RCPA: An Open-Source R Package for Data Processing, Differential Analysis, Consensus Pathway Analysis, and Visualization.

Identifying impacted pathways is important because it provides insights into the biology underlying conditions beyond the detection of differentially expressed genes. Because of the importance of such analysis, more than 100 pathway analysis methods have been developed thus far. Despite the availability of many methods, it is challenging for biomedical researchers to learn and properly perform pathway analysis. First, the sheer number of methods makes it challenging to learn and choose the correct method for a given experiment. Second, computational methods require users to be savvy with coding syntax, and comfortable with command-line environments, areas that are unfamiliar to most life scientists. Third, as learning tools and computational methods are typically implemented only for a few species (i.e., human and some model organisms), it is difficult to perform pathway analysis on other species that are not included in many of the current pathway analysis tools. Finally, existing pathway tools do not allow researchers to combine, compare, and contrast the results of different methods and experiments for both hypothesis testing and analysis purposes. To address these challenges, we developed an open-source R package for Consensus Pathway Analysis (RCPA) that allows researchers to conveniently: (1) download and process data from NCBI GEO; (2) perform differential analysis using established techniques developed for both microarray and sequencing data; (3) perform both gene set enrichment, as well as topology-based pathway analysis using different methods that seek to answer different research hypotheses; (4) combine methods and datasets to find consensus results; and (5) visualize analysis results and explore significantly impacted pathways across multiple analyses. This protocol provides many example code snippets with detailed explanations and supports the analysis of more than 1000 species, two pathway databases, three differential analysis techniques, eight pathway analysis tools, six meta-analysis methods, and two consensus analysis techniques. The package is freely available on the CRAN repository. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Processing Affymetrix microarrays Basic Protocol 2: Processing Agilent microarrays Support Protocol: Processing RNA sequencing (RNA-Seq) data Basic Protocol 3: Differential analysis of microarray data (Affymetrix and Agilent) Basic Protocol 4: Differential analysis of RNA-Seq data Basic Protocol 5: Gene set enrichment analysis Basic Protocol 6: Topology-based (TB) pathway analysis Basic Protocol 7: Data integration and visualization.

Estimating eGFR using serum creatinine or cystatin C in healthy Vietnamese population.

Very few studies worldwide have assessed the estimated glomerular filtration rate (eGFR) using serum cystatin C (ScysC) in comparison to the gold standard measured glomerular filtration rate (mGFR) with a gamma camera technique using 99m-Technetium-Diethylene Triaminepentoacetic Acid (99mTc-DTPA). To determine the eGFR formula with the most accurate estimate of glomerular filtration rate when compared with mGFR in a healthy population in Vietnam. We conducted a cross-sectional descriptive study of more than 100 adults without hypertension. The study subjects were examined for general characteristics and blood biochemistry tests to assess eGFR, and the glomerular filtration rate was measured using 99mTc-DTPA with the Gates technique to record mGFR. The estimated values of the eGFR formula were evaluated and compared with the actual mGFR using 99mTechnetium-DTPA. Serum creatinine (Scr) concentration showed a significant difference between males and females: 0.9 ±â€…0.1 versus 0.8 ±â€…0.1 (P < .001), while ScysC concentration did not show this difference. The mGFR in the age groups < 40, 40 to 59, and ≥ 60: 105.0 ±â€…9.9, 94.8 ±â€…8.6, and 93.4 ±â€…10.6, respectively (P < .001). The eGFR-CKD-EPI-cystatin C 2012 formula showed the highest positive correlation with mGFR (ΔGFR = -1.6, R = 0.68, P < .001). eGFR calculated using cystatin C does not require sex adjustment, whereas, for creatinine, sex adjustment is necessary. The eGFR-CKD-Epi-CysC formula showed the lowest difference and a strong correlation with mGFR.

Reporting on patient's body mass index (BMI) in recent clinical trials for patients with breast cancer: a systematic review.

