Miracle-dz/UniFAR-FTUs huggingface dataset:
Equitable and Timely Care of Febrile Neonates

Supplemental digital content is available in the text. Objectives In pediatric emergency departments (EDs), racial/ethnic minorities are less likely to receive needed and timely care; however, clinical protocols have the potential to mitigate disparities. Neonatal fever management is protocolized in many EDs, but the timeliness to antibiotic administration is likely variable. We investigated the timeliness of antibiotic administration for febrile neonates and whether timeliness was associated with patients' race/ethnicity. Methods Retrospective cross-sectional study of febrile neonates evaluated in one pediatric ED that uses an evidence-based guideline for the management of neonatal fever between March 2010 and December 2015. Primary outcome was time from ED arrival to antibiotic administration. Analysis of variance tests compared mean time with antibiotic administration across race/ethnicity. Multivariable linear regression investigated racial/ethnic differences in time to antibiotic administration after adjusting for patient demographics, timing of visit, the number of physicians involved, and ED census. Results We evaluated 317 febrile neonates. Of the 269 patients with racial/ethnic data (84.9%), 54% were white non-Hispanic, 13% were black non-Hispanic, and 23% were Hispanic. The mean time to antibiotic administration was 204 minutes (range = 51–601 minutes). There was no significant association between patient race/ethnicity and time to first antibiotic administration. Emergency department census was significantly associated with timeliness. Conclusions There was a 10-hour range in the time to antibiotic administration for febrile neonates; however, variability in timeliness did not differ by race or ethnicity. This study demonstrates the need to further examine the role of protocols in mitigating disparities as well as factors that influence timeliness in antibiotic administration to febrile neonates.
Whole-person care in general practice: The nature of whole-person care.

BACKGROUND AND OBJECTIVES Whole-person care (WPC) is a core value of general practice and is particularly relevant with increasing population multimorbidity. However, WPC has lacked consensus definition, and some argue that it is not consistently practised. The aim of this study was to determine Australian general practitioners' (GPs') understanding of WPC and factors affecting its provision. This article (the first in a three-part series) describes GPs' understanding of WPC. METHOD Semi-structured interviews were conducted with 20 Australian GPs or general practice registrars and analysed using grounded theory methodology. RESULTS Four themes encapsulated GPs' understanding of WPC: 1) treats patients as multidimensional persons; 2) length, breadth and depth of scope; 3) based on the foundation of a doctor-patient relationship; and 4) may involve team-based care. DISCUSSION WPC encompasses several defining characteristics of generalism. Previous evidence supports the efficacy of several of its dimensions. The current findings provide a basis for education, self-reflection and assessment of implementation and outcomes of WPCs.
Rational design of a cocktail of inhibitors against Aβ aggregation.

It has been reported that many molecules could inhibit the aggregation of Aβ (β-amyloid) through suppressing either primary nucleation, secondary nucleation or elongation processes. In order to suppress multiple pathways of Aβ aggregation, we screened 23 small molecules and found two types of inhibitors with different inhibiting mechanisms based on chemical kinetics analysis. Trp-glucose conjugates (AS2) could bind with fibril ends while natura(amyloid-β)(amyloid-β)l products (D3 and D4) could associate with monomers. A cocktail of these two kind of molecules achieved co-inhibition of various fibrillar species and avoid unwanted interference.
Diagnosis of some genital-tract infections: part 2. Molecular tests and the new challenges

Promptly and accurately diagnosing genital-tract infections is key to instituting appropriate treatment and control of sexually transmitted infections (STIs). Ano-genital tract testing for STIs in the last two decades has not entirely moved away from insensitive methods but it is now at least dominated by highly sensitive molecular methods. These tests can be ordered through the internet for use at home, with self-taken specimens then returned, usually by post, to a clinic or laboratory for testing. The increasing ease of access of the public to this situation, together with increasing on-line health-seeking behaviour, has resulted in a gap between commercial and NHS management pathways for STIs. Crucially, patients who order multiplex test kits on-line for use at home, and other non-specialists, may not realize that it is worthwhile testing only for Neisseria gonorrhoeae, Chlamydia trachomatis, and possibly Trichomonas vaginalis, and Mycoplasma genitalium if the person is symptomatic or their current partner is infected. The detection and recommended treatment of micro-organisms which to some extent are part of the genital-tract microbiome, such as Mycoplasma hominis, Ureaplasma spp. or Gardnerella vaginalis, which do not cause symptoms in the majority of those infected, cannot be recommended. We argue that a shift from specialist-led to patient- and non-specialist-led STI management, in the presence of a clinical leadership vacuum, has increased the risk of inappropriate and unnecessary treatment which will drive macrolide, tetracycline and metronidazole antimicrobial resistance. However, in the past 5–6 years several groups have been able to show the value of on-line testing as a consequence of targeting the most important micro-organisms and using molecular tests to allow rapid and appropriately informed treatment. This should herald a brighter future, although there is still a need for leadership to expertly guide commercial and NHS sectors alike. In turn, this requires dedicated genito-urinary medicine commissioning to be maintained at a time when it appears to be most under threat.
Using the Collaborative Requirements Development Methodology to Build Laboratory Capacity for Timely Diagnosis During the Zika Epidemic in Puerto Rico.

