Nutrient-sensitizing drug repurposing screen identifies lomerizine as a mitochondrial metabolism inhibitor of chronic myeloid leukemia.

In chronic myeloid leukemia (CML), the persistence of leukemic stem cells (LSCs) after treatment with tyrosine kinase inhibitors (TKIs), such as imatinib, can lead to disease relapse. It is known that therapy-resistant LSCs rely on oxidative phosphorylation (OXPHOS) for their survival and that targeting mitochondrial respiration sensitizes CML LSCs to imatinib treatment. However, current OXPHOS inhibitors have demonstrated limited efficacy or have shown adverse effects in clinical trials, highlighting that identification of clinically safe oxidative pathway inhibitors is warranted. We performed a high-throughput drug repurposing screen designed to identify mitochondrial metabolism inhibitors in myeloid leukemia cells. This identified lomerizine, a US Food and Drug Administration (FDA)-approved voltage-gated Ca2+ channel blocker now used for the treatment of migraines, as one of the top hits. Transcriptome analysis revealed increased expression of voltage-gated CACNA1D and receptor-activated TRPC6 Ca2+ channels in CML LSCs (CD34+CD38-) compared with normal counterparts. This correlated with increased endoplasmic reticulum (ER) mass and increased ER and mitochondrial Ca2+ content in CML stem/progenitor cells. We demonstrate that lomerizine-mediated inhibition of Ca2+ uptake leads to ER and mitochondrial Ca2+ depletion, with similar effects seen after CACNA1D and TRPC6 knockdown. Through stable isotope-assisted metabolomics and functional assays, we observe that lomerizine treatment inhibits mitochondrial isocitrate dehydrogenase activity and mitochondrial oxidative metabolism and selectively sensitizes CML LSCs to imatinib treatment. In addition, combination treatment with imatinib and lomerizine reduced CML tumor burden, targeted CML LSCs, and extended survival in xenotransplantation model of human CML, suggesting this as a potential therapeutic strategy to prevent disease relapse in patients.

Multicolor Inks of Black Phosphorus for Midwave-Infrared Optoelectronics.

Black phosphorus (bP) based ink with a bulk bandgap of 0.33 eV (λ = 3.7 µm) has recently been shown to be promising for large-area, high performance mid-wave infrared (MWIR) optoelectronics. However, the development of multicolor bP inks expanding across the MWIR wavelength range has been challenging. Here a multicolor ink process based on bP with spectral emission tuned from 0.28 eV (λ = 4.4 µm) to 0.8 eV (λ = 1.5 µm) is demonstrated. Specifically, through the reduction of bP particle size distribution (i.e., lateral dimension and thickness), the optical bandgap systematically blueshifts, reaching up to 0.8 eV. Conversely, alloying bP with arsenic (bP1- xAsx) induces a redshift in the bandgap to 0.28 eV. The ink processed films are passivated with an infrared-transparent epoxy for stable infrared emission in ambient air. Utilizing these multicolor bP-based inks as an infrared light source, a gas sensing system is demonstrated that selectively detects gases, such as CO2 and CH4 whose absorption band varies around 4.3 and 3.3 µm, respectively. The presented ink formulation sets the stage for the advancement of multiplex MWIR optoelectronics, including spectrometers and spectral imaging using a low-cost material processing platform.

First Report of Phytopythium litorale Causing Root Rot on Kousa Dogwood in Tennessee and the United States.

