Seasonal Controls on Microbial Depolymerization and Oxidation of Organic Matter in Floodplain Soils.

Floodplain soils are vast reservoirs of organic carbon often attributed to anaerobic conditions that impose metabolic constraints on organic matter degradation. What remains elusive is how such metabolic constraints respond to dynamic flooding and drainage cycles characteristic of floodplain soils. Here we show that microbial depolymerization and respiration of organic compounds, two rate-limiting steps in decomposition, vary spatially and temporally with seasonal flooding of mountainous floodplain soils (Gothic, Colorado, USA). Combining metabolomics and -proteomics, we found a lower abundance of oxidative enzymes during flooding coincided with the accumulation of aromatic, high-molecular weight compounds, particularly in surface soils. In subsurface soils, we found that a lower oxidation state of carbon coincided with a greater abundance of chemically reduced, energetically less favorable low-molecular weight metabolites, irrespective of flooding condition. Our results suggest that seasonal flooding temporarily constrains oxidative depolymerization of larger, potentially plant-derived compounds in surface soils; in contrast, energetic constraints on microbial respiration persist in more reducing subsurface soils regardless of flooding. Our work underscores that the potential vulnerability of these distinct anaerobic carbon storage mechanisms to changing flooding dynamics should be considered, particularly as climate change shifts both the frequency and extent of flooding in floodplains globally.

A qualitative study to understand the barriers and facilitators in smoking cessation practices among oncology health care practitioners in one health system.

INTRODUCTION: Despite the benefits of quitting smoking for those who have cancer, including improved health outcomes and reduced therapeutic toxicities, it is unclear how many people are supported in quit attempts during this time. Variations in the availability and provision of smoking cessation (SC) services are reported, with little understanding of the challenges and solutions. This co-designed study aimed to understand the perspectives of health care professionals (HCPs) working in oncology settings to engage in SC practices and identify recommendations for developing an SC pathway. METHODS: This was a qualitative study. Eighteen HCPs participated in semi-structured interviews from July 2021 to May 2022. We used thematic analysis approaches to code data and present four emergent themes and SC strategies at micro, meso and organizational levels. RESULTS: Four themes emerged specifically: 1) timing and knowledge, 2) building a relationship, 3) frequent asking with infrequent action, and 4) removing the barriers and tailoring the system. While HCPs discuss SC, there are variations in documentation and when conversations occur. Primarily, HCPs value the time to build therapeutic relationships with patients and thus may limit SC discussions in preference to treatment in clinical interactions. The role of structural barriers, including prescriptive authority for nurses, hinders active SC processes, as it is the lack of continuity and embedding of services supported by a clinical champion for SC. CONCLUSIONS: The study suggests re-evaluating the status quo in SC service, highlighting service gaps and suggesting opportunities at organizational levels to reduce structural barriers. IMPLICATIONS: Variations in smoking cessation services exist in designated cancer centres. The data from this study can be used to inform a real time health systems approach for SC services in oncology settings. Developing tailored smoking cessation services and interventions that are patient-centred and informed by their experiences are required. The data in this study suggests developing specialist education and training to upskill HCPs for equitable engagement if we are to meet EU and Moonshot goals for cancer reduction.

Performance of Computer-Aided Detection and Quality of Bowel Preparation: A Comprehensive Analysis of Colonoscopy Outcomes.

