Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental design, formulation and in vivo evaluation of a novel topical in situ gel system to treat ocular infections

In situ gels have been extensively explored as ocular drug delivery system to enhance bioavailability and efficacy. The objective of present study was to design, formulate and evaluate ion-activated in situ gel to enhance the ocular penetration and therapeutic performance of moxifloxacin in ophthalmic delivery. A simplex lattice design was utilized to examine the effect of various factors on experimental outcomes of the in situ gel system. The influence of polymers (independent variables) such as gellan gum (X1), sodium alginate (X2), and HPMC (X3) on gel strength, adhesive force, viscosity and drug release after 10 h (Q10) were assessed. Selected formulation (MH7) was studied for ex vivo permeation, in vivo irritation and pharmacokinetics in rabbits. Data revealed that increase in concentration of polymers led to higher gel strength, adhesive force and viscosity, however, decreases the drug release. MH7 exhibited all physicochemical properties within acceptable limits and was stable for 6 months. Release profile of moxifloxacin from MH7 was comparable to the check point batches and followed Korsmeyer-Peppas matrix diffusion-controlled mechanism. Ocular irritation study signifies that selected formulation is safe and non-irritant for ophthalmic administration. In vivo pharmacokinetics data indicates significant improvement of moxifloxacin bioavailability (p < 0.0001) from MH7, as evidenced by higher Cmax (727 ± 56 ng/ml) and greater AUC (2881 ± 108 ng h/ml), when compared with commercial eye drops (Cmax; 503 ± 85 ng/ml and AUC; 978 ± 86 ng h/ml). In conclusion, developed in situ gel system (MH7) could offers a more effective and extended ophthalmic therapy of moxifloxacin in ocular infections when compared to conventional eye drops.
Development of a rapid and sensitive analytical system for Pseudomonas aeruginosa based on reverse transcription quantitative PCR targeting of rRNA molecules

ABSTRACT For Pseudomonas aeruginosa (PA), infection control and appropriate antimicrobial treatment have become important issues. Diagnosis is critical in managing PA infection, but conventional methods are not highly accurate or rapid. We developed a new PA quantification system based on 23S rRNA-targeted reverse transcription quantitative PCR (RT-qPCR). We confirmed that RT-qPCR can quantify PA directly from clinical samples quickly (within 6 h) and with high sensitivity (blood, 1 cell/mL; stool, 100 cells/g) and without cross-reaction. Also, under antibiotic treatment, PA viable counts detected by this system correlated well with the inflammatory response of infected Caco-2 cells compared to other methods such as culturing and qPCR. Next, we utilized this system on fecal samples collected from 65 septic ICU patients and 44 healthy volunteers to identify ICU infection status. We confirmed that the PA detection ratio in ICU patients was significantly higher than that in healthy volunteers (49.2% vs. 13.6%, P < 0.05). Additionally, we monitored drug-resistant PA in 4 ICU patients by this system. The trends in PA counts accurately reflected various treatment backgrounds such as antibiotic use and mechanical ventilator use. Our results suggest that this RT-qPCR system is beneficial for the early diagnosis and evaluation of appropriate antibacterial treatment and may be a useful tool in combating PA infection.
Multihazards Scenario Generator: A Network‐Based Simulation of Natural Disasters

The impact of natural disasters has been increasing in recent years. Despite the developing international interest in multihazard events, few studies quantify the dynamic interactions that characterize these phenomena. It is argued that without considering the dynamic complexity of natural catastrophes, impact assessments will underestimate risk and misinform emergency management priorities. The ability to generate multihazard scenarios with impacts at a desired level is important for emergency planning and resilience assessment. This article demonstrates a framework for using graph theory and networks to generate and model the complex impacts of multihazard scenarios. First, the combination of maximal hazard footprints and exposed nodes (e.g., infrastructure) is used to create the hazard network. Iterative simulation of the network, defined by actual hazard magnitudes, is then used to provide the overall compounded impact from a sequence of hazards. Outputs of the method are used to study distributional ranges of multihazards impact. The 2016 Kaikōura earthquake is used as a calibrating event to demonstrate that the method can reproduce the same scale of impacts as a real event. The cascading hazards included numerous landslides, allowing us to show that the scenario set generated includes the actual impacts that occurred during the 2016 events.
Psychosocial effects of social media on the Saudi society during the Coronavirus Disease 2019 pandemic: A cross-sectional study

