Effective Inclusion of Electronic Polarization Improves the Description of Electrostatic Interactions: The prosECCo75 Biomolecular Force Field.

prosECCo75 is an optimized force field effectively incorporating electronic polarization via charge scaling. It aims to enhance the accuracy of nominally nonpolarizable molecular dynamics simulations for interactions in biologically relevant systems involving water, ions, proteins, lipids, and saccharides. Recognizing the inherent limitations of nonpolarizable force fields in precisely modeling electrostatic interactions essential for various biological processes, we mitigate these shortcomings by accounting for electronic polarizability in a physically rigorous mean-field way that does not add to computational costs. With this scaling of (both integer and partial) charges within the CHARMM36 framework, prosECCo75 addresses overbinding artifacts. This improves agreement with experimental ion binding data across a broad spectrum of systems─lipid membranes, proteins (including peptides and amino acids), and saccharides─without compromising their biomolecular structures. prosECCo75 thus emerges as a computationally efficient tool providing enhanced accuracy and broader applicability in simulating the complex interplay of interactions between ions and biomolecules, pivotal for improving our understanding of many biological processes.

Novel calibration design improves knowledge transfer across products for the characterization of pharmaceutical bioprocesses.

Modern machine learning has the potential to fundamentally change the way bioprocesses are developed. In particular, horizontal knowledge transfer methods, which seek to exploit data from historical processes to facilitate process development for a new product, provide an opportunity to rethink current workflows. In this work, we first assess the potential of two knowledge transfer approaches, meta learning and one-hot encoding, in combination with Gaussian process (GP) models. We compare their performance with GPs trained only on data of the new process, that is, local models. Using simulated mammalian cell culture data, we observe that both knowledge transfer approaches exhibit test set errors that are approximately halved compared to those of the local models when two, four, or eight experiments of the new product are used for training. Subsequently, we address the question whether experiments for a new product could be designed more effectively by exploiting existing knowledge. In particular, we suggest to specifically design a few runs for the novel product to calibrate knowledge transfer models, a task that we coin calibration design. We propose a customized objective function to identify a set of calibration design runs, which exploits differences in the process evolution of historical products. In two simulated case studies, we observed that training with calibration designs yields similar test set errors compared to common design of experiments approaches. However, the former requires approximately four times fewer experiments. Overall, the results suggest that process development could be significantly streamlined when systematically carrying knowledge from one product to the next.

No evidence of attentional prioritization for threatening targets in visual search.

Throughout human evolutionary history, snakes have been associated with danger and threat. Research has shown that snakes are prioritized by our attentional system, despite many of us rarely encountering them in our daily lives. We conducted two high-powered, pre-registered experiments (total N = 224) manipulating target prevalence to understand this heightened prioritization of threatening targets. Target prevalence refers to the proportion of trials wherein a target is presented; reductions in prevalence consistently reduce the likelihood that targets will be found. We reasoned that snake targets in visual search should experience weaker effects of low target prevalence compared to non-threatening targets (rabbits) because they should be prioritized by searchers despite appearing rarely. In both experiments, we found evidence of classic prevalence effects but (contrasting prior work) we also found that search for threatening targets was slower and less accurate than for nonthreatening targets. This surprising result is possibly due to methodological issues common in prior studies, including comparatively smaller sample sizes, fewer trials, and a tendency to exclusively examine conditions of relatively high prevalence. Our findings call into question accounts of threat prioritization and suggest that prior attention findings may be constrained to a narrow range of circumstances.

An innovative hybrid modeling approach for simultaneous prediction of cell culture process dynamics and product quality.

