Miracle-dz/UniFAR-FTUs huggingface dataset:
Bevacizumab Alone or in Combination with Irinotecan in Recurrent WHO Grade II and Grade III Gliomas

Background: The repertoire of salvage regimens for patients with WHO grade II and III gliomas recurring or progressing after surgery, radiotherapy and temozolomide chemotherapy is limited. Based on promising response and progression-free survival (PFS) data in recurrent glioblastoma, the use of bevacizumab (BEV) has been extended to recurrent grade II/III gliomas. Methods: We retrospectively assessed the safety and efficacy of BEV alone or combined with irinotecan in 39 patients with recurrent grade II/III gliomas. Results: Both BEV monotherapy and its combination with irinotecan were well tolerated. Response rates were 26% as monotherapy and 33% in combination using Macdonald and RANO criteria. The median PFS was 4.2 months and the PFS rate at 6 months 29% for BEV alone, and 4.7 months and 42% for the combination. The median overall survival was 14.8 months for BEV monotherapy and 8.1 months for the combination. Outcome after failure of BEV was better when patients continued BEV beyond progression. Conclusion: BEV has limited activity in recurrent grade II/III gliomas. The additional value of irinotecan remains questionable. Prospective studies with BEV-free control groups are required to better define the role of BEV among the limited options in patients with recurrent grade II/III gliomas.
Deep learning for electroencephalogram (EEG) classification tasks: a review

Objective. Electroencephalography (EEG) analysis has been an important tool in neuroscience with applications in neuroscience, neural engineering (e.g. Brain–computer interfaces, BCI’s), and even commercial applications. Many of the analytical tools used in EEG studies have used machine learning to uncover relevant information for neural classification and neuroimaging. Recently, the availability of large EEG data sets and advances in machine learning have both led to the deployment of deep learning architectures, especially in the analysis of EEG signals and in understanding the information it may contain for brain functionality. The robust automatic classification of these signals is an important step towards making the use of EEG more practical in many applications and less reliant on trained professionals. Towards this goal, a systematic review of the literature on deep learning applications to EEG classification was performed to address the following critical questions: (1) Which EEG classification tasks have been explored with deep learning? (2) What input formulations have been used for training the deep networks? (3) Are there specific deep learning network structures suitable for specific types of tasks? Approach. A systematic literature review of EEG classification using deep learning was performed on Web of Science and PubMed databases, resulting in 90 identified studies. Those studies were analyzed based on type of task, EEG preprocessing methods, input type, and deep learning architecture. Main results. For EEG classification tasks, convolutional neural networks, recurrent neural networks, deep belief networks outperform stacked auto-encoders and multi-layer perceptron neural networks in classification accuracy. The tasks that used deep learning fell into five general groups: emotion recognition, motor imagery, mental workload, seizure detection, event related potential detection, and sleep scoring. For each type of task, we describe the specific input formulation, major characteristics, and end classifier recommendations found through this review. Significance. This review summarizes the current practices and performance outcomes in the use of deep learning for EEG classification. Practical suggestions on the selection of many hyperparameters are provided in the hope that they will promote or guide the deployment of deep learning to EEG datasets in future research.
Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord

ABSTRACT The coordinated spatial and temporal regulation of gene expression in the vertebrate neural tube determines the identity of neural progenitors and the function and physiology of the neurons they generate. Progress has been made deciphering the gene regulatory programmes that are responsible for this process; however, the complexity of the tissue has hampered the systematic analysis of the network and the underlying mechanisms. To address this, we used single cell mRNA sequencing to profile cervical and thoracic regions of the developing mouse neural tube between embryonic days 9.5-13.5. We confirmed that the data accurately recapitulates neural tube development, allowing us to identify new markers for specific progenitor and neuronal populations. In addition, the analysis highlighted a previously underappreciated temporal component to the mechanisms that generate neuronal diversity, and revealed common features in the sequence of transcriptional events that lead to the differentiation of specific neuronal subtypes. Together, the data offer insight into the mechanisms that are responsible for neuronal specification and provide a compendium of gene expression for classifying spinal cord cell types that will support future studies of neural tube development, function and disease. Summary: Single cell analysis provides an unbiased classification of neural tube cell populations and their associated gene expression profiles, identifying co-regulated genes that mediate a temporal programme of neuronal subtype specification.
Costs and quality of life effects of the first year of renal replacement therapy in one Finnish treatment centre

