Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.

Relationship of Thermostability and Binding Affinity in Metal-binding WW-Domain Minireceptors.

The design of metallo-miniproteins advances our understanding of the structural and functional roles of metals in proteins. We recently designed a metal-binding WW domain, WW-CA-Nle, which displays three histidine residues on its surface for coordination of divalent metals Ni(II), Zn(II) and Cu(II). However, WW-CA-Nle is a molten globule in the apo state and thus showed only moderate binding affinities with Kd values in the µM regime. In this report, we hypothesize that improved thermal stability of the apo state of the metal binding WW-domain scaffold should lead to improved preorganization of the metal-binding site and consequently to higher metal-binding affinities. By redesigning WW-CA-Nle, we obtained WW-CA variants, WW-CA-min and WW-CA-ANG, which were fully folded in the apo states and displayed moderate to excellent thermostabilities in the apo and holo states. We were able to show that the improved thermal stabilities led to improved metal binding, which was reflected in Kd values that were at least one order of magnitude lower compared to WW-CA-Nle. EPR spectroscopy and ITC measurements revealed a better defined and predisposed metal binding site in WW-CA-ANG.

Does Wound VAC Temporization Offer Patient-Reported Outcomes Similar to Single-Stage Excision Reconstruction After Myxofibrosarcoma Resection?

BACKGROUND: Vacuum-assisted closure (VAC) temporization is a promising technique to achieve local control in aggressive soft tissue sarcomas. Despite its previously reported efficacy, adoption of VAC temporization remains limited, primarily due to the scarce literature on patient-reported outcomes (PROs) supporting its efficacy. This study compared the postoperative PROs after VAC temporization or single-stage (SS) excision and reconstruction for patients undergoing surgical resection for myxofibrosarcoma management. METHODS: A retrospective analysis of myxofibrosarcoma patients who underwent surgical resections at our institution from 2016 to 2022 was performed. Postoperative PROs collected prospectively for those treated with VAC temporization or SS excision/reconstruction were compared using a visual analog scale (VAS) for pain and three Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires: Global Health Short-Form Mental (SF Mental), Global Health Short-Form Physical (SF Physical), and Physical Function Short-Form 10a (SF 10a). Absolute and differential (postoperative minus preoperative) scores at the 1-month, 3-month, 6-month, 1-year, and 2-year time points were compared. RESULTS: The analysis included 79 patients (47 treated with VAC temporization and 32 treated with SS excision/reconstruction). All outcomes were similar between the groups except for physical function 1 year after surgery, in which the differential PROMIS SF 10a scores were higher in the SS group (p = 0.001). All the remaining absolute and differential PROMIS and VAS pain scores were similar between the groups at all time points. Postoperative complications did not differ between the groups. CONCLUSION: The PROs for physical and mental health, physical function, and pain were similar between the myxofibrosarcoma patients who had VAC temporization and those who had SS excision/reconstruction after surgical resection.

LT and SOX9 expression are associated with gene sets that distinguish Merkel cell polyomavirus (MCPyV)-positive and MCPyV-negative Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive malignant neuroendocrine tumour. There are two subsets of MCC, one related to Merkel cell polyomavirus (MCPyV) and the other to ultraviolet radiation (UVR). MCPyV-positive and MCPyV-negative MCCs have been considered to be different tumours, as the former harbour few DNA mutations and are not related to UVR, and the latter usually arise in sun-exposed areas and may be found in conjunction with other keratinocytic tumours, mostly squamous cell carcinomas. Two viral oncoproteins, large T antigen (LT; coded by MCPyV_gp3) and small T antigen (sT; coded by MCPyV_gp4), promote different carcinogenic pathways. OBJECTIVES: To determine which genes are differentially expressed in MCPyV-positive and MCPyV-negative MCC; to describe the mutational burden and the most frequently mutated genes in both MCC subtypes; and to identify the clinical and molecular factors that may be related to patient survival. METHODS: Ninety-two patients with a diagnosis of MCC were identified from the medical databases of participating centres. To study gene expression, a customized panel of 172 genes was developed. Gene expression profiling was performed with nCounter technology. For mutational studies, a customized panel of 26 genes was designed. Somatic single nucleotide variants (SNVs) were identified following the GATK Best Practices workflow for somatic mutations. RESULTS: The expression of LT enabled the series to be divided into two groups (LT positive, n = 55; LT negative, n = 37). Genes differentially expressed in LT-negative patients were related to epithelial differentiation, especially SOX9, or proliferation and the cell cycle (MYC, CDK6), among others. Congruently, LT displayed lower expression in SOX9-positive patients, and differentially expressed genes in SOX9-positive patients were related to epithelial/squamous differentiation. In LT-positive patients, the mean SNV frequency was 4.3; in LT-negative patients it was 10 (P = 0.03). On multivariate survival analysis, the expression of SNAI1 [hazard ratio (HR) 1.046, 95% confidence interval (CI) 1.007-1.086; P = 0.02] and CDK6 (HR 1.049, 95% CI 1.020-1.080; P = 0.001) were identified as risk factors. CONCLUSIONS: Tumours with weak LT expression tend to co-express genes related to squamous differentiation and the cell cycle, and to have a higher mutational burden. These findings are congruent with those of earlier studies.

