Miracle-dz/UniFAR-FTUs huggingface dataset:
Prioritization of patient safety health policies: Delphi survey using patient safety experts in Japan

Various patient safety interventions have been implemented since the late 1990s, but their evaluation has been lacking. To obtain basic information for prioritizing patient safety interventions, this study aimed to extract high-priority interventions in Japan and to identify the factors that influence the setting of priority. Six perspectives (contribution, dissemination, impact, cost, urgency, and priority) on 42 patient safety interventions classified into 3 levels (system, organizational, and clinical) were evaluated by Japanese experts using the Delphi technique. We examined the relationships of the levels and the perspectives on interventions with the transition of the consensus state in rounds 1 and 3. After extracting the high-priority interventions, a chi-squared test was used to examine the relationship of the levels and the impact/cost ratio with high priority. Regression models were used to examine the influence of each perspective on priority. There was a significant relationship between the level of interventions and the transition of the consensus state (p = 0.033). System-level interventions had a low probability of achieving consensus. “Human resources interventions,” “professional education and training,” “medication management/reconciliation protocols,” “pay-for performance (P4P) schemes and financing for safety,” “digital technology solutions to improve safety,” and “hand hygiene initiatives” were extracted as high-priority interventions. The level and the impact/cost ratio of interventions had no significant relationships with high priority. In the regression model, dissemination and impact had an influence on priority (β = -0.628 and 0.941, respectively; adjusted R-squared = 0.646). The influence of impact and dissemination on the priority of interventions suggests that it is important to examine the dissemination degree and impact of interventions in each country for prioritizing interventions.
An Overview of Privileged Scaffold: Quinolines and Isoquinolines in Medicinal Chemistry as Anticancer Agents.

Cancer is one of the most difficult diseases and causes of death for many decades. Many pieces of research are continuously going on to get a solution for cancer. Quinoline and isoquinoline derivatives have shown their possibilities to work as an antitumor agent in anticancer treatment. The members of this privilege scaffold quinoline and isoquinoline have shown their controlling impacts in cancer treatment through various modes. In particular, this review suggests the current scenario of quinoline and isoquinoline derivatives as antitumor agents and refine the path of these derivatives to find and develop new drugs against an evil known as cancer.
Apoaequorin differentially modulates fear memory in adult and aged rats

Cognitive deficits during aging are pervasive across species and learning paradigms. One of the major mechanisms thought to play a role in age‐related memory decline is dysregulated calcium (Ca2+) homeostasis. Aging is associated with impaired function of several calcium‐regulatory mechanisms, including calcium‐binding proteins that normally support intracellular Ca2+ regulation. This age‐related calcium‐binding protein dysfunction and changes in expression lead to disrupted maintenance of intracellular Ca2+, thus contributing to memory decline. Other work has found that age‐related cognitive deficits can be mitigated by either blocking Ca2+ entry into the cytosol or preventing its release from intracellular Ca2+ stores. However, the effect of calcium‐binding protein administration on cognitive function during aging is not well‐understood. Our laboratory has previously shown that the calcium‐binding protein apoaequorin (AQ) is neuroprotective during oxygen–glucose deprivation, a model of in vitro ischemia characterized by calcium‐induced excitotoxicity. The current experiments assessed the effect of direct dorsal hippocampal AQ infusion on trace and context fear memory in adult and aged rats.
Experimentally induced intrasexual mating competition and sex‐specific evolution in female and male nematodes

Sexual dimorphism in life history traits and their trade‐offs is widespread among sexually reproducing animals and is strongly influenced by the differences in reproductive strategies between the sexes. We investigated how intrasexual competition influenced specific life history traits, important to fitness and their trade‐offs in the outcrossing nematode Caenorhabditis remanei. Here, we altered the strength of sex‐specific selection through experimental evolution with increased potential for intrasexual competition by skewing the adult sex ratio towards either females or males (1:10 or 10:1) over 30 generations and subsequently measured the phenotypic response to selection in three traits related to fitness: body size, fecundity and tolerance to heat stress. We observed a greater evolutionary change in females than males for body size and peak fitness, suggesting that females may experience stronger net selection and potentially harbour higher amounts of standing genetic variance compared to males. Our study highlights the importance of investigating direct and indirect effects of intrasexual competition in both sexes in order to capture sex‐specific responses and understand the evolution of sexual dimorphism in traits expressed by both sexes.
Warp Speed for Coronavirus Disease 2019 (COVID-19) Vaccines: Why Are Children Stuck in Neutral?

