Miracle-dz/UniFAR-FTUs huggingface dataset:
Whether histologic subtyping affect the oncological outcomes of patients with papillary renal cell carcinoma: evidence from a systematic review and meta-analysis

Background Whether the histologic subtype (type 1 and type 2) of papillary renal cell carcinoma (pRCC) is a tool to predict the prognosis is of great debate. This study is aimed to evaluate the prognostic significance of histologic subtype in patients with pRCC after surgery through a systematic review and meta-analysis. Methods We searched PubMed, the Web of Science, Cochrane library and EMBASE databases to identify studies published until January 20, 2021 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were deemed eligible if they compared the overall survival (OS), cancer specific survival (CSS), recurrence-free survival (RFS) or disease-free survival (DFS) between patients with type 1 or type 2 pRCC. And the corresponding hazard ratios (HRs) and 95% conference intervals (CIs) were collected for meta-analysis and further subgroup analysis. Results Overall 22 studies with a total of 4,494 patients were considered eligible and included for the systematic review and meta-analysis. The pooled results showed that type 2 pRCC was associated with a worse OS (pooled HR 1.61, 95% CI: 1.10–2.36, P=0.02) and CSS (pooled HR 1.59, 95% CI: 1.00–2.51, P=0.05). However, the subgroup analysis yielded the same result as the initial analysis only when the HRs were extracted from univariate analysis. In studies with multivariate analysis, type 2 pRCC was not statistically associated with a worse OS (pooled HR 1.22, 95% CI: 0.97–1.53, P=0.27), CSS (pooled HR 1.16, 95% CI: 0.67–2.00, P=0.60), and DFS (pooled HR 1.33, 95% CI: 0.93–1.91, P=0.12) compared to type 1 pRCC. Discussion Histologic subtype is not an independent prognostic factor for patients with pRCC, although the result needs to be taken with caution. And studies with retrospective study design, larger sample size and longer follow-up period are required to verify these results.
Detection of Enteroviruses: An Assessment of Ten Cell Lines

The routine monitoring of waters and wastewaters using the BGM - suspended cell plaque assay system has resulted in high isolation rates for polio and coxsackie B viruses with echoviruses only rarely being detected. Ten cell lines (five of human origin, five of simian derivation) were examined for their susceptibility to twenty six enteroviruses and their ability to isolate naturally occurring enteroviruses in wastewater effluent determined. All the viruses produced cytopathic effect in the simian cell lines but only in the FL amnion line of human cells. The detection of naturally occurring enteroviruses was most efficient when BGM cells were used with 82% of samples being positive. RD cells gave 73% positive whilst chimpanzee liver gave 64%. However, the number of plaques formed in the presence of each cell line showed that BGM detected 50% of all plaques observed with RD and chimpanzee liver detecting 21% and 9% respectively. The serotypes detected in this study were of the polio and coxsackie B groups, no echoviruses being identified.
A narrative review of plaque and brain imaging biomarkers for stroke risk stratification in patients with atherosclerotic carotid artery disease

Objective In this narrative review, we aim to review imaging biomarkers that carry the potential to non-invasively guide stroke risk stratification for treatment optimization. Background Carotid atherosclerosis plays a fundamental part in the occurrence of ischemic stroke. International guidelines select the optimal treatment strategy still mainly based on the presence of clinical symptoms and the degree of stenosis for stroke prevention in patients with atherosclerotic carotid plaques. These guidelines, based on randomized controlled trials that were conducted three decades ago, recommend carotid revascularization in symptomatic patients with high degree of stenosis versus a conservative approach for most asymptomatic patients. Due to optimization of best medical therapy and risk factor control, it is suggested that a subgroup of symptomatic patients is at lower risk of stroke and may not benefit from revascularization, whereas a selective subgroup of high-risk asymptomatic patients would benefit from this procedure. Methods A literature search was performed for articles published up to December 2020 using PubMed, EMBASE and Scopus. Based on the literature found, change in stenosis degree and volume, plaque echolucency, plaque surface, intraplaque haemorrhage, lipid-rich necrotic core, thin fibrous cap, inflammation, neovascularization, microembolic signals, cerebrovascular reserve, intracranial collaterals, silent brain infarcts, diffusion weighted imaging lesions and white matters lesions have the potential to predict stroke risk. Conclusions The applicability of imaging biomarkers needs to be further improved before the potential synergistic prognostic ability of imaging biomarkers can be verified on top of the clinical biomarkers. In the future, the routine and combined assessment of both plaque and brain imaging biomarkers might help to improve optimization of treatment strategies in individual patients with atherosclerotic carotid artery disease.
Measurement properties of UCLA Activity Scale for hip and knee arthroplasty patients and translation and cultural adaptation into Danish