BACKGROUND: The proportion of patients with breast cancer and obesity is increasing. While the therapeutic landscape of breast cancer has been expanding, we lack knowledge about the potential differential efficacy of most drugs according to the body mass index (BMI). Here, we conducted a systematic review on recent clinical drug trials to document the dosing regimen of recent drugs, the reporting of BMI and the possible exclusion of patients according to BMI, other adiposity measurements and/or diabetes (leading comorbidity of obesity). We further explored whether treatment efficacy was evaluated according to BMI. METHODS: A search of Pubmed and ClinicalTrials.gov was performed to identify phase I-IV trials investigating novel systemic breast cancer treatments. Dosing regimens and exclusion based on BMI, adiposity measurements or diabetes, documentation of BMI and subgroup analyses according to BMI were assessed. RESULTS: 495 trials evaluating 26 different drugs were included. Most of the drugs (21/26, 81%) were given in a fixed dose independent of patient weight. BMI was an exclusion criterion in 3 out of 495 trials. Patients with diabetes, the leading comorbidity of obesity, were excluded in 67/495 trials (13.5%). Distribution of patients according to BMI was mentioned in 8% of the manuscripts, subgroup analysis was performed in 2 trials. No other measures of adiposity/body composition were mentioned in any of the trials. Retrospective analyses on the impact of BMI were performed in 6 trials. CONCLUSIONS: Patient adiposity is hardly considered as most novel drug treatments are given in a fixed dose. BMI is generally not reported in recent trials and few secondary analyses are performed. Given the prevalence of patients with obesity and the impact obesity can have on pharmacokinetics and cancer biology, more attention should be given by investigators and study sponsors to reporting patient's BMI and evaluating its impact on treatment efficacy and toxicity.

Antibacterial efficacy of copper-based metal-organic frameworks against Escherichia coli and Lactobacillus.

The widespread and excessive use of antimicrobial drugs has resulted in a concerning rise in bacterial resistance, leading to a risk of untreatable infections. The aim of this study was to formulate a robust and efficient antibacterial treatment to address this challenge. Previous work focused on the effectiveness of the Cu-BTC metal-organic framework (MOF; BTC stands for 1,3,5-benzenetricarboxylate) in combatting various bacterial strains. Herein, we compare the antibacterial properties of Cu-BTC with our newly designed Cu-GA MOF, consisting of copper ions bridged by deprotonated gallate ligands (H2gal2-), against Escherichia coli (E. coli) and Lactobacillus bacteria. Cu-GA was synthesized hydrothermally from copper salt and naturally derived gallic acid (H4gal) and characterized for antibacterial evaluation. The gradual breakdown of Cu(H2gal) resulted in a significant antibacterial effect that is due to the release of copper ions and gallate ligands from the framework. Both copper MOFs were nontoxic to bacteria at low concentrations and growth was completely inhibited at high concentrations when treated with Cu-BTC (1500 µg for E. coli and 1700 µg for Lactobacillus) and Cu-GA (2000 µg for both bacterial strains). Furthermore, our agarose gel electrophoresis results indicate that both MOFs could disrupt bacterial cell membranes, hindering the synthesis of DNA. These findings confirm the antibacterial properties of Cu-BTC and the successful internalization of Cu2+ ions and gallic acid by bacteria from the Cu-GA MOF framework, suggesting the potential for a sustained and effective therapeutic approach against pathogenic microorganisms.

Clinical Epidemiological Characteristics and Risk Factors for Severity of SARS-CoV-2 Pneumonia in Pediatric Patients: A Hospital-Based Study in Vietnam.

