Measuring Mobile Phone Application Usability for Anticoagulation from the Perspective of Patients, Caregivers, and Healthcare Professionals.

Oral anticoagulants (OAC) are recommended for preventing stroke and systemic embolism in atrial fibrillation. Proper use is imperative for maximizing anticoagulation therapy's effectiveness and safety. In preparation for the implementation of a smartphone-based SmartMed app (application) aiming to promote patient self-management, medication adherence, and data collection for patients on anticoagulation therapy, its usability assessment can ensure the value of OAC app development and adoption. We evaluated the SmartMed app's usability using the System Usability Scale (SUS) and the app-specific domain of the Mobile App Rating Scale (MARS) for its perceived impact on taking OAC regularly. We recruited 25 OAC users and their home caregivers and 59 healthcare professionals, including pharmacists, nurses, and cardiac surgeons from one medical center and one regional hospital in Taiwan. All participants (n = 84) thought the SmartMed app was useful, with mean SUS and MARS scores of 81.49 (±14.42) and 4.65 (±0.49), respectively. Usability evaluation revealed that fewer experiences with smartphone apps and different healthcare professionals (pharmacists versus nurses or cardiac surgeons) were associated with lower SUS scores and perceived impact. Throughout the evaluation process, the SmartMed app's design was considered helpful from multiple stakeholders' perspectives. Further ongoing mobile technology supports are necessary to establish the SmartMed app's effectiveness.

Predictors of Acute Kidney Disease Severity in Hospitalized Patients with Acute Kidney Injury.

Acute kidney disease (AKD) forms part of the continuum of acute kidney injury (AKI) and worsens clinical outcomes. Currently, the predictors of AKD severity have yet to be established. We conducted a retrospective investigation involving 310 hospitalized patients with AKI and stratified them based on the AKD stages defined by the Acute Dialysis Quality Initiative criteria. Demographic, clinical, hematologic, and biochemical profiles, as well as 30-day outcomes, were compared between subgroups. In the analysis, the use of offending drugs (odds ratio, OR (95% confidence interval, CI), AKD stage 3 vs. non-AKD, 3.132 (1.304−7.526), p = 0.011, AKD stage 2 vs. non-AKD, 2.314 (1.049−5.107), p = 0.038), high AKI severity (OR (95% CI), AKD stage 3 vs. non-AKD, 6.214 (2.658−14.526), p < 0.001), and early dialysis requirement (OR (95% CI), AKD stage 3 vs. non-AKD, 3.366 (1.008−11.242), p = 0.049) were identified as independent predictors of AKD severity. Moreover, a higher AKD severity was associated with higher 30-day mortality and lower dialysis-independent survival rates. In conclusion, our study demonstrated that offending drug use, AKI severity, and early dialysis requirement were independent predictors of AKD severity, and high AKD severity had negative impact on post-AKI outcomes.

Nephrotoxins and acute kidney injury - The consensus of the Taiwan acute kidney injury Task Force.

The Taiwan Acute Kidney Injury (AKI) Task Force conducted a review of data and developed a consensus regarding nephrotoxins and AKI. This consensus covers: (1) contrast-associated AKI; (2) drug-induced nephrotoxicity; (3) prevention of drug-associated AKI; (4) follow up after AKI; (5) re-initiation of medication after AKI. Strategies for the avoidance of contrast media related AKI, including peri-procedural hydration, sodium bicarbonate solutions, oral N-acetylcysteine, and iso-osmolar/low-osmolar non-ionic iodinated contrast media have been recommended, given the respective evidence levels. Regarding anticoagulants, both warfarin and new oral anticoagulants have potential nephrotoxicity, and dosage should be reduced if renal pathology exam proves renal injury. Recommended strategies to prevent drug related AKI have included assessment of 5R/(6R) reactions - risk, recognition, response, renal support, rehabilitation and (research), use of AKI alert system and computerized decision support. In terms of antibiotics-associated AKI, avoiding concomitant administration of vancomycin and piperacillin-tazobactam, monitoring vancomycin trough level, switching from vancomycin to teicoplanin in high-risk patients, and replacing conventional amphotericin B with lipid-based amphotericin B have been shown to reduce drug related AKI. With respect to non-steroidal anti-inflammatory drug associated AKI, it is recommended to use these drugs cautiously in the elderly and in patients receiving renin-angiotensin-aldosterone system inhibitors/diuretics triple combinations.

