Insufficient pollinator visitation often limits yield in crop systems worldwide.

Declining pollinator populations could threaten global food production, especially if current crop yields are limited by insufficient pollinator visitation to flowers, in a phenomenon referred to as 'pollinator limitation'. Here, we assess the global prevalence of pollinator limitation, explore the risk factors, such as crop type or geographic region, that predict where pollinator limitation is more likely and ask by how much increases in pollinator visitation could improve crop yields. We address these questions using 198,360 plant-pollinator interactions and 2,083 yield measurements from 32 crop species grown in 120 study systems. We find that 28-61% of global crop systems are pollinator limited and that this limitation most frequently occurs in blueberry, coffee and apple crops. For a few datasets, we note that the probability of pollinator limitation decreases with greater forest land cover surrounding a crop field at 1 km, although average effect sizes are small. Finally, we estimate that for those crops we identify as pollinator limited, increasing pollinator visitation at all farms to existing levels observed in the 90th percentile of each study system would close 63% of yield gaps between high- and low-yielding fields. Our findings show variations in sensitivity to pollinator limitation across diverse crop systems and indicate that realistic increases in pollinator visitation could mitigate crop yield shortfalls attributable to pollinator limitation.

Left ventricular strain-volume loops in bicuspid aortic valve disease: new insights in cardiomechanics.

Aims: By combining temporal changes in left ventricular (LV) global longitudinal strain (GLS) with LV volume, LV strain-volume loops can assess cardiac function across the cardiac cycle. This study compared LV strain-volume loops between bicuspid aortic valve (BAV) patients and controls, and investigated the loop's prognostic value for clinical events. Methods and results: From a prospective cohort of congenital heart disease patients, BAV patients were selected and compared with healthy volunteers, who were matched for age and sex at group level. GLS analysis from apical views was used to construct strain-volume loops. Associations with clinical events, i.e. a composite of all-cause mortality, heart failure, arrhythmias, and aortic valve replacement, were assessed by Cox regression. A total of 113 BAV patients were included (median age 32 years, 40% female). BAV patients demonstrated lower Sslope (0.21%/mL, [Q1-Q3: 0.17-0.28] vs. 0.27%/mL [0.24-0.34], P < 0.001) and ESslope (0.19%/mL [0.12-0.25] vs. 0.29%/mL [0.21-0.43], P < 0.001) compared with controls, but also greater uncoupling during early (0.48 ± 1.29 vs. 0.05 ± 1.21, P = 0.04) and late diastole (0.66 ± 1.02 vs. -0.07 ± 1.07, P < 0.001). Median follow-up duration was 9.9 [9.3-10.4] years. Peak aortic jet velocity (HR 1.22, P = 0.03), enlarged left atrium (HR 3.16, P = 0.003), E/e' ratio (HR 1.17, P = 0.002), GLS (HR 1.16, P = 0.008), and ESslope (HR 0.66, P = 0.04) were associated with the occurrence of clinical events. Conclusion: Greater uncoupling and lower systolic and diastolic slopes were observed in BAV patients compared with healthy controls, suggesting presence of altered LV cardiomechanics. Moreover, lower ESslope was associated with clinical events, highlighting the strain-volume loop's potential as prognostic marker.

Analyzing the relative importance of habitat quantity and quality for boosting pollinator populations in agricultural landscapes.

To increase pollinator populations, international policy targets minimum levels of seminatural habitat cover, but it is unknown whether improving the quality of existing habitats could bring similar benefits without the need of reducing cropland area. Using data we collected in 26 Italian agricultural landscapes during the entire flying season, we explored the relative importance of habitat quantity (seminatural habitat cover) and quality (flower availability) on pollinator densities in seminatural habitats. We obtained transect-based counts and estimated the effect of habitat quantity (proportion of seminatural habitat) and quality (flower cover and richness) on wild bee and hoverfly densities. We used the relationships revealed in the data to simulate pollinator population sizes in landscapes with varying habitat quantity and quality. Wild bee densities were only related to flower availability, whereas hoverfly densities were additionally related to seminatural habitat cover. We found that in complex agricultural landscapes (above 15% seminatural habitat cover), improving habitat quality increased pollinator populations more effectively than increasing habitat quantity. However, increasing habitat quantity was by far the most effective approach for boosting pollinator populations in simple landscapes.

