Rootstock and Crop Load Effects on 'Honeycrisp' Photosynthetic Performance and Carbohydrate Accumulation.

Rootstock selection and crop load adjustment are key practices in apple orchard management; nevertheless, the effects of rootstocks and crop load levels on important physiological processes of the scions, such as photosynthetic performance and carbohydrate accumulation, are still unclear. To investigate the impact of different rootstocks and crop load levels on scion photosynthesis and carbohydrate buildup, in 2020, 'Honeycrisp' trees grafted on rootstocks 'G.41', 'G.935', and 'M.9-T337' were thinned to low and high crop load levels, and photosynthetic performance and carbohydrate accumulation in leaves and fruit were evaluated. Leaves from 'G.935' showed the highest net photosynthesis and electron use efficiency of photosynthesis and the lowest activity for non-net carboxylative processes, all together indicative of enhanced photosynthetic performance. High crop load determined an increase in gas exchange, suggesting a positive feedback of high fruit competition on carbon assimilation. While rootstock 'M.9-T337' showed a higher accumulation of starch in leaves, no pattern regarding the composition of leaf-soluble sugars among rootstocks could be identified. Conversely, by the end of the harvest season, leaves from low-cropping trees had higher fructose, glucose, and sorbitol than those from high-cropping trees, but differences in starch content were not significant. Fructose and sorbitol concentrations were affected by rootstock and crop load, respectively. Overall, this study showed that high cropping enhanced photosynthesis in 'Honeycrisp' apple and determined lower accumulation of some soluble carbohydrates (fructose, glucose, sorbitol) in leaves. This study also provided insights into how rootstocks affect photosynthetic performance of 'Honeycrisp', highlighting 'G.935' as the rootstock conferring the highest photosynthetic capacity under the present experimental conditions.

Combination of protein and cell internalization SELEX identifies a potential RNA therapeutic and delivery platform to treat EphA2-expressing tumors.

The EphA2 receptor tyrosine kinase is overexpressed in most solid tumors and acts as the major driver of tumorigenesis. In this study, we developed a novel approach for targeting the EphA2 receptor using a 2'-fluoro-modified pyrimidine RNA aptamer termed ATOP. We identified the ATOP EphA2 aptamer using a novel bioinformatics strategy that compared aptamers enriched during a protein SELEX using recombinant human EphA2 and a cell-internalization SELEX using EphA2-expressing MDA231 tumor cells. When applied to EphA2-expressing tumor cell lines, the ATOP EphA2 aptamer attenuated tumor cell migration and clonogenicity. In a mouse model of spontaneous metastasis, the ATOP EphA2 aptamer slowed primary tumor growth and significantly reduced the number of lung metastases. The EphA2 ATOP aptamer represents a promising candidate for the development of next-generation targeted therapies that provide safer and more effective treatment of EphA2-overexpressing tumors.

Shear-Wave Elastography Evaluation of Major Salivary Glands in Primary Sjögren's Syndrome.

OBJECTIVES: Salivary glands ultrasonography has recently been shown to be useful in the diagnosis of Primary Sjögren's Syndrome (pSS). Shear-wave elastography (SWE) is a promising tool for the quantitative assessment of tissues stiffness, but studies evaluating its role in pSS diagnosis are limited. This study aimed at investigating the diagnostic performance of SWE in pSS. MATERIALS AND METHODS: Cross-sectional study including patients fulfilling the 2016 ACR/EULAR classification criteria for pSS and healthy subjects. The four major salivary glands were assessed using SGUS. B-mode scans were rated using the Hocevar score, and shear-wave velocity (SWV) values were obtained using SWE. Intraclass-correlation coefficient (ICC) estimates were used to assess reliability. Cut-off values for differentiating pSS patients from healthy subjects were calculated using Receiver-Operating Characteristics (ROC) curves. RESULTS: We included 50 pSS and 25 healthy subjects. Inter-rater reliability of SWE was moderate (ICC=0.64) and intra-rater reliability was moderate to good (ICC= 0.73 to 0.83). Total SWV (2.09 m/s (0.32); p < 0.001), parotid SWV (2.25 m/s (0.40)) and submandibular SWV (1.92 m/s (0.38)) were significantly higher in pSS patients. Total and parotid SWV presented good diagnostic performance for pSS diagnosis (AUROC= 0.80 and 0.81, respectively). The Hocevar score demonstrated excellent diagnostic performance (AUROC= 0.98) and combining it with total SWV did not result in statistically significant improvement (p=0.301). CONCLUSIONS: SWE may contribute to the diagnosis of pSS. Large prospective studies including sicca and secondary SS patients, as well as the standardisation of SWE protocols, are warranted to assess the role of SWE in pSS management.

