Cu2MoS4 Nanocatalyst-Based Electrochemical Sensor for Ofloxacin Electro-Oxidation: Delineating the Combined Roles of Crystallinity and Morphology on the Analytical Performance.

In this study, we demonstrate the influence of crystallinity and morphology on the analytical performance of various Cu2MoS4 (CMS) nanocatalysts-based electrochemical sensors for the high-efficiency detection of Ofloxacin (OFX) antibiotic. The electrochemical kinetics parameters including peak current response (ΔIp), peak-to-peak separation (ΔEp), electrochemically active surface area (ECSA), electron-transfer resistance (Rct), were obtained through the electrochemical analyses, which indicate the single-crystalline nature of CMS nanomaterials (NMs) is beneficial for enhanced electron-transfer kinetics. The morphological features and the electrochemical results for OFX detection substantiate that by tuning the tube-like to plate-like structures of the CMS NMs, it might noticeably enhance multiple adsorption sites and more intrinsic active catalytic sites due to the diffusion of analytes into the interstitial spaces between CMS nanoplates. As results, highly single-crystalline and plate-shaped morphology structures of CMS NMs would significantly enhance the electrocatalytic OFX oxidation in terms of onset potential (Eonset), Tafel slope, catalytic rate constant (kcat), and adsorption capacity (Γ). The CMS NMs-based electrochemical sensing platform showed excellent analytical performance toward the OFX detection with two ultra-wide linear detection concentration ranges from 0.25-100 and 100-1000 µM, a low detection limit of 0.058 µM, and an excellent electrochemical sensitivity (0.743 µA µM-1 cm-2).

Intussusception and Other Adverse Event Surveillance after Pilot Introduction of Rotavirus Vaccine in Nam Dinh and Thua Thien Hue Provinces-Vietnam, 2017-2021.

Rotavin-M1 (POLYVAC) was licensed in Vietnam in 2012. The association of Rotavin-M1 with intussusception, a rare adverse event associated with rotavirus vaccines, and with adverse events following immunization (AEFI) have not been evaluated and monitored under conditions of routine use. From February 2017 to May 2021, we conducted a pilot introduction of Rotavin-M1 into the routine vaccination program in two provinces. Surveillance for intussusception was conducted at six sentinel hospitals. AEFI reports at 30 min and 7 days after vaccination were recorded. Among 443 children <12 months of age admitted for intussusception, most (92.3%) were children ≥ 6 months. Of the 388 children who were age-eligible to receive Rotavin-M1, 116 (29.9%) had received ≥1 dose. No intussusception cases occurred in the 1-21 days after dose 1 and one case occurred on day 21 after dose 2. Among the 45,367 children who received ≥1 dose of Rotavin-M1, 9.5% of children reported at least one AEFI after dose 1 and 7.3% after dose 2. Significantly higher AEFI rates occurred among children given Rotavin-M1 with pentavalent vaccines (Quinvaxem®, ComBE Five®) compared to Rotavin-M1 without pentavalent vaccines. There was no association between intussusception and Rotavin-M1. The vaccine was generally safe when administered alone and when co-administered with other vaccines.

Genetic diversity of G9, G3, G8 and G1 rotavirus group A strains circulating among children with acute gastroenteritis in Vietnam from 2016 to 2021.

