bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autotuning Hamiltonian Monte Carlo for efficient generalized nullspace exploration
Authors: Fichtner Andreas , Zunino Andrea , Gebraad Lars , Boehm Christian 
Published: July 2021

SUMMARYWe propose methods to efficiently explore the generalized nullspace of (non-linear) inverse problems, defined as the set of plausible models that explain observations within some misfit tolerance. Owing to the random nature of observational errors, the generalized nullspace is an inherently probabilistic entity, described by a joint probability density of tolerance values and model parameters. Our exploration methods rest on the construction of artificial Hamiltonian systems, where models are treated as high-dimensional particles moving along a trajectory through model space. In the special case where the distribution of misfit tolerances is Gaussian, the methods are identical to standard Hamiltonian Monte Carlo, revealing that its apparently meaningless momentum variable plays the intuitive role of a directional tolerance. Its direction points from the current towards a new acceptable model, and its magnitude is the corresponding misfit increase. We address the fundamental problem of producing independent plausible models within a high-dimensional generalized nullspace by autotuning the mass matrix of the Hamiltonian system. The approach rests on a factorized and sequentially preconditioned version of the L-BFGS method, which produces local Hessian approximations for use as a near-optimal mass matrix. An adaptive time stepping algorithm for the numerical solution of Hamilton’s equations ensures both stability and reasonable acceptance rates of the generalized nullspace sampler. In addition to the basic method, we propose variations of it, where autotuning focuses either on the diagonal elements of the mass matrix or on the macroscopic (long-range) properties of the generalized nullspace distribution. We quantify the performance of our methods in a series of numerical experiments, involving analytical, high-dimensional, multimodal test functions. These are designed to mimic realistic inverse problems, where sensitivity to different model parameters varies widely, and where parameters tend to be correlated. The tests indicate that the effective sample size may increase by orders of magnitude when autotuning is used. Finally, we present a proof of principle of generalized nullspace exploration in viscoelastic full-waveform inversion. In this context, we demonstrate (1) the quantification of inter- and intraparameter trade-offs, (2) the flexibility to change model parametrization a posteriori, for instance, to adapt averaging length scales, (3) the ability to perform dehomogenization to retrieve plausible subwavelength models and (4) the extraction of a manageable number of alternative models, potentially located in distinct local minima of the misfit functional.
Is fertility reduced in ovulatory women with polycystic ovary syndrome? An opinion paper
Authors: Palomba Stefano 
Published: July 2021

AbstractPolycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility; however, whether women with PCOS and spontaneous or drug-induced ovulatory cycles have the same reproductive potential as non-PCOS controls is a matter of debate. In the present opinion paper, the author takes the opportunity to summarize the collective evidence supporting the hypothesis of reduced fertility potential in women with PCOS, regardless of ovulatory status, and speculate that reduced reproductive potential may be caused by altered oocytes, embryo and endometrial competence, and infertility-related co-morbidities as well as an increased risk of pregnancy complications.
Elimination of CO2 insufflation-induced hypercapnia in open heart surgery using an additional venous reservoir
Authors: Nyman Jesper , Holm Manne , Fux Thomas , Sesartic Vanja , Fredby Magnus , Svenarud Peter , van der Linden Jan 
Published: July 2021

