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Wrapper methods are a type of feature selection method that finds a subset of variables to improve the performance of a classifier by removing redundant and irrelevant variables. The use of a wrapper implies that each time a candidate solution is explored, the classifier is evaluated on the quality measures selected (e.g. accuracy or precision). Though robust, this iteration across several candidate solutions can become computationally intensive and time-consuming. In this paper we propose a wrapper, that is based on binary Covering Arrays (CAs), and binary Incremental Covering Arrays (ICAs), that have been widely used for experimental design and fault detection in software and hardware testing. The new wrapper was evaluated with six classifiers on seven data sets. The results show that the CAs and ICAs with strength 6 significantly improve the performance and reduces the number of variables required by the classifier. A comparative analysis of the proposed method against wrappers based on other search approaches such as genetic algorithms (GA) and particle swarm optimization (PSO), shows that the proposed method yields results similar to GA, but not to PSO, with differences to PSO, in accuracy, which in the majority of cases is below 0.04. This lack of accuracy, by which the new wrapper fails to match PSO, is offset by the fact that the user does not need to fine tune algorithm parameters, such as velocity ranges, timing, cognitive coefficient, and social coefficient, while it is also much easier to program in parallel.

Background: Enough evidence exists to attribute the occurrence of diarrheal disease outbreaks due to open defecation practice and unsafe sanitation methods. Open defecation enables pathogens such as virus, bacteria, and protozoa to infect humans by means of fecal–oral transmission methods through contaminated fluids, water, and fomites. To curb the malefic effects of open defecation, the Indian government had initiated pro sanitation program namely Swachh Bharat Mission (SBM) in 2014. SBM became the world's largest toilet-building initiative. More than 95 million toilets have been built across rural and urban India since the launch of this mission. This articulation summarizes the trend analysis of acute diarrheal disease (ADD) outbreaks over a 9-year period with emphasis on changes due to the building of toilets under the clean India campaign. Methods: Weekly ADD outbreaks data from national-level Integrated Disease Surveillance Program between 2010 and 2018 were used for trend analysis along with the number of toilets constructed in rural areas under SBM from the year 2014. Results: ADD outbreaks were analyzed from 2010 to 2018. The number of ADD outbreaks per year during the past 2 years (i.e., 2017 and 2018) of SBM regime was lesser than in any year during the investigation period. Seasonal variations during the months of May, June, July, and August account for 55%–60% of ADD outbreaks in any of the years; but for 2018, the total outbreaks were 46%, which is significantly lower than that of regular range of outbreaks in the peak season. Conclusion: The recent pattern of ADD outbreaks exhibits a declining rate.

Background: Periostin, a matricellular protein, is downregulated in chronic inflammatory periodontal disease and is negatively modulated by tumor necrosis factor-α (TNF-α) in human periodontal fibroblast cell culture. The study aimed to estimate the gingival crevicular fluid (GCF) levels of periostin and TNF-α and to discern their relationship in chronic periodontitis (CP) individuals with and without Type II diabetes mellitus (DM). Materials and Methods: A total of 60 participants were divided into three groups, with 20 in each group. Group I – systemically and periodontally healthy, Group II – generalized CP, and Group III – generalized CP with Type II DM. Plaque index, gingival index, sulcular bleeding index, probing depth, and clinical attachment level were recorded. GCF periostin and TNF-α were quantified using the enzyme-linked immunosorbent assay. Results: Intergroup comparison was performed using the one-way ANOVA and Kruskal–Wallis. The relationship between the variables was analyzed using the Pearson's and Kendall's Tau correlation. The GCF periostin levels in Groups I, II, and III was 27.52 ± 2.39 ng/mL, 20.18 ± 1.42 ng/mL, and 16.77 ± 3.29 ng/mL, respectively. The GCF TNF-α levels in Groups I, II, and III was 92.41 ± 19.30 ng/L, 118.53 ± 21.93 ng/L, and 147.67 ± 16.35 ng/L, respectively. Periostin decreased, and TNF-α increased in periodontal disease; moreover, periostin level correlated negatively with all the site-specific clinical parameters whereas TNF-α positively correlated (P < 0.001). Conclusions: TNF-α strongly and negatively downregulates periostin in a chronically inflamed locale leading to compromised integrity of the periodontium.