Background and purpose — The UCLA Activity Scale (UCLA) is a questionnaire assessing physical activity level from 1 (low) to 10 (high) in patients undergoing hip or knee arthroplasty (HA/KA). After translation and cultural adaptation, we evaluated the measurement properties of the Danish UCLA. Patients and methods — After dual panel translation, cognitive interviews were performed among 55 HA/KA patients. An orthopedic surgeon and a physiotherapist estimated UCLA scores for 80 KA patients based on short interviews. Measurement properties were evaluated in 130 HA and 134 KA patients preoperatively and 1-year postoperatively. Results — To suit Danish patients of today, several adaptations were required. Prior to interviews, 4 patients were excluded, and 11 misinterpreted the answer options. Examiners rated the remaining 65 patients (mean age 67 years) 0.2–1.6 UCLA levels lower than patients themselves. The 130 HA and 134 KA patients (mean age 71/68 years) changed from 4.3 (SD 1.9)/4.5 (1.8) preoperatively to 6.6 (1.8)/6.2 (1.0) at 1-year follow-up. 103 (79%) HA and 89 (66%) KA patients reported increased activity. Effect sizes were large (1.2/0.96). Knee patients reaching minimal important change (MIC, ≥ 8 Oxford Knee Score points) had higher 1-year UCLA scores than patients not reaching MIC. Interpretation — Original scale development was undocumented. Content validity was questionable, and there was discrepancy between patient and examiner estimates. UCLA appears valuable for measuring change in self-reported physical activity on a group level. 4 out of 5 HA patients and 2 out of 3 KA patients were more physically active 1 year after joint replacement surgery.
De Novo Germline and Somatic Variants Convergently Promote Endothelial-to-Mesenchymal Transition in Simplex Brain Arteriovenous Malformation

Supplemental Digital Content is available in the text. Rationale: Brain arteriovenous malformations (bAVMs) are abnormal entanglement of blood vessels in brain, with direct connections from arteries to veins, lacking functional capillary bed. Although several somatic mutations were reported, the molecular mechanism and genetic disposition of bAVM remain poorly understood. Objective: We aim to identify transcriptional anomalies and critical functional pathways in bAVM lesions and explore their association with key de novo germline and somatic variants in bAVM patients. Methods and Results: We established a comprehensive bAVM dataset from 269 patients, by performing single-cell sequencing of 17 bAVM lesions, whole-exome sequencing of germline DNA from 60 case-unaffected-parental trios, and genomic/transcriptomic sequencing of 231 bAVM lesions. We found abnormal expression of endothelial and mesenchymal markers in bAVM at both bulk and single-cell level, which was validated by flow cytometric analysis and immunofluorescence staining, suggesting an involvement of endothelial-to-mesenchymal transition (EndMT) process in AVM (arteriovenous-malformation). Using data from the 60 trios, we identified nonsynonymous de novo germline mutations affecting 46 genes, including EXPH5 (detected in 2 independent cases), and vessel-related genes, such as EPAS1 and ENG. Interestingly, knockdown of epas1 in zebrafish embryo showed AVM-like phenotype exclusively in brain. Subsequent computational and experimental analyses demonstrated that expression of genes affected by de novo germline mutations was enriched in vascular cell types and was involved in EndMT-relevant behaviors including cell migration, angiogenesis, and cell marker transition. Moreover, we detected somatic KRAS mutations in 129 of 179 (72%) cases and showed that KRAS mutations were associated with bleeding as the first symptom (P=0.0072). Following experimental studies demonstrated that KRAS mutations independently regulated EndMT features, consolidating the involvement of EndMT in this disease. Lastly, we showed that lovastatin reversed EndMT features in vitro and ex vivo. Conclusions: Our results suggest the convergent role of de novo germline mutations and somatic mutations in regulating EndMT in bAVM and provided a potential therapeutic option.
Sex Differences in Protein Kinase A Signaling of the Latent Postoperative Pain Sensitization That Is Masked by Kappa Opioid Receptors in the Spinal Cord