The use of hybrid models is extensively described in the literature to predict the process evolution in cell cultures. These models combine mechanistic and machine learning methods, allowing the prediction of complex process behavior, in the presence of many process variables, without the need to collect a large amount of data. Hybrid models cannot be directly used to predict final product critical quality attributes, or CQAs, because they are usually measured only at the end of the process, and more mechanistic knowledge is needed for many classes of CQAs. The historical models can instead predict the CQAs better; however, they cannot directly relate manipulated process parameters to final CQAs, as they require knowledge of the process evolution. In this work, we propose an innovative modeling approach based on combining a hybrid propagation model with a historical data-driven model, that is, the combined hybrid model, for simultaneous prediction of full process dynamics and CQAs. The performance of the combined hybrid model was evaluated on an industrial dataset and compared to classical black-box models, which directly relate manipulated process parameters to CQAs. The proposed combined hybrid model outperforms the black-box model by 33% on average in predicting the CQAs while requiring only around half of the data for model training to match performance. Thus, in terms of model accuracy and experimental costs, the combined hybrid model in this study provides a promising platform for process optimization applications.

Unveiling the Borohydride Ion through Force-Field Development.

The borohydride ion, BH4-, is an essential reducing agent in many technological processes, yet its full understanding has been elusive, because of at least two significant challenges. One challenge arises from its marginal stability in aqueous solutions outside of basic pH conditions, which considerably limits the experimental thermodynamic data. The other challenge comes from its unique and atypical hydration shell, stemming from the negative excess charge on its hydrogen atoms, which complicates the accurate modeling in classical atomistic simulations. In this study, we combine experimental and computer simulation techniques to devise a classical force field for NaBH4 and deepen our understanding of its characteristics. We report the first measurement of the ion's activity coefficient and extrapolate it to neutral pH conditions. Given the difficulties in directly measuring its solvation free energies, owing to its instability, we resort to quantum chemistry calculations. This combined strategy allows us to derive a set of nonpolarizable force-field parameters for the borohydride ion for classical molecular dynamics simulations. The derived force field simultaneously captures the solvation free energy, the hydration structure, as well as the activity coefficient of NaBH4 salt across a broad concentration range. The obtained insights into the hydration shell of the BH4- ion are crucial for accurately modeling and understanding its interactions with other molecules, ions, materials, and interfaces.

Salt Effects on Caffeine across Concentration Regimes.

Salts affect the solvation thermodynamics of molecules of all sizes; the Hofmeister series is a prime example in which different ions lead to salting-in or salting-out of aqueous proteins. Early work of Tanford led to the discovery that the solvation of molecular surface motifs is proportional to the solvent accessible surface area (SASA), and later studies have shown that the proportionality constant varies with the salt concentration and type. Using multiscale computer simulations combined with vapor-pressure osmometry on caffeine-salt solutions, we reveal that this SASA description captures a rich set of molecular driving forces in tertiary solutions at changing solute and osmolyte concentrations. Central to the theoretical work is a new potential energy function that depends on the instantaneous surface area, salt type, and concentration. Used in, e.g., Monte Carlo simulations, this allows for a highly efficient exploration of many-body interactions and the resulting thermodynamics at elevated solute and salt concentrations.

Toward a reliable detection of arachnophobia: subjective, behavioral, and neurophysiological measures of fear response.

