibitors.

Hydroxyapatite: A journey from biomaterials to advanced functional materials.

Hydroxyapatite (HAp), a well-known biomaterial, has witnessed a remarkable evolution over the years, transforming from a simple biocompatible substance to an advanced functional material with a wide range of applications. This abstract provides an overview of the significant advancements in the field of HAp and its journey towards becoming a multifunctional material. Initially recognized for its exceptional biocompatibility and bioactivity, HAp gained prominence in the field of bone tissue engineering and dental applications. Its ability to integrate with surrounding tissues, promote cellular adhesion, and facilitate osseointegration made it an ideal candidate for various biomedical implants and coatings. As the understanding of HAp grew, researchers explored its potential beyond traditional biomaterial applications. With advances in material synthesis and engineering, HAp began to exhibit unique properties that extended its utility to other disciplines. Researchers successfully tailored the composition, morphology, and surface characteristics of HAp, leading to enhanced mechanical strength, controlled drug release capabilities, and improved biodegradability. These modifications enabled the utilization of HAp in drug delivery systems, biosensors, tissue engineering scaffolds, and regenerative medicine applications. Moreover, the exceptional biomineralization properties of HAp allowed for the incorporation of functional ions and molecules during synthesis, leading to the development of bioactive coatings and composites with specific therapeutic functionalities. These functionalized HAp materials have demonstrated promising results in antimicrobial coatings, controlled release systems for growth factors and therapeutic agents, and even as catalysts in chemical reactions. In recent years, HAp nanoparticles and nanostructured materials have emerged as a focal point of research due to their unique physicochemical properties and potential for targeted drug delivery, imaging, and theranostic applications. The ability to manipulate the size, shape, and surface chemistry of HAp at the nanoscale has paved the way for innovative approaches in personalized medicine and regenerative therapies. This abstract highlights the exceptional evolution of HAp, from a traditional biomaterial to an advanced functional material. The exploration of novel synthesis methods, surface modifications, and nanoengineering techniques has expanded the horizon of HAp applications, enabling its integration into diverse fields ranging from biomedicine to catalysis. Additionally, this manuscript discusses the emerging prospects of HAp-based materials in photocatalysis, sensing, and energy storage, showcasing its potential as an advanced functional material beyond the realm of biomedical applications. As research in this field progresses, the future holds tremendous potential for HAp-based materials to revolutionize medical treatments and contribute to the advancement of science and technology.

In vitro characterization of a novel Arg102 mutation in the ADAMTS13 metalloprotease domain.

BACKGROUND: Congenital thrombotic thrombocytopenic purpura is caused by defects in the ADAMTS13 gene. ADAMTS13 is normally preactivated by conformational changes of the Metalloprotease (M) domain. Studying a novel congenital thrombotic thrombocytopenic purpura p.R102S mutation in the M domain, which results in undetectable ADAMTS13 activity in the patient, could help to explain the patients' phenotype and to elucidate the currently unclear mechanism of allosteric preactivation. OBJECTIVES: To investigate the in vitro effect of p.R102S mutation on ADAMTS13 secretion, activity, and allosteric preactivation. METHODS: Molecular modeling was used to study the effect of the mutation on the stability of ADAMTS13. Recombinant mutant ADAMTS13 was generated by transient and stable transfection of, respectively, CHO K1 and HEK293-T cells. ADAMTS13 antigen was measured in enzyme-linked immunosorbent assay. ADAMTS13 activity was measured in a FRETS-VWF73 assay. Allosteric preactivation was assessed in FRETS-VWF73 assay, using monoclonal antibody (mAb) 17G2 that normally induces a ∼2-fold increase in activity, and in enzyme-linked immunosorbent assay using mAb 6A6 recognizing a cryptic epitope in the M domain that becomes exposed after binding of 17G2. RESULTS: p.R102S mutation destabilizes the interactions between the M and Disintegrin-like (D) domain. p.R102S mutant secretion was impaired (35% of wild type) and activity was severely reduced (12% of wild type). p.R102S mutant could still be activated and the cryptic epitope of 6A6 was still fully exposed by 17G2 addition. CONCLUSION: p.R102S mutation destabilizes the M-D domain interactions, causing impaired ADAMTS13 secretion and activity, which explains the patients' phenotype. Allosteric preactivation of ADAMTS13 remains conserved in the presence of the p.R102S mutation.