Latent sensitization (LS) of pain engages pronociceptive signaling pathways in the dorsal horn that include NMDA receptor (NMDAR)→adenylyl cyclase-1 (AC1)→protein kinase A (PKA), and exchange proteins directly activated by cyclic AMP (Epacs). To determine whether these pathways operate similarly between males and females or are under the inhibitory control of spinal κ opioid receptors (KOR), we allowed hyperalgesia to resolve after plantar incision and then blocked KOR with intrathecal administration of LY2456302, which reinstated hyperalgesia and facilitated touch-evoked immunoreactivity of phosphorylated extracellular signal-regulated kinase (pERK) in neurons (NeuN) but not astrocytes (GFAPs) nor microglia (Iba1). LY2456302 reinstated hyperalgesia even when administered 13 months later, indicating that chronic postoperative pain vulnerability persists for over a year in a latent state of remission. In both sexes, intrathecal MK-801 (an NMDAR competitive antagonist) prevented LY2456302-evoked reinstatement of hyperalgesia as did AC1 gene deletion or the AC1 inhibitor NB001. NB001 also prevented stimulus-evoked pERK. In both sexes, the Epac inhibitor ESI-09 prevented reinstatement, whereas the Epac activator 8-CPT reinstated hyperalgesia. By contrast, the PKA inhibitor H89 prevented reinstatement only in male mice, whereas the PKA activator 6-bnz-cAMP itself evoked reinstatement at all doses tested (3–30 nmol, i.t.). In neither sex did incision change gene expression of KOR, GluN1, PKA, or Epac1 in dorsal horn. We conclude that sustained KOR signaling inhibits spinal PKA-dependent mechanisms that drive postoperative LS in a sex-dependent manner. Our findings support the development of AC1, PKA, and Epac inhibitors toward a new pharmacotherapy for chronic postoperative pain. SIGNIFICANCE STATEMENT Because of neural mechanisms that are not well understood, men and women respond differently to treatments for chronic pain. We report that surgical incision recruits a pronociceptive latent pain sensitization that persisted for over a year and was kept in check by the sustained analgesic activity of κ opioid receptors. NMDAR→AC1→cAMP→Epac signaling pathways in the dorsal horn of the spinal cord maintain latent sensitization in both males and females; however, only males recruit a PKA-dependent mechanism. This work presents a novel male-specific mechanism for the promotion of chronic postoperative pain.
The relation between body mass index and body fat percentage in Brazilian adolescents: assessment of variability, linearity, and categorisation

Abstract Reliable but accessible measures to capture body composition are highly important as the world is in an era of obesity-increase. The most used measure, the body mass index (BMI), nevertheless, has been judged as non-reliable to estimate body fat percentage (BF%). The present manuscript assessed the criticisms of BMI as a predictor of BF% and the BMI-based categories of nutritional status. 4164 children/adolescents from 9 to 18 years of age from Porto Velho, Brazil, had their anthropometric and skinfold measures taken. Controlling for socioeconomic status, school (private, public), sex and age, we compared proposed models/variables in the literature relating BMI and BF%. We evaluated the functions and the residual data to understand the variability of BF% estimate per BMI and evaluated three possible categorisations from BMI to predict BF% nutritional status. The function utilising (linear) BMI was the best to predict BF% (R 2 = 0.70) with a variability of only 6.49% around the function. Nevertheless, no categorisation of nutritional status was reliable to predict the nutritional status of individuals. BMI is reliable to estimate BF%. Nevertheless, new normative values must be proposed; the original categorisation fails to capture the nutritional status of children/adolescents from this region.
Prognostic factors of unresectable hepatocellular carcinoma treated with yttrium-90 radioembolization: results from a large cohort over 13 years at a single center.

