Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by ...single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.
Several transition-metal dichalcogenides exhibit a striking crossover from indirect to direct band gap semiconductors as they are thinned down to a single monolayer. Here, we demonstrate how an ...electronic structure characteristic of the isolated monolayer can be created at the surface of a bulk MoS2 crystal. This is achieved by intercalating potassium in the interlayer van der Waals gap, expanding its size while simultaneously doping electrons into the conduction band. Our angle-resolved photoemission measurements reveal resulting electron pockets centered at the K̅ and K′ points of the Brillouin zone, providing the first momentum-resolved measurements of how the conduction band dispersions evolve to yield an approximately direct band gap of ∼1.8 eV in quasi-freestanding monolayer MoS2. As well as validating previous theoretical proposals, this establishes a novel methodology for manipulating electronic structure in transition-metal dichalcogenides, opening a new route for the generation of large-area quasi-freestanding monolayers for future fundamental study and use in practical applications.
We report a precision measurement of the parity-violating asymmetry APV in the elastic scattering of longitudinally polarized electrons from 208Pb. We measure APV= 550 ± 16 (stat) ±8 (syst) parts per ...billion, leading to an extraction of the neutral weak form factor FW(Q2= 0.00616 GeV2) = 0.368 ± 0.013. Combined with our previous measurement, the extracted neutron skin thickness is Rn-Rp= 0.283 ± 0.071 fm. The result also yields the first significant direct measurement of the interior weak density of 208Pb: ρ$^0_W$ = -0.0796 ± 0.0036(exp) ± 0.0013(theo) fm-3 leading to the interior baryon density ρ$^0_b$ = 0.1480 ± 0.0036(exp) ± 0.0013(theo) fm-3. Finally, the measurement accurately constrains the density dependence of the symmetry energy of nuclear matter near saturation density, with implications for the size and composition of neutron stars.
Two-dimensional electron gases (2DEGs) in SrTiO3 have become model systems for engineering emergent behaviour in complex transition metal oxides. Understanding the collective interactions that enable ...this, however, has thus far proved elusive. Here we demonstrate that angle-resolved photoemission can directly image the quasiparticle dynamics of the d-electron subband ladder of this complex-oxide 2DEG. Combined with realistic tight-binding supercell calculations, we uncover how quantum confinement and inversion symmetry breaking collectively tune the delicate interplay of charge, spin, orbital and lattice degrees of freedom in this system. We reveal how they lead to pronounced orbital ordering, mediate an orbitally enhanced Rashba splitting with complex subband-dependent spin-orbital textures and markedly change the character of electron-phonon coupling, co-operatively shaping the low-energy electronic structure of the 2DEG. Our results allow for a unified understanding of spectroscopic and transport measurements across different classes of SrTiO3-based 2DEGs, and yield new microscopic insights on their functional properties.
The echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) fusion gene has been identified as a potent oncogenic driver in non–small-cell lung cancer, in particular ...adenocarcinoma (ADC). It defines a unique subgroup of lung ADC, which may be responsive to ALK inhibitors. Detection of ALK rearrangement by fluorescence in situ hybridization (FISH) or reverse transcriptase polymerase chain reaction (RT-PCR) is considered to be the standard procedure, but each with its own limitation. We evaluated the practical usefulness of immunohistochemistry (IHC) to detect ALK expression as a reliable detection method of ALK rearrangement in lung ADC.
We tested 373 lung ADCs for ALK rearrangement by IHC and FISH. Multiplex RT-PCR was performed to confirm the fusion variants.
Twenty-two of 373 lung ACs (5.9%) were positive for ALK immunoreactivity. ALK-positive tumor cells demonstrated strong and diffused granular staining in the cytoplasm. All the ALK IHC-positive cases were confirmed to harbor ALK rearrangement, either by FISH, or RT-PCR. Two cases with positive ALK protein expression, but negative for breakapart FISH signal were shown to harbor EML4-ALK variant 1 by RT-PCR. None of the ALK IHC-negative cases were FISH-positive. In addition, we identified a novel EML4-ALK fusion variant (E3:ins53A20), and its potent transformation potential has been confirmed by in vivo tumorigenicity assay.
IHC can effectively detect ALK rearrangement in lung cancer. It might provide a reliable and cost-effective diagnostic approach in routine pathologic laboratories for the identification of suitable candidates for ALK-targeted therapy.
Circulating Epstein–Barr virus DNA was measured in 20,174 asymptomatic participants in Hong Kong; 34 of 309 with positive results had nasopharyngeal cancer. Stage distribution and progression-free ...survival were better in the 34 participants than in a historical cohort.