Merkel cell carcinoma (MCC) is an aggressive form of skin tumour. There are two subtypes of MCC: one of them is related to a virus called Merkel cell polyomavirus (MCPyV); the other one is related to persistent exposure to sunlight. The aim of this research was to find differences between these subtypes in their molecular behaviour (the genes that are expressed and the mutations that may be found). To do this, we carried out two studies, one to investigate gene expression (the process cells use to convert the instructions in our DNA into a functional product such as a protein) and one to look at gene mutations (changes in the DNA sequence). We found that the tumours that were not related to MCPyV expressed genes related to epithelial differentiation (the process by which unspecialized cells gain features characteristics of epithelial cells, which, among other things, make up the outer surface of the body), which means that the origin of both MCC subtypes may be different. We also found that MCPyV-related tumours had fewer mutations. Our findings are important because they help us to understand the biology of the MCC subtypes and could help with the development of new treatments for people diagnosed with skin tumours.

Cassia angustifolia and tacrolimus interaction in a liver transplant patient, a case report.

Cassia angustifolia is a species of plant from the Senna family that has traditionally been used as a laxative in different herbal products and commercial medicines. Even though there are few documented drug-plant interactions, the use of C. angustifolia with different drugs may have additive effects, such as with other laxatives or potassium-depleting diuretics. Its use also increases peristalsis which, may reduce drug absorption. The combination with digoxin has been associated with an increased risk of digoxin toxicity, probably due to an increase in plasma digoxin concentrations and hypokalaemia. We present a case with supratherapeutic trough concentration of tacrolimus, an immunosuppressive agent, and a herbal product in a liver transplant patient after concomitant intake of tacrolimus and a herbal product based on C. angustifolia, suggesting a possible drug-lant interaction through by P-glycoprotein. We observed an increase in the patient's blood concentration 2.8-fold and the area under the curve at steady state 2.1-fold. This interaction could be of clinical relevance, given the dose-dependent side effects of tacrolimus, such as nephrotoxicity, neurotoxicity, hypertension, hyperglycaemia, or electrolyte alterations.

Risk factors for local recurrence of upper extremity desmoid tumors.

INTRODUCTION: Upper extremity (UE) desmoid tumors are locally aggressive neoplasms with high recurrence rates. Our study sought to analyze the demographics and treatment strategies of UE desmoid tumors and identify risk factors for recurrence. MATERIALS AND METHODS: A retrospective review of 52 patients with histologically confirmed UE desmoid tumors treated at our institution between 1990 and 2015 was conducted. Survival was assessed using the Kaplan-Meier method and the Cox proportional hazards model was used for risk factor analysis. RESULTS: For the entire cohort, median age was 40 (29-47) years, 75% were female, and 48% had local recurrence. The median tumor size was 45 (15-111) cm3 on imaging. Twenty-two patients had a previous resection. The most common treatments were surgery alone (50%) and surgery with adjuvant radiotherapy (21%). Tumor size ≥5 cm and tumor volume ≥40 cm3 on imaging were associated with increased recurrence (p = 0.006 and p = 0.005, respectively). Age and sex were not associated with local recurrence. Patients with a tumor size ≥5 cm were 2.6 times more likely to present with recurrence. At the 10-year mark, a lower local recurrence-free survival was seen in patients with tumors ≥5 cm (72.2% vs. 36.3%, p = 0.042) or ≥40 cm3 (67.2% vs. 32.7%, p = 0.034). CONCLUSION: In our study, only tumor dimensions appeared to modify recurrence risk.

