Search

Dissolved organic matter (DOM) assemblages in freshwater rivers are formed from mixtures of simple to complex compounds that are highly variable across time and space. These mixtures largely form due to the environmental heterogeneity of river networks and the contribution of diverse allochthonous and autochthonous DOM sources. Most studies are, however, confined to local and regional scales, which precludes an understanding of how these mixtures arise at large, e.g., continental, spatial scales. The processes contributing to these mixtures are also difficult to study because of the complex interactions between various environmental factors and DOM. Here we propose the use of machine learning (ML) approaches to identify ecological processes contributing toward mixtures of DOM at a continental-scale. We related a dataset that characterized the molecular composition of DOM from river water and sediment with Fourier-transform ion cyclotron resonance mass spectrometry to explanatory physicochemical variables such as nutrient concentrations and stable water isotopes (2H and 18O). Using unsupervised ML, distinctive clusters for sediment and water samples were identified, with unique molecular compositions influenced by environmental factors like terrestrial input and microbial activity. Sediment clusters showed a higher proportion of protein-like and unclassified compounds than water clusters, while water clusters exhibited a more diversified chemical composition. We then applied a supervised ML approach, involving a two-stage use of SHapley Additive exPlanations (SHAP) values. In the first stage, SHAP values were obtained and used to identify key physicochemical variables. These parameters were employed to train models using both the default and subsequently tuned hyperparameters of the Histogram-based Gradient Boosting (HGB) algorithm. The supervised ML approach, using HGB and SHAP values, highlighted complex relationships between environmental factors and DOM diversity, in particular the existence of dams upstream, precipitation events, and other watershed characteristics were important in predicting higher chemical diversity in DOM. Our data-driven approach can now be used more generally to reveal the interplay between physical, chemical, and biological factors in determining the diversity of DOM in other ecosystems.

OBJECTIVES To analyse impact of segmentectomy on oncological outcomes of different peripheral early-stage lung adenocarcinoma patterns. METHODS Retrospective multicentre study including patients who underwent either lobectomy or segmentectomy in 6 European centres from 2015 to 2021, for ≤2 cm pathological peripheral lung adenocarcinoma. Overall and disease-free survivals were assessed by cox-regression and lung cancer-specific survival by competing regression analyses to adjust for patient- and tumour-related factors both in the entire dataset and the in aggressive adenocarcinoma patterns dataset. RESULTS Lobectomy and segmentectomy were performed in 481 (71%) and 193 (29%) patients, respectively. Propensity score matching was performed (n  = 191). One hundred and 8 patients had a least an aggressive pattern. Five-year disease-free, overall and lung cancer-specific survivals were similar between patients who underwent lobectomy or segmentectomy in both entire and aggressive pattern datasets. In patients with aggressive pattern, 5-year disease-free (lobectomy 87.3%; segmentectomy 86.6%, P  = 0.62), overall (lobectomy 86.4%; segmentectomy 95.6%, P  = 0.61) and lung cancer-specific (lobectomy 100%; segmentectomy 95.6%, P  = 0.13) survivals did not differ. Segmentectomy was not an independent risk factor for disease-free survival, neither for overall survival nor for lung cancer-specific survival in any of the 2 datasets. In patients with aggressive pattern, loco-regional recurrence (linearized risks: lobectomy 8.21; segmentectomy 11.3) was higher in patients who underwent segmentectomy. CONCLUSIONS Resection should not be extended (to lobectomy) on patients who underwent segmentectomy for pathologically proven early-stage adenocarcinoma with aggressive patterns. [ABSTRACT FROM AUTHOR]

Objectives: The choice of the best Video-Assisted Thoracic Surgery (VATS) surgical approach is still debated. Surgeons are often faced with the choice between innovation and self-confidence. The present study reports the experience of a high-volume single institute, comparing data of uni-portal, bi-portal and tri-portal VATS, to find out the safest and most effective mini-invasive approach, leading surgeon's choice. Methods: Between 2015 and 2022, a total of 210 matched patients underwent VATS lobectomy for early-stage cancer, using uni-portal (fifth intercostal space), bi-portal (seventh space for optic and the fifth), and tri-portal (seventh and the fifth/four) access. Patients were matched for age, BPCO, smoke, comorbidities, lesions (size and staging) to obtain three homogenous groups (A: uni-portal; B: bi-portal; C: tri-portal). The surgeons had comparable expertise. Data were retrospectively collected from institutional database and analyzed. Results: No differences were detected considering time of surgery, length of hospital stay, complications, conversion rate, specific survival, and days of chest tube length of stay. Better results on chest tube removal were described in group A (mean 1.1 days) compared to B (mean 2.6 days) and C (mean 4.7 days); nevertheless, they not statistically significant (p = 0.106). Conclusions: No significant differences among the groups were described, except for the reduction in chest tube permanence in group A. This allows to hypothesize an enhanced recovery after surgery in this group but the different approaches in this series seem to guarantee comparable safety and effectiveness. Considering no superiority of one method above the others, the best suggested approach should be the one for which the surgeon feels more confident. [ABSTRACT FROM AUTHOR]