The Coronavirus Disease 2019 (COVID-19) pandemic has been posing a substantial challenge to human survival and well-being, which rely on the actions and behaviors of individuals. It is essential that accurate information is distributed; however, misinformation has been spread via social media. Consequently, the resulting panic has to be addressed while putting essential public health measures in place. It is also important to explore the link between the social media exposure and well-being. Therefore, in the current study, we aimed to identify the levels of anxiety, depression, and social isolation among individuals during the COVID-19 pandemic. Additionally, we explored the relationship between exposure to misleading social media news and anxiety, depression, and social isolation. A cross sectional design was employed to collect data from 371 Saudi participants (aged 16–60 years), using the Generalized Anxiety Disorder-7, Centre for Epidemiological Studies Depression Scale, and de Jong Gierveld Loneliness Scale. Results showed that the prevalence of anxiety, depression, and social isolation was 47.82%, 47.57%, and 46.42%, respectively. Further, more than 83% of the participants reported using social media frequently during the pandemic. We found that exposure to misinformation via social media has a significant positive relationship with anxiety, depression, and social isolation. However, Due to the cross-sectional nature of this study it cannot be determined whether social media causes negative mental health outcomes, or if individuals experiencing greater depression, anxiety and social isolation turn to social media more than others, or if some third variable might explain both. Based on our findings, we present specific suggestions related to the COVID-19 pandemic to the government of Saudi Arabia. Minoring and filtering out misleading information with the cooperation of the World Health Organization (WHO) can promote the spread of accurate news in Saudi Arabia.
Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial

PURPOSE Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years. RESULTS There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years. CONCLUSION Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.
Estimating the basic reproduction number for COVID-19 in Western Europe

Objective To estimate the basic reproduction number (R0) for COVID-19 in Western Europe. Methods Data (official statistics) on the cumulative incidence of COVID-19 at the start of the outbreak (before any confinement rules were declared) were retrieved in the 15 largest countries in Western Europe, allowing us to estimate the exponential growth rate of the disease. The rate was then combined with estimates of the distribution of the generation interval as reconstructed from the literature. Results Despite the possible unreliability of some official statistics about COVID-19, the spread of the disease appears to be remarkably similar in most European countries, allowing us to estimate an average R0 in Western Europe of 2.2 (95% CI: 1.9–2.6). Conclusions The value of R0 for COVID-19 in Western Europe appears to be significantly lower than that in China. The proportion of immune persons in the European population required to stop the outbreak could thus be closer to 50% than to 70%.
Climbing the Activity Volcano: Core–Shell Ru@Pt Electrocatalysts for Oxygen Reduction

We outline a systematic approach to develop active catalyst materials for an electrochemical reaction. The strategy allows one to tune binding energies of oxygen reaction intermediates on a catalyst surface by taking advantage of two effects: weakening oxygen binding energies by means of thin-film overlayers, and strengthening oxygen binding energies through nanoscale effects. By engineering a core–shell nanoparticle morphology with the appropriate dimensions, that is, the thickness of the overlayer and the size of the nanoparticle, bonding properties can be modified to improve the catalytic activity of the core–shell system. We demonstrate the application of this strategy for oxygen reduction by identifying Ru@Pt as a candidate material using density functional theory calculations, and then use these calculations to guide the synthesis of active Ru@Pt core–shell catalysts. The Ru@Pt particles, synthesized using a wet chemical method, exhibit ∼2 times higher specific activity (based on electrochemical active surface area) than state-of-the-art Pt/C from TKK.
Foliar application of iron for recovering groundnut plants from lime-induced iron deficiency chlorosis and accompanying losses in yields

Abstract A field experiment was conducted at 2‐year interval to determine the optimum time, number of foliar sprays for applying water‐soluble iron fertilizers and chelates, and the relative efficiencies of four different sources of iron for recovery of groundnut (Arachis hypogaea L.) plants from iron‐deficiency chlorosis for plants grown on a calcareous soil. Severe interveinal to complete leaf chlorosis was observed in 38–42% of the population during 30–60 days after emergence (DAE). Foliar applications of iron at 2 kg/ha in the form of 0.1% aqueous solution helped plants recover from chlorosis. However, no significant differences were found among the four iron sources [iron sulphate, iron sulphate+citric acid (400 g/ha), iron citrate, and Fe‐EDTA] with an average recovery of 46, 49, 47, and 46%, respectively. The maximum increase (16 to 24%) in pod yield was obtained when iron sulphate+citric acid was the iron source, while yield increases were 13 to 19, 12 to 18, and 11 to 18% over the control when ir.
Mobile health technologies supporting colonoscopy preparation: A systematic review and meta-analysis of randomized controlled trials