Análisis de la importancia relativa de la cantidad y calidad del hábitat para incrementar las poblaciones de polinizadores en los paisajes agrícolas Resumen Las políticas internacionales buscan que existan niveles mínimos de cobertura seminatural del hábitat para incrementar las poblaciones de polinizadores y se desconoce si mejorar la calidad de los hábitats existentes podría brindar beneficios similares sin tener que reducir el área de cultivo. Usamos datos recolectados en 26 paisajes agrícolas de Italia durante la temporada de vuelo para analizar la importancia relativa de la cantidad (cobertura de hábitat seminatural) y calidad (disponibilidad de flores) del hábitat para la densidad de polinizadores en los hábitats seminaturales. Obtuvimos conteos basados en transectos y estimamos el efecto de la cantidad (proporción del hábitat seminatural) y calidad (riqueza y cobertura de flores) del hábitat sobre la densidad de las abejas silvestres y los sírfidos. Usamos la relación revelada por los datos para simular el tamaño poblacional de los polinizadores en los paisajes con diferente calidad y cantidad de hábitat. La densidad de las abejas silvestres sólo se relacionó con la disponibilidad de flores cuando la densidad de sírfidos se relacionó con la cobertura del hábitat seminatural. Descubrimos que en los paisajes agrícolas complejos (por encima del 15% de cobertura de hábitat seminatural) cuya calidad mejoraba, las poblaciones de polinizadores incrementaban de manera más eficiente que cuando se mejoraba la cantidad. Sin embargo, incrementar la cantidad del hábitat fue por mucho la estrategia más efectiva para acrecentar las poblaciones de polinizadores en paisajes simples.

Cardiac rehabilitation and adverse events among adult patients with simple congenital heart disease and heart failure.

Aims: Improved care has resulted in prolonged survival of patients with congenital heart disease (ConHD), increasing age-related cardiovascular comorbidities. Although cardiovascular rehabilitation (CR) represents evidence-based care for heart failure (HF), the clinical impact of CR in patients with ConHD who developed HF during adulthood is unclear. We investigated 12-month mortality and morbidity in patients with simple ConHD diagnosed with HF with CR versus without CR. Methods: A retrospective cohort study was conducted for the time period February 2004 - February 2024. Utilizing TriNetX, a global federated health research network, a real-world dataset of simple ConHD patients was acquired to compare patients with vs. without (controls) prescription for exercise-based CR. Patients were propensity-score matched for age, sex, ethnicity, comorbidities, procedures, and medication. The primary outcome was a composite of all-cause mortality, ischemic stroke, and acute coronary syndrome (major adverse cardiovascular events; MACE) within 12 months. Results: Following propensity score matching, the total cohort consisted of 6,866 simple ConHD patients with HF. CR was associated with significantly lower odds for MACE (odds ratio (OR) 0.61 [95 % confidence interval (CI): 0.54-0.69]) and its individual components all-cause mortality (OR 0.40 [95 % CI 0.33-0.47]) and ischemic stroke (OR 0.75 [95 % CI 0.64-0.88]), but not acute coronary syndrome (OR 1.24 [95 % CI 0.91-1.69]). Conclusion: CR was associated with significantly lower 12-month MACE in patients with simple ConHD with concomitant HF compared to usual care.

Left and right ventricular strain-volume/area loops: a narrative review of current physiological understanding and potential clinical value.

Traditionally, echocardiography is used for volumetric measurements to aid in assessment of cardiac function. Multiple echocardiographic-based assessment techniques have been developed, such as Doppler ultrasound and deformation imaging (e.g., peak global longitudinal strain (GLS)), which have shown to be clinically relevant. Volumetric changes across the cardiac cycle can be related to deformation, resulting in the Ventricular Strain-Volume/Area Loop. These Loops allow assessment of the dynamic relationship between longitudinal strain change and volumetric change across both systole and diastole. This integrated approach to both systolic and diastolic function assessment may offer additional information in conjunction with traditional, static, measures of cardiac function or structure. The aim of this review is to summarize our current understanding of the Ventricular Strain-Volume/Area Loop, describe how acute and chronic exposure to hemodynamic stimuli alter Loop characteristics, and, finally, to outline the potential clinical value of these Loops in patients with cardiovascular disease. In summary, several studies observed Loop changes in different hemodynamic loading conditions and various (patho)physiological conditions. The diagnostic and prognostic value, and physiological interpretation remain largely unclear and have been addressed only to a limited extent.

What Is the Patient-reported Outcome and Complication Incidence After Operative Versus Nonoperative Treatment of Minimally Displaced Tibial Plateau Fractures?

