Genetic mapping reveals the complex genetic architecture controlling slow canopy wilting in soybean.

In soybean [Glycine max (L.) Merr.], drought stress is the leading cause of yield loss from abiotic stress in rain-fed US growing areas. Only 10% of the US soybean production is irrigated; therefore, plants must possess physiological mechanisms to tolerate drought stress. Slow canopy wilting is a physiological trait that is observed in a few exotic plant introductions (PIs) and may lead to yield improvement under drought stress. Canopy wilting of 130 recombinant inbred lines (RILs) derived from Hutcheson × PI 471938 grown under drought stress was visually evaluated and genotyped with the SoySNP6K BeadChip. Over four years, field evaluations of canopy wilting were conducted under rainfed conditions at three locations across the US (Georgia, Kansas, and North Carolina). Due to the variation in weather among locations and years, the phenotypic data were collected from seven environments. Substantial variation in canopy wilting was observed among the genotypes in the RIL population across environments. Three QTLs were identified for canopy wilting from the RIL population using composite interval mapping on chromosomes (Chrs) 2, 8, and 9 based on combined environmental analyses. These QTLs inherited the favorable alleles from PI 471938 and accounted for 11, 10, and 14% of phenotypic variation, respectively. A list of 106 candidate genes were narrowed down for these three QTLs based on the published information. The QTLs identified through this research can be used as targets for further investigation to understand the mechanisms of slow canopy wilting. These QTLs could be deployed to improve drought tolerance through a targeted selection of the genomic regions from PI 471938.

Treatment of Patellofemoral Instability and Chondral Lesions.

Lateral patellar instability is one of the most common knee disorders among adolescents. Numerous anthropometric features, including trochlear dysplasia, patella alta, high tibial tubercle-to-trochlear groove distance, and coronal and rotational plane malalignment, are considered primary risk factors for patellar dislocation, and the understanding of their complex interplay is continuously evolving. Because of the multifactorial nature of patellar instability, there is a lack of consensus regarding many aspects of surgical intervention. Medial patellofemoral ligament reconstruction is considered to be the essential procedure in preventing recurrent instability. However, there is growing interest in addressing underlying anatomic risk factors that contribute to patellar instability. It is important to discuss the diagnosis and management of patellar instability, surgical considerations in medial patellofemoral ligament reconstruction, mitigation/correction of anatomic risk factors, and treatment of associated chondral lesions.

Ultrasound assessment of humeral shaft nonunion risk: a feasibility and proof of concept study.

PURPOSE: To determine the feasibility and reliability of ultrasound in the assessment of humeral shaft fracture healing and estimate the accuracy of 6wk ultrasound in predicting nonunion. METHODS: Twelve adults with a non-operatively managed humeral shaft fracture were prospectively recruited and underwent ultrasound scanning at 6wks and 12wks post-injury. Seven blinded observers evaluated sonographic callus appearance to determine intra- and inter-observer reliability. Nonunion prediction accuracy was estimated by comparing images for patients that united (n = 10/12) with those that developed a nonunion (n = 2/12). RESULTS: The mean scan duration was 8 min (5-12) and all patients tolerated the procedure. At 6wks and 12wks, sonographic callus (SC) was present in 11 patients (10 united, one nonunion) and sonographic bridging callus (SBC) in seven (all united). Ultrasound had substantial intra- (weighted kappa: 6wk 0.75; 12wk 0.75) and inter-observer reliability (intraclass correlation coefficient: 6wk 0.60; 12wk 0.76). At 6wks, the absence of SC demonstrated sensitivity 50%, specificity 100%, positive predictive value (PPV) 100% and negative predictive value (NPV) 91% in nonunion prediction (overall accuracy 92%). The absence of SBC demonstrated sensitivity 100%, specificity 70%, PPV 40% and NPV 100% in nonunion prediction (overall accuracy 75%). Of three patients at risk of nonunion (Radiographic Union Score for HUmeral fractures < 8), one had SBC on 6wk ultrasound (that subsequently united) and the others had non-bridging/absent SC (both developed nonunion). CONCLUSIONS: Ultrasound assessment of humeral shaft fracture healing was feasible, reliable and may predict nonunion. Ultrasound could be useful in defining nonunion risk among patients with reduced radiographic callus formation.