Introduction: The administration of questionnaires presents an easy way of obtaining important knowledge about phobic patients. However, it is not well known how these subjective measurements correspond to the patient's objective condition. Our study aimed to compare scores on questionnaires and image evaluation to the objective measurements of the behavioral approach test (BAT) and the neurophysiological effect of spiders extracted from fMRI measurements. The objective was to explore how reliably subjective statements about spiders and physiological and behavioral parameters discriminate between phobics and non-phobics, and what are the best predictors of overall brain activation. Methods: Based on a clinical interview, 165 subjects were assigned to either a "phobic" or low-fear "control" group. Finally, 30 arachnophobic and 32 healthy control subjects (with low fear of spiders) participated in this study. They completed several questionnaires (SPQ, SNAQ, DS-R) and underwent a behavioral approach test (BAT) with a live tarantula. Then, they were measured in fMRI while watching blocks of pictures including spiders and snakes. Finally, the respondents rated all the visual stimuli according to perceived fear. We proposed the Spider Fear Index (SFI) as a value characterizing the level of spider fear, computed based on the fMRI measurements. We then treated this variable as the "neurophysiological effect of spiders" and examined its contribution to the respondents' fear ratings of the stimuli seen during the fMRI using the redundancy analysis (RDA). Results: The results for fear ranks revealed that the SFI, SNAQ, DS-R, and SPQ scores had a significant effect, while BAT and SPQ scores loaded in the same direction of the first multivariate axis. The SFI was strongly correlated with both SPQ and BAT scores in the pooled sample of arachnophobic and healthy control subjects. Discussion: Both SPQ and BAT scores have a high informative value about the subject's fear of spiders and together with subjective emotional evaluation of picture stimuli can be reliable predictors of spider phobia. These parameters provide easy and non-expensive but reliable measurement wherever more expensive devices such as magnetic resonance are not available. However, SFI still reflects individual variability within the phobic group, identifying individuals with higher brain activation, which may relate to more severe phobic reactions or other sources of fMRI signal variability.

Human emotional evaluation of ancestral and modern threats: fear, disgust, and anger.

Introduction: Animal and human ancestors developed complex physiological and behavioral response systems to cope with two types of threats: immediate physical harm from predators or conspecifics, triggering fear, and the risk of infections from parasites and pathogens leading to the evolution of the behavioral immune system with disgust as the key emotion. Integration of the evolutionary concepts of the fear module and behavioral immune systems has been infrequent, despite the significant survival advantages of disgust in various contexts. Studies comparing attention to ancestral and modern threats accompanied by fear have yielded ambiguous results and what qualifies as salient modern disgusting stimuli remains unclear. We do not know whether disgust or the behavioral immune system, as inherent aspects of human psychology, have adapted to safeguard us from pandemic risks or poisoning by modern toxic substances. Methods: To test these effects, we have developed a survey comprised of 60 short vignettes describing threats evoking fear and disgust belonging to one of the three main categories of threats: (1) ancestral (phylogenetic), (2) modern (ontogenetic), and (3) pandemics of airborne disease. Each vignette was evaluated on a 7-point Likert scale based on fear, disgust, and anger. In total, 660 respondents completed the survey. The data were analysed using a factor analysis and general linear model with the respondent as a random factor. Results: The results show that the strongest fear is triggered by modern threats (electricity, car accidents), while the highest disgust is evoked by ancient threats (body waste products, worms, etc.). Interestingly, disgust does not respond to modern threat stimuli such as toxic substances or radioactivity as these evoke mainly fear and anger. Finally, a distinct response pattern was found for pandemic threats, in which both fear (e.g., of disease and death) and disgust (e.g., of used face masks) are employed. Discussion: Our study offers valuable insights into the emotional responses to ancestral and modern threats and their adaptation to pandemic challenges. Ancestral threats are not always more powerful stimuli than adequate threats of the modern type, but they function specifically. Thus, snakes and heights as fear-inducing ancestral threats form separate factors in a multivariate analysis, whereas all ancestral disgust stimuli group together. The threat of a pandemic forms a specific category and people process it emotionally and cognitively. These insights contribute to our understanding of human psychology and behavior in an ever-changing world.

Cosolvent Exclusion Drives Protein Stability in Trimethylamine N-Oxide and Betaine Solutions.

