Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular epidemiology of hepatitis A outbreaks in two districts in Indonesia in 2018: Same subtype, but different strains

The present study aimed to analyse molecular epidemiological data from hepatitis A virus (HAV) outbreaks in two affected areas. The association between the knowledge of hepatitis A and incidence of infection was also determined. Serum samples were obtained from 88 individuals with clinical manifestations of acute hepatitis in Lamongan (n=54) in January 2018 and Bangkalan (n=34) in March 2018. The outbreak investigation was started one day after the outbreaks were reported by the Public Health Offices in Lamongan and Bangkalan. Anti-HAV immunoglobulin M (IgM) and PCR amplification products of the VP1 capsid protein-P2A protease and VP1-VP3 junctions were analysed. Positive PCR products were sequenced, and a phylogenetic tree was constructed using Molecular Evolutionary Genetics Analysis X software. The control group comprised healthy students and staff members from the two affected areas. Thus, 172 responses from the control and hepatitis A case groups were analysed to assess the association between the students' knowledge level and the incidence of HAV infection. A total of 32 (59.25%) of the 54 individuals from Lamongan and 19 (55.9%) of the 34 participants from Bangkalan were positive for anti-HAV IgM; 26 PCR tests were positive in the VP3-VP1 and/or VP1-P2A junction, which were identified as HAV subgenotype IA. The subtype of HAV in the two areas was IA, similar to those identified previously, but the viruses did not originate from the same strain, as identified by multiple alignment. The knowledge level of the students and staff members in Lamongan studying and working at a half-day school exhibited a significant association with the incidence; however, no association was observed among the students in Bangkalan studying at a full-day school with a dormitory.
Sustained virological response by direct-acting antivirals reduces the recurrence risk of hepatitis C-related hepatocellular carcinoma after curative treatment

The present study aimed to assess the suppressive effect of direct-acting antivirals (DAAs) on hepatocellular carcinoma (HCC) recurrence following curative treatment, particularly compared with interferon (IFN)-based therapy. Among 117 curative cases of HCV-related initial HCC between 2006 and 2017 at Gifu University Hospital, 13 and 14 cases achieved a sustained virological response (SVR) by DAA- (DAA group) or IFN-based therapies (IFN group), and 64 cases were not treated with any antiviral therapy (non-treatment group). Recurrence-free survival (RFS) following curative treatment in each group was analyzed using the Kaplan-Meier method and log-rank test. A Cox proportional hazards model was used to analyze the factors that affected RFS. Age was significantly lower and serum alanine aminotransferase level was significantly higher in the IFN group than in both the DAA and non-treatment groups. There was a significant difference in RFS between the non-treatment group and antiviral therapy groups, including the DAA (P=0.014) and IFN groups (P=0.009); however, no significant difference was identified in RFS between the DAA and IFN groups (P=0.564). SVR achieved by DAA [P=0.011; hazard ratio (HR), 0.222; 95% CI, 0.069-0.758] or IFN therapy (P=0.007; HR, 0.327; 95% CI, 0.145-0.742) was an independent factor for the prevention of HCC recurrence. SVR by DAA therapy exhibited an anti-liver tumorigenesis effect equal to that of IFN-based therapy and reduced the risk of HCC recurrence.
Intramedullary-Extramedullary Triple Allograft-Prosthetic Composite: A Technique for Salvage of Failed Proximal Femoral Replacement With Cavitary Endosteal Bone Loss With Long-term Follow-up

Replacement of the proximal femur after en bloc resection for oncologic purposes frequently involves proximal femoral megaprosthetic reconstruction. When cemented megaprostheses fail, they often do so by aseptic loosening accompanied by massive cavitary endosteal bone loss. One option for restoring endosteal bone stock in this situation is a triple allograft technique, using a tubular intramedullary humeral allograft press-fit into the remaining bone and accepting a cemented stem from an allograft prosthetic composite with bridging external strut allografts at the junction. The patient in this case had a 16-year survival from her reconstruction, longer than the 12-year duration of the original megaprosthesis, and revision showed good healing of the intramedullary humeral and extramedullary strut allografts, facilitating revision.
First‐trimester blood urea nitrogen and risk of gestational diabetes mellitus

