Evolutionary-scale prediction of atomic-level protein structure with a language model.

Recent advances in machine learning have leveraged evolutionary information in multiple sequence alignments to predict protein structure. We demonstrate direct inference of full atomic-level protein structure from primary sequence using a large language model. As language models of protein sequences are scaled up to 15 billion parameters, an atomic-resolution picture of protein structure emerges in the learned representations. This results in an order-of-magnitude acceleration of high-resolution structure prediction, which enables large-scale structural characterization of metagenomic proteins. We apply this capability to construct the ESM Metagenomic Atlas by predicting structures for >617 million metagenomic protein sequences, including >225 million that are predicted with high confidence, which gives a view into the vast breadth and diversity of natural proteins.

Evaluation of Index of Cardiac Electrophysiological Balance in Patients With Myotonic Dystrophy Type 1.

BACKGROUND: Myotonic dystrophy type 1(MD1), which is characterized by decreased muscle tone, progressive muscle weakness, and cardiac involvement, is an autosomal dominant and progressive congenital muscle disease. Cardiac involvement more often manifests as conduction abnormalities and arrhythmias (such as supraventricular or ventricular). Approximately one-third of MD1-related deaths occur due to cardiac causes. The index of cardiac-electrophysiological balance (ICEB) is a current parameter calculated as QT interval/QRS duration. The increase in this parameter has been associated with malignant ventricular arrhythmias. In this study, our aim was to compare the ICEB values ​​of MD1 patients and the normal population. MATERIAL AND METHOD: A total of 62 patients were included in our study. They were divided into two groups - 32 MD patients and 30 controls. The demographic, clinical, laboratory, and electrocardiographic parameters of the two groups were compared. RESULTS: The median age of the study population was 24 (20-36 IQR), and 36 (58%) of these patients were female. Body mass index was higher in the control group (p = 0.037). While in the MD1 group creatinine kinase was significantly higher (p <0.001), In the control group creatinine, aspartate aminotransferase, alanine aminotransferase, calcium, and lymphocyte levels were significantly higher (p=0.031, p= 0.003, p=0.001, p=0.002, p=0.031, respectively). ICEB [3.96 (3.65-4.46) vs 3.74 (3.49-3.85) p=0.015] and corrected ICEB (ICEBc) [4.48 (4.08-4.92) vs 4.20 (4.03-4.51) p = 0.048] were significantly higher in the MD1 group. CONCLUSION: In our study, ICEB was found to be higher in MD1 patients than in the control group. Increased ICEB and ICEBc values ​​in MD1 patients may precipitate ventricular arrhythmias in the future. Close monitoring of these parameters can be helpful in predicting possible ventricular arrhythmias and in risk stratification.

The effect of coronavirus disease 2019 pneumonia on myocardial ischemia detected by single-photon emission computed tomography myocardial perfusion imaging.

OBJECTIVE: We aimed to examine the effects of COVID-19 pneumonia on cardiac ischemia detected by myocardial perfusion imaging with single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in patients presenting with chest pain and shortness of breath after recovery from COVID-19. MATERIALS AND METHOD: Patients with a history of COVID-19 confirmed by reverse transcriptase-PCR test who underwent SPECT-MPI for the evaluation of ischemia with the complaints of chest pain and shortness of breath were screened for this study. Patients who underwent thorax CT during the acute period of the COVID-19 were included. Patients with and without pneumonia were determined based on computed tomographic criteria. The patients with a summed stress score of at least 4 on SPECT-MPI were considered to have abnormal MPI in terms of ischemia. RESULTS: A total of 266 patients were included in the study. Sixty-five (24%) patients had ischemia findings on SPECT-MPI. Thorax CT showed pneumonia in 152 (57%) patients, and the patients were divided into two groups as pneumonia and nonpneumonia. Abnormal SPECT-MPI scores, which represented myocardial ischemia, were higher in the pneumonia group. Multivariate logistic regression analyses showed that the presence of hyperlipidemia and pneumonia on CT increased the risk of ischemia on SPECT-MPI (OR, 2.08; 95% CI, 1.08-3.99; P-value = 0.029; and OR, 2.90; 95% Cl, 1.52-5.54; P-value = 0.001, respectively). CONCLUSION: COVID-19 pneumonia was identified as an independent predictor of ischemia on SPECT-MPI. Symptoms including chest pain and shortness of breath in patients who have had COVID-19 pneumonia may be attributed to coronary ischemia.