Using a combination of molecular dynamics simulation, dialysis experiments, and electronic circular dichroism measurements, we studied the solvation thermodynamics of proteins in two osmolyte solutions, trimethylamine N-oxide (TMAO) and betaine. We showed that existing force fields are unable to capture the solvation properties of the proteins lysozyme and ribonuclease T1 and that the inaccurate parametrization of protein-osmolyte interactions in these force fields promoted an unphysical strong thermal denaturation of the trpcage protein. We developed a novel force field for betaine (the KBB force field) which reproduces the experimental solution Kirkwood-Buff integrals and density. We further introduced appropriate scaling to protein-osmolyte interactions in both the betaine and TMAO force fields which led to successful reproduction of experimental protein-osmolyte preferential binding coefficients for lysozyme and ribonuclease T1 and prevention of the unphysical denaturation of trpcage in osmolyte solutions. Correct parametrization of protein-TMAO interactions also led to the stabilization of the collapsed conformations of a disordered elastin-like peptide, while the uncorrected parameters destabilized the collapsed structures. Our results establish that the thermodynamic stability of proteins in both betaine and TMAO solutions is governed by osmolyte exclusion from proteins.

Measuring fear evoked by the scariest animal: Czech versions of the Spider Questionnaire and Spider Phobia Beliefs Questionnaire.

BACKGROUND: Although tiny in size and mostly harmless, spiders evoke exceptional fear in a significant part of the population and arachnophobia is one of the most common anxiety disorders with prevalence 2.7-6.1%. Two standard measures have been widely used to reliably assess the emotional and cognitive component of spider fear, the Spider Questionnaire (SPQ) and Spider Phobia Beliefs Questionnaire (SBQ). We aimed to develop and validate their Czech translations, describe distribution of spider fear in the Czech population, and analyse its association with disgust propensity and other sociodemographic characteristics. METHODS: In Phase 1, we developed Czech translations of both questionnaires using a back-translation procedure and then tested their psychometric properties against their English versions in a counterbalanced experimental design using the Mann-Whitney U test and two-sided t-test. In Phase 2, we analysed scores on the Czech SPQ and SBQ on a larger sample. We evaluated the effects of age, gender, level of education, biology background, and association with the assessments of snake fear (i.e. the Snake Questionnaire, SNAQ) and disgust propensity (i.e. the Disgust Scale-Revised, DS-R) using a Spearman correlation, redundancy analysis, and general linear models. RESULTS: We have demonstrated that the Czech SPQ and SBQ are equivalent to their originals and show excellent test-retest reliability (SPQ: 0.93; SBQ: 0.87-0.90). In total, 398 (10.3%) out of 3863 subjects reached the cut-off point for potential spider phobia. In addition, SPQ and SBQ scores were highly correlated (0.73-0.79), significantly more than with the SNAQ (0.21-0.32) or the DS-R (0.36-0.40). Two multivariate statistical methods revealed a significant association between the gender, age, level of education, biology background, or disgust propensity and the SPQ scores. CONCLUSION: The Czech SPQ and SBQ may produce reliable and valid assessments of spider fear, but they must be further psychometrically tested considering the limitation of this study before wider use. We corroborate previous findings that fear of spiders is significantly associated with sociodemographic variables, such as gender, age, or education, as well as with the individual level of disgust propensity.

Fear inoculation among snake experts.

BACKGROUND: Fear acquisition of certain stimuli, such as snakes, is thought to be rapid, resistant to extinction, and easily transferable onto other similar objects. It has been hypothesized that due to increased survival chances, preparedness to instantly acquire fear towards evolutionary threats has been hardwired into neural pathways of the primate brain. Here, we compare participants' fear of snakes according to experience; from those who often deal with snakes and even suffer snakebites to those unfamiliar with snakes. METHODS: The Snake Questionnaire-12 (SNAQ-12) and Specific Phobia Questionnaire (SPQ) were administered to three groups of participants with a different level of experience with snakes and snakebites: 1) snake experts, 2) firefighters, and 3) college students. RESULTS: This study shows that individuals more experienced with snakes demonstrate lower fear. Moreover, participants who have suffered a snakebite (either venomous or not) score lower on fear of snakes (SNAQ-12), but not of all other potentially phobic stimuli (SPQ). CONCLUSIONS: Our results suggest that a harmless benign exposure might immunize people to highly biologically prepared fears of evolutionary threats, such as snakes.

Venomous snakes elicit stronger fear than nonvenomous ones: Psychophysiological response to snake images.