Kousa dogwood (Cornus kousa) is an economically important woody ornamental crop that exhibits creamy, white, pointed bracts in late spring, and reddish to pink drupe fruits in late summer and fall. It bears shiny dark green leaves that become reddish-purple to scarlet in the fall. In August of 2023, 3-year-old container grown C. kousa var. chinensis plants in a commercial nursery in Warren Co., Tennessee, exhibited severe yellowing, dieback and root rot symptoms (Fig. 1a and 1b). Dark brown to black lesions were observed in the root and crown region of the plants. Disease severity was 40% to 60% of root area affected, and disease incidence was approximately 40% of 1,000 plants. Surface-sterilized (10% NaOCl: 1 min) symptomatic root tissues were plated on V8-PARPH and incubated at 25°C. Sparse aerial mycelium, showing a distinct rosette or faint radiate to chrysanthemum colony pattern, was observed within four days of incubation (Fig. 2). All isolates produced ovoid or subglose, papillate, and proliferating sporangia in grass blade water cultures (Dervis et al. 2020). Sporangia measured as 19.18 to 24.80 µm X 18.08 to 22.16 µm (n = 50) with a length/width ratio of 1.06 to 1.11. Zoospores observed were between 7.07 to 9.98 µm in diameter (n = 50). Oogonia and oospores were not produced. The ribosomal internal transcribed spacer (ITS) and large subunit (LSU), as well as mitochondrial cytochrome oxidase subunit II (COX-II) genetic markers were amplified and sequenced using primer pairs ITS1/ITS4 (White et al. 1990), NL1/NL4 (Baten et al. 2014), and cox2-F/cox2-RC4 (Choi et al. 2015), respectively. The ITS, LSU, and COX-II sequences of isolates FBG6343, FBG6344 (ITS: PP458373 and PP461387; LSU: PP461390 and PP461391; COXII: PP477112 and PP477113) were 100% identical to those of MN306118, HQ643386, and MN206732, respectively. Based on the morphology (Nechwatal and Mendgen 2006) and sequence data, the isolates were identified as Phytopythium litorale (Nechw.) Abad, De Cock, Bala, Robideau, Lodhi & Lévesque. The pathogenicity test was performed on 3-year-old C. kousa var. chinensis plants grown in a 3-gal container to fulfill Koch's postulates. Kousa dogwood plants were drench inoculated (800 ml/plant) with a pathogen slurry (two plates of 7-day-old culture/liter) of isolates FBG6343 and FBG6364 (five plants per isolate). Control plants were drenched with agar slurry without the pathogen. The study was conducted in a greenhouse maintained at 21 to 23°C and 70% relative humidity with a 16-h photoperiod and irrigated twice a day for 2 min using an overhead irrigation system. Forty-five days after inoculation, plants showed dieback symptoms, and dark brown lesions developed in the roots of all inoculated plants. Isolates with morphology and sequences identical to those of FBG6343 and FBG6364 were recovered from root tissues of all inoculated plants. All control plants remained symptom-free, and P. litorale was not isolated from the root tissue. Previously, P. litorale was reported to cause disease on apple, kiwi, planatus, and rhododendron (Dervis et al. 2020; Li et al. 2021; Mert et al. 2020; Polat et al. 2023). To our knowledge, this is the first report of P. litorale causing root rot of kousa dogwood in Tennessee and the United States. Identification of this pathogen as the causal agent is crucial to developing timely management practices.

Building evidence to advance health equity: a systematic review on care-related outcomes for older, minoritised populations in long-term care homes.

BACKGROUND: Advancing health equity requires more contextualised evidence. OBJECTIVES: To synthesise published evidence using an existing framework on the origins of health disparities and determine care-related outcome disparities for residents of long-term care, comparing minoritised populations to the context-specific dominant population. DESIGN: Systematic review. SUBJECTS: Residents of 24-hour long-term care homes. METHODS: The protocol was registered a priori with PROSPERO (CRD42021269489). Literature published between 1 January 2000 and 26 September 2021, was searched, including studies comparing baseline characteristics and outcomes in minoritised versus dominant populations. Dual screening, two-reviewer verification for extraction, and risk of bias assessments were conducted to ensure rigour. Studies were synthesized using a conceptual framework to contextualise evidence according to multi-level factors contributing to the development of care disparities. RESULTS: Twenty-one of 34 included studies demonstrated disparities in care outcomes for minoritised groups compared to majority groups. Thirty-one studies observed differences in individual-level characteristics (e.g. age, education, underlying conditions) upon entry to homes, with several outcome disparities (e.g. restraint use, number of medications) present at baseline and remaining or worsening over time. Significant gaps in evidence were identified, particularly an absence of literature on provider information and evidence on the experience of intersecting minority identities that contribute to care-related outcome disparities in long-term care. CONCLUSION: This review found differences in minoritised populations' care-related outcomes. The findings provide guidance for future health equity policy and research-supporting diverse and intersectional capacity building in long-term care.

Association between opioid use disorder and palliative care: a cohort study using linked health administrative data in Ontario, Canada.