Abstract OBJECTIVESCarbon dioxide (CO2) gas insufflation is used for continuous de-airing during open heart surgery. The aim was to evaluate if an additional separate venous reservoir eliminates CO2 insufflation-induced hypercapnia and keeps sweep gas flow of the oxygenator constant.METHODSA separate reservoir was used during cardiopulmonary bypass in addition to a standard venous reservoir. The additional reservoir received drained blood and CO2 gas continuously via a suction drain (1 l/min) and handheld suction devices from the surgical wound. CO2 gas was insufflated via a gas diffuser in the open wound at 10 l/min. In a cross-over design for each patient, gas and blood were either continuously drained from the additional to the standard venous reservoir or not. CO2 pressure in arterial blood (PaCO2) was measured after adjustment of sweep gas flow as necessary and after steady state of PaCO2 was observed. Mean values for each setup (median 4 times) for each patient were analysed with Wilcoxon rank-sum test.RESULTSTen adult patients undergoing open aortic valve replacement were included. Median PaCO2 did not differ between setups (5.41; 5.29–5.57, interquartile range vs 5.41; 5.24–5.58, P = 0.92), whereas sweep gas flow (l/min) was lower (2.58; 2.50–3.16 vs 4.42; 4.0–5.40, P = 0.002) when CO2 gas was not drained from the additional to the standard reservoir.CONCLUSIONSAn additional venous reservoir for the evacuation of blood from the open surgical wound eliminates CO2 insufflation-induced hypercapnia in open heart surgery keeping PaCO2 and sweep gas flow constant. This prevents possible CO2-induced hyperperfusion of the brain and decreases the risk of cerebral particulate embolization during CO2 insufflation for de-airing in open heart surgery.Clinical trial registrationNCT04202575.IRB approval dat and number2018-07-13 and 2018/1091-31.
Identification and characteristics of a novel aminoglycoside phosphotransferase, APH(3′)-IId, from an MDR clinical isolate of Brucella intermedia
Authors: Lu Wei , Li Kewei , Huang Jiansheng , Sun Zhewei , Li Aifang , Liu Hongmao , Zhou Danying , Lin Hailong , Zhang Xueya , Li Qiaoling , Lu Junwan , Lin Xi , Li Peizhen , Zhang Hailin , Xu Teng , Bao Qiyu 
Published: July 2021

Abstract

Objectives
To describe a novel chromosomal aminoglycoside phosphotransferase named APH(3′)-IId identified in an MDR Brucella intermedia ZJ499 isolate from a cancer patient.

Methods
Species identity was determined by PCR and MALDI-TOF MS analysis. WGS was performed to determine the genetic elements conferring antimicrobial resistance. Gene cloning, transcriptional analysis and targeted gene deletion, as well as protein purification and kinetic analysis, were performed to investigate the mechanism of resistance.

Results
APH(3′)-IId consists of 266 amino acids and shares the highest identity (48.25%) with the previously known APH(3′)-IIb. Expression of aph(3′)-IId in Escherichia coli decreased susceptibility to kanamycin, neomycin, paromomycin and ribostamycin. The aph(3′)-IId gene in ZJ499 was transcriptionally active under laboratory conditions and the relative abundance of this transcript was unaffected by treatment with the above four antibiotics. However, deletion of aph(3′)-IId in ZJ499 results in decreased MICs of these drugs. The purified APH(3′)-IId showed phosphotransferase activity against kanamycin, neomycin, paromomycin and ribostamycin, with catalytic efficiencies (kcat/Km) ranging from ∼105 to 107 M−1 s−1. Genetic environment and comparative genomic analyses suggested that aph(3′)-IId is probably a ubiquitous gene in Brucella, with no mobile genetic elements detected in its surrounding region.

Conclusions
APH(3′)-IId is a novel chromosomal aminoglycoside phosphotransferase and plays an important role in the resistance of B. intermedia ZJ499 to kanamycin, neomycin, paromomycin and ribostamycin. To the best of our knowledge, APH(3′)-IId represents the fourth characterized example of an APH(3′)-II enzyme.
Data-driven identification of temporal glucose patterns in a large cohort of nondiabetic patients with COVID-19 using time-series clustering
Authors: Mistry Sejal , Gouripeddi Ramkiran , Facelli Julio C 
Published: July 2021

Abstract

Objective
Hyperglycemia has emerged as an important clinical manifestation of coronavirus disease 2019 (COVID-19) in diabetic and nondiabetic patients. Whether these glycemic changes are specific to a subgroup of patients and persist following COVID-19 resolution remains to be elucidated. This work aimed to characterize longitudinal random blood glucose in a large cohort of nondiabetic patients diagnosed with COVID-19.

Materials and Methods
De-identified electronic medical records of 7502 patients diagnosed with COVID-19 without prior diagnosis of diabetes between January 1, 2020, and November 18, 2020, were accessed through the TriNetX Research Network. Glucose measurements, diagnostic codes, medication codes, laboratory values, vital signs, and demographics were extracted before, during, and after COVID-19 diagnosis. Unsupervised time-series clustering algorithms were trained to identify distinct clusters of glucose trajectories. Cluster associations were tested for demographic variables, COVID-19 severity, glucose-altering medications, glucose values, and new-onset diabetes diagnoses.

