The anterior cingulate cortex controls the hyperactivity in subthalamic neurons in male mice with comorbid chronic pain and depression.

Neurons in the subthalamic nucleus (STN) become hyperactive following nerve injury and promote pain-related responses in mice. Considering that the anterior cingulate cortex (ACC) is involved in pain and emotion processing and projects to the STN, we hypothesize that ACC neurons may contribute to hyperactivity in STN neurons in chronic pain. In the present study, we showed that ACC neurons enhanced activity in response to noxious stimuli and to alterations in emotional states and became hyperactive in chronic pain state established by spared nerve injury of the sciatic nerve (SNI) in mice. In naïve mice, STN neurons were activated by noxious stimuli, but not by alterations in emotional states. Pain responses in STN neurons were attenuated in both naïve and SNI mice when ACC neurons were inhibited. Furthermore, optogenetic activation of the ACC-STN pathway induced bilateral hyperalgesia and depression-like behaviors in naive mice; conversely, inhibition of this pathway is sufficient to attenuate hyperalgesia and depression-like behaviors in SNI mice and naïve mice subjected to stimulation of STN neurons. Finally, mitigation of pain-like and depression-like behaviors in SNI mice by inhibition of the ACC-STN projection was eliminated by activation of STN neurons. Our results demonstrate that hyperactivity in the ACC-STN pathway may be an important pathophysiology in comorbid chronic pain and depression. Thus, the ACC-STN pathway may be an intervention target for the treatment of the comorbid chronic pain and depression.

Topological wetting states of microdroplets on closed-loop structured surfaces: Breakdown of the Gibbs equation at the microscale.

Microdroplets are a class of soft matter that has been extensively employed for chemical, biochemical, and industrial applications. However, fabricating microdroplets with largely controllable contact-area shape and apparent contact angle, a key prerequisite for their applications, is still a challenge. Here, by engineering a type of surface with homocentric closed-loop microwalls/microchannels, we can achieve facile size, shape, and contact-angle tunability of microdroplets on the textured surfaces by design. More importantly, this class of surface topologies (with universal genus value = 1) allows us to reveal that the conventional Gibbs equation (widely used for assessing the edge effect on the apparent contact angle of macrodroplets) seems no longer applicable for water microdroplets or nanodroplets (evidenced by independent molecular dynamics simulations). Notably, for the flat surface with the intrinsic contact angle ~0°, we find that the critical contact angle on the microtextured counterparts (at edge angle 90°) can be as large as >130°, rather than 90° according to the Gibbs equation. Experiments show that the breakdown of the Gibbs equation occurs for microdroplets of different types of liquids including alcohol and hydrocarbon oils. Overall, the microtextured surface design and topological wetting states not only offer opportunities for diverse applications of microdroplets such as controllable chemical reactions and low-cost circuit fabrications but also provide testbeds for advancing the fundamental surface science of wetting beyond the Gibbs equation.

A droplet-based electricity generator with high instantaneous power density.

Extensive efforts have been made to harvest energy from water in the form of raindrops1-6, river and ocean waves7,8, tides9 and others10-17. However, achieving a high density of electrical power generation is challenging. Traditional hydraulic power generation mainly uses electromagnetic generators that are heavy, bulky, and become inefficient with low water supply. An alternative, the water-droplet/solid-based triboelectric nanogenerator, has so far generated peak power densities of less than one watt per square metre, owing to the limitations imposed by interfacial effects-as seen in characterizations of the charge generation and transfer that occur at solid-liquid1-4 or liquid-liquid5,18 interfaces. Here we develop a device to harvest energy from impinging water droplets by using an architecture that comprises a polytetrafluoroethylene film on an indium tin oxide substrate plus an aluminium electrode. We show that spreading of an impinged water droplet on the device bridges the originally disconnected components into a closed-loop electrical system, transforming the conventional interfacial effect into a bulk effect, and so enhancing the instantaneous power density by several orders of magnitude over equivalent devices that are limited by interfacial effects.