Snakes have been important ambush predators of both primates and human hunter-gatherers throughout their co-evolutionary history. Viperid snakes in particular are responsible for most fatal venomous snakebites worldwide and thus represent a strong selective pressure. They elicit intense fear in humans and are easily recognizable thanks to their distinctive morphotype. In this study, we measured skin resistance (SR) and heart rate (HR) in human subjects exposed to snake pictures eliciting either high fear (10 venomous viperid species) or disgust (10 nonvenomous fossorial species). Venomous snakes subjectively evaluated as frightening trigger a stronger physiological response (higher SR amplitude) than repulsive non-venomous snakes. However, stimuli presented in a block (more intense stimulation) do not trigger a stronger emotional response compared to sequentially presented stimuli (less intense stimulation). There are significant interindividual differences as subjects with high fear of snakes confronted with images of viperid snakes show stronger, longer-lasting, and more frequent changes in SR and higher HR compared to low-fear subjects. Thus, we show that humans demonstrate a remarkable ability to discriminate between dangerous viperids and harmless fossorial snakes, which is also reflected in distinct autonomous body responses.

Pressure, Peptides, and a Piezolyte: Structural Analysis of the Effects of Pressure and Trimethylamine-N-oxide on the Peptide Solvation Shell.

The osmolyte trimethylamine-N-oxide (TMAO) is able to increase the thermodynamic stability of folded proteins, counteracting pressure denaturation. Herein, we report experimental solubility data on penta-alanine (pAla) in aqueous TMAO solutions (at pH = 7 and pH = 13) together with molecular simulation data for pAla, penta-serine (pSer), and an elastin-like peptide (ELP) sequence (VPGVG) under varying pH and pressure conditions. The effect of the peptide end groups on TMAO-peptide interactions is investigated by comparing the solvation of zwitterionic and negatively charged pentamers with the solvation of pentamers with charge-neutral C- and N-termini and linear, virtually infinite, peptide chains stretched across the periodic boundaries of the simulation cell. The experiments and simulations consistently show that TMAO is net-depleted from the pAla-water interface, but local accumulation of TMAO is observed just outside the first hydration shell of the peptide. While the same observations are also made in the simulations of the zwitterionic pentamers (Ala, Ser, and ELP) and virtually infinite peptide chains (Ala and ELP), weak preferential binding of TMAO is instead observed for pAla with neutral end groups at a 1 M TMAO concentration and for an ELP pentamer with capped neutral end groups at a 0.55 M TMAO concentration studied in previous work (Y.-T. Liao et al. Proc. Natl. Acad. Sci. USA, 2017, 114, 2479-2484). The above observations made at 1 bar ambient pressure remain qualitatively unchanged at 500 bar and 2 kbar. Local accumulation of TMAO correlates with a reduction in the total number of peptide-solvent hydrogen bonds, independent of the peptide's primary sequence and the applied pressure. By weakening water hydrogen bonds with the protein backbone, TMAO indirectly contributes to stabilizing internal hydrogen bonds in proteins, thus providing a protein stabilization mechanism beyond net depletion.

Protein Stability in TMAO and Mixed Urea-TMAO Solutions.

Osmolytes are essential for cellular function under ubiquitous osmotic stress. Trimethylamine N-oxide (TMAO) is one such osmolyte that has gained remarkable attention due to its protein-protective ability against urea. This Review aims at providing a detailed account of recent theoretical and experimental developments in characterizing the structural changes and thermodynamic stability of proteins in the presence of TMAO and urea. New vapor pressure osmometry and molecular dynamics simulation results on urea-TMAO solutions are presented, and a unified molecular mechanism of TMAO counteraction of urea-induced protein denaturation is introduced. In addition, a detailed technical assessment of molecular dynamics force fields for TMAO and for urea-TMAO solutions is presented. The force field analysis highlights how many of the commonly used force field models are in fact incompatible with solvation thermodynamics and can lead to misleading conclusions. A new optimized force field for TMAO (Shea(m)) is presented, and a recently optimized force field for TMAO-urea (Netz(m)) that best reproduces experimental data is highlighted.