Physician Professional Fees Are Declining and Inpatient and Outpatient Facility Fees Are Increasing for Orthopaedic Procedures in the United States.

PURPOSE: To examine the trends in physician professional fees and inpatient and outpatient facility fees in orthopaedic surgery in the United States. METHODS: Physician professional fees and inpatient and outpatient facility fees were tracked from 2008 to 2021 for the most common orthopaedic procedures in each orthopaedic subspecialty. Using common procedure codes for physician and outpatient procedures and Medicare severity diagnosis related group codes for inpatient procedures, the Medicare Physician Fee Schedules were used to obtain the national payment amounts for physician professional fees and inpatient and outpatient facility fees. Trends in fees were tracked over time after adjustment for inflation. RESULTS: From 2008 to 2021, physician professional fees decreased by an average of 20%, whereas inpatient facility fees increased by 15%, and outpatient facility fees increased by 72%. The orthopaedic subspecialty with the largest decrease in physician professional fees was oncology, with an average decrease of 23.5%, followed by general orthopaedics (23.1%), and sports medicine (22.8%). The largest increase in outpatient facility fees was seen in the subspecialties of general orthopaedics (149.8%), spine (130.1%), and trauma (123.0%). CONCLUSIONS: Over the past 13 years, physician professional fees for the most common orthopaedic procedures have declined while inpatient and outpatient facility fees have increased. Understanding these changes is important to the practice of orthopaedic surgery in the United States. LEVEL OF EVIDENCE: IV, economic.

Potential of Magnetic Hyperthermia to Stimulate Localized Immune Activation.

Magnetic hyperthermia (MH) harnesses the heat-releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in the tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility of localized MH in vivo, SPIONs are injected intratumorally and their fate tracked by Zirconium-89-positron emission tomography, histological analysis, and electron microscopy. Experiments show that an average of 49% (21-87%, n = 9) of SPIONs are retained within the tumor or immediately surrounding tissue. In situ heating is subsequently generated by exposure to an externally applied alternating magnetic field and monitored by thermal imaging. Tissue response to hyperthermia, measured by immunohistochemical image analysis, reveals specific and localized heat-shock protein expression following treatment. Tumor growth inhibition is also observed. To evaluate the potential effects of MH on the immune landscape, flow cytometry is used to characterize immune cells from excised tumors and draining lymph nodes. Results show an influx of activated cytotoxic T cells, alongside an increase in proliferating regulatory T cells, following treatment. Complementary changes are found in draining lymph nodes. In conclusion, results indicate that biologically reactive MH is achievable in vivo and can generate localized changes consistent with an anti-tumor immune response.

Microsphere stem blockage as a screen for nitrogen-fixation drought tolerance in soybean.

Symbiotic nitrogen-fixation of soybean (Glycine max [Merr.] L) commonly decreases in response to soil drying in advance of other plant processes. While a few soybean lines express nitrogen-fixation drought tolerance, breeding for genetic variation is hampered by laborious phenotyping procedures. The objective of this research was to explore the potential of an initial screen for nitrogen-fixation drought-tolerant genotypes based on a possible relationship with xylem-vessel diameter. The hypothesis was that nitrogen-fixation drought tolerance might result from fewer, large-diameter xylem vessels in the stem that are vulnerable to disrupted flow as water deficit develops. The disrupted flow could cause nitrogen products to accumulate in nodules resulting in negative feedback on nitrogen-fixation rate. The proposed screen involved exposing de-rooted shoots to a suspension containing microspheres (45-53 µm diameter) and recording the decrease in transpiration rate as a result of microsphere xylem-blockage. Two soybean populations were tested. One population was progeny derived from mating of two parents with high and low nitrogen-fixation drought sensitivity. A high correlation (R2  = 0.68; P < 0.001) was found in this population between decreasing transpiration rate resulting from the microsphere treatment and increasing sensitivity of nitrogen-fixation to soil drying. The second tested population consisted of 16 genotypes, most of which had been previously identified in germplasm screens as expressing nitrogen-fixation drought tolerance. Nearly half of the lines in this second population were identified in the screen as showing minimum blockage of transpiration when exposed to the microspheres. Overall, these results showed the potential of using the microsphere screen to identify candidate genotypes expressing nitrogen-fixation drought tolerance.

