Suppressed thermal transport in silicon nanoribbons by inhomogeneous strain.

Nanoscale structures can produce extreme strain that enables unprecedented material properties, such as tailored electronic bandgap1-5, elevated superconducting temperature6,7 and enhanced electrocatalytic activity8,9. While uniform strains are known to elicit limited effects on heat flow10-15, the impact of inhomogeneous strains has remained elusive owing to the coexistence of interfaces16-20 and defects21-23. Here we address this gap by introducing inhomogeneous strain through bending individual silicon nanoribbons on a custom-fabricated microdevice and measuring its effect on thermal transport while characterizing the strain-dependent vibrational spectra with sub-nanometre resolution. Our results show that a strain gradient of 0.112% per nanometre could lead to a drastic thermal conductivity reduction of 34 ± 5%, in clear contrast to the nearly constant values measured under uniform strains10,12,14,15. We further map the local lattice vibrational spectra using electron energy-loss spectroscopy, which reveals phonon peak shifts of several millielectron-volts along the strain gradient. This unique phonon spectra broadening effect intensifies phonon scattering and substantially impedes thermal transport, as evidenced by first-principles calculations. Our work uncovers a crucial piece of the long-standing puzzle of lattice dynamics under inhomogeneous strain, which is absent under uniform strain and eludes conventional understanding.

A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Treatment with CM313, a novel anti-CD38 monoclonal antibody, can result in targeted clearance of CD38-positive cells, including plasma cells. METHODS: We conducted a phase 1-2, open-label study to evaluate the safety and efficacy of CM313 in adult patients with ITP. CM313 was administered intravenously at a dose of 16 mg per kilogram of body weight every week for 8 weeks, followed by a 16-week follow-up period. The primary outcomes were adverse events and documentation of two or more consecutive platelet counts of at least 50×109 per liter within 8 weeks after the first dose of CM313. The status of peripheral-blood immune cells in patients and changes in the mononuclear phagocytic system in passive mouse models of ITP receiving anti-CD38 therapy were monitored. RESULTS: Of the 22 patients included in the study, 21 (95%) had two consecutive platelet counts of at least 50×109 per liter during the treatment period, with a median cumulative response duration of 23 weeks (interquartile range, 17 to 24). The median time to the first platelet count of at least 50×109 per liter was 1 week (range, 1 to 3). The most common adverse events that occurred during the study were infusion-related reaction (in 32% of the patients) and upper respiratory tract infection (in 32%). After CD38-targeted therapy, the percentage of CD56dimCD16+ natural killer cells, the expression of CD32b on monocytes in peripheral blood, and the number of macrophages in the spleen of the passive mouse models of ITP all decreased. CONCLUSIONS: In this study, anti-CD38 targeted therapy rapidly boosted platelet levels by inhibiting antibody-dependent cell-mediated cytotoxicity on platelets, maintained long-term efficacy by clearing plasma cells, and was associated with mainly low-grade toxic effects. (Funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences and others; ClinicalTrials.gov number, NCT05694767).

Aqueous chemimemristor based on proton-permeable graphene membranes.

Memristive devices, electrical elements whose resistance depends on the history of applied electrical signals, are leading candidates for future data storage and neuromorphic computing. Memristive devices typically rely on solid-state technology, while aqueous memristive devices are crucial for biology-related applications such as next-generation brain-machine interfaces. Here, we report a simple graphene-based aqueous memristive device with long-term and tunable memory regulated by reversible voltage-induced interfacial acid-base equilibria enabled by selective proton permeation through the graphene. Surface-specific vibrational spectroscopy verifies that the memory of the graphene resistivity arises from the hysteretic proton permeation through the graphene, apparent from the reorganization of interfacial water at the graphene/water interface. The proton permeation alters the surface charge density on the CaF2 substrate of the graphene, affecting graphene's electron mobility, and giving rise to synapse-like resistivity dynamics. The results pave the way for developing experimentally straightforward and conceptually simple aqueous electrolyte-based neuromorphic iontronics using two-dimensional (2D) materials.