Introduction Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which can cause organ failure in several organs, cardiac problems, or acute respiratory distress syndrome (ARDS). Identifying clinical epidemiological characteristics and risk factors for complications of COVID-19 allows clinicians to diagnose and treat promptly. Objectives This study aims to describe the clinical epidemiological characteristics of COVID-19 and assess risk factors for the severity of SARS-CoV-2 pneumonia in children treated at Haiphong Children's Hospital. Methods A descriptive cross-sectional study was conducted in Haiphong Children's Hospital, Haiphong, Vietnam, for one year, from January 1, 2022, to December 31, 2022. Results In our study, 540 children were evaluated; the male-to-female ratio was 1.48/1; the median age was 23 months (IQR=6-74); Children aged under one year accounted for the highest proportion (n=202; 37.4%); 40 (7.4%) children had underlying illnesses. The number of admitted patients diagnosed with COVID-19 peaked in February 2022. Regarding severity, 380 (70.4%) cases were mild, 136 (25.2%) were moderate, only 24 (4.4%) cases were severe, and no children died. Common symptoms were fever in 483 (89.4%), coughing in 399 (73.9%), and tachypnea in 163 (30.2%) children. Laboratory features: white blood cell count, platelet count, serum CRP, and coagulation test showed little change. Around 116 (21.5%) had lymphopenia and 148 (27.4%) had pneumonia. Patients under one year were approximately 1.64 times more likely to experience pneumonia complications from COVID-19 than those without such a history (OR=1.64, 95%CI = 1.12 - 2.41, p=0.0112). Patients with underlying conditions were approximately 2.08 times more likely to experience pneumonia complications from COVID-19 compared to those without such conditions (OR=2.08, 95%CI =1.08 - 4.02, p=0.0289). Conclusion In COVID-19 pediatric patients, the severity of the disease was mild to moderate without any mortality. Children aged under one year accounted for the highest proportion of all COVID-19 patients. This study found that age under one year and underlying illnesses are related to pneumonia in COVID-19 pediatric patients.

Medication errors in emergency departments: a systematic review and meta-analysis of prevalence and severity.

BACKGROUND: Medication errors significantly compromise patient safety in emergency departments. Although previous studies have investigated the prevalence of these errors in this setting, results have varied widely. AIM: The aim was to report pooled data on the prevalence and severity of medication errors in emergency departments, as well as the proportion of patients affected by these errors. METHOD: Systematic searches were conducted in Embase, PubMed, and the Cochrane Library from database inception until June 2023. Studies provided numerical data on medication errors within emergency departments were eligible for inclusion. Random-effects meta-analysis was employed to pool the prevalence of medication errors, the proportion of patients experiencing these errors, and the error severity levels. Heterogeneity among studies was assessed using the I2 statistic and Cochran's Q test. RESULTS: Twenty-four studies met the inclusion criteria. The meta-analysis gave a pooled prevalence of medication errors in emergency departments of 22.6% (95% Confidence Interval [CI] 19.2-25.9%, I2 = 99.9%, p < 0.001). The estimated proportion of patients experiencing medication errors was 36.3% (95% CI 28.3-44.3%, I2 = 99.8%, p < 0.001). Of these errors, 42.6% (95% CI 5.0-80.1%) were potentially harmful but not life-threatening, while no-harm errors accounted for 57.3% (95% CI 14.1-100.0%). CONCLUSION: The prevalence of medication errors, particularly those potentially harmful, underscores potential safety issues in emergency departments. It is imperative to develop and implement effective interventions aimed at reducing medication errors and enhancing patient safety in this setting.

The heavy atom structure, "cis effect" on methyl internal rotation, and 14N nuclear quadrupole coupling of 1-cyanopropene from quantum chemical and microwave spectroscopic analysis.

The microwave spectrum of 1-cyanopropene (crotonitrile) was remeasured using two pulsed molecular jet Fourier transform microwave spectrometers operating from 2.0 to 40.0 GHz. The molecule exists in two isomer forms, E and Z, with respect to the orientation between the methyl and the cyano groups. The spectrum of the Z isomer is more intense. Due to internal rotation of the methyl group, doublets containing A and E torsional species were found for all rotational transitions. Hyperfine splittings arising from the 14N nuclear quadrupole coupling were resolved. The heavy atom structure of the Z isomer was determined by observation of 13C and 15N isotopologue spectra in natural abundances. The experimental results were supported by quantum chemistry. The complex spectral patterns were analyzed and fitted globally, and the barriers to methyl internal rotation are determined to be 478.325(28) cm-1 and 674.632(76) cm-1 for the Z and E isomers, respectively. The non-bonded intramolecular electrostatic attraction between the methyl group and the 1-cyano substituent overcomes steric hindrance, leading to higher stability of the Z isomer. The consequence is a slight opening of 3.2° of the C(1)-C(2)-C(3) angle and a radical decrease of the methyl torsional barrier in the Z isomer due to steric repulsion.

