Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation of prompt gamma-ray spectroscopy for proton range verification in tissue-mimicking and porcine samples

Objective. Proton therapy of cancer improves dose conformality to the target and sparing of surrounding healthy tissues compared to conventional photon treatments. However, proton therapy’s advantage could be even larger if proton range uncertainties were reduced. Sources of range uncertainties include computed tomography treatment planning images and variations in patient anatomy and setup. To reduce range uncertainties, we have developed a system for real-time in vivo range monitoring. The system is based on spectroscopy of prompt gamma-rays emitted through proton-nuclear interactions during irradiation. We validated the performance of our prompt gamma-ray spectroscopy detector prototype using tissue-mimicking and porcine samples. Approach. Measurements were performed in water, four tissue-mimicking samples (spongiosa, muscle, adipose tissue, and cortical bone), and two porcine samples (liver and brain). A dose of 0.9 Gy was delivered to a target at a depth of 12.5–17.5 cm. Multi-layer ionization chamber measurements were performed to determine stopping power ratios relative to water and ground truth proton ranges. Ground truth elemental compositions were determined using combustion analysis. Proton ranges and elemental compositions measured using prompt gamma-ray spectroscopy were compared to the ground truth. Main results. For all samples, the mean measured range over all pencil-beam spots differed from the ground truth by less than 1.2 mm. The mean standard deviation was 0.9 mm (range: 0.4–1.6 mm). The mean difference between ground truth and measured elemental compositions was 0.06 gcm3 (range: 0.00 gcm3 to 0.12 gcm3 ). Significance. We verified the performance of our prompt gamma-ray spectroscopy detector prototype for proton range verification using tissue-mimicking and porcine samples. Measured proton ranges and elemental sample compositions were in good agreement with the ground truth. These measurements confirm the system’s reliability for a variety of tissues and bridge the gap between previously-reported experiments and ongoing in vivo patient measurements.
Payer formulary exclusions of apixaban: how patients respond and potential implications

Abstract In recent years, US payers have increased usage of formulary exclusions as a means to help manage costs. Earlier this year, one of the largest pharmacy benefit managers in the country added Eliquis (apixaban), the most widely used anticoagulant, to its list of excluded medicines from its formulary, raising concerns by physicians and patients. In this commentary, we examine the potential impacts of formulary exclusion of a drug like apixaban—a treatment for patients with atrial fibrillation and venous thromboembolism to help prevent stroke and clotting events and which has been demonstrated to have a strong efficacy and safety profile. We discuss the effect of formulary exclusions on patients’ ability to access the most clinically appropriate treatment for their health needs, along with possible effects on their health and well-being. We also report descriptive results on apixaban-treated patients with traditional Medicare coverage who faced a formulary exclusion of apixaban in 2017, and these patients’ observed behaviors. We found that the majority of these patients remained on apixaban either through pre-emptively switching to a different Part D drug plan with apixaban coverage or applying for formulary exception. Our findings suggest that formulary exclusion did not help to achieve the goal of switching patients to less costly medications but created additional hurdles for patients to access their preferred treatment and increased patient burden. Alternative ways to manage payer costs may be needed to help avoid poor outcomes and reduce the burden placed on patients in their efforts to access life-saving medications.
Gendered citation patterns among the scientific elite

Diversity in science is necessary to improve innovation and increase the capacity of the scientific workforce. Despite decades-long efforts to increase gender diversity, however, women remain a small minority in many fields, especially in senior positions. The dearth of elite women scientists, in turn, leaves fewer women to serve as mentors and role models for young women scientists. To shed light on gender disparities in science, we study prominent scholars who were elected to the National Academy of Sciences. We construct author citation networks that capture the structure of recognition among scholars’ peers. We identify gender disparities in the patterns of peer citations and show that these differences are strong enough to accurately predict the scholar’s gender. In contrast, we do not observe disparities due to prestige, with few significant differences in the structure of citations of scholars affiliated with high-ranked and low-ranked institutions. These results provide further evidence that a scholar’s gender plays a role in the mechanisms of success in science.
Design of a Multi-Joint Passive Exoskeleton for Vertical Jumping Using Optimal Control