Rotavirus group A (RVA) is the most common cause of severe childhood diarrhea worldwide. The introduction of rotavirus vaccination programs has contributed to a reduction in hospitalizations and mortality caused by RVA. From 2016 to 2021, we conducted surveillance to monitor RVA prevalence and genotype distribution in Nam Dinh and Thua Thien Hue (TT Hue) provinces where a pilot Rotavin-M1 vaccine (Vietnam) implementation took place from 2017 to 2020. Out of 6626 stool samples, RVA was detected in 2164 (32.6%) by ELISA. RT-PCR using type-specific primers were used to determine the G and P genotypes of RVA-positive specimens. Whole genome sequences of a subset of 52 specimens randomly selected from 2016 to 2021 were mapped using next-generation sequencing. From 2016 to 2021, the G9, G3 and G8 strains dominated, with detected frequencies of 39%, 23%, and 19%, respectively; of which, the most common genotypes identified were G9P[8], G3P[8] and G8P[8]. G1 strains re-emerged in Nam Dinh and TT Hue (29.5% and 11.9%, respectively) from 2020 to 2021. G3 prevalence decreased from 74% to 20% in TT Hue and from 21% to 13% in Nam Dinh province between 2017 and 2021. The G3 strains consisted of 52% human typical G3 (hG3) and 47% equine-like G3 (eG3). Full genome analysis showed substantial diversity among the circulating G3 strains with different backgrounds relating to equine and feline viruses. G9 prevalence decreased sharply from 2016 to 2021 in both provinces. G8 strains peaked during 2019-2020 in Nam Dinh and TT Hue provinces (68% and 46%, respectively). Most G8 and G9 strains had no genetic differences over the surveillance period with very high nucleotide similarities of 99.2-99.9% and 99.1-99.7%, respectively. The G1 strains were not derived from the RVA vaccine. Changes in the genotype distribution and substantial diversity among circulating strains were detected throughout the surveillance period and differed between the two provinces. Determining vaccine effectiveness against circulating strains over time will be important to ensure that observed changes are due to natural secular variation and not from vaccine pressure.

N-recognins UBR1 and UBR2 as central ER stress sensors in mammals.

In eukaryotes, a primary protein quality control (PQC) process involves the destruction of conformationally misfolded proteins through the ubiquitin-proteasome system. Because approximately one-third of eukaryotic proteomes fold and assemble within the endoplasmic reticulum (ER) before being sent to their destinations, the ER plays a crucial role in PQC. The specific functions and biochemical roles of several E3 ubiquitin ligases involved in ER-associated degradation in mammals, on the other hand, are mainly unknown. We identified 2 E3 ligases, ubiquitin protein ligase E3 component N-recognin 1 (UBR1) and ubiquitin protein ligase E3 component N-recognin 2 (UBR2), which are the key N-recognins in the N-degron pathway and participate in the ER stress response in mammalian cells by modulating their stability. Cells lacking UBR1 and UBR2 are hypersensitive to ER stress-induced apoptosis. Under normal circumstances, these proteins are polyubiquitinated through Lys48-specific linkages and are then degraded by the 26S proteasome. In contrast, when cells are subjected to ER stress, UBR1 and UBR2 exhibit greater stability, potentially as a cellular adaptive response to stressful conditions. Although the precise mechanisms underlying these findings require further investigation, our findings show that cytoplasmic UBR1 and UBR2 have anti-ER stress activities and contribute to global PQC in mammals. These data also reveal an additional level of complexity within the mammalian ER-associated degradation system, implicating potential involvement of the N-degron pathway.

A novel method for preparing BiOI nanoplates and their use as precursors to synthesize porous BiVO4 water oxidation photocatalysts.

In this work, we report an innovative method for synthesizing BiOI nanoplate powder by a slow basification of an aqueous solution constituted of Bi(NO3)3 and KI. The basification was done with NH3 vapor which was naturally generated on top of an NH4OH solution kept in a closed space. The impact of the basification rate on the morphology and crystallinity of the BiOI product was investigated. Herein, we also report on the use of newly produced BiOI nanoplate powder together with the VO(acac)2 precursor for fabricating BiVO4 photoanodes for solar driven water splitting applications. We also discuss how the morphology of BiOI nanoplates and their orientation on a fluorine doped tin oxide substrate will affect the morphology, topology and photocatalytic performance of the electrode. The BiVO4 photoanode showed a photocatalytic current density of 0.55 mA cm-2 at 1.23 V vs. the Reversible Hydrogen Electrode (RHE) when assayed in a pH 7 phosphate buffer electrolyte and under 1 sun illumination.

Determinants of Hypoglycemia in Premature Vietnamese Infants: A Case-Control Study.