We present polar ice core organic matter (OM) fluorescence signatures to reconstruct ancient and modern atmospheric compositions and relate OM signals to past ecological changes. OM composition from three Arctic ice cores (Canada and Greenland) was characterized by fluorescence spectroscopy and compared to an Antarctic OM record. Diverse OM was measured in ancient and modern ice in both hemispheres and similarities existed across vast spatiotemporal scales. We determined three OM markers, indicating paleoclimate and modern carbon trends: (i) ‘humic-like’, detected in Holocene ice of more complex and aromatic character, supporting trends of higher plant influences in warmer climates, (ii) monolignol- and non-amino acid-like, describing simple, lignin-like OM precursors ubiquitous in the environment and the microbial degradation products of more complex materials from plants/soils, and (iii) amino acid- and tannin-like, indicating microbial degradation of simple OM chemical species, compared to the other markers. Concentration trends were inferred from fluorescence intensities of individual OM types and related to warmer temperatures. No indicators of freshly produced OM by microbes were detected; signals were interpreted as materials externally produced from the ice and transported to polar regions. This marks the first global comparison of atmospheric reconstructions from OM across vast spatiotemporal scales.

Purpose Pulmonary hamartoma is the most common benign tumor of the lung. We analyzed a 20-year historical series of patients with pulmonary hamartoma undergoing surgical resection, aiming to evaluate the characteristics, the outcomes, and the association between hamartoma and lung cancer. Methods It was a retrospective multicenter study including the data of all consecutive patients with pulmonary hamartoma undergoing surgical resection. The end-points were to evaluate: (i) the characteristics of hamartoma, (ii) outcomes, and (iii) whether hamartoma was a predictive factor for lung cancer development Results Our study population included 540 patients. Upfront surgical or endoscopic resection was performed in 385 (71%) cases while in the remaining 155 (29%) cases, the lesions were resected 20 ± 3.5 months later due to increase in size. In most cases, lung sparing resection was carried out including enucleation (n = 259; 48%) and wedge resection (n = 230; 43%) while 5 (1%) patients underwent endoscopic resection. Only two patients (0, 2%) had major complications. One patient (0.23%) had recurrence after endoscopic resection, while no cases of malignant degeneration were seen (mean follow-up:103.3 ± 93 months). Seventy-six patients (14%) had associated lung cancer, synchronous in 9 (12%) and metachronous in 67 (88%). Only age > 70-year-old (p = 0.0059) and smokers > 20 cigarettes/day (p < 0.0001) were the significant risk factors for lung cancer. Conclusion PH was a benign tumor, with no evidence of recurrence and/or of malignant degeneration after resection. The association between hamartoma and lung cancer was a spurious phenomenon due to common risk factors., Author(s): Alfonso Fiorelli [sup.1], Antonio D'Andrilli [sup.2], Annalisa Carlucci [sup.1], Giovanni Vicidomini [sup.1], Giacomo Argento [sup.2], Beatrice Trabalza Marinucci [sup.2], Francesco Ardissone [sup.3], Roberta Rapanà [sup.3], Simona Sobrero [sup.3], Paolo [...]

Estrogen deficiency, long‐term immobilization, and/or aging are commonly related to bone mass loss, thus increasing the risk of fractures. One option for bone replacement in injuries caused by either traumas or pathologies is the use of orthopedic cement based on polymethylmethacrylate (PMMA). Nevertheless, its reduced bioactivity may induce long‐term detachment from the host tissue, resulting in the failure of the implant. In view of this problem, we developed an alternative PMMA‐based porous cement (pPMMA) that favors cell invasion and improves osteointegration with better biocompatibility. The cement composition was changed by adding bioactive strontium‐nanoparticles that mimic the structure of bone apatite. The nanoparticles were characterized regarding their physical–chemical properties, and their effects on osteoblasts and osteoclast cultures were assessed. Initial in vivo tests were also performed using 16 New Zealand rabbits as animal models, in which the pPMMA‐cement containing the strontium nanoparticles were implanted. We showed that the apatite nanoparticles in which 90% of Ca2+ ions were substituted by Sr2+ (NanoSr 90%) upregulated TNAP activity and increased matrix mineralization. Moreover, at the molecular level, NanoSr 90% upregulated the mRNA expression levels of, Sp7, and OCN. Runx2 was increased at both mRNA and protein levels. In parallel, in vivo tests revealed that pPMMA‐cement containing NanoSr 90%, upregulated two markers of bone maturation, OCN and BMP2, as well as the formation of apatite minerals after implantation in the femur of rabbits. The overall data support that strontium nanoparticles hold the potential to up‐regulate mineralization in osteoblasts when associated with synthetic biomaterials. [ABSTRACT FROM AUTHOR]