BACKGROUND: Much controversy remains about whether minimally displaced tibial plateau fractures should be treated operatively or nonoperatively. It is generally accepted that gaps and stepoffs up to 2 mm can be tolerated, but this assumption is based on older studies using plain radiographs instead of CT to assess the degree of initial fracture displacement. Knowledge regarding the relationship between the degree of fracture displacement and expected functional outcome is crucial for patient counseling and shared decision-making, specifically in terms of whether to perform surgery. QUESTIONS/PURPOSES: (1) Is operative treatment associated with improved patient-reported outcomes compared with nonoperative treatment in minimally displaced tibial plateau fractures (fractures with up to 4 mm of displacement)? (2) What is the difference in the risk of complications after operative versus nonoperative treatment in minimally displaced tibial plateau fractures? METHODS: A multicenter, cross-sectional study was performed in patients treated for tibial plateau fractures between 2003 and 2019 at six hospitals. Between January 2003 and December 2019, a total of 2241 patients were treated for tibial plateau fractures at six different trauma centers. During that time, the general indication for open reduction and internal fixation (ORIF) was intra-articular displacement of > 2 mm. Patients treated with ORIF and those treated nonoperatively were potentially eligible; 0.2% (4) were excluded because they were treated with amputation because of severe soft tissue damage, whereas 4% (89) were excluded because of coexisting conditions that complicated outcome measurement including Parkinson disease, cerebrovascular accident, or paralysis (conditions causing an inability to walk). A further 2.7% (60) were excluded because their address was unknown, and 1.4% (31) were excluded because they spoke a language other than Dutch. Based on that, 1328 patients were potentially eligible for analysis in the operative group and 729 were potentially eligible in the nonoperative group. At least 1 year after injury, all patients were approached and asked to complete the Knee injury and Osteoarthritis Outcome Scale (KOOS) questionnaire. A total of 813 operatively treated patients (response percentage: 61%) and 345 nonoperatively treated patients (response percentage: 47%) responded to the questionnaire. Patient characteristics including age, gender, BMI, smoking, and diabetes were retrieved from electronic patient records, and imaging data were shared with the initiating center. Displacement (gap and stepoff) was measured for all participating patients, and all patients with minimally displaced fractures (gap or stepoff ≤ 4 mm) were included, leaving 195 and 300 in the operative and nonoperative groups, respectively, for analysis here. Multivariate linear regression was performed to assess the association of treatment choice (nonoperative or operative) with patient-reported outcomes in minimally displaced fractures. In the multivariate analysis, we accounted for nine potential confounders (age, gender, BMI, smoking, diabetes, gap, stepoff, AO/OTA classification, and number of involved segments). In addition, differences in complications after operative and nonoperative treatment were assessed. The minimum clinically important differences for the five subscales of the KOOS are 11 for symptoms, 17 for pain, 18 for activities of daily living, 13 for sports, and 16 for quality of life. RESULTS: After controlling for potentially confounding variables such as age, gender, BMI, and AO/OTA classification, we found that operative treatment was not associated with an improvement in patient-reported outcomes. Operative treatment resulted in poorer KOOS in terms of pain (-4.7 points; p = 0.03), sports (-7.6 points; p = 0.04), and quality of life (-7.8 points; p = 0.01) compared with nonoperative treatment, but those differences were small enough that they were likely not clinically important. Patients treated operatively had more complications (4% [7 of 195] versus 0% [0 of 300]; p = 0.01) and reoperations (39% [76 of 195] versus 6% [18 of 300]; p < 0.001) than patients treated nonoperatively. After operative treatment, most reoperations (36% [70 of 195]) consisted of elective removal of osteosynthesis material. CONCLUSION: No differences in patient-reported outcomes were observed at midterm follow-up between patients treated surgically and those treated nonsurgically for tibial plateau fractures with displacement up to 4 mm. Therefore, nonoperative treatment should be the preferred treatment option in minimally displaced fractures. Patients who opt for nonoperative treatment should be told that complications are rare, and only 6% of patients might undergo surgery by midterm follow-up. Patients who opt for surgery of a minimally displaced tibial plateau fracture should be told that complications may occur in up to 4% of patients, and 39% of patients may undergo a secondary intervention (most of which are elective implant removal). LEVEL OF EVIDENCE: Level III, therapeutic study.

Tibial plateau fracture morphology based on injury force mechanism is predictive for patient-reported outcome and conversion to total knee arthroplasty.

PURPOSES: The aim of this study was to assess the relationship between injury mechanism-based fracture patterns and patient-reported outcome as well as conversion rate to total knee arthroplasty (TKA) at follow-up. METHODS: A multicenter cross-sectional study was performed including 1039 patients treated for a tibial plateau fracture between 2003 and 2019. At a mean follow-up of 5.8 ± 3.7 years, patients completed the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire. For all patients, the injury force mechanism was defined based on CT images. Analysis of variance (ANOVA) was used to assess the relationship between different injury mechanisms and functional recovery. Cox regression was performed to assess the association with an increased risk on conversion to TKA. RESULTS: A total of 378 (36%) patients suffered valgus-flexion, 305 (29%) valgus-extension, 122 (12%) valgus-hyperextension, 110 (11%) varus-flexion, 58 (6%) varus-hyperextension, and 66 (6%) varus-extension injuries. ANOVA showed significant different KOOS values between injury fracture patterns in all subscales (P < 0.01). Varus-flexion injuries had the lowest average KOOS scores (symptoms 65; pain 67; ADL 72; sport 35; QoL 48). Varus-flexion mechanism was associated with an increased risk on a TKA (HR 1.8; P = 0.03) whereas valgus-extension mechanism was associated with a reduced risk on a TKA (HR 0.5; P = 0.012) as compared to all other mechanisms. CONCLUSION: Tibial plateau fracture patterns based on injury force mechanisms are associated with clinical outcome. Varus-flexion injuries have a worse prognosis in terms of patient-reported outcome and conversion rate to TKA at follow-up. Valgus-extension injuries have least risk on conversion to TKA.