Clinically Significant Outcomes Following the Treatment of Focal Cartilage Defects of the Knee With Microfracture Augmentation Using Cartilage Allograft Extracellular Matrix: A Multicenter Prospective Study.

PURPOSE: To determine the short-term outcomes following microfracture augmented with cartilage allograft extracellular matrix for the treatment of symptomatic focal cartilage defects of the adult knee. METHODS: Forty-eight patients enrolled by 8 surgeons from 8 separate institutions were included in this study. Patients underwent microfracture augmented by cartilage allograft extracellular matrix (BioCartilage; Arthrex, Naples, FL) and were followed at designated time points (3, 6, 12, and 24 months) to assess patient-reported outcomes (PROs), clinically significant outcomes (CSOs), and failure and complication rates. Magnetic resonance imaging (MRI) was offered at 2 years postoperatively regardless of symptomatology, and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score was documented. RESULTS: PRO compliance was 81.3% at 6 months, 72.9% at 12 months, and 47.9% at 2 years. All joint-specific and function-related PROs significantly improved compared to baseline at 3, 6, 12, 18, and 24 months of follow-up (P < .01), apart from Marx activity scale, which demonstrated a significant decline in postoperative scores at 2 years (P = .034). The percentage of patients achieving CSOs (as defined for microfracture) at 2 years was 90% for minimal clinically important difference and 85% for patient acceptable symptomatic state. Patient factors including age, sex, body mass index, symptoms duration, smoking, presence of a meniscal tear, lesion size, and location were not associated with CSO achievement at 2 years. One patient (2.1%) failed treatment 9.5 months postoperatively due to graft delamination and required a reoperation consisting of arthroscopic debridement. One complication (2.1%) consisting of complaints of clicking, grinding, and crepitus 15 months following the index procedure was reported. Two-year postoperative MRI demonstrated a mean 40.5 ± 22.9 MOCART 2.0 score. CONCLUSIONS: In this preliminary study, we found cartilage allograft extracellular matrix to be associated with improvement in functional outcomes, high rates of CSO achievement, and low failure and complication rates at 2-year follow-up. LEVEL OF EVIDENCE: Level III, prospective multicenter cohort study.

Assessing the diet quality of individuals with rheumatic conditions: a cross-sectional study.

Arthritis is a significant cause of chronic pain and disability, affecting around 3.5 million Australians. However, little is known regarding the overall diet quality of those living with arthritis. This study aimed to assess the dietary quality of Australians living in the Australian Capital Territory region with arthritis. This cross-sectional study analysed dietary intake data of individuals living with arthritis using a validated food frequency questionnaire. Dietary quality was assessed using the Healthy Eating Index-2015 (HEI-2015) to examine associations between diet composition, age, income and arthritis impact using the short form of the Arthritis Impact Measurement Scales 2 (AIMS2-SF). Participants, predominantly female (82.6%), were grouped by age: 18-50 years (n = 32), 50-64 years (n = 31), and 65 + years (n = 23). Significant correlations were observed between age and HEI-2015 (rs = 0.337, p = 0.002) and income and AIMS2-SF (rs = - 0.353, p < 0.001). The mean HEI-2015 score for the 18-49 years group was fair (72.1 ± 12.3), lower than both the 50-64 years group score of good (81.5 ± 9.72) (p = 0.004), and the 65 + years group score of good (81.8 ± 12.1) (p = 0.007). Dietary fibre, seafood and plant protein, fatty acids, and refined grains were identified as dietary components of concern for the 18-49 years group, and total fruit and added sugar were components of concern for people in the worst tertile for the AIMS2-SF. People aged between 18 and 49 years are consuming a lower quality diet compared to people aged 50 years and over. Further research is needed to understand why this association is occurring in this high socioeconomic region of Australia (a high-income country).

