Atmospheric drought dominates changes in global water use efficiency.

Water use efficiency (defined as the ratio of gross primary productivity to plant transpiration, WUET) describes the tradeoff between ecosystem carbon uptake and water loss. However, a comprehensive understanding of the impact of soil and atmospheric moisture deficits on WUET across large regions remains incomplete. Solar-induced chlorophyll fluorescence (SIF) serves as an effective signal for measuring both terrestrial vegetation photosynthesis and transpiration, thereby enabling a rapid response to changes in the physiological status of plants under water stress. The objectives of this study were to: 1) mechanistically calculate WUET using top-of-canopy SIF data and meteorological information by using the revised mechanistic light response model and the Penman-Monteith equation; 2) analyze the effects of atmospheric and soil water deficits on SIF-based WUET by using decoupled soil water content (SWC) and vapor pressure deficit (VPD); 3) evaluate estimated SIF-based WUET against data from 28 eddy covariance (EC) flux sites representing eight different vegetation types. Results indicated that the model performed well in ecosystems with dense canopies, explaining 56 % of the daily variability in EC tower-based WUET. For the years 2019-2020, the global average WUET derived from SIF was 3.49 g C/kg H2O. Notably, this value exceeded 4 g C/kg H2O in tropical rainforest regions near the equator and went beyond 5 g C/kg H2O in the high-latitude regions of the Northern Hemisphere. We found that SIF-based WUET was primarily influenced by VPD rather than SWC in over 90 % of the global vegetated area. The model used in this study increased our ability to mechanistically estimate WUET with SIF at the global scale, thereby highlighting the significance of the global response of SIF-based WUET to water stress, and also enhancing our understanding of the water­carbon cycle in terrestrial ecosystems.

A Three-in-One Hybrid Strategy for High-Performance Semiconducting Polymers Processed from Anisole.

The development of semiconducting polymers with good processability in green solvents and competitive electrical performance is essential for realizing sustainable large-scale manufacturing and commercialization of organic electronics. A major obstacle is the processability-performance dichotomy that is dictated by the lack of ideal building blocks with balanced polarity, solubility, electronic structures, and molecular conformation. Herein, through the integration of donor, quinoid and acceptor units, an unprecedented building block, namely TQBT, is introduced for constructing a serial of conjugated polymers. The TQBT, distinct in non-symmetric structure and high dipole moment, imparts enhanced solubility in anisole-a green solvent-to the polymer TQBT-T. Furthermore, PTQBT-T possess a highly rigid and planar backbone owing to the nearly coplanar geometry and quinoidal nature of TQBT, resulting in strong aggregation in solution and localized aggregates in film. Remarkably, PTQBT-T films spuncast from anisole exhibit a hole mobility of 2.30 cm2 V-1 s-1, which is record high for green solvent-processable semiconducting polymers via spin-coating, together with commendable operational and storage stability. The hybrid building block emerges as a pioneering electroactive unit, shedding light on future design strategies in high-performance semiconducting polymers compatible with green processing and marking a significant stride towards ecofriendly organic electronics.

Retraction of "Universal theranostic CRISPR/Cas13a RNA-editing system for glioma".

[This retracts the article DOI: 10.7150/thno.84429.].

A Novel Induction-Type Pressure Sensor based on Magneto-Stress Impedance and Magnetoelastic Coupling Effect for Monitoring Hand Rehabilitation.

Visualization of training effectiveness is critical to patients' confidence and eventual rehabilitation. Here, an innovative magnetoinductive pressure sensor is proposed for monitoring hand rehabilitation in stroke hemiplegic patients. It couples the giant magneto and stress-impedance effects of a square spiral amorphous wire with the giant magnetoelastic effect of a polymer magnet (NdFeB@PDMS). The addition of the magnetoelastic layer results in a sensitivity improvement of 178%, a wide sensing range (up to 1 MPa), fast response/recovery times (40 ms), and excellent mechanical robustness (over 15 000 cycles). Further integration with an LC oscillation circuit enables frequency adjustment into the MHz range resulting in a sensitivity of 6.6% kPa-1 and outstanding linearity (R2 =  0.99717) over a stress range of up to 100 kPa. When attached to a commercial split-fingerboard, the sensor is capable of dynamically monitoring the force in each finger, providing a reading of the rehabilitation process. Unlike conventional inductive sensors, the sensor is based on an inductive force-responsive material (amorphous wire), which significantly boosts the sensitivity. The approach also demonstrates the potential of magnetoelasticity in static pressure sensing, which is highly sensitive to dynamic pressure only through electromagnetic induction. This makes it more suitable for long-term and continuous human health monitoring.