BACKGROUND: Artificial intelligence (AI) has emerged as a promising tool for detecting and characterizing colorectal polyps during colonoscopy, offering potential enhancements in traditional colonoscopy procedures to improve outcomes in patients with inadequate bowel preparation. AIMS: This study aimed to assess the impact of an AI tool on computer-aided detection (CADe) assistance during colonoscopy in this population. METHODS: This case-control study utilized propensity score matching (PSM) for age, sex, race, and colonoscopy indication to analyze a database of patients who underwent colonoscopy at a single tertiary referral center between 2017 and 2023. Patients were excluded if the procedure was incomplete or aborted owing to poor preparation. The patients were categorized based on the use of AI during colonoscopy. Data on patient demographics and colonoscopy performance metrics were collected. Univariate and multivariate logistic regression models were used to compare the groups. RESULTS: After PSM patients with adequately prepped colonoscopies (n = 1466), the likelihood of detecting hyperplastic polyps (OR = 2.0, 95%CI 1.7-2.5, p < 0.001), adenomas (OR = 1.47, 95%CI 1.19-1.81, p < 0.001), and sessile serrated polyps (OR = 1.90, 95%CI 1.20-3.03, p = 0.007) significantly increased with the inclusion of CADe. In inadequately prepped patients (n = 160), CADe exhibited a more pronounced impact on the polyp detection rate (OR = 4.34, 95%CI 1.6-6.16, p = 0.049) and adenomas (OR = 2.9, 95%CI 2.20-8.57, p < 0.001), with a marginal increase in withdrawal and procedure times. CONCLUSION: This study highlights the significant improvement in detecting diminutive polyps (< 5 mm) and sessile polyps using CADe, although notably, this benefit was only seen in patients with adequate bowel preparation. In conclusion, the integration of AI in colonoscopy, driven by artificial intelligence, promises to significantly enhance lesion detection and diagnosis, revolutionize the procedure's effectiveness, and improve patient outcomes.

Patients' and Clinicians' Perceptions of the Clinical Utility of Predictive Risk Models for Chemotherapy-Related Symptom Management: Qualitative Exploration Using Focus Groups and Interviews.

BACKGROUND: Interest in the application of predictive risk models (PRMs) in health care to identify people most likely to experience disease and treatment-related complications is increasing. In cancer care, these techniques are focused primarily on the prediction of survival or life-threatening toxicities (eg, febrile neutropenia). Fewer studies focus on the use of PRMs for symptoms or supportive care needs. The application of PRMs to chemotherapy-related symptoms (CRS) would enable earlier identification and initiation of prompt, personalized, and tailored interventions. While some PRMs exist for CRS, few were translated into clinical practice, and human factors associated with their use were not reported. OBJECTIVE: We aim to explore patients' and clinicians' perspectives of the utility and real-world application of PRMs to improve the management of CRS. METHODS: Focus groups (N=10) and interviews (N=5) were conducted with patients (N=28) and clinicians (N=26) across 5 European countries. Interactions were audio-recorded, transcribed verbatim, and analyzed thematically. RESULTS: Both clinicians and patients recognized the value of having individualized risk predictions for CRS and appreciated how this type of information would facilitate the provision of tailored preventative treatments or supportive care interactions. However, cautious and skeptical attitudes toward the use of PRMs in clinical care were noted by both groups, particularly in relationship to the uncertainty regarding how the information would be generated. Visualization and presentation of PRM information in a usable and useful format for both patients and clinicians was identified as a challenge to their successful implementation in clinical care. CONCLUSIONS: Findings from this study provide information on clinicians' and patients' perspectives on the clinical use of PRMs for the management of CRS. These international perspectives are important because they provide insight into the risks and benefits of using PRMs to evaluate CRS. In addition, they highlight the need to find ways to more effectively present and use this information in clinical practice. Further research that explores the best ways to incorporate this type of information while maintaining the human side of care is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02356081; https://clinicaltrials.gov/study/NCT02356081.

Building research capacity and culture: Exploring nurses' experience of implementing a nurse-led clinical trial.

AIM: To explore the experiences of a nursing team who implemented an international nurse-led clinical trial in practice and understand the facilitators to their involvement. BACKGROUND: The role and responsibilities of the clinical nurse are advancing to encompass research activity to help inform evidence-based practice. However, several personal and organisational challenges can inhibit nurses' capacity to implement and undertake research within clinical practice. METHODS: Three focus groups were conducted with members of a nursing team (N = 18). Thematic analysis was employed, and themes were identified and agreed upon by the research team. RESULTS: Five themes were identified: 'Previous experience of and attitudes to participation in clinical research', 'Decision-making regarding participation in the clinical trial', 'Facilitators of participation in the clinical trial', 'Challenges of research in nursing practice' and 'Future orientation towards research'. CONCLUSION: Through their experiences of implementing a nurse-led clinical trial within practice, nurses recognized a number of facilitators and challenges to their participation. The perceived relevance of the clinical trial to the nurses' practice, potential to improve patient care and appreciation of the nurse leader's expertise and understanding of their context were key motivators. Reciprocal trust with the nurse leader who was encouraging, motivating, supportive and accessible resulted in the engagement and commitment of the nursing team. IMPLICATIONS FOR NURSING MANAGEMENT: This paper offers a perspective that can inform senior nursing management teams when implementing and conducting evidence-based research amongst nursing teams and in doing so meet the needs of developing research capacity amongst clinical nurses.

Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation.

Delayed engraftment is a major limitation of cord blood transplantation (CBT), due in part to a defect in the cord blood (CB) cells' ability to home to the bone marrow. Because this defect appears related to low levels of fucosylation of cell surface molecules that are responsible for binding to P- and E-selectins constitutively expressed by the marrow microvasculature, and thus for marrow homing, we conducted a first-in-humans clinical trial to correct this deficiency. Patients with high-risk hematologic malignancies received myeloablative therapy followed by transplantation with 2 CB units, one of which was treated ex vivo for 30 minutes with the enzyme fucosyltransferase-VI and guanosine diphosphate fucose to enhance the interaction of CD34(+) stem and early progenitor cells with microvessels. The results of enforced fucosylation for 22 patients enrolled in the trial were then compared with those for 31 historical controls who had undergone double unmanipulated CBT. The median time to neutrophil engraftment was 17 days (range, 12-34 days) compared with 26 days (range, 11-48 days) for controls (P = .0023). Platelet engraftment was also improved: median was 35 days (range, 18-100 days) compared with 45 days (range, 27-120 days) for controls (P = .0520). These findings support ex vivo fucosylation of multipotent CD34(+) CB cells as a clinically feasible means to improve engraftment efficiency in the double CBT setting. The trial is registered to www.clinicaltrials.gov as #NCT01471067.

Radiofrequency Ablation of Hepatic Tumor: Subjective Assessment of the Perilesional Vascular Network on Contrast-Enhanced Computed Tomography Before and After Ablation Can Reliably Predict the Risk of Local Recurrence.

OBJECTIVE: To determine whether simple, subjective analysis of the perilesional vascular network can predict the risk of local recurrence after radiofrequency ablation (RFA) of liver malignancies on contrast-enhanced computed tomography (CECT). METHODS: Contrast-enhanced computed tomography's 103 patients (59 men and 44 women; mean age, 63 years (range, 31-84 years) with 134 lesions who underwent RFA between 2000 and 2010 were retrospectively analyzed. The primary tumors include colorectal carcinoma (58 patients), hepatocellular carcinoma (n = 13), breast carcinoma (n = 8), neuroendocrine tumor (n = 5), and others (n = 19). Three blinded radiologists independently reviewed the CECT (a triple phase liver protocol for hypervascular tumors and a single phase for the hypovascular tumors) before and 6 weeks after RFA and subjectively estimated the width of the ablative margin on a 3-point scale (optimal, 1; suboptimal, 2; and residual tumor, 3). Local recurrence was determined on follow-up CECT. RESULTS: The consensus score was 1 in 94, 2 in 28, and 3 in 12 lesions. κ among readers was 0.75. Local recurrence occurred in 3 lesions with a score of 1 and 12 lesions with a score of 2. The consensus score was a significant univariate predictor of local recurrence. CONCLUSIONS: Subjective estimation of the width of ablative margin can reliably predict the risk of local recurrence.

Long-Term Outcomes after Treatment with Clofarabine ± Fludarabine with Once-Daily Intravenous Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and Myelodysplastic Syndrome.