Prognostic and biological significance of the proangiogenic factor EGFL7 in acute myeloid leukemia.

Epithelial growth factor-like 7 (EGFL7) is a protein that is secreted by endothelial cells and plays an important role in angiogenesis. Although EGFL7 is aberrantly overexpressed in solid tumors, its role in leukemia has not been evaluated. Here, we report that levels of both EGFL7 mRNA and EGFL7 protein are increased in blasts of patients with acute myeloid leukemia (AML) compared with normal bone marrow cells. High EGFL7 mRNA expression associates with lower complete remission rates, and shorter event-free and overall survival in older (age ≥60 y) and younger (age <60 y) patients with cytogenetically normal AML. We further show that AML blasts secrete EGFL7 protein and that higher levels of EGFL7 protein are found in the sera from AML patients than in sera from healthy controls. Treatment of patient AML blasts with recombinant EGFL7 in vitro leads to increases in leukemic blast cell growth and levels of phosphorylated AKT. EGFL7 blockade with an anti-EGFL7 antibody reduced the growth potential and viability of AML cells. Our findings demonstrate that increased EGFL7 expression and secretion is an autocrine mechanism supporting growth of leukemic blasts in patients with AML.

Editorial Commentary: Medial and Lateral Meniscus Allografts Using Bone Plug Fixation in Patients Without Advanced Arthritis Have 80% Positive Outcomes at 10 Years.

Meniscal allograft transplantation (MAT) for symptomatic knees after meniscectomy decreases pain and often improves function, but it does not replicate a normal meniscus. The ability of MAT to delay arthritic changes is an ongoing area of study, and it is known that outcomes and graft survivorship deteriorate with longer follow-up. Recommended indications are symptomatic patients after meniscectomy with mild (or at most moderate) degenerative changes and absence of (or surgically corrected) associated malalignment or ligament deficiency. When these indications are followed, 80% of patients improve, with survivorship of 83% at 10 years and 56.2% at 20 years. Medial or lateral MAT shows no difference with respect to graft survivorship or patient-reported outcome measures. Meniscus allografts fixed with bone have less graft extrusion than soft tissue fixation alone. While MAT can be beneficial in an arthritic knee in the short term, the survivorship in knees with advanced arthritis is much smaller, with an extensive rehabilitation requirement, and there is a limited supply of meniscal allograft tissue.

Meniscal Allograft Survivorship and Outcomes 20 Years After Implantation.

PURPOSE: To evaluate meniscal allograft survivorship and outcomes 20 years after implantation. METHODS: Fifty-six meniscal allograft patients at a minimum 20 years following implantation comprised the study group. Forty-eight (85.7%) were able to be contacted regarding the function of their knee and if any additional surgeries were performed. RESULTS: Of the 48 patients, 21 required surgical treatment of the graft. Thirteen patients had isolated partial meniscectomy. Eight patients had knee arthroplasty with 1 having prior partial graft removal and one also had a high tibial osteotomy. The average time to arthroplasty was 12.7 years. The graft survivorship was 56.2%. The activity levels at follow-up varied widely, but in general did not deteriorate compared to those preoperatively. Only 1 patient stated they would not have undergone the procedure. CONCLUSIONS: Meniscal allografts were able to provide subjective improvement at 20 years after surgery and while not as durable as the native meniscus, the overall graft survivorship was 56.2% after implantation. LEVEL OF EVIDENCE: Retrospective case series, Level of evidence IV.

