Miracle-dz/UniFAR-FTUs huggingface dataset:
Systemic medication requirement in post-surgical patients with eosinophilic chronic rhinosinusitis.

BACKGROUND Eosinophilic chronic rhinosinusitis (eCRS) is contemporarily managed by surgical creation of a 'neo-sinus' cavity and corticosteroid irrigations. While most patients gain control of their disease with this approach, similar to preventive inhaler therapy in asthma, some patients need systemic therapies. This study aimed to define those patients needing ongoing systemic therapy for eCRS. METHODS Consecutive adult patients (>18 years) who were seen at a tertiary referral clinic, diagnosed as eCRS and underwent endoscopic sinus surgery were included. Patients were followed up for a minimum of 12 months. All patients had a simple neo- sinus cavity surgically created and used initially a once daily topical corticosteroid irrigation maintenance therapy. Patients who re- quired long term systemic oral corticosteroids and/or biologic therapy were compared to those who remained on topical control. RESULTS 222 patients with eCRS were assessed (follow-up 2.76 years). Long term systemic therapy was required in 5.4% of pa- tients. Receiver operating curve analysis predicted local treatment failure at an eosinophil count cut-off level 0.455x109/L. Asthma, atopy and aspirin sensitivity also predicted long term systemic therapy. There were no associations with nasal polyposis or revi- sion surgery. Multivariate logistic regression showed elevated blood eosinophil count >0.455 x109/L was 9.27 times more likely to require for systemic medication. CONCLUSION Pre-operative blood eosinophil count >0.45 x109/L was associated with failure of local therapy following contem- porary management of eCRS. The quantitative value of serum eosinophilia may be a useful predictor of disease progression and those patients in need of systemic therapies, such as biologic agents.
Assessing spatial confounding in cancer disease mapping using R.

BACKGROUND Exploring spatial patterns in the context of cancer disease mapping (DM) is a decisive approach to bring evidence of geographical tendencies in assessing disease status and progression. However, this framework is not insulated from spatial confounding, a topic of significant interest in cancer epidemiology, where the latent correlation between the spatial random effects and fixed effects (such as covariates), often lead to misleading interpretation. AIMS To introduce three popular approaches (RHZ, HH and SPOCK; details in paper) often employed to tackle spatial confounding, and illustrate their implementation in cancer research via the popular statistical software R. METHODS As a solution to alleviate spatial confounding, restricted spatial regressions are constructed by either projecting the latent effect onto the orthogonal space of covariates, or by displacing the spatial locations. Popular parametric count data models, such as the Poisson, generalized Poisson and negative binomial, were considered for the areal count responses, while the spatial association is quantified via the conditional autoregressive (CAR) model. Our method of inference in Bayesian, sometimes aided by the integrated nested Laplace approximation (INLA) to accelerate computing. The methods are implemented in the R package RASCO available from the first author's GitHub page. RESULTS The results reveal that all three methods perform well in alleviating the bias and variance inflation present in the spatial models. The effects of spatial confounding were also explored, which, if ignored in practice, may lead to wrong conclusions. CONCLUSION Spatial confounding continues to remain a critical bottleneck in deriving precise inference from spatial DM models. Hence, its effects must be investigated, and mitigated. Several approaches are available in the literature, and they produce trustworthy results. The central contribution of this paper is providing the practitioners the R package RASCO, capable of fitting a large number of spatial models, as well as their restricted versions.
Association of toll-like receptors 2, 4, 9 and 10 genes polymorphisms and Helicobacter pylori-related gastric diseases in Saudi patients