Results
Time-series clustering identified a low-complexity model with 3 clusters and a high-complexity model with 19 clusters as the best-performing models. In both models, cluster membership differed significantly by death status, COVID-19 severity, and glucose levels. Clusters membership in the 19 cluster model also differed significantly by age, sex, and new-onset diabetes mellitus.

Discussion and Conclusion
This work identified distinct longitudinal blood glucose changes associated with subclinical glucose dysfunction in the low-complexity model and increased new-onset diabetes incidence in the high-complexity model. Together, these findings highlight the utility of data-driven techniques to elucidate longitudinal glycemic dysfunction in patients with COVID-19 and provide clinical evidence for further evaluation of the role of COVID-19 in diabetes pathogenesis.
Urinary Thromboxane B2 and Lethal Prostate Cancer in African American Men
Authors: Kiely Maeve , Milne Ginger L , Minas Tsion Z , Dorsey Tiffany H , Tang Wei , Smith Cheryl J , Baker Francine , Loffredo Christopher A , Yates Clayton , Cook Michael B , Ambs Stefan 
Published: July 2021

Abstract

Background
Thromboxane A2 (TXA2) is a platelet- and cyclooxygenase-derived eicosanoid that has been linked to metastasis. We investigated the role of TXA2 in the development of lethal prostate cancer in African American (AA) and European American (EA) men.

Methods
We measured urinary 11-dehydrothromboxane B2 (TXB2), a stable metabolite of TXA2, with mass spectrometry. Samples were obtained from 977 cases and 1022 controls at time of recruitment. We applied multivariable logistic and Cox regression modeling to examine associations of TXB2 with prostate cancer and patient survival. The median survival follow-up was 8.4 years, with 246 deaths among cases. Aspirin use was assessed with a questionnaire. Race was self-reported.

Results
Urinary TXB2 was inversely associated with aspirin use. High (&gt;median) TXB2 was associated with prostate cancer in AA (adjusted odds ratio [OR] = 1.50, 95% confidence interval [CI] = 1.13 to 2.00) but not EA men (OR = 1.07, 95% CI = 0.82 to 1.40), suggesting upregulated TXA2 synthesis in AA men with prostate cancer. High TXB2 was positively associated with metastatic prostate cancer (OR = 2.60, 95% CI = 1.08 to 6.28) compared with low (≤median) TXB2. Furthermore, high TXB2 was also associated with all-cause (adjusted hazard ratio = 1.59, 95% CI = 1.06 to 2.40) and prostate cancer-specific mortality (hazard ratio = 4.74, 95% CI = 1.62 to 13.88) in AA men only.

Conclusions
We report a distinct association of TXB2 with prostate cancer outcomes in AA men. In this high-risk group of men, upregulation of TXA2 synthesis may promote metastasis and lethal disease. Our observation identifies a potential benefit of aspirin in preventing lethal prostate cancer through inhibition of TXA2 synthesis.
Smoking and Incidence of Colorectal Cancer Subclassified by Tumor-Associated Macrophage Infiltrates
Authors: Ugai Tomotaka , Väyrynen Juha P , Haruki Koichiro , Akimoto Naohiko , Lau Mai Chan , Zhong Rong , Kishikawa Junko , Väyrynen Sara A , Zhao Melissa , Fujiyoshi Kenji , Dias Costa Andressa , Borowsky Jennifer , Arima Kota , Guerriero Jennifer L , Fuchs Charles S , Zhang Xuehong , Song Mingyang , Wang Molin , Giannakis Marios , Meyerhardt Jeffrey A , Nowak Jonathan A , Ogino Shuji 
Published: July 2021

Abstract

Background
Biological evidence indicates that smoking can influence macrophage functions and polarization, thereby promoting tumor evolution. We hypothesized that the association of smoking with colorectal cancer incidence might differ by macrophage infiltrates.

Methods
Using the Nurses’ Health Study and the Health Professionals Follow-up Study, we examined the association of smoking with incidence of colorectal cancer subclassified by macrophage counts. Multiplexed immunofluorescence (for CD68, CD86, IRF5, MAF, and MRC1 [CD206]) combined with digital image analysis and machine learning was used to identify overall, M1-polarized, and M2-polarized macrophages in tumor. We used inverse-probability–weighted multivariable Cox proportional hazards regression models to control for potential confounders and selection bias because of tissue data availability. All statistical tests were 2-sided.

