Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect on Treatment Adherence of Distributing Essential Medicines at No Charge

Key Points Question Does providing a comprehensive set of essential medicines at no charge to primary care patients who have difficulty affording medicines improve treatment adherence? Findings In this randomized clinical trial of 786 primary care patients, free distribution of essential medicines vs usual access resulted in greater adherence to treatment with medicines (absolute risk difference, 11.6%). Control of type 1 and 2 diabetes was not significantly improved by free distribution of essential medicines (hemoglobin A1c, −0.38%), systolic blood pressure was reduced (−7.2 mm Hg), and low-density lipoprotein cholesterol levels were not affected (−2.3 mg/dL). Meaning Distributing essential medicines at no charge increased adherence to appropriately prescribed treatment with medicines and improved some disease-specific surrogate health outcomes.
Will We Be Ready? Preparing Psychiatric-Mental Health Nurses for Future Practice

OBJECTIVE: To review the challenges and issues facing educators as they prepare the psychiatric-mental health (PMH) nursing workforce to meet the needs of future practice. METHODS: Based on the author’s 40-plus-year career as an educator, clinician, and researcher, combined with a review of the literature, this article analyzes the current educational milieu for undergraduate, graduate, postgraduate, and continuing education of PMH nurses, including urgent educational priorities. It also offers recommendations to meet the needs of PMH nurses both in education and in clinical practice. RESULTS: PMH nursing education must evolve to provide nursing experiences in nontraditional as well as traditional clinical settings, and incorporate simulation and telehealth/digital/mobile platforms for delivery of content. Development of qualified faculty members and preceptors who represent the diversity of the American population must be addressed to adequately train PMH nurses to meet the demands of their future roles. Methods must also be created to define, teach, and evaluate PMH nurses’ clinical competencies pre- and postclinical experiences. CONCLUSIONS: PMH nursing education must evolve and transform to attract, appropriately educate and prepare students for practice, and meet the growing need for qualified practitioners as well as faculty members and preceptors.
Preimplantation Genetic Testing for Monogenic Disease of Spinal Muscular Atrophy by Multiple Displacement Amplification: 11 unaffected livebirths

Background: Preimplantation genetic testing for monogenic disease (PGT-M) has become an effective method for providing couples with the opportunity of a pregnancy with a baby free of spinal muscular atrophy (SMA). Multiple displacement amplification (MDA) overcomes the innate dilemma of very limited genetic material available for PGT-M. Objective: To evaluate the use of MDA, combined with haplotype analysis and mutation amplification, in PGT-M for families with SMA. Methods: MDA was used to amplify the whole genome from single blastomeres or trophectoderm (TE) cells. Exon 7 of the survival motor neuron gene 1 (SMN1) and eleven STRs markers flanking the SMN1 gene were incorporated into singleplex polymerase chain reaction (PCR) assays on MDA products. Results: Sixteen cycles (19 ovum pick-up cycles) of PGT-M were initiated in 12 couples. A total of 141 embryos were tested: 90 embryos were biopsied at the cleavage stage and 51 embryos were biopsied at the blastocyst stage. MDA was successful on 94.44% (85/90) of the single blastomeres and on 92.16% (47/51) of the TE cells. And the PCR efficiency were 98.4% (561/570) and 100% (182/182), respectively. In addition, the average allele drop-out (ADO) rates were 13.3% (60/392) and 9.8% (11/112), respectively. The results for SMN1 exon 7 were all matched with haplotype analysis, which allowed an accurate diagnosis of 93.62% (132/141) embryos. Twelve families had unaffected embryos available for transfer and a total of 38 embryos were transferred in 20 embryo transfer cycles. Eight transfers were successful, resulting in a clinical pregnancy rate of 40% (8/20) and an implantation rate of 28.95% (11/38). Finally, 11 healthy babies were born. Among them, 5 SMA carriers were singleton live births and 3 SMA carriers had twin births. Conclusion: Careful handling during the MDA procedure can improve subsequent PCR efficiency and reduce the ADO rate. We suggest that this protocol is reliable for increasing the accuracy of the PGT-M for SMA.
Phosphatidylserine is critical for vesicle fission during clathrin‐mediated endocytosis