Atomic imaging of the edge structure and growth of a two-dimensional hexagonal ice.

The formation and growth of water-ice layers on surfaces and of low-dimensional ice under confinement are frequent occurrences1-4. This is exemplified by the extensive reporting of two-dimensional (2D) ice on metals5-11, insulating surfaces12-16, graphite and graphene17,18 and under strong confinement14,19-22. Although structured water adlayers and 2D ice have been imaged, capturing the metastable or intermediate edge structures involved in the 2D ice growth, which could reveal the underlying growth mechanisms, is extremely challenging, owing to the fragility and short lifetime of those edge structures. Here we show that noncontact atomic-force microscopy with a CO-terminated tip (used previously to image interfacial water with minimal perturbation)12, enables real-space imaging of the edge structures of 2D bilayer hexagonal ice grown on a Au(111) surface. We find that armchair-type edges coexist with the zigzag edges usually observed in 2D hexagonal crystals, and freeze these samples during growth to identify the intermediate edge structures. Combined with simulations, these experiments enable us to reconstruct the growth processes that, in the case of the zigzag edge, involve the addition of water molecules to the existing edge and a collective bridging mechanism. Armchair edge growth, by contrast, involves local seeding and edge reconstruction and thus contrasts with conventional views regarding the growth of bilayer hexagonal ices and 2D hexagonal matter in general.

Tuning Fe3O4 for sustainable cathodic heterogeneous electro-Fenton catalysis by acetylated chitosan.

Peroxidase-like catalysts are safe and low-cost candidates to tackle the dilemma in constructing sustainable cathodic heterogeneous electro-Fenton (CHEF) catalysts for water purification, but the elusive structure-property relationship of enzyme-like catalysts constitutes a pressing challenge for the advancement of CHEF processes in practically relevant water and wastewater treatment. Herein, we probe the origins of catalytic efficiency in the CHEF process by artificially tailoring the peroxidase-like activity of Fe3O4 through a series of acetylated chitosan-based hydrogels, which serve as ecofriendly alternatives to traditional carbon shells. The optimized acetylated chitosan wrapping Fe3O4 hydrogel on the cathode shows an impressive activity and stability in CHEF process, overcoming the complicated and environmentally unfavored procedures in the electro-Fenton-related processes. Structural characterizations and theoretical calculations reveal that the amide group in chitosan can modulate the intrinsic redox capacity of surficial Fe sites on Fe3O4 toward CHEF catalysis via the neutral hydrogen bond. This work provides a sustainable path and molecule-level insight for the rational design of high-efficiency CHEF catalysts and beyond.

Insula→Amygdala and Insula→Thalamus Pathways Are Involved in Comorbid Chronic Pain and Depression-Like Behavior in Mice.

The comorbidity of chronic pain and depression poses tremendous challenges for the treatment of either one because they exacerbate each other with unknown mechanisms. As the posterior insular cortex (PIC) integrates multiple somatosensory and emotional information and is implicated in either chronic pain or depression, we hypothesize that the PIC and its projections may contribute to the pathophysiology of comorbid chronic pain and depression. We show that PIC neurons were readily activated by mechanical, thermal, aversive, and stressful and appetitive stimulation in naive and neuropathic pain male mice subjected to spared nerve injury (SNI). Optogenetic activation of PIC neurons induced hyperalgesia and conditioned place aversion in naive mice, whereas inhibition of these neurons led to analgesia, conditioned place preference (CPP), and antidepressant effect in both naive and SNI mice. Combining neuronal tracing, optogenetics, and electrophysiological techniques, we found that the monosynaptic glutamatergic projections from the PIC to the basolateral amygdala (BLA) and the ventromedial nucleus (VM) of the thalamus mimicked PIC neurons in pain modulation in naive mice; in SNI mice, both projections were enhanced accompanied by hyperactivity of PIC, BLA, and VM neurons and inhibition of these projections led to analgesia, CPP, and antidepressant-like effect. The present study suggests that potentiation of the PIC→BLA and PIC→VM projections may be important pathophysiological bases for hyperalgesia and depression-like behavior in neuropathic pain and reversing the potentiation may be a promising therapeutic strategy for comorbid chronic pain and depression.