Abstract Background Video-Assisted Thoracic Surgery (VATS) lobectomy is now considered the preferred approach at many centers for early stage lung cancer. However, it needs an adequate learning curve, and it may be challenging in non-expert hands. The aim of this study was to evaluate the effectiveness of Transcollation Technology over Traditional Electrocautery to perform hilar and mediastinal dissection during VATS lobectomy. Methods This is a single-center retrospective study including consecutive patients undergoing VATS lobectomy for lung cancer. Patients were divided in two groups based on whether Transcollation Technology (TT Group) or Traditional Electrocautery (TE Group) was used for hilar and mediastinal lymphadenectomy. Operative time and surgical outcome, including number of transfusions, length of chest drainage, length of hospital stay, morbidity and mortality were registered, and the inter-group differences were statistically analyzed. Results 53 patients were included in the final analysis. The TT Group (n = 24) compared to the TE Group (n = 29) showed significant shorter operative time (75.2 ± 25.8 min versus 98.1 ± 33.3 min; p = 0.023), and reduction of length of chest tube stay (4.7 ± 0.8 days vs. 6.8 ± 1.1 days, p = 0.013) and length of hospital stay (5.3 ± 1.9 days vs. 6.8 ± 1.1 days, p = 0.007). No intraoperative or major postoperative complications were observed in either groups. Conclusions Transcollation Technology represents a valid alternative to standard electrocautery instruments during VATS lobectomy. It contributes to reduce the operative time and length of hospital stay. Further larger prospective studies are required to confirm our data.

Abstract Background Uniportal video‐assisted thoracoscopic surgery (VATS) lobectomy has become a common approach for the treatment of early stage lung cancer. Here, we aimed to establish whether the length of uniportal incision could affect postoperative pain and surgical outcomes in consecutive patients undergoing uniportal VATS lobectomy for early stage lung cancer. Methods This was a unicenter Randomized Control Trial (NCT 03218098). Consecutive patients undergoing uniportal VATS lobectomy for Stage I lung cancer were randomly assigned to a Small Incision group or Long Incision group in 1:1 ratio based on whether patients received a 4 cm or 8 cm incision. The endpoints were to compare the intergroup difference regarding (i) postoperative pain measured by brief pain inventory (BPI) questionnaire (first endpoint); (ii) operative time; (iii) length of chest drainage; (iv) length of hospital stay; (v) postoperative complications; and (vi) pulmonary functional status (secondary endpoints). Results A total of 48 patients were eligible for the study. Four patients were excluded; the study population included 44 patients: 23 within the Small Incision group, and 21 within the Long Incision group. The 11 BPI scores between the two groups showed no significant difference. Small Incision group presented higher operative time than Long Incision group (138.69 vs. 112.14 minutes; P = 0.0001) while no significant differences were found regarding length of hospital stay (P = 0.95); respiratory complications (P = 0.92); FEV1% (P = 0.63), and 6‐Minute Walking Test (P = 0.77). Conclusions A larger incision for uniportal VATS lobectomy significantly reduced the operative time due to better exposure of the anatomical structures without increasing postoperative pain or affecting the surgical outcome. Key points A larger incision for uniportal VATS lobectomy significantly reduced the operative time due to better exposure of the anatomical structures without increasing postoperative pain or affecting the surgical outcome. To perform a larger incision could be a valuable strategy, particularly in nonexpert hands or when the patient's anatomy or tumor size make exposure of anatomic structures through smaller incisions difficult.