Pretransplant conditioning regimens critically determine outcomes in the setting of allogeneic stem cell transplantation (allo-SCT). The use of nucleoside analogs such as fludarabine (Flu) in combination with i.v. busulfan (Bu) has been shown to be highly effective as a pretransplant conditioning regimen in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). Because leukemia relapse remains the leading cause of death after allo-SCT, we studied whether clofarabine (Clo), a nucleoside analog with potent antileukemia activity, can be used to complement Flu. In a preliminary report, we previously showed the safety and efficacy of Clo ± Flu with i.v. Bu in 51 patients with high-risk AML, CML, and MDS. The study has now been completed, and we present long-term follow-up data on the entire 70-patient population, which included 49 (70%), 8 (11%), and 13 (19%) patients with AML, MDS, and CML, respectively. Thirteen patients (19%) were in complete remission, and 41 patients (59%) received matched unrelated donor grafts. Engraftment was achieved in all patients. Sixty-three patients (90%) achieved complete remission. There were no deaths reported at day +30, and the 100-day nonrelapse mortality rate was 4% (n = 3). Thirty-one percent of patients (n = 22) developed grades II to IV acute graft-versus-host disease, and the median overall survival and progression-free survival times were 2.4 years and .9 years, respectively. Our results confirm the safety and overall and progression-free survival advantage of the arms with higher Clo doses and lower Flu doses, which was most prominent in the AML/MDS group.

Microcalcifications in 1657 Patients with Pure Ductal Carcinoma in Situ of the Breast: Correlation with Clinical, Histopathologic, Biologic Features, and Local Recurrence.

PURPOSE: This study was designed to determine the relationship of microcalcification morphology and distribution with clinical, histopathologic, biologic features, and local recurrence (LR) in patients with pure ductal carcinoma in situ (DCIS) of the breast. METHODS: All patients with pure DCIS who underwent preoperative mammography at our institution from 1996 through 2009 were identified. Mammographic findings were classified according to the ACR BI-RADS lexicon. Associations between mammographic findings and clinical, histopathologic, biologic characteristics, and LR were analyzed. Statistical inference used multiple logistic regression and Cox proportional hazards regression adjusted for age and confounding due to bias from nonrandomized selection of radiation therapy. RESULTS: We identified 1657 patients with microcalcifications visualized on mammography. The mean age at diagnosis was 55 years (SD, 11). The mean follow-up was 7 years (range 1-16). Ipsilateral LR was 4 % in segmentectomy (987) and 1.5 % in mastectomy (670) patients. Increased LR risk was seen in patients with dense breast tissue (p < 0.05) and larger DCIS size (p < 0.01). Radiation therapy was associated with a 2.8-fold decrease in the LR risk. Fine linear (branching) microcalcifications were associated with 5.2-fold increase in LR. Extremely dense breast tissue was associated with positive/close margins (p = 0.04) and multicentricity (p < 0.01). Younger women were more likely to have extremely dense breast tissue (p < 0.0001), multicentric disease (p < 0.0004), and undergo mastectomy (p < 0.0001). CONCLUSIONS: Dense breast tissue, large DCIS size, and fine linear (branching) microcalcifications were associated with increased LR, yet overall LR rates remained low. Extremely dense breast tissue was a risk factor for multicentricity and positive margins in DCIS.

Atypical chronic myeloid leukemia is clinically distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms.

Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) largely defined morphologically. It is, unclear, however, whether aCML-associated features are distinctive enough to allow its separation from unclassifiable MDS/MPN (MDS/MPN-U). To study these 2 rare entities, 134 patient archives were collected from 7 large medical centers, of which 65 (49%) cases were further classified as aCML and the remaining 69 (51%) as MDS/MPN-U. Distinctively, aCML was associated with many adverse features and an inferior overall survival (12.4 vs 21.8 months, P = .004) and AML-free survival (11.2 vs 18.9 months, P = .003). The aCML defining features of leukocytosis and circulating myeloid precursors, but not dysgranulopoiesis, were independent negative predictors. Other factors, such as lactate dehydrogenase, circulating myeloblasts, platelets, and cytogenetics could further stratify MDS/MPN-U but not aCML patient risks. aCML appeared to have more mutated RAS (7/20 [35%] vs 4/29 [14%]) and less JAK2p.V617F (3/42 [7%] vs 10/52 [19%]), but was not statistically significant. Somatic CSF3R T618I (0/54) and CALR (0/30) mutations were not detected either in aCML or MDS/MPN-U. In conclusion, within MDS/MPN, the World Health Organization 2008 criteria for aCML identify a subgroup of patients with features clearly distinct from MDS/MPN-U. The MDS/MPN-U category is heterogeneous, and patient risk can be further stratified by a number of clinicopathological parameters.