Abstract Objective: The main objective of the study was to assess the cost and quality of life (QoL) effects of elective dialysis patients during the first year of end-stage renal disease (ESRD) treatment in one Finnish treatment centre. Methods: A prospective case-series study was performed involving all elective dialysis patients (n=29) in a Finnish dialysis unit during 2003–2004. Direct costs of ESRD treatment were obtained from the hospital database and the Social Insurance Institution. The QoL effects were measured at the initiation of treatment, at 6 and at 12 months using 15D, a generic QoL instrument. Results: The average cost of ESRD treatment was €69,085. The improvement in the patients' QoL score was statistically and clinically significant during the first treatment year. The most significant changes were seen in the dimensions of breathing and vitality. The condition of patients commencing haemodialysis (HD) was more severe than that of patients commencing peritoneal dialysis (PD) as indicated by worse residual kidney function and poorer quality of life at the initiation. Conclusions: In this small patient population, treatment of ESRD during the first year seemed to improve or maintain the QoL of the patients.
Accelerating Typhoid Conjugate Vaccine Introduction: What Can Be Learned From Prior New Vaccine Introduction Initiatives?

Abstract The health consequences of typhoid, including increasing prevalence of drug-resistant strains, can stress healthcare systems. While vaccination is one of the most successful and cost-effective health interventions, vaccine introduction can take years and require considerable effort. The Typhoid Vaccine Acceleration Consortium (TyVAC) employs an integrated, proactive approach to accelerate the introduction of a new typhoid conjugate vaccine to reduce the burden of typhoid in countries eligible for support from Gavi, the Vaccine Alliance. TyVAC and its partners are executing a plan, informed by prior successful vaccine introductions, and tailored to the nuances of typhoid disease and the typhoid conjugate vaccine. The iterative process detailed herein summarizes the strategy and experience gained from the first 2 years of the project.
Introducing Transport “Surprises” in the Classroom: The Visible Fracture

Heterogeneity in aquifer properties, and the influence of transport processes other than advection and dispersion, often produce transport “surprises” in that measurements become difficult to reconcile with predictions from the traditional advection‐dispersion equation (ADE) that students are introduced to early in their hydrogeology training. Students should be aware of and prepared for the reasons why the ADE (as commonly applied) may not always “work” in the sense of generating valid predictions. Though the predictive limitations of the ADE have been frequently discussed in the hydrogeologic literature, our experience is that students are not appropriately skeptical of transport predictions. For this reason, we believe it is imperative that future generations of hydrogeologists are introduced to transport surprises early in their formative education. We present a laboratory activity, centered around a “Visible Fracture,” which was presented in a laboratory class period of 75 min. The Visible Fracture consists of two sheets of Plexiglas surrounding a heterogenous fluid‐filled aperture. Heated fluid is injected into the fracture, and thermochromic liquid crystal (TLC) materials are used to visualize the temperature both in the flowing fluid and in the surrounding Plexiglas “host rock. ” Visualization of the plume shows the complex shapes that can be produced due to macroscopic heterogeneity. Tracer particles within the fracture allow students to examine heterogeneous local advective velocities, and to observe retardation of the fluid temperature plume. Student self‐reported knowledge surveys indicate greater conceptual understanding of transport non‐idealities after experiencing this activity.
Education Policy and Outcomes Within the African American Population