Background Mobile health (mHealth) technologies are innovative solutions for delivering instructions to patients preparing for colonoscopy. Objective To systematically review the literature evaluating the effectiveness of mHealth technologies supporting colonoscopy preparation on patient and clinical outcomes. Methods MEDLINE, EMBASE, CINAHL and CENTRAL were searched for randomized controlled trials (RCTs) that evaluated the effectiveness of mHealth technologies for colonoscopy preparation on patient and clinical outcomes. Two reviewers independently assessed study eligibility, extracted data, and appraised methodological quality using the Cochrane Risk-of-Bias tool. Data were pooled using random effects models and when heterogeneity, assessed using I2, was statistically significant, a qualitative synthesis of the data was performed. Publication bias was assessed using a funnel plot. Results Ten RCTs (3,383 participants) met inclusion criteria. MHealth interventions included smartphone apps, SMS text messages, videos, camera apps, and a social media app. Outcomes were bowel cleanliness quality, user satisfaction, colonoscopy quality indicators (cecal intubation time, withdrawal time, adenoma detection rate), adherence to diet, and cancellation/no-show rates. MHealth interventions were associated with better bowel cleanliness scores on the Boston Bowel Preparation Scale [standardized mean difference (SMD) 0.57, 95%CI 0.37–0.77, I2 = 60%, p = 0.08] and the Ottawa Bowel Preparation Scale [SMD -0.39, 95%CI -0.59–0.19, I2 = 45%, p = 0.16], but they were not associated with rates of willingness to repeat the colonoscopy using the same regimen [odds ratio (OR) 1.88, 95%CI 0.85–4.15, I2 = 48%, p = 0.12] or cancellations/no-shows [OR 0.96, 95%CI 0.68–1.35, I2 = 0%]. Most studies showed that adequate bowel preparation, user satisfaction and adherence to diet were better in the intervention groups compared to the control groups, while inconsistent findings were observed for the colonoscopy quality indicators. All trials were at high risk of bias for lack of participant blinding. Visual inspection of a funnel plot revealed publication bias. Conclusions MHealth technologies show promise as a way to improve bowel cleanliness, but trials to date were of low methodological quality. High-quality research is required to understand the effectiveness of mHealth technologies on colonoscopy outcomes.
Review of methods for the detection of Lawsonia intracellularis infection in pigs

Lawsonia intracellularis is an obligate intracellular bacterium associated with enteric disease in pigs. Clinical signs include weight loss, diarrhea, and, in some cases, sudden death. The hallmark lesion is the thickening of the intestinal mucosa caused by increased epithelial cell replication, known as proliferative enteropathy. The immune response to L. intracellularis is not well defined, and detection of the infection, especially in the early stages, is still a significant challenge. We review here the main approaches used to identify this important but poorly understood pathogen. Detection of L. intracellularis infection as the cause of clinical disease is confounded by the high prevalence of the pathogen in many countries and that several other pathogens can produce similar clinical signs. A single L. intracellularis–specific ELISA and several amplification assays are available commercially to aid detection and surveillance, although histopathology remains the primary way to reach a conclusive diagnosis. There are major gaps in our understanding of L. intracellularis pathogenesis, especially how the host responds to infection and the factors that drive infection toward different clinical outcomes. Knowledge of pathogenesis will increase the predictive value of antemortem tests to guide appropriate interventions, including identification and treatment of subclinically affected pigs in the early stages of disease, given that this important manifestation reduces pig productivity and contributes to the economic burden of L. intracellularis worldwide.
Enfortumab Vedotin: Nursing Perspectives on the Management of Adverse Events in Patients With Locally Advanced or Metastatic Urothelial Carcinoma.

BACKGROUND Many patients with locally advanced or metastatic urothelial carcinoma (mUC) need additional treatment options beyond PD-1 or PD-L1 inhibitors and platinum-based chemotherapies. Enfortumab vedotin-ejfv (EV) is an antibody-drug conjugate directed at Nectin-4 that received accelerated approval for treatment of adults with locally advanced or mUC previously treated with PD-1/PD-L1 inhibitors and platinum- containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic settings. OBJECTIVES This article provides practical considerations and recommendations regarding common and potentially treatment-limiting adverse events that may arise with EV therapy. METHODS The clinical data that supported the approval of EV are reviewed, and supporting safety and management considerations are provided based on the authors' experience. FINDINGS EV therapy can be optimized through patient and caregiver education, proactive patient monitoring, early identification of adverse events, and timely intervention to alleviate symptoms.
Outcomes of a financial incentive scheme for dementia care by dementia specialist teams in acute‐care hospitals: A difference‐in‐differences analysis of a nationwide retrospective cohort study in Japan

The quality of care for dementia in acute‐care settings has been criticised. In 2016, the Japanese universal health insurance system introduced a financial incentive scheme for dementia care by dementia specialist teams in acute‐care hospitals. This study aimed to investigate the effectiveness of this financial incentive scheme on short‐term outcomes (in‐hospital mortality and 30‐day readmission).
Experimental investigation of pull-out performance of pedicle screws at different polyurethane (PU) foam densities

