Miracle-dz/UniFAR-FTUs huggingface dataset:
Assembly of Hepatocyte Spheroids Using Magnetic 3D Cell Culture for CYP450 Inhibition/Induction

There is a significant need for in vitro methods to study drug-induced liver injury that are rapid, reproducible, and scalable for existing high-throughput systems. However, traditional monolayer and suspension cultures of hepatocytes are difficult to handle and risk the loss of phenotype. Generally, three-dimensional (3D) cell culture platforms help recapitulate native liver tissue phenotype, but suffer from technical limitations for high-throughput screening, including scalability, speed, and handling. Here, we developed a novel assay for cytochrome P450 (CYP450) induction/inhibition using magnetic 3D cell culture that overcomes the limitations of other platforms by aggregating magnetized cells with magnetic forces. With this platform, spheroids can be rapidly assembled and easily handled, while replicating native liver function. We assembled spheroids of primary human hepatocytes in a 384-well format and maintained this culture over five days, including a 72 h induction period with known CYP450 inducers/inhibitors. CYP450 activity and viability in the spheroids were assessed and compared in parallel with monolayers. CYP450 activity was induced/inhibited in spheroids as expected, separate from any toxic response. Spheroids showed a significantly higher baseline level of CYP450 activity and induction over monolayers. Positive staining in spheroids for albumin and multidrug resistance-associated protein (MRP2) indicates the preservation of hepatocyte function within spheroids. The study presents a proof-of-concept for the use of magnetic 3D cell culture for the assembly and handling of novel hepatic tissue models.
Does the Open Payments Database Provide Sunshine on Neurosurgery?

BACKGROUND The Open Payments Database (OPD) was launched by the Centers for Medicare & Medicaid Services in 2014. Through this online searchable database, the public can explore physician-industry interactions. To date, there is no published literature on the accuracy of the database for neurosurgeons or any physician specialty. OBJECTIVE To study the accuracy of published records and scope of industry-neurosurgeon relationships between neurosurgeons and industry within the OPD. METHODS We searched 4.3 million records in 2013 and 11.41 million records in 2014 in the OPD for board-certified neurosurgeons verified by the American Board of Neurological Surgery. Delimit software was used to condense these data, Microsoft Access for database queries, and STATA to perform descriptive analyses. RESULTS Of the 3240 neurosurgeons in the OPD in 2013, 2020 were identified correctly as neurosurgeons within the database (62%). Of the 3593 neurosurgeons in the OPD in 2014, 2433 were identified correctly as neurosurgeons (68%). Within the OPD in 2013, there were 72 066 attributed records for neurosurgeons; within the 2014 OPD, there were 160 563 attributed records for neurosurgeons. Total payments to neurosurgeons in 2013 (for the 9 months published in OPD): $61 802 659.37; in 2014: $117 127 824.00. CONCLUSION The OPD details physician interactions with industry and has multiple inaccuracies. Publicly availing inaccurate information through a searchable governmental website that can be accessed by patients and journalists alike has the potential to tarnish individual neurosurgeons and undermine professional credibility. ABBREVIATIONS CMS, Centers for Medicare & Medicaid ServicesOPD, Open Payments Database.
An ultra-low-power voltage-mode asynchronous WTA-LTA circuit

This paper presents an asynchronous mixed-signal WTA-LTA circuit conceived to carry out local minimum maximum indexing in massively parallel image processing arrays. The hardware is focused on energy-efficient operation. We describe a realization for the standard CMOS base process of a commercial 3-D TSV stack featuring a power consumption of only 20pW per elementary cell at 30fps. The proposed block is also capable of resolving small voltage differences without requiring any external reference. This leads to a hit percentage greater than 90% even when taking into account global process variations and mismatch conditions.
Effectiveness of a web-based intervention in reducing binge drinking among nightclub patrons