INTRODUCTION In 2016, Puerto Rico became the focal point of the Zika epidemic, with more than 36 000 laboratory-confirmed cases before August. The Puerto Rico Department of Health (PRDH) responded by providing tests to symptomatic and asymptomatic pregnant women. The increased demand for Zika testing placed unprecedented strain on the laboratory capacity and information management processes used within the PRDH. The PRDH recognized the need to have an updated informatics system that securely manages, stores, and transmits digital data. The Centers for Disease Control and Prevention funded the Public Health Informatics Institute to collaborate with the PRDH to assess and improve the informatics capability to respond to the ongoing Zika virus transmission in Puerto Rico. APPROACH The team employed a 4-component approach to assess the informatics system and improve the information management processes for laboratory testing and reporting of arboviral diseases (Zika, chikungunya, and dengue). The method consisted of a (1) needs assessment, (2) business process analysis and requirements definition, (3) vendor analysis, and (4) solution implementation. RESULTS The needs assessment determined that the PRDH's procedures for arbovirus testing and reporting were highly complex and paper-based and thus did not maximize the use of existing technology. The solution was to build a Web portal. The business process analysis yielded information to create a map of the flow of specimens, an arbovirus context diagram, and more than 200 requirements. The requirements identified in this process guided the design and creation of the Web portal. DISCUSSION This report describes the process to build a Web portal to enhance laboratory testing and electronic reporting of Zika cases during the 2016 epidemic in Puerto Rico. We demonstrate the utility of applying the Collaborative Requirements Development Methodology, a proven informatics method, to the development of a Web portal for managing arboviruses in a health department.
Cervicovertebral anomalies and/or normal variants in patients with congenitally bilateral absent maxillary lateral incisors: A comparative lateral cephalometric study.

OBJECTIVE To determine whether there is a relationship between congenitally bilaterally absent maxillary lateral incisors (BAMLIs) and skeletal anomalies and/or normal variants. MATERIALS AND METHODS The records of 86 patients (62 girls, 24 boys; age 12-17 years) with congenitally BAMLIs and 86 patients (55 girls, 34 boys; age 13-18 years) without any dental or skeletal anomalies were collected and evaluated retrospectively. The study was based on the evaluation of lateral cephalometric and orthopantomographic radiographs. Posterior arch deficiency of the atlas bone (PADA); atlanto-occipital ligament calcification, known as "ponticulus posticus" (PP); and interclinoid ligament calcification, known as "sella turcica bridging" were recorded for each participant. Pearson χ2 and Fisher exact tests were used to evaluate and compare skeletal anomalies and/or normal variants between patients with BAMLIs and the control group. RESULTS The prevalence of cervicovertebral anomalies and/or normal variants seen in the lateral cephalometric radiographs was higher in patients with BAMLI than in the control group. The prevalence of PP was lower and that of PADA was higher in patients with BAMLIs than in the control group (P < .05). CONCLUSION The prevalence of PADA was increased and that of PP formation was decreased in patients with BAMLIs. There was a significant relationship between skeletal anomalies and/or normal variants.
Shearlet Transform-Based Light Field Compression Under Low Bitrates

Light field (LF) acquisition devices capture spatial and angular information of a scene. In contrast with traditional cameras, the additional angular information enables novel post-processing applications, such as 3D scene reconstruction, the ability to refocus at different depth planes, and synthetic aperture. In this paper, we present a novel compression scheme for LF data captured using multiple traditional cameras. The input LF views were divided into two groups: key views and decimated views. The key views were compressed using the multi-view extension of high-efficiency video coding (MV-HEVC) scheme, and decimated views were predicted using the shearlet-transform–based prediction (STBP) scheme. Additionally, the residual information of predicted views was also encoded and sent along with the coded stream of key views. The proposed scheme was evaluated over a benchmark multi-camera based LF datasets, demonstrating that incorporating the residual information into the compression scheme increased the overall peak signal to noise ratio (PSNR) by 2 dB. The proposed compression scheme performed significantly better at low bit rates compared to anchor schemes, which have a better level of compression efficiency in high bit-rate scenarios. The sensitivity of the human vision system towards compression artifacts, specifically at low bit rates, favors the proposed compression scheme over anchor schemes.
Histogram analysis in prostate cancer: a comparison of diffusion kurtosis imaging model versus monoexponential model

