Searching low-energy conformers of neutral and protonated di-, tri-, and tetra-glycine using first-principles accuracy assisted by the use of neural network potentials.

In the last ten years, combinations of state-of-the-art gas-phase spectroscopies and quantum chemistry calculations have suggested several intuitive trends in the structure of small polypeptides that may not hold true. For example, the preference for the cis form of the peptide bond and multiple protonated sites was proposed by comparing experimental spectra with low-energy minima obtained from limited structural sampling using various density functional theory methods. For understanding the structures of polypeptides, extensive sampling of their configurational space with high-accuracy computational methods is required. In this work, we demonstrated the use of deep-learning neural network potential (DL-NNP) to assist in exploring the structure and energy landscape of di-, tri-, and tetra-glycine with the accuracy of high-level quantum chemistry methods, and low-energy conformers of small polypeptides can be efficiently located. We hope that the structures of these polypeptides we found and our preliminary analysis will stimulate further experimental investigations.

A first-principles exploration of the conformational space of sodiated di-saccharides assisted by semi-empirical methods and neural network potentials.

Previous exploration of the conformational space of sodiated mono-saccharides using a random search algorithm leads to ∼103 structurally distinct conformers covering an energy range of ∼150 kJ mol-1. Thus, it is reasonable to expect that the number of distinct conformers for a given disaccharide would be on the order of 106. Efficient identification of distinct conformers at the first-principles level has been demonstrated with the assistance of neural network potential (NNP) with an accuracy of ∼1 kJ mol-1 compared to DFT. Leveraging a local minima database of neutral and sodiated glucose (Glc), we develop algorithms to systematically explore the conformation landscape of 19 Glc-based sodiated disaccharides. To accelerate the exploration, the NNP method is implemented. The NNP achieves an accuracy of ∼2.3 kJ mol-1 compared to DFT, offering a comparable quality to that of DFT. Through a multi-model approach integrating DFTB3, NNP and DFT, we can rapidly locate low-energy disaccharide conformers at the first-principles level. The methodology we show here can be used to efficiently explore the potential energy landscape of any di-saccharides when first-principles accuracy is required.

Validity and Reliability of Point-of-Care Ultrasound for Detecting Moderate- or High-Grade Carotid Atherosclerosis in an Outpatient Department.

The prevalence of carotid stenosis is considerably higher in asymptomatic individuals with multiple risk factors than in the general population. We investigated the validity and reliability of carotid point-of-care ultrasound (POCUS) for rapid carotid atherosclerosis screening. We prospectively enrolled asymptomatic individuals with carotid risk scores of ≥7 who underwent outpatient carotid POCUS and laboratory carotid sonography. Their simplified carotid plaque scores (sCPSs) and Handa's carotid plaque scores (hCPSs) were compared. Of 60 patients (median age, 81.9 years), 50% were diagnosed as having moderate- or high-grade carotid atherosclerosis. The overestimation and underestimation of outpatient sCPSs were more likely in patients with low and high laboratory-derived sCPSs, respectively. Bland-Altman plots indicated that the mean differences between the participants' outpatients and laboratory sCPSs were within two standard deviations of their laboratory sCPSs. A Spearman's rank correlation coefficient revealed a strong positive linear correlation between outpatient and laboratory sCPSs (r = 0.956, p < 0.001). An intraclass correlation coefficient analysis indicated excellent reliability between the two methods (0.954). Both carotid risk score and sCPS were positively and linearly correlated with laboratory hCPS. Our findings indicate that POCUS has satisfactory agreement, strong correlation, and excellent reliability with laboratory carotid sonography, making it suitable for rapid screening of carotid atherosclerosis in high-risk patients.

Structures of (Pyrazine)2 and (Pyrazine)(Benzene) Dimers Investigated with Infrared-Vacuum Ultraviolet Spectroscopy and Quantum-Chemical Calculations: Competition among π-π, CH···π, and CH···N Interactions.

