Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating treatment response to mepolizumab in patients with severe CRSwNP.

BACKGROUND The SYNAPSE study (NCT03085797) demonstrated that mepolizumab decreased nasal polyp (NP) size and nasal obstruction in patients with chronic rhinosinusitis with NP (CRSwNP). METHODS SYNAPSE, a randomized, double-blind study, included patients with recurrent, refractory, severe CRSwNP, eligible for repeated surgery despite receiving standard of care (SoC). Patients received 4-weekly mepolizumab 100 mg or placebo subcutaneously plus SoC for 52 weeks. This post hoc analysis further characterized treatment responses and association with patient characteristics. The proportion of patients meeting any and each of five response criteria indicating improvement in disease-specific quality of life, NP size, nasal obstruction, loss of smell, and overall symptoms at Weeks 24 and 52, were assessed in subgroups: 1) no surgery; 2) neither surgery nor systemic corticosteroids (SCS). RESULTS Of 407 patients in the intention-to-treat population, 381 and 343 patients had no sinus surgery by Weeks 24 and 52, respectively. More mepolizumab- versus placebo-treated patients without surgery by Weeks 24 and 52 met each response criteria. Of the mepolizumab-treated patients without surgery by Week 24, 109 (55%) responded across ≥ 3 criteria, increasing to 126 (67%) by Week 52. Similar response trends were seen for patients with neither surgery nor SCS by Weeks 24 and 52. At either timepoint, there were no major differences in baseline characteristics between mepolizumab-treated full- (5/5 categories) and non-responders (0/5 categories). CONCLUSIONS Most patients who completed SYNAPSE required neither surgery nor SCS use and in addition achieved a progressive and sustained clinical response to mepolizumab underscoring the therapeutic benefits of mepolizumab in severe CRSwNP.
Parallelized gene cluster editing illuminates mechanisms of epoxyketone proteasome inhibitor biosynthesis

Abstract Advances in DNA sequencing technology and bioinformatics have revealed the enormous potential of microbes to produce structurally complex specialized metabolites with diverse uses in medicine and agriculture. However, these molecules typically require structural modification to optimize them for application, which can be difficult using synthetic chemistry. Bioengineering offers a complementary approach to structural modification but is often hampered by genetic intractability and requires a thorough understanding of biosynthetic gene function. Expression of specialized metabolite biosynthetic gene clusters (BGCs) in heterologous hosts can surmount these problems. However, current approaches to BGC cloning and manipulation are inefficient, lack fidelity, and can be prohibitively expensive. Here, we report a yeast-based platform that exploits transformation-associated recombination (TAR) for high efficiency capture and parallelized manipulation of BGCs. As a proof of concept, we clone, heterologously express and genetically analyze BGCs for the structurally related nonribosomal peptides eponemycin and TMC-86A, clarifying remaining ambiguities in the biosynthesis of these important proteasome inhibitors. Our results show that the eponemycin BGC also directs the production of TMC-86A and reveal contrasting mechanisms for initiating the assembly of these two metabolites. Moreover, our data shed light on the mechanisms for biosynthesis and incorporation of 4,5-dehydro-l-leucine (dhL), an unusual nonproteinogenic amino acid incorporated into both TMC-86A and eponemycin.
Ultra-fast, high spatial resolution single-pulse scintillation imaging of synchrocyclotron pencil beam scanning proton delivery

Objective. To demonstrates the ability of an ultra-fast imaging system to measure high resolution spatial and temporal beam characteristics of a synchrocyclotron proton pencil beam scanning (PBS) system. Approach. An ultra-fast (1 kHz frame rate), intensified CMOS camera was triggered by a scintillation sheet coupled to a remote trigger unit for beam on detection. The camera was calibrated using the linear (R 2 > 0.9922) dose response of a single spot beam to varying currents. Film taken for the single spot beam was used to produce a scintillation intensity to absolute dose calibration. Main results. Spatial alignment was confirmed with the film, where the x and y-profiles of the single spot cumulative image agreed within 1 mm. A sample brain patient plan was analyzed to demonstrate dose and temporal accuracy for a clinically-relevant plan, through agreement within 1 mm to the planned and delivered spot locations. The cumulative dose agreed with the planned dose with a gamma passing rate of 97.5% (2 mm/3%, 10% dose threshold). Significance. This is the first system able to capture single-pulse spatial and temporal information for the unique pulse structure of a synchrocyclotron PBS systems at conventional dose rates, enabled by the ultra-fast sampling frame rate of this camera. This study indicates that, with continued camera development and testing, target applications in clinical and FLASH proton beam characterization and validation are possible.
Research of Image Registration Based on Maximum Entropy Template Selection Algorithm