Abstract While adult clinical trials of coronavirus disease 2019 (COVID-19) vaccines have moved quickly into phase 3 clinical trials, clinical trials have not started in children in the United States. The direct COVID-19 impact upon children is greater than that observed for a number of other pathogens for which we now have effective pediatric vaccines. Additionally, the role of children in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has clearly been underappreciated. Carefully conducted phase 2 clinical trials can adequately address potential COVID-19 vaccine safety concerns. Delaying phase 2 vaccine clinical trials in children will delay our recovery from COVID-19 and unnecessarily prolong its impact upon children’s education, health, and emotional well-being, and equitable access to opportunities for development and social success. Given the potential direct and indirect benefits of pediatric vaccination, implementation of phase 2 clinical trials for COVID-19 vaccines should begin now.
General and gender-specific dynamics determining the health status of employed family caregivers

ABSTRACT We examined whether gender plays a role in how financial strain moderates the relationship between health status and objective burden among employed family caregivers. Using data from “Caregiving in the U.S., 2015,” the sample included 704 employed caregivers (311 males and 393 females) of adults 50 years of age and older. The relationship between objective caregiver burden and self-reported health was moderated by financial strain in the full sample. However, in separate analyses by gender, this moderated relationship was limited to females. Findings inform interventions to improve caregiver health while accounting for the financial strain experienced by women in particular.
Association between doppler snuffbox resistive index and tissue perfusion in septic patients.

BACKGROUND Peripheral vascular disorders leading to tissue hypoperfusion play a central role in the pathophysiology of organ failure in septic shock. The Doppler snuffbox resistive index (SBRI) can be an accurate parameter to evaluate the status of peripheral vasculature at the bedside. We evaluated whether the SBRI is related to lactate levels or the peripheral perfusion index (PI) and its ability to predict lactate clearance in septic patients. METHODS We conducted a prospective observational study in a tertiary general and teaching hospital in China. From July 2019 to December 2019, all consecutive adult patients with septic shock who required ICU admission were included. At the same time, twenty stable postoperative patients were studied as a control group. We recorded the haemodynamic parameters, including the SBRI and PI, which were measured simultaneously after patient recruitment. RESULTS We evaluated 44 patients with septic shock in the study group and 20 stable postoperative patients in the control group. Patients with septic shock had higher Sequential Organ Failure Assessment scores, procalcitonin levels, cardiac index (CI) and lactate levels than patients in the control group. The SBRI was correlated with the PI and lactate level. The CI was not correlated with lactate level in the patients examined. Based on lactate clearance in the first 6 hours, the septic shock patients were divided into two groups: one with lactate clearance ≥20% (n = 28) and the other with lactate clearance <20% (n = 16). The CI was not significantly different between the two groups. The SBRI of the lactate clearance <20% group was higher than that of the lactate clearance ≥20% group and the control group. The PI of the lactate clearance <20% group was lower than that of the lactate clearance ≥20% group and the control group. The SBRI cutoff value for predicting 6-h lactate clearance after resuscitation was ≥1.09, with a sensitivity of 68.8% and a specificity of 85.7%. The PI cutoff value for predicting 6-h lactate clearance after resuscitation was ≤0.99, with a sensitivity of 64.3% and a specificity of 81.2%. The SBRI was significantly better than the PI for predicting 6-h lactate clearance after resuscitation [area under the curve (AUC): 0.805 vs. 0.703, P < 0.05]. CONCLUSIONS The Doppler SBRI is correlated with tissue perfusion parameters in critically ill patients. An abnormal SBRI may be better than the PI for predicting poor lactate clearance in septic patients. Further investigations are required to determine whether correcting an abnormal SBRI and PI may improve the success rate of septic shock resuscitation.
Synthesis of Resolvin E3, a Proresolving Lipid Mediator, and Its Deoxy Derivatives: Identification of 18-Deoxy-resolvin E3 as a Potent Anti-inflammatory Agent.