The structures of a pyrazine dimer (pyrazine)2 and (pyrazine)(benzene) hetero-dimer cooled in a supersonic beam were investigated by the measurement of the infrared spectra in the C-H stretching region with infrared-vacuum ultraviolet (IR-VUV) spectroscopy and quantum-chemical calculations. The stabilization energy calculation at the CCSD(T)/aug-cc-pVTZ level of theory predicted three isomers for (pyrazine)2 and three for (pyrazine)(benzene) with energy within 6 kJ/mol. Among them, the cross-displaced π-π stacked structure is the most stable in both dimers. In the observed IR spectra, both dimers exhibited two intense bands near 3065 cm-1, with intervals of 8 cm-1 in (pyrazine)2 and 11 cm-1 in (pyrazine)(benzene), while only one band appeared in the monomer. For (pyrazine)(benzene), we also measured the IR spectrum of (pyrazine)(benzene-d6), where the interval of the two bands was unchanged. The analysis of the observed IR spectra with anharmonic calculations suggested the coexistence of three isomers of (pyrazine)2 and (pyrazine)(benzene) in a supersonic jet. For (pyrazine)2, the two isomers which were previously assigned to the H-bonded planar and the π-π stacked structures respectively were reassigned to the cross-displaced π-π stacked and T-shaped structures, respectively. In addition, the quantum chemical calculation and IR-VUV spectral measurement suggested the coexistence of the H-bonded planar isomer in the jet. For (pyrazine)(benzene), the IR spectrum of the (pyrazine) site showed a similar spectral pattern to that of (pyrazine)2, especially the split at ∼3065 cm-1. However, the anharmonic analysis suggested that they are assigned to the different vibrational motions of (pyrazine). The anharmonic vibrational analysis is essential to associate the observed IR spectra with the correct structures of the dimer.

A first-principles exploration of the conformational space of sodiated pyranose assisted by neural network potentials.

Sampling the conformational space of monosaccharides using the first-principles methods is important and as a database of local minima provides a solid base for interpreting experimental measurements such as infrared photo-dissociation (IRPD) spectroscopy or collision-induced dissociation (CID). IRPD emphasizes low-energy conformers and CID can distinguish conformers with distinct reaction pathways. A typical computational approach is to engage empirical or semi-empirical methods to sample the conformational space first, and only selected minima are reoptimized at first-principles levels. In this work, we propose a computational scheme to explore the configurational space of 12 types of sodiated pyranoses with the assistance of a neural network potential (NNP). We demonstrated that it is possible to train an NNP based on the density functional calculations extracted from a previous study on sodiated glucose (Glc), galactose (Gal), and mannose (Man). This NNP yields a better description of the other five types of aldohexoses than the four types of ketohexoses. We further show that such a discrepancy in the accuracy of NNP can be resolved by an active learning scheme where the NNP model is engaged in generating the data and has itself updated. Through this iterative process, we can locate more than 17 000 distinct local minima at the B3LYP/6-311+G(d,p) level and an NNP with an accuracy of 1 kJ mol-1 was created, which can be used for further studies.

Capturing the potential energy landscape of large size molecular clusters from atomic interactions up to a 4-body system using deep learning.

Exploring the structure and properties of molecular clusters with accuracy using the ab initio methods is a resource intensive task due to the increasing cost of the ab initio methods and the number of distinct conformers as the size increases. The energy landscape of methanol clusters has been previously explored using computationally efficient empirical models to collect a database of structurally distinct minima, followed by re-optimization using ab initio methods. In this work, we propose a new method that utilizes the database of stable conformers and borrow the fragmentation concept of many-body-expansion (MBE) methods in ab initio methods to train a deep-learning machine learning (ML) model using SchNet. Picking 684 local minima of (CH3OH)5 to (CH3OH)8 from the existing database, we can generate ∼51 000 data points of one-body, two-body, three-body and four-body molecular systems to train an ML model to reach a mean absolute error (MAE) of 3.19 kJ mol-1 (in energy) and 2.48 kJ mol-1 Å-1 (in forces) tested against ab initio calculations up to (CH3OH)14. This ML model is then used to create a database of low energy isomers of (CH3OH)n (n = 15-20). The proposed scheme can be applied to other hydrogen bonded molecular clusters with an accuracy of first-principles methods and computational speed of empirical force-fields.

Collision-induced dissociation of Na+-tagged ketohexoses: experimental and computational studies on fructose.

