Verifying Quantum Advantage Experiments with Multiple Amplitude Tensor Network Contraction.

The quantum supremacy experiment, such as Google Sycamore [F. Arute et al., Nature (London) 574, 505 (2019).NATUAS0028-083610.1038/s41586-019-1666-5], poses a great challenge for classical verification due to the exponentially increasing compute cost. Using a new-generation Sunway supercomputer within 8.5 d, we provide a direct verification by computing 3×10^{6} exact amplitudes for the experimentally generated bitstrings, obtaining a cross-entropy benchmarking fidelity of 0.191% (the estimated value is 0.224%). The leap of simulation capability is built on a multiple-amplitude tensor network contraction algorithm which systematically exploits the "classical advantage" (the inherent "store-and-compute" operation mode of von Neumann machines) of current supercomputers, and a fused tensor network contraction algorithm which drastically increases the compute efficiency on heterogeneous architectures. Our method has a far-reaching impact in solving quantum many-body problems, statistical problems, as well as combinatorial optimization problems.

Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPα axis.

BACKGROUND: The dynamic interaction between cancer cells and tumour-associated macrophages (TAMs) in the hypoxic tumour microenvironment (TME) is an active barrier to the effector arm of the antitumour immune response. Cancer-secreted exosomes are emerging mediators of this cancer-stromal cross-talk in the TME; however, the mechanisms underlying this interaction remain unclear. METHODS: Exosomes were isolated with ExoQuick exosome precipitation solution. The polarizing effect of TAMs was evaluated by flow cytometry, western blot analysis, immunofluorescence staining and in vitro phagocytosis assays. Clinical cervical cancer specimens and an in vivo xenograft model were also employed. RESULTS: Our previous study showed that hypoxia increased the expression of ZEB1 in cervical squamous cell carcinoma (CSCC) cells, which resulted in increased infiltration of TAMs. Here, we found that hypoxia-induced ZEB1 expression is closely correlated with CD47-SIRPα axis activity in CSCC, which enables cancer cells to evade phagocytosis by macrophages and promotes tumour progression. ZEB1 was found to directly activate the transcription of the CD47 gene in hypoxic CSCC cells. We further showed that endogenous ZEB1 was characteristically enriched in hypoxic CSCC cell-derived exosomes and transferred into macrophages via these exosomes to promote SIRPα+ TAM polarization. Intriguingly, exosomal ZEB1 retained transcriptional activity and reprogrammed SIRPα+ TAMs via activation of the STAT3 signalling pathway in vitro and in vivo. STAT3 inhibition reduced the polarizing effect induced by exosomal ZEB1. Knockdown of ZEB1 increased the phagocytosis of CSCC cells by macrophages via decreasing CD47 and SIRPα expression. CONCLUSIONS: Our results suggest that hypoxia-induced ZEB1 promotes immune evasion in CSCC by strengthening the CD47-SIRPα axis. ZEB1-targeted therapy in combination with CD47-SIRPα checkpoint immunotherapy may improve the outcomes of CSCC patients in part by disinhibiting innate immunity.

[Research on Locating Device for the Entry Point of Intramedullary Nail Based on Inertial Navigation].

Objective: To introduce a locating device for the entry point of intramedullary nail based on the inertial navigation technology, which utilizes multi-dimensional angle information to assist in rapid and accurate positioning of the ideal direction of femoral anterograde intramedullary nails' entry point, and to verify its clinical value through clinical tests. Methods: After matching the locating module with the developing board, which are the two components of the locating device, they were placed on the skin surface of the proximal femur of the affected side. Anteroposterior fluoroscopy was performed. The developing angle corresponding to the ideal direction of entry point was selected based on the X-ray image, and then the yaw angle of the locating module was reset to zero. After resetting, the locating module was combined with the surgical instrument to guide the insertion angle of the guide wire. The ideal direction of entry point was accurately located based on the angle guidance. By setting up an experimental group and a control group for clinical surgical operations, the number of guide wire insertion times, surgical time, fluoroscopy frequency, and intraoperative blood loss with or without the locating device was recorded. Results: Compared to the control group, the experimental group showed significant improvement in the number of guide wire insertion times, surgical time, fluoroscopy frequency, and intraoperative blood loss, with a statistically significant difference (P<0.01). Conclusion: The locating device can assist doctors in quickly locating the entry point of intramedullary nail, effectively reducing the fluoroscopy frequency and surgical time by improving the success rate of the guide wire insertion with one shot, improving surgical efficiency, and possessing certain clinical value.

