Bidirectional Captioning for Clinically Accurate and Interpretable Models

Vision-language pretraining has been shown to produce high-quality visual encoders which transfer efficiently to downstream computer vision tasks. While generative language models have gained widespread attention, image captioning has thus far been mostly overlooked as a form of cross-modal pretraining in favor of contrastive learning, especially in medical image analysis. In this paper, we experiment with bidirectional captioning of radiology reports as a form of pretraining and compare the quality and utility of learned embeddings with those from contrastive pretraining methods. We optimize a CNN encoder, transformer decoder architecture named RadTex for the radiology domain. Results show that not only does captioning pretraining yield visual encoders that are competitive with contrastive pretraining (CheXpert competition multi-label AUC of 89.4%), but also that our transformer decoder is capable of generating clinically relevant reports (captioning macro-F1 score of 0.349 using CheXpert labeler) and responding to prompts with targeted, interactive outputs.Comment: 12 pages, 7 figures. Code release to follo

High-Dose-Rate Brachytherapy for the Treatment of Basal and Squamous Cell Carcinomas on Sensitive Areas of the Face: A Report of Clinical Outcomes and Acute and Subacute Toxicities

Purpose Basal cell and cutaneous squamous cell carcinoma are common malignancies (keratinocyte carcinomas [KCs]). Surgical resection is the standard of care. Radiation using high-dose rate brachytherapy (HDR-BT) may serve as a superior alternative where surgical scars may be of cosmetic concern or in elderly patients with significant comorbidity. We aim to describe the clinical and cosmetic outcomes as well as posttreatment radiation toxicities associated with HDR-BT in patients who were treated for KCs of the face. Methods and Materials Patients with KCs treated with HDR-BT from 2015 to 2018 were included in the study. Patient medical records and clinical photos were reviewed at multiple time points: start of treatment, end of treatment, short-term (2 week) follow-up, 3-month follow-up, and if needed at 6 months. Radiation toxicity was graded using the Radiation Therapy Oncology Grading (RTOG) acute toxicity scale. Median (range) toxicity grades at follow-up intervals were calculated. Clinical outcomes including local recurrence were evaluated for all patients. Results The study included 19 patients and 20 KCs. The median radiation dose was 42 Gy (39-42 Gy) over 6 fractions. The median toxicity at completion of treatment was RTOG grade 2 (85% of patients). At short-term follow-up, 50% of patients (n = 10) improved to RTOG grade 1 (0-2). At 3 months, 70% of patients (n = 14) had RTOG grade 0, and by 6 months, 100% of patients (n = 18) had RTOG grade 0. No RTOG grade 3 or higher skin toxicity was observed. With a median follow-up of 7.2 months (range, 1.3-54.4 months), the local recurrence-free survival was 95%. Conclusions We demonstrate that HDR-BT can be used as definitive treatment of KCs of the face with excellent cosmetic outcomes and local control. Acute and subacute skin toxicities were most commonly RTOG grade 2 or less with resolution of patient’s skin toxicity by 3 months

Canvass: a crowd-sourced, natural-product screening library for exploring biological space

NCATS thanks Dingyin Tao for assistance with compound characterization. This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Ministere des Eaux et Forets). O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C.B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W.acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819). (Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); CHE-1665145 - NSF; CHE-1665331 - NSF; CHE-1464898 - NSF; RUI: 213569 - NSF; CHE-1414298 - NSF; CHE1361173 - NSF; CHE1755698 - NSF; CHE-1463819 - NSF; GM126221 - NIH; 5R01GM110131 - NIH; GM 063557 - NIH; GM 084333 - NIH; R01GM071779 - NIH; GM116952 - NIH; DA045884-01 - NIH; DA046487-01 - NIH; AA026949-01 - NIH; R01 GM111476 - NIH; R01-HL25854 - NIH; R01-GM30859 - NIH; R0-1-NS-12389 - NIH; R35 GM-118173 - NIH; R24 GM-111625 - NIH; CA78747 - NIH; CA106150 - NIH; GM114353 - NIH; GM115575 - NIH; R01GM121656 - NIH; T32 CA062948-Gudas - NIH; P41 GM076267 - NIH; R01GM114061 - NIGMS, NIH; R15GM116032 - NIGMS, NIH; P30 GM103450 - NIGMS, NIH; GM129465 - NIGMS, NIH; GM119426 - NIGMS, NIH; TW009872 - Fogarty International Center, NIH; U01 TW00313 - Fogarty International Center, NIH; R01 CA158275 - National Cancer Institute (NCI), NIH; P01 AG012411 - NIH/National Institute of Aging; Camille and Henry Dreyfus Foundation; Arnold and Mabel Beckman Foundation; Scripps Institution of Oceanography; P01CA125066 - NCI, NIH; 1 R01 AT008088 - National Center for Complementary and Integrative Health; W81XWH-17-1-0256 - Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program; P30 CA008748 - NCI, NIH, through a Cancer Center Support Grant; California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board; American Lebanese Syrian Associated Charities (ALSAC); University of Oklahoma Startup funds; 53767-ND1 - ACS PRF; PhRMA Foundation; P30 CA008748 - CCSG NIH; RSG-12-253-01-CDD - American Cancer Society; RSG-13-011-01-CDD - American Cancer Society; CHE-0353662 - National Science Foundation; CHE-1005253 - National Science Foundation; CHE-1725142 - National Science Foundation; Beckman Foundation; Sherman Fairchild Foundation; John Stauffer Charitable Trust; Christian Scholars Foundation)Published versionSupporting documentatio