Background There is still little research about histogram analysis of diffusion kurtosis imaging (DKI) using in prostate cancer at present. Purpose To verify the utility of histogram analysis of DKI model in detection and assessment of aggressiveness of prostate cancer, compared with monoexponential model (MEM). Material and Methods Twenty-three patients were enrolled in this study. For DKI model and MEM, the Dapp, Kapp, and apparent diffusion coefficient (ADC) were obtained by using single-shot echo-planar imaging sequence. The pathologies were confirmed by in-bore magnetic resonance (MR)-guided biopsy. Regions of interest (ROI) were drawn manually in the position where biopsy needle was put. The mean values and histogram parameters in cancer and noncancerous foci were compared using independent-samples T test. Receiver operating characteristic curves were used to investigate the diagnostic efficiency. Spearman’s test was used to evaluate the correlation of parameters and Gleason scores. Results The mean, 10th, 25th, 50th, 75th, and 90th percentiles of ADC and Dapp were significantly lower in prostate cancer than non-cancerous foci (P < 0.001). The mean, 50th, 75th, and 90th percentiles of Kapp were significantly higher in prostate cancer (P < 0.05). There was no significant difference between the AUCs of two models (0.971 vs. 0.963, P > 0.05). With the increasing Gleason scores, the 10th ADC decreased (ρ = −0.583, P = 0.018), but the 90th Kapp increased (ρ = 0.642, P = 0.007). Conclusion Histogram analysis of DKI model is feasible for diagnosing and grading prostate cancer, but it has no significant advantage over MEM.
An exploration of the role of Sertoli cells on fetal testis development using cell ablation strategy

Sertoli cells (SCs) are presumed to be the center of testis differentiation because they provide both structural support and biological regulation for spermatogenesis. Previous studies suggest that SCs control germ cell (GC) count and Leydig cell (LC) development in mouse testes. However, the regulatory role of SCs on peritubular myoid (PTM) cell fate in fetal testis has not been clearly reported. Here, we employed Amh‐Cre; diphtheria toxin fragment A (DTA) mouse model to selectively ablate SCs from embryonic day (E) 14.5. Results found that SC ablation in the fetal stage caused the disruption of testis cords and the massive loss of GCs. Furthermore, the number of α‐smooth muscle actin‐labeled PTM cells was gradually decreased from E14.5 and almost lost at E18.5 in SC ablation testis. Interestingly, some Ki67 and 3β‐HSD double‐positive fetal LCs could be observed in Amh‐Cre; DTA testes at E16.5 and E18.5. Consistent with this phenomenon, the messenger RNA levels of Hsd3b1, Cyp11a1, Lhr, Star and the protein levels of 3β‐HSD and P450Scc were significantly elevated by SC ablation. SC ablation appears to induce ectopic proliferation of fetal LCs although the total LC number appeared reduced. Together, these findings bring us a better understanding of SCs’ central role in fetal testis development.
Flow Cytometry for the Diagnosis of Primary Immunodeficiency Diseases: A Single Center Experience

Purpose While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute. Methods Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing. Results Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring. Conclusions The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.
The Interaction between Price Negotiations and Heterogeneity: Implications for Economic Evaluations

Economic evaluation is an important element of the decision making process for the reimbursement of drugs. Heterogeneity can be considered an explained variation in clinical or economic outcomes based on the clinical and sociodemographic characteristics of patients. However, to our knowledge, the relationship between price negotiations and population heterogeneity has not been considered in the literature to date. If a company offers a conditional discount that is dependent on obtaining reimbursement in 2 subgroups or indications, an interaction is generated between groups that should be accounted for in economic evaluations. Critically, where the drug has 2 indications but is only cost-effective in 1 indication at the full price (herein “indication 1”), the cost savings realized from implementation of the discount in indication 1 can be used to offset the incremental cost of extending reimbursement to indication 2 at the discounted price. This reduces the incremental cost-effectiveness ratio and increases the probability of positive reimbursement compared to a stratified approach. Given the additional complexity that this introduces, we introduce a framework deemed the “hybrid approach” to guide the economic assessment. We present 2 worked examples. We show that failure to account for the interaction can lead to inaccurate conclusions regarding a drug’s cost effectiveness and that adoption of strategic behavior could theoretically increase the reimbursement price of drugs. By adopting this framework, cost-effective interventions are identified that may have been previously misclassified as not being cost-effective and vice versa. Recognition of the interaction in the literature by pharmaceutical companies may influence the forms of discounts offered to decision makers. Therefore, we expect this research to have far-reaching effects on medical decision making.
Acetaldehyde and cardiac arrhythmias.

