Combined Effects of Static and Dynamic Stretching on the Muscle-Tendon Unit Stiffness and Strength of the Hamstrings.

ABSTRACT: Takeuchi, K, Nakamura, M, Matsuo, S, Samukawa, M, Yamaguchi, T, and Mizuno, T. Combined effects of static and dynamic stretching on the muscle-tendon unit stiffness and strength of the hamstrings. J Strength Cond Res 38(4): 681-686, 2024-Combined static and dynamic stretching for 30 seconds is frequently used as a part of a warm-up program. However, a stretching method that can both decrease muscle-tendon unit (MTU) stiffness and increase muscle strength has not been developed. The purpose of this study was to examine the combined effects of 30 seconds of static stretching at different intensities (normal-intensity static stretching [NS] and high-intensity static [HS]) and dynamic stretching at different speeds (low-speed dynamic [LD] and high-speed dynamic stretching [HD]) on the MTU stiffness and muscle strength of the hamstrings. Thirteen healthy subjects (9 men and 4 women, 20.9 ± 0.8 years, 169.3 ± 7.2 cm, 61.1 ± 8.2 kg) performed 4 types of interventions (HS-HD, HS-LD, NS-HD, and NS-LD). Range of motion (ROM), passive torque, MTU stiffness, and muscle strength were measured before and immediately after interventions by using an isokinetic dynamometer machine. In all interventions, the ROM and passive torque significantly increased (p < 0.01). Muscle-tendon unit stiffness significantly decreased in HS-HD and HS-LD (both p < 0.01), but there was no significant change in NS-HD (p = 0.30) or NS-LD (p = 0.42). Muscle strength significantly increased after HS-HD (p = 0.02) and NS-LD (p = 0.03), but there was no significant change in HS-LD (p = 0.23) or NS-LD (p = 0.26). The results indicated that using a combination of 30 seconds of high-intensity static stretching and high-speed dynamic stretching can be beneficial for the MTU stiffness and muscle strength of the hamstrings.

Acute effects of static stretching on passive stiffness in older adults: A systematic review and meta-analysis.

BACKGROUND: Static stretching has been demonstrated to improve the health of older adults. One of its goals is to decrease passive stiffness of the muscle-tendon unit (MTU) and/or muscles. Decreased passive stiffness in older adults could increase the range of motion and movement efficiency. Herein, we conducted a meta-analysis of the acute effects of static stretching on passive stiffness in older adults as well as a meta-analysis of differences in these effects between older and young adults. BACKGROUND: PubMed, Web of Science, and EBSCO were searched for studies published before June 28, 2023. Manual searches were performed to identify additional studies. All included studies were critically reviewed by five authors. Meta-analyses of muscle and tendon injuries were performed using a random effect model. Of 4643 identified studies, 6 studies were included in the systematic review. RESULTS: The main meta-analysis in older adults showed that static stretching could decrease the passive stiffness of the MTU or muscles (effect size, 0.55; 95 % confidence interval, 0.27 to 0.84; p < 0.01; and I2 = 0.0 %). Moreover, for the comparison between young and old adults, three studies were included in the meta-analysis. The results revealed no significant difference in the effects of static stretching interventions on stiffness between older and young adults (effect size, 0.136; 95 % confidence interval, -0.301 to 0.5738; p = 0.541; and I2 = 17.4 %). Static stretching could decrease the passive stiffness of the MTU and/or muscles in older adults to a small magnitude, and the effects were comparable between older and young adults.

Acute and Long-Term Effects of Static Stretching on Muscle-Tendon Unit Stiffness: A Systematic Review and Meta-Analysis.