Sideband cooling of a trapped ion in strong sideband coupling regime.

Conventional theoretical studies on the ground-state laser cooling of a trapped ion have mostly focused on the weak sideband coupling (WSC) regime, where the cooling rate is inverse proportional to the linewidth of the excited state. In a recent work [New J. Phys.23, 023018 (2021)10.1088/1367-2630/abe273], we proposed a theoretical framework to study the ground state cooling of a trapped ion in the strong sideband coupling (SSC) regime, under the assumption of a vanishing carrier transition. Here we extend this analysis to more general situations with nonvanishing carrier transitions, where we show that by properly tuning the coupling lasers a cooling rate proportional to the linewidth can be achieved. Our theoretical predictions closely agree with the corresponding exact solutions in the SSC regime, which provide an important theoretical guidance for sideband cooling experiments.

Characteristics of multiple sclerosis and demyelinating disease in an Asian American population.

BACKGROUND: Race and ancestry influence the course of multiple sclerosis (MS). OBJECTIVES: Explore clinical characteristics of MS and neuromyelitis optica spectrum disorder (NMOSD) in Asian American patients. METHODS: Chart review was performed for 282 adults with demyelinating disease who self-identified as Asian at a single North American MS center. Demographics and clinical characteristics were compared to non-Asian MS patients and by region of Asian ancestry. RESULTS: Region of ancestry was known for 181 patients. Most (94.7%) preferred English, but fewer East Asian patients did (80%, p = 0.0001). South Asian patients had higher neighborhood household income (p = 0.002). Diagnoses included MS (76.2%) and NMOSD (13.8%). More patients with NMOSD than MS were East and Southeast Asian (p = 0.004). For MS patients, optic nerve and spinal cord involvement were similar across regions of ancestry. Asian MS patients were younger at symptom onset and diagnosis than non-Asian MS patients. MS Severity Scale scores were similar to non-Asian MS patients but worse among Southeast Asians (p = 0.006). CONCLUSIONS: MS severity was similar between Asian American patients and non-Asian patients. Region of ancestry was associated with differences in sociodemographics and MS severity. Further research is needed to uncover genetic, socioeconomic, or environmental factors causing these differences.

A pathogenic and clonally expanded B cell transcriptome in active multiple sclerosis.

Central nervous system B cells have several potential roles in multiple sclerosis (MS): secretors of proinflammatory cytokines and chemokines, presenters of autoantigens to T cells, producers of pathogenic antibodies, and reservoirs for viruses that trigger demyelination. To interrogate these roles, single-cell RNA sequencing (scRNA-Seq) was performed on paired cerebrospinal fluid (CSF) and blood from subjects with relapsing-remitting MS (RRMS; n = 12), other neurologic diseases (ONDs; n = 1), and healthy controls (HCs; n = 3). Single-cell immunoglobulin sequencing (scIg-Seq) was performed on a subset of these subjects and additional RRMS (n = 4), clinically isolated syndrome (n = 2), and OND (n = 2) subjects. Further, paired CSF and blood B cell subsets (RRMS; n = 7) were isolated using fluorescence activated cell sorting for bulk RNA sequencing (RNA-Seq). Independent analyses across technologies demonstrated that nuclear factor kappa B (NF-κB) and cholesterol biosynthesis pathways were activated, and specific cytokine and chemokine receptors were up-regulated in CSF memory B cells. Further, SMAD/TGF-ß1 signaling was down-regulated in CSF plasmablasts/plasma cells. Clonally expanded, somatically hypermutated IgM+ and IgG1+ CSF B cells were associated with inflammation, blood-brain barrier breakdown, and intrathecal Ig synthesis. While we identified memory B cells and plasmablast/plasma cells with highly similar Ig heavy-chain sequences across MS subjects, similarities were also identified with ONDs and HCs. No viral transcripts, including from Epstein-Barr virus, were detected. Our findings support the hypothesis that in MS, CSF B cells are driven to an inflammatory and clonally expanded memory and plasmablast/plasma cell phenotype.

[Early risk factors for death in neonates with persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide]. / ç»ä¸€æ°§åŒ–æ°®å¸å ¥æ²»ç–—çš„æ–°ç”Ÿå„¿æŒç»­è‚ºåŠ¨è„‰é«˜åŽ‹æ‚£å„¿æ­»äº¡çš„æ—©æœŸå½±å“å› ç´ åˆ†æž.