Synthesis of a Novel P/N-Triazine-Containing Ring Flame Retardant and Its Application in Epoxy Resin.

To meet the environmental protection and flame retardancy requirements for epoxy resins (EPs) in certain fields, in this study, a novel triazine-ring-containing DOPO-derived compound (VDPD), derived from vanillin, 2,4-Diamino-6-phenyl-1,3,5-triazine, and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO), was synthesized using a one-pot method. Flame-retardant epoxy resin (FREP) was prepared by adding various ratios of VDPD to EP and curing with 4,4-diaminodiphenylmethane (DDM). The curing behavior, thermal stability, mechanical properties, and flame-retardant properties of the FREP were examined in various tests. According to the results, when the amount of VDPD added to the EP increased, the glass transition temperature of the FREP decreased linearly, and the flame-retardant properties gradually improved. With a 0.4 wt.% P content, the vertical burning rating of EP/DDM/VDPD-0.4 (according to the theoretical content of VDPD) reached the V-0 level, and the LOI value reached 33.1%. In addition, the results of a CCT showed that the peak heat release rate (PHRR) of EP/DDM/VDPD-0.4 decreased by 32% in comparison with that of the EP. Furthermore, compared with those of the EP, the tensile strength of EP/DDM/VDPD-0.4 decreased from 80.2 MPa to 74.3 MPa, only decreasing by 6 MPa, and the tensile modulus increased. Overall, VDPD can maintain the mechanical properties of EP and effectively improve its flame-retardant properties.

Understanding the role of DNA methylation in colorectal cancer: Mechanisms, detection, and clinical significance.

Colorectal cancer (CRC) is one of the deadliest malignancies worldwide, ranking third in incidence and second in mortality. Remarkably, early stage localized CRC has a 5-year survival rate of over 90%; in stark contrast, the corresponding 5-year survival rate for metastatic CRC (mCRC) is only 14%. Compounding this problem is the staggering lack of effective therapeutic strategies. Beyond genetic mutations, which have been identified as critical instigators of CRC initiation and progression, the importance of epigenetic modifications, particularly DNA methylation (DNAm), cannot be underestimated, given that DNAm can be used for diagnosis, treatment monitoring and prognostic evaluation. This review addresses the intricate mechanisms governing aberrant DNAm in CRC and its profound impact on critical oncogenic pathways. In addition, a comprehensive review of the various techniques used to detect DNAm alterations in CRC is provided, along with an exploration of the clinical utility of cancer-specific DNAm alterations.

Outcomes for pembrolizumab stratified by pemetrexed maintenance post pembrolizumab-platinum-pemetrexed induction in metastatic non-small-cell lung cancer.

Aim: We assessed treatment patterns and outcomes in patients with metastatic nonsquamous non-small-cell lung cancer (mNSCLC) who initiated first-line pembrolizumab-platinum-pemetrexed (induction) in US community oncology settings. Methods: Patients initiating induction were retrospectively identified. Patients continuing pembrolizumab afterward underwent chart review. Clinical outcomes were described by maintenance pemetrexed exposure after inverse probability of treatment weighting (IPTW). Results: Median induction pembrolizumab and pemetrexed durations were 5.1 and 4.2 months. Among patients continuing pembrolizumab after induction, 64% received maintenance pemetrexed. Common discontinuation reasons for induction pemetrexed were completion of planned therapy (79%) and partial response (68%) and progressive disease (38%) and toxicity (29%) for maintenance pemetrexed. After IPTW, median overall survival and real-world progression-free survival were longer in patients continuing pembrolizumab with versus without maintenance pemetrexed (20.3 vs 12.0 months and 10.3 vs 5.8 months, respectively). Conclusion: Patient characteristics and planned treatment decisions affect maintenance pemetrexed utilization in the community oncology setting.