Prediction of 5-year survival in soft tissue leiomyosarcoma using a machine learning model algorithm.

BACKGROUND AND OBJECTIVES: Leiomyosarcoma (LMS) is associated with one of the poorest overall survivals among soft tissue sarcomas. We sought to develop and externally validate a model for 5-year survival prediction in patients with appendicular or truncal LMS using machine learning algorithms. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used for development and internal validation of the models; external validation was assessed using our institutional database. Five machine learning algorithms were developed and then tested on our institutional database. Area under the receiver operating characteristic curve (AUC) and Brier score were used to assess model performance. RESULTS: A total of 2209 patients from the SEER database and 81 patients from our tertiary institution were included. All models had excellent calibration with AUC 0.84-0.85 and Brier score 0.15-0.16. After assessing the performance indicators according to the TRIPOD model, we found that the Elastic-Net Penalized Logistic Regression outperformed other models. The AUCs of the institutional data were 0.83 (imputed) and 0.85 (complete-case analysis) with a Brier score of 0.16. CONCLUSION: Our study successfully developed five machine learning algorithms to assess 5-year survival in patients with LMS. The Elastic-Net Penalized Logistic Regression retained performance upon external validation with an AUC of 0.85 and Brier score of 0.15.

Wound vacuum-assisted closure temporization after tumor resection of soft tissue sarcomas-A cost analysis in a propensity-score matched population.

BACKGROUND: Vacuum-assisted closure (VAC) temporization is a technique associated with high local control rates used in myxofibrosarcoma. We sought to compare the costs and postoperative outcomes of VAC temporization and single-stage (SS) excision/reconstruction. METHODS: We conducted a retrospective analysis of patients with myxofibrosarcoma surgically treated at our institution between 2000 and 2022. Variables of interest included total, direct, and indirect costs for initial episode of care, 90 days and 1 year after initial admission, and postoperative outcomes. Costs were compared between the VAC temporization and SS groups. RESULTS: After matching, 13 patients in the SS group and 23 in the VAC group were analyzed. We found no difference in median and mean total inpatient costs, between the VAC temporization and SS group. While total 90-day and 1-year costs were higher in the VAC group compared to the SS group, mean costs were similar. There were no differences in postoperative complications between groups. A subanalysis of the entire cohort (n = 139) revealed lower local recurrence and overall death rates in the VAC temporization group. CONCLUSION: VAC temporization had similar inpatient costs and postoperative outcomes to SS excision/reconstruction. While median 90-day and 1-year costs were higher in the VAC group, mean costs did not differ.

Phosphaturic mesenchymal tumor: management and outcomes of ten patients treated at a single institution.

BACKGROUND: Phosphaturic mesenchymal tumor (PMT) is a rare tumor that causes tumor-induced osteomalacia. Patients present with non-specific symptoms secondary to renal phosphate wasting and decreased bone mineralization. We sought to assess: (1) What are the common presenting features, laboratory and imaging findings, histologic findings of phosphaturic mesenchymal tumors? (2) What are the available treatment strategies for phosphaturic mesenchymal tumors and their long-term outcomes in terms of local recurrence and symptom control after treatment? METHODS: We retrospectively identified patients with a histologic diagnosis of PMT located in the axial or appendicular skeleton, or surrounding soft tissues. A total of 10 patients were finally included in our study. RESULTS: Median tumor size was 1.9 cm (range, 1.1 to 6.1) and median time from symptom onset to diagnosis was 3 years (range, 0.5 to 15 years). All patients but one presented with hypophosphatemia (median 1.9 mg/dL, range 1.2 to 3.2). Pre-operative FGF-23 was elevated in all cases (median 423.5 RU/mL, range 235 to 8950). Six patients underwent surgical resection, three were treated percutaneously (radiofrequency ablation or cryoablation), and one refused treatment. Only one patient developed local recurrence and no patients developed metastatic disease. At last follow-up, nine patients showed no evidence of disease and one was alive with disease. CONCLUSION: Phosphaturic mesenchymal tumor is a rare tumor presenting with non-specific symptoms. Surgery is the standard treatment when negative margins can be achieved without significant morbidity. In patients with small tumors in surgically-inaccessible areas, radiofrequency ablation or cryoablation can be performed successfully.