OBJECTIVES: To evaluate the early risk factors for death in neonates with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (iNO). METHODS: A retrospective analysis was performed on 105 infants with PPHN (gestational age ≥34 weeks and age <7 days on admission) who received iNO treatment in the Department of Neonatology, Children's Hospital of Nanjing Medical University, from July 2017 to March 2021. Related general information and clinical data were collected. According to the clinical outcome at discharge, the infants were divided into a survival group with 79 infants and a death group with 26 infants. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for death in infants with PPHN treated with iNO. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values of the factors in predicting the death risk. RESULTS: A total of 105 infants with PPHN treated with iNO were included, among whom 26 died (26/105, 24.8%). The multivariate Cox regression analysis showed that no early response to iNO (HR=8.500, 95%CI: 3.024-23.887, P<0.001), 1-minute Apgar score ≤3 points (HR=10.094, 95%CI: 2.577-39.534, P=0.001), a low value of minimum PaO2/FiO2 within 12 hours after admission (HR=0.067, 95%CI: 0.009-0.481, P=0.007), and a low value of minimum pH within 12 hours after admission (HR=0.049, 95%CI: 0.004-0.545, P=0.014) were independent risk factors for death. The ROC curve analysis showed that the lowest PaO2/FiO2 value within 12 hours after admission had an area under the ROC curve of 0.783 in predicting death risk, with a sensitivity of 84.6% and a specificity of 73.4% at the cut-off value of 50, and the lowest pH value within 12 hours after admission had an area under the ROC curve of 0.746, with a sensitivity of 76.9% and a specificity of 65.8% at the cut-off value of 7.2. CONCLUSIONS: Infants with PPHN requiring iNO treatment tend to have a high mortality rate. No early response to iNO, 1-minute Apgar score ≤3 points, the lowest PaO2/FiO2 value <50 within 12 hours after admission, and the lowest pH value <7.2 within 12 hours after admission are the early risk factors for death in such infants. Monitoring and evaluation of the above indicators will help to identify high-risk infants in the early stage.

A novel lymphatic pattern promotes metastasis of cervical cancer in a hypoxic tumour-associated macrophage-dependent manner.

Lymphatic remodelling in the hypoxic tumour microenvironment (TME) is critically involved in the metastasis of cervical squamous cell carcinoma (CSCC); however, its underlying mechanisms remain unclear. Here, we uncovered a novel lymphatic pattern in the hypoxic TME, wherein lymphatic vessels (LVs) are encapsulated by tumour-associated macrophages (TAMs) to form an interconnected network. We describe these aggregates as LVEM (LVs encapsulated by TAMs) considering their advantageous metastatic capacity and active involvement in early lymph node metastasis (LNM). Mechanistic investigations revealed that interleukin-10 (IL-10) derived from hypoxic TAMs adjacent to LVs was a prerequisite for lymphangiogenesis and LVEM formation through its induction of Sp1 upregulation in lymphatic endothelial cells (LECs). Interestingly, Sp1high LECs promoted the transactivation of C-C motif chemokine ligand 1 (CCL1) to facilitate TAM and tumour cell recruitment, thereby forming a positive feedback loop to strengthen the LVEM formation. Knockdown of Sp1 or blockage of CCL1 abrogated LVEM and consequently attenuated LNM. Notably, CSCCnon-LNM is largely devoid of hypoxic TAMs and the resultant LVEM, which might explain its metastatic delay. These findings identify a novel and efficient metastasis-promoting lymphatic pattern in the hypoxic TME, which might provide new targets for anti-metastasis therapy and prognostic assessment.

Verifying Random Quantum Circuits with Arbitrary Geometry Using Tensor Network States Algorithm.

The ability to efficiently simulate random quantum circuits using a classical computer is increasingly important for developing noisy intermediate-scale quantum devices. Here, we present a tensor network states based algorithm specifically designed to compute amplitudes for random quantum circuits with arbitrary geometry. Singular value decomposition based compression together with a two-sided circuit evolution algorithm are used to further compress the resulting tensor network. To further accelerate the simulation, we also propose a heuristic algorithm to compute the optimal tensor contraction path. We demonstrate that our algorithm is up to 2 orders of magnitudes faster than the Schrödinger-Feynman algorithm for verifying random quantum circuits on the 53-qubit Sycamore processor, with circuit depths below 12. We also simulate larger random quantum circuits with up to 104 qubits, showing that this algorithm is an ideal tool to verify relatively shallow quantum circuits on near-term quantum computers.