Metabolomics profile and machine learning prediction of treatment responses in immune thrombocytopenia: A prospective cohort study.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by antibody-mediated platelet destruction and impaired platelet production. The mechanisms underlying ITP and biomarkers predicting the response of drug treatments are elusive. We performed a metabolomic profiling of bone marrow biopsy samples collected from ITP patients admission in a prospective study of the National Longitudinal Cohort of Hematological Diseases. Machine learning algorithms were conducted to discover novel biomarkers to predict ITP patient treatment responses. From the bone marrow biopsies of 91 ITP patients, we quantified a total of 4494 metabolites, including 1456 metabolites in the positive mode and 3038 metabolites in the negative mode. Metabolic patterns varied significantly between groups of newly diagnosed and chronic ITP, with a total of 876 differential metabolites involved in 181 unique metabolic pathways. Enrichment factors and p-values revealed the top metabolically enriched pathways to be sphingolipid metabolism, the sphingolipid signalling pathway, ubiquinone and other terpenoid-quinone biosynthesis, thiamine metabolism, tryptophan metabolism and cofactors biosynthesis, the phospholipase D signalling pathway and the phosphatidylinositol signalling system. Based on patient responses to five treatment options, we screened several metabolites using the Boruta algorithm and ranked their importance using the random forest algorithm. Lipids and their metabolism, including long-chain fatty acids, oxidized lipids, glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine biosynthesis, helped differentiate drug treatment responses. In conclusion, this study revealed metabolic alterations associated with ITP in bone marrow supernatants and a potential biomarker predicting the response to ITP.

Proteomics landscape and machine learning prediction of long-term response to splenectomy in primary immune thrombocytopenia.

This study aimed to identify key proteomic analytes correlated with response to splenectomy in primary immune thrombocytopenia (ITP). Thirty-four patients were retrospectively collected in the training cohort and 26 were prospectively enrolled as validation cohort. Bone marrow biopsy samples of all participants were collected prior to the splenectomy. A total of 12 modules of proteins were identified by weighted gene co-expression network analysis (WGCNA) method in the developed cohort. The tan module positively correlated with megakaryocyte counts before splenectomy (r = 0.38, p = 0.027), and time to peak platelet level after splenectomy (r = 0.47, p = 0.005). The blue module significantly correlated with response to splenectomy (r = 0.37, p = 0.0031). KEGG pathways analysis found that the PI3K-Akt signalling pathway was predominantly enriched in the tan module, while ribosomal and spliceosome pathways were enriched in the blue module. Machine learning algorithm identified the optimal combination of biomarkers from the blue module in the training cohort, and importantly, cofilin-1 (CFL1) was independently confirmed in the validation cohort. The C-index of CFL1 was >0.7 in both cohorts. Our results highlight the use of bone marrow proteomics analysis for deriving key analytes that predict the response to splenectomy, warranting further exploration of plasma proteomics in this patient population.

Characteristics and outcomes of COVID-19 in Chinese immune thrombocytopenia patients: A prospective cohort study.

The coronavirus disease 2019 (COVID-19) pandemic has a significant impact on the immune system. This is the first and largest study on pre-existing immune thrombocytopenia (ITP) patients infected with COVID-19 in China. We prospectively collected ITP patients infected with COVID-19 enrolled in the National Longitudinal Cohort of Hematological Diseases (NICHE, NCT04645199) and followed up for at least 1 month after infection. One thousand and one hundred forty-eight pre-existing ITP patients were included. Two hundred and twelve (18.5%) patients showed a decrease in the platelet (PLT) count after infection. Forty-seven (4.1%) patients were diagnosed with pneumonia. Risk factors for a decrease in the PLT count included baseline PLT count <50 × 109/L (OR, 1.76; 95% CI, 1.25-2.46; p = 0.001), maintenance therapy including thrombopoietin receptor agonists (TPO-RAs) (OR, 2.27; 95% CI, 1.60-3.21; p < 0.001) and previous splenectomy (OR, 1.98; 95% CI, 1.09-3.61; p = 0.03). Risk factors for pneumonia included age ≥40 years (OR, 2.45; 95% CI, 1.12-5.33; p = 0.02), ≥2 comorbidities (OR, 3.47; 95% CI, 1.63-7.64; p = 0.001), maintenance therapy including TPO-RAs (OR, 2.14; 95% CI, 1.17-3.91; p = 0.01) and immunosuppressants (OR, 3.05; 95% CI, 1.17-7.91; p = 0.02). In this cohort study, we described the characteristics of pre-existing ITP patients infected with COVID-19 and identified several factors associated with poor outcomes.

Single-Digit Nanobubble Sensing via Nanopore Technology.

