Cryoprobe biopsy increases the diagnostic yield in endobronchial tumor lesions

ObjectiveForceps biopsy is the standard method to obtain specimens in endoscopically visible lesions. It is common to combine forceps biopsy with cytology methods to increase the diagnostic yield. Although the flexible cryoprobe has been established for bronchoscopic interventions in malignant stenosis, the obtained biopsies, called “cryobiopsies,” have not been investigated in a large cohort of patients. The aim of this feasibility study was to prospectively evaluate the diagnostic yield and safety of cryobiopsy and forceps biopsy.MethodsDuring a 6-year period, 296 patients with visible endoluminal tumor lesions were included in the study at the bronchoscopy unit of a university hospital. In the first consecutively conducted 55 cases, both techniques, forceps biopsy and cryobiopsy, were applied simultaneously. Pathologic and quantitative image analyses were performed to evaluate the size and quality of the obtained specimens. We evaluated the safety and diagnostic yield to describe the feasibility of cryobiopsy.ResultsComparative analysis of the first conducted and randomly assigned 55 cases revealed a significantly higher diagnostic yield for cryobiopsy compared with forceps biopsy (89.1% vs 65.5%, P < .05). In this cohort, quantitative image analysis showed significantly larger biopsies regarding size and artifact-free tissue sections for cryobiopsy compared with forceps biopsy (P < .0001). The overall diagnostic yield of cryobiopsy was 89.5%. Mild bleeding occurred in 11 cases (3.7%), moderate bleeding occurred in 3 cases (1.0%), and severe bleeding occurred in 1 case (0.3%).ConclusionCryobiopsy is safe and increases the diagnostic yield in endobronchial tumor lesions. The method also is feasible under routine conditions

RNA-directed DNA methylation involves co-transcriptional small-RNA-guided slicing of polymerase V transcripts in Arabidopsis.

Small RNAs regulate chromatin modifications such as DNA methylation and gene silencing across eukaryotic genomes. In plants, RNA-directed DNA methylation (RdDM) requires 24-nucleotide small interfering RNAs (siRNAs) that bind to ARGONAUTE 4 (AGO4) and target genomic regions for silencing. RdDM also requires non-coding RNAs transcribed by RNA polymerase V (Pol V) that probably serve as scaffolds for binding of AGO4-siRNA complexes. Here, we used a modified global nuclear run-on protocol followed by deep sequencing to capture Pol V nascent transcripts genome-wide. We uncovered unique characteristics of Pol V RNAs, including a uracil (U) common at position 10. This uracil was complementary to the 5' adenine found in many AGO4-bound 24-nucleotide siRNAs and was eliminated in a siRNA-deficient mutant as well as in the ago4/6/9 triple mutant, suggesting that the +10 U signature is due to siRNA-mediated co-transcriptional slicing of Pol V transcripts. Expression of wild-type AGO4 in ago4/6/9 mutants was able to restore slicing of Pol V transcripts, but a catalytically inactive AGO4 mutant did not correct the slicing defect. We also found that Pol V transcript slicing required SUPPRESSOR OF TY INSERTION 5-LIKE (SPT5L), an elongation factor whose function is not well understood. These results highlight the importance of Pol V transcript slicing in RNA-mediated transcriptional gene silencing, which is a conserved process in many eukaryotes

Rapid generation and number-resolved detection of spinor Rubidium Bose-Einstein condensates

High data acquisition rates and low-noise detection of ultracold neutral atoms present important challenges for the state tomography and interferometric application of entangled quantum states in Bose-Einstein condensates. In this article, we present a high-flux source of $^{87}$Rb Bose-Einstein condensates combined with a number-resolving detection. We create Bose-Einstein condensates of $2\times10^5$ atoms with no discernible thermal fraction within $3.3$ s using a hybrid evaporation approach in a magnetic/optical trap. For the high-fidelity tomography of many-body quantum states in the spin degree of freedom [arXiv:2207.01270], it is desirable to select a single mode for a number-resolving detection. We demonstrate the low-noise selection of subsamples of up to $16$ atoms and their subsequent detection with a counting noise below $0.2$ atoms. The presented techniques offer an exciting path towards the creation and analysis of mesoscopic quantum states with unprecedented fidelities, and their exploitation for fundamental and metrological applications.Comment: Corrected figures, updated reference

Protocol of a Randomized Controlled Study of the PneumRx Endobronchial Coil System versus Standard-of-Care Medical Management in the Treatment of Subjects with Severe Emphysema (ELEVATE)

International audienc

Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens

Investigation of the diversity of malaria parasite antigens can help prioritize and validate them as vaccine candidates and identify the most common variants for inclusion in vaccine formulations. Studies of vaccine candidates of the most virulent human malaria parasite, Plasmodium falciparum, have focused on a handful of well-known antigens, while several others have never been studied. Here we examine the global diversity and population structure of leading vaccine candidate antigens of P. falciparum using the MalariaGEN Pf3K (version 5.1) resource, comprising more than 2600 genomes from 15 malaria endemic countries. A stringent variant calling pipeline was used to extract high quality antigen gene 'haplotypes' from the global dataset and a new R-package named VaxPack was used to streamline population genetic analyses. In addition, a newly developed algorithm that enables spatial averaging of selection pressure on 3D protein structures was applied to the dataset. We analysed the genes encoding 23 leading and novel candidate malaria vaccine antigens including csp, trap, eba175, ama1, rh5, and CelTOS. Our analysis shows that current malaria vaccine formulations are based on rare haplotypes and thus may have limited efficacy against natural parasite populations. High levels of diversity with evidence of balancing selection was detected for most of the erythrocytic and pre-erythrocytic antigens. Measures of natural selection were then mapped to 3D protein structures to predict targets of functional antibodies. For some antigens, geographical variation in the intensity and distribution of these signals on the 3D structure suggests adaptation to different human host or mosquito vector populations. This study provides an essential framework for the diversity of P. falciparum antigens to be considered in the design of the next generation of malaria vaccines