The effect of prior COVID-19 infection on coronary microvascular dysfunction.

BACKGROUND: Thrombolysis in Myocardial Infarction Frame Count (TFC) is an index that provides a quantitative evaluation of coronary microvascular dysfunction. In this study, we aimed to examine the effect of COVID-19 infection on TFC in patients admitted with chest pain and dyspnoea after COVID-19 disease and had abnormal findings in myocardial perfusion scintigraphy. METHODS: For this single-center retrospective study, patients with and without a history of COVID-19 who were underwent coronary angiography for abnormal findings in myocardial perfusion scintigraphy between January 1, 2021 and June 30, 2021 were analysed. Patients were divided into two groups as patients with COVID-19 history and those without. After exclusion criteria, patients with adequate angiographic monitoring and data were included in the study. RESULTS: A total of 210 patients, 48 with a history of COVID-19, were included in the study. The mean age was ±55 10 years, and 122 (58%) patients were women. In patients with a history of COVID-19, TFC was significantly higher in the LAD (p < 0.001) and LCx (p < 0.001) arteries and RCA TFC (p = 0.223) was similar in both groups. In the linear mix model, male gender (ß = 2.38, 95% CI = 1.26-3.51, p < 0.001) and history of COVID-19 (ß = 1.51, 95% CI = 0.49-2.53, p = 0.004) were significantly associated with TFC. CONCLUSION: TFC may be elevated due to coronary microvascular dysfunction in patients with a history of COVID-19.

The relationship of frontal QRS-T angle between patients with newly diagnosed true and white coat hypertension.

OBJECTIVES: The frontal QRS-T (f-QRST) angle is a measure of depolarization and repolarization heterogeneity and may be a predictor of poor ventricular health. We aimed to investigate whether the f-QRST angle indicates myocardial damage and predicts newly diagnosed true hypertension (HT) in patients with white coat hypertension. METHODS: We measured the f-QRST angle of 63 subjects with WHC and 105 patients with newly diagnosed HT. Laboratory tests and ABPM were followed up in all patients. The f-QRST angle was calculated on the surface ECGs. RESULTS: Of the patients in the study, 38.9% were female and 61.1% were male. The mean age was calculated as 59 ± 11 years. A comparison between both groups with the f-QRST angles was seen to be statistically significantly higher in the true HT group. The results of the receiving operating characteristic curve showed that the AUC value of the f-QRST angle was 0.94 (95% confidence interval, 0.91-0.97), the cutoff value was 60.5°, the sensitivity was 89.5%, and the specificity was 81%. CONCLUSION: In our study, the f-QRST angle was found to be lower in patients with WHC than in true hypertensive patients. We think that ECG, which is a simple test, can be used to distinguish between true HT and WHC.

The relationship between mean platelet volume and resistant hypertension.