ABSTRACT OBJECTIVE To evaluate the effectiveness of a web-based intervention in reducing binge drinking among nightclub patrons after six months. METHODS We carried out a website survey with probabilistic sample in 31 nightclubs in the city of São Paulo, Brazil, which originated a randomized controlled trial with 1,057 participants. Those classified as problem drinkers (n = 465) using the Alcohol Use Disorders Identification Test were randomized into two study groups – intervention and control. The web-based intervention consisted of exposing the participants to a normative feedback screen about their alcohol consumption, characterizing the risks associated with amount consumed, money spent on drinks, drinking and driving, risk classification of Alcohol Use Disorders Identification Test, and tips to reduce damage. RESULTS There was a significant reduction in the practice of binge drinking in the week estimated at 38% among participants in the intervention group after six months (p < 0.05). However, there was no significant reduction in the outcomes when we analyzed the intervention and control groups and at baseline and after sixth months, simultaneously. CONCLUSIONS We cannot conclude that digital tools reduce the pattern of binge drinking among party goers in São Paulo. More studies are needed with this methodology because of its attractiveness to this type of group, given the privacy and speed that personalized information is transmitted.
Hypothalamic paraventricular nucleus neuronal nitric oxide synthase activity is a major determinant of renal sympathetic discharge in conscious Wistar rats

What is the central question of this study? Does chronic reduction of neuronally generated nitric oxide in the hypothalamic paraventricular nucleus affect the set‐point regulation of blood pressure and sympathetic activity destined to the kidneys? What is the main finding and its importance? Within the hypothalamic paraventricular nucleus, nitric oxide generated by neuronal nitric oxide synthase plays a major constitutive role in suppressing long term the levels of both ongoing renal sympathetic activity and arterial pressure in conscious Wistar rats. This finding unequivocally demonstrates a mechanism by which the diencephalon exerts a tonic influence on sympathetic discharge to the kidney and may provide the basis for both blood volume and osmolality homeostasis.
A Combination Treatment Using Ethyl Formate and Phosphine to Control Planococcus citri (Hemiptera: Pseudococcidae) on Pineapples.

Citrus mealybug, Planococcus citri (Risso), is a known quarantine pest that is difficult to control with phosphine (PH3) or low concentrations of ethyl formate (EF), particularly at low temperatures. Methyl bromide (MB) is a fumigant used for quarantine and preshipment (QPS) that can eradicate target pests with short fumigation periods. However, MB, which is an ozone-depleting substance, is scheduled to be phased out in South Korea over the next decade. There is no ideal alternative fumigant to replace MB for QPS of perishable commodities. A laboratory study was conducted to compare the individual effects of EF and PH3 individually, and the effects of EF mixed with PH3 as an MB alternative for the control of P. citri adults, nymphs, and eggs. In comparison to treatments with EF and PH3 individually, EF mixed with PH3 resulted in high toxicity to all stages of P. citri. The eggs were more tolerant than the nymphs and adults. A mixed treatment of EF and PH3 achieved complete control of eggs infesting pineapples at concentrations of 25.1/1.0 (EF/PH3) mg/liter at 8 °C for 4 h of exposures. This new combined EF/PH3 fumigation technology could offer shorter exposure times and less damage to perishable commodities at low temperatures, and could potentially be extended to controlling other quarantine pests as a replacement treatment for fruit and vegetables in which methyl bromide is currently being used.
An Approach for Sequential Dictionary Learning in Nonuniform Noise

Dictionary learning algorithms have received widespread acceptance when it comes to data analysis and signal representation problems. However, most existing algorithms assume isotropic noise. This is a restrictive assumption as the noise across samples may be nonuniform in a number of real world application. The aim of this article is to propose a sequential dictionary learning algorithm for measurement data vectors affected by nonuniform noise. As most of the existing algorithms, the proposed method is a two stages iterative algorithm where the effect of the noise nature appears in the sparse coding and dictionary update stages. The cost function used to derive the dictionary update stage is developed based on the link between singular value decomposition and rank one matrix approximation. Results on the simulated dictionary recovery problem and an application on face recognition dataset shows that the proposed algorithm outperforms current state of the art dictionary learning methods.
Reading for Meaning: What Influences Paragraph Understanding in Aphasia?