ABSTRACT The educational status among African Americans is a story of continuing achievement and continuing disparities in outcomes. On one hand, there are continuing stories of high academic accomplishments among Black Americans who attend and graduate from high-ranking American institutions of higher education. On the other hand, the continuing gap in educational opportunities and outcomes within Black America is shaping present and future education disparities. This essay examines the impact of recent education policy on education reform and outcomes for African Americans. The dynamic characteristics of the Black American educational experience are discussed. Some attention is given to historical factors that helped shape present-day education reform measures and their impact on the African-American educational experience. Education policy as a public health issue is briefly addressed throughout this article. Suggestions are made for future policy initiatives and advocacy, teaching, and for human-service professionals working with Black children and youth in school settings.
Predator-Prey Games in Multiple Habitats Reveal Mixed Strategies in Diel Vertical Migration

Prey and predators continuously react to each other and to their environment, adjusting their behavior to maximize their fitness. In a pelagic environment, organisms can optimize their fitness by performing diel vertical migrations. We applied a game-theoretic approach to investigate the emergent patterns of optimal habitat selection strategies in a multiple-habitat arena. Our setup allows both players to choose their position at day and at night in the water column. The model reproduces features of vertical migrations observed in nature, including residency at depth or at the surface, vertical migrations, mixed strategies, and bimodal distributions within a population. The mixed strategies appear as a consequence of frequency-dependent processes and not of any intraspecies difference between individuals. The model also reveals a curious feature where natural selection on individuals can provoke distinct regime shifts and precipitate an irreversible collapse in fitness. In the case presented here, the increasing voracity of the predator triggers a behavioral shift in the prey, reducing the fitness of all members of the predator population.
Application of neurite orientation dispersion and density imaging to characterize brain microstructural abnormalities in type‐2 diabetics with mild cognitive impairment

Diffusion‐tensor‐imaging (DTI) is sensitive in detecting white matter changes in type‐2 diabetes mellitus (T2DM). However, DTI indices can be affected by either neurite density or spatial variation. A novel diffusion MRI technique, termed neurite orientation dispersion and density imaging (NODDI), can provide distinct indices of fiber density and dispersion.
Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation.

RATIONALE Prenatal exposure to tobacco smoke increases the risk for diseases later in the child's life that may be mediated through alterations in DNA methylation. OBJECTIVES To demonstrate that differences in DNA methylation patterns occur in children exposed to tobacco smoke and that variation in detoxification genes may alter these associations. METHODS Methylation of DNA repetitive elements, LINE1 and AluYb8, was measured using bisulfite conversion and pyrosequencing in buccal cells of 348 children participating in the Children's Health Study. Gene-specific CpG methylation differences associated with smoke exposure were screened in 272 participants in the Children's Health Study children using an Illumina GoldenGate panel. CpG loci that demonstrated a statistically significant difference in methylation were validated by pyrosequencing. Estimates were standardized across loci using a Z score to enable cross-comparison of results. MEASUREMENTS AND MAIN RESULTS DNA methylation patterns were associated with in utero exposure to maternal smoking. Exposed children had significantly lower methylation of AluYb8 (beta, -0.31; P = 0.03). Differences in smoking-related effects on LINE1 methylation were observed in children with the common GSTM1 null genotype. Differential methylation of CpG loci in eight genes was identified through the screen. Two genes, AXL and PTPRO, were validated by pyrosequencing and showed significant increases in methylation of 0.37 (P = 0.005) and 0.34 (P = 0.02) in exposed children. The associations with maternal smoking varied by a common GSTP1 haplotype. CONCLUSIONS Life-long effects of in utero exposures may be mediated through alterations in DNA methylation. Variants in detoxification genes may modulate the effects of in utero exposure through epigenetic mechanisms.
A practical generation interval-based approach to inferring the strength of epidemics from their speed

Infectious-disease outbreaks are often characterized by the reproductive number and 𝓡 exponential rate of growth r. 𝓡 provides information about out-break control and predicted final size. Directly estimating 𝓡 is difficult, while r can often be estimated from incidence data. These quantities are linked by the generation interval – the time between when an individual is infected by an infector, and when that infector was infected. It is often infeasible to ob-tain the exact shape of a generation-interval distribution, and to understand how this shape affects estimates of 𝓡. We show that estimating generation interval mean and variance provides insight into the relationship between and 𝓡 r. We use examples based on Ebola, rabies and measles to explore approximations based on gamma-distributed generation intervals, and find that use of these simple approximations are often sufficient to capture the r–𝓡 relationship and provide robust estimates of 𝓡.
Outcomes After Declining Increased Infectious Risk Kidney Offers for Pediatric Candidates in the United States.

