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Objective: Aberrantly methylated DNA may be used to detect minimal residual disease or early recurrence in breast cancer. As a 1st step, we aimed to develop an MDM panel to delineate between healthy women, stage I-III breast cancer in remission with no evidence of disease (NED), and metastatic breast cancer (MBC). Methods: We prospectively enrolled patients into 3 groups: healthy controls (adult females with a normal mammogram in past 12 months with no history of breast cancer), NED [stage I-III breast cancer with no clinical evidence of recurrence 6 months - 3 years post-treatment (adjuvant endocrine therapy allowed)], and MBC (collected either at initial diagnosis of untreated metastatic disease or radiographic progression). DNA was extracted from 6 mL of plasma derived from blood collected in LBgard tubes (Exact Sciences Corp., San Diego CA), and was bisulfite-treated and assayed by target enrichment long-probe quantitative amplified signal (TELQASTM) method for a panel of 15 previously identified MDMs [Table], normalized by the control gene, B3GALT6. Areas under the receiver operating characteristic curve (AUC) were calculated for each MDM to assess discrimination of MBC from other groups. With 60 patients per group, we had greater than 80% power to detect a difference of 0.20 from the null AUC of 0.7. Results: We tested samples from 60 MBC (10 untreated, 50 recurrent), 60 NED, and 60 healthy women. The median age was 63 (IQR, 55-72) and was not different between groups. The NED group was all hormone-receptor (HR) positive, with 47 (78%) being human epidermal growth factor receptor 2 negative (HER2-) and 13 (22%) HER2+; 48 (80%) were stage I and 9 (15%) were N+. The MBC group had 35 (58%) patients with HR+/HER2- tumors, 11 (18%) HR+/HER2+, and 6 (10%) HR-/HER2-, 4 (7%) HR-/HER2+, with 4 (7%) unknown. Of the 41 MBC whose original stage and nodal status were known 9 (22%) were stage I and 22 (54%) were N+. The markers were able to discriminate between MBC and NED patient samples with AUCs from 0.97 to 0.72. AUCs for 10/15 MDMs (ITPRIPL1, EMX1, C17orf64, OSR2, TRIM67, CHST2, IFFO1, TRH, FAM59B, and MPZ) were >0.90. No difference in MDMs was observed between the healthy and NED groups. Conclusions: MDMs, assayed from plasma, appear highly discriminant for metastatic breast cancer cases in comparison to control patients with NED or healthy controls. Further clinical validation of this MDM panel in a larger cohort is warranted. Table 1. Plasma MDM discrimination of metastatic breast cancer (MBC) from healthy controls and previously treated breast cancer patients with no evidence of disease (NED) Citation Format: Karthik V. Giridhar, Fergus J. Couch, Jason P. Sinnwell, Seth W. Slettedahl, William R. Taylor, Douglas W. Mahoney, Patrick H. Foote, Maria C. O’Connell, Mariah J. Robran, Mary E. Devens, Anna M. Gonser, Nicole Larson, Karen A. Doering, Kelli N. Burger, Michael Kaiser, Hatim Allawi, Kathryn Ruddy, Janet Olson, John B. Kisiel. Plasma assay of methylated DNA markers (MDM) detects patients with metastatic breast cancer (MBC) compared to healthy controls and treated breast cancer patients with no evidence of disease [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-06.

Background: The authors present a validated method for the simultaneous quantification of asundexian (BAY 2433334) and its pharmacologically inactive major human metabolite M-10 from human plasma and its application in clinical study sample analysis. Materials & methods: Sample preparation was performed by protein precipitation followed by reverse phase HPLC and positive/negative ESI-MS/MS. Results: Assay working ranges were 0.5–500 ng/ml for asundexian and 5.0–5000 ng/ml for M-10. Validation results met the requirements of pertinent guidelines. In clinical study sample analysis, accuracy and precision acceptance criteria for analyzed quality control samples were met and incurred sample reanalysis was fulfilled. Conclusion: The method proved to be selective, specific, sufficiently sensitive, reproducible and robust for the analysis of samples obtained from clinical trials.

