Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of bladder filling on doses to prostate and organs at risk: a treatment planning study

In the present study, we aimed to evaluate effects of bladder filling on dose–volume distributions for bladder, rectum, planning target volume (PTV), and prostate in radiation therapy of prostate cancer. Patients (n=21) were scanned with a full bladder, and after 1 hour, having been allowed to void, with an empty bladder. Radiotherapy plans were generated using a four‐field box technique and dose of 70 Gy in 35 fractions. First, plans obtained for full‐ and empty‐bladder scans were compared. Second, situations in which a patient was planned on full bladder but was treated on empty bladder, and vice versa, were simulated, assuming that patients were aligned to external tattoos. Doses to the prostate [equivalent uniform dose (EUD)], bladder and rectum [effective dose (Deff)], and normal tissue complication probability (NTCP) were compared. Dose to the small bowel was examined. Mean bladder volume was 354.3 cm3 when full and 118.2 cm3 when empty. Median prostate EUD was 70 Gy for plans based on full‐ and empty‐bladder scans alike. The median rectal Deff was 55.6 Gy for full‐bladder anatomy and 56.8 Gy for empty‐bladder anatomy, and the corresponding bladder Deff was 29.0 Gy and 49.3 Gy respectively. In 1 patient, part of the small bowel (7.5 cm3) received more than 50 Gy with full‐bladder anatomy, and in 6 patients, part (2.5 cm3−30 cm3) received more than 50 Gy with empty‐bladder anatomy. Bladder filling had no significant impact on prostate EUD or rectal Deff. A minimal volume of the small bowel received more than 50 Gy in both groups, which is below dose tolerance. The bladder Deff was higher with empty‐bladder anatomy; however, the predicted complication rates were clinically insignificant. When the multileaf collimator pattern was applied in reverse, substantial underdosing of the planning target volume (PTV) was observed, particularly for patients with prostate shifts in excess of 0.5 cm in any one direction. However, the prostate shifts showed no correlation with bladder filling, and therefore the PTV underdosing also cannot be related to bladder filling. For some patients, bladder dose–volume constraints were not fulfilled in the worst‐case scenario—that is, when a patient planned with full bladder consistently arrived for treatment with an empty bladder. PACS numbers: 87.53. ‐j, 87.53. Kn, 87.53. Tf
Expression of Tra2β in Cancer Cells as a Potential Contributory Factor to Neoplasia and Metastasis

The splicing regulator proteins SRSF1 (also known as ASF/SF2) and SRSF3 (also known as SRP20) belong to the SR family of proteins and can be upregulated in cancer. The SRSF1 gene itself is amplified in some cancer cells, and cancer-associated changes in the expression of MYC also increase SRSF1 gene expression. Increased concentrations of SRSF1 protein promote prooncogenic splicing patterns of a number of key regulators of cell growth. Here, we review the evidence that upregulation of the SR-related Tra2β protein might have a similar role in cancer cells. The TRA2B gene encoding Tra2β is amplified in particular tumours including those of the lung, ovary, cervix, stomach, head, and neck. Both TRA2B RNA and Tra2β protein levels are upregulated in breast, cervical, ovarian, and colon cancer, and Tra2β expression is associated with cancer cell survival. The TRA2B gene is a transcriptional target of the protooncogene ETS-1 which might cause higher levels of expression in some cancer cells which express this transcription factor. Known Tra2β splicing targets have important roles in cancer cells, where they affect metastasis, proliferation, and cell survival. Tra2β protein is also known to interact directly with the RBMY protein which is implicated in liver cancer.
A Lipopeptide HIV-1/2 Fusion Inhibitor with Highly Potent In Vitro, Ex Vivo, and In Vivo Antiviral Activity