Agricultural systems in Southeast Asia are rapidly transitioning from subsistence-oriented to market-oriented agriculture. Driven by the highly complex and variable decision processes of individual farm households, these transitions have produced a diverse landscape mosaic across the region. Elucidation and characterization of underlying decision-making processes, and the factors that influence land use choices, are thus essential for sustainable land use planning. To enable a study that seeks to understand these linkages, data on plot-level 10-year land use history, management and farm performance indicators were collected from 163 households in the Northern Lao uplands and in the Central Highlands of Vietnam, areas chosen to represent two extremes of the transition gradient. The objectives of the study were (i) to describe plot-level sequence patterns of seasonal variation of land use over several years, (ii) to apply a sequence dissimilarity metric, the complexity index (CI), to measure land use transition in an agricultural system, and (iii) to identify the key drivers of land use change and their linkages with farm performance indicators and plot level characteristics through multi-dimensional analysis. CI allowed compressing historical land use data and quantifying land use complexity in a simple and efficient manner. Land use dynamics varied strongly between the two sites, with 66% of the land use types in the Laos site being completely replaced by others during the recall periods, compared to only 15% in the Vietnam site. Associated key drivers of land use change also differed significantly: while end use of agricultural products was the main driver behind land use changes in the Vietnam site, a more complex relationship between topography and management vs. land use change was evident in the Laos site. Likewise, land use complexity does not exhibit the same relationship with farm performance in the two sites: in the Central Highlands, households with higher food availability are half as likely to transition, while in the Lao uplands, land use complexity was significantly correlated with the Progress out of Poverty index. Multidisciplinary studies remain necessary to assess the impact of innovative sustainable intensification options on system performance and environmental sustainability, before policies are enacted to support their dissemination in Southeast Asian smallholder agricultural systems. Context-specific CI thresholds associated with system quality indicators could support this by informing decision-makers on the pace of agricultural transformation and its environmental impacts.

Background. Solid organ transplants (SOTs) are life-saving interventions, recently challenged by coronavirus disease 2019 (COVID-19). SOTs require a multistep process, which can be affected by COVID-19 at several phases. Methods. SOT-specialists, COVID-19-specialists, and medical ethicists designed an international survey according to CHERRIES guidelines. Personal opinions about continuing SOTs, safe managing of donors and recipients, as well as equity of resources’ allocation were investigated. The survey was sent by e-mail. Multiple approaches were used (corresponding authors from Scopus, websites of scientific societies, COVID-19 webinars). After the descriptive analysis, univariate and multivariate ordinal regression analysis was performed. Results. There were 1819 complete answers from 71 countries. The response rate was 49%. Data were stratified according to region, macrospecialty, and organ of interest. Answers were analyzed using univariate-multivariate ordinal regression analysis and thematic analysis. Overall, 20% of the responders thought SOTs should not stop (continue transplant without restriction); over 70% suggested SOTs should selectively stop, and almost 10% indicated they should completely stop. Furthermore, 82% agreed to shift resources from transplant to COVID-19 temporarily. Briefly, main reason for not stopping was that if the transplant will not proceed, the organ will be wasted. Focusing on SOT from living donors, 61% stated that activity should be restricted only to “urgent” cases. At the multivariate analysis, factors identified in favor of continuing transplant were Italy, ethicist, partially disagreeing on the equity question, a high number of COVID-19-related deaths on the day of the answer, a high IHDI country. Factors predicting to stop SOTs were Europe except-Italy, public university hospital, and strongly agreeing on the equity question. Conclusions. In conclusion, the majority of responders suggested that transplant activity should be continued through the implementation of isolation measures and the adoption of the COVID-19-free pathways. Differences between professional categories are less strong than supposed.