Background: Turpentine-containing substances are considered effective in treating cutaneous bacterial infections, but reliable clinical data are scant. Objective: We investigated the efficacy and safety of an ointment containing larch turpentine (from Larix decidua), eucalyptus oil (from Eucalyptus globulus), and turpentine oil (from Pinus pinaster) in outpatients with painful skin abscesses in a randomized, placebo-controlled, double-blind study. Intervention: 116 outpatients with skin abscesses used verum or placebo for 10 days. Sum score of the patient’s discomforts, changes in abscess size, rate of therapeutic success, and complete healing served as outcome parameters. Results: Fifty-four patients were treated with verum and 56 with placebo. According to the patient’s discomfort sum score, patients in the verum group showed a better improvement compared to the placebo group (7.3 vs. 4.7; p = 0.024), and subjective assessment by the investigators revealed a higher treatment success rate after verum (70% vs. 48%; p = 0.021). Complete healing was documented in 67% of the patients receiving verum versus 46% in the placebo group (p = 0.037). There was a positive trend toward a larger decrease in the abscess sizes in the verum group compared to the placebo group (p = 0.07). Conclusion: The ointment studied is an effective and safe option for the treatment of bacterial skin diseases.

Cosmetic procedures for antiaging carry inherent risks of adverse events. One that has not yet been well characterized is transitory or permanent alopecia. This is attributable to numerous mechanisms including pressure, ischemia, inflammation, and necrosis. Cases of postcosmetic procedure alopecia have been reported after mesotherapy as well as hyaluronic acid filler, deoxycholic acid, and botulinum toxin injections.This review serves to describe the currently known causes of postcosmetic procedure alopecia and the mechanisms by which alopecia is attained. Furthermore, this review highlights the risk of unregulated mesotherapy injections for cosmetic enhancement and to bring attention to the increasing number reports of alopecia after these procedures.A systematic review of the literature from 2000 to 2022 was conducted looking for keywords such as "alopecia," "cosmetic procedures," "mesotherapy," and "hyaluronic acid" in Google Scholar and PubMed.Ten articles met the criteria set forth in the authors' literature review. Many of the procedures resulted in partial or complete resolution of alopecia.Alopecia after cosmetic injection procedures is an underreported adverse effect. More research is needed to further characterize the risk of alopecia after mesotherapy and other injection procedures.

Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn from the website of the journal Current Stem Cell Research & Therapy. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Restoring soil carbon (C) lost due to intensive farming is a long-term endeavor under current conservation management practices. Application of coal combustion residue (293 g C kg-1 ) from a sugar beet (Beta vulgaris L.) processing factory, hereafter referred to as char, could rapidly restore soil C and productivity in degraded croplands, but data on this potential strategy are unavailable. We assessed the impacts of char application to two relatively low-C soils (10.1 and 12.2 g C kg-1 ) and one relatively high-C soil (17.3 g C kg-1 ) on soil C, soil physical and fertility properties, and crop yields in no-till systems in the Great Plains after 2 yr. Char was disked to 15 cm soil depth at char-C application rates ranging from 0 to 19.7 Mg C ha-1 , corresponding to char application rates ranging from 0 to 67.3 Mg ha-1 . The highest char rate increased C concentration in all soils but increased C stock only in low-C soils. Char did not affect soil penetration resistance, available water, aggregate stability, most nutrients, and crop yields. Char application at high rates increased sulfate, Ca, Mg, and Na concentrations but did not influence other properties. Carbon recovery of the char applied at the highest rate varied among soils from 50 to 85%, but the mechanisms for such differences need further investigation. Short-term duration, low char C concentration, and low application rates may explain the limited char effects. Overall, char application at 19.7 Mg char-C ha-1 (i.e., 67.3 Mg char ha-1 ) increased soil C concentration but had negligible effects on other soil properties and crop yields after 2 yr.

