A Classification of Fitness Components in Elite Alpine Skiers: A Cluster Analysis.

The current study is an exploratory, secondary data analysis of a selection of physiological and biomechanical fitness components used to assess elite alpine skiers. The present study will provide new knowledge that can be used to aid training prescription and talent identification. A hierarchical cluster analysis was used to identify groups of variables that are crucial for elite alpine skiers and differences based on sex and competition level. The key findings of the study are the patterns that emerged in the generated dendrograms. Physiological and biomechanical fitness components are differentiated in the dendrograms of male and female world-cup-level alpine skiers, but not in non-world-cup athletes. Components related to the aerobic and anaerobic capacity tightly cluster in male athletes at world cup and non-world-cup level, and female world cup athletes. Lower body explosive force production appears to be more critical in male world cup athletes than female world cup athletes. More research is needed into the importance of isometric strength in the lower body. Future research should use larger sample sizes and consider other alpine ski demographics.

Evaluation of The Isometric and Dynamic Rates of Force Development in Multi-Joint Muscle Actions.

The rate of force development (RFD) in the isometric leg press (ILP), the countermovement jump (CMJ) and the squat jump (SJ) were examined in twenty-three (9 females) team sport athletes aged 21-24 years. Peak force (Fpeak), peak rate of force development (RFDpeak) and RFD at different time epochs (0-50, 50-100, 100-150, 150-200) were calculated from the force-time curve, as well as CMJ and SJ height and the center of mass displacement. RFDpeak, RFD at 0-50, 50-100 and 100-150 ms and Fpeak were similar between the CMJ and the SJ (p = 0.26 to 0.99). Furthermore, RFD0-50 ms was similar between the ILP, the CMJ, and the SJ (p = 0.99 to 0.57). Higher values were observed in the ILP compared with the CMJ and the SJ in RFD50-100 ms and RFD100-150 ms (p < 0.001) and these differences were maintained even when RFD was scaled to body mass. The higher RFD normalized to Fpeak was attained at the 50-100 ms time interval with no differences between the ILP, CMJ and SJ and between males and females. These results suggest that the ability to exert rapid force is similar between the CMJ and the SJ, irrespective of the type of muscle action. Furthermore, RFD normalized to Fpeak is a muscle-force independent index of explosive force production, facilitating comparisons between individuals with different levels of muscle strength. The similarities between the CMJ and the SJ in RFDpeak, Fpeak, and RFD at different time epochs may imply that these types of jumps could be used interchangeably to assess explosive lower limb performance.

Acute and long-term effects of two different static stretching training protocols on range of motion and vertical jump in preadolescent athletes.

This study examined the acute and long-term effects of two static stretching protocols of equal duration, performed either as a single stretch or multiple shorter duration repetitions on hip hyperextension range of motion (ROM) and single leg countermovement jump height (CMJ). Thirty female gymnasts were randomly assigned to stretching (SG) or control groups (CG). The SG performed two different protocols of static stretching, three times per week for 9 weeks. One leg performed repeated stretching (3 × 30 s with 30 s rest) while the other leg performed a single stretch (90 s). The CG continued regular training. ROM and CMJ were measured pre- and 2 min post-stretching on weeks 0, 3, 6, 9, and 3 weeks into detraining. CMJ height increased over time irrespective of group (main effect time, p = 0.001), with no statistical difference between groups (main effect group, p = 0.272). Three-way ANOVA showed that, CMJ height after stretching was not affected by either stretching protocol at any time point (p = 0.503 to 0.996). Both stretching protocols equally increased ROM on weeks 6 (10.9 ± 13.4%, p < 0.001, d = 0.42), and 9 (21.5 ± 13.4%, p < 0.001, d = 0.78), and this increase was maintained during detraining (17.0 ± 15.0%, p < 0.001, d = 0.68). No increase in ROM was observed in the CG (p > 0.874). Static stretching of long duration applied either as single or multiple bouts of equal duration, results in similar acute and long-term improvements in ROM. Furthermore, both stretching protocols do not acutely affect subsequent CMJ performance, and this effect is not influenced by the large increase in ROM and CMJ overtime.

Strain-specificity in the hydrogen sulphide signalling network following dietary restriction in recombinant inbred mice.