Establishment of an in-house real-time RT-PCR assay for the detection of severe acute respiratory syndrome coronavirus 2 using the first World Health Organization international standard in a resource-limited country.

BACKGROUND: The COVID-19 pandemic caused by SARS-CoV-2 remains public health burdens and many unresolved issues worldwide. Molecular assays based on real-time RT-PCR are critical for the detection of SARS-CoV-2 in clinical specimens from patients suspected of COVID-19. OBJECTIVE: We aimed to establish and validate an in-house real-time RT-PCR for the detection of SARS-CoV-2. METHODOLOGY: Primers and probes sets in our in-house real-time RT-PCR assay were designed in conserved regions of the N and E target genes. Optimized multiplex real-time RT-PCR assay was validated using the first WHO International Standard (NIBSC code: 20/146) and evaluated clinical performance. RESULTS: The limit of detection validated using the first WHO International Standard was 159 IU/ml for both E and N target genes. The evaluation of clinical performance on 170 clinical samples showed a positive percent agreement of 100% and the negative percent agreement of 99.08% for both target genes. The Kappa value of 0.99 was an excellent agreement, the strong correlation of Ct values observed between two tests with r2  = 0.84 for the E gene and 0.87 for the N gene. Notably, we assessed on 60 paired saliva and nasopharyngeal samples. The overall agreement was 91.66%, and Kappa value of 0.74 showed a high agreement between two types of samples. When using nasopharyngeal swabs as the reference standard, positive percent agreement, and negative percent agreement were 91.83% and 90.90%, respectively. CONCLUSION: In the present study, we established and validated an in-house real-time RT-PCR for molecular detection of SARS-CoV-2 in a resource-limited country.

Pilot Findings of Pharmacogenomics in Perioperative Care: Initial Results From the First Phase of the ImPreSS Trial.

BACKGROUND: Pharmacogenomics, which offers a potential means by which to inform prescribing and avoid adverse drug reactions, has gained increasing consideration in other medical settings but has not been broadly evaluated during perioperative care. METHODS: The Implementation of Pharmacogenomic Decision Support in Surgery (ImPreSS) Trial is a prospective, single-center study consisting of a prerandomization pilot and a subsequent randomized phase. We describe findings from the pilot period. Patients planning elective surgeries were genotyped with pharmacogenomic results, and decision support was made available to anesthesia providers in advance of surgery. Pharmacogenomic result access and prescribing records were analyzed. Surveys (Likert-scale) were administered to providers to understand utilization barriers. RESULTS: Of eligible anesthesiology providers, 166 of 211 (79%) enrolled. A total of 71 patients underwent genotyping and surgery (median, 62 years; 55% female; average American Society of Anesthesiologists (ASA) score, 2.6; 58 inpatients and 13 ambulatories). No patients required postoperative intensive care or pain consultations. At least 1 provider accessed pharmacogenomic results before or during 41 of 71 surgeries (58%). Faculty were more likely to access results (78%) compared to house staff (41%; P = .003) and midlevel practitioners (15%) ( P < .0001). Notably, all administered intraoperative medications had favorable genomic results with the exception of succinylcholine administration to 1 patient with genomically increased risk for prolonged apnea (without adverse outcome). Considering composite prescribing in preoperative, recovery, throughout hospitalization, and at discharge, each patient was prescribed a median of 35 (range 15-83) total medications, 7 (range 1-22) of which had annotated pharmacogenomic results. Of 2371 prescribing events, 5 genomically high-risk medications were administered (all tramadol or omeprazole; with 2 of 5 pharmacogenomic results accessed), and 100 genomically cautionary mediations were administered (hydralazine, oxycodone, and pantoprazole; 61% rate of accessing results). Providers reported that although results were generally easy to access and understand, the most common reason for not considering results was because remembering to access pharmacogenomic information was not yet a part of their normal clinical workflow. CONCLUSIONS: Our pilot data for result access rates suggest interest in pharmacogenomics by anesthesia providers, even if opportunities to alter prescribing in response to high-risk genotypes were infrequent. This pilot phase has also uncovered unique considerations for implementing pharmacogenomic information in the perioperative care setting, and new strategies including adding the involvement of surgery teams, targeting patients likely to need intensive care and dedicated pain care, and embedding pharmacists within rounding models will be incorporated in the follow-on randomized phase to increase engagement and likelihood of affecting prescribing decisions and clinical outcomes.