Factors associated with perinatal mortality in a Brazilian Northeastern capital. / Fatores associados à mortalidade perinatal em uma capital do Nordeste brasileiro.

This study investigated factors associated with perinatal mortality in São Luís, Maranhão, Northeastern Brazil. Data on perinatal mortality were obtained from the BRISA birth cohort and from the Mortality Information System, including records of 5,236 births, 70 of which referred to fetal deaths and 36 to early neonatal deaths. Factors associated with mortality were investigated using a hierarchical logistic regression model, resulting in a perinatal mortality coefficient equal to 20.2 per thousand births. Mothers with low education level and without a partner were associated with an increased risk of perinatal death. Moreover, children of mothers who did not have at least six antenatal appointments and with multiple pregnancies (OR= 9.15; 95%CI:4.08-20.53) were more likely to have perinatal death. Perinatal death was also associated with the presence of congenital malformations (OR= 4.13; 95%CI:1.23-13.82), preterm birth (OR= 3.36; 95%CI:1.56-7.22), and low birth weight (OR=11.87; 95%CI:5.46-25.82). In turn, families headed by other family members (OR= 0.29; 95%CI: 0.12 - 0.67) comprised a protective factor for such condition. Thus, the results indicate an association between perinatal mortality and social vulnerability, non-compliance with the recommended number of prenatal appointments, congenital malformations, preterm birth, and low birthweight.

O objetivo do estudo foi avaliar os fatores sociodemográficos, maternos e do recém-nascido associados à mortalidade perinatal em São Luís, Maranhão. Os óbitos perinatais foram identificados na coorte e pelo Sistema de Informações sobre Mortalidade. Foram incluídos 5.236 nascimentos, sendo 70 óbitos fetais e 36 neonatais precoces. Para investigar os fatores associados utilizou-se análise de regressão logística com modelo hierarquizado. O coeficiente de mortalidade perinatal foi 20,2 por mil nascimentos. A baixa escolaridade materna e a ausência de companheiro foram associadas a maior chance de óbito perinatal. A família ser chefiada por outros familiares foi fator de proteção. Tiveram maior chance de óbito perinatal filhos de mães que não realizaram pelo menos seis consultas de pré-natal (OR=4,61; IC95%:2,43-8,74) e com gravidez múltipla (OR=9,15; IC95%:4,08-20,53). Presença de malformações congênitas (OR=4,13; IC95%:1,23-13,82), nascimento pré-termo (OR= 3,36; IC95%: 1,56-7,22) e baixo peso ao nascer (BPN) (OR=11,87; IC95%:5,46-25,82) se associaram ao óbito perinatal. A mortalidade perinatal foi associada à vulnerabilidade social, não realização do número de consultas pré-natal recomendado, malformações congênitas, nascimento pré-termo e BPN.

Fatores associados à mortalidade perinatal em uma capital do Nordeste brasileiro / Factors associated with perinatal mortality in a Brazilian Northeastern capital

Resumo O objetivo do estudo foi avaliar os fatores sociodemográficos, maternos e do recém-nascido associados à mortalidade perinatal em São Luís, Maranhão. Os óbitos perinatais foram identificados na coorte e pelo Sistema de Informações sobre Mortalidade. Foram incluídos 5.236 nascimentos, sendo 70 óbitos fetais e 36 neonatais precoces. Para investigar os fatores associados utilizou-se análise de regressão logística com modelo hierarquizado. O coeficiente de mortalidade perinatal foi 20,2 por mil nascimentos. A baixa escolaridade materna e a ausência de companheiro foram associadas a maior chance de óbito perinatal. A família ser chefiada por outros familiares foi fator de proteção. Tiveram maior chance de óbito perinatal filhos de mães que não realizaram pelo menos seis consultas de pré-natal (OR=4,61; IC95%:2,43-8,74) e com gravidez múltipla (OR=9,15; IC95%:4,08-20,53). Presença de malformações congênitas (OR=4,13; IC95%:1,23-13,82), nascimento pré-termo (OR= 3,36; IC95%: 1,56-7,22) e baixo peso ao nascer (BPN) (OR=11,87; IC95%:5,46-25,82) se associaram ao óbito perinatal. A mortalidade perinatal foi associada à vulnerabilidade social, não realização do número de consultas pré-natal recomendado, malformações congênitas, nascimento pré-termo e BPN.