: Administration of acetaldehyde (i.v.) into cats anesthetized with halothane elicits severe cardiac ventricular arrhythmias which begin in about 10-13 sec with bolus doses of 5-10 mg/kg, and last about 2 min. Systemic blood pressure and heart rate rise concurrently with the arrhythmias. The cardiac effects are attributed to the release of endogenous catecholamines from cardiac tissue because they are prevented by beta-adrenergic blockade and are not dependent on adrenomedullary and splenic stores of catecholamines, since acute surgical removal of these tissues does not prevent the arrhythmias and other cardiovascular changes. This indirect arrhythmogenic action of acetaldehyde has not been previously reported, probably because other investigators have used anesthetics like pentobarbital which exert an antiarrhythmic effect that masks acetaldehyde's arrhythmogenic potential. The use of halothane to sensitize the heart to catecholamines greatly enhanced the arrhythmogenic effect of acetaldehyde. The question is raised whether the concomitant industrial or medical exposure of human subjects to large amounts of exogenous or endogenous acetaldehyde and certain hydrocarbons could provide the substrate for the expression of this arrhythmogenic effect of acetaldehyde.
Comparative and evolutionary analyses of the divergence of plant oligosaccharyltransferase STT3 isoforms

STT3 is a catalytic subunit of hetero‐oligomeric oligosaccharyltransferase (OST), which is important for asparagine‐linked glycosylation. In mammals and plants, OSTs with different STT3 isoforms exhibit distinct levels of enzymatic efficiency or different responses to stressors. Although two different STT3 isoforms have been identified in both plants and animals, it remains unclear whether these isoforms result from gene duplication in an ancestral eukaryote. Furthermore, the molecular mechanisms underlying the functional divergences between the two STT3 isoforms in plant have not been well elucidated. Here, we conducted phylogenetic analysis of the major evolutionary node species and suggested that gene duplications of STT3 may have occurred independently in animals and plants. Across land plants, the exon–intron structure differed between the two STT3 isoforms, but was highly conserved for each isoform. Most angiosperm STT3a genes had 23 exons with intron phase 0, while STT3b genes had 6 exons with intron phase 2. Characteristic motifs (motif 18 and 19) of STT3s were mapped to different structure domains in the plant STT3 proteins. These two motifs overlap with regions of high nonsynonymous‐to‐synonymous substitution rates, suggesting the regions may be related to functional difference between STT3a and STT3b. In addition, promoter elements and gene expression profiles were different between the two isoforms, indicating expression pattern divergence of the two genes. Collectively, the identified differences may result in the functional divergence of plant STT3s.
Prenatal dietary exposures and offspring body size from 6 months to 18 years: A systematic review.

BACKGROUND In utero dietary exposures may influence childhood obesity. OBJECTIVES To evaluate the relationship between prenatal dietary exposures and offspring body size from 6 months to 18 years. DATA SOURCES Articles were identified in PubMed and Web of Science (January 2010-March 2018) using the PRISMA guidelines. Additional studies were identified through a reference review of articles that met the inclusion criteria and related reviews. STUDY SELECTION Prospective cohort studies that assessed dietary patterns, foods, macronutrients, or beverages during healthy pregnancy and offspring body size. The extraction of articles was done using predefined data fields. SYNTHESIS One author extracted all information and evaluated bias with the NHLBI's Quality Assessment Tool. RESULTS A total of 851 research articles were evaluated. Twenty-one studies assessing dietary patterns, macronutrients, foods, and beverages met inclusion criteria. Consumption of a Mediterranean dietary pattern during pregnancy was associated with reduced body size, while refined carbohydrates were associated with offspring obesity. No association was observed between data-driven dietary patterns and offspring body size, as well as a pro-inflammatory diet pattern and offspring body size. Mixed and null findings were observed for the relationship between total carbohydrates, n-3 polyunsaturated fatty acids, protein, sugar-sweetened beverages, and artificially sweetened beverages and offspring body size. CONCLUSIONS Adhering to a Mediterranean diet and limiting refined carbohydrates during pregnancy may influence offspring body size between 6 months and 18 years. The diverging results that exist between studies highlight the complexity of this topic.