Collision-induced dissociation tandem mass spectrometry (CID-MSn) and computational investigation at the MP2/6-311+G(d,p) level of theory have been employed to study Na+-tagged fructose, an example of a ketohexose featuring four cyclic isomers: α-fructofuranose (αFruf), ß-fructofuranose (ßFruf), α-fructopyranose (αFrup), and ß-fructopyranose (ßFrup). The four isomers can be separated by high-performance liquid chromatography (HPLC) and they show different mass spectra, indicating that CID-MSn can distinguish the different fructose forms. Based on a simulation using a micro-kinetic model, we have obtained an overview of the mechanisms for the different dissociation pathways. It has been demonstrated that the preference for the C-C cleavage over the competing isomerization of linear fructose is the main reason for the previously reported differences between the CID-MS spectra of aldohexoses and ketohexoses. In addition, the kinetic modeling helped to confirm the assignment of the different measured mass spectra to the different fructose isomers. The previously reported assignment based on the peak intensities in the HPLC chromatogram had left some open questions as the preference for the dehydration channels did not always follow trends previously observed for aldohexoses. Setting up the kinetic model further enabled us to directly compare the computational and experimental results, which indicated that the model can reproduce most trends in the differences between the dissociation pathways of the four cyclic fructose isomers.

Levels and patterns of physical activity and sedentary behavior in adults with and without visual impairment.

BACKGROUND: Limited data are available on objectively measured physical activity (PA) and sedentary behavior (SB) among adults with and without visual impairment (VI). OBJECTIVE: To compare PA and SB levels and patterns in adults with and without VI and to examine how these differ based on sex and day of the week. METHODS: Thirty-two participants with VI and 32 participants without VI participated in this cross-sectional study. PA and SB were assessed using GT3X ActiGraph accelerometers during waking hours for 7 days, and variables were examined in terms of disability group, sex, and day of the week. Nonparametric Mann-Whitney U test and Wilcoxon signed-rank test were used, and significance was set at p < 0.05. RESULTS: PA did not differ in terms of sex or day of the week in participants with VI. The PA of participants without VI was significantly higher for men than it was for women and was significantly higher during weekdays than on weekend days. Total sedentary time and the duration of SB breaks were significantly longer for female participants with VI than for those without VI. The number of sedentary bouts lasting ≥10 min during weekend days was significantly higher for participants with VI than for those without VI. CONCLUSIONS: Most adults with and without VI did not meet the recommended levels of daily PA and spend a large portion of the day being sedentary. Interventions to enhance PA and reduce sedentary time in adults with and without VI are required.

Guided growth versus varus osteotomy for type II avascular necrosis following surgery for developmental dysplasia of the hip.

AIMS: The aim of this study was to compare outcomes of guided growth and varus osteotomy in treating Kalamchi type II avascular necrosis (AVN) after open reduction and Pemberton acetabuloplasty for developmental dysplasia of the hip (DDH). METHODS: This retrospective study reviewed patients undergoing guided growth or varus osteotomy for Kalamchi type II AVN between September 2009 and January 2019. All children who had undergone open reduction and Pemberton acetabuloplasty for DDH with a minimum two-year follow-up were enrolled in the study. Demographic and radiological data, which included the head-shaft angle (HSA), neck-shaft angle (NSA), articulotrochanteric distance (ATD), Sharp angle (SA), and lateral centre-edge angle (LCEA) at baseline, two years, and at the extended follow-up, were compared. Revision rates were evaluated. Clinical outcomes using the Harris Hip Score were assessed two years postoperatively. RESULTS: A total of 24 patients underwent guided growth and 19 underwent varus osteotomy, over a mean period of 3.3 years (95% confidence interval (CI) 2.8 to 3.8) and 5.2 years (95% CI 4.5 to 6.0), respectively. There were no differences in demographic and preoperative radiological data, except for a younger age at time of acetabuloplasty and larger ATD for the osteotomy group. The HSA did not differ at two years and the extended follow-up because of postoperative rebound in the osteotomy group. The NSA of the osteotomy group remained smaller postoperatively. There were no significant differences in the follow-up ATD, SA, and LCEA, except for a smaller two-year ATD of the osteotomy group. Seven patients (29.2%) in the guided growth group underwent revision surgery and none in the osteotomy group. The Harris Hip Score was similar between groups. CONCLUSION: Guided growth and varus osteotomy had comparable results in improving caput valgum deformity, given the rebound of lateral tilting of the physis after osteotomy correction. There were no differences in clinical outcomes at two years postoperatively. Cite this article: Bone Joint J 2022;104-B(7):902-908.