What is this summary about? Pembrolizumab is a drug that helps the lung cancer patient's immune system fight the cancer, even after the cancer has spread, or metastasized. After the patient gets better, the patient is treated with chemotherapy so the cancer will not come back. This is called 'maintenance treatment'. In KEYNOTE-189, a clinical trial, patients lived longer if they had pembrolizumab added to pemetrexed and platinum, which are chemotherapy drugs. If patients had maintenance treatment with pembrolizumab and pemetrexed, they also lived longer. However, do patients in community practices get those treatments? What were the results? We found that at cancer practices in the community instead of clinical trials, not all patients received pemetrexed in maintenance treatment. Many had finished their planned therapy and their tumors had shrunk. Also, some physicians chose not to give their patients pemetrexed. In addition, some women and some older and sicker patients did not get pemetrexed. Some patients had pemetrexed in maintenance but stopped because their cancer grew worse or because they had side effects. Those patients did not live as long as patients who did have maintenance pemetrexed. What do the results mean? Patients with metastatic non-small-cell lung cancer in the community practice do better on the treatments tested in clinical trials. However, certain patients do not get those treatments. The reasons need to be understood, to make sure that those patients get better treatments.

Effect of Continuous Positive Airway Pressure on Blood Pressure in Patients with Resistant Hypertension and Obstructive Sleep Apnea: An Updated Meta-analysis.

PURPOSE OF REVIEW: The effect of continuous positive airway pressure (CPAP) on resistant hypertension in patients at high risk with obstructive sleep apnea (OSA) needs further investigation. We aimed to determine the effect of CPAP on blood pressure in patients with resistant hypertension and OSA. Databases including PubMed, EMBASE, MEDLINE, the Cochrane Library, and CMB were searched. Data were pooled using a random-effects or fixed-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals (CIs). RECENT FINDINGS: A total of 12 trials and 718 participants were included. Compared with control, CPAP significantly reduced 24-h systolic blood pressure (SBP) (WMD: - 5.92 mmHg [ - 8.72, - 3.11]; P＜0.001), 24-h diastolic blood pressure (DBP) (WMD: - 4.44 mmHg [- 6.26 , - 2.62]; P ＜0.001),  daytime SBP (WMD: - 5.76 mmHg [ - 9.16, - 2.36]; P ＜0.001),  daytime DBP (WMD: - 3.92 mmHg [- 5.55, - 2.30];  nighttime SBP (WMD: - 4.87 mmHg [ - 7.96 , - 1.78]; P = 0.002), and nighttime DBP (WMD: - 2.05 mmHg [- 2.99, - 1.11]; P＜0.001) in patients with resistant hypertension and OSA. CPAP improved the blood pressure both in the short (＜3 months) and long term (≥ 3 months). No significant impact on mean heart rate was noted (WMD: -2.76 beats per min [- 7.50, 1.97]; P = 0.25). CPAP treatment was associated with BP reduction in patients with resistant hypertension and OSA.

Modulating Thermal Conductivity and Flame Retardancy of Polyolefin Composites via Distributed Structures of Magnesium Hydroxide and Hexagonal Boron Nitride.

Thermally conductive and flame-retardant polyolefin composites are facing great challenges in meeting the increasing demands for fire safety and thermal management. Aiming at simultaneously enhancing thermal conductivity and flame retardancy, hexagonal boron nitride (hBN) and magnesium hydroxide (MH) were adopted in ethylene-vinyl acetate copolymer/polyolefin elastomer (EVA/POE) blends to design composites with selective filler distributions and co-continuous networks via different processing schemes. The thermal conductivity and flame retardancy show strong dependence on the distributed structure of hBN and MH. The composites with hBN-rich centers and MH-rich edges in the filled POE phase show a thermal conductivity of 0.70 W/(m·K) and an LOI of 27.7%, which are very close to the thermal conductivity of EVA/POE/hBN and the LOI of EVA/POE/MH at the same total filler content. The composites with MH-rich centers and hBN-rich edges show pHRR, THR and TSP values of 169 kW/m2, 49.8 MJ/m2 and 1.8 m2, which are decreased by 40%, 33% and 62% in comparison with EVA/POE/MH, respectively. Modulating the filler structure distribution provides a strategy to co-enhance thermal conductivity and flame retardancy.