High Risk of Further Surgery After Radial Head Replacement for Unstable Fractures: Longer-term Outcomes at a Minimum Follow-up of 8 Years.

BACKGROUND: The evidence for treating acute, unreconstructable radial head fractures in unstable elbows with radial head replacement predominantly consists of short- to mid-term follow-up studies with a heterogenous mix of implants and operative techniques. Data on longer-term patient-reported outcomes after radial head replacement is lacking. QUESTIONS/PURPOSES: (1) What proportion of patients undergo revision or implant removal after radial head replacement? (2) At a minimum of 8 years follow-up, what are the patient-reported outcomes (QuickDASH, Oxford Elbow Score, and EuroQol-5D)? (3) What factors are associated with a superior long-term patient-reported outcome, according to the QuickDASH? METHODS: Between September 1994 and September 2010, we surgically treated 157 patients for acute radial head fractures. We excluded patients where the radial head was excised (n = 21), internally fixed (n = 15), or replaced as a secondary procedure after failed internal fixation (n = 2). A total of 119 patients who underwent radial head replacement surgery for an acute unreconstructable fracture were included, with a mean age of 50 years (range 15 to 93 ± 19 years), and 53% of patients (63) were women. All but two implants were uncemented, loose-fitting, monopolar prostheses, of which 86% (102) were metallic and 14% (17) were silastic. Implants were only cemented if they appeared unstable within the proximal radius. Silastic implants were used in the earlier series and replaced by metallic implants starting in 2000. We reviewed electronic records to document postoperative complications and prosthesis revision and removal. A member of the local research team (THC, CDC) who was not previously involved in patient care contacted patients to confirm complications, reoperations and to obtain long-term patient-reported outcomes scores. Nineteen patients had died at the point of outcome score collection. Of the remaining 100 patients, 80 were contacted (67% of total cohort), at a median of 11 years (range 8 to 24 years) after injury. The primary outcome measure was the QuickDASH score. RESULTS: Of 119 patients, 25% (30) underwent reoperation, with three patients undergoing revision and 27 patients undergoing prosthesis removal at a median of 7 months (range 0 to 125 months). Twenty-one of 30 procedures (70%) occurred within 1 year after implantation. Kaplan-Meier survivorship analysis demonstrated a cumulative implant survival rate of 71%. In the 80 patients contacted, the mean QuickDASH score was 13 ± 14, the mean Oxford Elbow Score was 43 ± 6, and the median EuroQol-5D score was 0.8 (-0.3 to 1.0). After controlling for covariates, we found that prothesis revision or removal (p = 0.466) and prosthesis type (p = 0.553) were not associated with patient-reported outcome, according to the QuickDASH. CONCLUSIONS: The management of acute unreconstructable fractures of the radial head in unstable elbow injuries with radial head replacement has a high risk of reoperation. Patients must be counselled regarding this risk of secondary intervention, of which the peak risk appears to be within 1 year after implantation. Despite this, patients report low disability according to the QuickDASH at a minimum follow-up of 8 years. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Editorial Commentary: Meniscal Allografts Can Be for Grandparents Too.

Meniscal allografts have come a long way since they were first thought to be a salvage procedure before a knee arthroplasty. The surgical procedure and indications have shown significant change, but the variable of patient age has not. Most clinical series report that patients should be <50-55 years of age to be considered as candidates. While outcomes are better for younger patients, good results can be obtained even when the upper age is extended beyond the current accepted limit.

Cost-Effectiveness Analysis of Needle Arthroscopy Versus Magnetic Resonance Imaging in the Diagnosis and Treatment of Meniscal Tears of the Knee.