Clinically actionable genotypes for anticancer prescribing among >1500 patients with pharmacogenomic testing.

BACKGROUND: In recent years, there has been increasing evidence supporting the role of germline pharmacogenomic factors predicting toxicity for anticancer therapies. Although somatic genomic data are used frequently in oncology care planning, germline pharmacogenomic testing is not. This study hypothesizes that comprehensive germline pharmacogenomic profiling could have high relevance for cancer care. METHODS: Between January 2011 and August 2020, patients at the University of Chicago Medical Center were genotyped across custom germline pharmacogenomic panels for reasons unrelated to cancer care. Actionable anticancer pharmacogenomic gene/drug interactions identified by the FDA were defined including: CYP2C9 (erdafitinib), CYP2D6 (gefitinib), DPYD (5-fluorouracil and capecitabine), TPMT (thioguanine and mercaptopurine), and UGT1A1 (belinostat, irinotecan, nilotinib, pazopanib, and sacituzumab-govitecan hziy). The primary objective was to determine the frequency of individuals with actionable or high-risk genotypes across these 5 key pharmacogenes, thus potentially impacting prescribing for at least 1 of these 11 commonly prescribed anticancer therapies. RESULTS: Data from a total of 1586 genotyped individuals were analyzed. The oncology pharmacogene with the highest prevalence of high-risk, actionable genotypes was UGT1A1, impacting 17% of genotyped individuals. Actionable TPMT and DPYD genotypes were found in 9% and 4% of patients, respectively. Overall, nearly one-third of patients genotyped across all 5 genes (161/525, 31%) had at least one actionable genotype. CONCLUSIONS: These data suggest that germline pharmacogenomic testing for 5 key pharmacogenes could identify a substantial proportion of patients at risk with standard dosing, an estimated impact similar to that of somatic genomic profiling. LAY SUMMARY: Differences in our genes may explain why some drugs work safely in certain individuals but can cause side effects in others. Pharmacogenomics is the study of how genetic variations affect an individual's response to medications. In this study, an evaluation was done for important genetic variations that can affect the tolerability of anticancer therapy. By analyzing the genetic results of >1500 patients, it was found that nearly one-third have genetic variations that could alter recommendations of what drug, or how much of, an anticancer therapy they should be given. Performing pharmacogenomic testing before prescribing could help to guide personalized oncology care.

Anesthesia providers as stakeholders to adoption of pharmacogenomic information in perioperative care.