Feature and impact of guideline-directed medication prescriptions for heart failure with reduced ejection fraction accompanied by chronic kidney disease.

Background: With respect to total mortality and cardiovascular mortality, the feature and impact of guideline-directed medication (GDM) prescriptions for heart failure with reduced ejection fraction (HFrEF) with chronic kidney disease (CKD) are unknown. Therefore, we aimed to determine these aspects. Methods: GDM prescriptions and their impact on discharged patients with and without CKD were analyzed. To analyze differences in one-year clinical outcomes, propensity score matching was conducted on a cohort of patients with concomitant HFrEF and CKD who received more and fewer GDM prescriptions. Results: A total of 1509 patients were enrolled in Taiwan's HFrEF registry from May 2013 to October 2014, and 1275 discharged patients with complete one-year follow-up were further analyzed. Of these patients, 468 (36.7%) had moderate CKD, whereas 249 (19.5%) had advanced CKD. Patients with advanced CKD received fewer prescribed GDMs than other patients. Multivariate analysis revealed that peripheral arterial occlusive disease, thyroid disorder, advanced HF at discharge, diastolic blood pressure, digoxin use, and fewer prescribed GDMs were independent predictors of one-year total mortality. After propensity score matching, patients with fewer prescribed GDMs had higher one-year total mortality rate than those with more prescribed GDMs (P=0.036). Conclusions: CKD at discharge from HF hospitalization was associated with fewer GDM prescriptions, particularly in patients with more advanced CKD. The propensity-matched analysis indicated that more GDM prescriptions led to better clinical outcomes in HFrEF patients with CKD. Careful interpretation of changes in renal function during HF hospitalization may improve GDM prescriptions.

Development of flexible electrochemical impedance spectroscopy-based biosensing platform for rapid screening of SARS-CoV-2 inhibitors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film electrode as the core sensing element was fabricated for the screening of potential inhibitors against S-protein-ACE2 binding. The platform could detect interference of small analytes against S-protein-ACE2 binding at low analyte concentration and small volume (0.1 µg/mL and ~1 µL, estimated total analyte consumption < 4 pg) within 21 min. Thus, a few potential inhibitors of S-protein-ACE2 binding were identified. This includes (2S,3aS,6aS)-1-((S)-N-((S)-1-Carboxy-3-phenylpropyl)alanyl)tetrahydrocyclopenta[b] pyrrole-2-carboxylic acid (ramiprilat) and (2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-Carboxybutyl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid (perindoprilat) that reduced the binding affinity of S-protein to ACE2 by 72% and 67%; and SARS-CoV-2 in vitro infectivity to the ACE2-expressing human oral cavity squamous carcinoma cells (OEC-M1) by 36.4 and 20.1%, respectively, compared to the PBS control. These findings demonstrated the usefulness of the developed biosensing platform for the rapid screening of modulators for S-protein-ACE2 binding.

Association of Statin and Its Lipophilicity With Cardiovascular Events in Patients Receiving Chronic Dialysis.

Lipophilicity of statins has been linked to extrahepatic cell penetration and inhibition of isoprenoid synthesis and coenzyme Q10, which may affect myocardial contraction. Whether statins' lipophilicity affects the risk of cardiovascular disease development in patients under dialysis is unclear. This population-based study included 114,929 patients undergoing chronic dialysis, retrieved from the Registry for Catastrophic Illness Patients from the National Health Insurance Research Database in Taiwan from 2000 to 2013. Statins were initiated after dialysis and classified into hydrophilic and lipophilic by the duration of use. In total, 17,015 statin users and match controls were identified by using propensity score matching in 1:1 ratio. New statin use was associated with higher cardiovascular disease risk (adjusted hazard ratio (aHR): 1.2, 95% confidence interval (CI), 1.13-1.28) but lower all-cause mortality (aHR: 0.93, 95% CI, 0.89-0.96). Hydrophilic statins were significantly associated with lower risk of cardiovascular disease compared with lipophilic statins (aHR: 0.91, 95% CI, 0.85-0.97).

Incidence, Outcomes, and Risk Factors of Community-Acquired and Hospital-Acquired Acute Kidney Injury: A Retrospective Cohort Study.