Tunable bandgaps, extraordinarily large exciton-binding energies, strong light-matter coupling and a locking of the electron spin with layer and valley pseudospins have established transition-metal ...dichalcogenides (TMDs) as a unique class of two-dimensional (2D) semiconductors with wide-ranging practical applications. Using angle-resolved photoemission (ARPES), we show here that doping electrons at the surface of the prototypical strong spin-orbit TMD WSe2, akin to applying a gate voltage in a transistor-type device, induces a counterintuitive lowering of the surface chemical potential concomitant with the formation of a multivalley 2D electron gas (2DEG). These measurements provide a direct spectroscopic signature of negative electronic compressibility (NEC), a result of electron-electron interactions, which we find persists to carrier densities approximately three orders of magnitude higher than in typical semiconductor 2DEGs that exhibit this effect. An accompanying tunable spin splitting of the valence bands further reveals a complex interplay between single-particle band-structure evolution and many-body interactions in electrostatically doped TMDs. Understanding and exploiting this will open up new opportunities for advanced electronic and quantum-logic devices.
Early-stage nasopharyngeal carcinoma (NPC) evades detection when the primary tumor is hidden from view on endoscopic examination. Therefore, in a prospective study of subjects being screened for NPC ...using plasma Epstein–Barr virus (EBV) DNA, we conducted a study to investigate whether magnetic resonance imaging (MRI) could detect endoscopically occult NPC.
Participants with persistently positive EBV DNA underwent endoscopic examination and biopsy when suspicious for NPC, followed by MRI blinded to the endoscopic findings. Participants with a negative endoscopic examination and positive MRI were recalled for biopsy or surveillance. Diagnostic performance was assessed by calculating sensitivity, specificity and accuracy, based on the histologic confirmation of NPC in the initial study or in a follow-up period of at least two years.
Endoscopic examination and MRI were performed on 275 participants, 34 had NPC, 2 had other cancers and 239 without cancer were followed-up for a median of 36months (24–60months). Sensitivity, specificity and accuracy were 76.5%, 97.5% and 94.9%, respectively, for endoscopic examination and 91.2%, 97.5% and 96.7%, respectively, for MRI. NPC was detected only by endoscopic examination in 1/34 (2.9%) participants (a participant with stage I disease), and only by MRI in 6/34 (17.6%) participants (stage I=4, II = 1, III = 1), two of whom had stage I disease and follow-up showing slow growth on MRI but no change on endoscopic examination for 36months.
MRI has a complementary role to play in NPC detection and can enable the earlier detection of endoscopically occult NPC.
Background: Antonovsky's concept of sense of coherence (SOC) - as a global orientation reflecting an individual's feeling of confidence in both the predictability of their internal and external ...environment and their ability to cope with stressful and challenging situations in life - shows a negative association with symptoms of post-traumatic stress. However, single studies varying in study characteristics provide heterogeneous effect size estimations.
Objective: The purpose of the current study is to investigate the relationship between SOC and post-traumatic stress disorder (PTSD) symptom severity for the first time on a meta-analytical level.
Method: The random-effects meta-analysis is based on zero-order correlations (r) and consists of 47 independent samples out of 45 studies (N = 10,883).
Results: After correcting for sampling error, the mean correlation between SOC and PTSD symptoms was M(r) = −.41 (excluding four outliers: −.39). However, this effect could not be generalized to all types of PTSD samples owing to substantial remaining heterogeneity. Subsequent moderator analyses investigating the influence of different SOC and PTSD measures, trauma type and duration, mean age and gender imbalances per sample did not reveal significant moderating effects.
Conclusions: The meta-analysis reveals a substantial correlation between SOC and PTSD symptom severity: higher SOC levels are associated with lower symptom severity. Thus, future research should progress to the question of whether the relationship between SOC and post-traumatic stress is causal, and by which factors it is moderated.
Abbreviations: CD, Cook's distance; DSM, Diagnostic and Statistical Manual of Mental Disorders; (G)RR, general (and specific) resistance resources; IES(-R), Impact of Event Scale (Revised); PDS, Posttraumatic Stress Diagnostic Scale; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PTSD, post-traumatic stress disorder; SDR, standard deleted residual; SOC, sense of coherence; SOC-R, Sense of Coherence Scale - Revised
* This meta-analysis reports a robust correlation between sense of coherence (SOC) and post-traumatic stress disorder (PTSD) symptoms. * Higher SOC levels are linked to lower PTSD symptom scores. * No significant moderating effects were found for the correlation between SOC and PTSD symptoms. * There were homogeneous correlations for Holocaust and war traumas and enduring stressors. * Future research needs to investigate a potential causal relationship.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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