Static stretching can increase the range of motion of a joint. Muscle-tendon unit stiffness (MTS) is potentially one of the main factors that influences the change in the range of motion after static stretching. However, to date, the effects of acute and long-term static stretching on MTS are not well understood. The purpose of this meta-analysis was to investigate the effects of acute and long-term static stretching training on MTS, in young healthy participants. PubMed, Web of Science, and EBSCO published before January 6, 2023, were searched and finally, 17 papers were included in the meta-analysis. Main meta-analysis was performed with a random-effect model and subgroup analyses, which included comparisons of sex (male vs. mixed sex and female) and muscle (hamstrings vs. plantar flexors) were also performed. Furthermore, a meta-regression was conducted to examine the effect of total stretching duration on MTS. For acute static stretching, the result of the meta-analysis showed a moderate decrease in MTS (effect size = -0.772, Z = -2.374, 95% confidence interval = -1.409 - -0.325, p = 0.018, I2 = 79.098). For long-term static stretching, there is no significant change in MTS (effect size = -0.608, Z = -1.761, 95% CI = -1.284 - 0.069, p = 0.078, I2 = 83.061). Subgroup analyses revealed no significant differences between sex (long-term, p = 0.209) or muscle (acute, p =0.295; long-term, p = 0.427). Moreover, there was a significant relationship between total stretching duration and MTS in acute static stretching (p = 0.011, R2 = 0.28), but not in long-term stretching (p = 0.085, R2 < 0.01). Whilst MTS decreased after acute static stretching, only a tendency of a decrease was seen after long-term stretching.

Long-term static stretching can decrease muscle stiffness: A systematic review and meta-analysis.

Stretch training increases the range of motion of a joint. However, to date, the mechanisms behind such a stretching effect are not well understood. An earlier meta-analysis on several studies reported no changes in the passive properties of a muscle (i.e., muscle stiffness) following long-term stretch training with various types of stretching (static, dynamic, and proprioceptive neuromuscular stretching). However, in recent years, an increasing number of papers have reported the effects of long-term static stretching on muscle stiffness. The purpose of the present study was to examine the long-term (≥2 weeks) effect of static stretching training on muscle stiffness. PubMed, Web of Science, and EBSCO published before December 28, 2022, were searched and 10 papers met the inclusion criteria for meta-analysis. By applying a mixed-effect model, subgroup analyses, which included comparisons of sex (male vs. mixed sex) and type of muscle stiffness assessment (calculated from the muscle-tendon junction vs. shear modulus), were performed. Furthermore, a meta-regression was conducted to examine the effect of total stretching duration on muscle stiffness. The result of the meta-analysis showed a moderate decrease in muscle stiffness after 3-12 weeks of static stretch training compared to a control condition (effect size = -0.749, p < 0.001, I2 = 56.245). Subgroup analyses revealed no significant differences between sex (p = 0.131) and type of muscle stiffness assessment (p = 0.813). Moreover, there was no significant relationship between total stretching duration and muscle stiffness (p = 0.881).

Predicting Potent Compounds Using a Conditional Variational Autoencoder Based upon a New Structure-Potency Fingerprint.

Prediction of the potency of bioactive compounds generally relies on linear or nonlinear quantitative structure-activity relationship (QSAR) models. Nonlinear models are generated using machine learning methods. We introduce a novel approach for potency prediction that depends on a newly designed molecular fingerprint (FP) representation. This structure-potency fingerprint (SPFP) combines different modules accounting for the structural features of active compounds and their potency values in a single bit string, hence unifying structure and potency representation. This encoding enables the derivation of a conditional variational autoencoder (CVAE) using SPFPs of training compounds and apply the model to predict the SPFP potency module of test compounds using only their structure module as input. The SPFP-CVAE approach correctly predicts the potency values of compounds belonging to different activity classes with an accuracy comparable to support vector regression (SVR), representing the state-of-the-art in the field. In addition, highly potent compounds are predicted with very similar accuracy as SVR and deep neural networks.

Discovery of a Novel ATP-Competitive MEK Inhibitor DS03090629 that Overcomes Resistance Conferred by BRAF Overexpression in BRAF-Mutated Melanoma.