Prior studies indicated that urea increased insulin resistance and higher blood urea nitrogen (BUN) was associated with incident diabetes mellitus. However, it remains unclear whether BUN during the first trimester of pregnancy increases risk of gestational diabetes mellitus (GDM). We aimed to investigate the association between first‐trimester BUN and risk of incident GDM. We conducted a prospective, multicenter cohort study of pregnant women. A total of 13 448 eligible pregnant women with measured first‐trimester BUN levels were included in this analysis. Logistic regression analysis was used to estimate the relationship between BUN and GDM. Discrimination and reclassification for GDM by BUN were analysed. A total of 2973 (22.1%) women developed GDM. Compared with the lowest quartile of BUN, the third and fourth quartiles were associated with increased risk of GDM (adjusted odds ratios 1.21 [95% CI 1.07‐1.37] and 1.50 [95% CI 1.33‐1.69], respectively, P for trend <.001). The addition of BUN to conventional factor model improved discrimination (C statistic 0.2%, P = .003) and reclassification (net reclassification index 14.67%, P < .001; integrated discrimination improvement 0.12%, P < .001) for GDM. In conclusion, higher BUN concentrations during the first trimester of pregnancy were associated with increased risk of GDM, suggesting that BUN could be a potential predictor for GDM.
Effects of oxycodone on sensitivity to reinforcement magnitude: implications for effects of opioids on impulsive and risky choice

Opioid addiction/dependence is associated with impulsive and risky behavior. Moreover, opioids can increase impulsive choice in preclinical studies with nonhumans. The objective of this study was to investigate a potential behavioral mechanism of opioids: a change in the impact of reinforcement magnitude on choice. Rats (n = 7) chose between smaller and larger reinforcers under a continuous-choice (concurrent-chains) procedure. The levers associated with the smaller and larger reinforcers alternated every five sessions. During baseline under this procedure, rats showed a reliable preference for the larger reinforcer. Effects of several doses (0.1–1.7 mg/kg, s.c.) of the prescription opioid, oxycodone, were examined on preference based upon reinforcement magnitude. Oxycodone dose-dependently decreased preference for the larger reinforcer (i.e. decreased sensitivity to reinforcement magnitude). The decrease in sensitivity to reinforcement magnitude was selective in that the intermediate doses did not affect, or had minimal impact on, other measures of performance (e.g. on general motivation to respond). These data suggest that a decrease in the sensitivity to reinforcement magnitude is a reliable outcome of μ-opioid administration, an effect that has important implications for the impact of these drugs on both impulsive and risky behavior.
Comparative Clinical Effectiveness and Safety of Bone Morphogenetic Protein Versus Autologous Iliac Crest Bone Graft in Lumbar Fusion

Compared with iliac crest bone graft (ICBG), there is insufficient evidence demonstrating superiority of recombinant human bone morphogenetic protein (RhBMP). We conducted a comprehensive systematic literature review and meta-analysis to compare the differences between rhBMP and ICBG. We suggest rhBMP especially rhBMP-2 as a suitable alternative to ICBG.
Comparing user-dependent and user-independent training of CNN for SSVEP BCI

Objective. We presented a comparative study on the training methodologies of a convolutional neural network (CNN) for the detection of steady-state visually evoked potentials (SSVEP). Two training scenarios were also compared: user-independent (UI) training and user-dependent (UD) training. Approach. The CNN was trained in both UD and UI scenarios on two types of features for SSVEP classification: magnitude spectrum features (M-CNN) and complex spectrum features (C-CNN). The canonical correlation analysis (CCA), widely used in SSVEP processing, was used as the baseline. Additional comparisons were performed with task-related components analysis (TRCA) and filter-bank canonical correlation analysis (FBCCA). The performance of the proposed CNN pipelines, CCA, FBCCA and TRCA were evaluated with two datasets: a seven-class SSVEP dataset collected on 21 healthy participants and a twelve-class publicly available SSVEP dataset collected on ten healthy participants. Main results. The UD based training methods consistently outperformed the UI methods when all other conditions were the same, as one would expect. However, the proposed UI-C-CNN approach performed similarly to the UD-M-CNN across all cases investigated on both datasets. On Dataset 1, the average accuracies of the different methods for 1 s window length were: CCA: 69.1% ± 10.8%, TRCA: 13.4% ± 1.5%, FBCCA: 64.8% ± 15.6%, UI-M-CNN: 73.5% ± 16.1%, UI-C-CNN: 81.6% ± 12.3%, UD-M-CNN: 87.8% ± 7.6% and UD-C-CNN: 92.5% ± 5%. On Dataset 2, the average accuracies of the different methods for data length of 1 s were: UD-C-CNN: 92.33% ± 11.1%, UD-M-CNN: 82.77% ± 16.7%, UI-C-CNN: 81.6% ± 18%, UI-M-CNN: 70.5% ± 22%, FBCCA: 67.1% ± 21%, CCA: 62.7% ± 21.5%, TRCA: 40.4% ± 14%. Using t-SNE, visualizing the features extracted by the CNN pipelines further revealed that the C-CNN method likely learned both the amplitude and phase related information from the SSVEP data for classification, resulting in superior performance than the M-CNN methods. The results suggested that UI-C-CNN method proposed in this study offers a good balance between performance and cost of training data. Significance. The proposed C-CNN based method is a suitable candidate for SSVEP-based BCIs and provides an improved performance in both UD and UI training scenarios.
Demographic Shifts, Case Mix, Activity, and Outcome for Elderly Patients Admitted to Adult General ICUs in the United Kingdom, Wales, and Northern Ireland.