Purpose The current study investigated the effect of text variables including length, readability, propositional content, and type of information on the reading comprehension of people with aphasia. Method The performance of 75 people with aphasia was compared with 87 healthy, age-matched control participants. Reading comprehension was considered in terms of both accuracy in responding to questions tapping comprehension and reading time. Participants with aphasia (PWA) were divided into 2 groups (no reading impairment [PWA:NRI] and reading impairment [PWA:RI]) depending on whether their performance fell within the 5th percentile of control participants. Results As groups, both PWA:NRI and PWA:RI differed significantly from control participants in terms of reading time and comprehension accuracy. PWA:NRI and PWA:RI differed from each other in terms of accuracy but not reading time. There was no significant effect of readability or propositional density on comprehension accuracy or reading time for any of the groups. There was a significant effect of length on reading time but not on comprehension accuracy. All groups found main ideas easier than details, stated information easier than inferred, and had particular difficulty with questions that required integration of information across paragraphs (gist). Conclusions Both accuracy of comprehension and reading speed need to be considered when characterizing reading difficulties in people with aphasia.
Long-Term Outcomes in the Treatment of Classical Trigeminal Neuralgia by Gamma Knife Radiosurgery: A Retrospective Study in Patients With Minimum 2-Year Follow-up.

BACKGROUND Gamma knife radiosurgery (GKRS) is one of the alternatives for treatment for classical trigeminal neuralgia (TN). OBJECTIVE To retrospectively analyze long-term outcomes for TN using GKRS achieved at our institution. METHODS One hundred seventeen patients with medically refractory TN treated by GKRS at our institution were followed up between 1993 and 2011. Mean maximum dose was 86.5 Gy (range: 80-90 Gy; median: 90 Gy). Clinical response was defined based on the Burchiel classification. We considered classes I and II as a complete response. For toxicity, we use the Barrow Neurological Institute facial numbness scale. Mean duration of follow-up was 66 months (range: 24-171 months). RESULTS Complete response at last follow-up in our patients was 81%, with an excellent response while off medication in 52%. Pain-free rates without medication (class I) were 85% at 3 years (confidence interval [CI]: 78%-94%), 81% at 5 years (CI: 72%-91%), and 76% at 7 years (CI: 65%-90%). Complete response rates (classes I-II) were 91% at 3 years (CI: 86%-97%), 86% at 5 years (CI: 79%-93%), and 82% at 7 years (CI: 72%-93%). Poor treatment response rates differed significantly between patients who had undergone previous surgery and were refractory to management with medication prior to GKRS. New or worsening facial numbness was reported in 32.5% (30% score II and 2.5% score III). No anesthesia dolorosa was reported. Permanent recurrence pain rate was 12%. CONCLUSION GKRS achieved favorable outcomes compared with surgery in terms of pain relief and complication rates in our cohort of patients, notwithstanding decreasing pain-free survival rates over time. We consider GKRS to be an initial treatment in the management of medically intractable TN in selected patients. ABBREVIATIONS CI, confidence intervalGKRS, gamma knife radiosurgeryMVD, microvascular decompressionRS, radiosurgeryTN, trigeminal neuralgia.
Mean-field Games for Bio-inspired Collective Decision-making in Dynamical Networks

Given a large number of homogeneous players that are distributed across three possible states, we consider the problem in which these players have to control their transition rates, while minimizing a cost. The optimal transition rates are based on the players' knowledge of their current state and of the distribution of all the other players, and this introduces mean-field terms in the running and the terminal cost. The first contribution involves a mean-field game model that brings together macroscopic and microscopic dynamics. We obtain the mean-field equilibrium associated with this model, by solving the corresponding initial-terminal value problem. We perform an asymptotic analysis to obtain a stationary equilibrium for the system. The second contribution involves the study of the microscopic dynamics of the system for a finite number of players that interact in a structured environment modeled by an interaction topology. The third contribution is the specialization of the model to describe honeybee swarms, virus propagation, and cascading failures in interconnected smart-grids. A numerical analysis is conducted which involves two types of cyber-attacks. We simulate in which ways failures propagate across the interconnected smart grids and the impact on the grids frequencies. We reframe our analysis within the context of Lyapunov's linearisation method and stability theory of nonlinear systems and Kuramoto coupled oscillators model.
Rethinking the Smaller-Norm-Less-Informative Assumption in Channel Pruning of Convolution Layers