This paper concerns an improved adaptive genetic algorithm, and the method is applied to the Maximum Entropy Template Selection Algorithm image registration. This method includes adjusting the probability of crossover and mutation in the evolutionary process. The method can overcome the disadvantage of traditional genetic algorithm that is easy to get into a local optimum answer. Results show our method is insensitive to the ordering, rotation and scale of the input images so it can be used in image stitching and retrieval of images & videos.
Hubble Space Telescope Imaging of the Mass-losing Supergiant VY Canis Majoris

The highly luminous M supergiant VY CMa is a massive star that appears to be in its final death throes, losing mass at high rate en route to exploding as a supernova. Subarcsecond-resolution optical images of VY CMa, obtained with the Faint Object Camera (FOC) aboard the Hubble Space Telescope, vividly demonstrate that mass loss from VY CMa is highly anisotropic. In the FOC images, the optical "star" VY CMa constitutes the bright, well-resolved core of an elongated reflection nebula. The imaged nebula is ∼3″ (∼4500 AU) in extent and is clumpy and highly asymmetric. The images indicate that the bright core, which lies near one edge of the nebula, is pure scattered starlight. We conclude that at optical wavelengths VY CMa is obscured from view along our line of sight by its own dusty envelope. The presence of the extended reflection nebula then suggests that this envelope is highly flattened and/or that the star is surrounded by a massive circumstellar disk. Such axisymmetric circumstellar density structure should have profound effects on post–red supergiant mass loss from VY CMa and, ultimately, on the shaping of the remnant of the supernova that will terminate its post–main-sequence evolution.
Hepatitis B immunization data of patients living with HIV/AIDS: a multi-centre study.

OBJECTIVES Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are the two leading viruses that cause the greatest number of virus-related morbidities in the world. HIV/HBV coinfection is correlated with high morbidity and mortality. For this particular reason hepatitis B vaccination is crucial for people living with HIV. METHODS Patients who are being followed-up for HIV/AIDS and who have received a hepatitis B vaccine in 4 HIV clinics over a 5-year time period have been studied. Our multi-centered, retrospective, cross-sectional and observational study investigates factors that affect hepatitis B vaccination immune response of individuals living with HIV. The patients have been studied for the parameters such as age, sex, CD4 count at the time of diagnosis or vaccination, HIV-RNA levels, comorbidities, vaccine dosage, success of immunization after vaccination, and the demographics of the patients who have and have not developed immunity. RESULTS Of 645 patients that are being followed-up in our clinics, 158 received hepatitis B vaccine; 39 of these 158 patients have been excluded from the study because they did not fulfil the inclusion criteria. Finally, 119 patients were evaluated in the study, 17 of the patients (14.3%) were females and 102 (85.7%) were males. The median age was 41.11 ± 10.09 (min-max: 18-75). Twenty-three of the patients (19.3%) were at the stage of AIDS during diagnosis while 80.7% were at the stage of HIV infection. Ninety-one of the patients (76.5%) have been administered a single dose hepatitis B vaccine on the standard 0, 1st, 6th month vaccination schedule, whereas 23.5% were administered a double dose on the same vaccination schedule. When further evaluated to find whether the patient was able to develop sufficient immunity (anti-HBs ≥ 10), it was found that the immune response was statistically significantly higher in the patients whose CD4 count was greater than 200 at the time of the first diagnosis and vaccination (p = 0.05 and p = 0.001, respectively). The patients have also been evaluated according to the number of doses they received (1 vs. 2). The immune response of the patients who received two doses was statistically significantly higher (p = 0.041). CONCLUSION We can conclude that in the patients with CD4 count less than 200 at the time of their diagnosis and vaccination a high dose recombinant hepatitis B vaccine should definitely be administered as the normal dose and higher dose have similar side effect profiles and the higher dose provides greater immunity.
Comment on Article by Müller and Mitra

Congratulations to the authors on a fine and comprehensive review of nonparametric Bayesian (BNP, or NPB? ) inference! The authors offer a whirlwind review of an enormous field that has seen explosive growth since the advent of MCMC methods for Bayesian computing; indeed, the two fields rose to prominence simultaneously around 1990, and enjoyed substantial cross-pollination (see Escobar and West, 1998, for a review). One of us (BPC) admits to being somewhat surprised to be asked to serve as a discussant for this paper, since if he has any professional reputation at all, it is that of an unapologetic Bayesian parametrician who prefers BUGS implementions, with theoretical properties simulated via repeated calls from R using BRugs or rjags. But the editors insisted this is precisely what they were looking for, and after reading the paper we agree with them: this is a very nice paper that is in need of a crabby parametrician or two to fuss about its breezy claims of heretofore-unimagined modeling freedom and insight, especially when there is often relatively modest payoff for the effort expended. As such, our outlook here is like an asymptotician’s wary view of the Gibbs sampler in 1990, or any frequentist’s view of the phrase “applied Bayesian statistics” before 1980. While the progressive Gibbs-applied viewpoint prevailed in both those cases, the other ideas hardly vanished; asymptotic approximations are even cool again thanks to the emergence of the INLA package (c.f. Rue et al., 2009). Thus we hope the reader will grant us our slightly peevish, “you-kids-get-off-my-lawn” tone so that we may fulfill our Prof. Cranky Pants role, as the editors (and we) believe we must.
Nonsingular path following control of a unicycle in the presence of parametric modelling uncertainties