Variational quantum Monte Carlo study of two-dimensional Wigner crystals: exchange, correlation, and magnetic field effects

The two-dimensional Wigner crystals are studied with the variational quantum Monte Carlo method. The close relationship between the ground-state wavefunction and the collective excitations in the system is illustrated, and used to guide the construction of the ground-state wavefunction of the strongly correlated solid. Exchange, correlation, and magnetic field effects all give rise to distinct physical phenomena. In the absence of any external magnetic field, interesting spin-orderings are observed in the ground-state of the electron crystal in various two-dimensional lattices. In particular, two-dimensional bipartite lattices are shown not to lead necessarily to an antiferromagnetic ground-state. In the quantum Hall effect regime, a strong magnetic field introduces new energy and length scales. The magnetic field quenches the kinetic energy and poses constraints on how the electrons may correlate with each other. Care is taken to ensure the appropriate translational properties of the wavefunction when the system is in a uniform magnetic field. We have examined the exchange, intra-Landau-level correlation as well as Landau-level-mixing effects with various variational wavefunctions. We also determine their dependences on the experimental parameters such as the carrier effective mass at a modulation-doped semiconductor heterojunction. Our results, when combined with some recent calculations for the energy of the fractional quantum Hall liquid including Landau-level-mixing, show quantitatively that in going from $n$-doping to $p$-doping in $GaAS/AlGaAS$ heterojunction systems, the crossover filling factor from the fractional quantum Hall liquid to the Wigner crystal changes from filling factor $\nu \sim 1/5$ to $\nu \sim 1/3$. This lends strong support to the claim that theComment: LaTex file, 14 figures available from [email protected]

Effects of dissipation on quantum phase transitions

We discuss the effect of dissipation on quantum phase transitions. In particular we concentrate on the Superconductor to Insulator and Quantum-Hall to Insulator transitions. By invoking a phenomenological parameter $\alpha$ to describe the coupling of the system to a continuum of degrees of freedom representing the dissipative bath, we obtain new phase diagrams for the quantum Hall and superconductor-insulator problems. Our main result is that, in two-dimensions, the metallic phases observed in finite magnetic fields (possibly also strictly zero field) are adiabatically deformable from one to the other. This is plausible, as there is no broken symmetry which differentiates them.Comment: 13 pages, 4 figure

Ticagrelor with or without Aspirin in High-Risk Patients after PCI.

BACKGROUND: Monotherapy with a P2Y12 inhibitor after a minimum period of dual antiplatelet therapy is an emerging approach to reduce the risk of bleeding after percutaneous coronary intervention (PCI). METHODS: In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points. RESULTS: We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority). CONCLUSIONS: Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.)

Limits of Calcium Clearance by Plasma Membrane Calcium ATPase in Olfactory Cilia

BACKGROUND: In any fine sensory organelle, a small influx of Ca(2+) can quickly elevate cytoplasmic Ca(2+). Mechanisms must exist to clear the ciliary Ca(2+) before it reaches toxic levels. One such organelle has been well studied: the vertebrate olfactory cilium. Recent studies have suggested that clearance from the olfactory cilium is mediated in part by plasma membrane Ca(2+)-ATPase (PMCA). PRINCIPAL FINDINGS: In the present study, electrophysiological assays were devised to monitor cytoplasmic free Ca(2+) in single frog olfactory cilia. Ca(2+) was allowed to enter isolated cilia, either through the detached end or through membrane channels. Intraciliary Ca(2+) was monitored via the activity of ciliary Ca(2+)-gated Cl(-) channels, which are sensitive to free Ca(2+) from about 2 to 10 microM. No significant effect of MgATP on intraciliary free Ca(2+) could be found. Carboxyeosin, which has been used to inhibit PMCA, was found to substantially increase a ciliary transduction current activated by cyclic AMP. This increase was ATP-independent. CONCLUSIONS: Alternative explanations are suggested for two previous experiments taken to support a role for PMCA in ciliary Ca(2+) clearance. It is concluded that PMCA in the cilium plays a very limited role in clearing the micromolar levels of intraciliary Ca(2+) produced during the odor response

Chemical intervention in plant sugar signalling increases yield and resilience

The pressing global issue of food insecurity due to population growth, diminishing land and variable climate can only be addressed in agriculture by improving both maximum crop yield potential and resilience. Genetic modification is one potential solution, but has yet to achieve worldwide acceptance, particularly for crops such as wheat. Trehalose-6-phosphate (T6P), a central sugar signal in plants, regulates sucrose use and allocation, underpinning crop growth and development. Here we show that application of a chemical intervention strategy directly modulates T6P levels in planta. Plant-permeable analogues of T6P were designed and constructed based on a ‘signalling-precursor’ concept for permeability, ready uptake and sunlight-triggered release of T6P in planta. We show that chemical intervention in a potent sugar signal increases grain yield, whereas application to vegetative tissue improves recovery and resurrection from drought. This technology offers a means to combine increases in yield with crop stress resilience. Given the generality of the T6P pathway in plants and other small-molecule signals in biology, these studies suggest that suitable synthetic exogenous small-molecule signal precursors can be used to directly enhance plant performance and perhaps other organism function