Microbial polyhydroxyalkanoates (PHAs) are bio-based aliphatic biopolyester produced by bacteria as an intracellular storage material of carbon and energy under stressed conditions. PHAs have been paid attention to due to their unique and impressive biological properties including high biodegradability, biocompatibility, low cytotoxicity, and different mechanical properties. Under this context, the development of drug-delivery nanosystems based on PHAs has been revealed to have numerous advantages compared with synthetic polymers that included biocompatibility, biodegradability, non-toxic, and low-cost production, among others. In this review article, we present the available state of the art of PHAs. Moreover, we discussed the potential benefits, weaknesses, and perspectives of PHAs to the develop drug delivery systems.

The Xerces Blue (Glaucopsyche xerces) is considered to be the first butterfly to become extinct in historical times. It was notable for its chalky lavender wings with conspicuous white spots on the ventral wings. The last individuals were collected in their restricted habitat, in the dunes near the Presidio military base in San Francisco, in 1941. We sequenced the genomes of four 80- to 100-year-old Xerces Blue, and seven historical and one modern specimens of its closest relative, the Silvery Blue (Glaucopsyche lygdamus). We compared these to a novel annotated genome of the Green-Underside Blue (Glaucopsyche alexis). Phylogenetic relationships inferred from complete mitochondrial genomes indicate that Xerces Blue was a distinct species that diverged from the Silvery Blue lineage at least 850,000 years ago. Using nuclear genomes, both species experienced population growth during the Eemian interglacial period, but the Xerces Blue decreased to a very low effective population size subsequently, a trend opposite to that observed in the Silvery Blue. Runs of homozygosity and deleterious load in the former were significantly greater than in the later, suggesting a higher incidence of inbreeding. These signals of population decline observed in Xerces Blue could be used to identify and monitor other insects threatened by human activities, whose extinction patterns are still not well known.

Pangenome graphs can represent all variation between multiple reference genomes, but current approaches to build them exclude complex sequences or are based upon a single reference. In response, we developed the PanGenome Graph Builder (PGGB), a pipeline for constructing pangenome graphs without bias or exclusion. PGGB uses all-to-all alignments to build a variation graph in which we can identify variation, measure conservation, detect recombination events, and infer phylogenetic relationships.

In this work, we study the luminosity that results from the conversion of QCD axion particles into photons in the magnetic field of the plasma accreting onto black holes (BHs). For the luminosities to be large two conditions need to be met: (i) there are large numbers of axions in the primordial BH surroundings as a result of the so-called superradiant instability; (ii) there exists a point inside the accreting region where the plasma and axion masses are similar and there is resonant axion-photon conversion. For BHs accreting from the interstellar medium in our Galaxy, the above conditions require the black hole to have subsolar masses and we are therefore led to consider a population of primordial black holes (PBHs). In the conservative window, where we stay within the nonrelativistic behavior of the plasma and neglect the possibility of nonlinear enhancement via magnetic stimulation, the typical frequencies of the emitted photons lie on the low-radio band. We thus study the prospects for detection using the LOFAR telescope, assuming the PBH abundance to be close to the maximal allowed by observations. We find that for PBH and QCD axion with masses in the range 10−5–10−4M⊙ and 4×10−8 and 4×10−7 eV, respectively, the flux density emitted by the closest PBH, assuming it accretes from the warm ionized medium, can be detected at the LOFAR telescope. Coincidentally, the PBH mass range coincides with the range that would explain the microlensing events found in OGLE. This might further motivate a dedicated search of these signals in the LOFAR data and other radio telescopes. Published by the American Physical Society 2024

Bipolar disorder (BD) has been reconceptualised as a progressive disorder that develops from mild to severe presentations. An empirical staging model - the Empirically Developed Clinical Staging Model for BD (EmDe-5) - was developed in a previous study. This study aims to further validate that model using a larger and more representative Spanish sample. 183 BD outpatients were recruited at 11 sites in Spain. Assessment included clinical characteristics of the BD (number of hospitalisations, number of suicide attempts, comorbid personality disorders), physical health (BMI, metabolic syndrome, number of physical illnesses), cognition (SCIP), functioning (permanently disabled due to BD, FAST), and quality of life (SF-36). The CGI-S, VAS-S, and psychopharmacological treatment pattern were used as external validators. Ten patients (51.5%) were classified as stage 1, 33 (18%) as stage 2, 93 (508%) as stage 3, 37 (202%) as stage 4, and 10 (55%) as stage 5. All profilers, other than number of suicide attempts (p=0.311) and comorbid personality disorder (p=0.061), exhibited worse scores from stage 1 to 5. As expected, VAS-S and CGI-S scores were worse in the later stages. Regarding treatment, early stages (1-2) were associated with the use of one to three drugs while late stages (4-5) were associated with four or more drugs (p=0.002). We confirm the EmDe-5 staging model's construct validity. The ease of obtaining the profilers, together with the operational criteria provided to quantify them, will facilitate the use of the EmDe-5 staging model in daily clinical practice.

Background and objectiveGrowing evidence supports the use of neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). However, the implications of residual UTUC at radical nephroureterectomy (RNU) after NAC are not well characterized. Our objective was to compare oncologic outcomes for pathologic risk–matched patients who underwent RNU for UTUC who either received NAC or were chemotherapy-naïve. MethodsWe retrospectively identified 1993 patients (including 112 NAC recipients) who underwent RNU for nonmetastatic, high-grade UTUC between 1985 and 2022in a large, international, multicenter cohort. We divided the cohort into low-risk and high-risk groups defined according to pathologic findings of muscle invasion and lymph node involvement at RNU. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) estimates were calculated using the Kaplan-Meier method. Multivariable analyses were performed to determine clinical and demographic factors associated with these outcomes. Key findings and limitationsAmong patients with low-risk pathology at RNU, RFS, OS, and CSS were similar between the NAC and chemotherapy-naïve groups. Among patients with high-risk pathology at RNU, the NAC group had poorer RFS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 2.10–4.48), OS (HR 2.06, 95% CI 1.33–3.20), and CSS (subdistribution HR 2.54, 95% CI 1.37–4.69) in comparison to the pathologic risk-matched, chemotherapy-naïve group. Limitations include the lack of centralized pathologic review. Conclusions and clinical implicationsPatients with residual invasive disease at RNU after NAC represent a uniquely high-risk population with respect to oncologic outcomes. There is a critical need to determine an optimal adjuvant approach for these patients. Patient summaryWe studied a large, international group of patients with cancer of the upper urinary tract who underwent surgery either with or without receiving chemotherapy beforehand. We identified a high-risk subgroup of patients with residual aggressive cancer after chemotherapy and surgery who should be prioritized for clinical trials and drug development.

We consider the problem of correctly identifying a malfunctioning quantum device that forms part of a network of N such devices, which can be considered as the quantum analog of classical anomaly detection. In the case where the devices in question are sources assumed to prepare identical quantum pure states, with the faulty source producing a different anomalous pure state, we show that the optimal probability of successful identification requires a global quantum measurement. We also put forth several local measurement strategies—both adaptive and nonadaptive—that achieve the same optimal probability of success in the limit where the number of devices to be checked is large. In the case where the faulty device performs a known unitary operation, we show that the use of entangled probes provides an improvement that even allows perfect identification for values of the unitary parameter that surpass a certain threshold. Finally, if the faulty device implements a known qubit channel, we find that the optimal probability for detecting the position of rank-one and rank-two Pauli channels can be achieved by product state inputs and separable measurements for any size of network, whereas for rank-three and general amplitude damping channels, optimal identification requires entanglement with N qubit ancillas. Published by the American Physical Society 2024