Background Premature infants are more likely to experience hypoglycemia. Early recognition and prompt therapy are essential to avoiding neurological sequelae in the future. This study aimed to identify the determinants of hypoglycemia in premature Vietnamese infants. Methodology This was a case-control study conducted at the Neonatal Intensive Care Unit, The Women and Children Hospital of An Giang, Vietnam. Hypoglycemia was defined as a plasma glucose value of less than 2.6 mmol/L (47 mg/dL) after two hours postpartum. Maternal and neonatal information was collected and analyzed. Both bivariate and multiple logistic regression models were used to identify the risk factors of neonatal hypoglycemia (NH) Results A total of 65 cases and 195 controls were included in the study. Gestational diabetes mellitus (GDM) (adjusted odds ratio [AOR] 3.78, 95% confidence interval [CI] 1.69-8.52; P < 0.001) and excessive gestational weight gain (GWG) (AOR 2.80, 95% CI 1.12-6.98; P < 0.026) were associated with NH in the multiple logistic regression model. An observed positive interaction between gestational hypertension and GDM on NH yielded an odds ratio (OR) of 6.29 (95% CI 2.46-16.64). Conclusions GDM, excessive GWG, and the interaction between gestational hypertension and GDM were the determinants of hypoglycemia in premature infants.

The CRL3gigaxonin ubiquitin ligase-USP15 pathway governs the destruction of neurofilament proteins.

Giant axonal neuropathy (GAN) is caused by mutations in the GAN gene encoding for gigaxonin (GIG), which functions as an adaptor of the CUL3-RBX1-GIG (CRL3GIG) E3 ubiquitin ligase complex. The pathological hallmark of GAN is characterized by the accumulation of densely packed neurofilaments (NFs) in the axons. However, there are fundamental knowledge gaps in our understanding of the molecular mechanisms by which the ubiquitin-proteasome system controls the homeostasis of NF proteins. Recently, the deubiquitylating enzyme USP15 was reported to play a crucial role in regulating ubiquitylation and proteasomal degradation of CRL4CRBN substrate proteins. Here, we report that the CRL3GIG-USP15 pathway governs the destruction of NF proteins NEFL and INA. We identified a specific degron called NEFLL12 degron for CRL3GIG. Notably, mutations in the C-terminal Kelch domain of GIG, represented by L309R, R545C, and C570Y, disrupted the binding of GIG to NEFL and INA, leading to the accumulation of these NF proteins. This accounts for the loss-of-function mutations in GAN patients. In addition to regulating NFs, CRL3GIG also controls actin filaments by directly targeting actin-filament-binding regulatory proteins TPM1, TPM2, TAGLN, and CNN2 for proteasomal degradation. Thus, our findings broadly impact the field by providing fundamental mechanistic insights into regulating extremely long-lived NF proteins NEFL and INA by the CRL3GIG-USP15 pathway and offering previously unexplored therapeutic opportunities to treat GAN patients and other neurodegenerative diseases by explicitly targeting downstream substrates of CRL3GIG.

Impact and effectiveness of Rotavin-M1 under conditions of routine use in two provinces in Vietnam, 2016-2021, an observational and case-control study.

Background: Half of diarrhea hospitalizations in children aged <5 years in Vietnam are due to rotavirus. Following introduction of a locally developed and licensed oral rotavirus vaccine, Rotavin-M1, into the routine immunization program in two Vietnamese provinces, Nam Dinh and TT Hue, we describe changes in rotavirus positivity among children hospitalized for diarrhea and calculate vaccine effectiveness against moderate-to-severe rotavirus hospitalizations. Methods: Active rotavirus surveillance among children <5 years began in December 2016 at sentinel hospitals in districts where rotavirus vaccine was introduced in December 2017. To estimate reductions in rotavirus detection, we calculated risk ratios comparing rotavirus positivity pre- and post-vaccine introduction. We used a test-negative case-control design to calculate vaccine effectiveness. Findings: From December 2016 to May 2021, 7228 children <5 years hospitalized for diarrhea were enrolled. Following introduction, Rotavin-M1 coverage was 77% (1066/1377) in Nam Dinh and 42% (203/489) in TT Hue. In Nam Dinh, rotavirus positivity among children <5 years significantly declined by 40.6% (95% CI: 34.8%-45.8%) during the three-year post-vaccine introduction period. In TT Hue, no change in rotavirus positivity was observed. Among children aged 6-23 months, a 2-dose series of Rotavin-M1 was 57% (95% CI: 39%-70%) effective against moderate-to-severe rotavirus hospitalizations. Interpretation: Higher vaccination coverage in Nam Dinh than TT Hue likely contributed to substantial declines in rotavirus positivity observed in Nam Dinh following rotavirus vaccine introduction. Robust vaccine effectiveness was observed through the second year of life. National rotavirus vaccine introduction with high coverage may have substantial impact on reducing rotavirus disease burden in Vietnam. Funding: Bill and Melinda Gates Foundation.