The SARS-CoV-2 virus that causes the COVID-19 disease has spread quickly and massively around the entire globe, causing millions of confirmed cases and deaths worldwide. The disease poses a serious ongoing threat to public health. This study aims to understand the disease potential of the virus in different regions by studying how average spring temperature and its strong predictor, latitude, affect epidemiological variables such as disease incidence, mortality, recovery cases, active cases, testing rate, and hospitalization. We also seek to understand the association of temperature and geographic coordinates with viral genomics. Epidemiological data along with temperature, latitude, longitude, and preparedness index were collected for different countries and US states during the early stages of the pandemic. Our worldwide epidemiological analysis showed a significant correlation between temperature and incidence, mortality, recovery cases and active cases. The same tendency was found with latitude, but not with longitude. In the US, we observed no correlation between temperature or latitude and epidemiological variables. Interestingly, longitude was correlated with incidence, mortality, active cases, and hospitalization. An analysis of mutational change and mutational change per time in 55 453 aligned SARS-CoV-2 genome sequences revealed these parameters were uncorrelated with temperature and geographic coordinates. The epidemiological trends we observed worldwide suggest a seasonal effect for the disease that is not directly controlled by the genomic makeup of the virus. Future studies will need to determine if correlations are more likely the result of effects associated with the environment or the innate immunity of the host.

The current scenario of the quest for microneedles (MNs) with biodegradability and biocompatibility properties is a potential research area of interest. Microneedles are considered to be robust, can penetrate the skin’s deep-seated layers, and are easy to manufacture, and their applications from the clinical perspective are still ongoing with standard escalation. This review paper focuses on some of the pivotal variants of polymeric microneedles which are specifically dissolvable and swell-based MNs. It further explores the drug dissolution kinetics and insertion behavior mechanisms with an emphasis on the need for mathematical modeling of MNs. This review further evaluates the multifarious fabrication methods, with an update on the advances in the fabrication of polymeric MNs, the choice of materials used for the fabrication, the challenges in polymeric MN fabrication, and the prospects of polymeric MNs with applications pertinent to healthcare, by exclusively focusing on the procurable literature over the last decade.

Previous studies assessing the antibody response (AbR) to mRNA COVID-19 vaccines in solid organ transplant (SOT) recipients are limited by short follow-up, hampering the analysis of AbR kinetics. We present the ORCHESTRA SOT recipients cohort assessed for AbR at first dose (t0), second dose (t1), and within 3 ± 1 month (t2) after the first dose. We analyzed 1062 SOT patients (kidney, 63.7%; liver, 17.4%; heart, 16.7%; and lung, 2.5%) and 5045 health care workers (HCWs). The AbR rates in the SOTs and HCWs were 52.3% and 99.4%. The antibody levels were significantly higher in the HCWs than in the SOTs (p < 0.001). The kinetics showed an increase (p < 0.001) in antibody levels up to 76 days and a non-significant decrease after 118 days in the SOT recipients versus a decrease up to 76 days (p = 0.02) and a less pronounced decrease between 76 and 118 days (p = 0.04) in the HCWs. Upon multivariable analysis, liver transplant, ≥3 years from SOT, mRNA-1273, azathioprine, and longer time from t0 were associated with a positive AbR at t2. Older age, other comorbidities, mycophenolate, steroids, and impaired graft function were associated with lower AbR probability. Our results may be useful to optimize strategies of immune monitoring after COVID-19 vaccination and indications regarding timing for booster dosages calibrated on SOT patients’ characteristics.

Premature newborns are at a higher risk for the development of respiratory distress syndrome (RDS), acute lung injury (ALI) associated with lung inflammation, disruption of alveolar structure, impaired alveolar growth, lung fibrosis, impaired lung angiogenesis, and development of bronchopulmonary dysplasia (BPD) with severe long-term developmental adverse effects. The current therapy for BPD is limited to supportive care including high-oxygen therapy and pharmacotherapy. Recognizing more feasible treatment options to improve lung health and reduce complications associated with BPD is essential for improving the overall quality of life of premature infants. There is a reduction in the resident stem cells in lungs of premature infants with BPD, which strongly suggests a critical role of stem cells in BPD pathogenesis; this warrants the exploration of the potential therapeutic use of stem-cell therapy. Stem-cell-based therapies have shown promise for the treatment of many pathological conditions including acute lung injury and BPD. Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) including exosomes are promising and effective therapeutic modalities for the treatment of BPD. Treatment with MSCs and EVs may help to reduce lung inflammation, improve pulmonary architecture, attenuate pulmonary fibrosis, and increase the survival rate.