Nanobubbles play an important role in diverse fields, including engineering, medicine, and agriculture. Understanding the characteristics of individual nanobubbles is essential for comprehending fluid dynamics behaviors and advancing nanoscale science across various fields. Here, we report a strategy based on nanopore sensors for characterizing single-digit nanobubbles. We investigated the sizes and diffusion coefficients of nanobubbles at different voltages. Additionally, the finite element simulation and molecular dynamics simulation were introduced to account for counterion concentration variation around nanobubbles in the nanopore. In particular, the differences in stability and surface charge density of nanobubbles under various solution environments have been studied by the ion-stabilized model and the DLVO theory. Additionally, a straightforward method to mitigate nanobubble generation in the bulk for reducing current noise in nanopore sensing was suggested. The results hold significant implications for enhancing the understanding of individual nanobubble characterizations, especially in the nanofluid field.

Synergistic Effect of Grain Boundaries and Oxygen Vacancies on Enhanced Selectivity for Electrocatalytic CO2 Reduction.

Dual-engineering involved of grain boundaries (GBs) and oxygen vacancies (VO) efficiently engineers the material's catalytic performance by simultaneously introducing favorable electronic and chemical properties. Herein, a novel SnO2 nanoplate is reported with simultaneous oxygen vacancies and abundant grain boundaries (V,G-SnOx/C) for promoting the highly selective conversion of CO2 to value-added formic acid. Attributing to the synergistic effect of employed dual-engineering, the V,G-SnOx/C displays highly catalytic selectivity with a maximum Faradaic efficiency (FE) of 87% for HCOOH production at -1.2 V versus RHE and FEs > 95% for all C1 products (CO and HCOOH) within all applied potential range, outperforming current state-of-the-art electrodes and the amorphous SnOx/C. Theoretical calculations combined with advanced characterizations revealed that GB induces the formation of electron-enriched Sn site, which strengthens the adsorption of *HCOO intermediate. While GBs and VO synergistically lower the reaction energy barrier, thus dramatically enhancing the intrinsic activity and selectivity toward HCOOH.

Reexamination of Damping in Sliding Friction.

Friction is responsible for about one-third of the primary energy consumption in the world. So far, a thorough atomistic understanding of the frictional energy dissipation mechanisms is still lacking. The Amontons' law states that kinetic friction is independent of the sliding velocity while the Prandtl-Tomlinson model suggests that damping is proportional to the relative sliding velocity between two contacting objects. Through careful analysis of the energy dissipation process in atomic force microscopy measurements, here we propose that damping force is proportional to the tip oscillation speed induced by friction. It is shown that a physically well-founded damping term can better reproduce the multiple peaks in the velocity-dependent friction force observed in both experiments and molecular dynamics simulations. Importantly, the analysis gives a clear physical picture of the dynamics of energy dissipation in different friction phases, which provides insight into long-standing puzzles in sliding friction, such as velocity weakening and spring-stiffness-dependent friction.

Single-dose rituximab plus glucocorticoid versus cyclophosphamide plus glucocorticoid in patients with newly diagnosed acquired hemophilia A: A multicenter, open-label, randomized noninferiority trial.

Acquired hemophilia A (AHA) is a rare but serious bleeding disorder. Randomized controlled trial (RCT) comparing the efficacy of immunosuppression therapy for AHA lacks. We conducted the first multicenter RCT aiming to establish whether the single-dose rituximab combination regimen was noninferior to the cyclophosphamide combination regimen. From 2017 to 2022, 63 patients with newly diagnosed AHA from five centers were randomly assigned 1:1 to receive glucocorticoid (methylprednisolone 0.8 mg/kg per day for the first 3 weeks and then tapered) plus single-dose rituximab (375 mg/m2 ; n = 31) or plus cyclophosphamide (2 mg/kg per day until inhibitor becomes negative, for a maximum of 5 weeks; n = 32). The primary outcome was complete remission (CR, defined as FVIII activity ≥50 IU/dL, FVIII inhibitor undetectable, immunosuppression tapered and no bleeding for 24 h without bypassing agents) rate measured within 8 weeks. The noninferiority margin was an absolute difference of 20%. Twenty-four (77.4%) patients in the rituximab group and 22 (68.8%) patients in the cyclophosphamide group achieved CR, which showed the noninferiority of the single-dose rituximab-based regimen (absolute difference = -8.67%, lower limit of the 95% confidence interval = -13.11%; Pnoninferiority = 0.005). No difference was found in the incidence of treatment-related adverse events. Single-dose rituximab plus glucocorticoid regimen showed similar efficacy and safety, without a reported risk of secondary malignancies or reproductive toxicity seen in cyclophosphamide, it might be recommended as a first-line therapy for AHA, especially in China where there is a young age trend in AHA patients. This trial was registered at ClinicalTrials.gov as #NCT03384277.