Precise assessment of soil organic carbon (OC) storage requires understanding of soil type and depth specific differences in organic matter (OM) stabilization. Therefore, we aimed to analyze OC dynamics down the soil profile and to clarify the effect of depth on the importance of aggregate formation and mineral adsorption for OC storage in mature beech forest soils developed from different parent materials. Aggregate size and density fractions were separated from samples of top and subsoil horizons, which were quantified and analyzed by infrared spectroscopy. We also determined the microbial biomass C (Cmic) and the amount of C decomposed within incubation experiments (CO2-C) for the bulk soil samples. OC stabilized via aggregate formation and mineral association significantly increased with soil depth. However, this stabilized pool seemed to fuel the labile OM stronger in the subsoil than in the topsoil because the CO2-C/SOC and CO2-C/Cmic ratios increased with depth. Measured differences in the magnitude of the detected stabilization and destabilization patterns were attributed to parent material and soil horizon, indicating pronounced spatial and vertical heterogeneity in the contribution of soils under temperate broadleaf forest to terrestrial C sequestration. Considering such site and depth specific differences will improve assessment and modelling of soil OC storage for areas covered with the same forest type but with high pedogenetic diversity.

Fertilizer N losses from agricultural systems have economic and environmental implications. Soil amendment with high C materials, such as coal char, may mitigate N losses. Char, a coal combustion residue, obtained from a sugar factory in Scottsbluff, NE, contained 29% C by weight. A 30-d laboratory study was conducted to evaluate the effects of char addition on N losses via nitrous oxide (N2 O) emission, ammonia (NH3 ) volatilization, and nitrate (NO3 -N) leaching from fertilized loam and sandy loam soils. Char was applied at five different rates (0, 6.7, 10.1, 13.4, and 26.8 Mg C ha-1 ; char measured in C equivalent) to soils fertilized with urea ammonium nitrate (UAN) at 200 kg N ha-1 . In addition, there were two negative-UAN control treatments: no char (no UAN) and char at 26.8 Mg C ha-1 (no UAN). Treatment applied at 6.7 and 10.1 Mg C ha-1 in fertilized sandy loam reduced NH3 volatilization by 26-37% and at 6.7, 10.1, and 13.4 Mg C ha-1 in fertilized loam soils by 24% compared with no char application. Nitrous oxide emissions and NO3 -N leaching losses were greater in fertilized compared with unfertilized soil, but there was no effect of char amendment on these losses. Because NO3 -N leaching loss was greater in sandy loam than in loam, soil residual N was twofold higher in loam than in sandy loam. This study suggests that adding coal char at optimal rates may reduce agricultural reactive N to the atmosphere by decreasing NH3 volatilization from fertilized soils.

Burn wounds are a major source of morbidity and mortality in both the military and the civilian settings. Research about the pathophysiology of thermal injury has revealed possible interventions that can aid this process to reduce scarring and wound contracture. Bone marrow derived Mesenchymal stem cells (BM-MSCs) have been an exciting topic in research for many years. They have been shown to facilitate wound healing and tissue regeneration, two areas that are vital in the healing process especially in burn wounds. More recently the discovery of Extracellular Vesicles (EVs) has allowed us to further characterize the immunomodulatory roles and understand the cellular pathways implicated in wound healing. The purpose of this review is to discuss the role of EVs in wound healing, and to propose that EVs are the main mechanism that deliver cellular materials to target cells to coordinate wound healing following tissue injury.

International audience; Published in OA on RESSI (http://www.ressi.ch/) at the end of Octobre 2021. We present here highlights from an enquiry on the innovations in scholarly writing in the Humanities and Social Sciences in the H2020 project OPERAS-P. This article explores the theme of Open Research Data and its role in the emergence of new models of scholarly writing. We examine more closely the obstacles and fostering conditions to the publication of research data, both from a social and a technical perspective.