PURPOSE: To determine whether needle arthroscopy (NA) compared with magnetic resonance imaging (MRI) in the diagnosis and treatment of meniscal tears is cost-effective when evaluated over a 2-year period via patient-reported outcomes. The hypothesis is that improved diagnostic accuracy with NA would lead to less costly care and similar outcomes. METHODS: A Markov model/decision tree analysis was performed using TreeAge Pro 2017 software. Patients were evaluated for degenerative and traumatic damage to the lateral/medial meniscus. Assumed sensitivities and specificities were derived from the medical literature. The direct costs for care were derived from the 2017 Medicare fee schedule and from private payer reimbursement rates. Costs for care included procedures performed for false-positive findings and for care for false-negative findings. Effectiveness was examined using the global knee injury and osteoarthritis outcome score (KOOS). Patients were evaluated over 2 years for costs and outcomes, including complications. Dominance and incremental cost-effectiveness were evaluated, and 1- to 2-way sensitivity analysis was performed to determine those variables that had the greatest effect. The consolidated economics evaluation and reporting standards checklist for reporting economic evaluations was used. RESULTS: NA was less costly and had similar KOOS versus MRI for both the medial/lateral meniscus with private pay. Costs were less for both Medicare and private pay for medial meniscus, $780 to $1,862, and lateral meniscus, $314 to $1,256, respectively. CONCLUSIONS: Based on the reported MRI incidence of false positives with the medial meniscus and false negatives with the lateral meniscus and based on assumed standards of care, more costly care is provided when using MRI compared with NA. Outcomes were similar with NA compared with MRI. LEVEL OF EVIDENCE: Level II, economic and decision analysis.

Harnessing the immune system in glioblastoma.

Glioblastoma is the most common primary malignant brain tumour. Survival is poor and improved treatment options are urgently needed. Although immunotherapies have emerged as effective treatments for a number of cancers, translation of these through to brain tumours is a distinct challenge, particularly due to the blood-brain barrier and the unique immune tumour microenvironment afforded by CNS-specific cells. This review discusses the immune system within the CNS, mechanisms of immune escape employed by glioblastoma, and the immunological effects of conventional glioblastoma treatments. Novel therapies for glioblastoma that harness the immune system and their current clinical progress are outlined, including cancer vaccines, T-cell therapies and immune checkpoint modulators.

Mapping and confirmation of loci for salt tolerance in a novel soybean germplasm, Fiskeby III.

KEY MESSAGE: The confirmation of a major locus associated with salt tolerance and mapping of a new locus, which could be beneficial for improving salt tolerance in soybean. Breeding soybean for tolerance to high salt conditions is important in some regions of the USA and world. Soybean cultivar Fiskeby III (PI 438471) in maturity group 000 has been reported to be highly tolerant to multiple abiotic stress conditions, including salinity. In this study, a mapping population of 132 F2 families derived from a cross of cultivar Williams 82 (PI 518671, moderately salt sensitive) and Fiskeby III (salt tolerant) was analyzed to map salt tolerance genes. The evaluation for salt tolerance was performed by analyzing leaf scorch score (LSS), chlorophyll content ratio (CCR), leaf sodium content (LSC), and leaf chloride content (LCC) after treatment with 120 mM NaCl under greenhouse conditions. Genotypic data for the F2 population were obtained using the SoySNP6K Illumina Infinium BeadChip assay. A major allele from Fiskeby III was significantly associated with LSS, CCR, LSC, and LCC on chromosome (Chr.) 03 with LOD scores of 19.1, 11.0, 7.7 and 25.6, respectively. In addition, a second locus associated with salt tolerance for LSC was detected and mapped on Chr. 13 with an LOD score of 4.6 and an R 2 of 0.115. Three gene-based polymorphic molecular markers (Salt-20, Salt14056 and Salt11655) on Chr.03 showed a strong predictive association with phenotypic salt tolerance in the present mapping population. These molecular markers will be useful for marker-assisted selection to improve salt tolerance in soybean.