Nomogram and Carotid Risk Score for Predicting Moderate or High Carotid Atherosclerosis among Asymptomatic Elderly Recycling Volunteers.

Carotid atherosclerosis is associated with cardiovascular and cerebrovascular events. We explored an appropriate method for selecting participants without ischemic cerebrovascular disease but with various comorbidities eligible for a carotid ultrasound. This was a retrospective subgroup analysis of the carotid plaque burden from a previous study involving a vascular and cognitive survey of 956 elderly recycling volunteers (778 women and 178 men; mean age: 70.8 years). We used carotid ultrasound to detect the carotid plaque and computed the carotid plaque score (CPS). A moderate or high degree of carotid atherosclerosis (MHCA) was defined as CPS > 5 and was observed in 22% of the participants. The CPS had positive linear correlations with age, systolic blood pressure, and fasting glucose. We stratified the participants into four age groups: 60−69, 70−74, 75−79, and ≥80 years. Multivariable analysis revealed that significant predictors for MHCA were age, male sex, hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, and a nonvegetarian diet. Coronary artery disease and advanced age were the two strongest predictors. We chose the aforementioned seven significant predictors to establish a nomogram for MHCA prediction. The area under the receiver operating characteristic curve in internal validation with 10-fold cross-validation and the classification accuracy of the nomogram were 0.785 and 0.797, respectively. We presumed people who have a ≥50% probability of MHCA warranted a carotid ultrasound. A flowchart table derived from the nomogram addressing the probabilities of all models of combinations of comorbidities was established to identify participants who had a probability of MHCA ≥ 50% (corresponding to a total nomogram score of ≥15 points). We further established a carotid risk score range from 0 to 17 comprising the seven predictors. A carotid risk score ≥ 7 was the most optimal cutoff value associated with a probability of MHCA ≥ 50%. Both total nomogram score ≥ 15 points and carotid risk score ≥ 7 can help in the rapid identification of individuals without stroke but who have a ≥50% probability of MHCA­these individuals should schedule a carotid ultrasound.

Infrared spectroscopy and theoretical structure analyses of protonated fluoroalcohol clusters: the impact of fluorination on the hydrogen bond networks.

To explore the impact of fluorination on the hydrogen bond networks of protonated alkylalcohols, infrared spectroscopy and theoretical computations of protonated 2,2,2-trifluoroethanol clusters, H+(TFE)n, (n = 4-7), were performed. It has been demonstrated that the development of the hydrogen bond networks from a linear type to cyclic types occurs in this size region for the protonated alkylalcohol clusters. In contrast, infrared spectroscopy of H+(TFE)n in the OH/CH stretch region clearly indicated that the linear type structures are held in the whole size range, irrespective of temperature of the clusters. The extensive stable isomer structure search of H+(TFE)n based on our latest sampling approach supported the strong preference of the linear type hydrogen bond networks. Detailed analyses of the free OH stretching vibrational bands evidenced the intra- and intermolecular OH⋯FC interactions in the clusters. In addition, infrared spectra of protonated clusters of 2,2-difluoroethanol, 2,2-difluoropropanol, and 3,3,3-trifluoropropanol were measured for n = 4 and 5, and their spectra also indicated the effective inhibition of the cyclic hydrogen bond network formation by the fluorination.

Correlation of Immune-Inflammatory Markers with Clinical Features and Novel Location-Specific Nomograms for Short-Term Outcomes in Patients with Intracerebral Hemorrhage.