Purpose: Helicobacter pylori is one of the most prevalent human pathogens worldwide. However, the outcomes of H. pylori infection are markedly variable from asymptomatic mild lesion to malignant transformation. Many factors are suggested to influence these infection outcomes, including host immunity and genetic susceptibility. Toll-like receptors (TLRs) can recognise different microbial components and play an essential role in the mucosal immune response against H. pylori infection. Materials and Methods: The association between the common single nucleotide polymorphisms (SNPs) in the genes of TLR2, 4, 9 and 10 and H. pylori-related gastric diseases were investigated by molecular methods after the confirmation of H. pylori infection. The study included 210 patients in three groups; chronic gastritis (n = 90), peptic ulcer disease (PUD) (n = 75) and gastric carcinoma (n = 45). Results: The results showed a significant association between TLR4 SNPs (rs 4986790 and rs 4986791) and the presence of H. pylori infection, especially in chronic gastritis patient group. Furthermore, TLR9-rs352140 TT genotype was more prevalent among chronic gastritis patient group. TLR10-rs 10004195 TT genotype was found to be less prevalent among H. pylori-related chronic gastritis and PUD and was suspected to have a protective effect. TLR2 SNPs (rs3804099 and rs3804100) showed no significant statistical difference between H. pylori-infected patients and the controls. Conclusion: TLR genes polymorphisms may play a role in H. pylori infection susceptibility and may influence its outcomes; however, the ethnic and other factors may modify this effect.
Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma

PURPOSE The immunomodulatory effect of lenvatinib (a multikinase inhibitor) on tumor microenvironments may contribute to antitumor activity when combined with programmed death receptor-1 (PD-1) signaling inhibitors in hepatocellular carcinoma (HCC). We report results from a phase Ib study of lenvatinib plus pembrolizumab (an anti–PD-1 antibody) in unresectable HCC (uHCC). PATIENTS AND METHODS In this open-label multicenter study, patients with uHCC received lenvatinib (bodyweight ≥ 60 kg, 12 mg; < 60 kg, 8 mg) orally daily and pembrolizumab 200 mg intravenously on day 1 of a 21-day cycle. The study included a dose-limiting toxicity (DLT) phase and an expansion phase (first-line patients). Primary objectives were safety/tolerability (DLT phase), and objective response rate (ORR) and duration of response (DOR) by modified RECIST (mRECIST) and RECIST version 1.1 (v1.1) per independent imaging review (IIR; expansion phase). RESULTS A total of 104 patients were enrolled. No DLTs were reported (n = 6) in the DLT phase; 100 patients (expansion phase; included n = 2 from DLT phase) had received no prior systemic therapy and had Barcelona Clinic Liver Cancer stage B (n = 29) or C disease (n = 71). At data cutoff, 37% of patients remained on treatment. Median duration of follow-up was 10.6 months (95% CI, 9.2 to 11.5 months). Confirmed ORRs by IIR were 46.0% (95% CI, 36.0% to 56.3%) per mRECIST and 36.0% (95% CI, 26.6% to 46.2%) per RECIST v1.1. Median DORs by IIR were 8.6 months (95% CI, 6.9 months to not estimable [NE]) per mRECIST and 12.6 months (95% CI, 6.9 months to NE) per RECIST v1.1. Median progression-free survival by IIR was 9.3 months per mRECIST and 8.6 months per RECIST v1.1. Median overall survival was 22 months. Grade ≥ 3 treatment-related adverse events occurred in 67% (grade 5, 3%) of patients. No new safety signals were identified. CONCLUSION Lenvatinib plus pembrolizumab has promising antitumor activity in uHCC. Toxicities were manageable, with no unexpected safety signals.
Early impact of COVID-19 on individuals with self-reported eating disorders: A survey of ~1,000 individuals in the United States and the Netherlands.