Faster detection of snake and spider phobia: revisited.

Snake and spider phobia are one of the most prevalent anxiety disorders, yet quick and reliable measures are rather scarce. Recently, attempts have been made to shorten two widespread measures of snake and spider fear, the Snake Questionnaire (SNAQ) and Spider Questionnaire (SPQ). The new 12-item scales demonstrate very good psychometric qualities in terms of internal consistency and discriminatory power. Using the same approach on a bigger sample from another cultural background, we aimed to verify psychometric properties of the short scales. In total, 2 644 Czechs completed the SNAQ, 1 816 of which also completed the SPQ. The item response theory revealed that nine and seven items on the shorter SNAQ and SPQ, respectively, were identical with the Hungarian study. The 12-item scales show excellent reliability (α = 0.84 and 0.91) and highly correlate with scores on the full versions (r = 0.81 and 0.89) as well as with fear and disgust ratings of snake and spider images. Thus, despite slight discrepancies in the selected items, we confirm that the shorter SNAQ and SPQ keep considerable diagnostic strengths and can be used in the clinical practice as reliable, easy-to- administer, and fast screening tools for snake and spider phobia.

Thermodynamics of N-Isopropylacrylamide in Water: Insight from Experiments, Simulations, and Kirkwood-Buff Analysis Teamwork.

The behavior of thermoresponsive polymer poly(N-isopropylacrylamide) (PNiPAM), an essential building block in the design of smart soft materials, in aqueous solutions has attracted much interest, which contrasts with our knowledge of N-isopropylacrylamide (NiPAM) monomer. Strikingly, the physicochemical properties of aqueous NiPAM are similarly rich, and their understanding is far from being complete. This stems from the lack of accurate thermodynamic data and quantitative model for atomistic simulations. In this joint study, we have probed the thermodynamic behavior of aqueous NiPAM by experimental methods, molecular dynamics (MD) simulations, and Kirkwood-Buff (KB) analysis at ambient conditions. From the partial molar volumes and simultaneously correlated osmotic coefficients, with excess partial molar enthalpies of NiPAM in water, the concentration and temperature dependence of KB integrals was determined. For the purpose of this work, we have developed and employed a novel NiPAM force field, which not only reproduces KB integrals (Gij) and adequately captures macroscopic thermodynamic quantities but also provides more accurate structural insight than the original force fields. We revealed in the vicinity of NiPAM the competing effect of amide hydration with interaction between nonpolar regions. This microscopic picture is reflected in the experimentally observed NiPAM-NiPAM association, which is present from highly dilute conditions up to the solubility limit and is evidenced by G22. From intermediate concentrations, it is accompanied by the existence of apparent dense-water regions, as indicated by positive G11 values. The here-employed KB-based framework provided a mutually consistent thermodynamic and microscopic insight into the NiPAM solution and may be further extended for ion-specific effects. Moreover, our findings contribute to the understanding of thermodynamic grounds behind PNiPAM collapse transition.

Emotional Reaction to Fear- and Disgust-Evoking Snakes: Sensitivity and Propensity in Snake-Fearful Respondents.