Rapid generation and number-resolved detection of spinor rubidium Bose-Einstein condensates

Hohe Datenerfassungsraten und rauscharme Detektion von ultrakalten neutralen Atomen stellen wichtige Herausforderungen für die Zustandstomographie und interferometrische Anwendung von verschränkten Quantenzuständen in Bose-Einstein-Kondensaten dar. In dieser Arbeit stellen wir eine Quelle mit hohem Fluss von Rb-87 Bose-Einstein-Kondensaten in Kombination mit einer Zahl-auflösenden Detektion vor. Wir erzeugen Bose-Einstein-Kondensate von 2*10^5 Atomen ohne erkennbaren thermischen Anteil innerhalb von 3,3 s mit einem hybriden Evaporationsverfahren in einer magnetischen und optischen Falle. Für die High-Fidelity-Tomographie von Vielkörper-Quantenzuständen im Spin-Freiheitsgrad ist es wünschenswert, eine einzelne Mode für eine Zahl-auflösende Detektion auszuwählen. Wir demonstrieren die rauscharme Auswahl von Teilmengen von bis zu 16 Atomen und deren anschließende Detektion mit einem Zählrauschen unter 0,2 Atomen. Die vorgestellten Techniken bieten einen spannenden Weg zur Erzeugung und Analyse mesoskopischer Quantenzustände mit verbesserter Zuverlässigkeit und zu deren Nutzung für fundamentale und metrologische Anwendungen

Type 2 deiodinase Thr92Ala polymorphism is not associated with cognitive impairment in older adults : a cross-sectional study

Background: Type 2 Deiodinase (DIO2) converts thyroxine (T4) into the active hormone triiodothyronine (T3). Thr92Ala DIO2 polymorphism has been associated with reduced conversion of T4 into T3 and central nervous system hypothyroidism. However, how Thr92Ala DIO2 polymorphism affects cognitive function is still unclear. Objective: To assess the association between Thr92Ala DIO2 polymorphism and cognitive performance in older adults. Design: Cross-sectional study. Setting: University-based tertiary hospital in Brazil. Patients: > 65-year-old with no limiting clinical disease. Interventions: All participants answered a standard questionnaire before undergoing thyroid function laboratory evaluation and genotyping of the Thr92Ala DIO2 polymorphism. Main Outcomes: Cognitive impairment measured by the Word List Memory task from the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Battery (CERAD-NB) and the Brief Cognitive Screening Battery (BCSB). Results: A hundred individuals were included. Clinical and laboratory characteristics were similar among DIO2 genotypes (all p > 0.05). No differences were found in the Word List Memory, recall, or recognition tests of the CERAD-NB assuming a recessive model for the Ala/Ala vs. Thr/Ala-Thr/Thr genotypes. Results of Clock Drawing Test, Animal Fluency Test, Mini-Mental State Exam, and Figure Memory Test of the BCSB were similar between groups. Conclusions: These findings suggest that Thr92Ala DIO2 polymorphism is not associated with relevant cognitive impairment in older adults

Magnetism and Pairing in Hubbard Bilayers.

We study the Hubbard model on a bilayer with repulsive on-site interactions, $U$, in which fermions undergo both intra-plane ($t$) and inter-plane ($t_z$) hopping. This situation is what one would expect in high-temperature superconductors such as YBCO, with two adjacent CuO$_2$ planes. Magnetic and pairing properties of the system are investigated through Quantum Monte Carlo simulations for both half- and quarter-filled bands. We find that in all cases inter-planar pairing with $d_{x^2-z^2}$ symmetry is dominant over planar pairing with $d_{x^2-y^2}$ symmetry, and that for $t_z$ large enough pair formation is possible through antiferromagnetic correlations. However, another mechanism is needed to make these pairs condense into a superconducting state at lower temperatures. We identify the temperature for pair formation with the spin gap crossover temperature. [Submitted to Phys. Rev. B]Comment: 7 pages, uuencoded self-unpacking PS file with text and figures

Phase locking the spin precession in a storage ring

This letter reports the successful use of feedback from a spin polarization measurement to the revolution frequency of a 0.97 GeV/$c$ bunched and polarized deuteron beam in the Cooler Synchrotron (COSY) storage ring in order to control both the precession rate ($\approx 121$ kHz) and the phase of the horizontal polarization component. Real time synchronization with a radio frequency (rf) solenoid made possible the rotation of the polarization out of the horizontal plane, yielding a demonstration of the feedback method to manipulate the polarization. In particular, the rotation rate shows a sinusoidal function of the horizontal polarization phase (relative to the rf solenoid), which was controlled to within a one standard deviation range of $\sigma = 0.21$ rad. The minimum possible adjustment was 3.7 mHz out of a revolution frequency of 753 kHz, which changes the precession rate by 26 mrad/s. Such a capability meets a requirement for the use of storage rings to look for an intrinsic electric dipole moment of charged particles