Left ventricular strain-volume loops and myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy.

BACKGROUND: The left ventricular strain-volume loop (SVL) combines changes in global longitudinal strain (GLS) and LV volume across a cardiac cycle, providing insight into cardiac dynamics. This study explored the association between left ventricular SVL and presence of fibrosis, assessed with late gadolinium enhancement, in patients with Duchenne muscular dystrophy (DMD). METHODS AND RESULTS: 34 pediatric patients with DMD were included. Feature tracking analysis was used to assess endocardial GLS and volumetric measurements to construct the SVL. Mean age at the time of assessment was 14 ± 3 and 11 ± 2 years old (p < 0.01) in the group with (n = 18) versus without fibrosis (n = 16), respectively. Left ventricular ejection fraction was not significantly different between groups (fibrosis: 56.4 ± 3.8% versus without fibrosis: 54.0 ± 6.3%, p = 0.18). After adjusting for age, the late diastolic slope of the SVL was significantly associated with presence of fibrosis (OR 0.39 [95% CI 0.18-0.85]; area under the receiver operating characteristic curve: 0.83 [95% CI 0.70-0.97]) No significant association was observed for peak strain and fibrosis (OR 1.15 [95% CI 0.86-1.546]). CONCLUSION: A lower late diastolic slope of the left ventricular SVL, related to the interplay between longitudinal deformation and volume changes late in diastole, is associated with presence of myocardial fibrosis in pediatric patients with DMD.

The Effect of Remote Ischemic Postconditioning on Quality of Life and Clinical Events after an Ischemic Stroke.

OBJECTIVES: Repeated remote ischemic postconditioning (rIPostC) may be an easily applicable treatment following ischemic stroke to improve quality of life (QoL) and clinical outcomes. rIPostC consists of repeated, brief periods of limb ischemia (through inflation of a blood pressure cuff), followed by reperfusion. This study investigated the 1-year follow-up of rIPostC on QoL and clinical events. METHODS: As part of a randomized controlled trial, adult patients with an ischemic stroke within 24 hours after onset of symptoms were randomized to repeated rIPostC or sham-conditioning. rIPostC was applied twice daily during hospitalization (maximum of 4 days). QoL and patientreported outcome measures (PROMs) were assessed at 12-week and 1-year follow-ups. Additionally, we explored the effect of repeated rIPostC on clinical events (recurrent cerebrovascular events, hospitalization, and mortality). RESULTS: The trial was preliminarily stopped due to limitations in recruitment after the inclusion of 88 patients (rIPostC: 40; sham-conditioning: 48) (70 years, 68% male). Questionnaires were returned by 69 (78%) and 63 (72%) participants after 12 weeks and 1 year, respectively. The median difference of the stroke-specific QoL between rIPostC and sham-conditioning was 0.05 (p =0.986) and -0.16 (p =0.654) after 12 weeks and 1-year, respectively. No significant effect of rIPostC on the different domains of PROMs was detected. We observed no between-group differences in recurrent cerebrovascular events, hospitalization, or all-cause mortality (Hazard Ratios p >0.05). CONCLUSION: In this exploratory analysis, we observed no significant difference between repeated rIPostC and usual care on QoL and clinical outcomes at 12 weeks and 1 year in patients with an ischemic stroke. CLINICAL TRIAL REGISTRATION NUMBER: NTR6880.

Left ventricular deformation and myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy.

BACKGROUND: Left ventricular (LV) strain and rotation are emerging functional markers for early detection of LV dysfunction and have been associated with the burden of myocardial fibrosis in several disease states. This study examined the association between LV deformation (i.e., LV strain and rotation) and extent and location of LV myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy (DMD). METHODS AND RESULTS: 34 pediatric patients with DMD underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) to assess LV myocardial fibrosis. Offline CMR feature-tracking analysis was used to assess global and segmental longitudinal and circumferential LV strain, and LV rotation. Patients with fibrosis (n = 18, 52.9%) were older than those without fibrosis (14 ± 3 years (yrs) vs 11 ± 2 yrs., p = 0.01). There was no significant difference in LV ejection fraction (LVEF) between subjects with and without fibrosis (54 ± 6% vs 56 ± 4%, p = 0.18). However, lower endocardial global circumferential strain (GCS), but not LV rotation, was associated with presence of fibrosis (adjusted Odds Ratio 1.25 [95% CI 1.01-1.56], p = 0.04). Both GCS and global longitudinal strain correlated with the extent of fibrosis (r = .52, p = 0.03 and r = .75, p < 0.01, respectively). Importantly, segmental strain did not seem to correspond to location of fibrosis. CONCLUSION: A lower global, but not segmental, strain is associated with presence and extent of LV myocardial fibrosis in pediatric DMD patients. Therefore, strain parameters might detect structural myocardial alterations, however currently more research is needed to evaluate its value (e.g., prognostic) in clinical practice.