Unfolding of protein using MoS2/SnS2heterostructure for nanopore-based sequencing.

Protein sequencing is crucial for understanding the complex mechanisms driving biological functions. However, proteins are usually folded in their native state and the mechanism of fast protein conformation transitions still remains unclear, which make protein sequencing challenging. Molecular dynamics simulations with accurate force field are now able to observe the entire folding/unfolding process, providing valuable insights into protein folding mechanisms. Given that proteins can be unfolded, nanopore technology shows great potential for protein sequencing. In this study, we proposed to use MoS2/SnS2heterostructures to firstly unfold proteins and then detect them by a nanopore in the heterostructural membrane. All-atom molecular dynamics simulations performed in this work provided rich atomic-level information for a comprehensive understanding of protein unfolding process and mechanism on the MoS2/SnS2heterostructure, it was found that the strong binding of protein to SnS2nanostripe and hydrogen bond breaking were the main reasons for unfolding the protein on the heterostructure. After the protein was fully unfolded, it was restrained on the nanostripe because of the affinity of protein to the SnS2nanostripe. Thus by integrating the proposed unfolding technique with nanopore technology, detection of linear unfolded peptide was realized in this work, allowing for the identification of protein components, which is essential for sequencing proteins in the near future.

Acute caval thrombosis leading to obstructive shock in the early post insertion period of an inferior vena cava filter: a case report and literature review.

BACKGROUND: Obstructive shock is extremely rare in clinical practice and is caused by acute blood flow obstruction in the central vessels of either the systemic or pulmonary circulation. Utilizing inferior vena cava filters (IVCFs) to prevent pulmonary embolism (PE) is associated with some potential complications, such as inferior vena cava thrombosis (IVCT). Shock as a direct result of IVCT is rare. We present a case of obstructive shock secondary to extensive IVCT caused by inadequate anticoagulant therapy after the placement of an IVCF. CASE PRESENTATION: A 63-year-old male patient with a traffic accident injury presented orthopaedic trauma and lower limb deep vein thrombosis (DVT). He experienced sudden and severe abdominal pain with hypotension, tachycardia, tachypnea, oliguria and peripheral oedema 5 days after IVCF placement and 3 days after cessation of anticoagulant therapy. Considering that empirical anti-shock treatment lasted for a while and the curative effect was poor, we finally recognized the affected vessels and focused on the reason for obstructive shock through imaging findings-inferior vena cava thrombosis and occlusion. The shock state immediately resolved after thrombus aspiration. The same type of shock occurred again 6 days later during transfer from the ICU to general wards and the same treatment was administered. The patient recovered smoothly in the later stage, and the postoperative follow-up at 1, 3, and 12 months showed good results. CONCLUSION: This case alerts clinicians that it is crucial to ensure adequate anticoagulation therapy after IVCF placement, and when a patient presents with symptoms such as hypotension, tachycardia, and lower limb and scrotal oedema postoperatively, immediate consideration should be given to the possibility of obstructive shock, and prompt intervention should be based on the underlying cause.

TERRA regulates DNA G-quadruplex formation and ATRX recruitment to chromatin.

The genome consists of non-B-DNA structures such as G-quadruplexes (G4) that are involved in the regulation of genome stability and transcription. Telomeric-repeat containing RNA (TERRA) is capable of folding into G-quadruplex and interacting with chromatin remodeler ATRX. Here we show that TERRA modulates ATRX occupancy on repetitive sequences and over genes, and maintains DNA G-quadruplex structures at TERRA target and non-target sites in mouse embryonic stem cells. TERRA prevents ATRX from binding to subtelomeric regions and represses H3K9me3 formation. G4 ChIP-seq reveals that G4 abundance decreases at accessible chromatin regions, particularly at transcription start sites (TSS) after TERRA depletion; such G4 reduction at TSS is associated with elevated ATRX occupancy and differentially expressed genes. Loss of ATRX alleviates the effect of gene repression caused by TERRA depletion. Immunostaining analyses demonstrate that knockdown of TERRA diminishes DNA G4 signals, whereas silencing ATRX elevates G4 formation. Our results uncover an epigenetic regulation by TERRA that sequesters ATRX and preserves DNA G4 structures.

Fast Probing Amyloid Polymorphism via Nanopore Translocation.