Background A previous study of patients with unresectable hepatocellular carcinoma (HCC) was extended to further examine factors associated with overall survival (OS) after selective internal radiation therapy with yttrium-90 resin microspheres (Y90 SIRT). Methods Data from patients of any age diagnosed with unresectable HCC and treated with Y90 SIRT at our institution from 2004 through 2017 were retrospectively analyzed. Among other criteria, patients had to have Eastern Cooperative Oncology Group performance status 0 to 2, not have received Y90 SIRT previously, and not have extrahepatic disease. Primary outcome was OS; secondary outcomes included tumor response and adverse events (AEs). Kaplan-Meier survival analyses and multivariable Cox proportional hazards models were used to evaluate prognostic factors for OS. Results Of the 226 patients, 59% were White, 77% were male, and the mean age at first SIRT procedure was 65.1±9.4 years. More than half had received previous treatment for HCC. The most common etiology was hepatitis C (n=138/224 available, 62%), followed by alcohol use (n=45, 20%), and nonalcoholic steatohepatitis (n=27, 12%). The mean model for end-stage liver disease score at baseline was 8.8±2.2. Patients were followed-up for a median of 12.2 months (95% CI, 0.0-62.6). Median OS was 16.6 months (95% CI, 13.1 to not reached). Bilobar disease, higher albumin-bilirubin score at baseline, prior treatment with sorafenib, alcohol use etiology, and higher administered dose were associated with shorter survival, whereas subsequent liver transplant [in 26 patients (11.5%)] was associated with longer survival. Of the 186 patients with AEs data, 75 (40.3%) patients reported an event and, of these, 13 (17.3%) patients had grade 4 bilirubin values. Conclusions In a large, diverse population treated at a single center over 13 years, Y90 SIRT produced a median OS of 16.6 months in patients with unresectable HCC and enabled subsequent transplantation in a subset of patients. Factors affecting the length of survival should be considered when making treatment decisions for unresectable HCC.
The role of clinician assistants in addressing perinatal depression

Abstract Background Upwards of one in seven individuals experience perinatal depression and many individuals cannot access treatment. In response, perinatal depression is increasingly being managed in the obstetric setting. This study aimed to characterize the experiences of clinicians and clinician assistants to inform the extent to which clinician assistants can help address depression in obstetric settings. Methods This cross-sectional analysis used data from an ongoing cluster randomized control trial: The PRogram In Support of Moms (PRISM). Participants included clinicians (physicians, certified nurse midwives, nurse practitioners) and clinician assistants (medical assistants, nursing assistants). Baseline data regarding practices and attitudes of clinicians and clinician assistants toward addressing depression in the obstetric setting were described. Logistic regressions were used to examine the association of clinician time to complete work and depression management. Results Clinician assistants experienced significantly fewer time constraints than did clinicians. However, having adequate time to complete work was not significantly associated with increased depression management in clinicians. Clinician assistants reported feeling that addressing depression is an important part of their job, despite variation in doing so. Conclusion Clinician assistants are interacting with perinatal women extensively and are a vital part of obstetric care workflows. Clinician assistants report that they want to address depression and have time to do so. Thus, clinician assistants may be poised to help address the mental health needs of perinatal individuals.
Modelling axial mixing of char - application to the dense bottom bed in CFB boilers

This work presents a semi-empirical two-phase model for the axial mixing of a spherical tracer particle, aiming to represent a char particle, with application to conditions relevant for the dense bottom bed flow in CFB boilers. The velocity fields of both the bubble and emulsion phases are modelled with validated expressions from literature, while the velocity of the tracer particle in the emulsion phase is obtained from the equation of motion. A correlation for the drag force created by the bed and acting on the tracer particle is found with the help of experimental data from fluid-dynamically down-scaled tests (Kohler et al, 2017). The model is used to predict trends in axial mixing with operational parameters (fluidization velocity, dense bed height) and tracer properties (size and density), which agree well with experimental findings in literature.
On Uncertainty in Information Architecture