ABSTRACT Peptides derived from the C-terminal heptad repeat (CHR) region of the human immunodeficiency virus type 1 (HIV-1) fusogenic protein gp41 are potent viral entry inhibitors, and currently, enfuvirtide (T-20) is the only one approved for clinical use; however, emerging drug resistance largely limits its efficacy. In this study, we generated a novel lipopeptide inhibitor, named LP-19, by integrating multiple design strategies, including an N-terminal M-T hook structure, an HIV-2 sequence, intrahelical salt bridges, and a membrane-anchoring lipid tail. LP-19 showed stable binding affinity and highly potent, broad, and long-lasting antiviral activity. In in vitro studies, LP-19 efficiently inhibited HIV-1-, HIV-2-, and simian immunodeficiency virus (SIV)-mediated cell fusion, viral entry, and infection, and it was highly active against diverse subtypes of primary HIV-1 isolates and inhibitor-resistant mutants. Ex vivo studies demonstrated that LP-19 exhibited dramatically increased anti-HIV activity and an extended half-life in rhesus macaques. In short-term monotherapy, LP-19 reduced viral loads to undetectable levels in acutely and chronically simian-human immunodeficiency virus (SHIV)-infected monkeys. Therefore, this study offers an ideal HIV-1/2 fusion inhibitor for clinical development and emphasizes the importance of the viral fusion step as a drug target. IMPORTANCE The peptide drug T-20 is the only viral fusion inhibitor in the clinic, which is used for combination therapy of HIV-1 infection; however, it requires a high dosage and easily induces drug resistance, calling for a new drug with significantly improved pharmaceutical profiles. Here, we have developed a short-lipopeptide-based fusion inhibitor, termed LP-19, which mainly targets the conserved gp41 pocket site and shows highly potent inhibitory activity against HIV-1, HIV-2, and even SIV isolates. LP-19 exhibits dramatically increased antiviral activity and an extended half-life in rhesus macaques, and it has potent therapeutic efficacy in SHIV-infected monkeys, highlighting its high potential as a new viral fusion inhibitor for clinical use.
Pilot evaluation of medical student perception of a novel pharmacology-based role-play game: Braincept

We would like to share with you our progress in adopting a gamification approach to support pharmacology learning in medical students. Here, we focus on player‐perceived benefits when learning pharmacology using the game. This work complements our ongoing research exploring the impact on knowledge and translation of learning through this manner into practice. Gamification in higher education is a relatively new (in the last decade) application of a trend widely used in higher education to support small group learning. One significant benefit to game‐based approaches is that games have an intrinsic motivation inbuilt through their structured, goal‐oriented play that facilitates continual engagement with the subject, which can be a powerful aid to learning.
Differential use of coronary revascularization and hospital mortality following acute myocardial infarction.

BACKGROUND The effect of racial/ethnic disparity in the use of cardiac procedures on short-term outcomes, such as hospital mortality, is limited. We sought to determine the association of revascularization procedures (percutaneous transluminal coronary angioplasty or coronary artery bypass graft) to hospital mortality in non-Hispanic black and white patients and Hispanic patients with acute myocardial infarction. METHODS Analysis of the New York State Department of Health Statewide Planning and Research Cooperate System (SPARCS) data for 12 555 patients admitted to New York City hospitals with acute myocardial infarction in 1996. Revascularization procedure frequencies and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for hospital mortality were calculated. RESULTS Whites were older than Hispanics and blacks (mean +/- SD age, 70 +/- 13.3 vs 64 +/- 13.3 and 64 +/- 12.9 years, respectively; P<.001) and more likely to have heart failure (36.3% vs 29.1% and 29.6%, respectively; P<.001). Blacks were least likely to be revascularized compared with Hispanics and whites (15.8% vs 25.8% and 25.2%, respectively; P<.001). Hispanics were more likely to survive than whites (adjusted OR, 0.73 [95% CI, 0.59-0.91]); this difference was not significant for blacks (adjusted OR, 0.83 [95% CI, 0.69-1.00]). Nonrevascularized blacks and Hispanics were more likely to be discharged alive than nonrevascularized whites (OR, 0.80 [95% CI, 0.66-0.98] for blacks; OR, 0.74 [95% CI, 0.59-0.93] for Hispanics). There were no significant racial/ethnic differences in hospital survival among revascularized patients. CONCLUSIONS Nonclinical and clinical factors appear to account for blacks being least likely to have been revascularized. Despite these differences in revascularization rates, survival was similar for blacks and whites, whereas Hispanics were more likely to survive than whites.
High Local Diversity of Trypanosoma in a Common Bat Species, and Implications for the Biogeography and Taxonomy of the T. cruzi Clade