T-cell count and T-cell telomere length in patients with severe COVID-19.

Lymphocyte telomere length (TL) is highly variable and shortens with age. Short telomeres may impede TL-dependent T-cell clonal expansion with viral infection. As SARS-CoV-2 infection can induce prolonged and severe T-cell lymphopenia, infected adults, and particularly older adults with short telomeres, may display severe T-cell lymphopenia. To examine the relationship between T-cell TL parameters and T-cell counts, we studied 40 patients hospitalized with severe COVID-19. T-cells were isolated from lymphocytes, counted using flow cytometry, and their TL parameters were measured using the Telomere Shortest Length Assay. The cohort (median age = 62 years, 27% female) was racially and ethnically diverse (33% White, 35% Black, and 33% Other). On intensive care unit study day 1, T-cell count (mean=1.03 x109/L) was inversely related to age (p=0.007) and higher in females than males (p=0.025). Mean TL was 3.88 kilobases (kb), and 45.3% of telomeres were shorter than 3 kb. Using multiple regression analysis and adjusting for age and sex, T-cell count decreased with increased proportion of T-cell telomeres shorter than 3 kb (p=0.033) and increased with mean TL (p=0.052). Our findings suggest an association between the buildup of short telomeres within T-cells and explain in part reduced peripheral blood T-cell counts in patients with severe COVID-19. Shortened T-cell telomeres may be a risk factor for COVID-19-associated T-cell lymphopenia.

EPIC-0628 abrogates HOTAIR/EZH2 interaction and enhances the temozolomide efficacy via promoting ATF3 expression and inhibiting DNA damage repair in glioblastoma.

The efficacy of temozolomide (TMZ) treatment in glioblastoma (GBM) is influenced by various mechanisms, mainly including the level of O6-methylguanine-DNA methyltransferase (MGMT) and the activity of DNA damage repair (DDR) pathways. In our previous study, we had proved that long non-coding RNA HOTAIR regulated the GBM progression and mediated DDR by interacting with EZH2, the catalytic subunit of PRC2. In this study, we developed a small-molecule inhibitor called EPIC-0628 that selectively disrupted the HOTAIR-EZH2 interaction and promoted ATF3 expression. The upregulation of ATF3 inhibited the recruitment of p300, p-p65, p-Stat3 and SP1 to the MGMT promoter. Hence, EPIC-0628 silenced MGMT expression. Besides, EPIC-0628 induced cell cycle arrest by increasing the expression of CDKN1A and impaired DNA double-strand break repair via suppressing the ATF3-p38-E2F1 pathway. Lastly, EPIC-0628 enhanced TMZ efficacy in GBM in vitro and vivo. Hence, this study provided evidence for the combination of epigenetic drugs EPIC-0628 with TMZ for GBM treatment through the above mechanisms.

The Global Prevalence of Methicillin-Resistant Staphylococcus Aureus in Patients with Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis.

Objective: Diabetic foot ulcer (DFU) frequently leads to infections, with infected DFUs being a common cause of amputation. Infection by methicillin-resistant Staphylococcus aureus (MRSA) notably increases the necessity for amputation and surgical debridement in affected individuals. Consequently, determining the prevalence and trends of MRSA in patients with DFU is of critical importance. This study aimed to assess the global prevalence and to identify trends in the occurrence of MRSA in tissue or wound swab samples from DFU patients. Methods: We conducted a comprehensive literature search across PubMed, Embase, Scopus, and Ovid, spanning from the inception of these databases to July 2023, imposing no language restrictions. The inclusion criteria required that the studies report on 30 or more patients with DFU. Additionally, we categorized our analysis based on geographic region, publication date, and the economic status of the patient's domicile. Our primary endpoint was to ascertain the prevalence of MRSA in DFUs. This systematic review has been registered at (https://www.crd.york.ac.uk/prospero/), with the identifier CRD 42023444360. Results: Our analysis encompassed 40 studies involving 12,924 patients across 20 countries. We found that the overall prevalence of MRSA in DFU was 17% (95% Confidence Interval [CI] 0.14-0.20). Regional prevalence varied significantly: in South America, it was 61% (95% CI 0.46-0.76), in North America 20% (95% CI 0.12-0.27), in Europe 19% (95% CI 0.14-0.25), in Africa 13% (95% CI 0.06-0.20), and in other subgroups 11% (95% CI 0.08-0.15). The prevalence of MRSA in DFUs also differed according to the economic status of the countries: 19% (95% CI 0.15-0.23) in high-income countries, 24% (95% CI 0.1-0.37) in upper-middle-income countries, 11% (95% CI 0.07-0.15) in lower-middle-income countries, and 20% (95% CI 0.13-0.27) in low-income countries. Notably, there has been a decline in MRSA prevalence, from 25% before 2010 to 9% thereafter. Conclusion: This meta-analysis reveals a decreasing yet still significant global prevalence of MRSA in DFUs. This trend has important implications for antimicrobial resistance and underscores the need for developing targeted programs focusing on infection prevention and exploring alternative therapeutic strategies.