Anomalous water transport in narrow-diameter carbon nanotubes.

Carbon nanotubes (CNTs) mimicking the structure of aquaporins support fast water transport, making them strong candidates for building next-generation high-performance membranes for water treatment. The diffusion and transport behavior of water through CNTs or nanoporous graphene can be fundamentally different from those of bulk water through a macroscopic tube. To date, the nanotube-length-dependent physical transport behavior of water is still largely unexplored. Herein, on the basis of molecular dynamics simulations, we show that the flow rate of water through 0.83-nm-diameter (6,6) and 0.96-nm-diameter (7,7) CNTs exhibits anomalous transport behavior, whereby the flow rate increases markedly first and then either slowly decreases or changes slightly as the CNT length l increases. The critical range of l for the flow-rate transition is 0.37 to 0.5 nm. This anomalous water transport behavior is attributed to the l-dependent mechanical stability of the transient hydrogen-bonding chain that connects water molecules inside and outside the CNTs and bypasses the CNT orifice. The results unveil a microscopic mechanism governing water transport through subnanometer tubes, which has important implications for nanofluidic manipulation.

Strong Sliding Ferroelectricity and Interlayer Sliding Controllable Spintronic Effect in Two-Dimensional HgI2 Layers.

Exploration of two-dimensional (2D) sliding ferroelectric (FE) materials with experimentally detectable ferroelectricity and value-added novel functionalities is highly sought for the development of 2D "slidetronics". Herein, based on first-principles calculations, we identify the synthesizable van der Waals (vdW) layered crystals HgX2 (X = Br and I) as a new class of 2D sliding ferroelectrics. Both HgBr2 and HgI2 in 2D multilayered forms adopt the preferential stacking sequence, leading to room temperature stable out-of-plane (vertical) ferroelectricity that can be reversed via the sliding of adjacent monolayers. Owing to strong interlayer coupling and interfacial charge rearrangement, 2D HgI2 layers possess strong sliding ferroelectricity up to 0.16 µC/cm2, readily detectable in experiment. Moreover, robust sliding ferroelectricity and interlayer sliding controllable Rashba spin texture of FE-HgI2 layers enable potential applications as 2D spintronic devices such that the electric control of electron spin detection can be realized at the 2D regime.

Enhanced Direct Exchange Interaction and Hybridization by Single-Atom Linkers for High Curie Temperature and Superior Visible-Light Harvesting in Cr3(CN3)2.

Designing two-dimensional (2D) ferromagnetic (FM) semiconductors with elevated Curie temperature, high carrier mobility, and strong light harvesting is challenging but crucial to the development of spintronics with multifunctionalities. Herein, we show first-principles computation evidence of the 2D metal-organic framework Kagome ferromagnet Cr3(CN3)2. Monolayer Cr3(CN3)2 is predicted to be an FM semiconductor with a record-high Curie temperature of 943 K owing to the use of a single-atom linker (N), which results in strong direct d-p exchange interaction and hybridization between dyz/xz and pz of Cr and N, as well as excellent matching characteristics in energy and symmetry. The single-atom linker structural feature also leads to notable band dispersion and a relatively high carrier mobility of 420 cm2 V-1 s-1. Moreover, under the in-plane strain, 2D Cr3(CN3)2 can be tuned to possess a strong visible-light-harvesting functionality. These novel properties render monolayer Cr3(CN3)2 a distinct 2D ferromagnet with high potential for the development of multifunctional spintronics.

Tunable Surface Wettability via Terahertz Electrowave Controlled Vicinal Subnanoscale Water Layer.