Pedicle bone screws are one of the most critical materials used in spinal orthopaedic operations. Screw loosening and pull-out (PO) are basic complications encountered during or after surgery. Pull-out Strength (POS) of the bone is one of the significant parameters to understand the mechanical behaviour of a screw fixed to poor quality or osteoporotic bone. This study investigates how the POS of a pedicle screw is affected by the factors of the screw diameter and the polyurethane (PU) foam density by experimental analysis. In the experiments, two different diameter (5.5 and 6.5 mm) of conical pedicle screws and five different density (0.08, 0.16, 0.24, 0.32 and 0.48 g·cm−3) PU foams were used. According to the force-displacement curves obtained from experimental results, the POS increased with the increases in screw diameter and PU foam density.
A decision-neuroscientific intervention to improve cognitive recovery after stroke

See Doogan and Leff (doi:10.1093/brain/awab169) for a scientific commentary on this article. Our neuroscientific decision add-on intervention strongly increased the amount of effective cognitive training performed by severely impaired stroke patients. These results warrant a full clinical trial to link decision-based neuroscientific interventions directly with clinical outcome.
Optimal timing of one-shot interventions for epidemic control

The interventions and outcomes in the ongoing COVID-19 pandemic are highly varied. The disease and the interventions both impose costs and harm on society. Some interventions with particularly high costs may only be implemented briefly. The design of optimal policy requires consideration of many intervention scenarios. In this paper we investigate the optimal timing of interventions that are not sustainable for a long period. Specifically, we look at at the impact of a single short-term non-repeated intervention (a “one-shot intervention”) on an epidemic and consider the impact of the intervention’s timing. To minimize the total number infected, the intervention should start close to the peak so that there is minimal rebound once the intervention is stopped. To minimise the peak prevalence, it should start earlier, leading to initial reduction and then having a rebound to the same prevalence as the pre-intervention peak rather than one very large peak. To delay infections as much as possible (as might be appropriate if we expect improved interventions or treatments to be developed), earlier interventions have clear benefit. In populations with distinct subgroups, synchronized interventions are less effective than targeting the interventions in each subcommunity separately.
Kinetics of the interaction of HO/sub 2/ and O/sub 2//sup -/ radicals with hydrogen peroxide. The Haber--Weiss reaction. [Gamma radiation]

The rates of reaction of HO/sub 2/ and O/sub 2//sup -/ with hydrogen peroxide, known as the Haber--Weiss reactions, were studied by /sup 60/Co . gamma. radiolysis as a function of pH at 23.5/sup 0/C. The numerical values for the two rate constants, k/sub HO/sub 2/+H/sub 2/O/sub 2// = (0.50 +- 0.09) M/sup -1/ s/sup -1/ and k/sub O/sub 2/-+H/sub 2/O/sub 2// = (0.13 +- 0.07) M/sup -1/ s/sup -1/, were computed from molecular oxygen yields which result from the radiation-induced chain decomposition of aqueous hydrogen peroxide solutions. The experimental results are consistent with a chain mechanism which takes into account the dissociation of HO/sub 2/ in equilibrium O/sub 2//sup -/ + H/sup +/ (pK = 4.7) and the competition between the Haber--Weiss reactions (HO/sub 2/ + H/sub 2/O/sub 2/ and O/sub 2//sup -/ + H/sub 2/O/sub 2/) and the recombination reactions of the superoxide and perhydroxyl radicals (HO/sub 2/ + HO/sub 2/ and HO/sub 2/ + O/sub 2//sup -/).
Parasites, niche modification and the host microbiome: A field survey of multiple parasites

Parasites can affect and be affected by the host's microbiome, with consequences for host susceptibility, parasite transmission, and host and parasite fitness. Yet, two aspects of the relationship between parasite infection and host microbiota remain little understood: the nature of the relationship under field conditions, and how the relationship varies among parasites. To overcome these limitations, we performed a field survey of the within‐leaf fungal community in a tall fescue population. We investigated how diversity and composition of the fungal microbiome associate with natural infection by fungal parasites with different feeding strategies. A parasite's feeding strategy affects both parasite requirements of the host environment and parasite impacts on the host environment. We hypothesized that parasites that more strongly modify niches available within a host will be associated with greater changes in microbiome diversity and composition. Parasites with a feeding strategy that creates necrotic tissue to extract resources (necrotrophs) may not only have different niche requirements, but also act as particularly strong niche modifiers. Barcoded amplicon sequencing of the fungal ITS region revealed that leaf segments symptomatic of necrotrophs had lower fungal diversity and distinct composition compared to segments that were asymptomatic or symptomatic of other parasites. There were no clear differences in fungal diversity or composition between leaf segments that were asymptomatic and segments symptomatic of other parasite feeding strategies. Our results motivate future experimental work to test how the relationship between the microbiome and parasite infection is impacted by parasite feeding strategy and highlight the potential importance of parasite traits.