Abstract Background Tumor with adjacent lobe invasion (T‐ALI) is an uncommon condition. Controversy still exists regarding the optimal resection of adjacent lobe invasion, and the prognostic value in relation to fissure integrity at the tumor invasion point. The aims of this paper were to evaluate the prognosis of T‐ALI with regard to fissure integrity, and type of resection. Methods This was a retrospective multicenter study which included all consecutive patients with T‐ALI undergoing surgical treatment. Based on radiological, intraoperative and histological findings, T‐ALI patients were differentiated into two groups based on whether the fissure was complete (T‐ALI‐A group) or incomplete (T‐ALI‐D Group) at the level of tumor invasion point. Clinico‐pathological features and survival of two study groups were analyzed and compared. Results Study population included 135 patients, of these 98 (72%) were included into T‐ALI‐A group, and 37 (38%) into T‐ALI‐D Group. T‐ALI‐D patients had better overall survival than T‐ALI‐A patients (63.9 ± 7.0 vs. 48.9 ± 3.9; respectively, P = 0.01) who presented with a higher incidence of lymph node involvement (35% vs. 4%; P = 0.004), and recurrence rate (43% vs. 16%; P = 0.01). At multivariable analysis, T‐ALI‐D (P = 0.01), pN0 stage (P = 0.0002), and pT≤5 cm (P = 0.0001) were favorable survival prognostic factors. Conclusions T‐ALI‐D presented a better prognosis than T‐ALI‐A while extent of resection had no effect on survival. Thus, in patients with small T‐ALI‐D and without lymph node involvement, sublobar resection of adjacent lobe rather than lobectomy could be indicated. Key points The extent of resection of adjacent lobe had no effect on survival while T‐ALI‐D, pN0 stage, and pT≤5 cm were significant prognostic factors. In patients with small T‐ALI‐D and without lymph node involvement, sublobar resection of adjacent lobe could be indicated as an alternative to lobectomy.

(1) Introduction: Leiomyosarcomas are highly aggressive mesenchymal neoplasm derived from smooth muscle cells which, in the mediastinum, are present in various primary organs; To our knowledge, less than 10 cases of primary mediastinal leiomyosarcoma have been described. Here, we report a compelling case of primary mediastinal leiomyosarcoma. (2) Case presentation: A 79-year-old woman was admitted to the Thoracic Surgery Unit of S. Andrea University Hospital for persisting cough, exertional dyspnea, and sternal pain. After multidisciplinary consultation, a CT-guided core needle biopsy of the mass was performed, resulting in a provisional diagnosis of mesenchymal neoplasm with smooth muscle differentiation without apparent signs of atypia. The patient underwent surgery that revealed a large irregularly shaped mass with a whorled pattern cut surface, showing admixed yellowish areas of necrosis and areas of hemorrhage. Histologic examination showed a smooth muscle neoplasm with atypia and necrosis, and a grade 2 primary mediastinal leiomyosarcoma diagnosis was given. (3) Conclusions: Soft tissue sarcomas represent a challenging diagnostic group of tumors due to their location, morphologic spectrum, and unique molecular background. Our case of primary mediastinal leiomyosarcoma shows how tumor heterogeneity and limited tissue sampling impact diagnosis. Further studies are needed to shed light on the disease by finding an appropriate molecular signature for each leiomyosarcoma subgroup, providing a more precise diagnosis and the correct background for tailored therapy.

This report describes the innovative application of high sensitivity Boron-doped nanocrystalline diamond microelectrodes for tracking small changes in Ca2+ concentration due to binding to Annexin-A5 inserted into the lipid bilayer of liposomes (proteoliposomes), which could not be assessed using common Ca2+ selective electrodes. Dispensing proteoliposomes to an electrolyte containing 1 mM Ca2+ resulted in a potential jump that decreased with time, reaching the baseline level after ~300 s, suggesting that Ca2+ ions were incorporated into the vesicle compartment and were no longer detected by the microelectrode. This behavior was not observed when liposomes (vesicles without AnxA5) were dispensed in the presence of Ca2+. The ion transport appears Ca2+-selective, since dispensing proteoliposomes in the presence of Mg2+ did not result in potential drop. The experimental conditions were adjusted to ensure an excess of Ca2+, thus confirming that the potential reduction was not only due to the binding of Ca2+ to AnxA5 but to the transfer of ions to the lumen of the proteoliposomes. Ca2+ uptake stopped immediately after the addition of EDTA. Therefore, our data provide evidence of selective Ca2+ transport into the proteoliposomes and support the possible function of AnxA5 as a hydrophilic pore once incorporated into lipid membrane, mediating the mineralization initiation process occurring in matrix vesicles.