Abstract This study investigated factors associated with perinatal mortality in São Luís, Maranhão, Northeastern Brazil. Data on perinatal mortality were obtained from the BRISA birth cohort and from the Mortality Information System, including records of 5,236 births, 70 of which referred to fetal deaths and 36 to early neonatal deaths. Factors associated with mortality were investigated using a hierarchical logistic regression model, resulting in a perinatal mortality coefficient equal to 20.2 per thousand births. Mothers with low education level and without a partner were associated with an increased risk of perinatal death. Moreover, children of mothers who did not have at least six antenatal appointments and with multiple pregnancies (OR= 9.15; 95%CI:4.08-20.53) were more likely to have perinatal death. Perinatal death was also associated with the presence of congenital malformations (OR= 4.13; 95%CI:1.23-13.82), preterm birth (OR= 3.36; 95%CI:1.56-7.22), and low birth weight (OR=11.87; 95%CI:5.46-25.82). In turn, families headed by other family members (OR= 0.29; 95%CI: 0.12 - 0.67) comprised a protective factor for such condition. Thus, the results indicate an association between perinatal mortality and social vulnerability, non-compliance with the recommended number of prenatal appointments, congenital malformations, preterm birth, and low birthweight.

Effective Pollination Period and Parentage Effect on Pollen Tube Growth in Apple.

Flower receptivity is a limiting factor for the fertilization of several tree fruit. The effective pollination period (EPP) can be used to determine flower longevity and identify limiting factors by assessing stigmatic receptivity, pollen tube growth rate, and ovule longevity. EPPs were determined for three apple cultivars under natural field conditions in Washington State in 2019 and 2020. In addition, a greenhouse study, performed under semi-controlled conditions, evaluated the influence of six maternal parents on the pollen tube growth performance of six pollen sources. The duration of the stigmatic receptivity ranged from 6.3 to 8.1 days, depending on the cultivar and year-pollen tubes required between 5.5 and 7.0 days from the stigma to reach the ovules. Ovule longevity of non-pollinated flowers varied between 8.2 and 11.3 days. Combinations of these factors resulted in EPPs ranging from 3.0 days for 'Rubinstar' to 5.6 days for 'Olsentwo Gala' in the present experimental conditions. The greenhouse study revealed that parentage affected pollen tube growth performance. Importantly, a significant interaction between maternal and paternal factors indicated that the performance of different pollen sources depended on the maternal parent and that general recommendations on pollination need to account for the maternal parent.

Jerks of the latissimus dorsi muscle and intercostal neuralgia after posterolateral thoracotomy.

INTRODUCTION: Post-thoracotomy pain syndrome (PTPS) is a common complication related to intercostal nerve injury. During this type of surgery, although less frequently, thoracodorsal and long thoracic nerves can also be injured, and jerks of peripheral origins may appear. We report a case with intercostal neuralgia and latissimus dorsi muscle jerks after posterolateral thoracotomy. CASE REPORT: A 55-year-old woman with Ehlers-Danlos Syndrome presented with a typical picture of PTPS along the right T5 dermatome following posterolateral thoracotomy at the level of the fifth intercostal space. Approximately six months after the surgery she developed frequent jerk-like involuntary movements of the right latissimus dorsi muscle. Neuropathic pain along the T5 dermatome was partially relieved with thoracic epidural block. No special attention was paid to the jerks until three years later. A neurophysiological study demonstrated a peripheral origin of these movements and the patient was then treated with periodic injections of botulinum toxin. In response, involuntary movements of the latissimus dorsi muscle disappeared. SIGNIFICANCE: To our knowledge, this is the first case with PTPS and post-thoracotomy latissimus dorsi muscle jerks in a patient with Ehlers-Danlos Syndrome. A correct diagnosis together with identification of iatrogenic neuropathic disorders allow the delivery of targeted treatments. In such cases clinical neurophysiology helps to determine a correct diagnosis.