Neurodegenerative diseases are characterized by the presence of cross-ß-sheet amyloid fibrils and a rich mesoscopic polymorphism, requiring noninvasive detection with high fidelity. Here, we introduce a methodology that can probe via a sensitive synthetic nanopore the complex polymorphism of amyloid fibrils by an automated and fast screening protocol. Statistically analyzing the translocation events on two model amyloid systems derived from ß-lactoglobulin and lysozyme allows extracting the cross-sectional configuration of hydrated amyloid fibrils from current block amplitude and correlating dwell time with fibril length. These findings are consistent with the amyloid polymorphs observed in solution by atomic force microscopy. Furthermore, the ionic current signal of a single translocation event can reveal abnormally aggregated conformations of amyloid fibrils without potential artifacts associated with microscopy methods. This study introduces an effective approach to physically discriminating and separating amyloid and may serve in the rapid diagnosis of early aggregating pathological amyloidosis.

When to expect scalp hair regrowth during treatment of severe alopecia areata with baricitinib: insights from trajectories analyses of patients enrolled in two phase III trials.

BACKGROUND: Baricitinib is approved for the treatment of adults with severe alopecia areata (AA). In the absence of robust data on the patterns of regrowth during treatment of severe AA, there is a gap in the knowledge regarding treatment expectations. OBJECTIVES: To examine whether different clinical response subgroups could be identified in baricitinib-treated patients with severe AA and factors that contribute to these subgroups. METHODS: The BRAVE-AA1 and BRAVE-AA2 phase III trials enrolled patients with severe AA [Severity of Alopecia Tool (SALT) score ≥ 50 (≥ 50% scalp hair loss)]. Patients randomized to baricitinib 4 mg or 2 mg retained their treatment allocation for 52 weeks. Based on patterns identified through growth mixture modelling (GMM), patients were categorized into responder subgroups according to when they first achieved ≥ 30% improvement from baseline in SALT score (SALT30). For each responder subgroup, trajectories of response (i.e. achievement of a SALT score ≤ 20, SALT score ≤ 10 and ≥ 50% change from baseline in SALT score) and baseline disease characteristics are reported. RESULTS: Respectively, 515 and 340 patients were randomized to once-daily baricitinib 4 mg and 2 mg at baseline; 69% and 51%, respectively, achieved SALT30 at least once by week 52. Based on GMM findings, we identified three responder subgroups: early (SALT30 by week 12), gradual (SALT30 after week 12-week 36) and late (SALT30 after week 36-week 52). The proportions of early, gradual and late responders and nonresponders were, respectively, 33%, 28%, 8% and 31% among patients treated with baricitinib 4 mg, and 20%, 23%, 9% and 49%, respectively, among those treated with baricitinib 2 mg. Early responders had a shorter trajectory to maximal clinical outcomes (e.g. > 78% achieved a SALT score ≤ 20 by week 36) vs. gradual or late responders. Early responders were more frequent among patients with baseline severe AA (SALT score 50 to < 95) vs. very severe AA (SALT score 95-100). Overall, responders (early to late) were more frequent in patients with short (< 4 years) episodes of hair loss. CONCLUSIONS: These analyses identified early, gradual and late responder subgroups for scalp hair regrowth in baricitinib-treated patients with severe AA, and that these subgroups are influenced by baseline characteristics. Findings from these analyses will help to inform treatment expectations for scalp hair regrowth.

Clinical features and current treatment status of essential thrombocythemia in older adults: a multicenter real-world study in China.

Approximately half of patients diagnosed with essential thrombocythemia (ET) are older adults (aged ≥ 60 years), but to date, little is known about the clinical and molecular characteristics of older patients diagnosed according to the 2016 World Health Organization criteria. We retrospectively collected clinical and molecular data from 282 older (≥ 60 years) and 621 younger ET patients (18-59 years) in China from March 1, 2012 to November 1, 2021 and summarized the clinical characteristics and treatment of these older ET patients. Compared to younger patients, older patients had a higher incidence of the JAK2V617F mutation (P = 0.001), a lower incidence of CALR mutations (P = 0.033) and a higher rate of epigenetic mutations (P < 0.001), TP53 mutations (P = 0.005), and RNA splicing mutations (P < 0.001). Older patients had not only a higher incidence of thrombosis but also a higher incidence of bleeding events. Furthermore, older patients had a significantly higher mortality rate after disease progression (P = 0.050) or after thrombotic events (P = 0.013). Risk factors for thrombosis or prognosis were significantly different between older patients and the entire ET cohort. In older patients, non-driver mutations contributed significantly to thrombotic complications and a poor prognosis, while the JAK2V617F mutation was a risk factor for overall survival but not for thrombotic events. The application of interferon in older ET patients was not inferior to that of hydroxyurea in terms of efficacy and safety. Older patients presented unique characteristics different from those of younger patients, which could provide new information for formulating more appropriate treatment and follow-up strategies.