RNA-Seq study reveals genetic responses of diverse wild soybean accessions to increased ozone levels.

BACKGROUND: Ozone is an air pollutant widely known to cause a decrease in productivity in many plant species, including soybean (Glycine max (L.) Merr). While the response of cultivated soybean to ozone has been studied, very little information is available regarding the ozone response of its wild relatives. RESULTS: Ozone-resistant wild soybean accessions were identified by measuring the response of a genetically diverse group of 66 wild soybean (Glycine soja Zucc. and Sieb.) accessions to elevated ozone levels. RNA-Seq analyses were performed on leaves of different ages from selected ozone-sensitive and ozone-resistant accessions that were subjected to treatment with an environmentally relevant level of ozone. Many more genes responded to elevated ozone in the two ozone-sensitive accessions than in the ozone-resistant accessions. Analyses of the ozone response genes indicated that leaves of different ages responded differently to ozone. Older leaves displayed a consistent reduction in expression of genes involved in photosynthesis in response to ozone, while changes in expression of defense genes dominated younger leaf tissue in response to ozone. As expected, there is a substantial difference between the response of ozone-sensitive and ozone-resistant accessions. Genes associated with photosystem 2 were substantially reduced in expression in response to ozone in the ozone-resistant accessions. A decrease in peptidase inhibitors was one of several responses specific to one of the ozone resistant accessions. CONCLUSION: The decrease in expression in genes associated with photosynthesis confirms that the photosynthetic apparatus may be an early casualty in response to moderate levels of ozone. A compromise of photosynthesis would substantially impact plant growth and seed production. However, the resistant accessions may preserve their photosynthetic apparatus in response to the ozone levels used in this study. Older leaf tissue of the ozone-resistant accessions showed a unique down-regulation of genes associated with endopeptidase inhibitor activity. This study demonstrates the existence of significant diversity in wild soybean for ozone response. Wild soybean accessions characterized in this study can be used by soybean breeders to enhance ozone tolerance of this important food crop.

Expression and prognostic impact of lncRNAs in acute myeloid leukemia.

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged ≥60 y) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. An independent set of 71 untreated older patients with CN-AML was used to validate the outcome scores using RNA sequencing. Distinctive lncRNA profiles were found associated with selected mutations, such as internal tandem duplications in the FLT3 gene (FLT3-ITD) and mutations in the NPM1, CEBPA, IDH2, ASXL1, and RUNX1 genes. Using the lncRNAs most associated with event-free survival in a training cohort of 148 older patients with CN-AML, we derived a lncRNA score composed of 48 lncRNAs. Patients with an unfavorable compared with favorable lncRNA score had a lower complete response (CR) rate [P < 0.001, odds ratio = 0.14, 54% vs. 89%], shorter disease-free survival (DFS) [P < 0.001, hazard ratio (HR) = 2.88] and overall survival (OS) (P < 0.001, HR = 2.95). The validation set analyses confirmed these results (CR, P = 0.03; DFS, P = 0.009; OS, P = 0.009). Multivariable analyses for CR, DFS, and OS identified the lncRNA score as an independent marker for outcome. In conclusion, lncRNA expression in AML is closely associated with recurrent mutations. A small subset of lncRNAs is correlated strongly with treatment response and survival.

Phenotypic variation and identification of quantitative trait loci for ozone tolerance in a Fiskeby III × Mandarin (Ottawa) soybean population.