Worldwide study of the taste of bitter medicines and their modifiers.

The bitter taste of medicines hinders patient compliance, but not everyone experiences these difficulties because people worldwide differ in their bitterness perception. To better understand how people from diverse ancestries perceive medicines and taste modifiers, 338 adults, European and recent US and Canada immigrants from Asia, South Asia, and Africa, rated the bitterness intensity of taste solutions on a 100-point generalized visual analog scale and provided a saliva sample for genotyping. The taste solutions were five medicines, tenofovir alafenamide (TAF), moxifloxacin, praziquantel, amodiaquine, and propylthiouracil (PROP), and four other solutions, TAF mixed with sucralose (sweet, reduces bitterness) or 6-methylflavone (tasteless, reduces bitterness), sucralose alone, and sodium chloride alone. Bitterness ratings differed by ancestry for two of the five drugs (amodiaquine and PROP) and for TAF mixed with sucralose. Genetic analysis showed that people with variants in one bitter receptor variant gene (TAS2R38) reported PROP was more bitter than did those with a different variant (p= 7.6e-19) and that people with either an RIMS2 or a THSD4 genotype found sucralose more bitter than did others (p=2.6e-8, p=7.9e-11, resp.). Our findings may help guide the formulation of bad-tasting medicines to meet the needs of those most sensitive to them.

Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa.

The oral mucosa functions as a physico-chemical and immune barrier to external stimuli, and an adequate width of the keratinized mucosa around the teeth or implants is crucial to maintaining them in a healthy and stable condition. In this study, for the first time, bulk RNA-seq analysis was performed to explore the gene expression of laser microdissected epithelium and lamina propria from mice, aiming to investigate the differences between keratinized and non-keratinized oral mucosa. Based on the differentially expressed genes (DEGs) and Gene Ontology (GO) Enrichment Analysis, bone morphogenetic protein 2 (BMP-2) was identified to be a potential regulator of oral mucosal keratinization. Monoculture and epithelial-mesenchymal cell co-culture models in the air-liquid interface (ALI) indicated that BMP-2 has direct and positive effects on epithelial keratinization and proliferation. We further performed bulk RNA-seq of the ALI monoculture stimulated with BMP-2 in an attempt to identify the downstream factors promoting epithelial keratinization and proliferation. Analysis of the DEGs identified, among others, IGF2, ID1, LTBP1, LOX, SERPINE1, IL24, and MMP1 as key factors. In summary, these results revealed the involvement of a well-known growth factor responsible for bone development, BMP-2, in the mechanism of oral mucosal keratinization and proliferation, and pointed out the possible downstream genes involved in this mechanism.

Metastases of primary mixed no-special type and lobular breast cancer display an exclusive lobular histology.

Primary tumors with a mixed invasive breast carcinoma of no-special type (IBC-NST) and invasive lobular cancer (ILC) histology are present in approximately five percent of all patients with breast cancer and are understudied at the metastatic level. Here, we characterized the histology of metastases from two patients with primary mixed IBC-NST/ILC from the postmortem tissue donation program UPTIDER (NCT04531696). The 14 and 43 metastatic lesions collected at autopsy had morphological features and E-cadherin staining patterns consistent with pure ILC. While our findings still require further validation, they may challenge current clinical practice and imaging modalities used in these patients.

Effects of Maturation on Antibacterial Properties of Vietnamese Mango (Mangifera indica) Leaves.

This study, for the first time, has investigated the relationships between alterations of mangiferin contents in mango leaves at different maturity stages and their antibacterial properties. Leaves were classified into six different maturity stages based on their color: (1) young dark reddish brown, (2) young yellow, (3) young light green, (4) mature green, (5) old dark green, and (6) old yellow leaves. Ethanol extracts were then examined against Gram-positive and Gram-negative bacteria, applying broth dilution and agar well diffusion methods. In addition, we also measured the mangiferin contents in leaves at different stages for the purpose of evaluating how the changes in this phytochemistry value affects their activities against bacteria. The results showed that extracts from leaves at young ages had better antibacterial properties than those from old leaves, as evidenced by the lower minimum inhibitory concentrations and larger inhibitory zones. In addition, we also found that the contents of mangiferin were significantly decreased followed the maturation process. These results suggest that mango leaves at young stages, especially dark reddish brown and young yellow leaves, are preferable for application in bacterial infections and other therapies related to mangiferin's constituents.