Identifying the factors controlling surface water and groundwater chemical characteristics and irrigation suitability in the Yarkant River Basin, northwest China.

This study investigated the geochemical processes and the suitability for irrigation purposes of surface water and groundwater in the Yarkant River Basin, northwest China. The results showed that the surface water was moderately alkaline and neutral to slightly alkaline in the groundwater. The mean values for most ions in the groundwater were higher than those in the surface water. Geochemical method and hydrogen and oxygen isotope revealed that hydrochemical were mainly affected by dissolved evaporite minerals, ion exchange processes, and anthropogenic activities. Still, the geochemical processes of in surface water and groundwater were different. Additionally, three and four factors were extracted by factor analyses of surface water and groundwater, respectively, which distinguished the hydrochemical from natural origins and anthropogenic activities in more detail. The surface water and some groundwater in the south of the study area were suitable for irrigation processes. However, many groundwaters in the north were unsuitable for irrigation, because of their high sodium levels and salinity. The study results provide a theoretical basis for the sustainable utilization of regional water resources.

Machine learning analyses constructed a novel model to predict recurrent thrombosis in adults with essential thrombocythemia.

The current study involving 318 essential thrombocythemia (ET) patients with prior thrombosis was designed to identify risk factors that were predictive of recurrent thrombosis. The whole cohort was randomly split into derivation and validation cohorts. The random forest method, support vector machine with built-in recursive feature elimination model, and logistic multivariable analysis were performed in the derivation cohort, and cardiovascular risk factor (CVF) and RBC distribution width with standard deviation (RDW-SD) were finally selected as independent predictors. Subsequently we devise a 3-tiered model (low risk: 0 points; intermediate risk: 1-1.5 points; and high risk: 2.5 points) and it showed good discrimination in all cohorts. Moreover, the model was significantly correlated with rethrombosis-free survival (rTFS) (p = 0.0007 in the derivation cohort; p = 0.0019 in the validation cohort). In the whole cohort, cytoreductive therapy was more effective than antiplatelet agents alone for 10-year rTFS (p = 0.0336). No significant difference in 10-year rTFS was observed among interferon (IFN), hydroxyurea (HU), and IFN + HU therapy (p = 0.444). The present study helps identify individuals who need close monitoring and provides valuable risk signals for recurrence in ET patients with prior thrombosis.

Early improvements in signs and symptoms predict clinical response to baricitinib in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Early prediction of therapeutic response can optimize treatment strategies in atopic dermatitis (AD). Baricitinib is approved for moderate-to-severe AD in Europe, Japan and other countries. OBJECTIVES: To identify early clinical improvements that can reliably predict a later clinical response to baricitinib in adults with moderate-to-severe AD. METHODS: Using data from one topical corticosteroid combination study [BREEZE-AD7 (NCT03733301)] and data pooled from two monotherapy studies [(BREEZE-AD1 (NCT03334396) and BREEZE-AD2 (NCT03334422)], we calculated the sensitivity and specificity, along with the positive predictive value (PPV) and negative predictive value (NPV), of predefined changes in single and combined clinical scores at weeks 2, 4 and 8, to predict clinical response at week 16. Clinical response was defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI 75), ≥ 4-point improvement in Itch Numeric Rating Scale (Itch NRS ≥ 4), or a combination of both. RESULTS: Composite predictors had higher predictive accuracy for week 16 response outcomes than did single parameters. This was evident as early as week 4 for the combination of EASI 50 or Itch NRS ≥ 3 and of validated Investigator Global Assessment for AD (vIGA-AD) score ≤ 2 or Itch NRS ≥ 3 (sensitivity 87-100%; NPV 68-100%). The predictive accuracy of these composite clinical predictors for week 16 response outcomes was highest at week 8 (sensitivity 92-100%; NPV 80-100%). At both weeks 4 and 8, EASI 50 or Itch NRS ≥ 3 had higher sensitivity and NPV than did vIGA-AD score ≤ 2 or Itch NRS ≥ 3. CONCLUSIONS: Improvement in signs and symptoms early during treatment with baricitinib 4 mg once daily predicts clinical response at week 16, providing a tool for dermatologists when choosing treatment strategies for patients with moderate-to-severe AD.