The disease burden and outcomes of community-acquired (CA-) and hospital-acquired acute kidney injury (HA-AKI) are not well understood. The aim of the study was to investigate the incidence, outcomes, and risk factors of AKI in a large Taiwanese adult cohort.This retrospective cohort study examined 734,340 hospital admissions from a group of hospitals within an organization in Taiwan between January 1, 2010 and December 31, 2014. Patients with AKI at discharge were classified as either CA- or HA-AKI based on the RIFLE (risk, injury, failure, loss of function, end stage of kidney disease) classification criteria. Outcomes were in-hospital mortality, dialysis, recovery of renal function, and length of stay. Risks of developing AKI were determined using multivariate logistic regression based on demographic and baseline clinical characteristics and nephrotoxin use before admission.AKI occurred in 1.68% to 2% hospital discharges among adults without and with preexisting chronic kidney disease (CKD), respectively. The incidence of CA-AKI was 17.25 and HA-AKI was 8.14 per 1000 admissions. The annual rate of CA-AKI increased from 12.43 to 19.96 per 1000 people, but the change in HA-AKI was insignificant. Comparing to CA-AKI, those with HA-AKI had higher levels of in-hospital mortality (26.07% vs 51.58%), mean length of stay (21.25 ±â€Š22.35 vs 35.84 ±â€Š34.62 days), and dialysis during hospitalization (1.45% vs 2.06%). Preexisting systemic diseases, including CKD were associated with increased risks of CA-AKI, and nephrotoxic polypharmacy increased risk of both CA- and HA-AKI.Patients with HA-AKI had more severe outcomes than patients with CA-AKI, and demonstrated different spectrum of risk factors. Although patients with CA-AKI with better outcomes, the incidence increased over time. It is also clear that optimal preventive and management strategies of HA- and CA-AKI are urgently needed to limit the risks in susceptible individuals.

The impact of normalization and phylogenetic information on estimating the distance for metagenomes.

Metagenomics enables the study of unculturable microorganisms in different environments directly. Discriminating between the compositional differences of metagenomes is an important and challenging problem. Several distance functions have been proposed to estimate the differences based on functional profiles or taxonomic distributions; however, the strengths and limitations of such functions are still unclear. Initially, we analyzed three well-known distance functions and found very little difference between them in the clustering of samples. This motivated us to incorporate suitable normalizations and phylogenetic information into the functions so that we could cluster samples from both real and synthetic data sets. The results indicate significant improvement in sample clustering over that derived by rank-based normalization with phylogenetic information, regardless of whether the samples are from real or synthetic microbiomes. Furthermore, our findings suggest that considering suitable normalizations and phylogenetic information is essential when designing distance functions for estimating the differences between metagenomes. We conclude that incorporating rank-based normalization with phylogenetic information into the distance functions helps achieve reliable clustering results.

MetaRank: a rank conversion scheme for comparative analysis of microbial community compositions.

MOTIVATION: Metagenomics involves sampling and studying the genetic materials in microbial communities. Several statistical methods have been proposed for comparative analysis of microbial community compositions. Most of the methods are based on the estimated abundances of taxonomic units or functional groups from metagenomic samples. However, such estimated abundances might deviate from the true abundances in habitats due to sampling biases and other systematic artifacts in metagenomic data processing. RESULTS: We developed the MetaRank scheme to convert abundances into ranks. MetaRank employs a series of statistical hypothesis tests to compare abundances within a microbial community and determine their ranks. We applied MetaRank to synthetic samples and real metagenomes. The results confirm that MetaRank can reduce the effects of sampling biases and clarify the characteristics of metagenomes in comparative studies of microbial communities. Therefore, MetaRank provides a useful rank-based approach to analyzing microbiomes. CONTACT: hktsai@iis.sinica.edu.tw SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MetaABC--an integrated metagenomics platform for data adjustment, binning and clustering.

SUMMARY: MetaABC is a metagenomic platform that integrates several binning tools coupled with methods for removing artifacts, analyzing unassigned reads and controlling sampling biases. It allows users to arrive at a better interpretation via series of distinct combinations of analysis tools. After execution, MetaABC provides outputs in various visual formats such as tables, pie and bar charts as well as clustering result diagrams. AVAILABILITY: MetaABC source code and documentation are available at http://bits2.iis.sinica.edu.tw/MetaABC/ CONTACT: dywang@gate.sinica.edu.tw; hktsai@iis.sinica.edu.tw SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Surface modification of electrospun PLLA nanofibers by plasma treatment and cationized gelatin immobilization for cartilage tissue engineering.