Novel Metrics to Characterize In Vitro Pollen Tube Growth Performance of Apple Cultivars.

In vitro germination assays are frequently used in screening trials to evaluate the pollen viability of pollinizers. To be effective, screening trials must have defined threshold criteria, from which individuals can then be assessed. However, despite decades of research on pollen viability, no established threshold is available to categorize apple cultivars based on their in vitro pollen tube lengths. This study aimed to identify and characterize the subgroups of cultivars based on their pollen tube growth performance. In vitro pollen tube lengths of 41 individuals were determined by incubating samples on artificial germination media at 15 and 25 °C. A six-number summary statistic was calculated, and hierarchical clustering on principal component (HCPC) analysis was used to determine and characterize subgroups. Furthermore, a decision tree model was used to predict class membership for future datasets. HCPC analysis partitioned the 41 individuals into three subgroups with different performances. The decision tree quickly predicted the cluster membership based on the second quartile at 15 °C and the third quartile at 25 °C. The thresholds from the decision tree can be used to characterize new observations. The use of the methods will be demonstrated using a case study with 29 apple accessions.

Transcriptomics of Differential Ripening in 'd'Anjou' Pear (Pyrus communis L.).

Estimating maturity in pome fruits is a critical task that directs virtually all postharvest supply chain decisions. This is especially important for European pear (Pyrus communis) cultivars because losses due to spoilage and senescence must be minimized while ensuring proper ripening capacity is achieved (in part by satisfying a fruit chilling requirement). Reliable methods are lacking for accurate estimation of pear fruit maturity, and because ripening is maturity dependent it makes predicting ripening capacity a challenge. In this study of the European pear cultivar 'd'Anjou', we sorted fruit at harvest based upon on-tree fruit position to build contrasts of maturity. Our sorting scheme showed clear contrasts of maturity between canopy positions, yet there was substantial overlap in the distribution of values for the index of absorbance difference (I AD ), a non-destructive spectroscopic measurement that has been used as a proxy for pome fruit maturity. This presented an opportunity to explore a contrast of maturity that was more subtle than I AD could differentiate, and thus guided our subsequent transcriptome analysis of tissue samples taken at harvest and during storage. Using a novel approach that tests for condition-specific differences of co-expressed genes, we discovered genes with a phased character that mirrored our sorting scheme. The expression patterns of these genes are associated with fruit quality and ripening differences across the experiment. Functional profiles of these co-expressed genes are concordant with previous findings, and also offer new clues, and thus hypotheses, about genes involved in pear fruit quality, maturity, and ripening. This work may lead to new tools for enhanced postharvest management based on activity of gene co-expression modules, rather than individual genes. Further, our results indicate that modules may have utility within specific windows of time during postharvest management of 'd'Anjou' pear.

High patient global assessment scores in patients with rheumatoid arthritis otherwise in remission do not reflect subclinical inflammation.

OBJECTIVES: To assess whether high patient global assessment (PGA) scores by patients with rheumatoid arthritis (RA) otherwise in remission reflect subclinical inflammation. METHODS: Cross-sectional, single-center study, including consecutive RA patients. Remission states were defined based on the ACR/EULAR Boolean definition: 4V-remission (tender and swollen 28-joint counts (TJC28/SJC28), C-reactive protein (CRP), and PGA all≤1), PGA-near-remission (the same, except PGA>1), and non-remission (any of TJC28, SJC28, CRP>1). A blinded expert musculoskeletal ultrasonographer scanned 44 joints, 38 tendon sheaths, 4 bursae on the same day of the clinical evaluation. Each structure was assessed for the presence of Grey Scale synovial hypertrophy (GS) and Power Doppler (PD), both scored using a semi-quantitative scale (0-3 points). The Global OMERACT-EULAR Synovitis Score (GLOESS, 0-132, primary outcome), and a global tenosynovitis/bursitis score (GTBS) were compared between remission states, using non-parametric tests. Different sensitivity analyses comparing GS and PD subscores were performed. RESULTS: In total, 130 patients (mean age 63 years, 86% female, average disease duration 14 years) were included 40 being in 4V-remission, 40 in PGA-near-remission, 50 in non-remission. 4v-remission and PGA-near-remission presented similar median (IQR) GLOESS, [6 (5-11) and 4 (1-7), P>0.05, respectively] and GTBS [0 (0-1) and 0 (0-2), P>0.05, respectively]. The same was observed in GS, PD scores, and in global synovitis score considering only the 16 joints not included in 28-joint counts. These observations were confirmed in patients with≤5 years disease duration. CONCLUSIONS: Subclinical inflammation is not present among persons with elevated PGA who are otherwise in remission. PGA-near-remission patients would be exposed to the risk of overtreatment if current treatment recommendations were strictly followed. This study supports the need to reconsider the role of PGA in definitions used to target immunosuppressive therapy and to provide a separate and enhanced focus to the patient's experience of the disease.