Association of left ventricular strain-volume loop characteristics with adverse events in patients with heart failure with preserved ejection fraction.

AIMS: Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by impaired diastolic function. Left ventricular (LV) strain-volume loops (SVL) represent the relation between strain and volume during the cardiac cycle and provide insight into systolic and diastolic function characteristics. In this study, we examined the association of SVL parameters and adverse events in HFpEF. METHODS AND RESULTS: In 235 patients diagnosed with HFpEF, LV-SVL were constructed based on echocardiography images. The endpoint was a composite of all-cause mortality and Heart Failure (HF)-related hospitalization, which was extracted from electronic medical records. Cox-regression analysis was used to assess the association of SVL parameters and the composite endpoint, while adjusting for age, sex, and NYHA class. HFpEF patients (72.3% female) were 75.8 ± 6.9 years old, had a BMI of 29.9 ± 5.4 kg/m2, and a left ventricular ejection fraction of 60.3 ± 7.0%. Across 2.9 years (1.8-4.1) of follow-up, 73 Patients (31%) experienced an event. Early diastolic slope was significantly associated with adverse events [second quartile vs. first quartile: adjusted hazards ratio (HR) 0.42 (95%CI 0.20-0.88)] after adjusting for age, sex, and NYHA class. The association between LV peak strain and adverse events disappeared upon correction for potential confounders [adjusted HR 1.02 (95% CI 0.96-1.08)]. CONCLUSION: Early diastolic slope, representing the relationship between changes in LV volume and strain during early diastole, but not other SVL-parameters, was associated with adverse events in patients with HFpEF during 2.9 years of follow-up.

Radiographic Predictors of Conversion to Total Knee Arthroplasty After Tibial Plateau Fracture Surgery: Results in a Large Multicenter Cohort.

BACKGROUND: Radiographic measurements of initial displacement of tibial plateau fractures and of postoperative reduction are used to determine treatment strategy and prognosis. We assessed the association between radiographic measurements and the risk of conversion to total knee arthroplasty (TKA) at the time of follow-up. METHODS: A total of 862 patients surgically treated for tibial plateau fractures between 2003 and 2018 were eligible for this multicenter cross-sectional study. Patients were approached for follow-up, and 477 (55%) responded. The initial gap and step-off were measured on the preoperative computed tomography (CT) scans of the responders. Condylar widening, residual incongruity, and coronal and sagittal alignment were measured on postoperative radiographs. Critical cutoff values for gap and step-off were determined using receiver operating characteristic curves. Postoperative reduction measurements were categorized as adequate or inadequate on the basis of cutoff values in international guidelines. Multivariable analysis was performed to assess the association between each radiographic measurement and conversion to TKA. RESULTS: Sixty-seven (14%) of the patients had conversion to TKA after a mean follow-up of 6.5 ± 4.1 years. Assessment of the preoperative CT scans revealed that a gap of >8.5 mm (hazard ratio [HR] = 2.6, p < 0.001) and step-off of >6.0 mm (HR = 3.0, p < 0.001) were independently associated with conversion to TKA. Assessment of the postoperative radiographs demonstrated that residual incongruity of 2 to 4 mm was not associated with increased risk of TKA compared with adequate fracture reduction of <2 mm (HR = 0.6, p = 0.176). Articular incongruity of >4 mm resulted in increased risk of TKA. Coronal (HR = 1.6, p = 0.05) and sagittal malalignment (HR = 3.7 p < 0.001) of the tibia were strongly associated with conversion to TKA. CONCLUSIONS: Substantial preoperative fracture displacement was a strong predictor of conversion to TKA. Postoperative gaps or step-offs of >4 mm as well as inadequate alignment of the tibia were strongly associated with an increased risk of TKA. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Left ventricular strain-volume loops and diastolic dysfunction in suspected heart failure with preserved ejection fraction.