Development and validation of a 6-plex Luminex-based assay for measuring human serum antibodies to group B streptococcus capsular polysaccharides.

Six serotypes (Ia, Ib, II, III, IV, and V) cause nearly all group B streptococcal (GBS) disease globally. Capsular polysaccharide (CPS) conjugate vaccines aim to prevent GBS disease, however, licensure of a vaccine would depend on a standardized serological assay for measuring anti-CPS IgG responses. A multiplex direct Luminex-based immunoassay (dLIA) has been developed to simultaneously measure the concentration of serum IgG specific for the six prevalent GBS CPS serotypes. Assay validation was performed using serum samples obtained from human subjects vaccinated with an investigational 6-valent GBS CPS conjugate vaccine. Results for the assay are expressed as IgG concentrations (µg/mL) using a human serum reference standard composed of pooled sera from vaccinated subjects. The lower limits of quantitation (LLOQ) for all serotypes covered in the 6-plex GBS IgG dLIA fell within the range of 0.002-0.022 µg/mL IgG. Taken together, the 6-plex GBS IgG dLIA platform is specific for the six GBS serotypes included in Pfizer's investigational vaccine, has a wide dilution adjusted assay range, and is precise (<18.5% relative standard deviation) for all serotypes, and, therefore, is suitable for quantitatively measuring vaccine-induced or naturally acquired serotype-specific anti-CPS IgG responses against GBS.

Antibiotic prescribing practices of medical doctors in a resource-limited setting and the influence of individual perceptions and stewardship support: a survey in three tertiary hospitals in Vietnam.

Objectives: To understand antibiotic prescribing and influencing factors to inform antimicrobial stewardship (AMS) interventions to reduce unwanted consequences of antibiotic use in hospitals in Vietnam, a lower-middle-income country in Asia. Methods: We conducted a cross-sectional study of doctors at three tertiary hospitals using non-probability convenience sampling, through a paper-based (Hospitals 1 and 2) or electronic (Hospital 3) survey. Questions included items on perceptions regarding antibiotic resistance and AMS, prescribing practices, knowledge, demographics and training. We used principal components analysis and mixed-effects models to examine practices and identify influencing factors. Results: Among 314 surveyed participants, 61%, 57% and 59% in Hospitals 1, 2 and 3, respectively, felt certain about the appropriateness of their antibiotic prescriptions. In total, 9% reported sometimes prescribing antibiotics when not needed to meet patients' expectations, and 13% reported doing so to avoid perceived complications. Higher prescribing confidence was found among those with positive perceptions about AMS (P < 0.0001), whereas negative perceptions about colleagues' practices reduced this confidence (P < 0.0001). Individual preference for branded antibiotics was associated with more unnecessary prescribing whereas having higher prescribing confidence decreased the habits of prescribing when not needed. Conclusions: This study provides important implications for design of hospital interventions to address influencing factors on antibiotic prescribing in Vietnam and similar resource-limited settings. Specific interventions should target improving knowledge through education and training for doctors, enhancing the support from the AMS team, and promoting guidelines and policies for appropriate antibiotic use in hospital.

Association of the neutrophil-to-lymphocyte ratio with the occurrence of venous thromboembolism and arterial thrombosis.

OBJECTIVE: This study aimed to assess the association of the neutrophil-to-lymphocyte ratio (NLR) with the occurrence of venous thromboembolism (VTE) and arterial thrombosis (AT). METHODS: This was a retrospective cross-sectional study including 585 medical records obtained from all consecutive patients who were suspected of having thrombosis. RESULTS: The AT group had a higher neutrophil count and NLR and a lower lymphocyte count than the non-thrombosis group. Receiver operating characteristic curve analysis showed the ability of the NLR to predict the presence of AT. The cut-off value for the NLR was 4.44. No distinction was found in the NLR between the VTE and non-thrombosis groups. Regression analysis showed that a high NLR was an independent factor related to the presence of AT. Patients with an NLR ≥ 4.44 had a higher risk of AT than those with an NLR < 4.44 (odds ratio = 2.015, 95% confidence interval: 1.180-3.443). CONCLUSION: A high NLR may be considered a predictive factor for the occurrence of AT, but an association with the presence of VTE was not found.

