Genome-wide footprints in the carob tree (Ceratonia siliqua) unveil a new domestication pattern of a fruit tree in the Mediterranean

Intense research efforts over the last two decades have renewed our understanding of plant phylogeography and domestication in the Mediterranean basin. Here we aim to investigate the evolutionary history and the origin of domestication of the carob tree (Ceratonia siliqua), which has been cultivated for millennia for food and fodder. We used >1000 microsatellite genotypes to delimit seven carob evolutionary units (CEUs). We investigated genome-wide diversity and evolutionary patterns of the CEUs with 3557 single nucleotide polymorphisms generated by restriction-site associated DNA sequencing (RADseq). To address the complex wild vs. cultivated status of sampled trees, we classified 56 sampled populations across the Mediterranean basin as wild, seminatural or cultivated. Nuclear and cytoplasmic loci were identified from RADseq data and separated for analyses. Phylogenetic analyses of these genomic-wide data allowed us to resolve west-to-east expansions from a single long-term refugium probably located in the foothills of the High Atlas Mountains near the Atlantic coast. Our findings support multiple origins of domestication with a low impact on the genetic diversity at range-wide level. The carob was mostly domesticated from locally selected wild genotypes and scattered long-distance westward dispersals of domesticated varieties by humans, concomitant with major historical migrations by Romans, Greeks and Arabs. Ex situ efforts to preserve carob genetic resources should prioritize accessions from both western and eastern populations, with emphasis on the most differentiated CEUs situated in southwest Morocco, south Spain and eastern Mediterranean. Our study highlights the relevance of wild and seminatural habitats in the conservation of genetic resources for cultivated trees

Long-term benefit of lurbinectedin as palliative chemotherapy in progressive malignant pleural mesothelioma (MPM): final efficacy and translational data of the SAKK 17/16 study.

BACKGROUND The SAKK 17/16 study showed promising efficacy data with lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma. Here, we evaluated long-term outcome and analyzed the impact of lurbinectedin monotherapy on the tumor microenvironment at the cellular and molecular level to predict outcomes. MATERIAL AND METHODS Forty-two patients were treated with lurbinectedin in this single-arm study. Twenty-nine samples were available at baseline, and seven additional matched samples at day one of cycle two of treatment. Survival curves and rates between groups were compared using the log-rank test and Kaplan-Meier method. Statistical significance was set at P value <0.05. RESULTS Updated median overall survival (OS) was slightly increased to 11.5 months [95% confidence interval (CI) 8.8-13.8 months]. Thirty-six patients (85%) had died. The OS rate at 12 and 18 months was 47% (95% CI 32.1% to 61.6%) and 31% (95% CI 17.8% to 45.0%), respectively. Median progression-free survival was 4.1 months (95% CI 2.6-5.5 months). No new safety signals were observed. Patients with lower frequencies of regulatory T cells, as well as lower tumor-associated macrophages (TAMs) at baseline, had a better OS. Comparing matched biopsies, a decrease of M2 macrophages was observed in five out of seven patients after exposure to lurbinectedin, and two out of four patients showed increased CD8+ T-cell infiltrates in tumor. DISCUSSION Lurbinectedin continues to be active in patients with progressing malignant pleural mesothelioma. According to our very small sample size, we hypothesize that baseline TAMs and regulatory T cells are associated with survival. Lurbinectedin seems to inhibit conversion of TAMs to M2 phenotype in humans

First interim analysis of the GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib) non‐interventional study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92068/1/j.1742-1241.2012.02940.x.pd

Nasopharyngeal oxygen insufflation following pre-oxygenation using the four deep breath technique

Summary This paper evaluates the effectiveness of nasopharyngeal oxygen insufflation following preoxygenation using the four deep breath technique within 30 s, on the onset of haemoglobin desaturation during the subsequent apnoea. Thirty ASA I or II patients were randomly allocated to one of two groups. In the study group (n = 15), pre-oxygenation was followed by insufflation of oxygen at a flow of 5 l.min )1 via a nasopharyngeal catheter commenced at the onset of apnoea. In the control group, pre-oxygenation was not followed by nasopharyngeal oxygen insufflation (n = 15). In the control group, S p O 2 fell to 95% within a mean (SD) apnoea time of 3.65 (1.15) min, whereas in the study group, S p O 2 was maintained in all patients at 100% throughout the 6 min of apnoea, at which point apnoea was terminated and positive pressure ventilation commenced. We conclude that nasopharyngeal oxygen insufflation following pre-oxygenation using the four deep breath technique can delay the onset of haemoglobin desaturation for a significant period of time during the subsequent apnoea. Increasing ambient O 2 fraction from 0.9 to 1.0 more than doubled the time before haemoglobin desaturation fell to 50% and extended the period of apnoea to a greater extent than when the ambient O 2 fraction was increased from 0.21 to 0.9. During brainstem death testing, only one study has compared the effects of 100% oxygen and air as alternative ambient gases on P a O 2 ; patients who had been pre-oxygenated with 100% O 2 developed little or no hypoxaemia when compared to those receiving ai

Finite element analysis of cracking and delamination of concrete beam due to steel corrosion

