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Purpose Ovarian cancer (OC) is characterized by a high recurrence rate, and homologous recombination deficiency (HRD) is an important biomarker in the clinical management of OC. We investigated the differences in clinical genomic profiles between the primary and platinum-sensitive recurrent OC (PSROC), focusing on HRD status. Materials and methods A total of 40 formalin-fixed paraffin-embedded (FFPE) tissues of primary tumors and their first platinum-sensitive recurrence from 20 OC patients were collected, and comprehensive genomic profiling (CGP) analysis of FoundationOne ® CDx (F1CDx) was applied to explore the genetic (dis)similarities of the primary and recurrent tumors. Results By comparing between paired samples, we found that genomic loss of heterozygosity (gLOH) score had a high intra-patient correlation (r 2  = 0.79) and that short variants (including TP53, BRCA1/2 and NOTCH1 mutations), tumor mutational burden (TMB) and microsatellite stability status remained stable. The frequency of (likely) pathological BRCA1/2 mutations was 30% (12/40) in all samples positively correlated with gLOH scores, but the proportion of gLOH-high status (score > 16%) was 50% (10/20) and 55% (11/20) in the primary and recurrent samples, respectively. An additional 20% (4/20) of patients needed attention, a quarter of which carried the pathological BRCA1 mutation but had a gLOH-low status (gLOH < 16%), and three-quarters had different gLOH status in primary-recurrent pairs. Furthermore, we observed the PSROC samples had higher gLOH scores (16.1 ± 9.24 vs. 19.4 ± 11.1, p  = 0.007), more CNVs (36.1% vs. 15.1% of discordant genomic alternations), and significant enrichment of altered genes in TGF-beta signaling and Hippo signaling pathways ( p  < 0.05 for all) than their paired primaries. Lastly, mutational signature and oncodrive gene analyses showed that the computed mutational signature similarity in the primary and recurrent tumors were best matched the COSMI 3 signature (Aetiology of HRD) and had consistent candidate cancer driver genes of MSH2, NOTCH1 and MSH6. Conclusion The high genetic concordance of the short variants remains stable along OC recurrence. However, the results reveal significantly higher gLOH scores in the recurrent setting than in paired primaries, supporting further clinically instantaneity HRD assay strategy.

Purpose In this paper, we study the bursting dynamics and mechanisms of a class of 3-D Hindmarsh-Rose neuron models with single and dual external periodic excitation terms. The aim of this study is to further enrich the compound bursting dynamics and provide guidance for the diagnosis and treatment of neurological diseases. Methods Initially, the stability of equilibrium and bifurcation of the system are analyzed. When two external periodic excitations exist in the system, by using the De Moivre equation to transform it into a new form of a single slow variable, and the classical fast-slow analysis method is used to study the bursting oscillations. Numerical simulations are employed to obtain the bifurcation structures of the system under single and dual excitations. Results Two typical bursting oscillation modes: fold/supHopf-homoclinic bursting and fold/supHopf-fold bursting are observed under one external excitation. And the transformation of discharge rhythm has been revealed by bifurcation portrait. With two external excitations, multiple types compound bursting patterns have been revealed, such as “fold/homoclinic cycle/fold/suphopf-homoclinic/fold/homoclinic cycle” bursting. Additionally, we observed that variations in the excitation frequency can influence the delay behavior of subHopf bifurcations. Conclusions Compared with the simple bursting modes of single periodic excitation, the dual one has more abundant compound bursting mechanism. The firing mechanism of neurons studied in this paper will be helpful for the regulation of neurons.

This decade has seen the first measurements of extrasolar planetary obliquities, characterizing how an exoplanet's spin axis is oriented relative to its orbital axis. These measurements are enabled by combining projected rotational velocities, planetary rotation periods, and astrometric orbits for directly-imaged super-Jupiters. This approach constrains both the spin axis and orbital inclination relative to the line of sight, allowing obliquity measurements for individual systems and offering new insights into their formation. To test whether these super-Jupiters form more like scaled-up planets or scaled-down stars, we develop a hierarchical Bayesian framework to infer their population-level obliquity distribution. Using a single-parameter Fisher distribution, we compare two models: a planet-like formation scenario (\\(\\kappa=5\\)) predicting moderate alignment, versus a brown dwarf-like formation scenario (\\(\\kappa=0\\)) predicting isotropic obliquities. Based on a sample of four young super-Jupiter systems, we find early evidence favoring the isotropic case with a Bayes factor of 15, consistent with turbulent fragmentation.