BACKGROUND: Presence of left ventricular diastolic dysfunction (DD) is key in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, non-invasive assessment of diastolic function is complex, cumbersome, and largely based on consensus recommendations. Novel imaging techniques may help detecting DD. Therefore, we compared left ventricular strain-volume loop (SVL) characteristics and diastolic (dys-)function in suspected HFpEF patients. METHOD AND RESULTS: 257 suspected HFpEF patients with sinus rhythm during echocardiography were prospectively included. 211 patients with quality-controlled images and strain and volume analysis were classified according to the 2016 ASE/EACVI recommendations. Patients with indeterminate diastolic function were excluded, resulting in two groups: normal diastolic function (control; n = 65) and DD (n = 91). Patients with DD were older (74.8 ± 6.9 vs. 68.5 ± 9.4 years, p < 0.001), more often female (88% vs 72%, p = 0.021), and more often had a history of atrial fibrillation (42% vs. 23%, p = 0.024) and hypertension (91% vs. 71%, p = 0.001) compared to normal diastolic function. SVL analysis showed a larger uncoupling i.e., a different longitudinal strain contribution to volume change, in DD compared to controls (0.556 ± 1.10% vs. -0.051 ± 1.14%, respectively, P < 0.001). This observation suggests different deformational properties during the cardiac cycle. After adjustment for age, sex, history of atrial fibrillation and hypertension, we found an adjusted odds ratio of 1.68 (95% confidence interval 1.19-2.47) for DD per unit increase in uncoupling (range: -2.95-3.20). CONCLUSION: Uncoupling of the SVL is independently associated with DD. This might provide novel insights in cardiac mechanics and new opportunities to assess diastolic function non-invasively.

Consensus molecular subtype 4 (CMS4)-targeted therapy in primary colon cancer: A proof-of-concept study.

Background: Mesenchymal Consensus Molecular Subtype 4 (CMS4) colon cancer is associated with poor prognosis and therapy resistance. In this proof-of-concept study, we assessed whether a rationally chosen drug could mitigate the distinguishing molecular features of primary CMS4 colon cancer. Methods: In the ImPACCT trial, informed consent was obtained for molecular subtyping at initial diagnosis of colon cancer using a validated RT-qPCR CMS4-test on three biopsies per tumor (Phase-1, n=69 patients), and for neoadjuvant CMS4-targeting therapy with imatinib (Phase-2, n=5). Pre- and post-treatment tumor biopsies were analyzed by RNA-sequencing and immunohistochemistry. Imatinib-induced gene expression changes were associated with molecular subtypes and survival in an independent cohort of 3232 primary colon cancer. Results: The CMS4-test classified 52/172 biopsies as CMS4 (30%). Five patients consented to imatinib treatment prior to surgery, yielding 15 pre- and 15 post-treatment samples for molecular analysis. Imatinib treatment caused significant suppression of mesenchymal genes and upregulation of genes encoding epithelial junctions. The gene expression changes induced by imatinib were associated with improved survival and a shift from CMS4 to CMS2. Conclusion: Imatinib may have value as a CMS-switching drug in primary colon cancer and induces a gene expression program that is associated with improved survival.

Potential tradeoffs between effects of arbuscular mycorrhizal fungi inoculation, soil organic matter content and fertilizer application in raspberry production.

Ecological intensification has been proposed as an alternative paradigm for intensive agriculture to boost yield sustainably through utilizing ecosystem services. A prerequisite to achieving this is to understand the relations between multiple ecosystem services and production, while taking growth conditions such as nutrient availability into consideration. Here, we conducted a pot-field experiment to study the interactive effects of soil organic matter (SOM) content and arbuscular mycorrhizal fungi (AMF) inoculation on the production of raspberry (Rubus idaeus L.) under four levels of fertilizer application. Raspberry flower number, fruit number and yield only significantly increased with fertilizer inputs but were not impacted by SOM content or AMF inoculation. Fruit set and single berry weight were influenced by both SOM content and AMF inoculation, in complex three-way interactions with fertilizer application. Fruit set of AMF inoculated plants increased with fertilizer inputs in low SOM soils, but decreased with fertilizer inputs under high SOM soils, with the highest fruit set occurring at no fertilizer inputs. In low SOM soils, the relation between single berry weight and fertilizer application was more pronounced in inoculated plants than in non-inoculated plants, while in high SOM soils the relative benefits of AMF inoculation on single berry weight decreased with increasing fertilizer inputs. We attribute the lack of effects of AMF inoculation and SOM content on flower number, fruit number and yield mainly to potential tradeoffs between the experimental variables that all influence resource uptake by plant root systems. Our results suggest that potentially beneficial effects of AMF and SOM can be offset by each other, probably driven by the dynamic relations between AMF and the host plants. The findings reveal fundamental implications for managing AMF inoculation and SOM management simultaneously in real-world agricultural systems.

Functional Outcome After Nonoperative Management of Tibial Plateau Fractures in Skeletally Mature Patients: What Sizes of Gaps and Stepoffs Can be Accepted?