Achieving timely, reversible, and long-range remote tunability over surface wettability is highly demanded across diverse fields, including nanofluidic systems, drug delivery, and heterogeneous catalysis. Herein, using molecular dynamic simulations, we show, for the first time, a theoretical design of electrowetting to achieve remotely controllable surface wettability via using a terahertz wave. The key idea driving the design is the unique terahertz collective vibration identified in the vicinal subnanoscale water layer, which is absent in bulk water, enabling efficient energy transfer from the terahertz wave to the rotational motion of the vicinal subnanoscale water layer. Consequently, a frequency-specific alternating terahertz electric field near the critical strength can significantly affect the local hydrogen-bonding network of the contact water layer on the solid surface, thereby achieving tunable surface wettability.

Evidence of Spontaneous Formation of Two-Dimensional Amorphous Clathrates on Superhydrophilic Surfaces.

Clathrate hydrates reserved in the seabed are often dispersed in the pores of coarse-grained sediments; hence, their formation typically occurs under nanoconfinement. Herein, we show the first molecular dynamics (MD) simulation evidence of the spontaneous formation of two-dimensional (2D) clathrate hydrates on crystal surfaces without conventional nanoconfinement. The kinetic process of 2D clathrate formation is illustrated via simulated single-molecule deposition. 2D amorphous patterns are observed on various superhydrophilic face-centered cubic surfaces. Notably, the formation of 2D amorphous clathrate can occur over a wide range of temperatures, even at room temperature. The strong water-surface interaction, the characteristic properties of guest-gas molecules, and the underlying surface structure dictate the formation of 2D amorphous clathrates. Semiquantitative phase diagrams of 2D clathrates are constructed where representative patterns of 2D clathrates for characteristic gas molecules on prototypical Pd(111) and Pt(111) surfaces are confirmed by independent MD simulations. A tunable pattern of 2D amorphous clathrates is demonstrated by changing the lattice strain of the underlying substrate. Moreover, ab initio MD simulations confirm the stability of 2D amorphous clathrate. The underlining physical mechanism for 2D clathrate formation on superhydrophilic surfaces is elucidated, which offers deeper insight into the crucial role of water-surface interaction.

Superdiffusive Rotation of Interfacial Water on Noble Metal Surface.

Interfacial water on a metal surface acts as an active layer through the reorientation of water, thereby facilitating the energy transfer and chemical reaction across the metal surface in various physicochemical and industrial processes. However, how this active interfacial water collectively behaves on flat noble metal substrates remains largely unknown due to the experimental limitation in capturing librational vibrational motion of interfacial water and prohibitive computational costs at the first-principles level. Herein, by implementing a machine-learning approach to train neural network potentials, we enable performing advanced molecular dynamics simulations with ab initio accuracy at a nanosecond scale to map the distinct rotational motion of water molecules on a metal surface at room temperature. The vibrational density of states of the interfacial water with two-layer profiles reveals that the rotation and vibration of water within the strong adsorption layer on the metal surface behave as if the water molecules in the bulk ice, wherein the O-H stretching frequency is well consistent with the experimental results. Unexpectedly, the water molecules within the adjacent weak adsorption layer exhibit superdiffusive rotation, contrary to the conventional diffusive rotation of bulk water, while the vibrational motion maintains the characteristic of bulk water. The mechanism underlying this abnormal superdiffusive rotation is attributed to the translation-rotation decoupling of water, in which the translation is restrained by the strong hydrogen bonding within the bilayer interfacial water, whereas the rotation is accelerated freely by the asymmetric water environment. This superdiffusive rotation dynamics may elucidate the experimentally observed large fluctuation of the potential of zero charge on Pt and thereby the conventional Helmholtz layer model revised by including the contribution of interfacial water orientation. The surprising superdiffusive rotation of vicinal water next to noble metals will shed new light on the physicochemical processes and the activity of water molecules near metal electrodes or catalysts.

Highly Efficient and Scalable p-i-n Perovskite Solar Cells Enabled by Poly-metallocene Interfaces.