While many hot Jupiter systems have a measured obliquity, few warm Jupiter systems do. The longer orbital periods and transit durations of warm Jupiters make it more difficult to measure the obliquities of their host stars. However, the longer periods also mean any misalignments persist due to the longer tidal realignment timescales. As a result, measuring these obliquities is necessary to understand how these types of planets form and how their formation and evolution differ from that of hot Jupiters. Here, we report the measurement of the Rossiter-McLaughlin effect for the TOI-4127 system using the HARPS-N spectrograph. We model the system using our new HARPS-N radial velocity measurements in addition to archival TESS photometry and NEID and SOPHIE radial velocities. We find that the host star is well-aligned with the highly eccentric (e=0.75) warm Jupiter TOI-4127 b, with a sky-projected obliquity \\({\\lambda} = {4^\\circ}^{+17^\\circ}_{-16^\\circ}\\). This makes TOI-4127 one of the most eccentric well-aligned systems to date and one of the longest period systems with a measured obliquity. Conclusions. The origin of its highly eccentric yet well-aligned orbit remains a mystery, however, and we investigate possible scenarios that could explain it. While typical in-situ formation and disk migration scenarios cannot explain this system, certain scenarios involving resonant interactions between the planet and protoplanetary disc could. Similarly, specific cases of planet-planet scattering or Kozai-Lidov oscillations can result in a highly-eccentric and well-aligned orbit. Coplanar high-eccentricity migration could also explain this system. However, both this mechanism and Kozai-Lidov oscillations require an additional planet in the system that has not yet been detected.

Transitional disks are protoplanetary disks with large and deep central holes in the gas, possibly carved by young planets. Dong, R., & Dawson, R. 2016, ApJ, 825, 7 simulated systems with multiple giant planets that were capable of carving and maintaining such gaps during the disk stage. Here we continue their simulations by evolving the systems for 10 Gyr after disk dissipation and compare the resulting system architecture to observed giant planet properties, such as their orbital eccentricities and resonances. We find that the simulated systems contain a disproportionately large number of circular orbits compared to observed giant exoplanets. Large eccentricities are generated in simulated systems that go unstable, but too few of our systems go unstable, likely due to our demand that they remain stable during the gas disk stage to maintain cavities. We also explore whether transitional disk inspired initial conditions can account for the observed younger ages of 2:1 resonant systems orbiting mature host stars. Many simulated planet pairs lock into a 2:1 resonance during the gas disk stage, but those that are disrupted tend to be disrupted early, within the first 10 Myr. Our results suggest that systems of giant planets capable of carving and maintaining transitional disks are not the direct predecessors of observed giant planets, either because the transitional disk cavities have a different origin or another process is involved, such as convergent migration that pack planets close together at the end of the transitional disk stage.

Hot Jupiters may have formed in situ, or been delivered to their observed short periods through one of two categories of migration mechanisms: disk migration or high-eccentricity migration. If hot Jupiters were delivered by high-eccentricity migration, we would expect to observe some \"super-eccentric\" Jupiters in the process of migrating. We update a prediction for the number of super-eccentric Jupiters we would expect to observe in the Kepler sample if all hot Jupiters migrated through high-eccentricity migration and estimate the true number observed by Kepler. We find that the observations fail to match the prediction from high-eccentricity migration with 94.3% confidence and show that high-eccentricity migration can account for at most ~62% of the hot Jupiters discovered by Kepler.

Stellar obliquity, the angle between a planet's orbital axis and its host star's spin axis, traces the formation and evolution of a planetary system. In transiting exoplanet observations, only the sky-projected stellar obliquity can be measured, but this can be de-projected using an estimate of the stellar obliquity. In this paper, we introduce a flexible, hierarchical Bayesian framework that can be used to infer the stellar obliquity distribution solely from sky-projected stellar obliquities, including stellar inclination measurements when available. We demonstrate that while a constraint on the stellar inclination is crucial for measuring the obliquity of an individual system, it is not required for robust determination of the population-level stellar obliquity distribution. In practice, the constraints on the stellar obliquity distribution are mainly driven by the sky-projected stellar obliquities. When applying the framework to all systems with measured sky-projected stellar obliquity, which are mostly Hot Jupiter systems, we find that the inferred population-level obliquity distribution is unimodal and peaked at zero degrees. The misaligned systems have nearly isotropic stellar obliquities with no strong clustering near 90 degrees. The diverse range of stellar obliquities prefers dynamic mechanisms, such as planet-planet scattering after a convergent disk migration, which could produce both prograde and retrograde orbits of close-in planets with no strong inclination concentrations other than 0 degrees.