BACKGROUND: Gap and stepoff measurements provide information about fracture displacement and are used for clinical decision-making when choosing either operative or nonoperative management of tibial plateau fractures. However, there is no consensus about the maximum size of gaps and stepoffs on CT images and their relation to functional outcome in skeletally mature patients with tibial plateau fractures who were treated without surgery. Because this is important for patient counseling regarding treatment and prognosis, it is critical to identify the limits of gaps and stepoffs that are well tolerated. QUESTIONS/PURPOSES: (1) In patients treated nonoperatively for tibial plateau fractures, what is the association between initial fracture displacement, as measured by gaps and stepoffs at the articular surface on a CT image, and functional outcome? (2) What is the survivorship of the native joint, free from conversion to a total knee prosthesis, among patients with tibial plateau fractures who were treated without surgery? METHODS: A multicenter cross-sectional study was performed in all patients who were treated nonoperatively for a tibial plateau fracture between 2003 and 2018 in four trauma centers. All patients had a diagnostic CT scan, and a gap and/or stepoff more than 2 mm was an indication for recommending surgery. Some patients with gaps and/or stepoffs exceeding 2 mm might not have had surgery based on shared decision-making. Between 2003 and 2018, 530 patients were treated nonoperatively for tibial plateau fractures, of which 45 had died at follow-up, 30 were younger than 18 years at the time of injury, and 10 had isolated tibial eminence avulsions, leaving 445 patients for follow-up analysis. All patients were asked to complete the validated Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire consisting of five subscales: symptoms, pain, activities of daily living (ADL), function in sports and recreation, and knee-related quality of life (QOL). The score for each subscale ranged from 0 to 100, with higher scores indicating better function. A total of 46% (203 of 445) of patients participated at a mean follow-up of 6 ± 3 years since injury. All knee radiographs and CT images were reassessed, fractures were classified, and gap and stepoff measurements were taken. Nonresponders did not differ much from responders in terms of age (53 ± 16 years versus 54 ± 20 years; p = 0.89), gender (70% [142 of 203] women versus 59% [142 of 242] women; p = 0.01), fracture classifications (Schatzker types and three-column concept), gaps (2.1 ± 1.3 mm versus 1.7 ± 1.6 mm; p = 0.02), and stepoffs (2.1 ± 2.2 mm versus 1.9 ± 1.7 mm; p = 0.13). In our study population, the mean gap was 2.1 ± 1.3 mm and stepoff was 2.1 ± 2.2 mm. The participating patients divided into groups with increasing fracture displacement based on gap and/or stepoff (< 2 mm, 2 to 4 mm, or > 4 mm), as measured on CT images. ANOVA was used to assess whether an increase in the initial fracture displacement was associated with poorer functional outcome. We estimated the survivorship of the knee free from conversion to total knee prosthesis at a mean follow-up of 5 years using a Kaplan-Meier survivorship estimator. RESULTS: KOOS scores in patients with a less than 2 mm, 2 to 4 mm, or greater than 4 mm gap did not differ (symptoms: 83 versus 83 versus 82; p = 0.98, pain: 85 versus 83 versus 86; p = 0.69, ADL: 87 versus 84 versus 89; p = 0.44, sport: 65 versus 64 versus 66; p = 0.95, QOL: 70 versus 71 versus 74; p = 0.85). The KOOS scores in patients with a less than 2 mm, 2 to 4 mm, or greater than 4 mm stepoff did not differ (symptoms: 84 versus 83 versus 77; p = 0.32, pain: 85 versus 85 versus 81; p = 0.66, ADL: 86 versus 87 versus 82; p = 0.54, sport: 65 versus 68 versus 56; p = 0.43, QOL: 71 versus 73 versus 61; p = 0.19). Survivorship of the knee free from conversion to total knee prosthesis at mean follow-up of 5 years was 97% (95% CI 94% to 99%). CONCLUSION: Patients with minimally displaced tibial plateau fractures who opt for nonoperative fracture treatment should be told that fracture gaps or stepoffs up to 4 mm, as measured on CT images, could result in good functional outcome. Therefore, the arbitrary 2-mm limit of gaps and stepoffs for tibial plateau fractures could be revisited. The survivorship of the native knee free from conversion to a total knee prosthesis was high. Large prospective cohort studies with high response rates are needed to learn more about the relationship between the degree of fracture displacement and functional recovery after tibial plateau fractures. LEVEL OF EVIDENCE: Level III, prognostic study.

Water Loss from Protonated XxxSer and XxxThr Dipeptides Gives Oxazoline-Not Oxazolone-Product Ions.