Summary: Dityrosine (DiY), via the cross-linking of tyrosine residues, is a marker of protein oxidation, which increases with aging. Amyloid-β (Aβ) forms DiY in vitro and DiY-cross-linked Aβ is found in the brains of patients with Alzheimer disease. Metal- or UV- catalyzed oxidation of Aβ42 results in an increase in DiY cross-links. Using DiY as a marker of oxidation, we compare the self-assembly propensity and DiY cross-link formation for a non-assembly competent variant of Aβ42 (vAβ) with wild-type Aβ42. Oxidation results in the formation of trapped wild-type Aβ assemblies with increased DiY cross-links that are unable to elongate further. Assembly-incompetent vAβ and trapped Aβ assemblies are non-toxic to neuroblastoma cells at all stages of self-assembly, in contrast to oligomeric, non-cross-linked Aβ. These findings point to a mechanism of toxicity that necessitates dynamic self-assembly whereby trapped Aβ assemblies and assembly-incompetent variant Aβ are unable to result in cell death.

Food environments in Southeast Asia's emerging economies are rapidly evolving, alongside fast-paced socioeconomic and demographic changes. The widespread expansion of supermarkets and parallel restructuring of traditional markets in Vietnam are likely to impact patterns of household food acquisition. Using provincial-level time series data on the abundance of supermarkets and multiyear household survey data, this paper examines the impact of the differential country-wide presence of supermarkets with indices of food quality and quantity acquired by households. We classified provinces into three clusters based on the number of supermarkets: high (HighSM), medium (MedSM), and low (LowSM). We found that a higher number of supermarkets associated with the exceedable Vietnamese recommendation composition of macronutrients at the household-level, but not food quantity. Households with higher per capita food expenditure in HighSM provinces tended to procure foods with higher protein content and lower shares of fat and carbohydrate as compared to similar households in the others provinces. Ethnic minority households in MedSM clusters obtained food with lower carbohydrate and higher fat:protein ratios in comparison to ethnic majority households. Additionally, larger-sized households in HighSM provinces typically bought foods with higher fat shares than smaller-sized households. In contrast, in MedSM and LowSM provinces, larger-sized households typically procured foods with higher protein and lower fat shares. The diversity of foods obtained by households in MedSM and LowSM provinces decreased over time. Within the Midlands and Northern Mountains Area we observed a decrease in the diversity of food acquired among households in the LowSM clusters. This study elucidates potential impacts of the supermarket expansion on household food baskets. Insights from this study can be used to provide evidences for policy recommendation and to design and target interventions aimed at strengthening food environments to address the challenge of the double burden of malnutrition in the country.

Background and Objectives: Non-alcoholic steatohepatitis (NASH) has become the leading indication for liver transplantation in many countries, with a growing rate in the Western world. NASH patients are older and share a higher risk of comorbidities and cancer than patients with viral and/or alcoholic etiologies. The aims of this study were to evaluate waiting list (WL) registration and liver transplantation rates in patients with NASH-related cirrhosis at Padua University Hospital in the last fifteen years (1.2006–6.2020) and to compare clinical characteristics and indications for liver transplantation between patients with and without NASH, as well as the WL survival and post-transplant outcome. Materials and Methods: All adult patients with cirrhosis listed for liver transplantation at Padua University Hospital between 1.2006 and 6.2020 were retrospectively collected using a prospectively updated database; patients with NASH-related cirrhosis were divided by indication for liver transplantation (Dec-NASH vs. hepatocellular carcinoma (HCC)-NASH) and compared with patients with other etiologies of liver disease. The outcomes in terms of waiting list survival and post-transplant outcome were assessed. Results: One thousand four hundred and ninety-one adult cirrhotic patients were waitlisted during the study period. NASH patients accounted for 12% of all WL registrations, showing an increasing trend over time (from 2.5% in 2006 to 23% in 2020). In the last five years, NASH was the third, but most rapidly growing, indication for liver transplantation at our center. This trend was confirmed both for patients with decompensated cirrhosis (from 1.8% to 18%) and HCC as leading indication for transplantation (from 4% to 30%). NASH patients were older than non-NASH ones (mean ± SD age 59 ± 9 vs. 56 ± 9 years; p < 0.01), whereas no difference was found in gender or Child-Pugh of the model for end-stage liver disease score at WL registration. A majority (60.9%) of NASH patients underwent liver transplantation, showing 1-, 5- and 10-y post-transplant survivals of 86%, 73% and 60%, respectively. Conclusion: NASH cirrhosis has become a rapidly growing indication for liver transplantation at our center, both for HCC and decompensated disease, with good post-transplant survival.