Complications and Functional Outcomes after Reconstruction of the Proximal Humerus with Allograft-Prosthetic Composite - A Systematic Review of the Literature.

INTRODUCTION: Allograft prosthetic composite (APC) reconstruction is performed after resection of proximal humerus tumors or failure of arthroplasty implants. There is limited literature on the postoperative outcomes of this technique. We sought to assess implant survival, failure rates, and postoperative functional outcomes after APC reconstruction of the proximal humerus. METHODS: A systematic review of the PubMed and Embase databases was conducted. The study was registered on PROSPERO (ID: 448663). The STROBE checklist was used for quality assessment. Implant failure was determined using the Henderson classification for biological reconstruction. Functional outcome was primarily assessed using the Musculoskeletal Tumor Society (MSTS) score at last follow-up. RESULTS: Twenty-five studies with a total of 488 patients were included. Mean follow-up in reporting studies ranged from 2.5 to 10 years. Five-year revision-free survival for implants ranged from 41 to 92%. Overall implant failure rate ranged from 9 to 54%, and reoperation rate ranged from 0 to 55%. Graft-host non-union (type 2) was the most common mode of failure, with rates ranging from 0 to 75%. The mean MSTS scores at last follow-up ranged from 57 to 90% across studies. A trend towards better functional outcomes was seen in patients having an APC with a reverse total shoulder arthroplasty (rTSA) compared with those with hemiarthroplasty (HA). CONCLUSIONS: APCs show promise in proximal shoulder reconstruction, with heterogenous functional outcomes that are non-inferior to other reconstruction techniques. Graft host non-union is a common mode of failure and remains a concern in this type of prosthesis. Future studies should compare rTSA-APCs and rTSA endoprostheses while controlling for potential confounders.

Reconstruction of the elbow with distal humerus endoprosthetic replacement after tumor resection: a systematic review of the literature and institutional case series.

BACKGROUND: Distal humerus replacement (DHR) is a modular endoprosthesis mainly used for bone reconstruction after resection of primary or metastatic bone lesions. Studies on DHR failure rates and postoperative functional outcomes are scarce. We sought to assess implant survival, modes of failure, and functional outcomes in patients undergoing DHR for oncologic indications. METHODS: A systematic review of the PubMed and Embase databases was performed. PRISMA guidelines were followed for this manuscript. Our study was registered on PROSPERO (457,260). Quality appraisal of included studies was conducted using the STROBE checklist. Prosthetic failure was assessed using the Henderson classification for megaprosthetic failures. We additionally performed a retrospective review of patients treated with a DHR for oncologic indications at a large tertiary care academic center. Weighted means were calculated to pool data. RESULTS: Eleven studies with a total of 162 patients met the inclusion criteria. Mean follow-up was 3.7 years (range, 1.66-8 years). Henderson type 2 failures (aseptic loosening) were the most common mode of failure, occurring in 12% of cases (range, 0%-33%). Five-year implant survival was 72% (range, 49%-93.7%). Mean postoperative Musculoskeletal Tumor Society (MSTS) score was 81.1 (range, 74-84.3). In our institutional case series, 2 out of 5 patients had DHR revision for periprosthetic fracture and aseptic loosening at 16 and 27 months after surgery, respectively. CONCLUSIONS: Distal humerus replacement is a successful reconstruction strategy for tumors of the distal humerus, with high implant survival and good to excellent functional outcomes.

Debridement, Antibiotics, and Implant Retention (DAIR) Plus Offers Similar Periprosthetic Joint Infection Treatment Success Rates to Two-Stage Revision in Oncologic Megaprosthesis.