OBJECTIVE We evaluated the early impact of COVID-19 on people with self-reported eating disorders. METHOD Participants in the United States (US, N = 511) and the Netherlands (NL, N = 510), recruited through ongoing studies and social media, completed an online survey that included both quantitative measures and free-text responses assessing the impact of COVID-19 on situational circumstances, eating disorder symptoms, eating disorder treatment, and general well-being. RESULTS Results revealed strong and wide-ranging effects on eating disorder concerns and illness behaviors that were consistent with eating disorder type. Participants with anorexia nervosa (US 62% of sample; NL 69%) reported increased restriction and fears about being able to find foods consistent with their meal plan. Individuals with bulimia nervosa and binge-eating disorder (US 30% of sample; NL 15%) reported increases in their binge-eating episodes and urges to binge. Respondents noted marked increases in anxiety since 2019 and reported greater concerns about the impact of COVID-19 on their mental health than physical health. Although many participants acknowledged and appreciated the transition to telehealth, limitations of this treatment modality for this population were raised. Individuals with past histories of eating disorders noted concerns about relapse related to COVID-19 circumstances. Encouragingly, respondents also noted positive effects including greater connection with family, more time for self-care, and motivation to recover. DISCUSSIONS COVID-19 is associated with increased anxiety and poses specific disorder-related challenges for individuals with eating disorders that require attention by healthcare professionals and carers.
Quality changes in the fresh water prawn, Macrobrachium rosenbergii during storage on ice

Summary The effect of stratification in ice on the quality of fresh water prawns was monitored by microbiological, subjective and objective textural analyses. In general, prawns in the lower layers of ice exhibited more marked textural changes and greater numbers of potential spoilage bacteria were found on them. No connection was found between the number of proteolytic bacteria and textural changes in the prawn muscle.
Leukocidins and the Nuclease Nuc Prevent Neutrophil-Mediated Killing of Staphylococcus aureus Biofilms

Bacterial biofilms are linked with chronic infections and have properties distinct from those of planktonic, single-celled bacteria. The virulence mechanisms associated with Staphylococcus aureus biofilms are becoming better understood. Human neutrophils are critical for the innate immune response to S. aureus infection. Here, we describe two virulence strategies that converge to promote the ability of S. aureus biofilms to evade killing by neutrophils. ABSTRACT Bacterial biofilms are linked with chronic infections and have properties distinct from those of planktonic, single-celled bacteria. The virulence mechanisms associated with Staphylococcus aureus biofilms are becoming better understood. Human neutrophils are critical for the innate immune response to S. aureus infection. Here, we describe two virulence strategies that converge to promote the ability of S. aureus biofilms to evade killing by neutrophils. Specifically, we show that while neutrophils exposed to S. aureus biofilms produce extracellular traps (NETs) and phagocytose bacteria, both mechanisms are inefficient in clearance of the biofilm biomass. This is attributed to the leukocidin LukAB, which promotes S. aureus survival during phagocytosis. We also show that the persistence of biofilm bacteria trapped in NETs is facilitated by S. aureus nuclease (Nuc)-mediated degradation of NET DNA. This study describes key aspects of the interaction between primary human neutrophils and S. aureus biofilms and provides insight into how S. aureus evades the neutrophil response to cause persistent infections.
Production of effective microorganism using halal- based sources: A review

Contemporary Malaysia faces rapid population growth that will increase competition for land and water resources for industrial use and urban growth. Solutions are needed to increase agricultural productivity to combat hunger and poverty. Since the agriculture sector has long been the backbone of the economy, the nation has found effective microorganism (EM) technology that has potential use in developing a sustainable agriculture sector. Malaysia is recognized as a modern Islamic country; citizens have concerns regarding halal issues associated with EM ingredients, which are not clearly mentioned by the manufacturer. Hence, a halal-based source is suggested in the utilization of EM technology. This study presents the development and applications of EMs that are not restricted to the agriculture system.
The optimum N:P ratio of kitchen wastewater and oil-extracted fermented soybean water for cultivation of Spirulina platensis: pigment content and biomass production.

