Search

Sarah Sharman Moser,1 Lior Apter,1,2 Idit Livnat,3 Roni Ginsburg,3 Adva Yarden,3 Michal Drori,1 Anat Drizon,1 Gabriel Chodick,1,4 Nava Siegelmann-Danieli1,4 1Maccabi Institute for Research and Innovation (Maccabitech), Maccabi Healthcare Services, Tel Aviv, Israel; 2Department of Health Systems Management, Ben-Gurion University of the Negev, Beer-Sheva, Israel; 3Medical Affairs, AstraZeneca, Kefar Sava, Israel; 4Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelCorrespondence: Sarah Sharman Moser, Email moser_sa@mac.org.ilBackground: In this observational study, we analyzed the treatment patterns and clinical outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) who developed brain metastases during their disease in a 2.7 million-member public health-provider in Israel.Methods: Newly diagnosed patients with mBC who initiated first-line treatment between January 2013 and June 2021 were identified. Time on treatment (ToT) and overall survival (OS) were assessed at a minimum of 6 months follow-up (cutoff: December 2021).Results: We identified a total of 61 patients: 98.4% females, median age 50 years (IQR = 44– 63), 85% invasive ductal tumors, 44% hormone receptor positive, 51% performance status 0– 1. The median duration of follow-up was 6.2 years. All patients initiated a combination treatment of trastuzumab, pertuzumab, and chemotherapy (TPC), and 72% moved to second-line treatment during the study follow-up period (82% ado-trastuzumab emtansine). The median ToT for first-line and second-line treatments were 16.9 months (95% CI = 13.9– 27.7) and 7.9 months (95% CI = 5.6– 10.9), respectively. The median overall survival (OS) was 45.5 months (95% CI = 35.4– 71.2) from the initiation of first-line treatment. When considering the timing of brain metastases, the median OS was 36.3 months (95% CI = 10.0–NR) for those diagnosed upfront (n = 15, 25%), 59.1 months (95% CI = 32.5–NR) for those diagnosed while on TPC (n = 25, 41%), and 40.8 months (95% CI = 35.4–NR) for those diagnosed at a later stage (n = 21, 34%). The median OS from brain metastases diagnosis was 25.1 months (95% CI = 17.0– 34.6).Conclusion: Patients with upfront brain involvement at the time of mBC diagnosis had shorter survival compared to those who started TPC without brain metastases. Nonetheless, the overall results from this study compare favorably with previous studies and contribute to understanding the value of traditional treatment options, which will serve as a baseline for future treatment strategies in the real-world setting.Keywords: HER2 positive, metastatic, breast cancer, observational study, real-world

An unexploited property of graphene-based heterojunctions is the tunable doping of the junction via electrostatic gating. This unique property may be key in advancing electronic transport across interfaces with semiconductors. Here, we engineer transport in semiconducting TMDs by constructing a lateral heterostructure with epitaxial graphene and tuning its intrinsic doping to form a p–n junction between the graphene and the semiconducting TMDs. Graphene grown on SiC (epitaxial graphene) is intrinsically doped via substrate polarization without the introduction of an external dopant, thus enabling a platform for pristine heterostructures with a target band alignment. We demonstrate an electrostatically tunable graphene/MoS2p–n junction with >20× reduction and >10× increased tunability in contact resistance (Rc) compared with metal/TMD junctions, attributed to band alignment engineering and the tunable density of states in graphene. This unique concept provides improved control over transport across 2D p–n junctions.

Trigonal tellurium, a small-gap semiconductor with pronounced magneto-electric and magneto-optical responses, is among the simplest realizations of a chiral crystal. We have studied by spin- and angle-resolved photoelectron spectroscopy its unconventional electronic structure and unique spin texture. We identify Kramers-Weyl, composite, and accordionlike Weyl fermions, so far only predicted by theory, and show that the spin polarization is parallel to the wave vector along the lines in k space connecting high-symmetry points. Our results clarify the symmetries that enforce such spin texture in a chiral crystal, thus bringing new insight in the formation of a spin vectorial field more complex than the previously proposed hedgehog configuration. Our findings thus pave the way to a classification scheme for these exotic spin textures and their search in chiral crystals.