Targeting Adenosine with Adenosine Deaminase 2 to Inhibit Growth of Solid Tumors.

Extracellular adenosine in tumors can suppress immune responses and promote tumor growth. Adenosine deaminase 2 (ADA2) converts adenosine into inosine. The role of ADA2 in cancer and whether it can target adenosine for cancer therapy has not been investigated. Here we show that increased ADA2 expression is associated with increased patient survival and enrichment of adaptive immune response pathways in several solid tumor types. Several ADA2 variants were created to improve catalytic efficiency, and PEGylation was used to prolong systemic exposure. In mice, PEGylated ADA2 (PEGADA2) inhibited tumor growth by targeting adenosine in an enzyme activity-dependent manner and thereby modulating immune responses. These findings introduce endogenous ADA2 expression as a prognostic factor and PEGADA2 as a novel immunotherapy for cancer. SIGNIFICANCE: This study identifies ADA2 as a prognostic factor associated with prolonged cancer patient survival and introduces the potential of enzymatic removal of adenosine with engineered ADA2 for cancer immunotherapy.

Determination of Post-Harvest Biochemical Composition, Enzymatic Activities, and Oxidative Browning in 14 Apple Cultivars.

Phenolic compounds in fruit provide human health benefits, and they contribute to color, taste, and the preservation of post-harvest fruit quality. Phenolic compounds also serve as modifiers of enzymatic activity, whether inhibition or stimulation. Polyphenol oxidases (PPO) and peroxidases (POD) use phenolic compounds as substrates in oxidative browning. Apple browning leads to flesh color, taste, texture, and flavor degradation, representing a drawback for the variety and its' market appraisal. This study was conducted to investigate the process of browning in 14 apple cultivars throughout post-harvest at three-time points: immediately (T0), one hour (T1), and 24 h (T2) after apples were cut in half. Color parameters L* (lightness), a* (red/green), b* (yellow/blue) were measured, and chroma (ΔC*) and color (ΔE) were calculated to quantify differences between T0₋T1 and T1₋T2 on the fruit surface. Enzymatic activity (PPO, POD) and phenolic composition were also quantified for each cultivar. 'Granny Smith' and 'Cripps Pink' browned minimally. In contrast, 'Fiesta' and 'Mondial Gala' browned severely, reporting high enzymatic activity and quantified phenolic concentration (QPC). Phenolic compound polymerization appears to play a significant role in enzymatic inhibition. 'Topaz' does not fit the high QPC, PPO, and browning formula, suggesting alternative pathways that contribute to apple browning.

Targeting of the A2A adenosine receptor counteracts immunosuppression in vivo in a mouse model of chronic lymphocytic leukemia.

Tumor immunosuppression is a major cause for treatment failure and disease relapse, both in solid tumors and leukemia. Local hypoxia is among the conditions that cause immunosuppression, acting at least in part through the upregulation of extracellular adenosine levels, which potently suppress T cell responses and skew macrophages towards an M2 phenotype. Hence, there is intense investigation to identify drugs that target this axis. By using the TCL1 adoptive transfer CLL mouse model, we show that adenosine production and signaling are upregulated in the hypoxic lymphoid niches, where intense colonization of leukemic cells occurs. This leads to a progressive remodeling of the immune system towards tolerance, with expansion of T regulatory cells (Tregs), loss of CD8+ T cell cytotoxicity and differentiation of murine macrophages towards the patrolling (M2-like) subset. In vivo administration of SCH58261, an inhibitor the A2A adenosine receptor, re-awakens T cell responses, while limiting Tregs expansion, and re-polarizes monocytes towards the inflammatory (M1-like) phenotype. These results show for the first time the in vivo contribution of adenosine signaling to immune tolerance in CLL, and the translational implication of drugs interrupting this pathway. Although the effects of SCH58261 on leukemic cells are limited, interfering with adenosine signaling may represent an appealing strategy for combination-based therapeutic approaches.