Patients with melanoma with activating BRAF mutations (BRAF V600E/K) initially respond to combination therapy of BRAF and MEK inhibitors. However, their clinical efficacy is limited by acquired resistance, in some cases driven by amplification of the mutant BRAF gene and subsequent reactivation of the MAPK pathway. DS03090629 is a novel and orally available MEK inhibitor that inhibits MEK in an ATP-competitive manner. In both in vitro and in vivo settings, potent inhibition of MEK by DS03090629 or its combination with the BRAF inhibitor dabrafenib was demonstrated in a mutant BRAF-overexpressing melanoma cell line model that exhibited a higher MEK phosphorylation level than the parental cell line and then became resistant to dabrafenib and the MEK inhibitor trametinib. DS03090629 also exhibited superior efficacy against a melanoma cell line-expressing mutant MEK1 protein compared with dabrafenib and trametinib. Biophysical analysis revealed that DS03090629 retained its affinity for the MEK protein regardless of its phosphorylation status, whereas the affinity of trametinib declined when the MEK protein was phosphorylated. These results suggest that DS03090629 may be a novel therapeutic option for patients who acquire resistance to the current BRAF- and MEK-targeting therapies.

Effects of Speed and Amplitude of Dynamic Stretching on the Flexibility and Strength of the Hamstrings.

Dynamic stretching for more than 90 seconds is useful for improving muscle strength, although dynamic stretching for 30 seconds or less is commonly used in sports settings. The effects of dynamic stretching are influenced by the speed and amplitude of stretching, but no study examined these factors for 30 seconds of dynamic stretching. Therefore, the purpose of the present study was to examine the effects of speed (fast- or slow-speed) and amplitude (normal- or wide amplitude) of dynamic stretching for 30 seconds on the strength (peak torque during maximum isokinetic concentric contraction) and flexibility (range of motion, passive torque at maximum knee extension angle, and muscle-tendon unit stiffness) of the hamstrings. The passive torque and muscle-tendon unit stiffness reflect stretching tolerance and viscoelastic properties of the hamstrings, respectively. Fifteen healthy participants performed 4 types of 30 seconds of dynamic stretching. The muscle strength and flexibility were measured before and immediately after the dynamic stretching. The range of motion did not change after dynamic stretching at low speed and normal amplitude (p = 0.12, d = 0.59, 103.3%), but it was increased by other interventions (p < 0.01, d = 0.90-1.25, 104.5-110.1%). In all interventions, the passive torque increased (main effect for time, p < 0.01, d = 0.51 - 0.74, 111.0 - 126.9%), and muscle-tendon unit stiffness did not change. The muscle strength increased only after dynamic stretching at fast speed with normal amplitude (p < 0.01, d = 0.79, 107.1%). The results of the present study indicated that 30 seconds of dynamic stretching at fast speed and with normal amplitude can be beneficial for the measured parameters.

Acute Effects of Different Intensity and Duration of Static Stretching on the Muscle-Tendon Unit Stiffness of the Hamstrings.

The effects of static stretching are influenced by prescribed and applied loads of stretching. The prescribed load is calculated from the stretching duration and intensity, whereas the applied load is assessed from the force of static stretching exerted on the targeted muscle. No previous study has investigated the prescribed and applied loads of static stretching on the muscle-tendon unit stiffness simultaneously. Therefore, the purpose of the present study was to examine the acute effects of the prescribed and applied load of static stretching on the change in the muscle-tendon unit stiffness of the hamstrings by using different intensities and durations of static stretching. Twenty-three participants underwent static stretching at the intensity of high (50 seconds, 3 sets), moderate (60 seconds, 3 sets), and low (75 seconds, 3 sets), in random order. The parameters were the range of motion, passive torque, and muscle-tendon unit stiffness. These parameters were measured before stretching, between sets, and immediately after stretching by using a dynamometer machine. The static stretching load was calculated from the passive torque during static stretching. The muscle-tendon unit stiffness decreased in high- and moderate-intensity after 50 (p < 0.01, d = -0.73) and 180 seconds (p < 0.01, d = -1.10) of stretching respectively, but there was no change in low-intensity stretching for 225 seconds (p = 0.48, d = -0.18). There were significant correlations between the static stretching load and relative change in the muscle-tendon unit stiffness in moderate- (r = -0.64, p < 0.01) and low-intensity (r = -0.54, p < 0.01), but not in high-intensity (r = -0.16, p = 0.18). High-intensity static stretching was effective for a decrease in the muscle-tendon unit stiffness even when the prescribed load of static stretching was unified. The applied load of static stretching was an important factor in decreasing the muscle-tendon unit stiffness in low- and moderate-intensity static stretching, but not in high-intensity stretching.