Phosphatidylserine (PS), a negatively charged phospholipid present predominantly at the inner leaflet of the plasma membrane, has been widely implicated in many cellular processes including membrane trafficking. Along this line, PS has been demonstrated to be important for endocytosis, however, the involved mechanisms remain uncertain. By monitoring clathrin‐mediated endocytosis (CME) of single vesicles in mouse chromaffin cells using cell‐attached capacitance measurements that offer millisecond time resolution, we demonstrate in the present study that the fission‐pore duration is reduced by PS addition, indicating a stimulatory role of PS in regulating the dynamics of vesicle fission during CME. Furthermore, our results show that the PS‐mediated effect on the fission‐pore duration is Ca2+‐dependent and abolished in the absence of synaptotagmin 1 (Syt1), implying that Syt1 is necessary for the stimulatory role of PS in vesicle fission during CME. Consistently, a Syt1 mutant with a defective PS–Syt1 interaction increases the fission‐pore duration. Taken together, our study suggests that PS–Syt1 interaction may be critical in regulating fission dynamics during CME.
Quantification of visits of wild fauna to a commercial free‐range layer farm in the Netherlands located in an avian influenza hot‐spot area assessed by video‐camera monitoring

Abstract Free‐range poultry farms have a high risk of introduction of avian influenza viruses (AIV), and it is presumed that wild (water) birds are the source of introduction. There is very scarce quantitative data on wild fauna visiting free‐range poultry farms. We quantified visits of wild fauna to a free‐range area of a layer farm, situated in an AIV hot‐spot area, assessed by video‐camera monitoring. A total of 5,016 hr (209 days) of video recordings, covering all 12 months of a year, were analysed. A total of 16 families of wild birds and five families of mammals visited the free‐range area of the layer farm. Wild birds, except for the dabbling ducks, visited the free‐range area almost exclusively in the period between sunrise and the moment the chickens entered the free‐range area. Known carriers of AIV visited the outdoor facility regularly: species of gulls almost daily in the period January–August; dabbling ducks only in the night in the period November–May, with a distinct peak in the period December–February. Only a small fraction of visits of wild fauna had overlap with the presence of chickens at the same time in the free‐range area. No direct contact between chickens and wild birds was observed. It is hypothesized that AIV transmission to poultry on free‐range poultry farms will predominantly take place via indirect contact: taking up AIV by chickens via wild‐bird‐faeces‐contaminated water or soil in the free‐range area. The free‐range poultry farmer has several possibilities to potentially lower the attractiveness of the free‐range area for wild (bird) fauna: daily inspection of the free‐range area and removal of carcasses and eggs; prevention of forming of water pools in the free‐range facility. Furthermore, there are ways to scare‐off wild birds, for example use of laser equipment or trained dogs.
Seasonal Declines in Cry1Ac and Cry2Ab Concentration in Maturing Cotton Favor Faster Evolution of Resistance to Pyramided Bt Cotton in Helicoverpa zea (Lepidoptera: Noctuidae)

Abstract Under ideal conditions, widely adopted transgenic crop pyramids producing two or more distinct insecticidal proteins from Bacillus thuringiensis (Bt) that kill the same pest can substantially delay evolution of resistance by pests. However, deviations from ideal conditions diminish the advantages of such pyramids. Here, we tested the hypothesis that changes in maturing cotton producing Cry1Ac and Cry2Ab affect evolution of resistance in Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae), a pest with low inherent susceptibility to both toxins. In terminal leaves of field-grown Bt cotton, the concentration of both toxins was significantly higher for young, squaring plants than for old, fruiting plants. We used laboratory bioassays with plant material from field-grown cotton to test H. zea larvae from a strain selected for resistance to Cry1Ac in the laboratory, its more susceptible parent strain, and their F1 progeny. On young Bt cotton, no individuals survived to pupation. On old Bt cotton, survival to pupation was significantly higher for the lab-selected strain and the F1 progeny relative to the unselected parent strain, indicating dominant inheritance of resistance. Redundant killing, the extent to which insects resistant to one toxin are killed by another toxin in a pyramid, was complete on young Bt cotton, but not on old Bt cotton. No significant fitness costs associated with resistance were detected on young or old non-Bt cotton. Incorporation of empirical data into simulations indicates the observed increased selection for resistance on old Bt cotton could accelerate evolution of resistance to cotton producing Cry1Ac and Cry2Ab in H. zea.
Isolation and characterization of sequences homologous to the tobacco clone axi 1 (auxin independent) from a Vicia sativa nodule cDNA library