Electrospun poly(lactic acid) (PLLA) nanofibers (NF) were modified with cationized gelatin (CG) to improve their compatibility with chondrocytes and to show in vitro and in vivo the potential applications of CG-grafted PLLA nanofibrous membranes (CG-PLLA NFM) as a cartilage tissue engineering scaffold. PLLA NF were first treated with oxygen plasma to introduce -COOH groups on the surface, followed by covalent grafting of CG molecules onto the fiber surface, using water-soluble carbodiimide as the coupling agent. The effects of CG grafting and properties of NFM were characterized by scanning electron microscopy (SEM), transmission electron microscopy, thermogravimetric analysis, atomic force microscope, X-ray photoelectron spectra and Fourier transform infrared spectroscopy. In vitro studies indicated that CG-PLLA NFM could enhance viability, proliferation and differentiation of rabbit articular chondrocytes compared with pristine PLLA NFM. SEM observations of the cell-scaffold construct confirmed the tight attachment of chondrocytes to CG-PLLA NF and in-growth of cells into the interior of the membrane with proper maintenance of cell morphology. Improved cell differentiation in CG-PLLA NFM was confirmed by enhanced glycoaminoglycan and collagen secretion, histological analysis and reverse transcription-polymerase chain reaction studies, which showed that the cells were able to maintain the expression of characteristic markers (collagen II, aggregan and SOX 9) of chondrocytes. Subcutaneous implantation of the cell-scaffold constructs with autologous chondrocytes also confirmed the formation of ectopic cartilage tissues after 28 days by histological examination and immunostaining.

Reanalyze unassigned reads in Sanger based metagenomic data using conserved gene adjacency.

BACKGROUND: Investigation of metagenomes provides greater insight into uncultured microbial communities. The improvement in sequencing technology, which yields a large amount of sequence data, has led to major breakthroughs in the field. However, at present, taxonomic binning tools for metagenomes discard 30-40% of Sanger sequencing data due to the stringency of BLAST cut-offs. In an attempt to provide a comprehensive overview of metagenomic data, we re-analyzed the discarded metagenomes by using less stringent cut-offs. Additionally, we introduced a new criterion, namely, the evolutionary conservation of adjacency between neighboring genes. To evaluate the feasibility of our approach, we re-analyzed discarded contigs and singletons from several environments with different levels of complexity. We also compared the consistency between our taxonomic binning and those reported in the original studies. RESULTS: Among the discarded data, we found that 23.7 ± 3.9% of singletons and 14.1 ± 1.0% of contigs were assigned to taxa. The recovery rates for singletons were higher than those for contigs. The Pearson correlation coefficient revealed a high degree of similarity (0.94 ± 0.03 at the phylum rank and 0.80 ± 0.11 at the family rank) between the proposed taxonomic binning approach and those reported in original studies. In addition, an evaluation using simulated data demonstrated the reliability of the proposed approach. CONCLUSIONS: Our findings suggest that taking account of conserved neighboring gene adjacency improves taxonomic assignment when analyzing metagenomes using Sanger sequencing. In other words, utilizing the conserved gene order as a criterion will reduce the amount of data discarded when analyzing metagenomes.

Genome-wide analysis of the cis-regulatory modules of divergent gene pairs in yeast.

In budding yeast, approximately a quarter of adjacent genes are divergently transcribed (divergent gene pairs). Whether genes in a divergent pair share the same regulatory system is still unknown. By examining transcription factor (TF) knockout experiments, we found that most TF knockout only altered the expression of one gene in a divergent pair. This prompted us to conduct a comprehensive analysis in silico to estimate how many divergent pairs are regulated by common sets of TFs (cis-regulatory modules, CRMs) using TF binding sites and expression data. Analyses of ten expression datasets show that only a limited number of divergent gene pairs share CRMs in any single dataset. However, around half of divergent pairs do share a regulatory system in at least one dataset. Our analysis suggests that genes in a divergent pair tend to be co-regulated in at least one condition; however, in most conditions, they may not be co-regulated.