BACKGROUND: Prosthetic joint infections (PJIs) after megaprosthesis implantation are associated with high rates of treatment failure and amputation. Our study analyzed PJI treatment success rates by surgical strategy and assessed risks of reinfection and amputation. METHODS: We retrospectively analyzed the outcomes of patients diagnosed with PJI after undergoing megaprosthesis implantation for oncologic indications. The 2011 Musculoskeletal Infection Society criteria were used to define PJI. Reinfection, reoperation, and amputation for PJI recurrence were assessed. A total of 67 patients with megaprosthesis PJIs were included. There were fourteen patients who were treated with debridement, antibiotics, and implant retention (DAIR), 31 with DAIR plus (DAIR with modular component exchange and stem retention), and 21 with two-stage revisions. Kaplan-Meier estimates were used for survival analyses and Cox proportional hazards for risk factor analyses. RESULTS: The two-year reinfection-free survival was 25% for DAIR and 60% for DAIR plus or two-stage revision (P = .049). The five-year amputation-free survival was 84% for DAIR plus or two-stage revision, and 48% for DAIR (P = .13). Reinfection-free, reoperation-free, and amputation-free survival were similar between DAIR plus and two-stage revision at the 2- and 5-year marks. Body mass index ≥30 (hazard ratio [HR] = 2.65) and chronic kidney disease (HR = 11.53) were risk factors for reinfection. Treatment with DAIR plus or two-stage revision (HR = 0.44) was a protective factor against reinfection. CONCLUSIONS: A DAIR was associated with high rates of treatment failure and higher amputation rates than DAIR plus or 2-stage surgery. A DAIR plus was not inferior to 2-stage revision clearing a PJI and might be performed in patients who cannot withstand two-stage revision surgery.

Reverse Fragility Index: Comparing Revision Rates Between Direct Anterior and Other Approaches in Total Hip Arthroplasty. A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Despite increasing adoption of the direct anterior (DA) approach in total hip arthroplasty (THA), uncertainty persists regarding its outcomes beyond the 1-year mark in comparison to other approaches. We used the reverse fragility index (RFI) to evaluate the robustness of reported findings in the literature. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) comparing implant revision rates between DA and other approaches in THA, defined as all those different from DA. Our primary outcome was the RFI, which gauges the number of events needed for a nonsignificant result to become significant, in the revision rate between DA and other approaches. We also calculated the reverse fragility quotient by dividing the RFI by each study's sample size. Median values and interquartile ranges (IQRs) were displayed. RESULTS: A total of 10 RCTs with a total of 971 patients were included. The median RFI was 5 (IQR, 4 to 5), indicating the study's results would be statistically significant if the outcomes of 5 patients in 1 treatment arm were reversed. The median reverse fragility quotient was 0.049 (IQR, 0.04 to 0.057), indicating that a change of outcome in 4.9% of patients would render the revision rate significant. The median number of patients lost to follow-up was 4 (IQR, 0 to 7). Of the 10 RCTs, 6 had more patients lost to follow-up than their respective RFI values. CONCLUSIONS: Notable fragility was evidenced in most studies comparing DA to other approaches for THA. Surgeons should not solely rely on the P value to determine clinical significance and instead use multiple metrics. LEVEL OF EVIDENCE: II.

Candida spondylodiscitis: a systematic review and meta-analysis of seventy two studies.

OBJECTIVES: Knowledge of Candida spondylodiscitis is limited to case reports and smaller case series. Controversy remains on the most effective diagnostical and therapeutical steps once Candida is suspected. This systematic review summarized all cases of Candida spondylodiscitis reported to date concerning baseline demographics, symptoms, treatment, and prognostic factors. METHODS: A PRISMA-based search of PubMed, Web of Science, Embase, Scopus, and OVID Medline was performed from database inception to November 30, 2022. Reported cases of Candida spondylodiscitis were included regardless of Candida strain or spinal levels involved. Based on these criteria, 656 studies were analyzed and 72 included for analysis. Kaplan-Meier curves, Fisher's exact, and Wilcoxon's rank sum tests were performed. RESULTS: In total, 89 patients (67% males) treated for Candida spondylodiscitis were included. Median age was 61 years, 23% were immunocompromised, and 15% IV drug users. Median length of antifungal treatment was six months, and fluconazole (68%) most commonly used. Thirteen percent underwent debridement, 34% discectomy with and 21% without additional instrumentation. Median follow-up was 12 months. The two year survivorship free of death was 80%. The two year survivorship free of revision was 94%. Younger age (p = 0.042) and longer length of antifungal treatment (p = 0.061) were predictive of survival. CONCLUSION: Most patients affected by Candida spondylodiscitis were males in their sixties, with one in four being immunocompromised. While one in five patients died within two years of diagnosis, younger age and prolonged antifungal treatment might play a protective role.

Theoretical Study of Cyanidin-Resveratrol Copigmentation by the Functional Density Theory.