OBJECTIVES: Integration of pharmacogenomics into clinical care is being studied in multiple disciplines. We hypothesized that understanding attitudes and perceptions of anesthesiologists, critical care and pain medicine providers would uncover unique considerations for future implementation within perioperative care. METHODS: A survey (multiple choice and Likert-scale) was administered to providers within our Department of Anesthesia and Critical Care prior to initiation of a department-wide prospective pharmacogenomics implementation program. The survey addressed knowledge, perceptions, experiences, resources and barriers. RESULTS: Of 153 providers contacted, 149 (97%) completed the survey. Almost all providers (92%) said that genetic results influence drug therapy, and few (22%) were skeptical about the usefulness of pharmacogenomics. Despite this enthusiasm, 87% said their awareness about pharmacogenomic information is lacking. Feeling well-informed about pharmacogenomics was directly related to years in practice/experience: only 38% of trainees reported being well-informed, compared to 46% of those with 1-10 years of experience, and nearly two-thirds with 11+ years (P < 0.05). Regarding barriers, providers reported uncertainty about availability of testing, turnaround time and whether testing is worth financial costs. CONCLUSIONS: Anesthesiology, critical care and pain medicine providers are optimistic about the potential clinical utility of pharmacogenomics, but are uncertain about practical aspects of testing and desire clear guidelines on the use of results. These findings may inform future institutional efforts toward greater integration of genomic results to improve medication-related outcomes.

2D-Material-integrated hydrogels as multifunctional protective skins for soft robots.

Soft robots provide compliant object-machine interactions, but they exhibit insufficient material stability, which restricts them from working in harsh environments. Herein, we developed a class of soft robotic skins based on two-dimensional materials (2DMs) and gelatin hydrogels, featuring skin-like multifunctionality (stretchability, thermoregulation, threat protection, and strain sensing). The 2DM-integrated hydrogel (2DM/H) skins enabled soft robots to execute designated missions in the presence of high levels of heat and various environmental threats while maintaining mild machine temperatures. Via adopting different 2DMs (graphene oxide (GO), montmorillonite (MMT), and titanium carbide (MXene)), the 2DM/H-protected robots were able to perform soft grasping in organic liquids (GO/H) and open fire (MMT/H), and in the presence of electromagnetic radiation and biocontamination (MXene/H). Through blending MXene nanosheets into gelatin, the MXene-blended hydrogel (M-H) skin became strain sensitive, and a GO/M-H gripper exhibited the high-level integration of skin-mimicking capabilities. Finally, we incorporated 2DM/H skins onto an origami-inspired walker robot and a soft batoid-like robot to execute vision-guided searching in fire and underwater locomotion/navigation in chemical spills.

Appraisal and development of evidence-based clinical decision support to enable perioperative pharmacogenomic application.

Variable responses to medications complicates perioperative care. As a potential solution, we evaluated and synthesized pharmacogenomic evidence that may inform anesthesia and pain prescribing to identify clinically actionable drug/gene pairs. Clinical decision-support (CDS) summaries were developed and were evaluated using Appraisal of Guidelines for Research and Evaluation (AGREE) II. We found that 93/180 (51%) of commonly-used perioperative medications had some published pharmacogenomic information, with 18 having actionable evidence: celecoxib/diclofenac/flurbiprofen/ibuprofen/piroxicam/CYP2C9, codeine/oxycodone/tramadol CYP2D6, desflurane/enflurane/halothane/isoflurane/sevoflurane/succinylcholine/RYR1/CACNA1S, diazepam/CYP2C19, phenytoin/CYP2C9, succinylcholine/mivacurium/BCHE, and morphine/OPRM1. Novel CDS summaries were developed for these 18 medications. AGREE II mean ± standard deviation scores were high for Scope and Purpose (95.0 ± 2.8), Rigor of Development (93.2 ± 2.8), Clarity of Presentation (87.3 ± 3.0), and Applicability (86.5 ± 3.7) (maximum score = 100). Overall mean guideline quality score was 6.7 ± 0.2 (maximum score = 7). All summaries were recommended for clinical implementation. A critical mass of pharmacogenomic evidence exists for select medications commonly used in the perioperative setting, warranting prospective examination for clinical utility.

Creation of a pharmacogenomics patient portal complementary to an existing institutional provider-facing clinical decision support system.