Strong Quantum Computational Advantage Using a Superconducting Quantum Processor.

Scaling up to a large number of qubits with high-precision control is essential in the demonstrations of quantum computational advantage to exponentially outpace the classical hardware and algorithmic improvements. Here, we develop a two-dimensional programmable superconducting quantum processor, Zuchongzhi, which is composed of 66 functional qubits in a tunable coupling architecture. To characterize the performance of the whole system, we perform random quantum circuits sampling for benchmarking, up to a system size of 56 qubits and 20 cycles. The computational cost of the classical simulation of this task is estimated to be 2-3 orders of magnitude higher than the previous work on 53-qubit Sycamore processor [Nature 574, 505 (2019)NATUAS0028-083610.1038/s41586-019-1666-5. We estimate that the sampling task finished by Zuchongzhi in about 1.2 h will take the most powerful supercomputer at least 8 yr. Our work establishes an unambiguous quantum computational advantage that is infeasible for classical computation in a reasonable amount of time. The high-precision and programmable quantum computing platform opens a new door to explore novel many-body phenomena and implement complex quantum algorithms.

Assessment of SENP3-interacting proteins in hepatocytes treated with diethylnitrosamine by BioID assay.

SUMOylation of proteins regulates cell behaviors and is reversibly removed by small ubiquitin-like modifier (SUMO)-specific proteases (SENPs). The SENP family member SENP3 is involved in SUMO2/3 deconjugation and has been reported to sense cell stress and accumulate in several human cancer cells and macrophages. We previously reported that Senp3-knockout heterozygous mice showed smaller liver, but the pertinent mechanisms of SENP3 and SUMOylated substrates remain unclear. Thus, in this study, we investigated the interacting proteins with SENP3 and the alteration in hepatocytes treated with the xenobiotic diethylnitrosamine (DEN), which is specifically transformed in the liver and induces DNA double-strand breaks. Our data revealed that a certain amount of SENP3 was present in normal, untreated hepatocytes; however, DEN treatment promoted rapid SENP3 accumulation. SENP3 was mainly localized in the nuclei, and its level was significantly increased in the cytoplasm after 2 h of DEN treatment. The application of the recent proximity-dependent biotinylation (BioID) method led to the identification of 310 SENP3-interacting proteins that were involved in not only gene transcription but also RNA splicing, protein folding, and metabolism. Furthermore, after DEN exposure for a short duration, ribosomal proteins as well as proteins associated with mitochondrial ATP synthesis, membrane transport, and bile acid synthesis, rather than DNA repair proteins, were identified. This study provides insights into the diverse regulatory roles of SENP3, and the BioID method seems to be efficient for identifying physiologically relevant insoluble proteins.

Anti-gamma-aminobutyric acid receptor type A encephalitis: a review.

PURPOSE OF REVIEW: To systematically review the clinical features, diagnosis, and management of anti-gamma-aminobutyric acid receptor Type A (GABAA) autoimmune encephalitis with a focus on recent data. RECENT FINDINGS: In a review of published reports, we identified 50 cases of anti-GABAA receptor encephalitis with clinical features reported. The median age at presentation was 47 years old (range, 2.5 months-88 years old), 64% were adults, 36% were children and it occurred in both males and females. Eight-two percent (41/50) presented with seizures, 72% (36/50) with encephalopathy, and 58% (29/50) with both. Of those presenting with seizures, 42% developed status epilepticus during their disease course. Ninety-six percent (48/50) had MRI results reported, with 83% of these cases having abnormal findings, most commonly multifocal/diffuse cortical and subcortical T2/FLAIR hyperintense lesions without associated gadolinium enhancement. Almost one-third, 28% (14/50), had an associated malignancy detected by the time of diagnosis, 64% (9/14) of which was thymoma. Of 44 patients with outcomes reported, 80% had partial or complete recovery, whereas 20% had poor outcomes including 11% (5/44) who died. Of the 42 patients with type of treatment(s) and outcomes reported, 54% (23/42) received only first-line immunotherapy and 31% (13/42) received first-line and second-line immunotherapy. Receiving a combination of first-line and second-line immunotherapy may be associated with higher likelihood of complete recovery. When follow-up MRIs were reported, all showed improvement, and sometimes complete resolution, of T2/FLAIR hyperintensities. SUMMARY: Anti-GABAA receptor encephalitis can present across the age spectrum and should be considered in patients who present with rapidly progressive encephalopathy and/or seizures. Brain MRI often shows a distinctive pattern of multifocal cortical and subcortical T2/FLAIR hyperintense lesions, generally not typical of other known central nervous system autoantibody associated encephalitis syndromes. High clinical suspicion and early diagnosis are important given the potential for clinical improvement with immunotherapy.