Knowledge, attitudes, and practices toward emergency contraceptive pills among community pharmacists and pharmacy customers: A cross-sectional study in urban Vietnam.

OBJECTIVES: This study aimed to investigate Vietnamese community pharmacists and pharmacy customers' knowledge, attitudes, and practices about emergency contraceptive pills (ECPs). STUDY DESIGN: We recruited 400 pharmacists and 396 customers via a nonprobability convenience sampling technique. We used univariate and multivariate linear regression models to determine factors associated with the knowledge and attitudes toward ECPs among pharmacists and customers. We selected variables in the multivariate models through the Bayesian Model Averaging method using R software (version 4.2.3). RESULTS: In medicine outlets, levonorgestrel and mifepristone (ECPs) were highly available. The average knowledge scores on ECPs among pharmacists and customers were 9.98 ± 2.00 and 6.24 ± 2.33, respectively. Many pharmacists did not have adequate knowledge of ECPs' mechanism of action, dosage, and contraindications. Customers lacked knowledge about their legislation, effectiveness, and side effects. The attitudes toward ECPs among participants were relatively positive. Reliable information sources about ECPs (such as the package leaflet, courses, and books) played an essential role in increasing ECP knowledge and attitudes (p < 0.001). The availability of ECPs (p < 0.001), being educated (p < 0.01 and 0.01), and daily sales (p < 0.001) were significantly associated with pharmacists' knowledge/attitudes. Age, education level, marital status, and occupation were significantly associated with customers' knowledge. Participants' knowledge of was significantly associated with their attitude toward ECPs (p = 0.02 and p < 0.001, respectively). CONCLUSIONS: The knowledge of ECPs among pharmacists was relatively good, while that of customers was poor. There is a need to have policies and interventions to enhance the knowledge and attitudes toward ECPs for both pharmacists and customers. IMPLICATIONS: Community pharmacies are ideal settings to dispense contraceptive methods, especially over-the-counter ECPs. Community pharmacists can help ensure the availability of ECPs in medicine outlets, increase women's access to ECPs, and counsel customers on up-to-date and comprehensive knowledge about these medications, thereby guaranteeing rational ECP use.

Self-Aggregating Tau Fragments Recapitulate Pathologic Phenotypes and Neurotoxicity of Alzheimer's Disease in Mice.

In tauopathy conditions, such as Alzheimer's disease (AD), highly soluble and natively unfolded tau polymerizes into an insoluble filament; however, the mechanistic details of this process remain unclear. In the brains of AD patients, only a minor segment of tau forms ß-helix-stacked protofilaments, while its flanking regions form disordered fuzzy coats. Here, it is demonstrated that the tau AD nucleation core (tau-AC) sufficiently induced self-aggregation and recruited full-length tau to filaments. Unexpectedly, phospho-mimetic forms of tau-AC (at Ser324 or Ser356) show markedly reduced oligomerization and seeding propensities. Biophysical analysis reveal that the N-terminus of tau-AC facilitates the fibrillization kinetics as a nucleation motif, which becomes sterically shielded through phosphorylation-induced conformational changes in tau-AC. Tau-AC oligomers are efficiently internalized into cells via endocytosis and induced endogenous tau aggregation. In primary hippocampal neurons, tau-AC impaired axon initial segment plasticity upon chronic depolarization and is mislocalized to the somatodendritic compartments. Furthermore, it is observed significantly impaired memory retrieval in mice intrahippocampally injected with tau-AC fibrils, which corresponds to the neuropathological staining and neuronal loss in the brain. These findings identify tau-AC species as a key neuropathological driver in AD, suggesting novel strategies for therapeutic intervention.

Feruloyl Esterase (LaFae) from Lactobacillus acidophilus: Structural Insights and Functional Characterization for Application in Ferulic Acid Production.