Modulation of the ageing process by dietary restriction (DR) across multiple taxa is well established. While the exact mechanism through which DR acts remains elusive, the gasotransmitter hydrogen sulphide (H2S) may play an important role. We employed a comparative-type approach using females from three ILSXISS recombinant inbred mouse strains previously reported to show differential lifespan responses following 40% DR. Following long-term (10 months) 40% DR, strain TejJ89-reported to show lifespan extension under DR-exhibited elevated hepatic H2S production relative to its strain-specific ad libitum (AL) control. Strain TejJ48 (no reported lifespan effect following 40% DR) exhibited significantly reduced hepatic H2S production, while H2S production was unaffected by DR in strain TejJ114 (shortened lifespan reported following 40% DR). These differences in H2S production were reflected in highly divergent gene and protein expression profiles of the major H2S production and disposal enzymes across strains. Increased hepatic H2S production in TejJ89 mice was associated with elevation of the mitochondrial H2S-producing enzyme 3-mercaptopyruvate sulfurtransferase (MPST). Our findings further support the potential role of H2S in DR-induced longevity and indicate the presence of genotypic-specificity in the production and disposal of hepatic H2S in response to 40% DR in mice.

Preparing for a National Weightlifting Championship: A Case Series.

Travis, SK, Mizuguchi, S, Stone, MH, Sands, WA, and Bazyler, CD. Preparing for a national weightlifting championship: A case series. J Strength Cond Res 34(7): 1842-1850, 2020-This study aimed to characterize psychological, physiological, and performance changes of a high-level female (24.5 years; 53.8 ± 0.3 kg; 155.4 cm) and male (25.8 years; 92.7 ± 1.2 kg; 189 cm) weightlifter over 28 weeks while preparing for a national championship. Body mass, hydration, psychological inventories, serum biomarkers, vastus lateralis muscle cross-sectional area (CSA), and squat jump (SJ) performance were assessed weekly beginning 11 weeks from the competition date. Weightlifting performance goals were met for the female athlete (actual total = 159 kg) but not for the male athlete (actual total = 292 kg). Reductions in vastus lateralis CSA possibly took place the week leading into competition for both athletes. Both athletes reported positive recovery-stress states on the day of competition relative to baseline values. Fluctuations between steroid hormone concentrations and inflammatory markers were unpredictable and inconsistent for both athletes throughout the training program. Unloaded SJ height and rate of force development were the highest on competition day for both athletes. Based on these findings, it is possible for high-level male and female weightlifters to achieve and maintain peak preparedness 3-4 days before competition following a 1-week overreach and 3-week exponential taper, where training volume-load is reduced by half and intensity maintained or slightly increased relative to pretaper values. Furthermore, the short recovery and stress scale and SJ testing seem to be useful tools for sport scientists and coaches when monitoring high-level weightlifters preparing for competition.

Effect of Plyometric Training on Jumping, Sprinting and Change of Direction Speed in Child Female Athletes.

BACKGROUND: This study examined the effects of 8 weeks of plyometric training on jumping, sprinting, and change of direction (COD) performance. METHODS: Fifty female 7-9-year-old gymnasts were randomly assigned to a plyometric training group (PG; n = 33), that performed supplementary plyometric training twice per week, and a control group (CG; n = 17) that continued regular training. The following tests were performed before and after the intervention: 10 and 20 m sprints, 5 + 5 m and 10 + 10 m COD tests, one-leg and two-leg countermovement jump (CMJ), drop jump (DJ), squat jump (SJ), and standing long jump (SLJ). RESULTS: Only a main effect for time was found for all jumping performance parameters (p = 0.001). However, the improvement of one- and two-leg CMJ in PG had a greater effect size than CG (0.72 and 0.67 vs. 0.34 and 0.18, respectively). Group × time interactions were found for 10 and 20 m sprint tests (p = 0.018 and p = 0.011, respectively) and for 10 + 10 m COD (p = 0.008) with the post hoc test showing improvement only for the PG (p = 0.001, 0.001, and 0.003 and d = 1.1, 1.14, and 0.6, respectively). CONCLUSIONS: Supplementary plyometric training increased sprint and COD performance more than regular gymnastics training, while jumping performance was equally improved in both groups.

Long-Term Changes in Jump Performance and Maximum Strength in a Cohort of National Collegiate Athletic Association Division I Women's Volleyball Athletes.