Anthocyanins are colored water-soluble plant pigments. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lowers the risk of neurodegenerative diseases. The copigmentation caused by copigments is considered an effective way to stabilize anthocyanins against adverse environmental conditions. This is attributed to the covalent and noncovalent interactions between colored forms of anthocyanins (flavylium ions and quinoidal bases) and colorless or pale-yellow organic molecules (copigments). The present work carried out a theoretical study of the copigmentation process between cyanidin and resveratrol (CINRES). We used three levels of density functional theory: M06-2x/6-31g+(d,p) (d3bj); ωB97X-D/6-31+(d,p); APFD/6-31+(d,p), implemented in the Gaussian16W package. In a vacuum, the CINRES was found at a copigmentation distance of 3.54 Å between cyanidin and resveratrol. In water, a binding free energy ∆G was calculated, rendering -3.31, -1.68, and -6.91 kcal/mol, at M06-2x/6-31g+(d,p) (d3bj), ωB97X-D/6-31+(d,p), and APFD/6-31+(d,p) levels of theory, respectively. A time-dependent density functional theory (TD-DFT) was used to calculate the UV spectra of the complexes and then compared to its parent molecules, resulting in a lower energy gap at forming complexes. Excited states' properties were analyzed with the ωB97X-D functional. Finally, Shannon aromaticity indices were calculated and isosurfaces of non-covalent interactions were evaluated.

Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene-α-amino Esters.

The reaction of arylidene-α-amino esters with electrophilic alkenes to yield Michael-type addition compounds is optimized using several phosphines as organocatalysts. The transformation is very complicated due to the generation of several final compounds, including those derived from the 1,3-dipolar cycloadditions. For this reason, the selection of the reaction conditions is a very complex task and the slow addition of the acrylic system is very important to complete the process. The study of the variation in the structural components of the starting imino ester is performed as well as the expansion of other electron-poor alkenes. The crude products have a purity higher than 90% in most cases without any purification. A plausible mechanism is detailed based on the bibliography and the experimental results. The synthesis of pyroglutamate entities, after the reduction of the imino group and cyclization, is performed in high yields. In addition, the hydrolysis of the imino group, under acidic media, represents a direct access to glutamate surrogates.

Transcriptomic characterization of the response to a microalgae extract in Arabidopsis thaliana and Solanum lycopersicum.

BACKGROUND: The steady world population growth and the current climate emergency crisis demand the development of sustainable methods to increase crop performance and resilience to the abiotic and biotic stresses produced by global warming. Microalgal extracts are being established as sustainable sources to produce compounds that improve agricultural yield, concurrently contributing during their production process to atmospheric CO2 abatement through the photosynthetic activity of microalgae. RESULTS: In the present study, we characterize the transcriptomic response in the model plant Arabidopsis thaliana and the plant of horticultural interest Solanum lycopersicum to the foliar application of a microalgae-based commercial preparation LRM™ (AlgaEnergy, Madrid, Spain). The foliar spray of LRM™ has a substantial effect over both transcriptomes potentially mediated by various compounds within LRM™, including its phytohormone content, activating systemic acquired resistance, possibly mediated by salicylic acid biosynthetic processes, and drought/heat acclimatization, induced by stomatal control and wax accumulation during cuticle development. Specifically, the agronomic improvements observed in treated S. lycopersicum (tomato) plants include an increase in the number of fruits, an acceleration in flowering time and the provision of higher drought resistance. The effect of LRM™ foliar spray in juvenile and adult plants was similar, producing a fast response detectable 2 h from its application that was also maintained 24 h later. CONCLUSION: The present study improves our knowledge on the transcriptomic effect of a novel microalgal extract on crops and provides the first step towards a full understanding of the yield and resistance improvement of crops. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Enhancement of the CO2 adsorption and hydrogenation to CH4 capacity of Ru-Na-Ca/γ-Al2O3 dual function material by controlling the Ru calcination atmosphere.