OBJECTIVES Major increases in the proportion of elderly people in the population are predicted worldwide. These population increases, along with improving therapeutic options and more aggressive treatment of elderly patients, will have major impact on the future need for healthcare resources, including critical care. Our objectives were to explore the trends in admissions, resource use, and risk-adjusted hospital mortality for older patients, admitted over a 20-year period between 1997 and 2016 to adult general ICUs in the United Kingdom, Wales, and Northern Ireland. DESIGN RETROSPECTIVE ANALYSIS OF NATIONAL CLINICAL AUDIT DATABASE. SETTING The Intensive Care National Audit & Research Centre Case Mix Programme Database, the national clinical audit for adult general ICUs in the United Kingdom, Wales, and Northern Ireland. PATIENTS All adult patients 16 years old or older admitted to adult general ICUs contributing data to the Case Mix Programme Database between January 1, 1997, and December 31, 2016. MEASUREMENTS AND MAIN RESULTS The annual number, trends, and outcomes for patients across four age bands (16-64, 65-74, 75-84, and 85+ yr) admitted to ICUs contributing to the Case Mix Programme Database from 1997 to 2016 were examined. Case mix, activity, and outcome were described in detail for the most recent cohort of patients admitted in 2015-2016. Between 1997 to 2016, the annual number of admissions to ICU of patients in the older age bands increased disproportionately, with increases that could not be explained solely by general U.K. demographic shifts. The risk-adjusted acute hospital mortality decreased significantly within each age band over the 20-year period of the study. Although acute severity at ICU admission was comparable with that of the younger age group, apart from cardiovascular and renal dysfunction, older patients received less organ support. Older patients stayed longer in hospital post-ICU discharge, and hospital mortality increased with age, but the majority of patients surviving to hospital discharge returned home. CONCLUSIONS Over the past two decades, elderly patients have been more commonly admitted to ICU than can be explained solely by the demographic shift. Importantly, as with the wider population, outcomes in elderly patients admitted to ICU are improving over time, with most patients returning home.
Mesenchymal Stromal Cells Protect the Blood-Brain Barrier, Reduce Astrogliosis, and Prevent Cognitive and Behavioral Alterations in Surviving Septic Mice.