The optimum N: P ratio of kitchen wastewater (Kw) and oil-extracted fermented soybean water (Sw) for cultivation of S. platensis (Nordstedt) Geiteler was evaluated. A Complete Randomized Design (CRD) was carried out with 22 treatments and 3 replicates: Zarrouk media (Zm), 10 dilutions of Kw and 11 dilutions of Sw. The water quality, biomass production and pigment content of S. platensis were determined every 5 days for a period of 15 days. The chemical properties of cultivated wastewater had pH 6.84-9.50. The optimum levels of N: P ratio (N: P ∼ 6: 1) for algal cultured in the 5% Sw and Zm, with biomass production of 0.90 gL -1 and 0.84 g L -1 (dry weight), respectively. The highest levels of β-carotene and C-phycocyanin of S. platensis, when cultured in 10%Sw with the optimum N: P ratio (N: P~5.7: 1.0), were achieved 0.37 mg g -1 and 21.27 mg g -1 , respectively. Implications for using S. platensis for β -carotene and C-phycocyanin production when cultured with 10% Sw are discussed.
Adropin as a potential mediator of the metabolic system‐autonomic nervous system‐chronobiology axis: Implementing a personalized signature‐based platform for chronotherapy

Adropin is a peptide hormone, which plays a role in energy homeostasis and controls glucose and fatty acid metabolism. Its levels correlate with changes in carbohydrate‐lipid metabolism, metabolic diseases, central nervous system function, endothelial function and cardiovascular disease. Both metabolic pathways and adropin are regulated by the circadian clocks. Here, we review the roles of the autonomic nervous system and circadian rhythms in regulating metabolic pathways and energy homeostasis. The beneficial effects of chronotherapy in various systems are discussed. We suggest a potential role for adropin as a mediator of the metabolic system‐autonomic nervous system axis. We discuss the possibility of establishing an individualized adropin and circadian rhythm‐based platform for implementing chronotherapy, and variability signatures for improving the efficacy of adropin‐based therapies are discussed.
A sensorimotor model shows why a spectral jamming avoidance response does not help bats deal with jamming

For decades, researchers have speculated how echolocating bats deal with masking by conspecific calls when flying in aggregations. To date, only a few attempts have been made to mathematically quantify the probability of jamming, or its effects. We developed a comprehensive sensorimotor predator-prey simulation, modeling numerous bats foraging in proximity. We used this model to examine the effectiveness of a spectral Jamming Avoidance Response (JAR) as a solution for the masking problem. We found that foraging performance deteriorates when bats forage near conspecifics, however, applying a JAR does not improve insect sensing or capture. Because bats constantly adjust their echolocation to the performed task (even when flying alone), further shifting the signals' frequencies does not mitigate jamming. Our simulations explain how bats can hunt successfully in a group despite competition and despite potential masking. This research demonstrates the advantages of a modeling approach when examining a complex biological system.
Bayesian optimality of testing procedures for survival data

Most statistical tests for treatment effects used in randomized clinical trials with survival outcomes are based on the proportional hazards assumption, which often fails in practice. Data from early exploratory studies may provide evidence of non-proportional hazards which can guide the choice of alternative tests in the design of practice-changing confirmatory trials. We study a test to detect treatment effects in a late-stage trial which accounts for the deviations from proportional hazards suggested by early-stage data. Conditional on early-stage data, among all tests which control the frequentist Type I error rate at a fixed $\alpha$ level, our testing procedure maximizes the Bayesian prediction of the finite-sample power. Hence, the proposed test provides a useful benchmark for other tests commonly used in presence of non-proportional hazards, for example weighted log-rank tests. We illustrate the approach in a simulations based on data from a published cancer immunotherapy phase III trial.
“Calm Down,” “Cheer Up”: How Age Influences the Way We Manage Emotion in Social Partners

This study examines how individuals (regulators) manage emotion in their social partners (targets) and whether the age of the regulator or the age of the target influences extrinsic emotion regulation strategy preference. An online questionnaire was used to assess extrinsic emotion regulation among 580 participants aged 18–87 years (M = 50.04, SD = 18.13). Participants (regulators) indicated the extent to which they would be likely to use different strategies when interacting with a younger or older target who was upset. Results of multi-level modeling showed that older regulators endorsed less use of situation modification than younger regulators, but age differences in regulators’ use of other strategies were not significant. After adjustment for relationship-specific covariates, regulators endorsed less use of attentional deployment and cognitive change, for older targets than younger targets. Results are discussed in the context of lifespan perspectives on social behavior and emotion regulation.
Frontline therapy for newly diagnosed patients with multiple myeloma