Integrated CO2 capture and utilization (ICCU) technology requires dual functional materials (DFMs) to carry out the process in a single reaction system. The influence of the calcination atmosphere on efficiency of 4% Ru-8% Na2CO3-8% CaO/γ-Al2O3 DFM is studied. The adsorbent precursors are first co-impregnated onto alumina and calcined in air. Then, Ru precursor is impregnated and four aliquotes are subjected to different calcination protocols: static air in muffle or under different mixtures (10% H2/N2, 50% H2/N2 and N2) streams. Samples are characterized by XRD, N2 adsorption-desorption, H2 chemisorption, TEM, XPS, H2-TPD, H2-TPR, CO2-TPD and TPSR. The catalytic behavior is evaluated, in cycles of CO2 adsorption and hydrogenation to CH4, and temporal evolution of reactants and products concentrations is analyzed. The calcination atmosphere influences the physicochemical properties and, ultimately, activity of DFMs. Characterization data and catalytic performance discover the acccomodation of Ru nanoparticles disposition and basic sites is mostly influencing the catalytic activity. DFM calcined under N2 flow (RuNaCa-N2) shows the highest CH4 production (449 µmol/g at 370°C), because a well-controlled decomposition of precursors which favors the better accomodation of adsorbent and Ru phases, maximizing the specific surface area, the Ru-basic sites interface and the participation of different basic sites in the CO2 methanation reaction. Thus, the calcination in a N2 flow is revealed as the optimal calcination protocol to achieve highly efficient DFM for integrated CO2 adsorption and hydrogenation applications.

Siglec-6 is a novel target for CAR T-cell therapy in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an attractive entity for the development of chimeric antigen receptor (CAR) T-cell immunotherapy because AML blasts are susceptible to T-cell-mediated elimination. Here, we introduce sialic acid-binding immunoglobulin-like lectin 6 (Siglec-6) as a novel target for CAR T cells in AML. We designed a Siglec-6-specific CAR with a targeting domain derived from the human monoclonal antibody JML-1. We found that Siglec-6 is commonly expressed on AML cell lines and primary AML blasts, including the subpopulation of AML stem cells. Treatment with Siglec-6 CAR T cells confers specific antileukemia reactivity that correlates with Siglec-6 expression in preclinical models, including induction of complete remission in a xenograft AML model in immunodeficient mice (NSG/U937). In addition, we confirmed Siglec-6 expression on transformed B cells in chronic lymphocytic leukemia (CLL), and specific anti-CLL reactivity of Siglec-6 CAR T cells in vitro. Of particular interest, we found that Siglec-6 is not detectable on normal hematopoietic stem and progenitor cells (HSPCs) and that treatment with Siglec-6 CAR T cells does not affect their viability and lineage differentiation in colony-formation assays. These data suggest that Siglec-6 CAR T-cell therapy may be used to effectively treat AML without the need for subsequent allogeneic hematopoietic stem cell transplantation. In mature normal hematopoietic cells, we detected Siglec-6 in a proportion of memory (and naïve) B cells and basophilic granulocytes, suggesting the potential for limited on-target/off-tumor reactivity. The lack of expression of Siglec-6 on normal HSPCs is a key to differentiating it from other Siglec family members (eg, Siglec-3 [CD33]) and other CAR target antigens (eg, CD123) that are under investigation in AML, and it warrants the clinical investigation of Siglec-6 CAR T-cell therapy.

Risk factors for 30-day soft tissue complications after pelvic sarcoma surgery: A National Surgical Quality Improvement Program study.

INTRODUCTION: Soft tissue (ST) complications after resection of bone and ST sarcomas of the pelvis occur more frequently than in appendicular tumors. We sought to identify risk factors for complications within 30 days of surgery. METHODS: The National Surgical Quality Improvement Program database was used for this study. Patients with sarcomas of bone and ST of the pelvis were retrieved using Current Procedural Terminology and International Classification of Diseases codes. Outcomes assessed were ST complications, overall complication rates, 30-day reoperation, and mortality. RESULTS: A total of 770 patients with pelvic bone and ST sarcoma were included. The ST complication rate was 12.6%, including 4.9% superficial and 4.7% deep surgical site infections. Higher ST complication rates were seen in patients >30 years, with partially dependent health status, hematocrit <30%, bone tumors, tumor >5 cm, amputation procedures, and longer operative times. ST complication rates were 1.5 and 3 times higher in pelvic sarcoma surgeries than in the lower and upper extremities, respectively. Age >30 years (odds ratio [OR] = 5.07), hematocrit <30% (OR = 1.84), operative time 1-3 h (OR = 2.97), and >3 h (OR = 4.89) were risk factors for ST complications. CONCLUSION: One in nine patients with pelvic sarcoma surgery will develop ST complications within 30 days. Risk factors for ST complications were age >30, hematocrit <30%, and longer operative time.