In nodal-line semimetals, linearly dispersing states form Dirac loops in the reciprocal space with a high degree of electron-hole symmetry and a reduced density of states near the Fermi level. The result is reduced electronic screening and enhanced correlations between Dirac quasiparticles. Here we investigate the electronic structure of ZrSiSe, by combining time- and angle-resolved photoelectron spectroscopy with ab initio density functional theory (DFT) complemented by an extended Hubbard model (DFT+U+V) and by time-dependent DFT+U+V. We show that electronic correlations are reduced on an ultrashort timescale by optical excitation of high-energy electrons-hole pairs, which transiently screen the Coulomb interaction. Our findings demonstrate an all-optical method for engineering the band structure of a quantum material.

The layered van der Waals antiferromagnet MnBi2Te4 has been predicted to combine the band ordering of archetypical topological insulators such as Bi2Te3 with the magnetism of Mn, making this material a viable candidate for the realization of various magnetic topological states. We have systematically investigated the surface electronic structure of MnBi2Te4(0001) single crystals by use of spin- and angle-resolved photoelectron spectroscopy experiments. In line with theoretical predictions, the results reveal a surface state in the bulk band gap and they provide evidence for the influence of exchange interaction and spin-orbit coupling on the surface electronic structure.

The interplay between strong spin-orbit coupling and electron correlations has recently been the subject of intense investigation, due to a number of theoretically predicted phases such as quantum spin liquids, unconventional superconductivity, complex magnetic orders, and correlated topological phases of matter. In particular, iridates have been proposed as a promising family of materials which could host a number of these phases. Here we report the existence of Dirac nodal lines in the binary oxide IrO2, through a combination of reactive oxide molecular beam epitaxy and angle-resolved photoemission spectroscopy. Unlike in other such materials reported to date, these Dirac nodal lines have the unique property of being simultaneously (i) robust against spin-orbit coupling, as they are protected by the nonsymmorphic symmetry of the rutile structure, and (ii) only partially occupied, since they cross the Fermi level. This should have direct implications on the low-energy physics properties tied to the band velocity such as magnetoresistance and spin Hall effect.

The new Microscopic and Electronic Structure Observatory (MAESTRO) at the Advanced Light Source (ALS) in Berkeley provides X-rays of variable polarization, produced by an elliptically polarized undulator (EPU), for angle resolved photoemission (ARPES) and photoemission electron microscopy (PEEM) experiments. The interpretation of photoemission data, in particular of dichroism effects in ARPES, requires the precise knowledge of the exact polarization state. Numerical simulations show that the first harmonics of the EPU at MAESTRO provides soft X-rays of almost 100% on axis polarization. However, the higher harmonics as well as the downstream optical elements of the beamline, have a considerable impact on the polarization of the light delivered to the experimental end-station. Employing a simple reflective polarimeter, the polarization is characterized for variable EPU and beamline settings and the overall degree of polarization in the MAESTRO end-stations is estimated to be on the order of 83%.

The efficiency and stability of RuO2 in electrocatalysis has made this material a subject of intense fundamental and industrial interest. The surface functionality is rooted in its electronic and magnetic properties, determined by a complex interplay of lattice-, spin-rotational, and time-reversal symmetries, as well as the competition between Coulomb and kinetic energies. This interplay was predicted to produce a network of Dirac nodal lines (DNLs), where the valence and conduction bands touch along continuous lines in momentum space. Here we uncover direct evidence for three DNLs in RuO2 by angle-resolved photoemission spectroscopy. These DNLs give rise to a flat-band surface state that is readily tuned by the electrostatic environment, and that presents an intriguing platform for exotic correlation phenomena. Our findings support high spin-Hall conductivities and bulk magnetism in RuO2, and are likely related to its catalytic properties.