Since the introduction of an alkylator to the treatment of multiple myeloma (MM), new effective agents have been developed, such as immunomodulatory drugs including thalidomide, lenalidomide, and pomalidomide; proteasome inhibitors including bortezomib, carfilzomib, and ixazomib; monoclonal antibodies including daratumumab and elotuzumab; and deacetylase inhibitors including panobinostat. Numerous regimens with these new agents have been developed and they have contributed in improving survival outcomes in MM patients. In addition, the recommended therapies for newly diagnosed MM change every year based on the results of clinical trials. This review will discusses the appropriate induction therapies based on recent clinical trials for patients with newly diagnosed MM.
OPTIMIZATION OF SHAPE OF CONVERGENT-DIVERGENT NOZZLES BY USING IMPROVED SIMPLE GENETIC ALGORITHMS

Genetic Algorithms (GAs) have initiated a new scheme for solution of the complicated optimization problems. Here a genetic algorithm is developed for optimization of the convergent-divergent nozzles. First, a popular numerical method is chosen for solving the fluid dynamic problem. Then, optimization criterion and evaluation parameters (such as maximum thrust force) are determined. After introduction of the simple genetic algorithm, parameters of this method such as crossover probability, mutation probability and population size in each generation are used for optimization of the algorithm. After independent verification of the computational fluid dynamic scheme and the genetic algorithm, these two are integrated, and using different values for the above parameters, performance of the optimization algorithm for shape optimization of a nozzle is studied. Finally an optimum range of GA parameters are found, and are used to find optimum shape by less than 0.1% exhaustive search CPU time.
Unique Needs for the Implementation of Emergency Department Human Immunodeficiency Virus Screening in Adolescents

The Centers for Disease Control and Prevention (CDC) recommend universal human immunodeficiency virus (HIV) screening starting at 13 years, which has been implemented in many general U.S. emergency departments (EDs) but infrequently in pediatric EDs. We aimed to 1) implement a pilot of routine adolescent HIV screening in a pediatric ED and 2) determine the unique barriers to CDC‐recommended screening in this region of high HIV prevalence.
Multiple novel non-canonically transcribed sub-genomic mRNAs produced by avian coronavirus infectious bronchitis virus

Coronavirus sub-genomic mRNA (sgmRNA) synthesis occurs via a process of discontinuous transcription involving complementary transcription regulatory sequences (TRSs), one (TRS-L) encompassing the leader sequence of the 5′ untranslated region (UTR), and the other upstream of each structural and accessory gene (TRS-B). Several coronaviruses have an ORF located between the N gene and the 3′-UTR, an area previously thought to be non-coding in the Gammacoronavirus infectious bronchitis virus (IBV) due to a lack of a canonical TRS-B. Here, we identify a non-canonical TRS-B allowing for a novel sgmRNA relating to this ORF to be produced in several strains of IBV: Beaudette, CR88, H120, D1466, Italy-02 and QX. Interestingly, the potential protein produced by this ORF is prematurely truncated in the Beaudette strain. A single nucleotide deletion was made in the Beaudette strain allowing for the generation of a recombinant IBV (rIBV) that had the potential to express a full-length protein. Assessment of this rIBV in vitro demonstrated that restoration of the full-length potential protein had no effect on viral replication. Further assessment of the Beaudette-derived RNA identified a second non-canonically transcribed sgmRNA located within gene 2. Deep sequencing analysis of allantoic fluid from Beaudette-infected embryonated eggs confirmed the presence of both the newly identified non-canonically transcribed sgmRNAs and highlighted the potential for further yet unidentified sgmRNAs. This HiSeq data, alongside the confirmation of non-canonically transcribed sgmRNAs, indicates the potential of the coronavirus genome to encode a larger repertoire of genes than has currently been identified.