Ferulic acid and related hydroxycinnamic acids, used as antioxidants and preservatives in the food, cosmetic, pharmaceutical and biotechnology industries, are among the most abundant phenolic compounds present in plant biomass. Identification of novel compounds that can produce ferulic acid and hydroxycinnamic acids, that are safe and can be mass-produced, is critical for the sustainability of these industries. In this study, we aimed to obtain and characterize a feruloyl esterase (LaFae) from Lactobacillus acidophilus. Our results demonstrated that LaFae reacts with ethyl ferulate and can be used to effectively produce ferulic acid from wheat bran, rice bran and corn stalks. In addition, xylanase supplementation was found to enhance LaFae enzymatic hydrolysis, thereby augmenting ferulic acid production. To further investigate the active site configuration of LaFae, crystal structures of unliganded and ethyl ferulate-bound LaFae were determined at 2.3 and 2.19 Å resolutions, respectively. Structural analysis shows that a Phe34 residue, located at the active site entrance, acts as a gatekeeper residue and controls substrate binding. Mutating this Phe34 to Ala produced an approximately 1.6-fold increase in LaFae activity against p-nitrophenyl butyrate. Our results highlight the considerable application potential of LaFae to produce ferulic acid from plant biomass and agricultural by-products.

[Mo2 S12 ]2- Complex as a Precursor for In-situ Generation of Molybdenum Sulfide Catalyst During the H2 Evolution.

For decades, the sulfido molybdenum complexes like [MoS4 ]2- , [Mo2 S12 ]2- , [Mo3 S13 ]2- have gained great attention because of their chemical versatility as well as their structural similarity to the edge-plan of the molybdenum disulfide (MoS2 ) which shows promising catalytic ability for the H2 generation. In this work, we report on the investigation of the dinuclear complex [Mo2 S12 ]2- in both organic and aqueous solution. We demonstrate that [Mo2 S12 ]2- is not intact during the H2 evolution catalysis when it is assayed as a homogeneous catalyst in an electrolyte solution (e. g. in DMF or water solvent) nor when it is immobilized on an electrode surface (e. g. mesoporous carbon black). It transforms into the polymeric amorphous molybdenum sulfide [MoS] which subsequently acts as an actual catalyst. We discuss on the possible [Mo2 S12 ]2- to [MoS] transformation mechanism by employing an arsenal of electrochemical analysis, spectroscopic analyses and microscopic analyses. Effects of the electrochemical operating conditions to the [Mo2 S12 ]2- to [MoS] transformation as well as to the chemical nature and the catalytic performance of the [MoS] product are also emphasized.

Exploring the Sub-nanoscale Structure of Cobalt Molybdenum Sulfide and the Role of a Cobalt Promoter in Catalytic Hydrogen Evolution.

Cobalt-promoted molybdenum sulfide (CoMoS) is known as a promising catalyst for H2 evolution reaction and hydrogen desulfurization reaction. This material exhibits superior catalytic activity as compared to its pristine molybdenum sulfide counterpart. However, revealing the actual structure of cobalt-promoted molybdenum sulfide as well as the plausible contribution of a cobalt promoter is still challenging, especially when the material has an amorphous nature. Herein, we report, for the first time, on the use of positron annihilation spectroscopy (PAS), being a nondestructive nuclear radiation-based method, to visualize the position of a Co promoter within the structure of MoS at the atomic scale, which is inaccessible by conventional characterization tools. It is found that at low concentrations, a Co atom occupies preferably the Mo-vacancies, thus generating the ternary phase CoMoS whose structure is composed of a Co-S-Mo building block. Increasing the Co concentration, e.g., a Co/Mo molar ratio of higher than 1.12/1, leads to the occupation of both Mo-vacancies and S-vacancies by Co. In this case, secondary phases such as MoS and CoS are also produced together with the CoMoS one. Combining the PAS and electrochemical analyses, we highlight the important contribution of a Co promoter to enhancing the catalytic H2 evolution activity. Having more Co promoter in the Mo-vacancies promotes the H2 evolution rate, whereas having Co in the S-vacancies causes a drop in H2 evolution ability. Furthermore, the occupation of Co to the S-vacancies leads also to the destabilization of the CoMoS catalyst, resulting in a rapid degradation of catalytic activity.

A Multicenter Study of Clinicopathology and Immunohistochemical Distinction between Adult and Pediatric Large B-Cell Lymphoma.