KEY MESSAGE: Soybean quantitative trait loci for ozone response. Ground-level ozone reduces yield in crops such as soybean (Glycine max (L.) Merr.). Phenotypic variation has been observed for this trait in multiple species; however, breeding for ozone tolerance has been limited. A recombinant inbred population was developed from soybean genotypes differing in tolerance to ozone: tolerant Fiskeby III and sensitive Mandarin (Ottawa). Plants were exposed to ozone treatment for 5 days in greenhouse chambers followed by visual scoring for foliar injury. Mean injury score in the mid-canopy was 16 % for Fiskeby III, and 81 % for Mandarin (Ottawa). Injury scores were lower in younger leaves for both parents and progeny, compared to scores in the older leaves. Segregation was consistent with multigenic inheritance. Correlation coefficients for injury between leaf positions ranged from 0.34 to 0.81, with the closer leaf positions showing the greater correlation. Narrow sense heritability within an ozone treatment chamber was 0.59, 0.40, 0.29, 0.30, 0.19, and 0.35 for the 2nd, 3rd, 4th, 5th, 6th, and combined 3rd-5th main stem leaf positions (numbered acropetally), respectively, based on genotypic means over three independent replications. Quantitative trait loci (QTL) analysis showed that loci were associated with distinct leaf developmental stages. QTL were identified on Chromosome 17 for the 2nd and 3rd leaf positions, and on Chromosome 4 for the 5th and 6th leaf positions. Additional loci were identified on Chromosomes 6, 18, 19, and 20. Interacting loci were identified on Chromosomes 5 and 15 for injury on trifoliate 4. The ozone sensitive parent contributed one favorable allele for ozone response.

Strength and Power Correlates of Throwing Velocity on Subelite Male Cricket Players.

Throwing velocity is an important aspect of fielding in cricket to affect run-outs and reduce the opponent's run-scoring opportunities. Although a relationship between strength and/or power and throwing velocity has been well established in baseball, water polo, and European handball, it has not been adequately explored in cricket. Consequently, this study aimed to determine the relationship between measures of strength and/or power and throwing velocity in cricket players. Seventeen male cricket players (mean ± SD; age, 21.1 ± 1.6 years; height, 1.79 ± 0.06 m; weight, 79.8 ± 6.4 kg) from an elite athlete program were tested for maximal throwing velocity from the stretch position and after a 3-meter shuffle. They were also assessed for strength and power using a range of different measures. Throwing velocity from the stretch position (30.5 ± 2.4 m·s) was significantly related to dominant leg lateral-to-medial jump (LMJ) distance (r = 0.71; p < 0.01), dominant shoulder internal rotation (IR) strength (r = 0.55; p ≤ 0.05), and dominant (r = 0.73; p < 0.01) and nondominant (r = 0.54; p ≤ 0.05) medicine ball rotation (MB Rot) throw velocity and medicine ball chest pass (MB CP) distance (r = 0.67; p < 0.01). A nonsignificant trend was observed for vertical jump (VJ) height (p = 0.06), whereas no significant relationships were observed for nondominant LMJ distance (p = 0.97), nondominant shoulder IR strength (p = 0.80), 1 repetition maximum (RM) squat strength (p = 0.57), 1RM bench press strength (p = 0.90), height (p = 0.33), or weight (p = 0.29). Multiple regression analysis revealed that dominant MB Rot and MB CP explained 66% of the variance. The results were similar for velocity after a shuffle step (31.8 ± 2.1 m·s); however, VJ height reached statistical significance (r = 0.51; p ≤ 0.05). The multiple regression was also similar with MB Rot and MB CP explaining 70% of the variance. The cricketers in this study threw with greater velocity than elite junior and subelite senior cricketers but with lower velocities than elite senior cricketers and collegiate level and professional baseball players. This is the first study to demonstrate a link between strength and/or power and throwing velocity in cricket players and highlight the importance of power development as it relates to throwing velocity. Exercises that more closely simulated the speed (body weight jumps and medicine ball throws) or movement pattern (shoulder IR) of overhead throwing were greater predictors of throwing velocity. Strength and conditioning staff should assess and develop power to enhance throwing performance in cricket players. Exercises with greater movement and speed specificity to throwing should be used in preference over exercises that are slower and have less movement specificity to the throwing motion. Cricket players should engage in power training to bridge the gap in performance between them and baseball players.