A new type of control law is derived to steer the dynamic model of a wheeled robot of unicycle type along a desired path. The methodology adopted for path following control deals explicitly with vehicle dynamics and plant parameter uncertainty. Furthermore, it overcomes stringent initial condition constraints that are present in a number of path following control strategies described in the literature. This is done by controlling explicitly the rate of progression of a ‘virtual target’ to be tracked along the path, thus bypassing the problems that arise when the position of the virtual target is simply defined by the projection of the actual vehicle on that path. In the paper, a nonlinear adaptive control law is derived that yields convergence of the (closed‐loop system) path following error trajectories to zero. Controller design relies on Lyapunov theory and backstepping techniques. Simulation results illustrate the performance of the control system proposed. Copyright © 2006 John Wiley & Sons, Ltd.
Hyponatremia and hypernatremia in the emergency department: severity and outcomes

Objective Hyponatremia and hypernatremia are common electrolyte disorders. Few studies to date have focused on patients presenting to the emergency department (ED) with sodium (Na) disorders. Our objective was to determine the incidence and outcomes of hyponatremia and hypernatremia in ED patients. Methods This study was a retrospective, single-center review of electronic medical records at an academic suburban ED with approximately 100,000 annual visits. Subjects included consecutive adult ED patients with Na levels measured while in the ED in 2019. Demographic, clinical, and laboratory data were recorded. Outcomes data, including hospital admission, intensive care unit (ICU) admission, mortality, and length of stay (LOS), were recorded. The primary outcome was inhospital death. Secondary outcomes were hospital admission, ICU admission, ED LOS, and hospital LOS. Univariable and multivariable linear and logistic regression analyses were performed to explore the association of candidate predictor variables and outcomes. Results Na was measured in 57,427 adults (54%) among a total of 106,764 assessed ED visits in 2019. The mean±standard deviation age was 54±21 years, and 47% of participants were male. Mild, moderate, and severe hyponatremia and hypernatremia occurred in 8%, 2%, and 0.1% of patients and 1%, 0.2%, and <0.1% of patients, respectively. Hospital and ICU admission and mortality rates increased as Na levels increased or decreased further from normal. Adjusted odds ratio (95% confidence interval) values for hospital mortality were 2.39 (1.97–2.90) for mild hyponatremia, 3.93 (2.95–5.24) for moderate hyponatremia, 6.98 (2.87–16.40) for severe hyponatremia, 3.65 (2.47–5.40) for mild hypernatremia, 8.58 (4.92–14.94) for moderate hypernatremia, and 55.75 (11.37–273.30) for severe hypernatremia. Hypernatremia was associated with a greater risk of death than hyponatremia. Patients with hyponatremia and hypernatremia had increased LOS times compared to those with normal Na levels. Conclusion Hyponatremia and hypernatremia were associated with greater rates of hospital admission, ICU admission, mortality, and prolonged hospital LOS times.
Do gravitational waves create particles

Solving the Klein-Gordon equation for a free scalar field in a curved spacetime in the weak-field approximation we rederive the results of Gibbons et? al: no particle creation from the interaction between scalar fields and gravitational waves. We show, however, that particle creation would really occur when the matter field is constrained in space by some boundaries. Such an effect is likely to be related to the uncertainty principle, in connection with a sort of dimensional reduction (as in the Kaluza-Klein theory) that causes the field to acquire a mass term, also responsible for conformal symmetry breaking in a spatially flat FRW spacetime. Although derived in the weak-field approximation, the results seem also to be reasonably valid in the presence of exact gravitational waves.
A gait generating algorithm with smooth speed transition for the locomotion of legged robots