Comparison of The Effect of High- and Low-Frequency Vibration Foam Rolling on The Quadriceps Muscle.

Vibration foam rolling (VFR) intervention has recently gained attention in sports and rehabilitation settings since the superimposed vibration with foam rolling can affect several physiological systems. However, the sustained effect and a comparison of the effects of different VFR vibration frequencies on flexibility and muscle strength have not been examined. Therefore, in this study, we aimed to investigate the acute and sustained effects of three 60-s sets of VFR with different frequencies on knee flexion range of motion (ROM) and muscle strength of the knee extensors. Using a crossover, random allocation design, 16 male university students (21.2 ± 0.6 years) performed under two conditions: VFR with low (35 Hz) and high (67 Hz) frequencies. The acute and sustained effects (20 min after intervention) of VFR on knee flexion ROM, maximum voluntary isometric contraction (MVC-ISO) torque, maximum voluntary concentric contraction (MVC-CON) torque, rate of force development (RFD), and single-leg countermovement jump (CMJ) height were examined. Our results showed that knee flexion ROM increased significantly (p < 0.01) immediately after the VFR intervention and remained elevated up to 20 min, regardless of the vibration frequency. MVC-ISO and MVC-CON torque both decreased significantly (p < 0.01) immediately after the VFR intervention and remained significantly lowered up to 20 min, regardless of the vibration frequency. However, there were no significant changes in RFD or CMJ height. Our results suggest that VFR can increase knee flexion ROM but induces a decrease in muscle strength up to 20 min after VFR at both high and low frequencies.

Effects of stretching intensity on range of motion and muscle stiffness: A narrative review.

BACKGROUND: No review has yet investigated acute and chronic effects of different stretching intensities, including constant-angle (CA) and constant-torque (CT) stretching. OBJECTIVE: This review aimed to investigate the acute and chronic effects of different stretching intensities on the range of motion (ROM) and passive properties. METHODS: PubMed, Scopus, and Google Scholar were used for literature search. Advanced search functions were used to identify original studies using the terms stretching intensity, constant-torque stretching, constant-angle stretching, ROM, passive stiffness, shear elastic modulus in the title or abstract. The keywords were combined using the Boolean operators "AND" and "OR". The search for articles published from inception until 2021 was done in electronic databases. RESULTS AND CONCLUSION: Five studies compared CA and CT stretching. Three studies reported a greater decrease in passive stiffness, and two studies reported a greater ROM increase after CT than CA stretching. Twelve studies investigated the acute effects of different stretching intensities, and six reported a greater ROM increase at higher stretching intensities. Five studies reported a greater decrease in passive stiffness at higher stretching intensities, but three reported no significant differences in passive stiffness among stretching intensities. Five studies investigated the chronic effect, and four reported no significant difference in ROM change among different intensities. Three studies reported no significant changes in passive stiffness after the stretching program. We suggest that the acute effect of higher stretching intensity, including CT stretching, was more effective for changes in ROM and passive stiffness, but the chronic effect was weak.

The Time-Course Changes in Knee Flexion Range of Motion, Muscle Strength, and Rate of Force Development After Static Stretching.