We present the first measurement of the sky-projected orbital obliquity of a benchmark transiting brown dwarf host, HIP 33609, as a part of the Orbital Architectures of Transiting Massive Exoplanets And Low-mass stars (OATMEAL) survey. HIP 33609 b is a highly eccentric, 68 \\(M_{\\rm J}\\) brown dwarf orbiting a 10,300 K, A-type star with an orbital period of 39 days. Its host star is a known member of the 150 Myr old MELANGE-6 moving group, making it an excellent laboratory for testing sub-stellar evolutionary models. Using in-transit spectra collected by the Planet Finder Spectrograph (PFS) on the Magellan II Clay 6.5 m telescope, we measured a sky-projected orbital obliquity of \\(|\\lambda|= 12.7 \\pm 1.3\\){\\deg}. The mass of the brown dwarf is most consistent with a stellar-like fragmentation formation history followed by a period of migration. Given the high eccentricity (\\(e=0.557\\)) but low orbital obliquity of the brown dwarf, we claim that coplanar high eccentricity tidal migration seems to be the most plausible pathway, however, it remains difficult to conclusively rule out other migration mechanisms. The low orbital obliquity for HIP 33609 is consistent with previous measurements of high mass-ratio companions, and bears a striking resemblance to the obliquity distribution of transiting warm Jupiters. We suggest brown dwarfs may follow a dynamically quiescent migration pathway, consistent with them forming in isolated conditions.

A significant fraction of hot Jupiters have orbital axes misaligned with their host stars' spin axes. The large stellar obliquities of these giants have long been considered potential signatures of high-eccentricity migration, which is expected to clear out any nearby planetary companions. This scenario requires that only isolated hot Jupiters be spin-orbit misaligned while those with nearby companions, which must have more quiescent histories, maintain low-obliquity orbits, assuming they formed aligned within their primordial protoplanetary disks. Investigations of this stellar obliquity-companionship connection, however, have been severely limited by the lack of hot Jupiters found in compact multi-planet systems. Here we present the sky-projected stellar obliquity (\\(\\lambda\\)) of a hot Jupiter with a nearby inner companion recently discovered by NASA's Transiting Exoplanet Survey Satellite: TOI-5143 c. Specifically, we utilize the Doppler shadow caused by the planet's transit, enabled by the Rossiter-McLaughlin (RM) effect, to find that the planet is aligned with \\(\\lambda=2.1 ^{+2.8}_{-2.7} \\circ\\). Of the exoplanets with RM measurements, TOI-5143 c becomes just the third hot Jupiter with a nearby companion, and is part of the 19th compact multi-planet single-star system, with an RM measurement. The spin-orbit alignment of these 19 systems provides strong support for primordial alignment, and thus implies that large obliquities are gained primarily due to post-disk dynamical interactions such as those inherent to high-eccentricity migration. As such, the observed spin-orbit alignment of hot Jupiters with nearby companions affirms that some fraction of these giants instead have quiescent origins.

Despite decades of effort, the mechanisms by which the spin axis of a star and the orbital axes of its planets become misaligned remain elusive. Particularly, it is of great interest whether the large spin-orbit misalignments observed are driven primarily by high-eccentricity migration -- expected to have occurred for short-period, isolated planets -- or reflect a more universal process that operates across systems with a variety of present-day architectures. Compact multi-planet systems offer a unique opportunity to differentiate between these competing hypotheses, as their tightly-packed configurations preclude violent dynamical histories, including high-eccentricity migration, allowing them to trace the primordial disk plane. In this context, we report measurements of the sky-projected stellar obliquity (\\(\\lambda\\)) via the Rossiter-McLaughlin effect for two sub-Saturns in multiple-transiting systems: TOI-5126 b (\\(\\lambda=1\\pm 48 ^\\circ\\)) and TOI-5398 b (\\(\\lambda=-8.1^{+5.3 \\circ}_{-6.3}\\)). Both are spin-orbit aligned, joining a fast-growing group of just three other compact sub-Saturn systems, all of which exhibit spin-orbit alignment. In aggregate with archival data, our results strongly suggest that sub-Saturn systems are primordially aligned and become misaligned largely in the post-disk phase, as appears to be the case increasingly for other exoplanet populations.