Photoselective Protective Netting Improves "Honeycrisp" Fruit Quality.

High temperatures, wind, and excessive sunlight can negatively impact yield and fruit quality in semi-arid apple production regions. Netting was originally designed for hail protection, but it can modify the light spectrum and affect fruit quality. Here, pearl, blue, and red photoselective netting (≈20% shading factor) was installed in 2015 over a commercial "Cameron Select® Honeycrisp" orchard. Our research objectives were to (1) describe the light quantity and quality under the colored nets compared to an uncovered control and (2) investigate the effect of Photoselective nets on "Honeycrisp" apple quality for two growing seasons. Light transmittance and scattering for each treatment were measured with a spectroradiometer, and samples for fruit quality analyses were collected at harvest. PAR (photosynthetic active radiation), UV, blue, red, and far-red light were lower underneath all netting treatments compared to an uncovered control. The scattered light was higher under the pearl net compared to other colors, while red and far-red light were lower under the blue net. For two consecutive years, trees grown under the photoselective nets intercepted more incoming light than the uncovered trees with no differences among the three colors. In both years, trees under red and blue nets had more sunburn-free (clean) apples than pearl and control. Red color development for fruit was lower when nets were used. Interestingly, bitter pit incidence was lower underneath red nets for both years. Other than red color development, "Honeycrisp" fruit quality was not appreciably affected by the use of netting. These results highlight the beneficial effect of nets in improving light quality in orchards and mitigating physiological disorders such as bitter pit in "Honeycrisp" apple.

Determination of Biochemical Composition in Peach (Prunus persica L. Batsch) Accessions Characterized by Different Flesh Color and Textural Typologies.

The rising interest in beneficial health properties of polyphenol compounds in fruit initiated this investigation about biochemical composition in peach mesocarp/exocarp. Biochemical evaluation of phenolic compounds and ascorbic acid were quantified through high-performance liquid chromatography (HPLC) in relation to three flesh colors (white, yellow and red) and four flesh typologies (melting, non-melting, slow softening and stony hard) within six commercial cultivars and eight breeding selections of peach/nectarine in 2007. While in 2008, quality and sensorial analyses were conducted on only three commercial cultivars ('Big Top', 'Springcrest' and 'Ghiaccio 1'). The red flesh selection demonstrated the highest levels of phenolic compounds (in mesocarp/exocarp) and ascorbic acid. Total phenolic concentration was approximately three-fold higher in the exocarp than the mesocarp across all accessions. Breeding selections generally reported higher levels of phenolics than commercial cultivars. Flesh textural typologies justified firmness differences at harvest, but minimally addressed variations in quality and phenolic compounds. Flesh pigmentation explained variation in the biochemical composition, with the red flesh accession characterized by an abundancy of phenolic compounds and a high potential for elevated antioxidant activity. Sensorial analyses ranked the cultivar with high soluble solids concentration:titratable acidity (SSC:TA) and reduced firmness the highest overall. Red flesh is a highly desirable trait for breeding programs aiming to improve consumption of peaches selected for nutraceutical properties.

Portuguese recommendations for the use of ultrasound in rheumatology.