Research and the commercial use of exoskeletons that augment human activities are rapidly growing. However, the progress of the two is hindered by the time-consuming and costly process of designing and evaluating the exoskeleton. One of the solutions to reduce both is the use of simulations that model the users, exoskeleton, and their interaction. At the same time, most simulations focus on continuous tasks, such as walking, running, and industrial activities. The augmentation of human capability is essential in fast motion tasks (i.e., jumping, throwing), where the muscles are producing their maximum force. Thus, this study implemented a simulation of passive exoskeleton–human interactions using OpenSim and Moco software for optimal control to find muscle excitation that maximizes vertical jump height. The models include a planar human model with ankle, knee, and hip joints. The muscles were modeled as torque actuators for each joint, with a flexor and an extensor, and passive torques representing each joint’s ligaments. The simulation was used to study: a) the effect of different spring stiffness at the knee, hip, and ankle joints and combinations of these joints; b) multi-joints vs. single joints; c) the effect of an elliptic pulley and different initial engagement angle for springs. The results revealed that the jump height increased as the spring became stiffer, up to a maximum point. For a single joint, the knee exoskeleton was the most effective, compared with the hip and ankle joint exoskeletons. The multi-joint exoskeleton was slightly better than the single knee joint. If maximum spring tension is a limiting factor, an elliptic pulley has an advantage relative to a round pulley. An initial angle of engagement (with equal work) other than zero up to approximately 50 degrees does not decrease the jump height.
Applications of Semidefinite Programming in Quantum Cryptography

Coin-flipping is the cryptographic task of generating a random coin-flip between two mis- trustful parties. Kitaev [19] discovered that the security of quantum coin-flipping protocols can be analyzed using semidefinite programming. This lead to his result that one party can force a desired coin-flip outcome with probability at least 1/ √ 2. We give sufficient background in quantum computing and semidefinite programming to understand Kitaev’s semidefinite programming formulation for coin-flipping cheating strategies. These ideas are specialized to a specific class of protocols singled out by Nayak and Shor [29]. We also use semidefinite programming to solve for the maximum cheating probability of a particular protocol which has the best known security. Furthermore, we present a family of protocols where one party has a greater probability of forcing an outcome of 0 than an outcome of 1. We also discuss a computer search to find specific protocols which minimize the maximum cheating probability.
SIAH2 regulates DNA end resection and replication fork recovery by promoting CtIP ubiquitination

Abstract Human CtIP maintains genomic integrity primarily by promoting 5′ DNA end resection, an initial step of the homologous recombination (HR). A few mechanisms have been suggested as to how CtIP recruitment to damage sites is controlled, but it is likely that we do not yet have full understanding of the process. Here, we provide evidence that CtIP recruitment and functioning are controlled by the SIAH2 E3 ubiquitin ligase. We found that SIAH2 interacts and ubiquitinates CtIP at its N-terminal lysine residues. Mutating the key CtIP lysine residues impaired CtIP recruitment to DSBs and stalled replication forks, DSB end resection, overall HR repair capacity of cells, and recovery of stalled replication forks, suggesting that the SIAH2-induced ubiquitination is important for relocating CtIP to sites of damage. Depleting SIAH2 consistently phenocopied these results. Overall, our work suggests that SIAH2 is a new regulator of CtIP and HR repair, and emphasizes that SIAH2-mediated recruitment of the CtIP is an important step for CtIP’s function during HR repair.
Numerical Analysis of Rarefied Gas Flows by Finite-Difference Method

Recent results of accurate numerical analysis of rarefied gas flows on the basis of finite-difference methods are reported. Three different approaches: 1) the integral equation method for the linearized BGKW model, 2) the finite-difference method for the nonlinear BGKW model, and 3) the finite-difference method for the linearized Boltzmann equation are explained, with emphasis on their applications.
Method for noninvasive whole-body stimulation with spinning oscillating magnetic fields and its safety in mice