Inverted p-i-n perovskite solar cells (PSCs) are easy to process but need improved interface characteristics with reduced energy loss to prevent efficiency drops when increasing the active photovoltaic area. Here, we report a series of poly ferrocenyl molecules that can modulate the perovskite surface enabling the construction of small- and large-area PSCs. We found that the perovskite-ferrocenyl interaction forms a hybrid complex with enhanced surface coordination strength and activated electronic states, leading to lower interfacial nonradiative recombination and charge transport resistance losses. The resulting PSCs achieve an enhanced efficiency of up to 26.08% for small-area devices and 24.51% for large-area devices (1.0208 cm2). Moreover, the large-area PSCs maintain >92% of the initial efficiency after 2000 h of continuous operation at the maximum power point under 1-sun illumination and 65 °C.

Hypoxia-induced ALKBH5 aggravates synovial aggression and inflammation in rheumatoid arthritis by regulating the m6A modification of CH25H.

Previous studies have shown that epigenetic factors are involved in the occurrence and development of rheumatoid arthritis (RA). However, the role of N6-methyladenosine (m6A) methylation in RA has not been determined. The aim of this study was to investigate the role and regulatory mechanisms of hypoxia-induced expression of the m6A demethylase alkB homolog 5 (ALKBH5) in RA fibroblast-like synoviocytes (FLSs). Synovial tissues were collected from RA and osteoarthritis (OA) patients, and RA FLSs were obtained. ALKBH5 expression in RA FLSs and collagen-induced arthritis (CIA) model rats was determined using quantitative reverse transcription-PCR (qRT-PCR), western blotting and immunohistochemistry (IHC). Using ALKBH5 overexpression and knockdown, we determined the role of ALKBH5 in RA FLS aggression and inflammation. The role of ALKBH5 in RA FLS regulation was explored using m6A-methylated RNA sequencing and methylated RNA immunoprecipitation coupled with quantitative real-time PCR. The expression of ALKBH5 was increased in RA synovial tissues, CIA model rats and RA FLSs, and a hypoxic environment increased the expression of ALKBH5 in FLSs. Increased expression of ALKBH5 promoted the proliferation and migration of RA-FLSs and inflammation. Conversely, decreased ALKBH5 expression inhibited the migration of RA-FLSs and inflammation. Mechanistically, hypoxia-induced ALKBH5 expression promoted FLS aggression and inflammation by regulating CH25H mRNA stability. Our study elucidated the functional roles of ALKBH5 and mRNA m6A methylation in RA and revealed that the HIF1α/2α-ALKBH5-CH25H pathway may be key for FLS aggression and inflammation. This study provides a novel approach for the treatment of RA by targeting the HIF1α/2α-ALKBH5-CH25H pathway.

Pt─O Bond Accelerated Cu0/Cu+ Activity for Boosting Low-Energy Bipolar Hydrogen Production.

To address the imperative challenge of producing hydrogen in a low-energy consumption electrocatalytic system, this study emphasizes the utilization of thermodynamically favorable biomass oxidation for achieving energy-efficient hydrogen generation. This research integrates ultralow PtO2-loaded flower-like nanosheets (denoted as PtO2@Cu2O/Cu FNs) with Cu0/Cu+ pairs and Pt─O bonds, thereby yielding substantial enhancement in both hydrogen evolution reaction (HER, -0.042 VRHE at 10 mA cm-2) and furfural oxidation reaction (FFOR, 0.09 VRHE at 10 mA cm-2). As validated by DFT calculations, the dual built-in electric field (BIEF) is elucidated as the driving force behind the enhanced activities, in which Pt─O bonds expedite the HER, while Cu+/Cu0 promotes low-potential FFOR. By coupling the FFOR and HER together, the resulting bipolar-hydrogen production system requires a low power input (0.5072 kWh per m3) for producing H2. The system can generate bipolar hydrogen and high value-added furoic acid, significantly enhancing hydrogen production efficiency and concurrently mitigating energy consumption.

Low-Potential Iodide Oxidation Enables Dual-Atom CoFe─N─C Catalysts for Ultra-Stable and High-Energy-Efficiency Zn-Air Batteries.