In this research, partial nucleotide sequences of the axi 1 gene, which is related to auxin perception and transduction, isolated from Vicia sativa using cDNA library screening were investigated. Four V. sativa cDNA clones representing homologous of the tobacco axi 1 (auxin independent) cDNA clone were isolated and characterized. With sequence analysis two different clones were observed, called 10/3a and 16/3b. Sequences about 500 bp from the 5' end and 450 bp from the 3' end were determined from the 10/3a clone. The sequences from the 5' end of cDNA clone 10/3a shared about 58 % similarity at the nucleotide level and 61% identity at the polypeptide level with the sequences of the Nicotiana tabacum axi 1 cDNA clone. At the 3' end of 10/3a, 63 % similarity at the nucleotide level was observed with the clone. In 16/3b about 500 bp was sequenced from the 5' end. There was 64 % nucleotide sequence similarity and 61 % polypeptide sequence identity. Northern blot analysis showed that the size of the mRNA was about 2 kb, like that of the axi 1 isolated from tobacco. It was shown that homolog sequences of axi 1 were expressed in flowers, leaves, stems, roots and nodules of the V. sativa plants.
Social insurance literacy: a scoping review on how to define and measure it

Abstract Purpose Sickness insurance and workers’ compensation systems decide on peoples’ eligibility for benefits, and are commonly based on medical certificates and assessments of work ability. Systems differ in the extent to which they preserve clients’ dignity and right to fair assessments. In this article, we define a new concept for studying interactions between individuals and systems: social insurance literacy, which concerns how well people understand the different procedures and regulations in social insurance systems, and how well systems communicate with clients in order to help them understand the system. Methods The concept was defined through a scoping literature review of related concepts, a conceptual re-analysis in relation to the social insurance field, and a following workshop. Results Five related concepts were reviewed for definitions and operationalizations: health literacy, financial/economic literacy, legal capability/ability, social security literacy, and insurance literacy. Conclusions Social insurance literacy is defined as the extent to which individuals can obtain, understand and act on information in a social insurance system, related to the comprehensibility of the information provided by the system. This definition is rooted in theories from sociology, social medicine and public health. In the next step, a measure for the concept will be developed based on this review. Implications for rehabilitation Social insurance literacy is a new concept that is based on theories in sociology, social medicine and public health. It provides conceptual orientation for analyzing factors that may influence different outcomes of peoples’ contacts with social insurance systems. The concept is of relevance for rehabilitation professionals since it focuses on how interactions between individuals and systems can influence the rehabilitation process. The study will in the next step develop a measure of social insurance literacy which will have practical applications for rehabilitation professionals.
Comparison of 3 Treatment Methods for Distal Tibial Fractures: A Network Meta-Analysis

Background The choice of optimal internal fixation device for distal tibial fractures remains controversial. The purpose of our study was to evaluate the effectiveness and safety of open reduction and internal fixation, minimally invasive percutaneous osteosynthesis, and intramedullary nailing of distal tibial fractures in adults using network meta-analysis of data from clinical trials. Material/Methods The studies were abstracted from MEDLINE, EMBASE, CNKI, and the Cochrane Central Register of Controlled Trials. Randomized controlled trials meeting inclusion and exclusion criteria were selected. Statistical analyses were conducted using Stata software, version 13.0 (Stata Corporation, College Station, Texas, USA). Results Eleven randomized controlled trials were included. The total number of participants was 710 and the studies were published between 2005 and 2017. There were no significant differences in rates of delayed union, nonunion, or malunion among the various treatments (all p>0.05). The intramedullary nailing group had a lower incidence of wound complications than did the open reduction and internal fixation group and minimally invasive percutaneous osteosynthesis technique group. The SUCRA probabilities were 28.6% for ORIF, 98.4% for IMN, and 22.9% for MIPPO. Conclusions Given the superior results for intramedullary nailing in terms of wound complications, we recommend this procedure for treatment of distal tibial fractures. More RCTs focused on distal tibial fractures are needed to support the current evidence.
Vaccines against Ebola virus and Marburg virus: recent advances and promising candidates