Giant Spin Current Rectification Due to the Interplay of Negative Differential Conductance and a Non-Uniform Magnetic Field.

In XXZ chains with large enough interactions, spin transport can be significantly suppressed when the bias of the dissipative driving becomes large enough. This phenomenon of negative differential conductance is caused by the formation of two oppositely polarized ferromagnetic domains at the edges of the chain. Here, we show that this many-body effect, combined with a non-uniform magnetic field, can allow for a high degree of control of the spin current. In particular, by studying all of the possible shapes of local magnetic fields potentials, we find that a configuration in which the magnetic field points up for half of the chain and down for the other half, can result in giant spin-current rectification, for example, up to 108 for a system with only 8 spins. Our results show clear indications that the rectification can increase with the system size.

General-Purpose Quantum Circuit Simulator with Projected Entangled-Pair States and the Quantum Supremacy Frontier.

Recent advances on quantum computing hardware have pushed quantum computing to the verge of quantum supremacy. Here, we bring together many-body quantum physics and quantum computing by using a method for strongly interacting two-dimensional systems, the projected entangled-pair states, to realize an effective general-purpose simulator of quantum algorithms. The classical computing complexity of this simulator is directly related to the entanglement generation of the underlying quantum circuit rather than the number of qubits or gate operations. We apply our method to study random quantum circuits, which allows us to quantify precisely the memory usage and the time requirements of random quantum circuits. We demonstrate our method by computing one amplitude for a 7×7 lattice of qubits with depth (1+40+1) on the Tianhe-2 supercomputer.

Light-Cone and Diffusive Propagation of Correlations in a Many-Body Dissipative System.

We analyze the propagation of correlations after a sudden interaction change in a strongly interacting quantum system in contact with an environment. In particular, we consider an interaction quench in the Bose-Hubbard model, deep within the Mott-insulating phase, under the effect of dephasing. We observe that dissipation effectively speeds up the propagation of single-particle correlations while reducing their coherence. In contrast, for two-point density correlations, the initial ballistic propagation regime gives way to diffusion at intermediate times. Numerical simulations, based on a time-dependent matrix product state algorithm, are supplemented by a quantitatively accurate fermionic quasiparticle approach providing an intuitive description of the initial dynamics in terms of holon and doublon excitations.

Aspirin is an effective pretreatment for exercise in multiple sclerosis: A double-blind randomized controlled pilot trial.

Exercise benefits multiple sclerosis (MS) patients, but exercise-induced overheating is a deterrent for many. We conducted a double-blind crossover-design placebo-controlled pilot of aspirin to increase time-to-exhaustion (TTE) and reduce exercise-induced body temperature increase. A total of 12 patients participated. At enrollment, 8 of 12 reported heat sensitivity during exercise. After 650 mg of aspirin or placebo, participants performed lower body cycle ergometer exercise test. TTE increased after aspirin compared to placebo: t(11) = 2.405, p = 0.035 (Cohen's d = 1.45). Body temperature increase after exercise with acetylsalicylic acid (ASA) was reduced by 56% in heat-sensitive patients, although limited power precluded statistical significance. Aspirin may represent an effective pretreatment for exercise in MS.

[Research progress of the uremic toxin indoxyl sulfate in cardiovascular complication of end-stage renal diseases].

Cardiovascular disease is one of the most common complications and the main cause of death in patients with chronic kidney disease. Uremic toxins are the primary cause of cardiovascular disease in renal insufficiency. In patients with chronic kidney disease, the protein-bound uremic toxins represented by indoxyl sulfate are difficult to be removed by conventional dialysis and are extremely toxic. In recent years, studies have confirmed that the occurrence of cardiovascular disease induced by chronic kidney disease is closely related to the accumulation of indoxyl sulfate. Indoxyl sulfate can induce oxidative stress to cause endothelial injury, smooth muscle cell proliferation and migration, and promote the occurrence of atherosclerosis, thereby affecting multiple systems throughout the body. This article reviews the research progress of uremic toxin indoxyl sulfate in end-stage renal diseases associated cardiovascular diseases.