The low energy efficiency and limited cycling life of rechargeable Zn-air batteries (ZABs) arising from the sluggish oxygen reduction/evolution reactions (ORR/OERs) severely hinder their commercial deployment. Herein, a zeolitic imidazolate framework (ZIF)-derived strategy associated with subsequent thermal fixing treatment is proposed to fabricate dual-atom CoFe─N─C nanorods (Co1 Fe1 ─N─C NRs) containing atomically dispersed bimetallic Co/Fe sites, which can promote the energy efficiency and cyclability of ZABs simultaneously by introducing the low-potential oxidation redox reactions. Compared to the mono-metallic nanorods, Co1 Fe1 ─N─C NRs exhibit remarkable ORR performance including a positive half-wave potential of 0.933 V versus reversible hydrogen electrode (RHE) in alkaline electrolyte. Surprisingly, after introducing the potassium iodide (KI) additive, the oxidation overpotential of Co1 Fe1 ─N─C NRs to reach 10 mA cm-2 can be significantly reduced by 395 mV compared to the conventional destructive OER. Theoretical calculations show that the markedly decreased overpotential of iodide oxidation can be ascribed to the synergistic effects of neighboring Co─Fe diatomic sites as the unique adsorption sites. Overall, aqueous ZABs assembled with Co1 Fe1 ─N─C NRs and KI as the air-cathode catalyst and electrolyte additive, respectively, can deliver a low charging voltage of 1.76 V and ultralong cycling stability of over 230 h with a high energy efficiency of ≈68%.

Accessible Tetrathiafulvalene Moieties in a 3D Covalent Organic Framework for Enhanced Near-Infrared Photo-Thermal Conversion and Photo-Electrical Response.

Redox-active tetrathiafulvalene (TTF)-based covalent organic frameworks (COFs) exhibit distinctive electrochemical and photoelectrical properties, but their prevalent two-dimensional (2D) structure with densely packed TTF moieties limits the accessibility of redox center and constrains their potential applications. To overcome this challenge, an 8-connected TTF linker (TTF-8CHO) is designed as a new building block for the construction of three-dimensional (3D) COFs. This approach led to the successful synthesis of a 3D COF with the bcu topology, designated as TTF-8CHO-COF. In comparison to its 2D counterpart employing a 4-connected TTF linker, the 3D COF design enhances access to redox sites, facilitating controlled oxidation by I2 or Au3+ to tune physical properties. When irradiated with a 0.7 W cm-2 808 nm laser, the oxidized 3D COF samples ( I X - ${\mathrm{I}}_{\mathrm{X}}^{-}$ @TTF-8CHO-COF and Au NPs@TTF-8CHO-COF) demonstrated rapid temperature increases of 239.3 and 146.1 °C, respectively, which surpassed those of pristine 3D COF (65.6 °C) and the 2D COF counterpart (6.4 °C increment after I2 treatment). Furthermore, the oxidation of the 3D COF heightened its photoelectrical responsiveness under 808 nm laser irradiation. This augmentation in photothermal and photoelectrical response can be attributed to the higher concentration of TTF·+ radicals generated through the oxidation of well-exposed TTF moieties.

PPARG-mediated autophagy activation alleviates inflammation in rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease characterized by joint inflammation and bone damage, that not only restricts patient activity but also tends to be accompanied by a series of complications, seriously affecting patient prognosis. Peroxisome proliferator-activated receptor gamma (PPARG), a receptor that controls cellular metabolism, regulates the function of immune cells and stromal cells. Previous studies have shown that PPARG is closely related to the regulation of inflammation. However, the role of PPARG in regulating the pathological processes of RA is poorly understood. MATERIALS AND METHODS: PPARG expression was examined in the synovial tissues and peripheral blood mononuclear cells (PBMCs) from RA patients and the paw of collagen-induced arthritis (CIA) model rats. Molecular biology experiments were designed to examine the effect of PPARG and cannabidiol (CBD) on RAW264.7 cells and CIA rats. RESULTS: The results reveal that PPARG accelerates reactive oxygen species (ROS) clearance by promoting autophagy, thereby inhibiting ROS-mediated macrophage polarization and NLRP3 inflammasome activation. Notably, CBD may be a promising candidate for understanding the mechanism by which PPARG regulates autophagy-mediated inflammation. CONCLUSIONS: Taken together, these findings indicate that PPARG may have a role for distinguishing between RA patients and healthy control, and for distinguishing RA activity; moreover, PPARG could be a novel pharmacological target for alleviating RA through the mediation of autophagy. CBD can act as a PPARG agonist that alleviates the inflammatory progression of RA.