Results
During follow-up of 131 144 participants (3 648 370 person-years), we documented 3092 incident colorectal cancer cases, including 871 cases with available macrophage data. The association of pack-years smoked with colorectal cancer incidence differed by stromal macrophage densities (Pheterogeneity = .003). Compared with never smoking, multivariable-adjusted hazard ratios (95% confidence interval) for tumors with low macrophage densities were 1.32 (0.97 to 1.79) for 1-19 pack-years, 1.31 (0.92 to 1.85) for 20-39 pack-years, and 1.74 (1.26 to 2.41) for 40 or more pack-years (Ptrend = .004). In contrast, pack-years smoked was not statistically significantly associated with the incidence of tumors having intermediate or high macrophage densities (Ptrend &gt; .009, with an α level of .005). No statistically significant differential association was found for colorectal cancer subclassified by M1-like or M2-like macrophages.

Conclusions
The association of smoking with colorectal cancer incidence is stronger for tumors with lower stromal macrophage counts. Our findings suggest an interplay of smoking and macrophages in colorectal carcinogenesis.
A small cog in a large wheel: crucial role of miRNAs in root apical meristem patterning
Authors: Bertolotti Gaia , Scintu Daria , Dello Ioio Raffaele 
Published: July 2021

AbstractIn both animal and plants, establishment of body axes is fundamental for proper organ development. Plant roots show two main developmental axes: the proximo-distal axis, which spans from the hypocotyl–root junction to the root tip; and the radial axis, which traverses from the vascular tissue to the epidermis. Root axes are determined in the root meristem. The root meristem occupies the tip of the root and contains self-renewing stem cells, which continuously produce new root cells. An intricate network of signalling pathways regulates meristem function and patterning to ensure proper root development and growth. In the last decade, miRNAs, 20–21 nucleotide-long molecules with morphogenetic activity, emerged as central regulators of root cell patterning. Their activity intersects with master regulators of meristematic activity, including phytohormones. In this review, we discuss the latest findings about the activity of miRNAs and their interaction with other molecular networks in the formation of root meristem axes. Furthermore, we describe how these small molecules allow root growth to adapt to changes in the environment, while maintaining the correct patterning.
Antifungal susceptibility of clinical Cryptococcus gattii isolates from Colombia varies among molecular types
Authors: Firacative Carolina , Escandón Patricia 
Published: July 2021

Abstract

Cryptococcosis by Cryptococcus gattii is endemic in Colombia, affecting mostly immunocompetent hosts. Since antifungal susceptibility differs between molecular types of cryptococcal isolates, as reported elsewhere, the aim of this study was to determine if 42 Colombian clinical isolates, VGI, VGII and VGIII, differ in the susceptibility to commonly used antifungals, using Sensititre plates. Among the molecular types, six non-wild type isolates to fluconazole, voriconazole, and 5-flucytosine, were identified. Besides, VGI and VGII were less susceptible to 5-flucytosine and azoles, respectively, than other molecular types. These findings support the applicability of practicing susceptibility testing, which could better guide treatment in cryptococcosis.

Lay Summary
Cryptococcosis gattii affects immunocompetent people. For a correct treatment, antifungal susceptibility testing is essential. This study shows differences in the susceptibility to commonly used antimycotics among genotypes of Colombian clinical C. gattii isolates, some of which are non-wild-type.
Evolution of the galaxy stellar mass function: evidence for an increasing M* from z = 2 to the present day
Authors: Adams N J , Bowler R A A , Jarvis M J , Häußler B , Lagos C D P 
Published: July 2021