Previous studies have shown that longer-duration static stretching (SS) interventions can cause a decrease in muscle strength, especially explosive muscle strength. Furthermore, force steadiness is an important aspect of muscle force control, which should also be considered. However, the time course of the changes in these variables after an SS intervention remains unclear. Nevertheless, this information is essential for athletes and coaches to establish optimal warm-up routines. The aim of this study was to investigate the time course of changes in knee flexion range of motion (ROM), maximal voluntary isometric contraction (MVIC), rate of force development (RFD), and force steadiness (at 5 and 20% of MVIC) after three 60-s SS interventions. Study participants were sedentary healthy adult volunteers (n = 20) who performed three 60-s SS interventions of the knee extensors, where these variables were measured before and after SS intervention at three different periods, i.e., immediately after, 10 min, and 20 min the SS intervention (crossover design). The results showed an increase in ROM at all time points (d = 0.86-1.01). MVIC was decreased immediately after the SS intervention (d = -0.30), but MVIC showed a recovery trend for both 10 min (d = -0.17) and 20 min (d = -0.20) after the SS intervention. However, there were significant impairments in RFD at 100 m (p = 0.014, F = 6.37, ηp 2 = 0.101) and 200 m (p < 0.01, F = 28.0, ηp 2 = 0.33) up to 20 min after the SS intervention. Similarly, there were significant impairments in force steadiness of 5% (p < 0.01, F = 16.2, ηp 2 = 0.221) and 20% MVIC (p < 0.01, F = 16.0, ηp 2 = 0.219) at 20 min after the SS intervention. Therefore, it is concluded that three 60-s SS interventions could increase knee flexion ROM but impair explosive muscle strength and muscle control function until 20 min after the SS intervention.

Introducing a Chemically Intuitive Core-Substituent Fingerprint Designed to Explore Structural Requirements for Effective Similarity Searching and Machine Learning.

Fingerprint (FP) representations of chemical structure continue to be one of the most widely used types of molecular descriptors in chemoinformatics and computational medicinal chemistry. One often distinguishes between two- and three-dimensional (2D and 3D) FPs depending on whether they are derived from molecular graphs or conformations, respectively. Primary application areas for FPs include similarity searching and compound classification via machine learning, especially for hit identification. For these applications, 2D FPs are particularly popular, given their robustness and for the most part comparable (or better) performance to 3D FPs. While a variety of FP prototypes has been designed and evaluated during earlier times of chemoinformatics research, new developments have been rare over the past decade. At least in part, this has been due to the situation that topological (atom environment) FPs derived from molecular graphs have evolved as a gold standard in the field. We were interested in exploring the question of whether the amount of structural information captured by state-of-the-art 2D FPs is indeed required for effective similarity searching and compound classification or whether accounting for fewer structural features might be sufficient. Therefore, pursuing a "structural minimalist" approach, we designed and implemented a new 2D FP based upon ring and substituent fragments obtained by systematically decomposing large numbers of compounds from medicinal chemistry. The resulting FP termed core-substituent FP (CSFP) captures much smaller numbers of structural features than state-of-the-art 2D FPs. However, CSFP achieves high performance in similarity searching and machine learning, demonstrating that less structural information is required for establishing molecular similarity relationships than is often believed. Given its high performance and chemical tangibility, CSFP is also relevant for practical applications in medicinal chemistry.

Cross-education effect of 4-week high- or low-intensity static stretching intervention programs on passive properties of plantar flexors.

This study aimed to compare the cross-education effect of unilateral stretching intervention programs with two different intensities (high- vs. low-intensity) on dorsiflexion range of motion (DF ROM), muscle stiffness, and muscle architecture following a 4-week stretching intervention. Twenty-eight healthy males were randomly allocated into two groups: a high-intensity static stretching (HI-SS) intervention group (n = 14; stretch intensity 6-7 out of 10) and a low-intensity static stretching (LI-SS) intervention group (n = 14; stretch intensity 0-1 out of 10). The participants were asked to stretch their dominant leg (prefer to kick a ball) for 4 weeks (3 × week for 3 × 60 s). Before and after the intervention, the non-trained leg passive properties (DF ROM, passive torque, and muscle stiffness) of the plantar flexors and the muscle architecture of the gastrocnemius medialis (muscle thickness, pennation angle, and fascicle length) were measured. Non-trained DF ROM and passive torque at DF ROM were significantly increased in the HI-SS group (p < 0.01, d = 0.64, 50.6%, and p = 0.044, d = 0.36, 18.2%, respectively), but not in the LI-SS group. Moreover, there were no significant changes in muscle stiffness and muscle architecture in both groups. For rehabilitation settings, a high-intensity SS intervention is required to increase the DF ROM of the non-trained limb. However, the increases in DF ROM seem to be related to changes in stretch tolerance and not to changes in muscle architecture or muscle stiffness.