Medicaid Expansion Increases Access for Rural and Impoverished Patients with Pancreatic Ductal Adenocarcinoma in Southern States.

INTRODUCTION: Medicaid expansion (ME) impacted patients when assessed at a national level. However, of the 32 states in which Medicaid expansion occurred, only 3 were Southern states. Whether results apply to Southern states that share similar geopolitical perspectives remains elusive. We aimed to assess the impact of ME on pancreatic ductal adenocarcinoma (PDAC) treatment in eight Southern states in the USA. PATIENTS AND METHODS: We identified uninsured or Medicaid patients (age 40-64 years) diagnosed with PDAC between 2011 and 2018 in Southern states from the North American Association of Central Cancer Registries-Cancer in North America (NAACCR-CiNA) research dataset. Medicaid-expanded states (MES; Louisiana, Kentucky, and Arkansas) were compared with non-MES (NMES; Tennessee, Alabama, Mississippi, Texas, and Oklahoma) using multivariate logistic regression. P < 0.05 was considered statistically significant. RESULTS: Among 3036 patients, MES significantly increased odds of Medicaid insurance by 36%, and increased proportions of insured Black patients by 3.7%, rural patients by 3.8%, and impoverished patients by 18.4%. After adjusting for age, race, rural-urban status, poverty status, and summary stage, the odds of receiving radiation therapy decreased by 26% for each year of expansion in expanded states (P = 0.01). Last, ME did not result in a significant difference between MES and NMES in diagnosing early stage disease (P = 0.98) nor in receipt of chemotherapy or surgery (P = 0.23 and P = 0.63, respectively). CONCLUSIONS: ME in Southern states increased insurance access to traditionally underserved groups. Interestingly, ME decreased the odds of receiving radiation therapy yearly and had no significant impact on receipt of chemotherapy or surgery.

Deep learning uncertainty quantification for clinical text classification.

INTRODUCTION: Machine learning algorithms are expected to work side-by-side with humans in decision-making pipelines. Thus, the ability of classifiers to make reliable decisions is of paramount importance. Deep neural networks (DNNs) represent the state-of-the-art models to address real-world classification. Although the strength of activation in DNNs is often correlated with the network's confidence, in-depth analyses are needed to establish whether they are well calibrated. METHOD: In this paper, we demonstrate the use of DNN-based classification tools to benefit cancer registries by automating information extraction of disease at diagnosis and at surgery from electronic text pathology reports from the US National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) population-based cancer registries. In particular, we introduce multiple methods for selective classification to achieve a target level of accuracy on multiple classification tasks while minimizing the rejection amount-that is, the number of electronic pathology reports for which the model's predictions are unreliable. We evaluate the proposed methods by comparing our approach with the current in-house deep learning-based abstaining classifier. RESULTS: Overall, all the proposed selective classification methods effectively allow for achieving the targeted level of accuracy or higher in a trade-off analysis aimed to minimize the rejection rate. On in-distribution validation and holdout test data, with all the proposed methods, we achieve on all tasks the required target level of accuracy with a lower rejection rate than the deep abstaining classifier (DAC). Interpreting the results for the out-of-distribution test data is more complex; nevertheless, in this case as well, the rejection rate from the best among the proposed methods achieving 97% accuracy or higher is lower than the rejection rate based on the DAC. CONCLUSIONS: We show that although both approaches can flag those samples that should be manually reviewed and labeled by human annotators, the newly proposed methods retain a larger fraction and do so without retraining-thus offering a reduced computational cost compared with the in-house deep learning-based abstaining classifier.