Uncertainty, in general, is a fundamental aspect of human activity and underlies much of our decision making. The notion of uncertainty in information seeking, in particular, dates back to Shannon and Weaver (1949) and since then has been investigated in many forms. Kulthau’s (1993) work on information uncertainty is perhaps the most extensive. Through two specific examples, this article proposes uncertainty as a unifying heuristic in information architecture. Measurements of uncertainty can serve a diagnostic function in both the design and evaluation of information technologies and user interfaces. As a relatively new field of practice and study, information architecture borrows from established disciplines, such as computer science, human-computer interaction, and graphic design. Historically, library and information science (LIS) has proven to be a major source of guidance and of inspiration. For instance, existing knowledge from LIS on controlled vocabularies and facets informs thought on those subjects in information architecture. Borrowing from prior research in information-seeking behavior, this essay explores the idea of identifying a common, overarching principle in information architecture: uncertainty
Engineering Zeolites for Catalytic Cracking to Light Olefins

Propene is a key building block for the petrochemical industry whose demand is increasing strongly in recent years, even faster than that of ethene. The availability of propene is limited, and therefore, efforts to optimize its production are being pursued. On the occasion of the 75th anniversary of the first FCC unit, we analyze some recent advances that have been achieved in the understanding and development of zeolites aiming to increase the production of light olefins as petrochemical building blocks by means of catalytic cracking. We discuss a selected group of emerging strategies in zeolite engineering that have great prospects for research and that we consider could impact the sector in the near future. These include advances in crystal engineering and hierarchization achieved through bottom-up and top-down approaches, composite materials, tuning of the location of active sites among the different crystallographic positions available, and, importantly, how to characterize these modifications and th.
Functional and Structural Characterization of Acquired 16S rRNA Methyltransferase NpmB1 Conferring Pan-Aminoglycoside Resistance

Posttranslational methylation of the A site of 16S rRNA at position A1408 leads to pan-aminoglycoside resistance encompassing both 4,5- and 4,6-disubstituted 2-deoxystreptamine (DOS) aminoglycosides. To date, NpmA is the only acquired enzyme with such a function. ABSTRACT Posttranslational methylation of the A site of 16S rRNA at position A1408 leads to pan-aminoglycoside resistance encompassing both 4,5- and 4,6-disubstituted 2-deoxystreptamine (DOS) aminoglycosides. To date, NpmA is the only acquired enzyme with such a function. Here, we present the function and structure of NpmB1, whose sequence was identified in Escherichia coli genomes registered from the United Kingdom. NpmB1 possesses 40% amino acid identity with NpmA1 and confers resistance to all clinically relevant aminoglycosides, including 4,5-DOS agents. Phylogenetic analysis of NpmB1 and NpmB2, its single-amino-acid variant, revealed that the encoding gene was likely acquired by E. coli from a soil bacterium. The structure of NpmB1 suggests that it requires a structural change of the β6/7 linker in order to bind to 16S rRNA. These findings establish NpmB1 and NpmB2 as the second group of acquired pan-aminoglycoside resistance 16S rRNA methyltransferases.
Patient Interest in Receiving Assistance with Self-Reported Social Risks

Objectives: This study evaluated how often patients who reported social risk factors requested assistance with these risks in an integrated health system. Methods: We examined how self-reports of risk related to stated desire for help with that risk reported during social risk screenings at Kaiser Permanente Northwest (KPNW). We examined how patient characteristics were associated with desire for help with each social risk domain using logistic regression. Results: Approximately 24% (n = 7,807) of the 32,865 KPNW members aged ≥ 18 years who were screened between June 1, 2017, and December 31, 2019, reported at least 1 social risk. More than half of patients who reported a risk were risk/help concordant (i.e., they also wanted help with that risk). The highest concordance (81.7%) was observed among patients reporting medical financial hardship. Several demographic, health, and other factors were associated with concordance across domains. Conclusions: Patients do not request assistance for all reported social needs. Our findings could help shape future work examining patients' reasons for not accepting assistance and developing interventions to help patients with high social risk more effectively.