(1) Background: We investigated the association of four immune-inflammatory markers with clinical features and established location-specific nomograms to predict mortality risk in patients with intracerebral hemorrhage (ICH). (2) Methods: We retrospectively enrolled 613 inpatients with acute ICH. (3) Results: Overall mortality was 22%, which was highest in pontine hemorrhage and lowest in thalamic hemorrhage. All four immune-inflammatory markers exhibited a positive linear correlation with glucose, ICH volume, ICH score, and discharge Modified Rankin Scale (mRS) score. Significant predictors of death due to lobar/putaminal hemorrhage were age, glucose and creatinine levels, initial Glasgow Coma Scale (GCS) score, ICH volume, and presence of intraventricular hemorrhage. None of the immune-inflammatory markers were significant predictors of unfavorable outcome or death. We selected significant factors to establish nomograms for predicting death due to lobar/putaminal, thalamic, pontine, and cerebellar hemorrhages. The C-statistic for predicting death in model I (comprising factors in the establishment of the nomogram) in each type of ICH was higher than that in model II (comprising ICH score alone), except for cerebellar hemorrhage. These nomograms for predicting death had good discrimination (C-index: 0.889 to 0.975) and prediction probabilities (C-index: 0.890 to 0.965). (4) Conclusions: Higher immune-inflammatory markers were associated with larger ICH volume, worse initial GCS, and unfavorable outcomes, but were not independent prognostic predictors. The location-specific nomograms provided novel and accurate models for predicting mortality risk.

Comparison of Clinical Features, Immune-Inflammatory Markers, and Outcomes Between Patients with Acute In-Hospital and Out-of-Hospital Ischemic Stroke.

PURPOSE: We investigated the differences of clinical features, four immune-inflammatory markers, namely neutrophil counts, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII), as well as outcomes between patients with in-hospital ischemic stroke (IHIS) and out-of-hospital ischemic stroke (OHIS). PATIENTS AND METHODS: We retrospectively enrolled 72 patients with IHIS and 3330 patients with OHIS. RESULTS: IHIS accounted for 2% of all patients with ischemic stroke and occurred more often in cardiology and orthopedic surgery wards. Infection, cardiac disease, and pulmonary disorder were the most common causes of hospitalization. Compared with those with OHIS, patients with IHIS had higher levels of immune-inflammatory markers, initial National Institute of Health Stroke Scale (NIHSS) scores, longer hospital stays, higher rates of heart disease, large-artery atherosclerosis or cardioembolism, received more intravenous thrombolysis (IVT) or endovascular thrombectomies (EVTs), more complications, unfavorable outcomes, and mortality. Every immune-inflammatory marker exhibited positive correlations with initial NIHSS scores and discharge modified Rankin Scale scores among patients with OHIS. NLR and SII were higher among patients with a fatal outcome in both groups. Among patients receiving IVT, most of treatment time intervals were shorter for those with IHIS than those with OHIS. Significant factors for mortality were NLR >5.5, atrial fibrillation, and complications, with a C-statistic of 0.897 in those with IHIS; in those with OHIS, these factors were an initial NIHSS score of >10, NLR >6.0, atrial fibrillation, prior stroke, cancer history, and complications with a C-statistic of 0.902. The results were similar after replacing the NLR with SII. CONCLUSION: Patients with IHIS had more complicated clinical features, higher levels of immune-inflammatory markers, and higher rates of mortality than patients with OHIS. The most significant predictor for mortality among those with OHIS was NIHSS score >10, and the predictors among patients with IHIS were NLR >5.5 and SII >2120.

Is Dissociation of HCl in DMSO Clusters Bistable?

Dissociation of HCl embedded in dimethyl sulfoxide (DMSO) clusters was investigated by projecting the solvent electric field along the HCl bond using B3LYP-D3/6-31+G(d) and MP2/6-31+G(d,p) levels of theory. A large number of distinct structures (about 1500) consisting of up to five DMSO molecules were considered in the present work for statistical reliability. The B3LYP-D3 calculations reveal that the dissociation of HCl embedded in DMSO clusters requires a critical electric field of 138 MV cm-1 along the H-Cl bond. However, a large number of exceptions wherein the electric field values much higher than the critical electric field of 138 MV cm-1 did not result in dissociation of HCl were observed, in addition to several cases wherein the HCl dissociates with an electric field less than the critical electric field. On the other hand, the MP2 level calculations reveal that the critical electric field for HCl dissociation is about 181 MV cm-1 with almost no exceptions. A comparison of calculations carried out using the MP2 and the B3LYP-D3 levels suggests that the dissociation of HCl embedded in DMSO clusters is bistable at the B3LYP-D3 level, which is an artifact, suggesting that care must be exercised in interpreting the processes of proton transfer. The answer to the question raised as the title of this paper is NO.