The Trypanosoma cruzi clade is a group of parasites that comprises T. cruzi sensu lato and its closest relatives. Although several species have been confirmed phylogenetically to belong to this clade, it is uncertain how many more species can be expected to belong into this group. Here, we present the results of a survey of trypanosome parasites of the bat Artibeus jamaicensis from the Panamá Canal Zone, an important seed disperser. Using a genealogical species delimitation approach, the Poisson tree processes (PTP), we tentatively identified five species of trypanosomes – all belonging to the T. cruzi clade. A small monophyletic group of three putative Trypanosoma species places at the base of the clade phylogeny, providing evidence for at least five independent colonization events of these parasites into the New World. Artibeus jamaicensis presents a high diversity of these blood parasites and is the vertebrate with the highest number of putative trypanosome species reported from a single locality. Our results emphasize the need for continued efforts to survey mammalian trypanosomes.
Toward the human cellular microRNAome

microRNAs are short RNAs that serve as master regulators of gene expression and are essential components of normal development as well as modulators of disease. MicroRNAs generally act cell autonomously and thus their localization to specific cell types is needed to guide our understanding of microRNA activity. Current tissue-level data has caused considerable confusion and comprehensive cell-level data does not yet exist. Here we establish the landscape of human cell-specific microRNA expression. This project evaluated 8 billion small RNA-seq reads from 46 primary cell types, 42 cancer or immortalized cell lines, and 26 tissues. It identified both specific and ubiquitous patterns of expression that strongly correlate with adjacent super-enhancer activity. Analysis of unaligned RNA reads uncovered 207 unknown minor strand (passenger) microRNAs of known microRNA loci and 2,632 novel putative microRNA loci. Although cancer cell lines generally recapitulated the expression patterns of matched primary cells, their isomiR sequence families exhibited increased disorder suggesting Drosha and Dicer-dependent microRNA processing variability. Cell-specific patterns of microRNA expression were used to deconvolute variable cellular composition of adipose tissue samples highlighting one use of this cell-specific microRNA expression data. Characterization of cellular microRNA expression across a wide variety of cell types provides a new understanding of this critical regulatory RNA species.
Inductive heating kills cells that contribute to plaque: a proof-of-concept

Inducing cell death by heating targeted particles shows promise in cancer treatment. Here, we aim to demonstrate the feasibility of extending the use of this technique to treat and remove vascular deposits and thrombosis. We used induction heating of macrophages, which are key contributors to atherosclerosis and have demonstrated clear feasibility for heating and destroying these cells using ferromagnetic and pure iron particles. Specifically, iron particles achieved maximum temperatures of 51 ± 0.5 °C and spherical particles achieved a maximum temperature of 43.9 ± 0.2 °C (N = 6) after 30 min of inductive heating. Two days of subsequent observation demonstrated that inductive heating led to a significant reduction in cell number. Prior to induction heating, cell density was 105,000 ± 20,820 cells/ml (N = 3). This number was reduced to 6,666 ± 4,410 cells/ml for the spherical particles and 16,666 ± 9,280 cells/ml for the iron particles 24 h after inductive heating. Though cell density increased on the second day following inductive heating, the growth was minimal. Cells grew to 26,667 ± 6,670 cells/ml and 30,000 ± 15,280 cells/ml respectively. Compared to cell cultures with iron and spherical particles that were not subjected to induction heating, we observed a 97% reduction in cell count for the spherical particles and a 91% reduction for the iron particles after the first 24 h. After 48 h we observed a 95% reduction in cell growth for both spherical and iron particles. Induction heating of microparticles was thus highly effective in reducing the macrophage population and preventing their growth. These results demonstrate the feasibility of targeting cells involved in atherosclerosis and warrant further research into potential clinical applications.
A Uniquely Shaped Rod Improves Curve Correction in Surgical Treatment of Adolescent Idiopathic Scoliosis