We synthesized RvE3 and its deoxy derivatives, 17-deoxy-RvE3 and 18-deoxy-RvE3, by a common route via Sonogashira coupling as a key step. Evaluation of their anti-inflammatory activities revealed that 18-deoxy-RvE3 was remarkably more potent than parent RvE3 and was significantly active at a 300 fg dose in mice, additionally 17-deoxy-RvE3 was significantly less potent than the parent RvE3. For the first time, we found that the 17-hydroxy group of RvE3 is very important for anti-inflammatory activity.
The Neutrophil to Lymphocyte Ratio (NLR) Is Associated With Residual Syntax Score in Patients With ST-Segment Elevation Myocardial Infarction

The neutrophil to lymphocyte ratio (NLR) predicts adverse clinical outcomes in several cardiovascular diseases. Our aim was to investigate the association of residual SYNTAX score (rSS) with the NLR in patients (n = 613) with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Patients were divided into 2 groups: group 1 with low NLR (<2.59) and group 2 with high NLR (>2.59). Coronary artery disease severity was calculated for both groups besides baseline clinical and demographic variables. Receiver operating characteristic curve analysis demonstrated that NLR with a cutoff value of 2.59 had good predictive value for increased rSS (area under the curve = 0.707, 95% CI: 0.661-0.752, P < .001). The median rSS value of group 2 was higher (2.0 [0-6.0]; 4.0 [0-10.0], P < .001) compared with group 1; the number of patients with high rSS was also higher in group 2 (26 [9.7%]; 107 [31.0%], P < .001). In multivariate logistic regression analysis, the NLR (odds ratio = 3.933; 95% CI: 2.419-6.393; P < .001) was an independent predictor of high rSS. Additionally, there was a positive correlation between NLR and rSS (r = 0.216, P < .001). In conclusion, higher NLR was an independent predictor of increased rSS in patients with STEMI.
POPULATION DYNAMICS OF COTTON APHIDS ON COTTON DURING SQUARE-BOLL STAGE AND THE RELATION BETWEEN POPULATION AGE STRUCTURE AND PARASITIZATION

The population dynamics of cotton aphid Aphis gossypii on cotton in Sheshan region (Shanghai suburb) in summer of 1983 is described. From early July to early Septemper when the cotton was in the square-boll stage the aphid population grew into a size about 10 times that in the same period of the previous year and the density peaked to about 6.3 thousand per plant. The tendency of population growth is shown in Fig. 1. The change of age Structure in "the population was investigated. It was revealed that the decline in percentage of the first instar nymphs was caused by the reduction of birth pate and the decline in percentage of the second instar nymphs in population of high density was due to the increased mortality of the first instar nymphs. As time went on the percentages of the third and fourth instar nymphs would rise in groups of different population densities. Finally the percentage of adults would rise in groups of low density but would decrease in groups of high density because of the emigration of the winged forms which appeared there in a higher proportion.The change of age structure in aphid populations bore an intimate relation to the percentage of parasitizatiou by Trioxys spp. and Aphelinus sp. The first and second instar nymphs were rarely parasitized; therefore, the percentage of parasitization would rise when the proportion of young instar nymphs decreased. The percentage of parasi-tization differed with aphid densities on the leaves but not with the position of the leaves-on the plants.
Supplementation Effect of a Combination of Olive (Olea europea L.) Leaf and Fruit Extracts in the Clinical Management of Hypertension and Metabolic Syndrome