Altered spontaneous neurological activity in methamphetamine use disorders and its association with cognitive function.

BACKGROUND: Methamphetamine (MA) is a widely used and detrimental drug, yet the precise mechanisms by which MA affects cognitive function remain unclear. This study aims to investigate the relationship between cognitive function and brain functional imaging in individuals with MA use disorder (MUD). METHODS: This study involved 45 patients diagnosed with MUD and 43 healthy controls (HC). Cognitive function assessment utilized the MATRICS Consensus Cognitive Battery, and functional data were acquired using a 3.0 Tesla magnetic resonance imaging scanner. RESULTS: The MUD group exhibited lower regional homogeneity (ReHo) values in the bilateral postcentral, the left superior temporal, and the left lingual regions compared to the HC group. Additionally, the MUD group displayed higher amplitude of low-frequency fluctuation (ALFF) values in the bilateral fusiform and the left putamen compared to the HC group, along with lower ALFF values in the bilateral postcentral cortices and the left middle cingulate cortex compared to the HC group (all p < 0.05, with false discovery rate corrected). Linear regression analysis revealed a positive correlation between the ReHo value in the right postcentral cortex and the neuropsychology assessment battery-mazes test (p = 0.014). Furthermore, the ALFF value in the left putamen showed negative correlations with the scores of the digit-symbol coding test (p = 0.027), continuous performance test (p = 0.037), and battery-mazes test (p = 0.024). CONCLUSION: Patients with MUD exhibit altered brain spontaneous neurological activities, and the intensity of spontaneous neurological activity in the left putamen is strongly associated with cognitive function.

Developing Folate-Conjugated miR-34a Therapeutic for Prostate Cancer: Challenges and Promises.

Prostate cancer (PCa) remains a common cancer with high mortality in men due to its heterogeneity and the emergence of drug resistance. A critical factor contributing to its lethality is the presence of prostate cancer stem cells (PCSCs), which can self-renew, long-term propagate tumors, and mediate treatment resistance. MicroRNA-34a (miR-34a) has shown promise as an anti-PCSC therapeutic by targeting critical molecules involved in cancer stem cell (CSC) survival and functions. Despite extensive efforts, the development of miR-34a therapeutics still faces challenges, including non-specific delivery and delivery-associated toxicity. One emerging delivery approach is ligand-mediated conjugation, aiming to achieve specific delivery of miR-34a to cancer cells, thereby enhancing efficacy while minimizing toxicity. Folate-conjugated miR-34a (folate-miR-34a) has demonstrated promising anti-tumor efficacy in breast and lung cancers by targeting folate receptor α (FOLR1). Here, we first show that miR-34a, a TP53 transcriptional target, is reduced in PCa that harbors TP53 loss or mutations and that miR-34a mimic, when transfected into PCa cells, downregulated multiple miR-34a targets and inhibited cell growth. When exploring the therapeutic potential of folate-miR-34a, we found that folate-miR-34a exhibited impressive inhibitory effects on breast, ovarian, and cervical cancer cells but showed minimal effects on and targeted delivery to PCa cells due to a lack of appreciable expression of FOLR1 in PCa cells. Folate-miR-34a also did not display any apparent effect on PCa cells expressing prostate-specific membrane antigen (PMSA) despite the reported folate's binding capability to PSMA. These results highlight challenges in the specific delivery of folate-miR-34a to PCa due to a lack of target (receptor) expression. Our study offers novel insights into the challenges and promises within the field and casts light on the development of ligand-conjugated miR-34a therapeutics for PCa.

Enhanced Thermal Stability and Broad Temperature Range in High-Entropy (La0.2Ce0.2Nd0.2Sm0.2Eu0.2)NbO4 Ceramics.

Next-generation high-temperature applications increasingly rely heavily on advanced thermistor materials with enhanced thermal stability and electrical performance. However, thus far, the great challenge of realizing high thermal stability and precision in a wide temperature range has become a key bottleneck restricting the high-temperature application. Here, we propose a high-entropy strategy to design novel high-temperature thermistor ceramics (La0.2Ce0.2Nd0.2Sm0.2Eu0.2)NbO4. Differences in atomic size, mass, and electronegativity in this high-entropy system cause high lattice distortion, substantial grain boundaries, and high dislocation density. These enhance the charge carrier transport and reduce the grain boundary resistance, thus synergistically broadening the temperature range. Our samples maintain high precision and thermal stability over a wide temperature range from room temperature to 1523 K (ΔT = 1250 K) with an aging value as low as 0.42% after 1000 h at 1173 K, showing breakthrough progress in high-temperature thermistor ceramics. This study establishes an effective approach to enhancing the performance of high-temperature thermistor materials through high-entropy strategies.

Real-world comparative effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer.

Aim: Provide real-world data on palbociclib as evidence of effectiveness in patient populations from routine clinical practice. Methods: This was a retrospective, observational cohort study of patients with HR+/HER2- metastatic breast cancer treated with palbociclib plus aromatase inhibitor (AI) or AI alone as first-line therapy within the US Oncology Network. Results: Patients treated with palbociclib plus AI (n = 838) versus AI alone (n = 450) had a numerically longer median overall survival (42.1 vs 35.7 months; hazard ratio [HR] = 0.90 [95% CI: 0.75-1.07]; p = 0.117) and a significantly extended real-world progression-free survival (21.0 vs 15.7 months; HR = 0.75 [95% CI: 0.64-0.88]; p = 0.0002) after normalized inverse probability treatment weighting. Conclusion: These real-world results support the use of palbociclib plus AI as first-line treatment in routine clinical practice for patients with HR+/HER2- metastatic breast cancer.

What is this summary about? This summary describes how well palbociclib works when used with an aromatase inhibitor in the real-world setting for people with a certain type of breast cancer that has spread to other areas of the body. Palbociclib stops cancer cells from growing and dividing. An aromatase inhibitor prevents the body from making the hormone estrogen, which is needed for certain types of breast cancer cells to grow. Palbociclib with an aromatase inhibitor is a standard first treatment used for people with this type of breast cancer that needs estrogen to grow and has spread to other areas of the body. In clinics, doctors may not always prescribe the two treatments together. The study wanted to find out if using the two treatments together worked better than using an aromatase inhibitor alone in the real-world setting. What were the results? The results suggest that in this population of patients treated in a real-world setting, people with breast cancer that needs estrogen to grow and has spread to other areas of the body who were treated with palbociclib plus an aromatase inhibitor lived longer without their cancer getting worse than those treated with an aromatase inhibitor alone. What do the results of the study mean? The results support the use of palbociclib with an aromatase inhibitor as a first treatment for breast cancer that has spread to other areas of the body, rather than an aromatase inhibitor only.

A comparative study of synthetic and venous hematocrit for calculating cardiovascular magnetic resonance-derived extracellular volume.

The extracellular volume (ECV) fraction derived from cardiac magnetic resonance (CMR) can reflect various pathologies. The application of ECVs was limited by the strict requirement that hematocrit (Hct0) should be obtained within 24 hours of CMR scan. The aim of this study was to obtain accurate and convenient ECV calculated from the venous Hct and synthetic Hct in CMR. A total of 839 subjects were retrospectively enrolled. The subjects were divided into derivation cohort for local sex-specific models and validation cohort for assessing the accuracy of different ECVs. In the validation cohort, venous Hcts from 7 days before the scan (Hct1 - 7), outside 7 days (Hct> 7), the closest day (Hctclosest), and Hctsyn were compared with Hct0. The agreement and correlation of the conventional ECV (ECV0) with the corresponding ECVs were analyzed. The factors affecting the accuracy of ECVsyn were assessed. ECV1-7 and ECVclosest had the best correlation and smallest bias with ECV0 (R = 0.959 and 0.951, bias = 0.02% and - 0.03%). When using an absolute 2% error as the standard, the performance of ECV1-7 was the best, with an accuracy of 81.0%, followed by ECVclosest (78.8%), ECV> 7 (77.2%) and ECVsyn (70.7%). Abnormally low and high Hcts and decreased left ventricular ejection fractions were associated with miscalculation of ECVsyn, especially patients with dilated cardiomyopathy. We recommend extending the time interval between a Hct and a CMR scan to 7 days for ECV calculation. The synthetic ECV should be used cautiously, especially for patients with extremely low or high Hcts, decreased cardiac function, and dilated cardiomyopathy.

RUNX1/NPM1/H3K4me3 complex contributes to extracellular matrix remodeling via enhancing FOSL2 transcriptional activation in glioblastoma.

Extracellular matrix (ECM) remodeling has been implicated in the tumor malignant progression and immune escape in glioblastoma (GBM). Runt-related transcription factor 1 (RUNX1) is a vital transcriptional factor for promoting tumorigenesis and invasion in mesenchymal subtype of GBM. But the correlation between RUNX1 and ECM genes expression and regulatory mechanism of RUNX1 on ECM genes expression remain poorly understood to date. In this study, by using integral analysis of chromatin immunoprecipitation-sequencing and RNA sequencing, we reported that RUNX1 positively regulated the expression of various ECM-related genes, including Fibronectin 1 (FN1), Collagen type IV alpha 1 chain (COL4A1), and Lumican (LUM), in GBM. Mechanistically, we demonstrated that RUNX1 interacted with Nucleophosmin 1 (NPM1) to maintain the chromatin accessibility and facilitate FOS Like 2, AP-1 Transcription Factor Subunit (FOSL2)-mediated transcriptional activation of ECM-related genes, which was independent of RUNX1's transcriptional function. ECM remodeling driven by RUNX1 promoted immunosuppressive microenvironment in GBM. In conclusion, this study provides a novel mechanism of RUNX1 binding to NPM1 in driving the ECM remodeling and GBM progression.

Real-world Effectiveness of Azacitidine in Treatment-Naive Patients With Higher-risk Myelodysplastic Syndromes.

INTRODUCTION: Azacitidine (AZA) is an approved frontline therapy for higher-risk myelodysplastic syndromes (HR-MDS); however, poor survival denotes unmet needs to increase depth/duration of response (DOR). METHODS: This retrospective study with patient chart review evaluated AZA effectiveness in 382 treatment-naive patients with HR-MDS from a US electronic health record (EHR)-derived database. Responses were assessed using International Working Group (IWG) 2006 criteria; real-world equivalents were derived from EHRs. Primary endpoint was IWG 2006-based complete remission rate (CRR). Secondary endpoints were EHR-based CRR, IWG 2006- and EHR-based objective response rates (ORRs), duration of CR, DOR, progression-free survival, time-to-next-treatment, and overall survival (OS). RESULTS: Using IWG 2006 criteria, the CRR was 7.9% (n = 30); median duration of CR was 12.0 months (95% CI, 7.7-15.6). In poor cytogenetic risk (n = 101) and TP53 mutation (n = 46) subgroups, CRRs were 7.9% (n = 8) and 8.7% (n = 4), respectively. ORR was 62.8% (n = 240), including a hematologic improvement rate (HIR) of 46.9% (n = 179). Using EHR-based data, CRR was 3.7% (n = 14); median duration of CR was 13.5 months (95% CI, 4.5-21.5). ORR was 67.8% (n = 259), including an HIR of 29.3% (n = 112). Median follow-up was 12.9 months; median OS was 17.9 months (95% CI, 15.5-21.7). CONCLUSIONS: Consistent with other studies, CRRs and median OS with AZA in treatment-naive patients with HR-MDS were low in this large, real-world cohort. Novel agents/combinations are urgently needed to improve these outcomes in HR-MDS.