ABSTRACT The filoviruses Ebola virus and Marburg virus are among the most dangerous pathogens in the world. Both viruses cause viral hemorrhagic fever, with case fatality rates of up to 90%. Historically, filovirus outbreaks had been relatively small, with only a few hundred cases reported. However, the recent West African Ebola virus outbreak underscored the threat that filoviruses pose. The three year-long outbreak resulted in 28,646 Ebola virus infections and 11,323 deaths. The lack of Food and Drug Administration (FDA) licensed vaccines and antiviral drugs hindered early efforts to contain the outbreak. In response, the global scientific community has spurred the advanced development of many filovirus vaccine candidates. Novel vaccine platforms, such as viral vectors and DNA vaccines, have emerged, leading to the investigation of candidate vaccines that have demonstrated protective efficacy in small animal and nonhuman primate studies. Here, we will discuss several of these vaccine platforms with a particular focus on approaches that have advanced into clinical development.
Outcomes of nurse practitioner‐led care in patients with cardiovascular disease: A systematic review and meta‐analysis

Abstract Aim To assess randomized controlled trials evaluating the impact of nurse practitioner‐led cardiovascular care. Background Systematic review of nurse practitioner–led care in patients with cardiovascular disease has not been completed. Design Systematic review and meta‐analysis. Data sources The Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL, Web of Science, Scopus and ProQuest were systematically searched for studies published between January 2007 ‐ June 2017. Review Methods Cochrane methodology was used for risk of bias, data extraction and meta‐analysis. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation approach. Results Out of 605 articles, five articles met the inclusion criteria. There was no statistical difference between nurse practitioner‐led care and usual care for 30‐day readmissions, health‐related quality of life and length of stay. A 12% reduction in Framingham risk score was identified. Conclusion There are a few randomized control trials assessing nurse practitioner‐led cardiovascular care. Impact Low to moderate quality evidence was identified with no statistically significant associated outcomes of care. Nurse practitioner roles need to be supported to conduct and publish high‐quality research.
Cytochrome P450-Mediated Metabolic Characterization of a Mono-Carbonyl Curcumin Analog WZ35

WZ35 is a monocarbonyl analog of curcumin, which had been proved advantage over curcumin in chemical stability and antitumor activity. However, its pharmacokinetic profile has not been determined. In the present study, an ultraperformance liquid chromatography-tandem mass spectrometry assay was developed to detect concentration of WZ35 in rat plasma. Subsequently, pharmacokinetic study showed that the oral bioavailability of WZ35 is 10.56%. Cytochrome P450 (CYP450) plays a major role in metabolizing exogenous substance. The concentration of WZ35 was sharply decreased while incubating with microsome. It’s indicated that WZ35 is a substrate of CYP450s. Molecular docking assay showed that WZ35 can combine with CYP2B6 and CYP2C9 to form much more stable complex. The lowest docking energy was generated in complex with CYP2E1. The inhibition of CYP450s by WZ35 was also evaluated. Pan inhibitions of WZ35 on rat CYP3A2, CYP2B1, CYP2C11, CYP2D1, and CYP2E1 were observed by detecting probe substrates (midazolam, bupropion, tolbutamide, dextromethorphan, chlorzoxazone) and metabolites accordingly. On an average, 80% activities of enzymes were blocked. Mechanistically, the inhibitions of WZ35 on CYP3A2, CYP2B1, CYP2E1 were in a time-dependent manner according to the results of IC50 shift assay. The collective data demonstrated that the oral bioavailability of monocarbonyl analog of curcumin has significantly improved compared to curcumin. It’s both the substrate and inhibitor of CYP450s through in a time-dependent mechanism.
Target-related autobiographical memories affect dietary intake intentions*