Study Design. A retrospective cohort study. Objective. The aim of this study is to determine the initial curve correction in patients surgically treated for adolescent idiopathic scoliosis (AIS) using either beam-like rods (BRs) or traditional circular rods (CRs). Summary of Background Data. Posterior fusion using all pedicle screw instrumentation has become the standard for the surgical treatment of AIS. Traditionally, the rod is circular in the cross-sectional plane. Recent biomechanical studies suggest that a beam-like structure of the rod may enhance the stiffness of the construct and thereby possibly improve curve correction. Methods. Two consecutive series of patients surgically treated for AIS between May 2011 and May 2015 were included in the study. Patients were all treated with an ultralow profile all-pedicle screw implant system. In the first series, conventional 5.5 mm CoCr CR were used, and in the second series, 5.5 mm CoCr BR were used. Antero-posterior and lateral radiographs preoperatively and within seven days after surgery were used to measure the correction obtained. Results. The first 60 patients were operated with CR and the subsequent 69 with BR. There was no statistical difference in age, gender, preoperative curve magnitude, Lenke type, or number of levels instrumented (P = 0.451). Major curve correction was significantly better in the BR group than in the CR group (66 vs. 57%) (P < 0.001). We found no difference in preoperative flexibility, secondary curve correction, sagittal balance, or coronal balance (P > 0.058). A postoperative decrease in thoracic kyphosis was seen with no significant difference between groups. Median T5-T12 change was −7° versus −3° for BR and CR, respectively (P = 0.051). Conclusion. A BR design results in a significantly better curve correction than conventional rods, but the difference is moderate and the clinical value is uncertain. Level of Evidence: 3
Accurate determination of CT point‐spread‐function with high precision

The measurement of modulation transfer functions (MTFs) in computed tomography (CT) is often performed by scanning a point source phantom such as a thin wire or a microbead. In these methods the region of interest (ROI) is generally placed on the scanned image to crop the point source response. The aim of the present study was to examine the effect of ROI size on MTF measurement, and to optimize the ROI size. Using a 4 multidetector‐row CT, MTFs were measured by the wire and bead methods for three types of reconstruction kernels designated as ‘smooth', ‘standard', and ‘edge‐enhancement’ kernels. The size of a square ROI was changed from 30 to 50 pixels (approximately 2.9 to 4.9 mm). The accuracies of the MTFs were evaluated using the verification method. The MTFs measured by the wire and bead methods were dependent on ROI size, particularly in MTF measurement for the ‘edge‐enhancement’ kernel. MTF accuracy evaluated by the verification method changed with ROI size, and we were able to determine the optimum ROI size for each method (wire/bead) and for each kernel. Using these optimal ROI sizes, the MTF obtained by the wire method was in strong agreement with the MTF obtained by the bead method in each kernel. Our data demonstrate that the difficulties in obtaining accurate MTFs for some kernels such as edge‐enhancement can be overcome by incorporating the verification method into the wire and bead methods, allowing optimization of the ROI size to accurately determine the MTF. PACS numbers: 87.57. ‐s, 87.57. cf, 87.57. Q‐
Low cell pH depresses peak power in rat skeletal muscle fibres at both 30°C and 15°C: implications for muscle fatigue

Historically, an increase in intracellular H+ (decrease in cell pH) was thought to contribute to muscle fatigue by direct inhibition of the cross‐bridge leading to a reduction in velocity and force. More recently, due to the observation that the effects were less at temperatures closer to those observed in vivo, the importance of H+ as a fatigue agent has been questioned. The purpose of this work was to re‐evaluate the role of H+ in muscle fatigue by studying the effect of low pH (6.2) on force, velocity and peak power in rat fast‐ and slow‐twitch muscle fibres at 15°C and 30°C. Skinned fast type IIa and slow type I fibres were prepared from the gastrocnemius and soleus, respectively, mounted between a force transducer and position motor, and studied at 15°C and 30°C and pH 7.0 and 6.2, and fibre force (P0), unloaded shortening velocity (V0), force–velocity, and force–power relationships determined. Consistent with previous observations, low pH depressed the P0 of both fast and slow fibres, less at 30°C (4–12%) than at 15°C (30%). However, the low pH‐induced depressions in slow type I fibre V0 and peak power were both significantly greater at 30°C (25%versus 9% for V0 and 34%versus 17% for peak power). For the fast type IIa fibre type, the inhibitory effect of low pH on V0 was unaltered by temperature, while for peak power the inhibition was reduced at 30°C (37%versus 18%). The curvature of the force–velocity relationship was temperature sensitive, and showed a higher a/P0 ratio (less curvature) at 30°C. Importantly, at 30°C low pH significantly depressed the ratio of the slow type I fibre, leading to less force and velocity at peak power. These data demonstrate that the direct effect of low pH on peak power in both slow‐ and fast‐twitch fibres at near‐in vivo temperatures (30°C) is greater than would be predicted based on changes in P0, and that the fatigue‐inducing effects of low pH on cross‐bridge function are still substantial and important at temperatures approaching those observed in vivo.
Daily wrist activity classification using a smart band