Introduction: Pediatric DLBCL is considered a homogenous group and has superior outcomes compared to adults. This study investigated the clinical pathology and immunohistochemical distinction between adult and pediatric large B-cell lymphoma. Methods: A cross-sectional study of 314 NHLs with the morphology of diffuse pattern, large B-cell, and CD20 expression was investigated. Results: Of 314 cases, there were 6 cases of pleomorphic MCL (all in adults), 19 cases of Burkitt lymphoma (all in children), and 289 cases of DLBCL. Pediatric DLBCL had many striking differences: More frequency in extra-nodal sites; a higher proportion of centroblastic morphology; a predominance of GCB-type; a high proliferation rate; an infrequency of Bcl2 protein expression, and a lack of double-expresser lymphoma. Conclusions: Our study demonstrated the significant biological differences between adult and pediatric DLBCL.

Measurement of anti-suprabasin antibodies, multiple cytokines and chemokines as potential predictive biomarkers for neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) varies in presentation and is one of the leading causes of morbidity and mortality among patients with SLE. This study determined the most critical serum biomarkers for the development of NPSLE as they may have clinical utility prior to the onset of neuropsychiatric symptoms. We retrospectively analyzed 35 NPSLE patients, 34 SLE patients, 20 viral meningitis (VM) patients, and 16 relapsing-remitting multiple sclerosis (MS) patients. We measured anti-suprabasin antibodies concentrations in serum by using Luciferase immunoprecipitation system (LIPS) assay. The serum concentrations of cytokines/chemokines were measured by using multiplex bead-based assay. We found serum FGF-2 level was significantly higher in the NPSLE group compared to the SLE group and the healthy control group. The anti-suprabasin antibody relative concentration (SRC) has high positive predictive values for the development of NPSLE. The most essential biomarkers are VEGF, anti-suprabasin antibodies, sCD40L, IL-10, GRO, MDC, IL-8, IL-9, TNF-α, MIP-1α.

iANP-EC: Identifying Anticancer Natural Products Using Ensemble Learning Incorporated with Evolutionary Computation.

Cancer is one of the most deadly diseases that annually kills millions of people worldwide. The investigation on anticancer medicines has never ceased to seek better and more adaptive agents with fewer side effects. Besides chemically synthetic anticancer compounds, natural products are scientifically proved as a highly potential alternative source for anticancer drug discovery. Along with experimental approaches being used to find anticancer drug candidates, computational approaches have been developed to virtually screen for potential anticancer compounds. In this study, we construct an ensemble computational framework, called iANP-EC, using machine learning approaches incorporated with evolutionary computation. Four learning algorithms (k-NN, SVM, RF, and XGB) and four molecular representation schemes are used to build a set of classifiers, among which the top-four best-performing classifiers are selected to form an ensemble classifier. Particle swarm optimization (PSO) is used to optimise the weights used to combined the four top classifiers. The models are developed by a set of curated 997 compounds which are collected from the NPACT and CancerHSP databases. The results show that iANP-EC is a stable, robust, and effective framework that achieves an AUC-ROC value of 0.9193 and an AUC-PR value of 0.8366. The comparative analysis of molecular substructures between natural anticarcinogens and nonanticarcinogens partially unveils several key substructures that drive anticancerous activities. We also deploy the proposed ensemble model as an online web server with a user-friendly interface to support the research community in identifying natural products with anticancer activities.

Digital Health Technologies to Improve Medication Adherence and Treatment Outcomes in Patients With Tuberculosis: Systematic Review of Randomized Controlled Trials.