BACKGROUND Kidneys from donors at increased risk for disease transmission (IRDs) confer substantial survival benefit in adults, yet the benefit of IRDs to pediatric candidates remains unclear in the context of high waitlist prioritization. METHODS Using 2010-2016 OPTN data, we studied 2417 pediatric candidates (age <18) who were offered an IRD kidney that was eventually used for transplantation. We followed candidates from date of first IRD offer until date-of-death or censorship and used Cox regression to estimate mortality risk associated with IRD acceptance vs decline adjusting for age, sex, race, diagnosis, and dialysis time. RESULTS Over the study period, 2250 (93.1%) pediatric candidates declined and 286 (11.8%) accepted an IRD offer; 119 (41.6%) of the 286 had previously declined a different IRD. Cumulative survival among those who accepted versus declined the IRD was 99.6% vs 99.4% 1yr and 96.3% vs 97.8% 6yrs post-decision (P = 0.1). Unlike the substantial survival benefit seen in adults (HR = 0.52), among pediatric candidates we did not detect a survival benefit associated with accepting an IRD (adjustedHR:0.791.723.73, P = 0.2). However, those who declined IRDs waited a median 9.6 months for a non-IRD kidney transplant (11.2 months among those <6yrs, 8.8 months among those on dialysis). KDPI of the eventually accepted non-IRD kidneys (median = 13, IQR = 6-23) was similar to KDPI of the declined IRDs (median = 16, IQR = 9-28). CONCLUSIONS Unlike in adults, IRDs conferred no survival benefit to pediatric candidates, although they did reduce waiting times. The decision to accept IRD kidneys should balance the advantage of faster transplantation against the risk of infectious transmission.
Long-term prognostic impact of hyperuricemia in community

Abstract The debate whether an elevated level of serum uric acid (SUA) is an independent marker of cardiovascular risk is still going on. We examined morbidity and mortality related to SUA and hyperuricemia in a well-characterized population with very long follow-up. Study included 4696 participants (aged 30–59 years at baseline) of the coronary heart disease (CHD) Study of the Finnish Mobile Clinic Health Examination Survey. Adjusted hazard ratios (HRs) of hyperuricemia (defined as ≥360 µmol/l and ≥420 µmol/l) and SUA quintiles for mortality and adverse cardiovascular outcomes are reported. During the mean follow up of 30.6 years there were 2723 deaths, 887 deaths for CHD of which 340 were classified as sudden cardiac deaths, 1642 hospitalizations due to CHD and 798 hospitalizations due to congestive heart failure. After adjusting to baseline risk factors and presence of cardiovascular diseases as well as the use of diuretics there were no significant differences in the risk of any of the outcomes when analyzed either according to quintiles of SUA or using a cut-off point SUA ≥360 µmol/l for hyperuricemia. Only a rare finding of hyperuricemia SUA ≥420 µmol/l among women (n = 17, 0.9%) was independently associated with significantly higher risk of mortality (adjusted HR: 2.59, 95% CI: 1.54–4.34) and a combination end-point of major adverse cardiac events (MACEs) (HR: 2.69; 95% CI: 1.56–4.66). SUA was not an independent indicator of morbidity and mortality, with the exception of particularly high levels of SUA among women.
The influence of serum‐supplemented culture media in a transwell migration assay

Our work cautions against the use of serum‐supplemented culture media in a transwell migration assay when using chemoattractants other than FBS. At 24 h, a 5% foetal bovine serum (FBS) gradient caused BV2 microglia to migrate toward the lower compartment of the transwell apparatus. Interestingly, FBS‐supplemented media in the absence of a gradient also resulted in notable microglia migration. Serum can therefore confound the interpretation of a transwell migration assay when another chemoattractant is used.
Diabetes Technology and Therapy in the Pediatric Age Group.