BACKGROUND: People with opioid use disorder (OUD) are at risk of premature death and can benefit from palliative care. We sought to compare palliative care provision for decedents with and without OUD. METHODS: We conducted a cohort study using health administrative databases in Ontario, Canada, to identify people who died between July 1, 2015, and Dec. 31, 2021. The exposure was OUD, defined as having emergency department visits, hospital admissions, or pharmacologic treatments suggestive of OUD within 3 years of death. Our primary outcome was receipt of 1 or more palliative care services during the last 90 days before death. Secondary outcomes included setting, initiation, and intensity of palliative care. We conducted a secondary analysis excluding sudden deaths (e.g., opioid toxicity, injury). RESULTS: Of 679 840 decedents, 11 200 (1.6%) had OUD. Compared with people without OUD, those with OUD died at a younger age and were more likely to live in neighbourhoods with high marginalization indices. We found people with OUD were less likely to receive palliative care at the end of their lives (adjusted relative risk [RR] 0.84, 95% confidence interval [CI] 0.82-0.86), but this difference did not exist after excluding people who died suddenly (adjusted RR 0.99, 95% CI 0.96-1.01). People with OUD were less likely to receive palliative care in clinics and their homes regardless of cause of death. INTERPRETATION: Opioid use disorder can be a chronic, life-limiting illness, and people with OUD are less likely to receive palliative care in communities during the 90 days before death. Health care providers should receive training in palliative care and addiction medicine to support people with OUD.

Imaging 3D chemistry at 1 nm resolution with fused multi-modal electron tomography.

Measuring the three-dimensional (3D) distribution of chemistry in nanoscale matter is a longstanding challenge for metrological science. The inelastic scattering events required for 3D chemical imaging are too rare, requiring high beam exposure that destroys the specimen before an experiment is completed. Even larger doses are required to achieve high resolution. Thus, chemical mapping in 3D has been unachievable except at lower resolution with the most radiation-hard materials. Here, high-resolution 3D chemical imaging is achieved near or below one-nanometer resolution in an Au-Fe3O4 metamaterial within an organic ligand matrix, Co3O4-Mn3O4 core-shell nanocrystals, and ZnS-Cu0.64S0.36 nanomaterial using fused multi-modal electron tomography. Multi-modal data fusion enables high-resolution chemical tomography often with 99% less dose by linking information encoded within both elastic (HAADF) and inelastic (EDX/EELS) signals. We thus demonstrate that sub-nanometer 3D resolution of chemistry is measurable for a broad class of geometrically and compositionally complex materials.

Oxygen Transport through Amorphous Cathode Coatings in Solid-State Batteries.

All solid-state batteries (SSBs) are considered the most promising path to enabling higher energy-density portable energy, while concurrently improving safety as compared to current liquid electrolyte solutions. However, the desire for high energy necessitates the choice of high-voltage cathodes, such as nickel-rich layered oxides, where degradation phenomena related to oxygen loss and structural densification at the cathode surface are known to significantly compromise the cycle and thermal stability. In this work, we show, for the first time, that even in an SSB, and when protected by an intact amorphous coating, the LiNi0.5Mn0.3Co0.2O2 (NMC532) surface transforms from a layered structure into a rocksalt-like structure after electrochemical cycling. The transformation of the surface structure of the Li3B11O18 (LBO)-coated NMC532 cathode in a thiophosphate-based solid-state cell is characterized by high-resolution complementary electron microscopy techniques and electron energy loss spectroscopy. Ab initio molecular dynamics corroborate facile transport of O2- in the LBO coating and in other typical coating materials. This work identifies that oxygen loss remains a formidable challenge and barrier to long-cycle life high-energy storage, even in SSBs with durable, amorphous cathode coatings, and directs attention to considering oxygen permeability as an important new design criteria for coating materials.

Storylines of family medicine II: foundational building blocks-context, community and health.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine, as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'II: foundational building blocks-context, community and health', authors address the following themes: 'Context-grounding family medicine in time, place and being', 'Recentring community', 'Community-oriented primary care', 'Embeddedness in practice', 'The meaning of health', 'Disease, illness and sickness-core concepts', 'The biopsychosocial model', 'The biopsychosocial approach' and 'Family medicine as social medicine.' May readers grasp new implications for medical education and practice in these essays.

Mid-Infrared, Optically Active Black Phosphorus Thin Films on Centimeter Scale.

Black phosphorus (BP) is a narrow bandgap (∼0.3 eV) semiconductor with a great potential for optoelectronic devices in the mid-infrared wavelength. However, it has been challenging to achieve a high-quality scalable BP thin film. Here we present the successful synthesis of optically active BP films on a centimeter scale. We utilize the pulsed laser deposition of amorphous red phosphorus, another allotrope of phosphorus, followed by a high-pressure treatment at ∼8 GPa to induce a phase conversion into BP crystals. The crystalline quality was improved through thermal annealing, resulting in the observation of photoluminescence emission at mid-infrared wavelengths. We demonstrate high-pressure conversion on a centimeter scale with a continuous film with a thickness of ∼18 nm using a flat-belt-type high-pressure apparatus. This synthesis procedure presents a promising route to obtain optical-quality BP films, enabling the exploration of integrated optoelectronic device applications such as light-emitting devices and mid-infrared cameras on a chip scale.

Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche.

Macrophages are fundamental cells of the innate immune system that support normal haematopoiesis and play roles in both anti-cancer immunity and tumour progression. Here we use a chimeric mouse model of chronic myeloid leukaemia (CML) and human bone marrow (BM) derived macrophages to study the impact of the dysregulated BM microenvironment on bystander macrophages. Utilising single-cell RNA sequencing (scRNA-seq) of Philadelphia chromosome (Ph) negative macrophages we reveal unique subpopulations of immature macrophages residing in the CML BM microenvironment. CML exposed macrophages separate from their normal counterparts by reduced expression of the surface marker CD36, which significantly reduces clearance of apoptotic cells. We uncover aberrant production of CML-secreted factors, including the immune modulatory protein lactotransferrin (LTF), that suppresses efferocytosis, phagocytosis, and CD36 surface expression in BM macrophages, indicating that the elevated secretion of LTF is, at least partially responsible for the supressed clearance function of Ph- macrophages.

Quantitative Mid-infrared Photoluminescence Characterization of Black Phosphorus-Arsenic Alloys.

Black phosphorus (bP) is a promising material for mid-infrared (mid-IR) optoelectronic applications, exhibiting high performance light emission and detection. Alloying bP with arsenic extends its operation toward longer wavelengths from 3.7 µm (bP) to 5 µm (bP3As7), which is of great practical interest. Quantitative optical characterizations are performed to establish black phosphorus-arsenic (bPAs) alloys optoelectronic quality. Anisotropic optical constants (refractive index, extinction coefficient, and absorption coefficient) of bPAs alloys from near-infrared to mid-IR (0.2-0.9 eV) are extracted with reflection measurements, which helps optical device design. Quantitative photoluminescence (PL) of bPAs alloys with different As concentrations are measured from room temperature to 77 K. PL quantum yield measurements reveal a 2 orders of magnitude decrease in radiative efficiency with increasing As concentration. An optical cavity is designed for bP3As7, which allows for up to an order of magnitude enhancement in the quantum yield due to the Purcell effect. Our comprehensive optical characterization provides the foundation for high performance mid-IR optical device design using bPAs alloys.

Patient-targeted education (ePRO-E) to increase ePRO intent within an Alliance clinical trial (A221805-SI1).

BACKGROUND: The Patient Cloud ePRO app was adopted by the National Cancer Institute National Clinical Trials Network (NCTN) to facilitate capturing electronic patient-reported (ePRO) outcome data, but use has been low. The study objectives were to test whether a patient-targeted ePRO educational resource (ePRO-E) would increase ePRO intent (number of users) and improve data quality (high quality: ≥80% of the required surveys submitted) within an ongoing NCTN study. METHODS: The ePRO-E intervention, a patient-targeted educational resource (written material and 6-minute animated YouTube video), was designed to address ePRO barriers. ePRO intent and data quality were compared between 2 groups (N = 69): a historical control group and a prospectively recruited intervention group exposed to ePRO-E. Covariates included technology attitudes, age, sex, education, socioeconomic status, and comorbidity. RESULTS: Intervention group ePRO intent (78.8%) was statistically significantly higher than historical control group intent (47.1%) (P = .03). Patients choosing ePRO versus paper surveys had more positive and higher technology attitudes scores (P = .03). The odds of choosing ePRO were 4.7 times higher (95% Confidence Interval [CI] = 1.2 to 17.8) (P = .02) among intervention group patients and 5.2 times higher (95% CI = 1.3 to 21.6) (P = .02) among patients with high technology attitudes scores, after controlling for covariates. However, the 80% submission rate (percentage submitting ≥80% of required surveys) in the ePRO group (30.6%) was statistically significantly lower than in the paper group (57.9%) (P = .05). CONCLUSIONS: ePRO-E exposure increased ePRO intent. High technology attitudes scores were associated with ePRO selection. Since the ePRO survey submission rate was low, additional strategies are needed to promote high-quality data submission.

Much more to explore with an oxidation state of nearly four: Pr valence instability in intermetallic m-Pr2Co3Ge5.