BACKGROUND: Applied pharmacogenomics presents opportunities for improving patient care through precision medicine, particularly when paired with appropriate clinical decision support (CDS). However, a lack of patient resources for understanding pharmacogenomic test results may hinder shared decision-making and patient confidence in treatment. We sought to create a patient pharmacogenomics education and results delivery platform complementary to a CDS system to facilitate further research on the relevance of patient education to pharmacogenomics. METHODS: We conceptualized a model that extended the data access layer of an existing institutional CDS tool to allow for the pairing of decision supports offered to providers with patient-oriented summaries at the same level of phenotypic specificity. We built a two-part system consisting of a secure portal for patient use and an administrative dashboard for patient summary creation. The system was built in an ASP.NET and AngularJS architecture, and all data was housed in a HIPAA-compliant data center, with PHI secure in transit and at rest. RESULTS: The YourPGx Patient Portal was deployed on the institutional network in June 2019. Fifty-eight unique patient portal summaries have been written so far, which can provide over 4500 results modules to the pilot population of 544 patients. Patient behavior on the portal is being logged for further research. CONCLUSIONS: To our knowledge, this is the first automated system designed and deployed to provide detailed, personalized patient pharmacogenomics education complementary to a clinical decision support system. Future work will expand upon this system to allow for telemedicine and patient notification of new or updated results.

Impact of CYP2D6 Pharmacogenomic Status on Pain Control Among Opioid-Treated Oncology Patients.

BACKGROUND: Several opioids have pharmacogenomic associations impacting analgesic efficacy. However, germline pharmacogenomic testing is not routinely incorporated into supportive oncology. We hypothesized that CYP2D6 profiling would correlate with opioid prescribing and hospitalizations. MATERIALS AND METHODS: We analyzed 61,572 adult oncology patients from 2012 to 2018 for opioid exposures. CYP2D6 metabolizer phenotype (ultra-rapid [UM], normal metabolizer [NM], intermediate [IM], or poor [PM]), the latter two of which may cause inefficacy of codeine, tramadol, and standard-dose hydrocodone, was determined for patients genotyped for reasons unrelated to pain. The primary endpoint was number of opioid medications received during longitudinal care (IM/PMs vs. NMs). Secondary endpoint was likelihood of pain-related hospital encounters. RESULTS: Most patients with cancer (n = 34,675, 56%) received multiple opioids (average 2.8 ± 1.6/patient). Hydrocodone was most commonly prescribed (62%), followed by tramadol, oxycodone, and codeine. In the CYP2D6 genotyped cohort (n = 105), IM/PMs received a similar number of opioids (3.4 ± 1.4) as NMs (3.3 ± 1.9). However, IM/PMs were significantly more likely to experience pain-related hospital encounters compared with NMs, independent of other variables (odds ratio [OR] = 5.4; 95% confidence interval [CI], 1.2-23.6; p = .03). IM/PMs were also more likely to be treated with later-line opioids that do not require CYP2D6 metabolism, such as morphine and hydromorphone (OR = 3.3; 95% CI, 1.1-9.8; p = .03). CONCLUSION: CYP2D6 genotype may identify patients with cancer at increased risk for inadequate analgesia when treated with typical first-line opioids like codeine, tramadol, or standard-dose hydrocodone. Palliative care considerations are an integral part of optimal oncology care, and these findings justify prospective evaluation of preemptive genotyping as a strategy to improve oncology pain management. IMPLICATIONS FOR PRACTICE: Genomic variation in metabolic enzymes can predispose individuals to inefficacy when receiving opioid pain medications. Patients with intermediate and/or poor CYP2D6 metabolizer status do not adequately convert codeine, tramadol, and hydrocodone into active compounds, with resulting increased risk of inadequate analgesia. This study showed that patients with cancer frequently receive CYP2D6-dependent opioids. However, patients with CYP2D6 intermediate and poor metabolizer status had increased numbers of pain-related hospitalizations and more frequently required the potent non-CYP2D6 opioids morphine and hydromorphone. This may reflect inadequate initial analgesia with the common "first-line" CYP2D6-metabolized opioids. Preemptive genotyping to guide opioid prescribing during cancer care may improve pain-related patient outcomes.