OBJECTIVE: Resistant hypertension (RH) is associated with an increased risk of cardiovascular events.Mean platelet volume (MPV) has been shown to indicate platelet activation and is associated with increased cardiovascular disease risk. In our study, we aimed to evaluate the relationship between mean platelet volume and resistant hypertension. METHOD: A total of 279 patientswere included in our study and divided into three groups (GroupI: seventy-eight patients with resistant hypertension, group II: seventy-nine patients with controlled hypertension and group III: one-hundred-five patients without hypertension). Routine laboratory tests and ambulatory blood pressure measurement (ABPM) were followed up in all patients. RESULTS: Of the patients in the study, 25% were female while 75% were male, and the mean age was 56.5 ± 11.8 years. The mean MPV values were found to be 9.34 ± 1.49 fL in the RHT group, 8.82 ± 0.83 fLin the controlled HT group, and 8.5 ± 0.85 fL in the normotensive individuals, and there was a significant correlation between the RHT group and the other groups (RHT versus controlled HT p1 = 0.008, RHT versus normotensive individuals p2 < 0,001). When we compared controlled HT and normotensive individuals, no significant relationship was found between MPV values (p3 = 0,157). CONCLUSION: The MPV value was found to be higher in resistant hypertensive patients compared to controlled hypertensive and normotensive patients. MPV values can be used to predict adverse cardiovascular events in RHT patients.

Relationship between frontal QRS-T duration and the severity of coronary artery disease in who were non-diabetic and had stable angina pectoris.

OBJECTIVE: There is a known relationship between frontal-QRS-T (F-QRS-T) angle and coronary artery disease (CAD). This study examined the relationship between F-QRS-T angle changes and CAD severity in patients with stable CAD. METHODS: A total of 202 patients were included in the study after the implementation of exclusion criteria among 894 patients, who were admitted to the outpatient clinic with stable angina pectoris between September 2018 and September 2019. The F-QRS-T angle calculated on the 12-lead electrocardiograms (ECGs) of the patients (taken in the outpatient clinic), and the CAD severity calculated using the Gensini score in patients undergoing coronary angiography were compared. RESULTS: Of the patients included in the study, 38.6% were female and 61.4% were male. The mean age was calculated as 60.16±11.27 years, and 52% of the patients had hypertension. There was no difference between the groups in terms of demographic and clinical values. In a comparison of CAD severity and F-QRS-T angles, the F-QRS-T angle was seen to be statistically significantly higher in the severe CAD group [91°° (102/79)] compared to the group with mild CAD [53°° (64/38)]. In the multivariate logistic regression analysis, there was a significant association between the F-QRS-T angle (odds ratio=1.09, 95% confidence interval=1.06-1.11, p<0.001) and CAD severity. CONCLUSION: It seems that CAD severity in patients who were non-diabetic and had stable angina pectoris is associated with the F-QRS-T angle.

The effect of idiopathic premature ventricular complexes on left ventricular ejection fraction.

AIM: Current literature lacks a definitive threshold of idiopathic premature ventricular complex (PVC) burden for predicting cardiomyopathy (CMP). The main objective of the present study was to evaluate relationship between the PVC burden and left ventricular ejection fraction (LVEF). METHOD: This multicenter, cross-sectional study included 341 consecutive patients with more than 1,000 idiopathic PVC in 24 hr of Holter monitoring admitted to the cardiology clinics between January 2019 and May 2019 in the nineteen different centers. The primary outcome was the LVEF measured during the echocardiographic examination. RESULT: Overall, the median age was 50 (38-60) and 139 (49.4%) were female. Percentage of median PVC burden was 9% (IQR: 4%-17.4%). Median LVEF was found 60% (55-65). We used proportional odds logistic regression method to examine the relationship between continuous LVEF and candidate predictors. Increase in PVC burden (%) (regression coefficient (RE) -0.644 and 95% CI -1.063, -0.225, p < .001), PVC QRS duration (RE-0.191 and 95% CI -0.529, 0.148, p = .049), and age (RE-0.249 and 95% CI -0.442, -0.056, p = .018) were associated with decrease in LVEF. This inverse relationship between the PVC burden and LVEF become more prominent when PVC burden was above 5%. A nomogram developed to estimate the individual risk for decrease in LVEF. CONCLUSION: Our study showed that increase in PVC burden %, age, and PVC QRS duration were independently associated with decrease in LVEF in patients with idiopathic PVC. Also, inverse relationship between PVC burden and LVEF was observed in lower PVC burden than previously known.