For some intermetallic compounds containing lanthanides, structural transitions can result in intermediate electronic states between trivalency and tetravalency; however, this is rarely observed for praseodymium compounds. The dominant trivalency of praseodymium limits potential discoveries of emergent quantum states in itinerant 4f1 systems accessible using Pr4+-based compounds. Here, we use in situ powder x-ray diffraction and in situ electron energy-loss spectroscopy (EELS) to identify an intermetallic example of a dominantly Pr4+ state in the polymorphic system Pr2Co3Ge5. The structure-valence transition from a nearly full Pr4+ electronic state to a typical Pr3+ state shows the potential of Pr-based intermetallic compounds to host valence-unstable states and provides an opportunity to discover previously unknown quantum phenomena. In addition, this work emphasizes the need for complementary techniques like EELS when evaluating the magnetic and electronic properties of Pr intermetallic systems to reveal details easily overlooked when relying on bulk magnetic measurements alone.

Effect of solid-electrolyte pellet density on failure of solid-state batteries.

Despite the potentially higher energy density and improved safety of solid-state batteries (SSBs) relative to Li-ion batteries, failure due to Li-filament penetration of the solid electrolyte and subsequent short circuit remains a critical issue. Herein, we show that Li-filament growth is suppressed in solid-electrolyte pellets with a relative density beyond ~95%. Below this threshold value, however, the battery shorts more easily as the density increases due to faster Li-filament growth within the percolating pores in the pellet. The microstructural properties (e.g., pore size, connectivity, porosity, and tortuosity) of [Formula: see text] with various relative densities are quantified using focused ion beam-scanning electron microscopy tomography and permeability tests. Furthermore, modeling results provide details on the Li-filament growth inside pores ranging from 0.2 to 2 µm in size. Our findings improve the understanding of the failure modes of SSBs and provide guidelines for the design of dendrite-free SSBs.

Activating p53 abolishes self-renewal of quiescent leukaemic stem cells in residual CML disease.

Whilst it is recognised that targeting self-renewal is an effective way to functionally impair the quiescent leukaemic stem cells (LSC) that persist as residual disease in chronic myeloid leukaemia (CML), developing therapeutic strategies to achieve this have proved challenging. We demonstrate that the regulatory programmes of quiescent LSC in chronic phase CML are similar to that of embryonic stem cells, pointing to a role for wild type p53 in LSC self-renewal. In support of this, increasing p53 activity in primitive CML cells using an MDM2 inhibitor in combination with a tyrosine kinase inhibitor resulted in reduced CFC outputs and engraftment potential, followed by loss of multilineage priming potential and LSC exhaustion when combination treatment was discontinued. Our work provides evidence that targeting LSC self-renewal is exploitable in the clinic to irreversibly impair quiescent LSC function in CML residual disease - with the potential to enable more CML patients to discontinue therapy and remain in therapy-free remission.

Uncovering the Network Modifier for Highly Disordered Amorphous Li-Garnet Glass-Ceramics.

Highly disordered amorphous Li7La3Zr2O12 (aLLZO) is a promising class of electrolyte separators and protective layers for hybrid or all-solid-state batteries due to its grain-boundary-free nature and wide electrochemical stability window. Unlike low-entropy ionic glasses such as LixPOyNz (LiPON), these medium-entropy non-Zachariasen aLLZO phases offer a higher number of stable structure arrangements over a wide range of tunable synthesis temperatures, providing the potential to tune the LBU-Li+ transport relation. It is revealed that lanthanum is the active "network modifier" for this new class of highly disordered Li+ conductors, whereas zirconium and lithium serve as "network formers". Specifically, within the solubility limit of La in aLLZO, increasing the La concentration can result in longer bond distances between the first nearest neighbors of Zr─O and La─O within the same local building unit (LBU) and the second nearest neighbors of Zr─La across two adjacent network-former and network-modifier LBUs, suggesting a more disordered medium- and long-range order structure in LLZO. These findings open new avenues for future designs of amorphous Li+ electrolytes and the selection of network-modifier dopants. Moreover, the wide yet relatively low synthesis temperatures of these glass-ceramics make them attractive candidates for low-cost and more sustainable hybrid- or all-solid-state batteries for energy storage.

Generalization Across Experimental Parameters in Neural Network Analysis of High-Resolution Transmission Electron Microscopy Datasets.