Young Adults' Intentions and Rationales for COVID-19 Vaccination Participation: Evidence from a Student Survey in Ho Chi Minh City, Vietnam.

The COVID-19 pandemic, a source of fear and anxiety worldwide, has caused many adverse impacts. Collaborative efforts to end COVID-19 have included extensive research on vaccines. Many vaccination campaigns have been launched in many countries, including Vietnam, to create community immunization. However, citizens' willingness to participate is a prerequisite for effective vaccination programs and other related policies. Among all demographic groups, participation rates among young adults are of interest because they are an important workforce and are a source of high infection risk in the community. In March 2021, a pool of approximately 6000 participants in Ho Chi Minh City were randomly polled using an email-based online survey. The exploratory results of 398 valid observations show that students' perceptions of the dangers of COVID-19 and the importance of vaccination were both relatively high (4.62/5 and 4.74/5, respectively). Furthermore, 83.41 percent of students polled (n = 332) chose vaccination, while 16.59 percent chose hesitation (n = 64) and not to be vaccinated (n = 2). More importantly, our estimated results of the Bayesian regression model (BRM) show that the perceived importance of the vaccine, concerns about the vaccine's side effects, and a lack of access to information are the top three reasons for their reluctance and/or refusal to get vaccinated. These findings are a valuable resource for politicians, researchers, and those interested in COVID-19 vaccinations to devise and execute campaigns to effectively combat this terrifying pandemic.

Application of Machine Learning for eutrophication analysis and algal bloom prediction in an urban river: A 10-year study of the Han River, South Korea.

The increasing release of nutrients to aquatic environments has led to great concern regarding eutrophication and the risk of unwanted algal blooms. Based on observational data of 20 water quality parameters measured on a monthly basis at 40 stations from 2011 to 2020, this study applied different Machine Learning (ML) algorithms to suggest the best option for algal bloom prediction in the Han River, a large river in South Korea. Eight different ML algorithms were categorized into several groups of statistical learning, regression family, and deep learning, and were then compared for their suitability to predict the chlorophyll-derived trophic index (TSI-Chla). ML algorithms helped identify the most important water quality parameters contributing to algal bloom prediction. The ML results confirmed that eutrophication and algal proliferation were governed by the complex interplay between nutrients (nitrogen and phosphorus), organic contaminants, and environmental factors. Of the models tested, the adaptive neuro-fuzzy inference system (ANFIS) exhibited the best performance owing to its consistent and outperforming prediction both quantitatively (i.e., via regression) and qualitatively (i.e., via classification), which was evidenced by the lowest value of mean absolute error (MAE) of 0.09, and the highest F1-score, Recall and Precision of 0.97, 0.98 and 0.96, respectively. In a further step, a representative web application was constructed to assist common users to predict the trophic status of the Han River. This study demonstrated that ML techniques are not only promising for highly accurate water quality modeling of urban rivers, but also reduce time and labor intensity for experiments, which decreases the number of monitored water quality parameters, providing further insights into the driving factors of water quality deterioration. They ultimately help devise proactive strategies for sustainable water management.

Effect of smartphone-based stress management programs on depression and anxiety of hospital nurses in Vietnam: a three-arm randomized controlled trial.

