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In this work, we investigate the correlation between tensile residual stress and Q-factor of double-clamped beams fabricated on epitaxial 3C-SiC layers grown on both and silicon substrates, using a completely optical measurement setup to measure the Q-factor of the resonators and the residual stress of the layers by means of purposely designed micromachined test structures. From the measurements, a clear correlation appears between the residual stress of the SiC layer and the Q-factor of the resonators, with Q-factor values above half a million for resonators fabricated on substrates, showing residual stress around 1 GPa.

Allogeneic stem cell transplantation remains the only therapy for congenital, severe haemoglobinopathies that is able to reverse the pathological phenotype. In the severe form of thalassemia, regular transfusions are needed early in life. This population of patients could benefit from allo-SCT. However, the great efficacy of transplantation must be counterbalanced by the mortality and morbidity related to the procedure. In this short review, we reviewed the most recent data in the field of transplantation in transfusion-dependent thalassemia (TDT), highlighting the factors that have a major impact on outcomes.

Introduction: Laboratories are inextricably dangerous work environments, as fatal incidents are reported in both academic and non-academic environments worldwide, where poor safety culture has been recognized as the major accident contributor. Workers can be exposed to chemical, biological, physical, or radioactive hazards, in addition to musculoskeletal stresses. In Brazil, hundreds of thousands of workers are employed in laboratories, either in private or public institutions. Although laboratory safety can be governed by local, state, or federal regulations, learning how to identify common laboratory hazards is the first step to preventing accidents in the lab environment. Methods: The study aimed to assess the degree level of safety culture in an academic population of research laboratories, located in the largest city in Brazil, and their compliance with occupational safety regulations during the COVID-19 outbreak. This study was carried out between October and November 2020. The results were obtained from the standardized questionnaire used to assess 98 researchers working in laboratories during the COVID-19 pandemic. Results: The majority of respondents (95%) reported being exposed to more than two risks, simultaneously. About two-thirds (66%) of them were not fully aware of the laboratory's risk map. About half of the researchers (50%) were lacking in safety culture, and 57%and 43% were preoccupied with chemical and non-chemical hazards, respectively. Personal protective equipment (PPE) during laboratory work was used by most researchers, but 75% of researchers claim that security awareness learning should be a high priority for admission to laboratories. About 39% of researchers agreed that awareness of security must be improved in their laboratories Conclusion: The survey proves the lack of information and attitudes about chemical safety, especially among less experienced researchers, even if they use personal protective equipment when necessary.

The peritoneum is an unusual site of metastases from lung cancer, and optimal management at the moment remains unclear and mostly based on palliative strategies. Therefore, the aim of the study was to investigate demographic characteristics, management and overall survival of patients with peritoneal metastases from lung cancer (PCLC). A PRISMA-compliant systematic review and pooled analysis was performed searching all English studies published until December 2022. PROSPERO, CRD42022349362. Inclusion criteria were original articles including patients with peritoneal carcinomatosis from lung cancer, specifying at least one outcome of interest. Exclusion criteria were being unable to retrieve patient data from articles, and the same patient series included in different studies. Among 1746 studies imported for screening, twenty-one were included (2783 patients). Mean overall survival was between 0.5 and 5 months after peritoneal carcinomatosis diagnosis and 9 and 21 months from lung cancer diagnosis. In total, 27% of patients underwent first-line or palliative chemotherapy and 7% of them surgery. Management differs significantly among published studies. The literature on PCLC is scarce. Its incidence is low but appears to be substantially rising and is likely to be an underestimation. Prognosis is very poor and therapeutic strategies have been limited and used in a minority of patients. Subcategories of PCLC patients may have an improved prognosis and may benefit from an aggressive oncological approach, including cytoreductive surgery. Further investigation would be needed in this regard.

International audience; Several interstellar molecules are highly reactive unsaturated carbon chains, which are unstable under terrestrial conditions. Laboratory studies in support of their detection in space thus face the issue of how to produce these species and how to correctly model their rotational energy levels. In this work, we introduce a general approach for producing and investigating unsaturated carbon chains by means of selected test cases. We report a comprehensive theoretical/experimental spectroscopic characterization of three species, namely, propadienone, cyanovinylacetylene, and allenylacetylene, all of them being produced by means of flash vacuum pyrolysis of a suitable precursor. For each species, quantum-chemical calculations have been carried out with the aim of obtaining accurate predictions of the missing spectroscopic information required to guide spectral analysis and assignment. Rotational spectra of the title molecules have been investigated up to 400 GHz by using a frequency-modulation millimeter-/submillimeter-wave spectrometer, thus significantly extending spectral predictions over a wide range of frequency and quantum numbers. A comparison between our results and those available in the literature points out the clear need of the reported laboratory measurements at higher frequencies for setting up accurate line catalogs for astronomical searches.

The present research shows some results obtained by the PON project entitled "An early warning system for cultural heritage / EWAS". In this national funded project, Sicilian research institutions, universities and companies work together with the common goal of developing new technologies for the protection and enhancement of historical and cultural heritage and also aim to improve its strategic management and protect it from risks. With a view to pursuing the primary objectives of the EWAS project, it was planned to realize two full-scale prototypes. The first one is a lightweight shelter, the second one is a micro-architecture for facilities. They are able to reduce the environmental impact, they are responsive and they are designed to protect the sensitive areas of the excavations and at the same time to facilitate the use of the archaeological site. In order to test these prototypes, the archaeological area of Megara Hyblaea has been chosen, the most ancient Greek colony in Sicily. It is immersed in an industrial landscape that stretches along the coast of eastern Sicily from Augusta to Syracuse. The sense of the original place has been erased by an indiscriminate occupation of the land by industries which has left, here and there, an archipelago of "heritage relics" of various kinds, which are equally close to the smelly chimneys and the horizon of the sea. This landscape of contrasts, dominated by petrochemical industries, has over time hindered a cultural tourism appropriate to the representativeness and importance of the findings, despite the efforts made by the authorities responsible for its protection.