Dissociating gas hydrates, submerged permafrost, and gas bearing sediments release methane to the water column from a multitude of seeps in the Arctic Ocean. The seeping methane dissolves and supports the growth of aerobic methane oxidizing bacteria (MOB), but the effect of seepage and seep related biogeochemical processes on water column dissolved organic matter (DOM) dynamics is not well constrained. We compared dissolved methane, nutrients, chlorophyll, and particulate matter concentrations and methane oxidation (MOx) rates from previously characterized seep and non-seep areas at the continental margin of Svalbard and the Barents Sea in May and June 2017. DOM molecular composition was determined by Electrospray Ionization Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS). We found that the chemical diversity of DOM was 3 to 5% higher and constituted more protein- and lipid-like composition near methane seeps when compared to non-seep areas. Distributions of nutrients, chlorophyll, and particulate matter however, were essentially governed by the water column hydrography and primary production. We surmise that the organic intermediates directly derived from seepage or indirectly from seep-related biogeochemical processes, e.g., MOx, modifies the composition of DOM leading to distinct DOM molecular-level signatures in the water column at cold seeps.

Introduction: Intensive oncological treatment integrated with resection of metastases raised the clinical outcome of metastatic colorectal cancer (MCRC). In clinical practice, complex evaluation of clinical (age, performance status, comorbidities), and biological (tumoral genotype, pharmacogenomic) parameters addresses tailored, personalized multidisciplinary treatment strategies. Patients with MCRC unsuitable for first-line intensive medical treatments are prevalent and showed worse clinical outcome. After progression to oxaliplatin-based chemotherapy, aflibercept/FOLFIRI significantly improved clinical outcome, even if no survival benefit was reported in adjuvant fast relapsers by aflibercept addition. The case reported a young-elderly (yE) patient with KRAS mutant colorectal cancer rapidly progressing to adjuvant chemotherapy, unfit owing to comorbidities, with multiple pharmacogenomic alterations, who gained long-term survival in clinical practice by multidisciplinary treatment strategy consisting of first-line and re-introduction of aflibercept-containing chemotherapy and two-stage lung metastasectomies.Case presentation: A 71-years-old yE patient, unfit for intensive oncological treatments owing to Cumulative Illness Rating Scale (CIRS) stage secondary, affected by KRAS c.35 G>T mutant colorectal cancer, rapidly progressing with lung metastases after adjuvant XelOx chemotherapy, reached long-term survival 66 months with no evidence of disease after first-line and re-introduction of tailored, modulated aflibercept (4 mg/kg) d1,15-irinotecan (120 mg/m2) d1,15-5-fluorouracil (750 mg/m2/day) dd1–4, 15–18; and secondary radical bilateral two-stage lung metastasectomies. Safety profile was characterized by limiting toxicity syndrome at multiple sites (LTS-ms), requiring 5-fluorouracil discontinuation and aflibercept reduction (2 mg/kg), because of G2 hand-foot syndrome (HFS) for >2 weeks, and G3 hypertension. Pharmacogenomic analyses revealed multiple alterations of fluoropyrimidine and irinotecan metabolism: severe deficiency of fluorouracil degradation rate (FUDR), single nucleotide polymorphisms of UGT1A1*28 variable number of tandem repeats (VNTR) 7R/7R homozygote, ABCB1 c.C3435T, c.C1236T, MTHFR c.C667T homozygote, DPYD c.A166G, TSER 28bp VNTR 2R/3R heterozygote.Conclusions: In clinical practice, a complex management evaluating clinical parameters and RAS/BRAF genotype characterizing an individual patient with MCRC, particularly elderly and/or unfit owing to comorbidities, is required to properly address tailored, multidisciplinary medical and surgical treatment strategies, integrated with careful monitoring of superimposing toxicity syndromes, also related to pharmacogenomic alterations, to gain optimal activity, and long-term efficacy.

Abstract Dissolved organic matter (DOM) in freshwater environments is an important source of organic carbon, supporting bacterial respiration. Frozen environments cover vast expanses of our planet, with glaciers and ice‐sheets storing upwards of 6 petagrams of organic carbon. It is generally believed that DOM liberated from ice stimulates downstream environments. If true, glacial DOM is an important component of global carbon cycling. However, coupling the release of DOM to microbial activity is challenging due to the molecular complexity of DOM and the metabolic connectivity within microbial communities. Using a single environmentally relevant organism, we demonstrate that processing of compositionally diverse DOM occurs, but, even though glacially derived DOM is chemically labile, it is unable to support sustained respiration. In view of projected changes in glacier DOM export, these findings imply that biogeochemical impacts on downstream environments will depend on the reactivity and heterogeneity of liberated DOM, as well as the timescale.