Rapid autopsies to enhance metastatic research: the UPTIDER post-mortem tissue donation program.

Research on metastatic cancer has been hampered by limited sample availability. Here we present the breast cancer post-mortem tissue donation program UPTIDER and show how it enabled sampling of a median of 31 (range: 5-90) metastases and 5-8 liquids per patient from its first 20 patients. In a dedicated experiment, we show the mild impact of increasing time after death on RNA quality, transcriptional profiles and immunohistochemical staining in tumor tissue samples. We show that this impact can be counteracted by organ cooling. We successfully generated ex vivo models from tissue and liquid biopsies from distinct histological subtypes of breast cancer. We anticipate these and future findings of UPTIDER to elucidate mechanisms of disease progression and treatment resistance and to provide tools for the exploration of precision medicine strategies in the metastatic setting.

Fourteen years of cellular deconvolution: methodology, applications, technical evaluation and outstanding challenges.

Single-cell RNA sequencing (scRNA-Seq) is a recent technology that allows for the measurement of the expression of all genes in each individual cell contained in a sample. Information at the single-cell level has been shown to be extremely useful in many areas. However, performing single-cell experiments is expensive. Although cellular deconvolution cannot provide the same comprehensive information as single-cell experiments, it can extract cell-type information from bulk RNA data, and therefore it allows researchers to conduct studies at cell-type resolution from existing bulk datasets. For these reasons, a great effort has been made to develop such methods for cellular deconvolution. The large number of methods available, the requirement of coding skills, inadequate documentation, and lack of performance assessment all make it extremely difficult for life scientists to choose a suitable method for their experiment. This paper aims to fill this gap by providing a comprehensive review of 53 deconvolution methods regarding their methodology, applications, performance, and outstanding challenges. More importantly, the article presents a benchmarking of all these 53 methods using 283 cell types from 30 tissues of 63 individuals. We also provide an R package named DeconBenchmark that allows readers to execute and benchmark the reviewed methods (https://github.com/tinnlab/DeconBenchmark).

Transcriptomic characterization of the histopathological growth patterns in breast cancer liver metastases.

Metastatic breast cancer (mBC) remains incurable and liver metastases (LM) are observed in approximately 50% of all patients with mBC. In some cases, surgical resection of breast cancer liver metastases (BCLM) is associated with prolonged survival. However, there are currently no validated marker to identify these patients. The interactions between the metastatic cancer cells and the liver microenvironment result in two main histopathological growth patterns (HGP): replacement (r-HGP), characterized by a direct contact between the cancer cells and the hepatocytes, and desmoplastic (d-HGP), in which a fibrous rim surrounds the tumor cells. In patients who underwent resection of BCLM, the r-HGP is associated with a worse postoperative prognosis than the d-HGP. Here, we aim at unraveling the biological differences between these HGP within ten patients presenting both HGP within the same metastasis. The transcriptomic analyses reveal overexpression of genes involved in cell cycle, DNA repair, vessel co-option and cell motility in r-HGP while angiogenesis, wound healing, and several immune processes were found overexpressed in d-HGP LM. Understanding the biology of the LM could open avenues to refine treatment of BC patients with LM.

Low barriers to internal rotation in the microwave spectrum of 2,5-dimethylfluorobenzene.