Background: The role of herbal products in the prevention of cardiovascular disease requires supporting evidence. This open pilot study assessed the effect of 2-month supplementation of a combination of olive leaf and fruit extracts (Tensiofytol®, Tilman SA, Baillonville, Belgium) in the clinical management of hypertension and metabolic syndrome (MetS). Methods: A total of 663 (pre)-hypertensive patients were enrolled by general practitioners and supplemented for two months with Tensiofytol®, two capsules per day (100 mg/d of oleuropein and 20 mg/d of hydroxytyrosol). Systolic and diastolic blood pressures (SBP/DBP) were measured before and after treatment. Markers of MetS, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), fasting blood glucose (FG) and waist circumference (WC), were also examined. Results: Significant reductions (p < 0.0001) in SBP/DBP (13 ± 10/7.1 ± 6.6 mmHg) were observed and similarly in pre-diabetic and diabetic patients. Improvements in SBP/DPB were independent of age and gender but greater for elevated baseline SBP/DBP. Tensiofytol® supplementation also significantly improved markers of MetS, with a decrease of TG (11%), WC (1.4%) and FG (4.8%) and an increase of HDL-C (5.3%). Minor side effects were reported in 3.2% patients. Conclusions: This real-life, observational, non-controlled, non-randomized pilot study shows that supplementation of a combination of olive leaf and fruit extracts may be used efficiently and safely in reducing hypertension and MetS markers.
Real-world utilization and outcomes of the Veterans Health Administration's smoking cessation text message program.

INTRODUCTION Smoking cessation mobile health (mHealth) programs are effective and have been recommended for integration into health care services but have not been evaluated in real-world health care settings. The Veterans Health Administration (VHA), a safety net health care provider, provides health care for 9 million U.S. military veterans. VHA implemented the SmokefreeVET text message program in 2013. METHODS A retrospective evaluation of 6,153 SmokefreeVET subscribers was conducted. The primary outcome was 30-day self-reported abstinence at 6 months. Secondary outcomes included percentage of opt outs, program completers, and 30-day self-reported abstinence at 3 months. RESULTS SmokefreeVET subscribers were on average 47.5 years old and 71.4% male. Smoking cessation medication use was reported by 11.5% of subscribers at the start of their quit attempt and subscribers enrolled in the program for an average of 29 days. Subscribers who were younger, female, and heavier smokers were more likely to opt out of the six-week program early. The abstinence rate for the primary outcome, self-reported 30-day abstinence at 6 months among all subscribers was 3.7%. CONCLUSIONS SmokefreeVET enrolled a younger and more female population of subscribers than other studies of veterans interested in tobacco treatment. The mHealth program was generally acceptable to veterans, yet strategies to increase retention may improve completion rates and outcomes. In this real-world setting, nearly half of the mHealth program subscribers combined use of the text program with smoking cessation medication. Further study of the optimal combination of mHealth with smoking cessation treatments is needed. IMPLICATIONS mHealth smoking cessation programs can be effectively implemented within real-world health care settings, even in those serving disadvantaged populations. Further research to improve mHealth program efficacy and integration into clinical settings will increase the population-level impact of these effective smoking cessation programs.
Impact of COVID-2019 outbreak on prevalence, clinical presentation and outcomes of ST-elevation myocardial infarction

Aims The aim of this study was to report the prevalence, clinical features and outcomes of patients with ST-elevation myocardial infarction (STEMI) hospitalized during the Corona-Virus Disease 2019 (COVID-19) outbreak compared with those admitted in a previous equivalent period. Methods and results Eighty-five patients admitted for STEMI at a high-volume Italian centre were included. Patients hospitalized during the COVID-19 outbreak (21 February–10 April 2020) (40%) were compared with those admitted in pre-COVID-19 period (3 January–20 February 2020) (60%). A 43% reduction in STEMI admissions was observed during the COVID-19 outbreak compared with the previous period. Time from symptom onset to first medical contact (FMC) and time from FMC to primary percutaneous coronary intervention (PPCI) were longer in patients admitted during the COVID-19 period compared with before [148 (79–781) versus 130 (30–185) min; P = 0.018, and 75 (59–148)] versus 45 (30–70) min; P < 0.001]. High-sensitive troponin T levels on admission were also higher. In-hospital mortality was 12% in the COVID-19 phase versus 6% in the pre-COVID-19 period. Incidence of the composite end-point, including free-wall rupture, severe left ventricular dysfunction, left ventricular aneurysm, severe mitral regurgitation and pericardial effusion, was higher during the COVID-19 than the pre-COVID-19 period (19.6 versus 41.2%; P = 0.030; odds ratio = 2.87; 95% confidence interval 1.09–7.58). Conclusion The COVID-19 pandemic had a significant impact on the STEMI care system reducing hospital admissions and prolonging revascularization time. This translated into a worse patient prognosis due to more STEMI complications.
Drug-Drug Binary Solids of Nitrofurantoin and Trimethoprim: Crystal Engineering and Pharmaceutical Properties.