ABSTRACT We recently reported shrinkage of untreatable recurrent glioblastoma (GBM) in an end-stage patient using noninvasive brain stimulation with a spinning oscillating magnetic field (sOMF)-generating device called the Oncomagnetic device. Our in vitro experiments demonstrated selective cancer cell death while sparing normal cells by sOMF-induced increase in intracellular reactive oxygen species (ROS) levels due to magnetic perturbation of mitochondrial electron transport. Here, we describe the results of an in vivo study assessing the toxicity of chronic sOMF stimulation in mice using a newly constructed apparatus comprised of the sOMF-generating active components of the Oncomagnetic device. We chronically stimulated 10 normal 60-day old female C57BL/6 mice in their housing cages for 2 h 3 times a day, as in the patient treatment protocol, over 4 months. We also studied the effects of 2-h acute sOMF stimulation. Our observations and those of blinded independent veterinary staff observers, indicated no significant adverse effects of chronic or acute sOMF stimulation on the health, behavior, electrocardiographic and electroencephalographic activities, hematologic profile, and brain and other tissue and organ morphology of treated mice compared to age-matched untreated control mice. These findings suggest that short- and long-term therapies with the Oncomagnetic device are safe and well tolerated.
The impact of age on genetic testing decisions in amyotrophic lateral sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative syndrome. In up to 20% of cases, a family history is observed. Although Mendelian disease gene variants are found in apparently sporadic ALS, genetic testing is usually restricted to those with a family history or younger patients with sporadic disease. With the advent of therapies targeting genetic ALS, it is important that everyone treatable is identified. We therefore sought to determine the probability of a clinically actionable ALS genetic test result by age of onset, globally, but using the UK as an exemplar. Blood-derived DNA was sequenced for ALS genes, and the probability of a clinically actionable genetic test result estimated. For a UK subset, age- and sex-specific population incidence rates were used to determine the number of such results missed by restricting testing by age of onset according to UK’s National Genomic Test Directory criteria. There were 6274 people with sporadic ALS, 1551 from the UK. The proportion with a clinically actionable genetic test result ranged between 0.21 [95% confidence interval (CI) 0.18–0.25] in the youngest age group to 0.15 (95% CI 0.13–0.17) in the oldest age group for a full gene panel. For the UK, the equivalent proportions were 0.23 (95% CI 0.13–0.33) in the youngest age group to 0.17 (95% CI 0.13–0.21) in the oldest age group. By limiting testing in those without a family history to people with onset below 40 years, 115 of 117 (98% of all, 95% CI 96%–101%) clinically actionable test results were missed. There is a significant probability of a clinically actionable genetic test result in people with apparently sporadic ALS at all ages. Although some countries limit testing by age, doing so results in a significant number of missed pathogenic test results. Age of onset and family history should not be a barrier to genetic testing in ALS.
The Association of Social Connectivity and Body Weight With the Onset of Type 2 Diabetes: Findings From the Population-Based Prospective MONICA/KORA Cohort

ABSTRACT Objective Low levels of social connectivity are related to the onset of type 2 diabetes mellitus (T2D), and this study investigates the role of body weight in this association. Methods In a sample of 9448 participants followed for a mean of 15.3 years (186,158.5 person-years) from the Monitoring of Trends and Determinants in Cardiovascular Disease Augsburg/Cooperative Health Research in the Region of Augsburg population-based cohort conducted in Germany, we investigated the association of social connectivity, measured by the Social Network Index, and body mass index (BMI) with the risk of clinically validated T2D incidence using stratified Cox proportional hazards regression models adjusted for sociodemographic, life-style, cardiometabolic, and psychosocial risk factors. Results During a mean follow-up of 14.1 years (186,158.5 person-years), 975 (10.3%) participants developed T2D. Participants with low social connectivity developed T2D at a higher rate than socially connected participants (10.0 versus 8.0 cases/10,000 person-years); however, BMI played a significant role in the association of social connectivity with T2D (p < .001). In comparison to their socially connected counterparts, low social connectivity was associated with a higher rate of T2D incidence in normal-weight (6.0 versus 2.0 cases/10,000 person-years), but not overweight (13.0 versus 13.0 cases/10,000 person-years) or obese participants (32.0 versus 30.0 cases/10,000 person-years). Correspondingly, Cox regression analysis showed that 5-unit increments in BMI increased the risk of T2D in socially connected participants (hazard ratio = 3.03, 95% confidence interval = 2.48–3.79, p < .001) at a substantially higher rate than in low socially connected participants (hazard ratio = 1.77, 95% confidence interval = 1.45–2.16, p < .001). Conclusion The detrimental link between low social connectivity and increased risk of T2D is substantially stronger in participants with a lower BMI.
A nonparametric method for classification trees using grouped covariates

A group of variables are commonly seen in diagnostic medicine when multiple prognostic factors are aggregated into a composite score to represent the risk profile. A model selection method considers these covariates as all‐in or all‐out types. Model selection procedures for grouped covariates and their applications have thrived in recent years, in part because of the development of genetic research in which gene–gene or gene–environment interactions and regulatory network pathways are considered groups of individual variables. However, little has been discussed on how to utilize grouped covariates to grow a classification tree. In this paper, we propose a nonparametric method to address the selection of split variables for grouped covariates and their following selection of split points. Comprehensive simulations were implemented to show the superiority of our procedures compared to a commonly used recursive partition algorithm. The practical use of our method is demonstrated through a real data analysis that uses a group of prognostic factors to classify the successful mobilization of peripheral blood stem cells.
Measurements below the detection limit.