We present a systematic growth study of epitaxial RuO2(110) and IrO2(110) on TiO2(110) substrates by pulsed laser deposition. We describe the main challenges encountered in the growth process, such as a deteriorating material flux due to laser-induced target metallization or the delicate balance of under- vs over-oxidation of the "stubborn" Ru and Ir metals. We identify growth temperatures and oxygen partial pressures of 700 K, 1 × 10−3 mbar for RuO2 and 770 K, 5 × 10−4 mbar for IrO2 to optimally balance between metal oxidation and particle mobility during nucleation. In contrast to IrO2, RuO2 exhibits layer-by-layer growth up to 5 unit cells if grown at high deposition rates. At low deposition rates, the large lattice mismatch between film and substrate fosters initial 3D island growth and cluster formation. In analogy to reports for RuO2 based on physical vapor deposition [He et al., J. Phys. Chem. C 119, 2692 (2015)], we find these islands to eventually merge and grow to continue in a step flow mode, resulting in highly crystalline, flat, stoichiometric films of RuO2(110) (up to 30 nm thickness) and IrO2(110) (up to 13 nm thickness) with well-defined line defects. [ABSTRACT FROM AUTHOR]

In two-dimensional (2D) semiconducting transition metal dichalcogenides (TMDs), new electronic phenomena such as tunable bandgaps 1-3 and strongly bound excitons and trions emerge from strong many-body effects 4-6 , beyond the spin and valley degrees of freedom induced by spin-orbit coupling and by lattice symmetry 7 . Combining single-layer TMDs with other 2D materials in van der Waals heterostructures offers an intriguing means of controlling the electronic properties through these many-body effects, by means of engineered interlayer interactions 8-10 . Here, we use micro-focused angle-resolved photoemission spectroscopy (microARPES) and in situ surface doping to manipulate the electronic structure of single-layer WS 2 on hexagonal boron nitride (WS 2 /h-BN). Upon electron doping, we observe an unexpected giant renormalization of the spin-orbit splitting of the single-layer WS 2 valence band, from 430 meV to 660 meV, together with a bandgap reduction of at least 325 meV, attributed to the formation of trionic quasiparticles. These findings suggest that the electronic, spintronic and excitonic properties are widely tunable in 2D TMD/h-BN heterostructures, as these are intimately linked to the quasiparticle dynamics of the materials 11-13 .

A paradigmatic case of multi-band Mott physics including spin-orbit and Hund's coupling is realized in Ca2RuO4. Progress in understanding the nature of this Mott insulating phase has been impeded by the lack of knowledge about the low-energy electronic structure. Here we provide-using angle-resolved photoemission electron spectroscopy-the band structure of the paramagnetic insulating phase of Ca2RuO4 and show how it features several distinct energy scales. Comparison to a simple analysis of atomic multiplets provides a quantitative estimate of the Hund's coupling J=0.4 eV. Furthermore, the experimental spectra are in good agreement with electronic structure calculations performed with Dynamical Mean-Field Theory. The crystal field stabilization of the dxy orbital due to c-axis contraction is shown to be essential to explain the insulating phase. These results underscore the importance of multi-band physics, Coulomb interaction and Hund's coupling that together generate the Mott insulating state of Ca2RuO4.