Objective: In this letter, we propose a novel method for classifying daily wrist activities by using a smart band. Approach: Triaxial acceleration data are collected by built-in sensors of the smart band during experiments regarding five activities, i.e. texting, calling, placing a hand in a pocket, carrying a suitcase, and swinging a hand. We analyze patterns in the sensor signals during these activities based on three types of features, i.e. norm, norm-variance, and frequency-domain features. After extracting the significant features, a multi-class support vector machine algorithm is applied to classify these activities. Main results: We obtained recognition error rates of approximately 2.7% by applying the proposed method to the experimental dataset.
Intersection-Validation: A Method for Evaluating Structure Learning without Ground Truth

To compare learning algorithms that differ by the adopted statistical paradigm, model class, or search heuristic, it is common to evaluate the performance on training data of varying size. Measuring the performance is straightforward if the data are generated from a known model, the ground truth. However, when the study concerns real-world data, the current methodology is limited to estimating predictive performance, typically by cross-validation. This work introduces a method to compare algorithms’ ability to learn the model structure, assuming no ground truth is given. The idea is to identify a partial structure on which the algorithms agree, and measure the performance in relation to that structure on subsamples of the data. The method is instantiated to structure learning in Bayesian networks, measuring the performance by the structural Hamming distance. It is tested using benchmark ground truth networks and algorithms that maximize various scoring functions. The results show that the method can produce evaluation outcomes that are close to those one would obtain if the ground truth was available.
Compositional Assessment of Human Tracheal Cartilage by Infrared Spectroscopy

Objectives To assess the potential of infrared fiber-optic spectroscopy to evaluate the compositional properties of human tracheal cartilage. Study Design Laboratory-based study. Methods Twenty human cadaveric distal tracheas were harvested (age range 20-78 years; 6 females, 14 males) for compositional analysis. Histologic staining, Fourier transform infrared imaging spectroscopy data on collagen and proteoglycan (PG) content, and near-infrared (NIR) fiber-optic probe spectroscopic data that reflect protein and water content were evaluated. NIR fiber-optic probe data were also obtained from the proximal trachea in 4 human cadavers (age range 51-65 years; 2 females, 2 males) in situ for comparison to distal trachea spectral data. Results In the distal trachea cohort, the spectroscopic-determined ratio of PG/amide I, indicative of the relative amount of PG, was significantly higher in the tissues from the younger group compared to the older group (0.37 ± 0.08 vs 0.32 ± 0.05, P = .05). A principal component analysis of the NIR spectral data enabled separation of spectra based on tracheal location, likely due to differences in both protein and water content. The NIR-determined water content based on the 5200-cm−1 peak was significantly higher in the distal trachea compared to the proximal trachea (P < .001). Conclusions Establishment of normative compositional values and further elucidating differences between the segments of trachea will enable more directed research toward appropriate compositional end points in regenerative medicine for tracheal repair.
Subgradient Methods for Structured Prediction

Promising approaches to structured learning problems have recently been developed in the maximum margin framework. Unfortunately, algorithms that are computationally and memory efficient enough to solve large scale problems have lagged behind. We propose using simple subgradient-based techniques for optimizing a regularized risk formulation of these problems in both online and batch settings, and analyze the theoretical convergence, generalization, and robustness properties of the resulting techniques. These algorithms are are simple, memory efficient, fast to converge, and have small regret in the online setting. We also investigate a novel convex regression formulation of structured learning. Finally, we demonstrate the benefits of the subgradient approach on three structured prediction problems.