ABSTRACT
Utilizing optical and near-infrared broad-band photometry covering &gt;5 deg2 in two of the most well-studied extragalactic legacy fields (COSMOS and XMM-LSS), we measure the galaxy stellar mass function (GSMF) between 0.1 &lt; z &lt; 2.0. We explore in detail the effect of two source extraction methods (SExtractor and ProFound) in addition to the inclusion/exclusion of Spitzer IRAC 3.6 and 4.5 μm photometry when measuring the GSMF. We find that including IRAC data reduces the number of massive (log10(M/M⊙) &gt; 11.25) galaxies found due to improved photometric redshift accuracy, but has little effect on the more numerous lower-mass galaxies. We fit the resultant GSMFs with double Schechter functions down to log10(M/M⊙) = 7.75 (9.75) at z = 0.1 (2.0) and find that the choice of source extraction software has no significant effect on the derived best-fitting parameters. However, the choice of methodology used to correct for the Eddington bias has a larger impact on the high-mass end of the GSMF, which can partly explain the spread in derived M* values from previous studies. Using an empirical correction to model the intrinsic GSMF, we find evidence for an evolving characteristic stellar mass with δlog10(M*/M⊙)/δz = $-0.16\pm 0.05 \, (-0.11\pm 0.05)$, when using SExtractor (ProFound). We argue that with widely quenched star formation rates in massive galaxies at low redshift (z &lt; 0.5), additional growth via mergers is required in order to sustain such an evolution to a higher characteristic mass.
A new radio census of neutron star X-ray binaries
Authors: van den Eijnden J , Degenaar N , Russell T D , Wijnands R , Bahramian A , Miller-Jones J C A , Hernández Santisteban J V , Gallo E , Atri P , Plotkin R M , Maccarone T J , Sivakoff G , Miller J M , Reynolds M , Russell D M , Maitra D , Heinke C O , Armas Padilla M , Shaw A W 
Published: July 2021

ABSTRACT
We report new radio observations of a sample of 36 neutron star (NS) X-ray binaries, more than doubling the sample in the literature observed at current-day sensitivities. These sources include 13 weakly magnetized (B &lt; 1010 G) and 23 strongly magnetized (B ≥ 1010 G) NSs. 16 of the latter category reside in high-mass X-ray binaries, of which only two systems were radio-detected previously. We detect four weakly and nine strongly magnetized NSs; the latter are systematically radio fainter than the former and do not exceed LR ≈ 3 × 1028 erg s−1. In turn, we confirm the earlier finding that the weakly magnetized NSs are typically radio fainter than accreting stellar-mass black holes. While an unambiguous identification of the origin of radio emission in high-mass X-ray binaries is challenging, we find that in all but two detected sources (Vela X-1 and 4U 1700-37) the radio emission appears more likely attributable to a jet than the donor star wind. The strongly magnetized NS sample does not reveal a global correlation between X-ray and radio luminosity, which may be a result of sensitivity limits. Furthermore, we discuss the effect of NS spin and magnetic field on radio luminosity and jet power in our sample. No current model can account for all observed properties, necessitating the development and refinement of NS jet models to include magnetic field strengths up to 1013 G. Finally, we discuss jet quenching in soft states of NS low-mass X-ray binaries, the radio non-detections of all observed very-faint X-ray binaries in our sample, and future radio campaigns of accreting NSs.
A consistent and robust measurement of the thermal state of the IGM at 2 ≤ z ≤ 4 from a large sample of  Ly α forest spectra: evidence for late and rapid He ii reionization
Authors: Gaikwad Prakash , Srianand Raghunathan , Haehnelt Martin G , Choudhury Tirthankar Roy 
Published: July 2021

ABSTRACT
We characterize the thermal state of the intergalactic medium (IGM) in 10 redshift bins in the range 2 ≤ z ≤ 4 with a sample of 103 high-resolution, high S/N  Ly α forest spectra using four different flux distribution statistics. Our measurements are calibrated with mock spectra from a large suite of hydrodynamical simulations post-processed with our thermal IGM evolution code cite, finely sampling amplitude, and slope of the expected temperature–density relation. The thermal parameters inferred from our measurements of the flux power spectrum, Doppler parameter distribution, as well as wavelet and curvature statistics agree well within their respective errors and all clearly show the peak in temperature and minimum in slope of the temperature density relation expected from  He ii reionization. Combining our measurements from the different flux statistics gives T0 = (14 750 ± 1322) K for the peak temperature at mean density and a corresponding minimum slope γ = 1.225 ± 0.120. The peak in the temperature evolution occurs around z ≈ 3, in agreement with previous measurements that had suggested the presence of such a peak, albeit with a large scatter. Using cite, we also calculate the thermal state of the IGM predicted by five widely used (spatially homogeneous) UV-background models. The rather rapid thermal evolution inferred by our measurements is well reproduced by two of the models, if we assume (physically well motivated) non-equilibrium evolution with photoheating rates that are reduced by a moderate factor of ∼0.7–0.8. The other three models predict  He ii reionization to be more extended with a higher temperature peak occurring somewhat earlier than our measurements suggest.