The current study assesses the Insulet model predictive control algorithm in youth, adolescents, and adults with type 1 diabetes (T1D). Insulet’s system utilizes the OmniPod patch pump, Dexcom G4 CGM, and a model predictive control algorithm running on a tablet for automated insulin delivery. during treatment with either dose of linagliptin.
National and regional dose escalation and cost of tumor necrosis factor blocker therapy in biologic-naïve rheumatoid arthritis patients in US health plans

Abstract Objective: This study examined the proportion and magnitude of dose escalation nationally and regionally among rheumatoid arthritis (RA) patients treated with TNF-blockers and estimated the costs of TNF-blocker therapy. Methods: This retrospective cohort study used claims data from US commercially-insured adult RA patients who initiated adalimumab, etanercept, or infliximab therapy between 2005–2009. Biologic-naïve patients enrolled in the health plan for ≥6 months before and ≥12 months after therapy initiation were followed for 12 months. Dose escalation was assessed using three methods: (1) average weekly dose > recommended label dose, (2) average ending dispensed dose > maintenance dose, and (3) average dose after maintenance dose > maintenance dose. Annual cost of therapy included costs for mean dose and drug administration fees. Results: Overall, 1420 etanercept, 874 adalimumab, and 454 infliximab patients were included. A significantly lower proportion of etanercept-treated patients had dose escalation using the average weekly dose (3.9% vs 21.4% adalimumab and 69.6% infliximab; p < 0.0001), average ending dispensed dose (1.1% vs 10.6% adalimumab and 63.0% infliximab; p < 0.0001), and average dose after maintenance dose methods (2.8% vs 15.7% adalimumab and 69.6% infliximab; p < 0.0001). Regional dose escalation rates and magnitudes of escalation were directionally consistent with national rates. Etanercept had the lowest cost per treated RA patient ($19,690) compared to adalimumab ($23,020) and infliximab ($24,030). Limitations: Exclusion of patients not on continuous TNF-blocker therapy limits the generalizability; however, ∼50% of patients were persistent on therapy for 12 months. The study population comprised RA patients in commercial health plans, thus the results may not be generalizable to Medicare or uninsured populations. Conclusions: In this retrospective study, etanercept patients had the lowest proportions and magnitudes of dose escalation across all methods compared to adalimumab and infliximab patients nationally and regionally. Mean annual cost was lowest for etanercept-treated patients.
Internet Usage by Women with Eating Disorders during Illness and Recovery

ABSTRACT Internet usage may have both positive and negative impacts on people with eating disorders. In research to date, most of the focus has been put on the harms connected with platforms that support people in continuing their disorder. Less studied have been the benefits of other technology platforms used by people with eating disorders. When these different platforms were investigated, users were rarely interviewed about their experience. To fill this gap, we conducted 30 interviews with participants aged 16 to 28, all female, living in the Czech Republic. The interviews focused on their experiences with the harmful and helpful impacts of the internet on the course of their eating disorders. The data were analyzed via thematic analysis. The results provided insight into the participants’ experience with the following online environments: 1) nonprofessional pro-eating disorder platforms; 2) nonprofessional pro-recovery platforms; 3) social networking sites (SNS); 4) platforms for counting calories and setting weight goals; 5) platforms about food, exercise, and lifestyle; and 6) platforms providing professional help. The participants noted many benefits these platforms could provide; however, their ability to achieve the benefits was affected by their motivation for treatment. As a result, even platforms designed to support recovery could be used for illness maintenance. The results are discussed in the context of research on the changing motivations for recovery in people with eating disorders and the theory of different processes connected to the course of the eating disorders according to the differential interactivity of digital platforms.