INTRODUCTION: Ultrasound (US) is a relatively cheap, easily available and reliable method to improve the care of rheumatic patients. However, its use in rheumatology practice is very heterogeneous and needs to be standardized. OBJECTIVES: To develop recommendations for the use of US in rheumatic diseases endorsed by the Portuguese Society of Rheumatology. METHODS: A systematic literature review of the available recommendations on the use of ultrasound in rheumatic diseases was performed and presented in a Portuguese Society of Rheumatology meeting to a subgroup of rheumatologists and rheumatology trainees with special interest in the subject. The most important topics to be addressed were selected and assigned to subgroups for literature review and draft recommendations. Following an iterative process of consensus, the final recommendations were developed, and their level of agreement voted anonymously online. A recommendation was approved when the average level of agreement was ≥ 7.5 in a 10-point Likert scale. RESULTS: Fourteen recommendations were produced regarding nine rheumatology topics: rheumatoid arthritis, spondyloarthritis, connective tissue diseases, polymyalgia rheumatica, vasculitis, crystal-deposition diseases, soft tissue rheumatism, osteoarthritis and ultrasound-guided procedures. CONCLUSION: We developed an up-to-date guidance in the form of recommendations for the use of US in nine different areas of rheumatology. As ultrasound is an important imaging modality with increasing use in the rheumatology setting, and there are frequent technological advances in the ultrasound machines and probes, in parallel with continuous associated research, these recommendations should be regularly updated.

Canopy attachment position influences metabolism and peel constituency of European pear fruit.

BACKGROUND: Inconsistent pear fruit ripening resulting from variable harvest maturity within tree canopies can contribute to postharvest losses through senescence and spoilage that would otherwise be effectively managed using crop protectant and storage regimes. Because those inconsistencies are likely based on metabolic differences, non-targeted metabolic profiling peel of 'd'Anjou' pears harvested from the external or internal canopy was used to determine the breadth of difference and link metabolites with canopy position during long-term controlled atmosphere storage. RESULTS: Differences were widespread, encompassing everything from expected distinctions in flavonol glycoside levels between peel of fruit from external and internal canopy positions to increased aroma volatile production and sucrose hydrolysis with ripening. Some of the most substantial differences were in levels of triterpene and phenolic peel cuticle components among which acyl esters of ursolic acid and fatty acyl esters of p-coumaryl alcohol were higher in the cuticle of fruit from external tree positions, and acyl esters of α-amyrin were elevated in peel of fruit from internal positions. Possibly the most substantial dissimilarities were those that were directly related to fruit quality. Phytosterol conjugates and sesquiterpenes related to elevated superficial scald risk were higher in pears from external positions which were to be potentially rendered unmarketable by superficial scald. Other metabolites associated with fruit aroma and flavor became more prevalent in external fruit peel as ripening progressed and, likewise, with differential soluble solids and ethylene levels, suggesting the final product not only ripens differentially but the final fruit quality following ripening is actually different based on the tree position. CONCLUSIONS: Given the impact tree position appears to have on the most intrinsic aspects of ripening and quality, every supply chain management strategy would likely lead to diverse storage outcomes among fruit from most orchards, especially those with large canopies. Metabolites consistently associated with peel of fruit from a particular canopy position may provide targets for non-destructive pre-storage sorting used to reduce losses contributed by this inconsistency.

Novel Richter Syndrome Xenograft Models to Study Genetic Architecture, Biology, and Therapy Responses.

Richter syndrome represents the evolution of chronic lymphocytic leukemia into an aggressive tumor, most commonly diffuse large B-cell lymphoma. The lack of in vitro and in vivo models has severely hampered drug testing in a disease that is poorly responsive to common chemoimmunotherapeutic combinations as well as to novel kinase inhibitors. Here we report for the first time the establishment and genomic characterization of two patient-derived tumor xenograft (PDX) models of Richter syndrome, RS9737 and RS1316. Richter syndrome xenografts were genetically, morphologically, and phenotypically stable and similar to the corresponding primary tumor. RS9737 was characterized by biallelic inactivation of CDKN2A and TP53, monoallelic deletion of 11q23 (ATM), and mutations of BTK, KRAS, EGR2, and NOTCH1 RS1316 carried trisomy 12 and showed mutations in BTK, KRAS, MED12, and NOTCH2 RNA sequencing confirmed that in both cases >80% of the transcriptome was shared between primary tumor and PDX. In line with the mutational profile, pathway analyses revealed overactivation of the B-cell receptor, NFκB, and NOTCH pathways in both tumors, potentially providing novel tumor targets. In conclusion, these two novel models of Richter syndrome represent useful tools to study biology and response to therapies of this highly aggressive and still incurable tumor.Significance: Two patient-derived xenograft models of Richter syndrome represent the first ex vivo model to study biology of the disease and to test novel therapeutic strategies. Cancer Res; 78(13); 3413-20. ©2018 AACR.