Kavanaugh, AA, Mizuguchi, S, Sands, WA, Ramsey, MW, and Stone, MH. Long-term changes in jump performance and maximum strength in a cohort of NCAA division I women's volleyball Athletes. J Strength Cond Res 32(1): 66-75, 2018-The purpose of this investigation was to quantify the magnitude of change in maximal strength and jumping abilities over approximately 1, 2, and 3 years of supervised sport and resistance training in National Collegiate Athletic Association (NCAA) division I women's volleyball athletes. This was an exploratory study on a cohort of women's volleyball athletes (n = 29) split into 3 groups based on the length of the time spent in a supervised resistance training program: group 1 (n = 11): 0.7 ± 0.3 years, group 2 (n = 9): 1.6 ± 0.2 years, and group 3 (n = 9): 2.4 ± 0.6 years. Monitoring tests consisted of standing height (cm), body mass (kg), body fat (%), static jump height (SJH) and countermovement JH (CMJH) with 0-, 11-, and 20-kg loads (cm), and midthigh clean pull isometric peak force (IPF) and allometrically scaled IPF (IPFa) (N·kg). Increasing trends were observed for all variables from groups 1 to 2 to 3. Statistically greater improvements (p ≤ 0.05) with moderate to large effect sizes were found between groups 1 and 3 for SJH 0 (19.7%, d = 1.35), SJH 11 (23.8%, d = 1.23), SJH 20 (30.6%, d = 1.20), CMJH 11 (22.6%, d = 1.18), IPF (44.4%, d = 1.22), and IPFa (41.2%, d = 1.32). A combination of traditional resistance training exercises and weightlifting variations at various loads, in addition to volleyball practice, seem to be effective at increasing maximal strength by 44% and vertical JH by 20-30% in NCAA division I women's volleyball athletes after about 2.5 years of training. Furthermore, these characteristics can be improved in the absence of additional plyometric training outside normal volleyball-specific practice.

Flexibility training in preadolescent female athletes: Acute and long-term effects of intermittent and continuous static stretching.

This study compared the acute and long-term effects of intermittent and continuous static stretching training on straight leg raise range of motion (ROM). Seventy-seven preadolescent female gymnasts were divided into a stretching (n = 57), and a control group (n = 20). The stretching group performed static stretching of the hip extensors of both legs, three times per week for 15 weeks. One leg performed intermittent (3 × 30 s with 30 s rest) while the other leg performed continuous stretching (90 s). ROM pre- and post-stretching was measured at baseline, on weeks 3, 6, 9, 12, 15 and after 2 weeks of detraining. ROM was increased during both intermittent and continuous stretching training, but remained unchanged in the control group. Intermittent stretching conferred a larger improvement in ROM compared to both continuous stretching and control from week 3, until the end of training, and following detraining (p = 0.045 to 0.001 and d = 0.80 to 1.41). During detraining, ROM after the intermittent protocol decreased (p = 0.001), while it was maintained after the continuous protocol (p = 0.36). Acute increases in ROM following the intermittent stretching were also larger than in the continuous (p = 0.038). Intermittent stretching was more effective than continuous, for both long-term and acute ROM enhancement in preadolescent female athletes.

Proteostasis and ageing: insights from long-lived mutant mice.

The global increase in life expectancy is creating significant medical, social and economic challenges to current and future generations. Consequently, there is a need to identify the fundamental mechanisms underlying the ageing process. This knowledge should help develop realistic interventions capable of combatting age-related disease, and thus improving late-life health and vitality. While several mechanisms have been proposed as conserved lifespan determinants, the loss of proteostasis - where proteostasis is defined here as the maintenance of the proteome - appears highly relevant to both ageing and disease. Several studies have shown that multiple proteostatic mechanisms, including the endoplasmic reticulum (ER)-induced unfolded protein response (UPR), the ubiquitin-proteasome system (UPS) and autophagy, appear indispensable for longevity in many long-lived invertebrate mutants. Similarly, interspecific comparisons suggest that proteostasis may be an important lifespan determinant in vertebrates. Over the last 20 years a number of long-lived mouse mutants have been described, many of which carry single-gene mutations within the growth-hormone, insulin/IGF-1 or mTOR signalling pathways. However, we still do not know how these mutations act mechanistically to increase lifespan and healthspan, and accordingly whether mechanistic commonality occurs between different mutants. Recent evidence supports the premise that the successful maintenance of the proteome during ageing may be linked to the increased lifespan and healthspan of long-lived mouse mutants.