Neural networks are promising tools for high-throughput and accurate transmission electron microscopy (TEM) analysis of nanomaterials, but are known to generalize poorly on data that is "out-of-distribution" from their training data. Given the limited set of image features typically seen in high-resolution TEM imaging, it is unclear which images are considered out-of-distribution from others. Here, we investigate how the choice of metadata features in the training dataset influences neural network performance, focusing on the example task of nanoparticle segmentation. We train and validate neural networks across curated, experimentally collected high-resolution TEM image datasets of nanoparticles under various imaging and material parameters, including magnification, dosage, nanoparticle diameter, and nanoparticle material. Overall, we find that our neural networks are not robust across microscope parameters, but do generalize across certain sample parameters. Additionally, data preprocessing can have unintended consequences on neural network generalization. Our results highlight the need to understand how dataset features affect deployment of data-driven algorithms.

Analysis of Strain and Defects in Tellurium-WSe2 Moiré Heterostructures Using Scanning Nanodiffraction.

In recent years, there has been an increasing focus on 2D nongraphene materials that range from insulators to semiconductors to metals. As a single-elemental van der Waals semiconductor, tellurium (Te) has captivating anisotropic physical properties. Recent work demonstrated growth of ultrathin Te on WSe2 with the atomic chains of Te aligned with the armchair directions of the substrate using physical vapor deposition (PVD). In this system, a moiré superlattice is formed where micrometer-scale Te flakes sit on top of the continuous WSe2 film. Here, we determined the precise orientation of the Te flakes with respect to the substrate and detailed structure of the resulting moiré lattice by combining electron microscopy with image simulations. We directly visualized the moiré lattice using center of mass-differential phase contrast (CoM-DPC). We also investigated the local strain within the Te/WSe2 layered materials using scanning nanodiffraction techniques. There is a significant tensile strain at the edges of flakes along the direction perpendicular to the Te chain direction, which is an indication of the preferred orientation for the growth of Te on WSe2. In addition, we observed local strain relaxation regions within the Te film, specifically attributed to misfit dislocations, which we characterize as having a screw-like nature. The detailed structural analysis gives insight into the growth mechanisms and strain relaxation in this moiré heterostructure.

Solving complex nanostructures with ptychographic atomic electron tomography.

Transmission electron microscopy (TEM) is essential for determining atomic scale structures in structural biology and materials science. In structural biology, three-dimensional structures of proteins are routinely determined from thousands of identical particles using phase-contrast TEM. In materials science, three-dimensional atomic structures of complex nanomaterials have been determined using atomic electron tomography (AET). However, neither of these methods can determine the three-dimensional atomic structure of heterogeneous nanomaterials containing light elements. Here, we perform ptychographic electron tomography from 34.5 million diffraction patterns to reconstruct an atomic resolution tilt series of a double wall-carbon nanotube (DW-CNT) encapsulating a complex ZrTe sandwich structure. Class averaging the resulting tilt series images and subpixel localization of the atomic peaks reveals a Zr11Te50 structure containing a previously unobserved ZrTe2 phase in the core. The experimental realization of atomic resolution ptychographic electron tomography will allow for the structural determination of a wide range of beam-sensitive nanomaterials containing light elements.

Nurse practitioner and physician end-of-life home visits and end-of-life outcomes.

OBJECTIVES: Physicians and nurse practitioners (NPs) play critical roles in supporting palliative and end-of-life care in the community. We examined healthcare outcomes among patients who received home visits from physicians and NPs in the 90 days before death. METHODS: We conducted a retrospective cohort study using linked data of adult home care users in Ontario, Canada, who died between 1 January 2018 and 31 December 2019. Healthcare outcomes included medications for pain and symptom management, emergency department (ED) visits, hospitalisations and a community-based death. We compared the characteristics of and outcomes in decedents who received a home visit from an NP, physician and both to those who did not receive a home visit. RESULTS: Half (56.9%) of adult decedents in Ontario did not receive a home visit from a provider in the last 90 days of life; 34.5% received at least one visit from a physician, 3.8% from an NP and 4.9% from both. Compared with those without any visits, having at least one home visit reduced the odds of hospitalisation and ED visits, and increased the odds of receiving medications for pain and symptom management and achieving a community-based death. Observed effects were larger in patients who received at least one visit from both. CONCLUSIONS: Beyond home care, receiving home visits from primary care providers near the end of life may be associated with better outcomes that are aligned with patients' preferences-emphasising the importance of NPs and physicians' role in supporting people near the end of life.