OBJECTIVES Survivors of sepsis are frequently left with significant cognitive and behavioral impairments. These complications derive from nonresolving inflammation that persists following hospital discharge. To date, no study has investigated the effects of mesenchymal stromal cell therapy on the blood-brain barrier, astrocyte activation, neuroinflammation, and cognitive and behavioral alterations in experimental sepsis. DESIGN Prospective, randomized, controlled experimental study. SETTING Government-affiliated research laboratory. SUBJECTS Male Swiss Webster mice (n = 309). INTERVENTIONS Sepsis was induced by cecal ligation and puncture; sham-operated animals were used as control. All animals received volume resuscitation (1 mL saline/mouse subcutaneously) and antibiotics (meropenem 10 mg/kg intraperitoneally at 6, 24, and 48 hours). Six hours after surgery, mice were treated with mesenchymal stromal cells IV (1 × 10 cells in 0.05 mL of saline/mouse) or saline (0.05 mL IV). MEASUREMENTS AND MAIN RESULTS At day 1, clinical score and plasma levels of inflammatory mediators were increased in cecal ligation and puncture mice. Mesenchymal stromal cells did not alter clinical score or survival rate, but reduced levels of systemic interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1. At day 15, survivor mice completed a battery of cognitive and behavioral tasks. Cecal ligation and puncture mice exhibited spatial and aversive memory deficits and anxiety-like behavior. These effects may be related to increased blood-brain barrier permeability, with altered tight-junction messenger RNA expression, increased brain levels of inflammatory mediators, and astrogliosis (induced at day 3). Mesenchymal stromal cells mitigated these cognitive and behavioral alterations, as well as reduced blood-brain barrier dysfunction, astrocyte activation, and interleukin-1β, interleukin-6, tumor necrosis factor-α, and interleukin-10 levels in vivo. In cultured primary astrocytes stimulated with lipopolysaccharide, conditioned media from mesenchymal stromal cells reduced astrogliosis, interleukin-1β, and monocyte chemoattractant protein-1, suggesting a paracrine mechanism of action. CONCLUSIONS In mice who survived experimental sepsis, mesenchymal stromal cell therapy protected blood-brain barrier integrity, reduced astrogliosis and neuroinflammation, as well as improved cognition and behavior.
Projection Space Implementation of Deep Learning–Guided Low-Dose Brain PET Imaging Improves Performance over Implementation in Image Space

Our purpose was to assess the performance of full-dose (FD) PET image synthesis in both image and sinogram space from low-dose (LD) PET images and sinograms without sacrificing diagnostic quality using deep learning techniques. Methods: Clinical brain PET/CT studies of 140 patients were retrospectively used for LD-to-FD PET conversion. Five percent of the events were randomly selected from the FD list-mode PET data to simulate a realistic LD acquisition. A modified 3-dimensional U-Net model was implemented to predict FD sinograms in the projection space (PSS) and FD images in image space (PIS) from their corresponding LD sinograms and images, respectively. The quality of the predicted PET images was assessed by 2 nuclear medicine specialists using a 5-point grading scheme. Quantitative analysis using established metrics including the peak signal-to-noise ratio (PSNR), structural similarity index metric (SSIM), regionwise SUV bias, and first-, second- and high-order texture radiomic features in 83 brain regions for the test and evaluation datasets was also performed. Results: All PSS images were scored 4 or higher (good to excellent) by the nuclear medicine specialists. PSNR and SSIM values of 0.96 ± 0.03 and 0.97 ± 0.02, respectively, were obtained for PIS, and values of 31.70 ± 0.75 and 37.30 ± 0.71, respectively, were obtained for PSS. The average SUV bias calculated over all brain regions was 0.24% ± 0.96% and 1.05% ± 1.44% for PSS and PIS, respectively. The Bland–Altman plots reported the lowest SUV bias (0.02) and variance (95% confidence interval, −0.92 to +0.84) for PSS, compared with the reference FD images. The relative error of the homogeneity radiomic feature belonging to the gray-level cooccurrence matrix category was −1.07 ± 1.77 and 0.28 ± 1.4 for PIS and PSS, respectively. Conclusion: The qualitative assessment and quantitative analysis demonstrated that the FD PET PSS led to superior performance, resulting in higher image quality and lower SUV bias and variance than for FD PET PIS.
Emerging roles of the centrosome in neuronal development

The role of the centrosome—a microtubule‐organizing center—in neuronal development has been under scrutiny and is controversial. The function and position of the centrosome have been shown to play an important role in selecting the position of axon outgrowth in cultured neurons and in situ. However, other studies have shown that axonal growth is independent of centrosomal functions. Recent discoveries define the centrosome as an F‐actin organizing organelle in various cell types; thus, giving a whole new perspective to the role of the centrosome in lymphocyte polarity, cell division, and neuronal development. These discoveries compel the need to revisit centrosomal functions by investigating the fundamental mechanisms that regulate centrosomal F‐actin remodeling during neuronal differentiation and polarization. In this review, we summarize the up‐to‐date knowledge regarding the function of the centrosome in neuronal differentiation. We put special emphasis on recent findings describing the centrosome as an F‐actin organizing center. Additionally, with the available data regarding centrosome, microtubules and F‐actin organization, we provide a model on how centrosomal F‐actin could be modulating neuronal differentiation and polarity.
Dietary effect of low fish meal aquafeed on gut microbiota in olive flounder (Paralichthys olivaceus) at different growth stages