Modern Techniques and Technologies Applied to Training and Performance Monitoring.

Athlete preparation and performance continue to increase in complexity and costs. Modern coaches are shifting from reliance on personal memory, experience, and opinion to evidence from collected training-load data. Training-load monitoring may hold vital information for developing systems of monitoring that follow the training process with such precision that both performance prediction and day-to-day management of training become adjuncts to preparation and performance. Time-series data collection and analyses in sport are still in their infancy, with considerable efforts being applied in "big data" analytics, models of the appropriate variables to monitor, and methods for doing so. Training monitoring has already garnered important applications but lacks a theoretical framework from which to develop further. As such, we propose a framework involving the following: analyses of individuals, trend analyses, rules-based analysis, and statistical process control.

Disentangling the effect of dietary restriction on mitochondrial function using recombinant inbred mice.

Dietary restriction (DR) extends lifespan and healthspan in many species, but precisely how it elicits its beneficial effects is unclear. We investigated the impact of DR on mitochondrial function within liver and skeletal muscle of female ILSXISS mice that exhibit strain-specific variation in lifespan under 40% DR. Strains TejJ89 (lifespan increased under DR), TejJ48 (lifespan unaffected by DR) and TejJ114 (lifespan decreased under DR) were studied following 10 months of 40% DR (13 months of age). Oxygen consumption rates (OCR) within isolated liver mitochondria were unaffected by DR in TejJ89 and TejJ48, but decreased by DR in TejJ114. DR had no effect on hepatic protein levels of PGC-1a, TFAM, and OXPHOS complexes IV. Mitonuclear protein imbalance (nDNA:mtDNA ratio) was unaffected by DR, but HSP90 protein levels were reduced in TejJ114 under DR. Surprisingly hepatic mitochondrial hydrogen peroxide (H2O2) production was elevated by DR in TejJ89, with total superoxide dismutase activity and protein carbonyls increased by DR in both TejJ89 and TejJ114. In skeletal muscle, DR had no effect on mitochondrial OCR, OXPHOS complexes or mitonuclear protein imbalance, but H2O2 production was decreased in TejJ114 and nuclear PGC-1a increased in TejJ89 under DR. Our findings indicate that hepatic mitochondrial dysfunction associated with reduced lifespan of TejJ114 mice under 40% DR, but similar dysfunction was not apparent in skeletal muscle mitochondria. We highlight tissue-specific differences in the mitochondrial response in ILSXISS mice to DR, and underline the importance and challenges of exploiting genetic heterogeneity to help understand mechanisms of ageing.

Effects of Short-Term Free-Weight and Semiblock Periodization Resistance Training on Metabolic Syndrome.

South, MA, Layne, AS, Stuart, CA, Triplett, NT, Ramsey, MW, Howell, ME, Sands, WA, Mizuguchi, S, Hornsby, WG, Kavanaugh, AA, and Stone, MH. Effects of short-term free-weight and semiblock periodization resistance training on metabolic syndrome. J Strength Cond Res 30(10): 2682-2696, 2016-The effects of short-term resistance training on performance and health variables associated with prolonged sedentary lifestyle and metabolic syndrome (MS) were investigated. Resistance training may alter a number of health-related, physiological, and performance variables. As a result, resistance training can be used as a valuable tool in ameliorating the effects of a sedentary lifestyle including those associated with MS. Nineteen previously sedentary subjects (10 with MS and 9 with nonmetabolic syndrome [NMS]) underwent 8 weeks of supervised resistance training. Maximum strength was measured using an isometric midthigh pull and resulting force-time curve. Vertical jump height (JH) and power were measured using a force plate. The muscle cross-sectional area (CSA) and type were examined using muscle biopsy and standard analysis techniques. Aerobic power was measured on a cycle ergometer using a ParvoMedics 2400 Metabolic system. Endurance was measured as time to exhaustion on a cycle ergometer. After training, maximum isometric strength, JH, jump power, and V[Combining Dot Above]O2peak increased by approximately 10% (or more) in both the metabolic and NMS groups (both male and female subjects). Over 8 weeks of training, body mass did not change statistically, but percent body fat decreased in subjects with the MS and in women, and lean body mass increased in all groups (p ≤ 0.05). Few alterations were noted in the fiber type. Men had larger CSAs compared those of with women, and there was a fiber-specific trend toward hypertrophy over time. In summary, 8 weeks of semiblock free-weight resistance training improved several performance variables and some cardiovascular factors associated with MS.