BACKGROUND: Nonadherence to medication in tuberculosis (TB) hampers optimal treatment outcomes. Digital health technology (DHT) seems to be a promising approach to managing problems of nonadherence to medication and improving treatment outcomes. OBJECTIVE: This paper systematically reviews the effect of DHT in improving medication adherence and treatment outcomes in patients with TB. METHODS: A literature search in PubMed and Cochrane databases was conducted. Randomized controlled trials (RCTs) that analyzed the effect of DHT interventions on medication adherence outcomes (treatment completion, treatment adherence, missed doses, and noncompleted rate) and treatment outcomes (cure rate and smear conversion) were included. Adult patients with either active or latent TB infection were included. The Jadad score was used for evaluating the study quality. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was followed to report study findings. RESULTS: In all, 16 RCTs were selected from 552 studies found, and 6 types of DHT interventions for TB were identified: 3 RCTs examined video directly observed therapy (VDOT), 1 examined video-observed therapy (VOT), 1 examined an ingestible sensor, 1 examined phone call reminders, 2 examined medication monitor boxes, and 8 examined SMS text message reminders. The outcomes used were treatment adherence, including treatment completion, treatment adherence, missed dose, and noncompleted rate, as well as clinical outcomes, including cure rate and smear conversion. In treatment completion, 4 RCTs (VDOT, VOT, ingestible sensor, SMS reminder) found significant effects, with odds ratios and relative risks (RRs) ranging from 1.10 to 7.69. Treatment adherence was increased in 1 study by SMS reminders (RR 1.05; 95% CI 1.04-1.06), and missed dose was reduced in 1 study by a medication monitor box (mean ratio 0.58; 95% CI 0.42-0.79). In contrast, 3 RCTs of VDOT and 3 RCTs of SMS reminders did not find significant effects for treatment completion. Moreover, no improvement was found in treatment adherence in 1 RCT of VDOT, missed dose in 1 RCT of SMS reminder, and noncompleted rate in 1 RCT of a monitor box, and 2 RCTs of SMS reminders. For clinical outcomes such as cure rate, 2 RCTs reported that phone calls (RR 1.30; 95% CI 1.07-1.59) and SMS reminders (OR 2.47; 95% CI 1.13-5.43) significantly affected cure rates. However, 3 RCTs found that SMS reminders did not have a significant impact on cure rate or smear conversion. CONCLUSIONS: It was found that DHT interventions can be a promising approach. However, the interventions exhibited variable effects regarding effect direction and the extent of improving TB medication adherence and clinical outcomes. Developing DHT interventions with personalized feedback is required to have a consistent and beneficial effect on medication adherence and outcomes among patients with TB.

Dual functional roles of a novel bifunctional ß-lactamase/esterase from Lactococcus garvieae.

A novel bifunctional ß-lactamase/esterase (LgLacI), which is capable of hydrolyzing ß-lactam-containing antibiotics including ampicillin, oxacillin, and cefotaxime as well as synthesizing biodiesels, was cloned from Lactococcus garvieae. Unlike most bacterial esterases/lipases that have G-x-S-x-G motif, LgLacI, which contains S-x-x-K catalytic motif, has sequence similarities to bacterial family VIII esterase as well as ß-lactamases. The catalytic properties of LgLacI were explored using a wide range of biochemical methods including spectroscopy, assays, structural modeling, mutagenesis, and chromatography. We confirmed the bifunctional property of LgLacI hydrolyzing both esters and ß-lactam antibiotics. This study provides novel perspectives into a bifunctional enzyme from L. garvieae, which can degrade ß-lactam antibiotics with high esterase activity.

iCYP-MFE: Identifying Human Cytochrome P450 Inhibitors Using Multitask Learning and Molecular Fingerprint-Embedded Encoding.

The human cytochrome P450 (CYP) superfamily holds responsibilities for the metabolism of both endogenous and exogenous compounds such as drugs, cellular metabolites, and toxins. The inhibition exerted on the CYP enzymes is closely associated with adverse drug reactions encompassing metabolic failures and induced side effects. In modern drug discovery, identification of potential CYP inhibitors is, therefore, highly essential. Alongside experimental approaches, numerous computational models have been proposed to address this biochemical issue. In this study, we introduce iCYP-MFE, a computational framework for virtual screening on CYP inhibitors toward 1A2, 2C9, 2C19, 2D6, and 3A4 isoforms. iCYP-MFE contains a set of five robust, stable, and effective prediction models developed using multitask learning incorporated with molecular fingerprint-embedded features. The results show that multitask learning can remarkably leverage useful information from related tasks to promote global performance. Comparative analysis indicates that iCYP-MFE achieves three predominant tasks, one equivalent task, and one less effective task compared to state-of-the-art methods. The area under the receiver operating characteristic curve (AUC-ROC) and the area under the precision-recall curve (AUC-PR) were two decisive metrics used for model evaluation. The prediction task for CYP2D6-inhibition achieves the highest AUC-ROC value of 0.93 while the prediction task for CYP1A2-inhibition obtains the highest AUC-PR value of 0.92. The substructural analysis preliminarily explains the nature of the CYP-inhibitory activity of compounds. An online web server for iCYP-MFE with a user-friendly interface was also deployed to support scientific communities in identifying CYP inhibitors.