ABSTRACT Although there is evidence that autobiographical memory (AM) recall impacts behaviour in multiple domains, the mechanisms for this effect are unclear. Two experiments examined how AM Frame and Relatedness to target behaviour affect intention to control future dietary intake. Participants completed an AM task where they recalled success or fail-framed memories of behaviour in the target domain (dietary intake), a related domain (exercise), and an unrelated domain (work). Next they completed questionnaires about attitudes, self-efficacy, and behavioural intention for controlling dietary intake. In Experiment 1, Frame and Relatedness of AMs recalled did not affect attitudes or self-efficacy ratings of controlling dietary intake. However, Related AMs resulted in higher intention ratings to control future dietary intake compared to Unrelated AMs. Experiment 2 replicated these results for attitude and self-efficacy, but showed no effect on behavioural intention. A mini-meta analysis was conducted to clarify the effect of AM recall on intention. This analysis confirmed a significant effect of AM Relatedness on intention ratings (meta-analysis Cohen’s d = .25, Z = 2.54, p = .011). These results provide evidence that recalling related AM can affect dietary behaviour intentions directly, without changes attitudes or ratings of personal control regarding dietary intake.
Secondary metabolites from Diaporthe lithocarpus isolated from Artocarpus heterophyllus

Abstract Fractionation and purification of the ethyl acetate extract of Diaporthe lithocarpus, an endophytic fungus from the leaves of Artocarpus heterophyllus, yielded one new compound, diaporthindoic acid (1), along with seven known compounds (2–8). The new compound was characterized and established by the basis of extensive spectroscopic methods including NMR (1D and 2D) and HRMS. Compound 6 showed the best citotoxicity against murine leukemia P-388 cells with an IC50 value of 0.41 μg/mL. All compounds (1–8) were also tested for their antimicrobial activities. To the best of our knowledge, this is the first chemical evaluation of fungal Diaporthe derived from Artocarpus. Graphical Abstract
Sudden cardiac arrest and ventricular arrhythmias following first type I myocardial infarction in the contemporary era

Myocardial infarction (MI) is associated with an increase in subsequent heart failure (HF), recurrent ischemic events, sudden cardiac arrest, and ventricular arrhythmias (SCA‐VA). The primary objective of the study to determine the role of intercurrent HF and ischemic events on the development of SCA‐VA following first type I MI.
Dynamic Multi-Atlas Selection Based Consensus Segmentation of Head and Neck Structures from CT Images.

PURPOSE Manual delineation of head and neck (H&N) organ-at-risk (OAR) structures for radiation therapy planning is time consuming and highly variable. Therefore, we developed a dynamic multi-atlas selection-based approach for fast and reproducible segmentation. METHODS Our approach dynamically selects and weights the appropriate number of atlases for weighted-label fusion and generates segmentations and consensus maps indicating voxel-wise agreement between different atlases. Atlases were selected for a target as those exceeding an alignment weight called dynamic atlas attention index. Alignment weights were computed at the image-level and called global weighted voting (GWV) or at the structure-level and called structure weighted voting (SWV) by using a normalized metric computed as the sum of squared distances of CT-radiodensity and Modality Independent Neighborhood Descriptors (extracting edge information). Performance comparisons were performed using 77 H&N CT images from an internal Memorial Sloan-Kettering Cancer Center dataset (N=45) and an external dataset (N=32) using Dice Similarity Coefficient (DSC), Hausdorff distance (HD), 95th percentile of HD, Median of Maximum Surface Distance, and Volume Ratio Error against expert delineation. Pair-wise DSC accuracy comparisons of proposed (GWV, SWV) vs. single best atlas (BA) or majority voting (MV) methods were performed using Wilcoxon rank-sum tests. RESULTS Both SWV and GWV methods produced significantly better segmentation accuracy than BA (p < 0.001) and MV (p < 0.001) for all OARs within both datasets. SWV generated most accurate segmentations with DSC of: 0.88 for oral cavity, 0.85 for mandible, 0.84 for cord, 0.76 for brainstem and parotids, 0.71 for larynx, and 0.60 for submandibular glands. SWV's accuracy exceeded GWV's for submandibular glands (DSC=0.60 vs 0.52, p=0.019). CONCLUSIONS The contributed SWV and GWV methods generated more accurate automated segmentations than the other two MABAS techniques. The consensus maps could be combined with segmentations to visualize voxel-wise consensus between atlases within OARs during manual review.