This study was conducted to investigate the long‐term effect of a low fish meal (FM) diet comprising plant‐based protein sources (PPS) on changes of gut microbial diversity in olive flounder (Paralichthys olivaceus) over the course of life. Two experimental diets were prepared to contain 74% FM (control) or 52% FM with 22% PPS (30% FM replacement, FM30). Fish were fed one of the two experimental diets for 8 months, and we collected the midgut contents to analyze the gut bacterial community by Illumina MiSeq based on the metagenomic sequences in the V3–V4 regions of 16S rRNA. We found that there were nine dominant phyla, which in turn presented Proteobacteria, Firmicutes, and Actinobacteria as the three major phyla in the gut microbiota of the flounder. At genus level, the dominant genera were Delftia, Prevotella, and Chthoniobacter at the juvenile stage (below 100 g/fish); Chthoniobacter, Bacillus, and Bradyrhizobium at the grower stage (400 g/fish); Chthoniobacter, Bacillus, and Delftia at the subadult stage (800 g/fish); and Lactobacillus and Prevotella at the adult stage (over 1,000 g/fish). The microbial diversity in olive flounders arched from the juvenile and subadult stage and reached a plateau thereafter. The fish fed the FM30 diet significantly had an increased abundance of Lactobacillus and Photobacterium and had less abundance of Prevotella and Paraprevotella than the control. However, the effect of dietary PPS was not significant on total microbial richness, indicating no negative effect as feed sources on the intestinal microbiota in olive flounder. These results indicate that the life stage of olive flounder is more important in modulating intestinal microbiota than is the diet. It could also be concluded that dietary PPS might be used as a potential fish meal alternative without any compromising effects on microbial diversity of olive flounder for long‐term feeding.
Share the wealth: trees with greater ectomycorrhizal species overlap share more carbon.

The mutualistic symbiosis between forest trees and ectomycorrhizal fungi (EMF) is among the most ubiquitous and successful interactions in terrestrial ecosystems. Specific species of EMF are known to colonize specific tree species, benefitting from their carbon source, and in turn, improving their access to soil water and nutrients. EMF also form extensive mycelial networks that can link multiple root-tips of different trees. Yet the number of tree species connected by such mycelial networks, and the traffic of material across them, are just now under study. Recently we reported substantial belowground carbon transfer between Picea, Pinus, Larix and Fagus trees in a mature forest. Here we analyze the EMF community of these same individual trees and identify the most likely taxa responsible for the observed carbon transfer. Among the nearly 1200 EMF root-tips examined, 50-70% belong to operational taxonomic units (OTUs) that were associated with 3 or 4 tree host species, and 90% of all OTUs were associated with at least two tree species. Sporocarp 13 C signals indicated that carbon originating from labeled Picea trees was transferred among trees through EMF networks. Interestingly, phylogenetically more closely related tree species exhibited more similar EMF communities and exchanged more carbon. Our results show that belowground carbon transfer is well orchestrated by the evolution of EMFs and tree symbiosis.
Glaucoma in pregnancy: an update.

PURPOSE OF REVIEW Glaucoma management during pregnancy is a complex challenge, which requires balancing the clinical disease of the mother with the potential risks of therapy to the developing child. Because systematic studies are lacking in the pregnant population, this review aims to collect the array of available data from observational studies and case reports to provide the reader with guidance and context for the safety of glaucoma interventions during pregnancy. RECENT FINDINGS Surgical glaucoma is a rapidly expanding field with many new technologies and procedures. We review the surgical options for the gravid patient with reference to traditional procedures like trabeculectomy and tube-shunts, and newer MIGS procedures. When indicated, orphan trabeculectomy, or with collagen matrix implant may be a viable solution for severe glaucoma during pregnancy. Newer MIGS procedures such as the gelatin stent may also provide minimally invasive options for pregnant patients. Two new medications, Vyzulta and Rhopressa, were recently released in 2018 and have limited data to support their safety for use during pregnancy. SUMMARY The careful consideration of fetal health in the management of glaucoma during pregnancy is best done as a part of a multidisciplinary team including obstetrics and neonatology. When medication is necessary, steps to minimize systemic absorption should be employed. Surgical management should not be excluded for pregnant patients and may be considered before medical management in some cases to prevent fetal exposures and maternal harm.