With the aim of developing multidrug solids through a tuned crystal engineering approach, we have selected two anti-urinary infective drugs, namely, nitrofurantoin (NF) and trimethoprim (TMP) and isolated eight binary drug-drug solid solvates along with a non-solvated cocrystal. Crystal structure analyses were performed for eight of these solids and rationalized in terms of known supramolecular synthons formed by pyrimidine, imide and amine functionalities. Notably, the TMP-NF anhydrous cocrystal and its ionic cocrystal hydrate exhibit enhanced equilibrium solubilities compared to pure NF or the simple NF hydrate. Further, the ionic cocrystal hydrate exhibits greater antibacterial activity against the Gram-negative bacteria, E. coli, compared to the parent TMP and NF at the lowest concentration of 3.9 µg/ml. This study indicates initial pathways using cocrystal methodology that would help to eventually arrive at an anti-urinary cocrystal with optimal properties.
Different Sources of Allelic Variation Drove Repeated Color Pattern Divergence in Cichlid Fishes

Abstract The adaptive radiations of East African cichlid fish in the Great Lakes Victoria, Malawi, and Tanganyika are well known for their diversity and repeatedly evolved phenotypes. Convergent evolution of melanic horizontal stripes has been linked to a single locus harboring the gene agouti-related peptide 2 (agrp2). However, where and when the causal variants underlying this trait evolved and how they drove phenotypic divergence remained unknown. To test the alternative hypotheses of standing genetic variation versus de novo mutations (independently originating in each radiation), we searched for shared signals of genomic divergence at the agrp2 locus. Although we discovered similar signatures of differentiation at the locus level, the haplotypes associated with stripe patterns are surprisingly different. In Lake Malawi, the highest associated alleles are located within and close to the 5′ untranslated region of agrp2 and likely evolved through recent de novo mutations. In the younger Lake Victoria radiation, stripes are associated with two intronic regions overlapping with a previously reported cis-regulatory interval. The origin of these segregating haplotypes predates the Lake Victoria radiation because they are also found in more basal riverine and Lake Kivu species. This suggests that both segregating haplotypes were present as standing genetic variation at the onset of the Lake Victoria adaptive radiation with its more than 500 species and drove phenotypic divergence within the species flock. Therefore, both new (Lake Malawi) and ancient (Lake Victoria) allelic variation at the same locus fueled rapid and convergent phenotypic evolution.
Global reprogramming of virulence and antibiotic resistance in Pseudomonas aeruginosa by a single nucleotide polymorphism in elongation factor, fusA1

Clinical isolates of the opportunistic pathogen Pseudomonas aeruginosa from patients with cystic fibrosis (CF) frequently contain mutations in the gene encoding an elongation factor, FusA1. Recent work has shown that fusA1 mutants often display elevated aminoglycoside resistance due to increased expression of the efflux pump, MexXY. However, we wondered whether these mutants might also be affected in other virulence-associated phenotypes. Here, we isolated a spontaneous gentamicin-resistant fusA1 mutant (FusA1P443L) in which mexXY expression was increased. Proteomic and transcriptomic analyses revealed that the fusA1 mutant also exhibited discrete changes in the expression of key pathogenicity-associated genes. Most notably, the fusA1 mutant displayed greatly increased expression of the Type III secretion system (T3SS), widely considered to be the most potent virulence factor in the P. aeruginosa arsenal, and also elevated expression of the Type VI (T6) secretion machinery. This was unexpected because expression of the T3SS is usually reciprocally coordinated with T6 secretion system expression. The fusA1 mutant also displayed elevated exopolysaccharide production, dysregulated siderophore production, elevated ribosome synthesis, and transcriptomic signatures indicative of translational stress. Each of these phenotypes (and almost all of the transcriptomic and proteomic changes associated with the fusA1 mutation) were restored to levels comparable with that in the progenitor strain by expression of the WT fusA1 gene in trans, indicating that the mutant gene is recessive. Our data show that in addition to elevating antibiotic resistance through mexXY expression (and also additional contributory resistance mechanisms), mutations in fusA1 can lead to highly selective dysregulation of virulence gene expression.