Stretching the Spines of Gymnasts: A Review.

Gymnastics is noted for involving highly specialized strength, power, agility and flexibility. Flexibility is perhaps the single greatest discriminator of gymnastics from other sports. The extreme ranges of motion achieved by gymnasts require long periods of training, often occupying more than a decade. Gymnasts also start training at an early age (particularly female gymnasts), and the effect of gymnastics training on these young athletes is poorly understood. One of the concerns of many gymnastics professionals is the training of the spine in hyperextension-the ubiquitous 'arch' seen in many gymnastics positions and movements. Training in spine hyperextension usually begins in early childhood through performance of a skill known as a back-bend. Does practising a back-bend and other hyperextension exercises harm young gymnasts? Current information on spine stretching among gymnasts indicates that, within reason, spine stretching does not appear to be an unusual threat to gymnasts' health. However, the paucity of information demands that further study be undertaken.

Exploratory Investigation of Impact Loads During the Forward Handspring Vault.

The purpose of this study was to examine kinematic and kinetic differences in low and high intensity hand support impact loads during a forward handspring vault. A high-speed video camera (500 Hz) and two portable force platforms (500 Hz) were installed on the surface of the vault table. Two-dimensional analyses were conducted on 24 forward handspring vaults performed by 12 senior level, junior Olympic program female gymnasts (16.9 ±1.4 yr; body height 1.60 ±0.1 m; body mass 56.7 ±7.8 kg). Load intensities at impact with the vault table were classified as low (peak force < 0.8 × body weight) and high (peak force > 0.8 × body weight). These vaults were compared via crucial kinetic and kinematic variables using independent t-tests and Pearson correlations. Statistically significant (p < 0.001) differences were observed in peak force (t(24) = 4.75, ES = 3.37) and time to peak force (t(24) = 2.07, ES = 1.56). Statistically significant relationships between the loading rate and time to peak force were observed for high intensity loads. Peak force, time to peak force, and a shoulder angle at impact were identified as primary variables potentially involved in the determination of large repetitive loading rates on the forward handspring vault.

A new approach to determining net impulse and identification of its characteristics in countermovement jumping: reliability and validity.

Examining a countermovement jump (CMJ) force-time curve related to net impulse might be useful in monitoring athletes' performance. This study aimed to investigate the reliability of alternative net impulse calculation and net impulse characteristics (height, width, rate of force development, shape factor, and proportion) and validate against the traditional calculation in the CMJ. Twelve participants performed the CMJ in two sessions (48 hours apart) for test-retest reliability. Twenty participants were involved for the validity assessment. Results indicated intra-class correlation coefficient (ICC) of ≥ 0.89 and coefficient of variation (CV) of ≤ 5.1% for all of the variables except for rate of force development (ICC = 0.78 and CV = 22.3%). The relationship between the criterion and alternative calculations was r = 1.00. While the difference between them was statistically significant (245.96 ± 63.83 vs. 247.14 ± 64.08 N s, p < 0.0001), the effect size was trivial and deemed practically minimal (d = 0.02). In conclusion, variability of rate of force development will pose a greater challenge in detecting performance changes. Also, the alternative calculation can be used practically in place of the traditional calculation to identify net impulse characteristics and monitor and study athletes' performance in greater depth.

Dynamic Compression Enhances Pressure-to-Pain Threshold in Elite Athlete Recovery: Exploratory Study.