Model pruning has become a useful technique that improves the computational efficiency of deep learning, making it possible to deploy solutions in resource-limited scenarios. A widely-used practice in relevant work assumes that a smaller-norm parameter or feature plays a less informative role at the inference time. In this paper, we propose a channel pruning technique for accelerating the computations of deep convolutional neural networks (CNNs) that does not critically rely on this assumption. Instead, it focuses on direct simplification of the channel-to-channel computation graph of a CNN without the need of performing a computationally difficult and not-always-useful task of making high-dimensional tensors of CNN structured sparse. Our approach takes two stages: first to adopt an end-to- end stochastic training method that eventually forces the outputs of some channels to be constant, and then to prune those constant channels from the original neural network by adjusting the biases of their impacting layers such that the resulting compact model can be quickly fine-tuned. Our approach is mathematically appealing from an optimization perspective and easy to reproduce. We experimented our approach through several image learning benchmarks and demonstrate its interesting aspects and competitive performance.
Significantly Increased Odds of Reporting Previous Shoulder Injuries in Female Marines Based on Larger Magnitude Shoulder Rotator Bilateral Strength Differences

Background: Musculoskeletal injuries to the extremities are a primary concern for the United States (US) military. One possible injury risk factor in this population is side-to-side strength imbalance. Purpose: To examine the odds of reporting a previous shoulder injury in US Marine Corps Ground Combat Element Integrated Task Force volunteers based on side-to-side strength differences in isokinetic shoulder strength. Study Design: Cohort study; Level of evidence, 3. Methods: Male (n = 219) and female (n = 91) Marines were included in this analysis. Peak torque values from 5 shoulder internal/external rotation repetitions were averaged and normalized to body weight. The difference in side-to-side strength measurements was calculated as the absolute value of the limb difference divided by the mean peak torque of the dominant limb. Participants were placed into groups based on the magnitude of these differences: <10%, 10% to 20%, and >20%. Odds ratios (ORs) and 95% CIs were calculated. Results: When separated by sex, 13.2% of men reported an injury, while 5.5% of women reported an injury. Female Marines with >20% internal rotation side-to-side strength differences demonstrated increased odds of reporting a previous shoulder injury compared with female Marines with <10% strength differences (OR, 15.4; 95% CI, 1.4-167.2; P = .03 ) and female Marines with 10% to 20% strength differences (OR, 13.9; 95% CI, 1.3-151.2; P = .04). No significant ORs were demonstrated in male Marines. Conclusion: Marines with larger magnitude internal rotation strength differences demonstrated increased odds of reporting a previous shoulder injury compared with those with lesser magnitude differences. Additionally, female sex appears to drastically affect the increased odds of reporting shoulder injuries (OR, 13.9-15.4) with larger magnitude differences (ie, >20%) compared with those with lesser magnitude differences (ie, <10% and 10%-20%). The retrospective cohort design of this study cannot delineate cause and effect but establishes a relationship between female Marines and greater odds of larger magnitude strength differences after returning from an injury.
The alignment imperative in curriculum renewal