The effects of using a combination of static stretching and aerobic exercise on muscle tendon unit stiffness and strength in ankle plantar-flexor muscles.

The purpose of the present study was to investigate the effects of using a combination of static stretching and aerobic exercise on muscle tendon unit stiffness and muscle strength in the ankle plantar-flexor muscles. Fifteen healthy males (23.3 ± 2.7 years, 170.3 ± 6.5 cm, 64.9 ± 8.7 kg) received three different interventions, in random order. Intervention 1 received 10 min of aerobic exercise after five cycles of one minute of static stretching. Intervention 2 received 10 min of aerobic exercise before the static stretching. Intervention 3 received 5 min of aerobic exercise both before and after the static stretching. The range of motion of ankle dorsiflexion, stretch tolerance, muscle tendon unit stiffness, peak torque of ankle plantarflexion, and the amplitude of electromyography were measured. In all interventions, the range of motion and stretch tolerance significantly increased (p < 0.05), but muscle tendon unit stiffness decreased significantly for all interventions (p < 0.05). Peak torque of ankle plantar flexion and amplitude of electromyography significantly increased for Interventions 1 and 3 (p < 0.05), while these significantly decreased for Intervention 2 (p < 0.05). These data indicated that range of motion and stretch tolerance were increased, but muscle tendon unit stiffness was decreased regardless of the order of static stretching and aerobic exercise. Aerobic exercise after static stretching increased the peak torque and amplitude of electromyography.

Change in dynamic postural control after a training program in collegiate soccer players with unilateral chronic ankle instability.

BACKGROUND: Improving dynamic postural stability after lateral ankle sprain due to chronic ankle instability helps prevent recurrence, and changes in dynamic postural stability can be assessed with the Star Excursion Balance Test. To date, no studies have examined the change in Star Excursion Balance Test score after the end of a balance training program or whether chronic ankle instability affects the rate of change. To examine the effect of chronic ankle instability on changes in Star Excursion Balance Test. score over time after a balance training program. METHODS: Fifteen collegiate soccer players with chronic ankle instability selected with the Cumberland Ankle Instability Tool and ultrasonography. Participants completed a 6-week balance training program. We assessed the Star Excursion Balance Test 5 times (before and immediately after the program and 2, 4, and 6 weeks later) and examined differences in the duration of training effects by a 2-way analysis of variance, with Bonferroni correction for post hoc comparisons to explain any significant interactions. The significance level for all analyses was set at P<0.05. We performed statistical analyses with SPSS v. 25. RESULTS: Analysis of the posterolateral and posteromedial scores in Star Excursion Balance Test showed a significant effect of time. Post hoc analysis of the posterolateral score showed that for each leg, participants reached significantly farther after the program than before (P=0.012). The posterolateral scores at 2, 4, and 6 weeks after the training program did not differ from before the program, but the posteromedial score was significantly improved immediately after the program (P=0.008) and also 2 (P=0.004) and 4 weeks later (P=0.006). CONCLUSIONS: A 6-week balance training program to improve dynamic postural control can improve posterolateral and posteromedial scores in people with chronic ankle instability, and the improvements in posteromedial are still present 4 weeks after program completion.

Association between static stretching load and changes in the flexibility of the hamstrings.

The purpose of the present study was to examine the association between static stretching load and changes in the flexibility of the hamstrings. Twelve healthy men received static stretching for 60 s at two different intensities based on the point of discomfort (100%POD and 120%POD intensity), in random order. To assess the flexibility of the hamstrings, the knee extension range of motion (ROM). Passive torque at end ROM, and muscle-tendon unit stiffness were measured before and after stretching. The static stretching load was calculated from the passive torque throughout static stretching. The knee extension ROM and passive torque at end ROM increased in both intensities (p < 0.01). The muscle-tendon unit stiffness decreased only in the 120%POD (p < 0.01). There were significant correlations between the static stretching load and the relative changes in the knee extension ROM (r = 0.56, p < 0.01) and muscle-tendon unit stiffness (r = - 0.76, p < 0.01). The results suggested that the static stretching load had significant effects on changes in the knee extension ROM and muscle-tendon unit stiffness of the hamstrings, and high-intensity static stretching was useful for improving the flexibility of the hamstrings because of its high static stretching load.