There are growing concerns on stress among nurses in low- and middle-income countries (LMICs) in South-East Asia. It is important to improve mental health among nurses in these countries. The objective of this study was to examine the efficacy of two types of newly developed smartphone-based stress management programs in improving depressive and anxiety symptoms among hospital nurses in Vietnam. This study was a three-arm (including two intervention groups and one control group) randomized trial. Participants were recruited from nurses in a large general hospital in Hanoi, Vietnam. Two types (free-choice and fixed sequential order) of smartphone-based stress management programs were developed. Participants were randomly allocated to Program A (a free-choice, multimodule stress management), Program B (a fixed-order, internet cognitive behavioral therapy, iCBT), or a control group (treatment as usual). The depressive and anxiety symptoms were measured by using the Depression Anxiety and Stress Scales at baseline, 3-, and 7-month follow-up surveys. 951 participants were randomly allocated to each of the three groups. Program B showed a statistically significant effect on improving depressive symptoms at 3-month (p = 0.048), but not at 7-month (p = 0.92); Cohen's d was - 0.18 (95% CI - 0.34 to - 0.02) and 0.03 (95% CI - 1.00 to 1.05), respectively. Program A failed to show a significant intervention effect on any of the outcomes at 3- or 7-month follow-up (p > 0.05). Despite the small effect size, the present fixed-order iCBT program seems effective in improving depression of hospital nurses in Vietnam. A public health impact of the intervention can be scalable, when considering its accessibility and minimal cost.Trial registration number: The study protocol is registered at the UMIN Clinical Trials Registry (UMINCTR; ID = UMIN000033139). Registered date of the protocol is 1st Jul. 2018. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037796.

Intersecting Stigmas among HIV-Positive People Who Inject Drugs in Vietnam.

HIV-related stigma remains a barrier to ART adherence among people living with HIV (PLWH) globally. People who inject drugs (PWID) may face additional stigma related to their behavior or identity; yet, there is little understanding of how these stigmas may co-exist and interact among these key populations. This study aims to explore the existence of multiple dimensions of HIV-related stigma, and how they may intersect with stigma related to drug injection. The study took place in Vietnam, where the HIV epidemic is concentrated among 3 key population groups; of those, PWID account for 41% of PLWH. The vast majority (95%) of PWID in Vietnam are male. Data came from in-depth interviews with 30 male PWID recruited from outpatient clinics, where they had been receiving ART medications. Deductive, thematic analysis was employed to organize stigma around the 3 dimensions: enacted, anticipated, and internalized stigma. Findings showed that HIV- and drug use-related stigma remained high among participants. All 3 stigma dimensions were prevalent and perceived to come from different sources: family, community, and health workers. Stigmas related to HIV and drug injection intersected among these individuals, and such intersection varied widely across types of stigma. The study revealed nuanced perceptions of stigma among this marginalized population. It is important for future studies to further investigate the influence of each dimension of stigma, and their interactive effects on HIV and behavioral outcomes among PWID.

Peanut sprout rich in p-coumaric acid ameliorates obesity and lipopolysaccharide-induced inflammation and the inhibition of browning in adipocytes via mitochondrial activation.

Obesity is accompanied by adipose tissue inflammation that subsequently reduces thermogenic potential in brown and beige (brown-like) adipocytes. We previously reported that peanut sprout (PS) inhibited triglyceride accumulation via fatty acid oxidation in adipocytes. However, it is unknown whether PS reverses diet-induced obesity/inflammation and protects against the inflammation-induced inhibition of browning. To investigate this, C57BL/6 male mice, as an in vivo model, were randomly assigned to three different diets and fed for 8 weeks: (i) low-fat diet (LF, 11% kcal from fat), (ii) high-fat diet (HF, 61% kcal from fat), or (iii) HF diet with PS (4% PS in diet, HF + PS). As an in vitro model, lipopolysaccharides (LPS)-induced macrophages and 3T3-L1 adipocytes in the absence (white adipocytes) or presence of dibutyryl-cAMP (Bt-cAMP, beige adipocytes) were used. The supplementation of PS improved HF-diet-mediated body weight gain, dyslipidemia, and hyperglycemia as compared to the HF group. Although there was a marginal impact on visceral hypertrophy, PS reversed the adipocyte inflammation. In parallel, LPS-mediated induction of inflammation was impeded by PS extract (PSE) in macrophages and adipocytes. PSE also protected against LPS-induced suppression of adipocyte browning in Bt-cAMP-treated adipocytes with mitochondrial activation. The phenolic acid analysis showed that among the constituent of PSE, p-coumaric acid (PCA) was identified as a polyphenol that showed a similar effect to PSE. PCA treatment was also able to maintain a higher temperature than the control group upon cold exposure. Taken together, PCA-enriched PS attenuated HF-diet-induced obesity and protected against LPS-induced inflammation and the inhibition of browning via mitochondrial activation.