We investigated the rotational spectrum of 2,5-dimethylfluorobenzene containing coupled large amplitude motions of two methyl groups in the frequency range from 2 to 26.5 GHz using a pulsed molecular jet Fourier transform microwave spectrometer. The internal rotation of two inequivalent methyl groups with low torsional barriers (around 16 and 226 cm-1) causes splittings of all rotational transitions into quintets with separations of up to hundreds of MHz between the torsional components. Spectral analysis and modeling of the observed splittings were performed using the programs XIAM and BELGI-Cs-2Tops, whereby the latter achieved measurement accuracy. The methyl internal rotation can be used to examine the electronic and steric environments around the methyl group because they affect the methyl torsional barrier. Electronic properties play a particularly important role in aromatic molecules in the presence of a π-conjugated double bond system. The experimental results were compared with those of quantum chemistry. Benchmark calculations resulted in the conclusion that the B3LYP-D3BJ/6-311++G(d,p) level of theory can be recommended for predicting rotational constants to guide the microwave spectral assignment of dimethylfluorobenzenes in particular and toluene derivatives in general.

Thiazolidinediones are Partially Effective Bitter Blockers.

PURPOSE: The bad bitter taste of some medicines is a barrier to overcoming noncompliance with medication use, especially life-saving drugs given to children and the elderly. Here, we evaluated a new class of bitter blockers (thiazolidinediones, TZDs). METHODS: In this study, 2 TZDs were tested, rosiglitazone (ROSI) and a simpler form of TZD, using a high-potency sweetener as a positive control (neohesperidin dihydrochalcone, NHDC). We tested bitter-blocking effects using the bitter drugs tenofovir alafenamide fumarate (TAF), a treatment for HIV and hepatitis B infection, and praziquantel (PRAZ), a treatment for schistosomiasis, by conducting taste testing with 2 separate taste panels: a general panel (N = 97, 20-23 years, 82.5% female, all Eastern European) and a genetically informative panel (N = 158, including 68 twin pairs, 18-82 years, 76% female, 87% European ancestry). Participants rated the bitterness intensity of the solutions on a 100-point generalized visual analog scale. FINDINGS: Person-to-person differences in drug bitterness were striking; TAF and PRAZ were weakly or not bitter for some people but moderately to highly bitter for others. Participants in both taste panels rated the bitter drugs TAF and PRAZ as less bitter on average when mixed with NHDC than when sampled alone. ROSI partially suppressed the bitterness of TAF and PRAZ, but effectiveness differed between the 2 panels: bitterness was significantly reduced for PRAZ but not TAF in the general panel and for TAF but not PRAZ in the genetically informative panel. ROSI was a more effective blocker than the other TZD. IMPLICATIONS: These results suggest that TZDs are partially effective bitter blockers and the suppression efficacy differs from drug to drug, from person to person, and from panel to panel, suggesting other TZDs should be designed and tested with more drugs and on diverse populations to define which ones work best with which drugs and for whom. The discovery of bitter receptor blockers can improve compliance with medication use.

Surface ligand modified silver nanoparticles-based SERS sensing platform for ultrasensitive detection of the pesticide thiram in green tea leaves: roles of coating agents in sensing performance.

Silver nanoparticles (AgNPs) have been regarded as a highly promising substrate for surface-enhanced Raman scattering (SERS) sensors. In this study, we focused on the electrochemical synthesis method by developing three kinds of AgNPs using three different electrolytes: citrate (e-Ag-C), oleic acid (e-Ag-O) and fish mint (Houttuynia cordata Thunb.) extract (e-Ag-bio). The as-prepared AgNPs were characterized and then employed as SERS substrates to detect the pesticide thiram. The obtained results show that e-Ag-O exhibits the best SERS performance. The effect of the coating agent was explained by chemical and electromagnetic enhancements (CM and EM). Although thiram could absorb onto e-Ag-C at the highest level, allowing its Raman signal to be best enhanced via the CM, the smallest interparticle distance of e-Ag-O could have resulted in the largest improvement in the EM. Using e-Ag-O to develop SERS-based sensors for thiram, we obtain the impressive detection limit of 1.04 × 10-10 M in standard samples and 10-9 M in tea leaves. The linear ranges are from 10-4 M to 10-7 M and from 10-7 M to 10-9 M, covering the maximum residue levels for plant commodities established by the United States Environment Protection Agency and European Food Safety Authority (2-13 ppm ∼7.7 × 10-6 M to 5 × 10-5 M).