Structures of Pyridine-Water Clusters Studied with Infrared-Vacuum Ultraviolet Spectroscopy.

The infrared (IR) spectra of the O-H stretching vibrations of pyridine-water clusters (Pyd)m(H2O)n, with m, n = 1-4, have been investigated with infrared-vacuum ultraviolet (VUV) spectroscopy under a jet-cooled condition. The time-of-flight mass spectrum of (Pyd)m(H2O)n+ by VUV ionization at ∼9 eV showed an unusual intensity pattern with very weak ion signals for m = 1 and 2 and stronger signals for m ≥ 3. This unusual mass pattern was explained by a drastic structural change of (Pyd)m(H2O)n upon the VUV ionization, which was followed by the elimination of water molecules. Among the recorded IR spectra, only one spectrum monitored, (Pyd)2+ cation, showed a well-resolved structure. The spectrum was analyzed by comparing with the simulated ones of possible stable isomers of (Pyd)2(H2O)n, which were obtained with quantum-chemical calculations. Most of the calculated (Pyd)2(H2O)n clusters had the characteristic structure in which H2O or (H2O)2 forms a hydrogen-bonded bridge between two pyridines to form the π-stacked (Pyd)2, and an additional H2O molecule(s) extends the H-bonded network. The π-stacked (Pyd)2(H2O)n moiety is very stable and is thought to exist as a local structure in a pyridine/water mixed solution. The Fermi resonance between the O-H stretch fundamentals and the overtones of the O-H bending vibrations in (Pyd)m(H2O)n was found to be less pronounced in the case of (Pyd)m(NH3)n studied previously.

Effects of a Floor Hockey Intervention on Motor Proficiency, Physical Fitness, and Adaptive Development in Youths with Mild Intellectual Disabilities.

This study examined the effects of a 12-week floor hockey training program on the motor proficiency, physical fitness, and adaptive development of youths with mild intellectual disabilities (IDs). A total of 54 youths with IDs were divided into two groups: a floor hockey exercise group (EG; n = 27; age, 16.59 ± 0.56 years) and a control group (CG; n = 27; age, 16.65 ± 0.63 years). The participants in the EG attended sessions of a floor hockey training program 3 times per week over a 12-week period. The CG group maintained their standard activities of daily living. The participants' scores on the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, Brockport Physical Fitness Test, and traditional Chinese version of the teacher form of the Adaptive Behavior Assessment System, Second Edition, were obtained before and after the intervention. The results of the study indicate that the 12-week floor hockey training program significantly increased the participants' scores for most indicators of motor proficiency (p < 0.01), physical fitness (p < 0.01), and adaptive development (p < 0.01). The findings provide evidence that physical activity interventions focusing on floor hockey training are a viable therapeutic option for treating youths with IDs.

Sedentary Time, Physical Activity Levels and Physical Fitness in Adults with Intellectual Disabilities.

Purpose: This cross-sectional study assessed the associations of gender, age, level of intellectual disabilities (IDs) and of daily sedentary and physical activity (PA) time with physical fitness in adults with ID. Materials and methods: Sixty adults (mean age = 39.19 ± 11.70 years) with ID participated in this cross-sectional study. PA was monitored for 7 days using an ActiGraph GT3X monitor. Physical fitness was measured with a 6-min walking test, isometric push-up test, modified curl-up test, handgrip strength test, and back-saver sit-and-reach test. Results: (a) An age of ≥39 years and female gender were associated with lower performance in multiple aspects of physical fitness. (b) More moderate-to-vigorous PA (MVPA) was associated with greater muscular strength and endurance (modified curl-ups: ß = 0.36, p < 0.01; handgrip strength: right, ß = 0.52, p < 0.01; left, ß = 0.52, p < 0.01). (c) More light-intensity PA (LPA) was associated with greater upper-body muscular endurance (ß = 0.42, p < 0.01) and greater flexibility (right leg: ß = 0.36, p < 0.01; left leg: ß = 0.38, p < 0.01). Conclusion: LPA may be as beneficial as MVPA to the physical fitness of adults with ID. Future studies should focus on developing effective PA interventions for adults with ID, especially for women and individuals aged ≥39 years, by incorporating both LPA and MVPA.