Patient insights on features of an effective pharmacogenomics patient portal.

OBJECTIVES: We built a novel mock pharmacogenomics web portal to deliver pharmacogenomic information and results to patients. Utilizing a patient focus group, we then sought to understand patient insights on desired features of an effective pharmacogenomics patient portal. METHODS: The mock YourPGx Portal delivered four sample pharmacogenomic results (omeprazole, simvastatin, clopidogrel, and codeine). Patients from our existing institutional, prospective pharmacogenomics implementation study were recruited to pilot the mock portal and then asked to participate in a focus group discussion led by two facilitators. All patients had been previously genotyped, but none had been directly provided access to their own genotyping results and none had previously used the YourPGx portal. The focus group discussion explored nine domains: (1) factors influencing drug response, (2) concerns about drug effects, (3) understanding of genomics and pharmacogenomics, (4) reasons to undergo pharmacogenomic testing, (5) sources of pharmacogenomic information for patient education, (6) attributes of pharmacogenomic sources of information, (7) considerations about privacy and personal pharmacogenomic information, (8) sharing of pharmacogenomic information, and (9) features of an effective patient portal. RESULTS: The median age of patients (n = 10) was 65.5 years old (range 38-72), 70% female, 50% Caucasian/30% Black, and 60% held a bachelor/advanced degree. When asked about resources for seeking pharmacogenomic information, patients preferred consulting their providers first, followed by self-education, then using information provided by university research organizations. A theme emerged regarding attributes of these sources, namely a desire for understandability and trust. Patients said that the effectiveness of a pharmacogenomics patient portal is improved with use of symbolisms/graphics and clear and concise content. Effective use of colors, quantifying information, consistency, and use of layperson's language were additional important facets. Patients communicated the appeal of secured phone/app-enabled access and said that they would desire linking to their electronic medical records to allow sharing of information with different members of their healthcare team. CONCLUSIONS: Patients named providers as their primary source of pharmacogenomic information, but a pharmacogenomics patient portal that is carefully constructed to incorporate desired features may be a favorable tool to effectively deliver pharmacogenomic information and results to patients.

Reliability and validity of the Vietnamese version of the 9-item Utrecht Work Engagement Scale.

OBJECTIVES: The present study investigated the reliability and validity of a newly developed Vietnamese version of the 9-item Utrecht Work Engagement Scale (UWES-9-V) in a sample of hospital nurses in Hanoi, Vietnam. METHODS: The UWES-9 was translated into Vietnamese following a standard procedure. A survey was conducted of 949 registered nurses in a large tertiary general hospital in Hanoi, Vietnam, in 2018, using a self-administered questionnaire including the Vietnamese UWES-9, other scales measuring health status, work performance, job demand, job control, and workplace social support, and questions pertaining to demographic variables. Cronbach's alpha and interclass correlation coefficients (ICC) were calculated to assess reliability. Explanatory and confirmatory factor analyses were conducted to assess factorial validity. Convergent validity was tested based on associations between the UWES-9-V and subscales and other scales. RESULTS: The Cronbach's alpha coefficients of the UWES-9-V and the Vigor, Absorption, and Dedication subscales were 0.93, 0.86, 0.77, and 0.90, respectively. ICC of the UWES-9-V in a subsample after 3 months was 0.48. Confirmatory factor analyses indicated an acceptable fit of both one-factor and three-factor structures, with the three-factor model having the better fit. The UWES-9-V and its subscales correlated with depression, anxiety and stress, health-related quality of life and health condition, job performance, and psychosocial work environment. CONCLUSIONS: The study findings suggest that the UWES-9-V is a reliable and valid instrument to measure work engagement among hospital nurses in Vietnam, a low- and middle-income country. Future studies should confirm the validity and reliability of the UWES-9-V among various occupations.