Introduction: Advancements in DNA sequence detection technology and assay design have enabled molecular residual disease (MRD) assays to detect cancer earlier and with greater sensitivity. In Tumor-Informed (TI) strategies, mutations from the tumor are used to define a set of patient-specific markers that are tracked in the blood as circulating tumor DNA (ctDNA). Whereas tumor-naïve (TN) approaches do not require prior genomic information from the tumor and instead employ a fixed panel of marker(s). Methylated DNA Markers (MDMs) can be used to distinguish cancer from non-cancer and can be found in plasma. We have developed a proprietary TN MRD platform for colorectal cancer (CRC) capable of measuring as few as 1-5 strands of MDM target. Additionally, we are actively developing a TI MRD assay platform. Here we describe the evaluation of both TI and TN approaches for the detection of circulating tumor DNA (ctDNA) in blood across all stages of colorectal cancer and explore the complementarity of these two approaches in the context of MRD monitoring. Procedures: A 20-sample cohort of paired tumor/normal and pre-surgery plasma specimens from stage I (6/20), stage II (7/20), stage III (6/20), and stage IV (1/20) CRC patients and 20 demographically matched non-cancer controls were acquired for our study. All cancer plasma samples were collected prior to tumor resection. Neat and diluted plasma samples were tested for the presence of ctDNA containing short variants specifically derived from the corresponding primary tumor and for a pre-defined set of MDMs and protein cancer biomarkers. Tumor-specific short variants were characterized by whole exome sequencing of the primary tumors. MDMs were detected from bisulfite converted cfDNA by Target Enrichment Long probe Quantitative Amplified Signal (TELQAS) for 35 MDMs. A cancer detection classifier for the TN assay was trained and validated using a separate cohort of non-cancer and CRC plasma samples and employed for this study. Protein was detected by high throughput ELISA.Results: Tumor sequencing of the 20 CRC samples identified between 122 and 7146 (median = 230) somatic mutations per tumor sample. The combination of features from TI and TN assays achieved 95% accuracy, demonstrating an improvement over either assay in isolation. Indeed, 5 “positive” calls were made for cancer samples for which only one of the two methods met pre-defined RUO thresholds for ctDNA detection. Comparison of median variant allele fraction from the TI assay with median percent methylation of CRC markers for these CRC samples had a Pearson’s correlation of 0.967. Conclusion: TI and TN assays show high concordance in cancer detection, but also complement each other. Additionally, ctDNA quantifications produced from TI and TN assays are linearly correlated. The combination of data from both assays can be used to further differentiate cancer samples from non-cancer samples. Citation Format: Alanna Chan, Martin You, Oliver Limbo, Billyana Tsevtanova, Gerald Dodson, Brenda Curiel, Karma Farhat, Samantha Scott, Archana Ramesh, Jacquelyn Hennek, Viacheslav Katerov, Michael Kaiser, Hatim Allawi, Brady P. Culver, Michael Reshatoff, Jorge Garces, Gina Costa. Evaluation of a multi-omics approach to molecular residual disease detection. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6694.

Nutrient retention in biochar amended soil has yielded variable results, with poorly understood mechanisms. Identification of changes on biochar surfaces during in situ soil aging can provide mechanistic information on the role of biochar on nutrient retention. In the current greenhouse study, we analyzed changes of biochar surface characteristics aging in two soils with different iron levels and amended with two types of manure types under corn. On pristine biochar surfaces, we detected no iron species. In contrast, after soil aging (70 days), a self-functionalization of biochar surfaces with iron oxides was observed, which can be explained by soil redox cycles allowing reduced iron(II) to migrate on biochar surfaces followed by its re-oxidation. This self-functionalization is proposed as an underlying mechanism explaining the significantly (p 0.01) increased nitrate retention by 29-180 % in biochar amended soil. Significant (p 0.05) reductions in leachate phosphate (18-41 %) and dissolved organic carbon (8.8-55 %) were also observed after biochar surface functionalization. Our results indicate that redox-driven iron oxide formation on surfaces of biochar in the soil can be a critical process explaining the dynamic nature of nutrient retention observed in biochar amended soils. Identifying soil environmental conditions most beneficial for such surface functionalization, which has the potential to increase nutrient retention, is critical for implementing efficient biochar amendment strategies and for increased resource efficiency in agroecosystems.