Abstract Rationale: There are perennial calls for MD curricula to reform in order to meet the changing needs of students, patients, and society. And yet, efforts at renewal have also been suggested to have minimal impact on the pedagogy and outcomes of medical education. One reason may be misalignment between the components of the curriculum during design and implementation. The University of Toronto MD program recently renewed its undergraduate preclinical Foundations curriculum. Mindful of the pitfalls of misalignment, the renewal process focused deliberately on alignment between the various components of the curriculum: instructional methods, student assessment, faculty development, and the larger purpose of serving students and society. Innovation: Educational evidence was used to drive the alignment process which resulted in three major changes. First, we created a spiral curriculum centered on 72 virtual patient cases designed to integrate content and prepare students for clinical learning. Second, we introduced a novel medical psychiatry component to address a core societal need in mental health. This exposed students early to experiences of complexity, ambiguity, and integrated patient care. Lastly, a shift to assessment for learning and programmatic assessment was designed and implemented concurrently to reinforce the pedagogy of the curriculum. Synchronous faculty development was developed for the new roles required of faculty. Conclusions: Early program evaluation shows alignment of these curricular components requires ongoing attention and resources in order to be successful. The potential benefits of this alignment are well prepared students who can meet the needs of their patients and society in an increasingly complex health system.
Genetic analysis of primary and secondary immune responses in the chicken.

Abstract Total agglutinin antibody titers, 2-mercaptoethanol (2-ME) sensitive, and 2-ME resistant antibody titers were determined in 561 White Plymouth Rock chicks. At 38 days of age chicks were intramuscularly injected with . 25 ml packed sheep red blood cells (SRBC) and at 66 days of age with . 5 ml SRBC. Antibody titers were determined on Days 0, 3, 5, 7, and 10 post-injection. Mean total titer (5.2, log2 value) was highest on Day 7 for the primary response and the secondary response peak titer (7.0) was measured on Day 5. The primary response was characterized by a very low level of 2-ME resistant antibodies. The secondary response consisted of both types of antibody. The heritability estimates indicate that selection for total antibody titer of the primary response can be based on the titer level of Day 5 postinjection (h2s = .39). For the secondary response, Days 3 (h2s = .34) and 5 (h2s = .28) postinjection can be considered. Phenotypic correlations between total antibody titers of first and second injection are not significant on Days 5, 7, and 10 post second injection. The negative relationship between primary and secondary 2-ME sensitive antibody titers in contrast with a positive relationship between primary 2-ME sensitive antibody titers and secondary 2-ME resistant antibody titers explains this result. Additive genetic correlations between total antibody titers of first and second injection tend to be quite negative on Days 5, 7, and 10 post second injection. Selection for an improved prophylactic response, therefore, appears to be not easily achieved either via selection of parameters of the primary immune response or via the secondary response.
Survival Rate of Resin and Ceramic Inlays, Onlays, and Overlays

This systematic review and meta-analysis aimed to evaluate the survival rate of ceramic and resin inlays, onlays, and overlays and to identify the complication types associated with the main clinical outcomes. Two reviewers searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for articles published between 1983 through April 2015, conforming to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews. Clinical studies meeting the following criteria were included: 1) studies related to resin and ceramic inlays, onlays, and overlays; 2) prospective, retrospective, or randomized controlled trials conducted in humans; 3) studies with a dropout rate of less than 30%; and 4) studies with a follow-up longer than 5 y. Of 1,389 articles, 14 met the inclusion criteria. The meta-regression indicated that the type of ceramic material (feldspathic porcelain vs. glass-ceramic), study design (retrospective vs. prospective), follow-up time (5 vs. 10 y), and study setting (university vs. private clinic) did not affect the survival rate. Estimated survival rates for glass-ceramics and feldspathic porcelain were between 92% and 95% at 5 y (n = 5,811 restorations) and were 91% at 10 y (n = 2,154 restorations). Failures were related to fractures/chipping (4%), followed by endodontic complications (3%), secondary caries (1%), debonding (1%), and severe marginal staining (0%). Odds ratios (95% confidence intervals) were 0.19 (0.04 to 0.96) and 0.54 (0.17 to 1.69) for pulp vitality and type of tooth involved (premolars vs. molars), respectively. Ceramic inlays, onlays, and overlays showed high survival rates at 5 y and 10 y, and fractures were the most frequent cause of failure.