The crystal structure of Jann_2411 from Jannaschia sp. strain CCS1, a member of the Pfam PF07336 family classified as a domain of unknown function (DUF1470), was solved to a resolution of 1.45 Å by multiple-wavelength anomalous dispersion (MAD). This protein is the first structural representative of the DUF1470 Pfam family. Structural analysis revealed a two-domain organization, with the N-terminal domain presenting a new fold called the ABATE domain that may bind an as yet unknown ligand. The C-terminal domain forms a treble-clef zinc finger that is likely to be involved in DNA binding. Analysis of the Jann_2411 protein and the broader ABATE-domain family suggests a role as stress-induced transcriptional regulators.

The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1 Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis.

Proteins with the DUF2063 domain constitute a new Pfam family, PF09836. The crystal structure of a member of this family, NGO1945 from Neisseria gonorrhoeae, has been determined and reveals that the N-terminal DUF2063 domain is likely to be a DNA-binding domain. In conjunction with the rest of the protein, NGO1945 is likely to be involved in transcriptional regulation, which is consistent with genomic neighborhood analysis. Of the 216 currently known proteins that contain a DUF2063 domain, the most significant sequence homologs of NGO1945 (∼40-99% sequence identity) are from various Neisseria and Haemophilus species. As these are important human pathogens, NGO1945 represents an interesting candidate for further exploration via biochemical studies and possible therapeutic intervention.

Background: Acute kidney injury (AKI) is a strong predictor of morbidity and mortality after cardiac surgery. Lack of valid early biomarkers for predicting AKI has hampered the ability to take therapeutic measures for preventive cause. Hyperphosphatemia that occurs in AKI due to renal excretion defect was not studied in this context and could be simple marker of AKI. Therefore, we tested role of serum phosphorus in prediction of AKI as a biomarker after cardiac surgery in children. Methodology: We prospectively evaluated 51 children aged between 3 weeks and 12 years undergoing elective cardiac surgery. Serum creatinine and phosphorus were measured preoperatively and postoperatively at 24 and 48 h. As per the Kidney Disease Improving Global Outcomes criteria, patients were grouped into AKI and non-AKI on the basis of the development of AKI within 48 h postsurgery. The postoperative diagnostic performance of phosphorus thresholds was analyzed by the area under receiver operating characteristic curves (AUC-ROC). Results: From 51 children included, 10 developed AKI. In AKI group, serum phosphorus increased significantly from 4.47 ± 0.43 baseline to 6.29 ± 0.32 at 24 h postsurgery (P = 0.01) while serum creatinine increased from baseline 0.33 (0.24–0.46) to 0.49 (0.26–0.91) at 24 h which is statistically insignificant (P = 0.16). ROC analysis showed that serum phosphorus at 24 h, the AUC was 0.84 with sensitivity 0.75 and specificity 0.93 for a cutoff value of 6.4 mg/dl. Whereas serum phosphorus at 48 h, the AUC was 0.86 with sensitivity 66.67% and specificity 97.62% for a cutoff value of 5.4 mg/dl. Conclusion: Serum phosphorus can be an alternative biomarker as early as 24 h for early prediction of AKI in pediatric cardiac surgery.