Athlete recovery-adaptation is crucial to the progress and performance of highly trained athletes. The purpose of this study was to assess peristaltic pulse dynamic compression (PPDC) in reducing short-term pressure-to-pain threshold (PPT) among Olympic Training Center athletes after morning training. Muscular tenderness and stiffness are common symptoms of fatigue and exercise-induced muscle microtrauma and edema. Twenty-four highly trained athletes (men = 12 and women = 12) volunteered to participate in this study. The athletes were randomly assigned to experimental (n = 12) and control (n = 12) groups. Pressure-to-pain threshold measurements were conducted with a manual algometer on 3 lower extremity muscles. Experimental group athletes underwent PPDC on both legs through computer-controlled circumferential inflated leggings that used a peristaltic-like pressure pattern from feet to groin. Pressures in each cell were set to factory defaults. Treatment time was 15 minutes. The control group performed the same procedures except that the inflation pump to the leggings was off. The experimental timeline included a morning training session, followed by a PPT pretest, treatment application (PPDC or control), an immediate post-test (PPT), and a delayed post-test (PPT) after the afternoon practice session. Difference score results showed that the experimental group's PPT threshold improved after PPDC treatment immediately and persisted the remainder of the day after afternoon practice. The control group showed no statistical change. We conclude that PPDC is a promising means of accelerating and enhancing recovery after the normal aggressive training that occurs in Olympic and aspiring Olympic athletes.

Acute static vibration-induced stretching enhanced muscle viscoelasticity but did not affect maximal voluntary contractions in footballers.

The aim of this study was to compare the effects of acute vibration-enhanced static stretching and/or static stretching alone on the strength and flexibility of the hamstrings and quadriceps muscles. Twenty-one male footballers participated in this study (21.9 ± 1.8 years; 75.54 ± 7.3 kg; 178.7 ± 6.5 cm). The experiment started with 5 minutes standardized warm-up followed by (a) baseline flexibility pretest (Split Test); (b) maximal voluntary flexion and extension (isokinetic strength) of the knee; (c) Treatment or Sham involving 45-second stretch with or without vibration for the hamstring and quadriceps muscle groups with 10-second rest between; and (d) posttest repeating the measures of the pretest. Each player randomly performed both trials on separate occasions. The vibration device operated at 35 Hz with 2 mm amplitude. Stretching with vibration statistically increased hamstring flexibility by 7.8% (p ≤ 0.05) when compared with stretching without vibration. No statistical differences for hamstring or quadriceps strength were noted between treatment conditions. There was no statistical correlation between flexibility and strength measurements. In conclusion, flexibility increased with vibration-enhanced static stretching; however, no change was evident in the maximal voluntary contractions of the knee flexors and extensors.

Peristaltic pulse dynamic compression of the lower extremity enhances flexibility.

This study investigated the effects of peristaltic pulse dynamic compression (PPDC) on range-of-motion (ROM) changes in forward splits. Serious stretching usually involves discomfort and large time investments. Tissue structural changes and stretch tolerance have heretofore been considered the primary mechanisms of enhanced ROM. The PPDC treatment was computer controlled. Circumferential and segmented inflation pressures were induced by feet to hip leggings. Nine subjects, experienced in stretching and a forward split position, volunteered. The subjects were familiarized with the protocol and randomly assigned to an initial condition: experimental (PPDC), or control (CONT). The study involved a crossover design. Second conditions were tested within 1-5 days. All tests were 2 trials of right and left forward splits. Split flexibility was assessed by measuring the height of the anterior superior iliac spine of the rear leg from the floor. Pelvic posture was controlled by rear leg position. The PPDC treatment was 15 minutes of seated PPDC. The control condition was the same except that leggings were not inflated. Pressures of 5 cells in the leggings were set at factory defaults, 70 mm Hg sequentially. Difference score results indicated statistically significant (p ≤ 0.05) differences by condition and the condition by leg interaction. The rapid acute changes in ROM (PPDC: right 25.3%, left 33.3%; CONT: right 12.2%, left 1.0%) support the premise that changes in ROM were dependent on mechanisms other than tissue structural changes and/or stretch tolerance. PPDC provides a means of rapidly enhancing acute ROM requiring less discomfort and time.

Targeting self-renewal pathways in myeloid malignancies.

A fundamental property of hematopoietic stem cells (HSCs) is the ability to self-renew. This is a complex process involving multiple signal transduction cascades which control the fine balance between self-renewal and differentiation through transcriptional networks. Key activators/regulators of self-renewal include chemokines, cytokines and morphogens which are expressed in the bone marrow niche, either in a paracrine or autocrine fashion, and modulate stem cell behaviour. Increasing evidence suggests that the downstream signaling pathways induced by these ligands converge at multiple levels providing a degree of redundancy in steady state hematopoiesis. Here we will focus on how these pathways cross-talk to regulate HSC self-renewal highlighting potential therapeutic windows which could be targeted to prevent leukemic stem cell self-renewal in myeloid malignancies.