Roles of Mitogen-Activating Protein Kinase Kinase Kinase Kinase-3 (MAP4K3) in Preterm Skeletal Muscle Satellite Cell Myogenesis and Mammalian Target of Rapamycin Complex 1 (mTORC1) Activation Regulation.

BACKGROUND Preterm skeletal muscle genesis is a paradigm for myogenesis. The role of mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3) in preterm skeletal muscle satellite cells myogenesis or its relationship to mammalian target of rapamycin complex 1 (mTORC1) activity have not been previously elaborated. MATERIAL AND METHODS Small interfering RNA (siRNA) interference technology was used to inhibit MAP4K3 expression. Leucine stimulation experiments were performed following MAP4K3-siRNA interference. The differentiation of primary preterm skeletal muscle satellite cells was observed after siRNA-MAP4K3 interference. Western blot analysis was used to determine the expression of MAP4K3, MyHC, MyoD, myogenin, p-mTOR, and p-S6K1. The immunofluorescence fusion index of MyHC and myogenin were detected. MAP4K3 effects on preterm rat satellite cells differentiation and its relationship to mTORC1 activity are reported. RESULTS MAP4K3 siRNA knockdown inhibited myotube formation and both MyoD and myogenin expression in primary preterm rat skeletal muscle satellite cells, but MAP4K3 siRNA had no effect on the activity of mTORC1. In primary preterm rat skeletal muscle satellite cells, MAP4K3 knockdown resulted in significantly weaker, but not entirely blunted, leucine-induced mTORC1 signaling. CONCLUSIONS MAP4K3 positively regulates preterm skeletal muscle satellite cell myogenesis, but may not regulate mTORC1 activity. MAP4K3 may play a role in mTORC1 full activation in response to leucine.

A Closed-Loop Digital Health Tool to Improve Depression Care in Multiple Sclerosis: Iterative Design and Cross-Sectional Pilot Randomized Controlled Trial and its Impact on Depression Care.

BACKGROUND: People living with multiple sclerosis (MS) face a higher likelihood of being diagnosed with a depressive disorder than the general population. Although many low-cost screening tools and evidence-based interventions exist, depression in people living with MS is underreported, underascertained by clinicians, and undertreated. OBJECTIVE: This study aims to design a closed-loop tool to improve depression care for these patients. It would support regular depression screening, tie into the point of care, and support shared decision-making and comprehensive follow-up. After an initial development phase, this study involved a proof-of-concept pilot randomized controlled trial (RCT) validation phase and a detailed human-centered design (HCD) phase. METHODS: During the initial development phase, the technological infrastructure of a clinician-facing point-of-care clinical dashboard for MS management (BRIDGE) was leveraged to incorporate features that would support depression screening and comprehensive care (Care Technology to Ascertain, Treat, and Engage the Community to Heal Depression in people living with MS [MS CATCH]). This linked a patient survey, in-basket messages, and a clinician dashboard. During the pilot RCT phase, a convenience sample of 50 adults with MS was recruited from a single MS center with 9-item Patient Health Questionnaire scores of 5-19 (mild to moderately severe depression). During the routine MS visit, their clinicians were either asked or not to use MS CATCH to review their scores and care outcomes were collected. During the HCD phase, the MS CATCH components were iteratively modified based on feedback from stakeholders: people living with MS, MS clinicians, and interprofessional experts. RESULTS: MS CATCH links 3 features designed to support mood reporting and ascertainment, comprehensive evidence-based management, and clinician and patient self-management behaviors likely to lead to sustained depression relief. In the pilot RCT (n=50 visits), visits in which the clinician was randomized to use MS CATCH had more notes documenting a discussion of depressive symptoms than those in which MS CATCH was not used (75% vs 34.6%; χ21=8.2; P=.004). During the HCD phase, 45 people living with MS, clinicians, and other experts participated in the design and refinement. The final testing round included 20 people living with MS and 10 clinicians including 5 not affiliated with our health system. Most scoring targets for likeability and usability, including perceived ease of use and perceived effectiveness, were met. Net Promoter Scale was 50 for patients and 40 for clinicians. CONCLUSIONS: Created with extensive stakeholder feedback, MS CATCH is a closed-loop system aimed to increase communication about depression between people living with MS and their clinicians, and ultimately improve depression care. The pilot findings showed evidence of enhanced communication. Stakeholders also advised on trial design features of a full year long Department of Defense-funded feasibility and efficacy trial, which is now underway. TRIAL REGISTRATION: ClinicalTrials.gov NCT05865405; http://tinyurl.com/4zkvru9x.