This paper continues our previous study in which we examined the respondents' reaction to two morphologically different snake stimuli categories - one evoking exclusively fear and another evoking exclusively disgust. Here we acquired Likert-type scale scores of fear and disgust evoked by the same snake stimuli by a total of 330 respondents. Moreover, we collected data about the respondents' age, gender, education, snake fear [Snake Questionnaire (SNAQ)], and disgust propensity [Disgust Scale-Revised (DS-R)], and we analyzed the effect of these variables on the emotional scores (with special focus on snake-fearful respondents). In addition, we collected the SNAQ and DS-R scores from the respondents tested in the previous study using the rank-ordering method to directly compare the results of these two approaches. The results showed that non-fearful respondents give high scores of fear to the fear-eliciting snakes and high scores of disgust to the disgust-eliciting snakes, but they give low scores of the other emotional dimension (disgust/fear) to each. In contrast, snake-fearful respondents not only give higher fear and disgust scores to the respective snake stimuli, but they also give high scores of fear to the disgust-eliciting snakes and high scores of disgust to the fear-eliciting snakes. Both Likert-scale scores and rank-ordering data show that the clear border dividing both snake stimuli categories dissolves when evaluated by the snake-fearful respondents.

The semi-automated algorithm for the detection of bone marrow oedema lesions in patients with axial spondyloarthritis.

The aim of the study was to create the efficient tool for semi-automated detection of bone marrow oedema lesions in patients with axial spondyloarthritis (axSpA). MRI examinations of 22 sacroiliac joints of patients with confirmed axSpA-related sacroiliitis (median SPARCC score: 14 points) were included into the study. Design of our algorithm is based on Maksymowych et al. evaluation method and consists of the following steps: manual segmentation of bones (T1W sequence), automated detection of reference signal region, sacroiliac joint central lines and ROIs, a division of ROIs into quadrants, automated detection of inflammatory changes (STIR sequence). As a gold standard, two sets of manual lesion delineations were created. Two approaches to the performance assessment of lesion detection were considered: pixel-wise (detections compared pixel by pixel) and quadrant-wise (quadrant to quadrant). Statistical analysis was performed using Spearman's correlation coefficient. Correlation coefficient obtained for pixel-wise comparison of semi-automated and manual detections was 0.87 (p = 0.001), while for quadrant-wise analysis was 0.83 (p = 0.001). The correlation between two sets of manual detections was 0.91 for pixel-wise comparison (p = 0.001) and 0.88 (p = 0.001) for quadrant-wise approach. Spearman's correlation between two manual assessments was not statistically different from the correlation between semi-automated and manual evaluations, both for pixel- (p = 0.14) and quadrant-wise (p = 0.17) analysis. Average single slice processing time: 0.64 ± 0.30 s. Our method allows for objective detection of bone marrow oedema lesions in patients with axSpA. The quantification of affected pixels and quadrants has comparable reliability to manual assessment.

The superficial temporal artery: A meta-analysis of its prevalence and morphology.

INTRODUCTION: The superficial temporal artery (STA) is a terminal branch of the external carotid artery. It supplies the regions of scalp and face. The morphometrical data concerning STAs are not consistent; therefore, in this systemic review and meta-analysis, we aimed in this to provide an up-to-date data on its anatomic features. MATERIAL AND METHODS: In order to do this, PubMed, Embase, ScienceDirect, and Web of Science were searched. We followed the Preferred Reporting Items and Review and Meta-Analyses guidelines for the meta-analysis. Studies that reported the prevalence and anatomical data regarding STA were included in further analyses. RESULTS: Out of 1,446 studies initially evaluated, 21 were included in the meta-analysis (874 patients/donors). The STA diameter was 1.5 mm (95% confidence interval [CI]: 1.47-1.53 mm). The frontal and parietal branches of the STA were present in 97.6% (95% CIs: 94.6-99.5%) and 96.4% (95% CIs: 93.5-98.5%) of the cases, respectively. The STA bifurcation point was located above the zygomatic arch in 79.1% (95% CI: 68.0-84.3), below the zygomatic arch in 6.7% (95% CI: 2.4-12.1), and on the zygomatic arch in 11.1% of the cases (95% CI: 5.4-17.5). There was no bifurcation of the STA in 3.1% of the cases (95% CI: 0.4-7.3). CONCLUSION: The most comprehensive analysis of STA morphological features is presented. The results from this evidence-based anatomical study will improve understanding of the clinical STA anatomy, which in turn has major implications for understanding the STA in clinical practice.