Neutral loss of water and ammonia are often significant fragmentation channels upon collisional activation of protonated peptides. Here, we deploy infrared ion spectroscopy to investigate the dehydration reactions of protonated AlaSer, AlaThr, GlySer, GlyThr, PheSer, PheThr, ProSer, ProThr, AsnSer, and AsnThr, focusing on the question of the structure of the resulting [M + H - H2O]+ fragment ion and the site from which H2O is expelled. In all cases, the second residue of the selected peptides contains a hydroxyl moiety, so that H2O loss can potentially occur from this side-chain, as an alternative to loss from the C-terminal free acid of the dipeptide. Infrared action spectra of the product ions along with quantum-chemical calculations unambiguously show that dehydration consistently produces fragment ions containing an oxazoline moiety. This contrasts with the common oxazolone structure that would result from dehydration at the C-terminus analogous to the common b/y dissociation forming regular b2-type sequence ions. The oxazoline product structure suggests a reaction mechanism involving water loss from the Ser/Thr side-chain with concomitant nucleophilic attack of the amide carbonyl oxygen at its ß-carbon, forming an oxazoline ring. However, an extensive quantum-chemical investigation comparing the potential energy surfaces for three entirely different dehydration reaction pathways indicates that it is actually the backbone amide oxygen atom that leaves as the water molecule.

Effects of landscape complexity on pollinators are moderated by pollinators' association with mass-flowering crops.

Conserving and restoring semi-natural habitat, i.e. enhancing landscape complexity, is one of the main strategies to mitigate pollinator decline in agricultural landscapes. However, we still have limited understanding of how landscape complexity shapes pollinator communities in both crop and non-crop habitat, and whether pollinator responses to landscape complexity vary with their association with mass-flowering crops. Here, we surveyed pollinator communities on mass-flowering leek crops and in nearby semi-natural habitat in landscapes of varying complexity. Surveys were done before and during crop bloom and distinguished between pollinators that visit the crop frequently (dominant), occasionally (opportunistic), or not at all (non-crop). Forty-seven per cent of the species in the wider landscape were also observed on leek flowers. Crop pollinator richness increased with local pollinator community size and increasing landscape complexity, but relationships were stronger for opportunistic than for dominant crop pollinators. Relationships between pollinator richness in semi-natural habitats and landscape complexity differed between groups with the most pronounced positive effects on non-crop pollinators. Our results indicate that while dominant crop pollinators are core components of crop pollinator communities in all agricultural landscapes, opportunistic crop pollinators largely determine species-richness responses and complex landscapes are local hotspots for both biodiversity conservation and potential ecosystem service provision.

12-Week Exercise Training, Independent of the Type of Exercise, Attenuates Endothelial Ischaemia-Reperfusion Injury in Heart Failure Patients.

Introduction: Reperfusion is required to salvage ischaemic tissue, but also causes further damage (i.e., ischaemia/reperfusion-injury). Heart failure patients reveal exaggerated ischaemia/reperfusion-injury, whilst traditional ischaemic preconditioning cannot prevent ischaemia/reperfusion-injury. Exercise training may be a more powerful preconditioning stimulus, especially high-intensity interval training given the similarities with ischaemic preconditioning. Therefore, we examined the impact of 12-week continuous training vs. high-intensity interval training on brachial artery endothelial ischaemia/reperfusion-injury in heart failure patients New York Heart Association-class II-III. Methods: Twenty heart failure patients (male:female 19:1, 64 ± 8 years, ejection fraction 38 ± 6%) were allocated to 12-weeks of high-intensity interval training (10∗1-min 90% maximal workload - 2.5-min 30% maximal workload) or continuous training (30-min 60-75% maximal workload). Before and after the intervention, we measured brachial artery endothelial function with flow-mediated dilation (FMD) before and after ischaemia/reperfusion (5-min ischemic exercise, 15-min reperfusion). Results: Ischaemia/reperfusion caused a significant decline in FMD (continuous training (n = 10): 5.2 ± 2.5 to 3.4 ± 1.6%, high-intensity interval training (n = 10): 5.3 ± 2.6 to 3.5 ± 1.6%, P = 0.01), which was not different between groups (P > 0.05). Training improved maximal workload and fitness (P < 0.05), with no differences between groups (P > 0.05). Exercise training did not alter FMD (P > 0.05), whilst ischaemia/reperfusion did not impair FMD after exercise training (continuous training: 4.8 ± 3.0 to 4.2 ± 2.3%, high-intensity interval training: 4.7 ± 2.5 to 3.8 ± 2.3%, P > 0.05). No changes were found in FMD before or after ischaemia/reperfusion after 12-weeks in controls (n = 9). Conclusion: We found that 12-week exercise training in heart failure patients mitigated endothelial ischaemia-reperfusion injury, an effect independent of the type of exercise. These changes may contribute to the cardioprotective effects of exercise training, whilst our findings highlight the potency of exercise as a preconditioning stimulus.