Low-temperature lattice effects in the spin-liquid candidate κ\kappa-(BEDT-TTF)2_2Cu2_2(CN)3_3

The quasi-two-dimensional organic charge-transfer salt $\kappa$-(BEDT-TTF)$_2$Cu$_2$(CN)$_3$ is one of the prime candidates for a quantum spin-liquid due the strong spin frustration of its anisotropic triangular lattice in combination with its proximity to the Mott transition. Despite intensive investigations of the material's low-temperature properties, several important questions remain to be answered. Particularly puzzling are the 6\,K anomaly and the enigmatic effects observed in magnetic fields. Here we report on low-temperature measurements of lattice effects which were shown to be particularly strongly pronounced in this material (R. S. Manna \emph{et al.}, Phys. Rev. Lett. \textbf{104}, 016403 (2010)). A special focus of our study lies on sample-to-sample variations of these effects and their implications on the interpretation of experimental data. By investigating overall nine single crystals from two different batches, we can state that there are considerable differences in the size of the second-order phase transition anomaly around 6\,K, varying within a factor of 3. In addition, we find field-induced anomalies giving rise to pronounced features in the sample length for two out of these nine crystals for temperatures $T <$ 9 K. We tentatively assign the latter effects to $B$-induced magnetic clusters suspected to nucleate around crystal imperfections. These $B$-induced effects are absent for the crystals where the 6\,K anomaly is most strongly pronounced. The large lattice effects observed at 6\,K are consistent with proposed pairing instabilities of fermionic excitations breaking the lattice symmetry. The strong sample-to-sample variation in the size of the phase transition anomaly suggests that the conversion of the fermions to bosons at the instability is only partial and to some extent influenced by not yet identified sample-specific parameters

Field-induced effects in the spin liquid candidate PbCuTe2_{2}O6_{6}

PbCuTe$_2$O$_6$ is considered as one of the rare candidate materials for a three-dimensional quantum spin liquid (QSL). This assessment was based on the results of various magnetic experiments, performed mainly on polycrystalline material. More recent measurements on single crystals revealed an even more exotic behavior, yielding ferroelectric order below $T_{\text{FE}}\approx 1\,\text{K}$, accompanied by distinct lattice distortions, and a somewhat modified magnetic response which is still consistent with a QSL. Here we report on low-temperature measurements of various thermodynamic, magnetic and dielectric properties of single crystalline PbCuTe$_2$O$_6$ in magnetic fields $B\leq 14.5\,\text{T}$. The combination of these various probes allows us to construct a detailed $B$-$T$ phase diagram including a ferroelectric phase for $B \leq$ $8\,\text{T}$ and a $B$-induced magnetic phase at $B \geq$ $11\,\text{T}$. These phases are preceded by or coincide with a structural transition from a cubic high-temperature phase into a distorted non-cubic low-temperature state. The phase diagram discloses two quantum critical points (QCPs) in the accessible field range, a ferroelectric QCP at $B_{c1}$ = $7.9\,\text{T}$ and a magnetic QCP at $B_{c2}$ = $11\,\text{T}$. Field-induced lattice distortions, observed in the state at $T>$ $1\,\text{K}$ and which are assigned to the effect of spin-orbit interaction of the Cu$^{2+}$-ions, are considered as the key mechanism by which the magnetic field couples to the dielectric degrees of freedom in this material

Spin liquid and ferroelectricity close to a quantum critical point in PbCuTe2O6

Geometrical frustration among interacting spins combined with strong quantum fluctuations destabilize long-range magnetic order in favour of more exotic states such as spin liquids. By following this guiding principle, a number of spin liquid candidate systems were identified in quasi-two-dimensional (quasi-2D) systems. For 3D, however, the situation is less favourable as quantum fluctuations are reduced and competing states become more relevant. Here we report a comprehensive study of thermodynamic, magnetic and dielectric properties on single crystalline and pressed-powder samples of PbCuTe$_2$O$_6$, a candidate material for a 3D frustrated quantum spin liquid featuring a hyperkagome lattice. Whereas the low-temperature properties of the powder samples are consistent with the recently proposed quantum spin liquid state, an even more exotic behaviour is revealed for the single crystals. These crystals show ferroelectric order at $T_{\text{FE}} \approx 1\,\text{K}$, accompanied by strong lattice distortions, and a modified magnetic response -- still consistent with a quantum spin liquid -- but with clear indications for quantum critical behaviour.Comment: 59 pages, 15 figures, This version of the article has been accepted for publication, after peer review but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available onlin

Molecular profiling of single circulating tumor cells with diagnostic intention

Several hundred clinical trials currently explore the role of circulating tumor cell (CTC) analysis for therapy decisions, but assays are lacking for comprehensive molecular characterization of CTCs with diagnostic precision. We therefore combined a workflow for enrichment and isolation of pure CTCs with a non-random whole genome amplification method for single cells and applied it to 510 single CTCs and 189 leukocytes of 66 CTC-positive breast cancer patients. We defined a genome integrity index (GII) to identify single cells suited for molecular characterization by different molecular assays, such as diagnostic profiling of point mutations, gene amplifications and whole genomes of single cells. The reliability of >90% for successful molecular analysis of high-quality clinical samples selected by the GII enabled assessing the molecular heterogeneity of single CTCs of metastatic breast cancer patients. We readily identified genomic disparity of potentially high relevance between primary tumors and CTCs. Microheterogeneity analysis among individual CTCs uncovered pre-existing cells resistant to ERBB2-targeted therapies suggesting ongoing microevolution at late-stage disease whose exploration may provide essential information for personalized treatment decisions and shed light into mechanisms of acquired drug resistance

Molecular profiling of single circulating tumor cells with diagnostic intention

Several hundred clinical trials currently explore the role of circulating tumor cell (CTC) analysis for therapy decisions, but assays are lacking for comprehensive molecular characterization of CTCs with diagnostic precision. We therefore combined a workflow for enrichment and isolation of pure CTCs with a non-random whole genome amplification method for single cells and applied it to 510 single CTCs and 189 leukocytes of 66 CTC-positive breast cancer patients. We defined a genome integrity index (GII) to identify single cells suited for molecular characterization by different molecular assays, such as diagnostic profiling of point mutations, gene amplifications and whole genomes of single cells. The reliability of >90% for successful molecular analysis of high-quality clinical samples selected by the GII enabled assessing the molecular heterogeneity of single CTCs of metastatic breast cancer patients. We readily identified genomic disparity of potentially high relevance between primary tumors and CTCs. Microheterogeneity analysis among individual CTCs uncovered pre-existing cells resistant to ERBB2-targeted therapies suggesting ongoing microevolution at late-stage disease whose exploration may provide essential information for personalized treatment decisions and shed light into mechanisms of acquired drug resistance

Localization Techniques for Non-Palpable Breast Lesions : Current Status, Knowledge Gaps, and Rationale for the MELODY Study (EUBREAST-4/iBRA-NET, NCT 05559411)

Funding: The MELODY study will be financially supported by: Hologic, Merit Medical, Endomag and Sirius Medical.Peer reviewedPublisher PD

Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy : Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical)

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease