MYC Protein Interactome Profiling Reveals Functionally Distinct Regions that Cooperate to Drive Tumorigenesis.

Transforming members of the MYC family (MYC, MYCL1, and MYCN) encode transcription factors containing six highly conserved regions, termed MYC homology boxes (MBs). By conducting proteomic profiling of the MB interactomes, we demonstrate that half of the MYC interactors require one or more MBs for binding. Comprehensive phenotypic analyses reveal that two MBs, MB0 and MBII, are universally required for transformation. MBII mediates interactions with acetyltransferase-containing complexes, enabling histone acetylation, and is essential for MYC-dependent tumor initiation. By contrast, MB0 mediates interactions with transcription elongation factors via direct binding to the general transcription factor TFIIF. MB0 is dispensable for tumor initiation but is a major accelerator of tumor growth. Notably, the full transforming activity of MYC can be restored by co-expression of the non-transforming MB0 and MBII deletion proteins, indicating that these two regions confer separate molecular functions, both of which are required for oncogenic MYC activity.

Segregation, immunohistochemical, molecular and functional analyses classify a novel missense variant in fumarate hydratase (FH) as pathogenic.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant cancer predisposition syndrome characterized by cutaneous leiomyomas, uterine leiomyomas, and aggressive renal cancer. Germline variants in the fumarate hydratase (FH) gene predispose to HLRCC. Identifying germline pathogenic FH variants enables lifetime renal cancer screening and genetic testing for family members. In this report, we present a FH missense variant (c.1039T>C (p.S347P)), initially classified as a variant of uncertain significance. Clinical assessment, histopathological findings, molecular genetic studies, and enzymatic activity studies support the re-classification of the FH c.1039T>C variant to "pathogenic" based on ACMG/AMP criteria. Further insights into pathological recognition of FH-deficient renal cancer are discussed and should be recognized. This study has shown how (a) detailed multi-disciplinary analyses of a single variant can reclassify rare missense variants in FH and (b) careful pathological review of renal cancers is obligatory when HLRCC is suspected.

Discovery of a novel class of rosmarinic acid derivatives as antibacterial agents: Synthesis, structure-activity relationship and mechanism of action.

Twenty-seven rosmarinic acid derivatives were synthesized, among which compound RA-N8 exhibited the most potent antibacterial ability. The minimum inhibition concentration of RA-N8 against both S. aureus (ATCC 29213) and MRSA (ATCC BAA41 and ATCC 43300) was found to be 6 µg/mL, and RA-N8 killed E. coli (ATCC 25922) at 3 µg/mL in the presence of polymyxin B nonapeptide (PMBN) which increased the permeability of E. coli. RA-N8 exhibited a weak hemolytic effect at the minimum inhibitory concentration. SYTOX Green assay, SEM, and LIVE/DEAD fluorescence staining assay proved that the mode of action of RA-N8 is targeting bacterial cell membranes. Furthermore, no resistance in wildtype S. aureus developed after incubation with RA-N8 for 20 passages. Cytotoxicity studies further demonstrated that RA-N8 is non-toxic to the human normal cell line (HFF1). RA-N8 also exerted potent inhibitory ability against biofilm formation of S. aureus and even collapsed the shaped biofilm.

The structural dynamics of full-length divisome transmembrane proteins FtsQ, FtsB, and FtsL in FtsQBL complex formation.

FtsQBL is a transmembrane protein complex in the divisome of Escherichia coli that plays a critical role in regulating cell division. Although extensive efforts have been made to investigate the interactions between the three involved proteins, FtsQ, FtsB, and FtsL, the detailed interaction mechanism is still poorly understood. In this study, we used hydrogen-deuterium exchange mass spectrometry to investigate these full-length proteins and their complexes. We also dissected the structural dynamic changes and the related binding interfaces within the complexes. Our data revealed that FtsB and FtsL interact at both the periplasmic and transmembrane regions to form a stable complex. Furthermore, the periplasmic region of FtsB underwent significant conformational changes. With the help of computational modeling, our results suggest that FtsBL complexation may bring the respective constriction control domains (CCDs) in close proximity. We show that when FtsBL adopts a coiled-coil structure, the CCDs are fixed at a vertical position relative to the membrane surface; thus, this conformational change may be essential for FtsBL's interaction with other divisome proteins. In the FtsQBL complex, intriguingly, we show only FtsB interacts with FtsQ at its C-terminal region, which stiffens a large area of the ß-domain of FtsQ. Consistent with this, we found the connection between the α- and ß-domains in FtsQ is also strengthened in the complex. Overall, the present study provides important experimental evidence detailing the local interactions between the full-length FtsB, FtsL, and FtsQ protein, as well as valuable insights into the roles of FtsQBL complexation in regulating divisome activity.

Endoscopic submucosal dissection for colorectal polyps: outcome determining factors.

BACKGROUND: Endoscopic submucosal dissection (ESD) has gained increasing popularity in the management of complicated colorectal polyps. However, clinical outcomes for ESD have remained highly inconsistent worldwide. This study investigated and analysed factors that significantly affect ESD outcomes. METHODS: We conducted a single-centred retrospective study on 220 colorectal polyps removed by ESD from 1st January 2016 to 31st December 2020. Data were collected and retrieved from clinical records. Variables studied included patient demographics, ESD technicalities and polyp characteristics. The primary outcome was completeness of resection based on en bloc and R0 resection rates. The secondary outcomes were recurrence, complications and hospital stay. Further analysis was performed for significant outcome determining factors. RESULTS: The en bloc resection and R0 resection rates were 97.3% and 65% respectively. Intraprocedural and delayed perforation rates were 3.2% and 0.5% respectively. Intraprocedural and delayed bleeding rates were both 1.8%. Post-polypectomy syndrome rate was 2.7%. The median hospital stay was 4 days. Submucosal fibrosis was a significant determining factor for lower en bloc resection (p = 0.004), lower R0 resection (p = 0.002), intraprocedural perforation (p = 0.001), intraprocedural bleeding (p = 0.025) and post-polypectomy syndrome (p = 0.039). Hybrid snaring was associated with lower en bloc resection (p < 0.001), while longer ESD time was associated with lower R0 resection (p = 0.003) and post-polypectomy syndrome (p = 0.025). Other significant factors for post-polypectomy syndrome included young age (p = 0.021) and large polyp size (p = 0.018). Secondary analysis showed that submucosal fibrosis was significantly associated with non-granular lesions (p < 0.001) and prior biopsy (p = 0.003). CONCLUSION: Submucosal fibrosis, hybrid snaring, ESD time, age and polyp size were significant outcome determining factors for ESD. By identifying these factors, strategies may be formulated to improve ESD outcomes.

Interpretable ensemble imbalance learning strategies for the risk assessment of severe-low-level wind shear based on LiDAR and PIREPs.

The occurrence of severe low-level wind shear (S-LLWS) events in the vicinity of airport runways poses a significant threat to flight safety and exacerbates a burgeoning problem in civil aviation. Identifying the risk factors that contribute to occurrences of S-LLWS can facilitate the improvement of aviation safety. Despite the significant influence of S-LLWS on aviation safety, its occurrence is relatively infrequent in comparison to non-SLLWS incidents. In this study, we develop an S-LLWS risk prediction model through the utilization of ensemble imbalance learning (EIL) strategies, namely, BalanceCascade, EasyEnsemble, and RUSBoost. The data for this study were obtained from PIREPs and LiDAR at Hong Kong International Airport. The analysis revealed that the BalanceCascade strategy outperforms EasyEnsemble and RUSBoost in terms of prediction performance. Afterward, the SHapley Additive exPlanations (SHAP) interpretation tool was used in conjunction with the BalanceCascade model for the risk assessment of various factors. The four most influential risk factors, according to the SHAP interpretation tool, were hourly temperature, runway 25LD, runway 25LA, and RWY (encounter location of LLWS). S-LLWS was likely to happen at Runway 25LD and Runway 25LA in temperatures ranging from low to moderate. Similarly, a high proportion of S-LLWS events occurred near the runway threshold, and a relatively small proportion occurred away from it. The EIL strategies in conjunction with the SHAP interpretation tool may accurately predict the S-LLWS without the need for data augmentation in the data pre-processing phase.

Design of a 0.5 V Chopper-Stabilized Differential Difference Amplifier for Analog Signal Processing Applications.

This paper presents a low-voltage low-power chopper-stabilized differential difference amplifier (DDA) realized using 40 nm CMOS technology. Operating with a supply voltage of 0.5 V, a three-stage DDA has been employed to achieve an open-loop gain of 89 dB, while consuming just 0.74 µW of power. The proposed DDA incorporates feed-forward frequency compensation and a Type II compensator to achieve pole-zero cancellation and damping factor control. The DDA has a unity-gain bandwidth (UGB) of 170 kHz, a phase margin (PM) of 63.98°, and a common-mode rejection ratio (CMRR) of up to 100 dB. This circuit can effectively drive a 50 pF capacitor in parallel with a 300 kΩ resistor. The use of the chopper stabilization technique effectively mitigates the offset and 1/f noise. The chopping frequency of the chopper modulator is 5 kHz. The input noise is 245 nV/sqrt (Hz) at 1 kHz, and the input-referred offset under Monte Carlo cases is only 0.26 mV. Such a low-voltage chopper-stabilized DDA will be very useful for analog signal processing applications. Compared to the reported chopper DDA counterparts, the proposed DDA is regarded as that with one of the lowest supply voltages. The proposed DDA has demonstrated its effectiveness in tradeoff design when dealing with multiple parameters pertaining to power consumption, noise, and bandwidth.

Value of liver biopsy in anorexia nervosa-related transaminitis: A case study and literature review.

Anorexia nervosa (AN) is a complex eating disorder that affects multiple organs. 60% of patients have liver injury with transaminitis. The mechanism of liver injury in AN remains unclear. We present a case of a 19-year-old female with AN was admitted to our hospital with marked transaminitis but near normal liver histology on biopsy. Her transaminitis eventually improved as she regained weight. We also conducted a literature review of similar cases to delineate the clinicopathologic spectrum of liver injury in AN patients. English published cases of adult AN patients with elevated transaminases who underwent a liver biopsy or autopsy were selected. 32 cases (including ours). All except four patients were female, with median age of 26.5 years and median body mass index 11.9 kg/m2 . Presentations mainly included hypoglycemic coma and weight loss. 63% of patients had severe transaminitis (AST >15x ULN). Other lab findings included elevated international normalized ratio (72%) and hypoalbuminemia (47%). Microscopically, all cases showed intact hepatic architecture. Fibrosis was reported in 12 cases and necroinflamfmation in 8, but only half of each had severe transaminitis. AN patients display a wide spectrum of liver histopathology which often does not correlate with the degree of transaminitis. In severe persistent AN-related transaminitis, liver biopsy is useful to assess the degree of liver injury and to exclude other potential etiologies.

Impact of the COVID-19 on the vertical distributions of major pollutants from a tower in the Pearl River Delta.

The outbreak of the 2019 novel coronavirus (COVID-19) had a large impact on human health and socio-economics worldwide. The lockdown implemented in China beginning from January 23, 2020 led to sharp reductions in human activities and associated emissions. The declines in primary pollution provided a unique opportunity to examine the relationship between anthropogenic emissions and air quality. This study reports on air pollutant and meteorological measurements at different heights from a tall tower in the Pearl River Delta. These measurements were used to investigate the vertical scale response of pollutants to understand reductions in human activities. Compared to that in the pre-lockdown period (from December 16, 2019), the concentrations of surface layer nitric oxide (NOx), fine particulate matter (PM2.5), and daily maximum 8 h average ozone (MDA8O3) declined significantly during the lockdown by 76.8%, 49.4%, and 18.6%, respectively. Although the vertical profiles of NOx and O3 changed during the lockdown period, those of PM2.5 remained the same. During the lockdown period, there were statistically significant correlations between PM2.5 and O3 but not between PM2.5 and NOx at four heights, indicating that the main composition of PM2.5 have dramatically changed, during which the impact of NOx on PM2.5 became insignificant. Additionally, O3 concentrations were also insensitive to NOx concentrations during the lockdown, implying that O3 levels were more of a representative of regional background level. In this case, local photochemical formation is no longer a significant ozone source. This evidence suggests that it is possible to mitigation of PM2.5 and O3 levels simultaneously by significant reductions in anthropogenic emissions.

Design of Precision-Aware Subthreshold-Based MOSFET Voltage Reference.

A new precision-aware subthreshold-based MOSFET voltage reference is presented in this paper. The circuit was implemented TSMC-40 nm process technology. It consumed 9.6 µW at the supply voltage of 1.2 V. In this proposed work, by utilizing subthreshold-based MOSFET instead of bipolar junction transistor (BJT), relatively lower power consumption was obtained in the design while offering comparable precision to that offered by its BJT counterpart. Through the proposed second-order compensation, it achieved the temperature coefficient (T.C.) of 3.0 ppm/°C in the TT corner case and a 200-sample Monte-Carlo T.C. of 12.51 ppm/°C from -40 °C to 90 °C. This shows robust temperature insensitivity. The process sensitivity of Vref without and with trimming was 2.85% and 0.75%, respectively. The power supply rejection (PSR) was 71.65 dB at 100 Hz and 52.54 dB at 10 MHz. The Figure-of-Merit (FOM) for the total variation in output voltage was comparable with representative BJT circuits and better than subthreshold-based MOSFET circuits. Due to low T.C., low process sensitivity, and simplicity of the circuit architecture, the proposed work will be useful for sensor circuits with stringent requirements or other analog circuits that require high precision applications.

Probable cross-corridor transmission of SARS-CoV-2 due to cross airflows and its control.

A COVID-19 outbreak occurred in May 2020 in a public housing building in Hong Kong - Luk Chuen House, located in Lek Yuen Estate. The horizontal cluster linked to the index case' flat (flat 812) remains to be explained. Computational fluid dynamics simulations were conducted to obtain the wind-pressure coefficients of each external opening on the eighth floor of the building. The data were then used in a multi-zone airflow model to estimate the airflow rate and aerosol concentration in the flats and corridors on that floor. Apart from flat 812 and corridors, the virus-laden aerosol concentrations in flats 811, 813, 815, 817 and 819 (opposite to flat 812, across the corridor) were the highest on the eighth floor. When the doors of flats 813 and 817 were opened by 20%, the hourly-averaged aerosol concentrations in these two flats were at least four times as high as those in flats 811, 815 and 819 during the index case's home hours or the suspected exposure period of secondary cases. Thus, the flats across the corridor that were immediately downstream from flat 812 were at the highest exposure risk under a prevailing easterly wind, especially when their doors or windows that connected to the corridor were open. Given that the floorplan and dimension of Luk Chuen House are similar to those of many hotels, our findings provide a probable explanation for COVID-19 outbreaks in quarantine hotels. Positive pressure and sufficient ventilation in the corridor would help to minimise such cross-corridor infections.

A CMOS PSR Enhancer with 87.3 mV PVT-Insensitive Dropout Voltage for Sensor Circuits.

A new power supply rejection (PSR) based enhancer with small and stable dropout voltage is presented in this work. It is implemented using TSMC-40 nm process technology and powered by 1.2 V supply voltage. A number of circuit techniques are proposed in this work. These include the temperature compensation for Level-Shifted Flipped Voltage Follower (LSFVF) and the Complementary-To-Absolute Temperature (CTAT) current reference. The typical output voltage and dropout voltage of the enhancer is 1.1127 V and 87.3 mV, respectively. The Monte-Carlo simulation of this output voltage yields a mean T.C. of 29.4 ppm/°C from -20 °C and 80 °C. Besides, the dropout voltage has been verified with good immunity against Process, Temperature and Process (PVT) variation through the worst-case simulation. Consuming only 4.75 µA, the circuit can drive load up to 500 µA to yield additional PSR improvement of 36 dB and 20 dB of PSR at 1 Hz and 1 MHz, respectively for the sensor circuit of interest. This is demonstrated through the application of an enhancer on the instrumentation Differential Difference Amplifier (DDA) for sensing floating bridge sensor signal. The comparative Monte-Carlo simulation results on a respective DDA circuit have revealed that the process sensitivity of output voltage of this work has achieved 14 times reduction in transient metrics with respect to that of the conventional counterpart over the operation temperature range in typical operation condition. Due to simplicity without voltage reference and operational amplifier(s), low power and small consumption of supply voltage headroom, the proposed work is very useful for supply noise sensitive analog or sensor circuit applications.

On the Use of Dynamic Calibration to Correct Drop Counter Rain Gauge Measurements.

Dynamic calibration was performed in the laboratory on two catching-type drop counter rain gauges manufactured as high-sensitivity and fast response instruments by Ogawa Seiki Co. Ltd. (Japan) and the Chilbolton Rutherford Appleton Laboratory (UK). Adjustment procedures were developed to meet the recommendations of the World Meteorological Organization (WMO) for rainfall intensity measurements at the one-minute time resolution. A dynamic calibration curve was derived for each instrument to provide the drop volume variation as a function of the measured drop releasing frequency. The trueness of measurements was improved using a post-processing adjustment algorithm and made compatible with the WMO recommended maximum admissible error. The impact of dynamic calibration on the rainfall amount measured in the field at the annual and the event scale was calculated for instruments operating at two experimental sites. The rainfall climatology at the site is found to be crucial in determining the magnitude of the measurement bias, with a predominant overestimation at the low to intermediate rainfall intensity range.

Dual challenges of heat wave and protective facemask-induced thermal stress in Hong Kong.

During the COVID-19 pandemic, wearing protective facemasks (PFMs) can effectively reduce infection risk, but the use of PFMs can amplify heat-related health risks. We studied the amplified PFM-induced human thermal stress via both field measurements and model simulations over a typical subtropical mountainous city, Hong Kong. First, a hot and humid PFM microenvironment has been observed with high temperature (34-35 °C) and high humidity (80-95%), resulting in an aggravated facial thermal stress with a maximal PFM-covered facial heat flux of 500 W/m2 under high-intensity activities. Second, to predict the overall PFM-inclusive human thermal stress, we developed a new facial thermal load model, S PFM and a new human-environment adaptive thermal stress (HEATS) model by coupling S PFM with an enhanced thermal comfort model to resolve modified human-environment interactions with the intervention of PFM under realistic climatic and topographical conditions. The model was then applied to predict spatiotemporal variations of PFM-inclusive physiological subjective temperature (PST) and corresponding heat stress levels during a typical heat wave event. It was found wearing PFM can significantly aggravate human thermal stress over Hong Kong with a spatially averaged PST increment of 5.0 °C and an additional spatial area of 158.4% exposed to the severest heat risks. Besides, PFM-inclusive PST was found to increase nonlinearly with terrain slopes at a rate of 1.3-3.9 °C/10°(slope), owing to elevated metabolic heat production. Furthermore, urban residents were found to have higher PFM-aggravated heat risks than rural residents, especially at night due to synergistic urban heat and moisture island effects.

Synchronized abdominal compression as a novel treatment of life-threatening preschool asthma.

Introduction: In severe asthma, management of life-threatening air trapping that persists despite initiation of standard asthma treatment is difficult in the absence of extracorporeal membranous oxygenation.Case study: Three children with life-threatening asthma could not be adequately ventilated despite maximum conventional treatment because of severe air trapping. A novel method of active expiration by abdominal compression with a standard ventilator was adopted with immediate effect with significant improvement in ventilation.Conclusion: Synchronized abdominal compression is a novel and simple method that allows an effective treatment of severe air trapping in an intubated paralyzed asthma child.

Review on colorectal endoscopic submucosal dissection focusing on the technical aspect.

BACKGROUND: Endoscopic submucosal dissection (ESD) enables removal of broad-based colorectal polyps or lateral spreading tumors with a higher rate of en bloc resection and a lower risk of local recurrence. However, it is technically demanding. Over the past 20 years, various equipment and innovative techniques have been developed to reduce the difficulty of ESD. The information in the literature is scattered. Our aim is to provide a comprehensive review on the setup and technical aspects of colorectal ESD. METHODS: We searched the PubMed database and systemically reviewed all original and review articles related to colorectal ESD. Further manual search according to reference lists of identified articles were done. The selected articles were categorized and reviewed. Original figures were created to help readers understand some of the ESD techniques. RESULTS: A total of 216 articles were identified, in which 25 of them were review articles and 191 of them were original articles. They were categorized and reviewed. An in-depth appraisal of the setting, equipment, and technical aspects of colorectal ESD was performed. CONCLUSIONS: Although ESD is a technically demanding procedure that requires expert endoscopic skills, it can be mastered. With good peri-procedural preparation, sufficient knowledge of the equipment, and thorough understanding of the useful endoscopic tricks and maneuvers, colorectal ESD can be performed smoothly and safely.

Close contact behavior in indoor environment and transmission of respiratory infection.

Close contact was first identified as the primary route of transmission for most respiratory infections in the early 20th century. In this review, we synthesize the existing understanding of the mechanisms of close contact transmission. We focus on two issues: the mechanism of transmission in close contact, namely the transmission of the expired particles between two people, and the physical parameters of close contact that affect the exposure of particles from one individual to another, or how the nature of close contact plays a role in transmission. We propose the existence of three sub-routes of transmission: short-range airborne, large droplets, and immediate body-surface contact. We also distinguish a "body contact," which is defined with an interpersonal distance of zero, from a close contact. We demonstrate herein that the short-range airborne sub-route may be most common. The timescales over which data should be collected to assess the transmission risk during close contact events are much shorter than those required for the distant airborne or fomite routes. The current paucity of high-resolution data over short distances and timescales makes it very difficult to assess the risk of infection in these circumstances.

Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention of Recurrent Cardiovascular Events in a Real-World Cohort of Post-Acute Myocardial Infarction Patients.

BACKGROUND: Patients who survive myocardial infarction (MI) are at risk of recurrent cardiovascular (CV) events. This study stratified post-MI patients for risk of recurrent CV events using the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P). Methods and Results: This was an observational study that applied TRS 2°P to a consecutive cohort of post-MI patients. The primary outcome was a composite endpoint of CV death, non-fatal MI, and non-fatal ischemic stroke. A total of 1,688 post-MI patients (70.3±13.6 years; male, 63.1%) were enrolled. After a mean follow-up of 41.5±34.4 months, 405 patients (24.0%) had developed a primary outcome (9.3%/year) consisting of 278 CV deaths, 134 non-fatal MI, and 33 non-fatal strokes. TRS 2°P was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P 0 was 1.0%, and increased progressively to 39.9% for those with TRS 2°P ≥6 (HR, 27.6; 95% CI: 9.87-77.39, P<0.001). The diagnostic sensitivity of TRS 2°P for the primary composite endpoint was 76.3% (95% CI: 72.1-80.5%). Similar associations were also observed between TRS 2°P and CV death and non-fatal MI, but not non-fatal ischemic stroke. CONCLUSIONS: TRS 2°P reliably stratified post-MI patients for risk of future CV events.

Prognostic implications of statin intolerance in stable coronary artery disease patients with different levels of high-sensitive troponin.

BACKGROUND: The prognostic implication of statin in tolerance (SI) in those with stable CAD remains unclear. We hypothesized that SI is of higher prognostic significance in stable CAD patients with elevated high-sensitive cardiac troponin I (hs-cTnI). METHODS: A total of 952 stable CAD patients from the prospective Hong Kong CAD study who had complete clinical data, biomarker measurements and who were prescribed statin therapy were studied. RESULTS: We identified 13 (1.4%) and 125 (13.1%) patients with complete and partial SI, respectively. At baseline, patients with SI were more likely to have diabetes mellitus and a higher hs-cTnI level, but no difference in LDL-C level compared with those without SI. After 51 months of follow-up, patients with SI had a higher mean LDL-C level than those without SI. A total of 148 (15.5%) patients developed major adverse cardiovascular events (MACEs). Both SI (HR 1.52, 95% CI 1.06-2.19, P = 0.02) and elevated hs-cTnI (HR 3.18, 95% CI 2.07-4.89, P < 0.01) were independent predictors of a MACE in patients with stable CAD. When stratified by hs-cTnI level, SI independently predicted MACE-free survival only in those with elevated hs-cTnI (HR 1.51, 95% CI 1.01-2.24, P = 0.04). CONCLUSIONS: SI independently predicted MACE in patients with stable CAD and high hs-cTnI, but not in those with low hs-cTnI. Hs-cTnI may be used to stratify stable CAD patients who have SI for intensive lipid-lowering therapy using non-statin agents.

TIMI risk score for secondary prevention of recurrent cardiovascular events in a real-world cohort of post-non-ST-elevation myocardial infarction patients.

BACKGROUND: Patients who survive non-ST-elevation myocardial infarction (NSTEMI) are at heightened risk of recurrent cardiovascular events. Data on long-term secondary atherothrombotic risk stratification are limited. OBJECTIVES: To stratify post-NSTEMI patients for risk of recurrent cardiovascular events to maximise benefit from aggressive secondary prevention strategies using the TIMI Risk Score for Secondary Prevention (TRS 2°P) score in a real-world cohort of NSTEMI patients. METHODS AND RESULTS: This was a single-centre observational study of 891 post-NSTEMI patients (73.7 ± 12.7 years; male: 54.2%). The TRS 2°P is a nine-point risk stratification tool to predict cardiovascular events in patients with established cardiovascular disease. The primary outcome was a composite endpoint of cardiovascular death, non-fatal MI and non-fatal ischaemic stroke. After a median follow-up of 31 months (IQR: 11.4 - 60.2), 281 patients (31.5%) had developed a primary outcome (13.3%/year) including 196 cardiovascular deaths, 94 non-fatal MIs and 22 non-fatal strokes. The TRS 2°P score was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P score =0 was 1.6%, and increased progressively to 47.4% for those with a TRS 2°P score ≥6 (HR: 20.18, 95% CI: 4.85 to 84.05, p<0.001). Similar associations were also observed between the TRS 2°P score and cardiovascular death and MI (fatal and non-fatal), but not non-fatal ischaemic stroke. CONCLUSION: The TRS 2°P score stratified post-NSTEMI patients for risk of future cardiovascular events and potentially help guide the selection of more aggressive secondary prevention therapy.