Many infectious disease forecasting models in the United States (US) are built with data partitioned into geopolitical regions centered on human activity as opposed to regions defined by natural ecosystems; although useful for data collection and intervention, this has the potential to mask biological relationships between the environment and disease. We explored this concept by analyzing the correlations between climate and West Nile virus (WNV) case data aggregated to geopolitical and ecological regions. We compared correlations between minimum, maximum, and mean annual temperature; precipitation; and annual WNV neuroinvasive disease (WNND) case data from 2005 to 2019 when partitioned into (a) climate regions defined by the National Oceanic and Atmospheric Administration (NOAA) and (b) Level I ecoregions defined by the Environmental Protection Agency (EPA). We found that correlations between climate and WNND in NOAA climate regions and EPA ecoregions were often contradictory in both direction and magnitude, with EPA ecoregions more often supporting previously established biological hypotheses and environmental dynamics underlying vector‐borne disease transmission. Using ecological regions to examine the relationships between climate and disease cases can enhance the predictive power of forecasts at various scales, motivating a conceptual shift in large‐scale analyses from geopolitical frameworks to more ecologically meaningful regions. Plain Language Summary: In the United States (US), geopolitical subdivisions like states and counties are the governing regions that collect public health data and implement health interventions like risk messaging, mask mandates, or spraying chemicals for mosquito control. These subdivisions were mostly decided by politics and other human activity, not similarities in ecosystems and climate. This can make it difficult to understand how climate affects illnesses like mosquito‐borne disease since mosquitoes will live within specific ecosystems and aren't confined to geopolitical boundaries as health data are. We explored this idea by analyzing the relationships between temperature, precipitation, and the mosquito‐borne pathogen called West Nile virus (WNV) from 2005 to 2019. We grouped our data using two different regional boundaries: (a) climate regions from the National Oceanic and Atmospheric Administration (NOAA), primarily based on state boundaries, and (b) ecoregions from the Environmental Protection Agency (EPA), based on similar ecosystems. We found that these groupings resulted in some contradictory results. The results using EPA ecoregions more often agreed with biological hypotheses, so it may be a better approach to dividing the US for similar studies. We encourage other scientists to consider this conceptual shift from analyzing data by geopolitical boundaries to more ecologically meaningful regions. Key Points: While health data is collected within geopolitical boundaries, environmental disease dynamics are influenced by ecosystem characteristicsFor West Nile virus, correlations between cases and climate were different depending on geopolitical or ecosystem regional groupings of dataWe propose a conceptual shift from analyzing climate and health data at geopolitical boundaries to more ecologically meaningful regions [ABSTRACT FROM AUTHOR]

Sarah Sharman Moser,1 Gabriel Chodick,1,2 Shikma Bar-On,3 Varda Shalev1,2 1Kahn-Sagol-Maccabi Research and Innovation Institute, Maccabi Healthcare Services, Tel Aviv, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Lis Maternity Hospital, Tel-Aviv Medical Center, Tel-Aviv, IsraelCorrespondence: Sarah Sharman MoserKahn-Sagol-Maccabi Research and Innovation Institute, Maccabi Healthcare Services, 27 Hamered St, Tel Aviv 6812509, IsraelTel +972-37462778Email moser_sa@mac.org.ilObjective: Self-reported studies estimated that as many as 50– 75% of women experience symptoms during menopause; however, limited real-world clinical data are available to support this observation. The electronic databases of Maccabi Healthcare Services were used to describe the prevalence of menopause symptoms in Israel and to characterize patients with regard to socioeconomic status, comorbidities and use of healthcare services.Methods: Females aged 45– 54 years diagnosed with menopausal symptoms (N=17,046, cumulative incidence of 8% during the study period) were identified from the Maccabi Healthcare Services electronic database and matched to female members without menopause symptoms, one-to-one on birth year and enumeration area.Results: Symptomatic peri- and post-menopausal women, and particularly those under 52 years, were more likely to have a higher prevalence of comorbid conditions such as depression, anxiety, osteoporosis and insomnia in the year following index. Correspondingly, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors and hypnotic drug use were significantly higher in symptomatic women as was healthcare utilization including hospitalization (OR=1.10; 95% CI=1.00– 1.20), primary care visits (1.90; 1.73– 2.08), gynecologist visits (24.84; 22.36– 27.59) and hysterectomy procedures (2.26; 1.63– 3.14).Conclusion: Medically documented menopausal symptoms are associated with increased burden of disease (particularly among women diagnosed with menopausal symptoms prior to age 52 years), healthcare utilization and greater likelihood of undergoing hysterectomy within one year of diagnosis. This burden is expected to rise further as awareness and social acceptance of peri- and post-menopausal symptoms increase.Keywords: menopause, peri-menopause, real-world study, healthcare utilization