Much of what is known about the gait-generated method is based on specified gait pattern. Yet in the wild, animals can move over terrains with widely varying properties in various gait patterns. Previous studies have realized gait types such as trot or walk in various legged robots, but no detailed relationship descriptions of different gaits are currently available. This paper addresses the intrinsic relationship between all kinds of gait for legged robot locomotion in order to realize the gait transition smoothly. Based on their relations, the proposed gait-generated method is constructed by a support factor and a delay factor, which describe locomotion efficiency and leg difference motion, respectively. A gait ring concept is proposed to explain their intrinsic relation, and a gait algorithm is proposed to realize the speed transition for legged robot locomotion. A quadruped robot called MATA_ I with 12 DOFs is specially designed for realizing gait transition. This kind of robot has a 4RRRS parallel motion structure, and each joint is driven by motor modules. The algorithm with smooth transition between different gaits was applied in this kind of robot. The simulation results have shown that the proposed gait-generated algorithms can effectively realize gait transition for legged robot.
Microbial Interactions Related to N2O Emissions and Temperature Sensitivity from Rice Paddy Fields

Soil microorganisms drive emissions of nitrous oxide from soils; this is a powerful greenhouse gas and the dominant ozone-depleting agent. N2O emissions can be partly predicted from soil properties and specific microbial groups, whereas a possible role of below-ground microbial interactions has largely been overlooked. ABSTRACT The soil microbiome is a driver of nitrous oxide (N2O) emissions in terrestrial ecosystems. Identifying the core microbiome of N2O emissions and its temperature sensitivity from trillions of soil microorganisms is a great challenge and is essential to improving the predictability of soil-climate feedback related to increasing temperature. Here, the integrated soil microbiome covering archaeal, bacterial, fungal, algal, and microfaunal communities was studied to disengage the potential linkage with its N2O emissions and its temperature sensitivity in paddy fields by hunting for core species pairs. The results showed that between-group interactions of core bacterial and archaeal members and the within-group interactions of core bacterial members jointly contributed to the N2O emissions and its temperature sensitivity. The contribution of between-group interactions (32 to 33%) was greater than that of within groups (10 to 18%). These results suggested that N2O emissions and their fluctuations related to climate warming are affected by the within- and between-group interactions of the soil microbiome. Our results help advance the knowledge on the importance of microbial keystone species and network associations in controlling N2O production and their responses to increasing temperature. IMPORTANCE Soil microorganisms drive emissions of nitrous oxide from soils; this is a powerful greenhouse gas and the dominant ozone-depleting agent. N2O emissions can be partly predicted from soil properties and specific microbial groups, whereas a possible role of below-ground microbial interactions has largely been overlooked. Here, the integrated soil microbiome covering archaeal, bacterial, fungal, algal, and microfaunal communities was studied to disengage the potential linkage with the N2O emissions and temperature sensitivity of the microbiome in paddy fields by hunting for core species pairs. The results showed that between-group interactions of core bacterial and archaeal members and the within-group interactions of core bacterial members jointly contributed to the N2O emissions. The contribution of between-group interactions (32 to 33%) was greater than that of within-group interactions (10 to 18%). Our results help advance the knowledge on the importance of microbial keystone species and interactions in controlling N2O production and their responses to increasing temperature.
Angiotensin II Type 1 Receptor Blocker Prevents Abdominal Aortic Aneurysm Progression in Osteoprotegerin‐Deficient Mice via Upregulation of Angiotensin (1–7)

Background Angiotensin II type 1 receptor blockers (ARBs) have been shown to limit the growth of abdominal aortic aneurysm (AAA), but their efficacy is controversial. This study aimed to investigate the molecular mechanism underlying the protective effect of ARBs against AAA progression. Methods and Results Olmesartan, an ARB, was administered to wild‐type and osteoprotegerin‐knockout (Opg‐KO) mice starting 2 weeks before direct application of CaCl2 to aortas to induce AAA. The protective effect of olmesartan against AAA in wild‐type and Opg‐KO mice was compared at 6 weeks after AAA induction. Olmesartan prevented AAA progression in Opg‐KO mice, including excessive aortic dilatation and collapse of tunica media, but not in wild‐type mice. Deficiency of the Opg gene is known to cause excessive activation of the tumor necrosis factor–related apoptosis‐inducing ligand–induced c‐Jun N‐terminal kinase/matrix metalloproteinase 9 pathway, resulting in prolonged AAA progression. Olmesartan attenuated the upregulation of phosphorylated c‐Jun N‐terminal kinase and matrix metalloproteinase 9 expression in the aortic wall of Opg‐KO mice. In cultured vascular smooth muscle cells, tumor necrosis factor–related apoptosis‐inducing ligand–induced c‐Jun N‐terminal kinase phosphorylation and matrix metalloproteinase 9 expression were inhibited by angiotensin (1–7), the circulating levels of which are increased by ARBs. Furthermore, administering an angiotensin (1–7) antagonist to Opg‐KO mice diminished the protective effect of olmesartan against AAA progression. Conclusions Olmesartan prevented AAA progression in Opg‐KO mice by upregulating angiotensin (1–7), suggesting that angiotensin (1–7) may be a key factor that mediates the protective effect of ARBs.