Let's start with an example: Figure 1 shows a fictional dataset of measurements of serum levels of a substance in two patient groups. The crosses indicate the actual values, but only those above the lower detection limit can be measured. We know how many values are below the detection limit, but not the actual values. These data are missing not at random (MNAR) because the probability depends on the non-observed values being below the detection limit (1).
PhaMMseqs: a new pipeline for constructing phage gene phamilies using MMseqs2

Abstract The diversity and mosaic architecture of phage genomes present challenges for whole-genome phylogenies and comparative genomics. There are no universally conserved core genes, ∼70% of phage genes are of unknown function, and phage genomes are replete with small (<500 bp) open reading frames. Assembling sequence-related genes into “phamilies” (“phams”) based on amino acid sequence similarity simplifies comparative phage genomics and facilitates representations of phage genome mosaicism. With the rapid and substantial increase in the numbers of sequenced phage genomes, computationally efficient pham assembly is needed, together with strategies for including newly sequenced phage genomes. Here, we describe the Python package PhaMMseqs, which uses MMseqs2 for pham assembly, and we evaluate the key parameters for optimal pham assembly of sequence- and functionally related proteins. PhaMMseqs runs efficiently with only modest hardware requirements and integrates with the pdm_utils package for simple genome entry and export of datasets for evolutionary analyses and phage genome map construction.
The role of hyaluronic acid in polidocanol foam: An in vitro study

Objective To study the role of hyaluronic acid (HA) in polidocanol (POL) foam. Methods The dose-dependent effect of HA-POL on cultured human umbilical vein endothelial cells (HUVECs) as well as foam stability was evaluated by measuring optical density (OD) values and foam half-life time (FHT), respectively. An in vitro model was utilized for estimating the foam blood-displacement capacity by adopting maximum displacement distance (MDD) and displacement time. A comparison of foam viscosity was also carried out. Results The OD values of HUVECs treated with HA first increased and then decreased with the growing dosage of HA while cells treated with HA-POL died. Both FHT and displacement time were prolonged statistically with a gradually enhanced foam viscosity. As to MDD, there were no significant differences. Conclusions HA was found to promote HUVECs proliferation slightly, but this was almost negligible when compared to the cell-killing capacity of 1% POL. The viscosity of POL foam was enhanced by HA indicating its positive correlation with both stability and displacement capacity of POL foam.
The optimal decay estimates for the Euler-Poisson two-fluid system

This work is devoted to the optimal decay problem for the Euler-Poisson two-fluid system, which is a classical hydrodynamic model arising in semiconductor sciences. By exploring the influence of the electronic field on the dissipative structure, it is first revealed that the \textit{irrotationality} plays a key role such that the two-fluid system has the same dissipative structure as generally hyperbolic systems satisfying the Shizuta-Kawashima condition. The fact inspires us to give a new decay framework which pays less attention on the traditional spectral analysis. Furthermore, various decay estimates of solution and its derivatives of fractional order on the framework of Besov spaces are obtained by time-weighted energy approaches in terms of low-frequency and high-frequency decompositions. As direct consequences, the optimal decay rates of $L^{p}(\mathbb{R}^{3})$-$L^{2}(\mathbb{R}^{3})(1\leq p<2)$ type for the Euler-Poisson two-fluid system are also shown.
Work resumption and retention in patients with advanced cancer: Experiences and perspectives of general and occupational health care professionals

Abstract Objective The objectives of this study were to explore the experiences and perspectives of general and occupational health care professionals regarding work resumption and work retention of patients with advanced cancer, and to identify barriers and facilitators these professionals may encounter. Methods A qualitative design was applied, and individual semistructured interviews were conducted. General and occupational health care professionals were eligible to participate if they were involved in the work participation guidance of patients with advanced cancer, and were recruited through the network of the research team. Interview data were transcribed verbatim and analysed thematically via ATLAS.ti 9. Results Interviewees (N = 17) had various occupational backgrounds, for example, occupational physician, reintegration consultant, and general practitioner. Four main themes emerged from the data: (1) Assumptions and hesitations, (2) Patient initiates stakeholder communication, (3) Role dispersion: who is in charge of what? and (4) Experience with legislation creates opportunities. Conclusion Whereas most interviewees had positive experiences with, and/or optimistic expectations of, the work resumption and work retention of patients with advanced cancer, several barriers to the work participation guidance of these patients were identified. Suggestions for improvement include creating widespread awareness of the possibility of work participation of patients with advanced cancer and developing reintegration guidelines for advanced cancer.
Anomalous Behavior of the Magnetization Process of the S = 1/2 Kagome-Lattice Heisenberg Antiferromagnet at One-Third Height of the Saturation

The magnetization process of the S = 1/2 Heisenberg antiferromagnet on the kagome lattice is studied by the numerical-diagonalization method. We successfully obtain a new result of the magnetization process of a 42-site cluster in the entire range. Our analysis clarifies that the critical behavior around one-third of the height of the saturation is different from the typical behavior of the well-known magnetization plateau in two-dimensional systems. We also examine the effect of the \(\sqrt{3} \times \sqrt{3} \)-type distortion added to the kagome lattice. We find at one-third of the height of the saturation in the magnetization process that the undistorted kagome point is just the boundary between two phases that show their own properties that are different from each other. Our results suggest a relationship between the anomalous critical behavior at the undistorted point and the fact that the undistorted point is the boundary.