Searchable database of frequent R-groups in medicinal chemistry and their preferred replacements.

In compound optimization, analogue series (ASs) are generated by introducing different R-groups (substituents, functional groups) at specific substitution sites. Systematic investigations of R-groups in medicinal chemistry have so far been rare. We have carried out a large-scale computational analysis of R-groups on the basis of ASs covering currently available bioactive compounds (Takeuchi et al., 2021). With the aid of a network data structure, frequently used R-groups and preferred replacements were identified. On the basis of these data, R-group replacement hierarchies were derived and organized in a searchable database that is made freely available. This contribution complements our systematic analysis (Takeuchi et al., 2021) by specifying the data we have generated and detailing their open access deposition.

Time course of changes in the range of motion and muscle-tendon unit stiffness of the hamstrings after two different intensities of static stretching.

OBJECTIVES: The purpose of this study was to examine the time course of changes in the range of motion and muscle-tendon unit stiffness of the hamstrings after two different intensities of static stretching. METHODS: Fourteen healthy men (20.9 ± 0.7 years, 169.1 ± 7.5cm, 61.6 ± 6.5kg) received static stretching for 60 seconds at two different intensities based on the point of discomfort (100%POD and 120%POD) of each participant, in random order. To evaluate the time course of changes in the flexibility of the hamstrings, the knee extension range of motion (ROM), passive torque at end ROM, and muscle-tendon unit stiffness were measured pre-stretching, post-stretching, and at both 10 and 20 minutes after static stretching. RESULTS: For both intensities, ROM and passive torque at pre-stretching were significantly smaller than those at post-stretching (p < 0.01 in both intensities), 10 minutes (p < 0.01 in both intensities), and 20 minutes (p < 0.01 in both intensities). The muscle-tendon unit stiffness at pre-stretching was significantly higher than that at post-stretching (p < 0.01), 10 minutes (p < 0.01), and 20 minutes (p < 0.01) only in the 120%POD, but it showed no change in the 100%POD. CONCLUSION: The results showed that ROM and passive torque increased in both intensities, and the effects continued for at least 20 minutes after stretching regardless of stretching intensity. However, the muscle-tendon unit stiffness of the hamstrings decreased only after static stretching at the intensity of 120%POD, and the effects continued for at least 20 minutes after stretching.

Systematic mapping of R-group space enables the generation of an R-group replacement system for medicinal chemistry.

Selection of R-groups (substituents, functional groups) is of critical importance for the generation of analogues during hit-to-lead and lead optimization. In the practice of medicinal chemistry, R-group selection is mostly driven by chemical experience and intuition taking synthetic criteria into account. However, systematic analyses of substituents are currently rare. In this work, we have computationally isolated R-groups from more than 17,000 analog series comprising ∼315,000 bioactive compounds. From more than 50,000 unique substituents, frequently used R-groups were identified. For these R-groups, preferred replacements over more than 60,000 individual substitution sites were identified with the aid of a network data structure. These data provided the basis for the generation of a searchable R-group replacement system for medicinal chemistry containing replacement hierarchies for frequently used R-groups, which is made freely available as the central component of our study.

R-group replacement database for medicinal chemistry.

AIM: Generation of an R-group replacement system for compound optimization in medicinal chemistry. MATERIALS & METHODS: From bioactive compounds, analogue series (ASs) were systematically extracted and from these ASs, all R-groups were isolated and further analyzed. EXEMPLARY RESULTS & DATA: From more than 17,000 ASs, more than 50,000 unique R-groups were isolated. For the 500 most frequently used R-groups, preferred replacements were identified and organized in hierarchies. All original data and an R-group replacement database are made available in an open access deposition. LIMITATIONS & NEXT STEPS: The searchable database has no limitations and can easily be modified using the source data we provide. The next step will be applying this R-group resource in practical medicinal chemistry projects as decision support.