Dipole moment enhanced π-π stacking in fluorophenylacetylenes is carried over from gas-phase dimers to crystal structures propagated through liquid like clusters.

The aggregates of monofluorinated phenylacetylenes in the gas-phase, investigated using the IR-UV double resonance spectroscopic method in combination with extensive structural search and electronic structure calculations, reveal the formation of liquid-like clusters with a π-stacked dimeric core. The structural assignment based on the IR spectra in the acetylenic and aromatic C-H stretching regions suggests that, unlike the parent non-fluorinated phenylacetylene, the substitution of a F atom on the phenyl ring increases the dipole moment, leading to robustness in the formation of a ππ stacked dimer, which propagates incorporating C-Hπ_{Ar/Ac} and C-HF interactions involving both acetylenic and aromatic C-H groups. The structural evolution of fluorophenylacetylene aggregates in the gas phase shows marginal effects due to fluorine atom position on the phenyl ring, with substitution in the para-position tending towards phenylacetylene. The present study signifies that the ππ stacked dimers act as a nucleus for the growth of higher clusters to which other molecular units are added predominantly via the {Ar}_C-Hπ_{Ar} type of interaction and the dominant interactions present in the crystal structures gradually emerge with increasing cluster size. Based on these features, gas-phase clusters of fluorophenylacetylene are hypothesized as "liquid-like clusters" acting as intermediates in the generation of various polymorphic forms starting from a ππ stacked dimer as the core molecular unit.

Size of the hydrogen bond network in liquid methanol: a quantum cluster equilibrium model with extensive structure search.

Studies have debated what is a favorable cluster size in liquid methanol. Applications of the quantum cluster equilibrium (QCE) model on a limited set of cluster structures have demonstrated the dominance of cyclic hexamers in liquid methanol. In this study, we examined the aforementioned question by integrating our implementation of QCE with a molecular-dynamics-based structural searching scheme. QCE simulations were performed using a database comprising extensively searched stable conformers of (MeOH)n for n = 2-14, which were optimized by B3LYP/6-31+G(d,p) with and without the dispersion correction. Our analysis indicated that an octamer structure can contribute significantly to cluster probability. By reoptimizing selected conformers with high probability at the MP2 level, we found that the aforementioned octamer became the dominant species due to favorable vibrational free energy, which was attributed to modes of intermolecular vibration.

Association of a High Neutrophil-to-Lymphocyte Ratio with Hyperdense Artery Sign and Unfavorable Short-Term Outcomes in Patients with Acute Ischemic Stroke.

PURPOSE: Immune-inflammatory processes are involved in all the stages of stroke. This study investigated the association of the neutrophil-to-lymphocyte ratio (NLR) with the hyperdense artery sign (HAS) observed on brain computed tomography (CT) and with clinical features in patients with acute ischemic stroke. METHODS: We retrospectively enrolled 2903 inpatients with acute ischemic stroke from May 2010 to May 2019. Data collected included imaging studies, risk factors, laboratory parameters, and clinical features during hospitalization. RESULTS: The HAS was identified in 6% of the 2903 patients and 66% of the 236 patients with acute middle cerebral artery occlusion. Patients with the HAS had a higher NLR. HAS prevalence was higher in men and patients with cardioembolism. The NLR exhibited positive linear correlations with age, glucose and creatinine levels, length of hospital stay, initial National Institutes of Health Stroke Scale (NIHSS) scores, and mRS scores at discharge. The NLR was significantly higher in patients with large-artery atherosclerosis and cardioembolism and was the highest in patients with other determined etiology. Multivariate analysis revealed that an initial NIHSS score of ≥10 and an NLR of >3.5 were significant positive factors, whereas diabetes mellitus and age > 72 years were significant negative factors for the HAS, with a predictive performance of 0.893. An initial NIHSS score of ≥5, positive HAS, age > 75 years, diabetes mellitus, an NLR of >3.5, female sex, a white blood cell count of >8 × 103/mL, and elevated troponin I were significant predictors of unfavorable outcomes, with a predictive performance of 0.886. CONCLUSION: An NLR of >3.5 enabled an efficient prediction of CT HAS. In addition to conventional risk factors and laboratory parameters, both an NLR of >3.5 and CT HAS enabled improved prediction of unfavorable stroke outcomes.