This paper presents the analytical results to investigate cracking and delamination of concrete beam due to steel corrosion. A series of concrete beams were idealised as two dimensional models via their cross section and analysed using the finite element software – LUSAS. The corrosion of steel bars was simulated using a radial expansion. The FE results show that cracking of beam section due to steel corrosion can be clarified into four types, i.e., Internal Cracking, Internal Penetration, External Cracking (HS) and External Cracking (VB). The amount of corrosion in term of radial expansion required to causes Internal Cracking, Internal Penetration, External Cracking (HS) and External Cracking (VB) varies almost linearly with bar diameter d, bar clear distance s and concrete cover c, respectively. If the ratio s/c was less than the critical value of about 2.2, the delamination of concrete cover could occur before the cracks can be visualised on the concrete surface, which does concern engineers

Working sick and out of sorts: a cross-cultural approach on presenteeism climate, organizational justice and work-family conflict

A climate of presenteeism has important effects on employee well-being and the organization itself. Our study, based on surveys of health sector employees in six different countries (Brazil, Ecuador, Lebanon, Portugal, Russia and Spain) examines whether organizational justice plays a mediating role in the relationship between a presenteeism climate in the organization and work-family conflict (WFC). Our results indicate that the perception of organizational justice and the presenteeism climate do influence WFC. Moreover, higher levels of WFC were found in non-Latin countries. This study contributes to the work attendance and life balance field by providing cross-cultural empirical evidence corroborating the effect of justice and presenteeism climate on the WFC

The immunopeptidome landscape associated with T cell infiltration, inflammation and immune editing in lung cancer.

One key barrier to improving efficacy of personalized cancer immunotherapies that are dependent on the tumor antigenic landscape remains patient stratification. Although patients with CD3 &lt;sup&gt;+&lt;/sup&gt; CD8 &lt;sup&gt;+&lt;/sup&gt; T cell-inflamed tumors typically show better response to immune checkpoint inhibitors, it is still unknown whether the immunopeptidome repertoire presented in highly inflamed and noninflamed tumors is substantially different. We surveyed 61 tumor regions and adjacent nonmalignant lung tissues from 8 patients with lung cancer and performed deep antigen discovery combining immunopeptidomics, genomics, bulk and spatial transcriptomics, and explored the heterogeneous expression and presentation of tumor (neo)antigens. In the present study, we associated diverse immune cell populations with the immunopeptidome and found a relatively higher frequency of predicted neoantigens located within HLA-I presentation hotspots in CD3 &lt;sup&gt;+&lt;/sup&gt; CD8 &lt;sup&gt;+&lt;/sup&gt; T cell-excluded tumors. We associated such neoantigens with immune recognition, supporting their involvement in immune editing. This could have implications for the choice of combination therapies tailored to the patient's mutanome and immune microenvironment

Simultaneous resection of colorectal cancer and synchronous liver metastases: what determines the risk of unfavorable outcomes? An international multicenter retrospective cohort study

BACKGROUND: The use of a simultaneous resection (SIMR) in patients with synchronous colorectal liver metastases (sCRLM) has increased over the past decades. However, it remains unclear when a SIMR is beneficial and when it should be avoided. The aim of this retrospective cohort study was therefore to compare the outcomes of a SIMR for sCRLM in different settings, and to assess which factors are independently associated with unfavorable outcomes. METHODS: To perform this retrospective cohort study, patients with sCRLM undergoing SIMR (2004-2019) were extracted from an international multicenter database, and their outcomes were compared after stratification according to the type of liver and colorectal resection performed. Factors associated with unfavorable outcomes were identified through multivariable logistic regression. RESULTS: Overall, 766 patients were included, encompassing colorectal resections combined with a major liver resection (n=122), minor liver resection in the anterolateral (n=407), or posterosuperior segments ('Technically major', n=237). Minor and technically major resections, compared to major resections, were more often combined with a rectal resection (29.2 and 36.7 vs. 20.5%, respectively, both P=0.003) and performed fully laparoscopic (22.9 and 23.2 vs. 6.6%, respectively, both P = 0.003). Major and technically major resections, compared to minor resections, were more often associated with intraoperative transfusions (42.9 and 38.8 vs. 20%, respectively, both P = 0.003) and unfavorable incidents (9.6 and 9.8 vs. 3.3%, respectively, both P≤0.063). Major resections were associated, compared to minor and technically major resections, with a higher overall morbidity rate (64.8 vs. 50.4 and 49.4%, respectively, both P≤0.024) and a longer length of stay (12 vs. 10 days, both P≤0.042). American Society of Anesthesiologists grades ≥3 [adjusted odds ratio (aOR): 1.671, P=0.015] and undergoing a major liver resection (aOR: 1.788, P=0.047) were independently associated with an increased risk of severe morbidity, while undergoing a left-sided colectomy was associated with a decreased risk (aOR: 0.574, P=0.013). CONCLUSIONS: SIMR should primarily be reserved for sCRLM patients in whom a minor or technically major liver resection would suffice and those requiring a left-sided colectomy. These findings should be confirmed by randomized studies comparing SIMR with staged resections

Attentive Learning of Sequential Handwriting Movements: A Neural Network Model

Defense Advanced research Projects Agency and the Office of Naval Research (N00014-95-1-0409, N00014-92-J-1309); National Science Foundation (IRI-97-20333); National Institutes of Health (I-R29-DC02952-01)