In the era of precision measurements of the neutrino oscillation parameters, upcoming neutrino experiments will also be sensitive to physics beyond the Standard Model. KM3NeT/ORCA is a neutrino detector optimised for measuring atmospheric neutrinos from a few GeV to around 100 GeV. In this paper, the sensitivity of the KM3NeT/ORCA detector to neutrino decay has been explored. A three-flavour neutrino oscillation scenario, where the third neutrino mass state $\nu_3$ decays into an invisible state, e.g. a sterile neutrino, is considered. We find that KM3NeT/ORCA would be sensitive to invisible neutrino decays with $1/\alpha_3=\tau_3/m_3 < 180$~$\mathrm{ps/eV}$ at $90\%$ confidence level, assuming true normal ordering. Finally, the impact of neutrino decay on the precision of KM3NeT/ORCA measurements for $\theta_{23}$, $\Delta m^2_{31}$ and mass ordering have been studied. No significant effect of neutrino decay on the sensitivity to these measurements has been found., Comment: 27 pages, 14 figures, bibliography updated, typos corrected

COVID-19 infection causes respiratory pathology with severe interstitial pneumonia and extra-pulmonary complications; in particular, it may predispose to thromboembolic disease. The current guidelines recommend the use of thromboprophylaxis in patients with COVID-19, however, the optimal heparin dosage treatment is not well-established. We conducted a multicentre, Italian, retrospective, observational study on COVID-19 patients admitted to ordinary wards, to describe clinical characteristic of patients at admission, bleeding and thrombotic events occurring during hospital stay. The strategies used for thromboprophylaxis and its role on patient outcome were, also, described. 1091 patients hospitalized were included in the START-COVID-19 Register. During hospital stay, 769 (70.7%) patients were treated with antithrombotic drugs: low molecular weight heparin (the great majority enoxaparin), fondaparinux, or unfractioned heparin. These patients were more frequently affected by comorbidities, such as hypertension, atrial fibrillation, previous thromboembolism, neurological disease, and cancer with respect to patients who did not receive thromboprophylaxis. During hospital stay, 1.2% patients had a major bleeding event. All patients were treated with antithrombotic drugs; 5.4%, had venous thromboembolism [30.5% deep vein thrombosis (DVT), 66.1% pulmonary embolism (PE), and 3.4% patients had DVT + PE]. In our cohort the mortality rate was 18.3%. Heparin use was independently associated with survival in patients aged ≥ 59 years at multivariable analysis. We confirmed the high mortality rate of COVID-19 in hospitalized patients in ordinary wards. Treatment with antithrombotic drugs is significantly associated with a reduction of mortality rates especially in patients older than 59 years.

Nongenetic predisposition to colorectal cancer continues to be difficult to measure precisely, hampering efforts in targeted prevention and screening. Epigenetic changes in the normal mucosa of patients with colorectal cancer can serve as a tool in predicting colorectal cancer outcomes. We identified epigenetic changes affecting the normal mucosa of patients with colorectal cancer. DNA methylation profiling on normal colon mucosa from 77 patients with colorectal cancer and 68 controls identified a distinct subgroup of normally-appearing mucosa with markedly disrupted DNA methylation at a large number of CpGs, termed as “Outlier Methylation Phenotype” (OMP) and are present in 15 of 77 patients with cancer versus 0 of 68 controls (P < 0.001). Similar findings were also seen in publicly available datasets. Comparison of normal colon mucosa transcription profiles of patients with OMP cancer with those of patients with non-OMP cancer indicates genes whose promoters are hypermethylated in the OMP patients are also transcriptionally downregulated, and that many of the genes most affected are involved in interactions between epithelial cells, the mucus layer, and the microbiome. Analysis of 16S rRNA profiles suggests that normal colon mucosa of OMPs are enriched in bacterial genera associated with colorectal cancer risk, advanced tumor stage, chronic intestinal inflammation, malignant transformation, nosocomial infections, and KRAS mutations. In conclusion, our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Prospective studies are needed to determine whether OMP could serve as a biomarker for an elevated epigenetic risk for colorectal cancer development. Prevention Relevance: Our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Identification of OMPs in healthy controls and patients with colorectal cancer will lead to prevention and better prognosis, respectively.

Poster presented at the e-MRS Spring Meeting 2023.&nbsp

Presentation done atWOCSDICE - EXMATEC 2023 - Palermo.&nbsp

Integrating optically active III-V materials on silicon/insulator platforms is one potential path towards improving the energy efficiency and performance of modern computing. Here we demonstrate the applicability of direct wafer bonding combined with plasma etching to the fabrication of complex nanophotonic systems out of InP layers. We explore and optimise the plasma etching of InP, validating existing processes and developing improved ones. We explore the use of microdisk lasing as a way to evaluate fabrication fidelity, and demonstrate that we can create complex lasing systems of interest to us: coupled disk cavities and random network lasers.

The concept of gray-zone lymphoma (GZL) has been progressively refined since its in-troduction in the literature in 1998. For several years, it was applied to a rather broad spectrum of conditions, posing the problem of the differential diagnosis between any type of Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma, with special reference to primary mediasti-nal forms (PMBL). Officially recognized as a provisional entity in the 4th and revised 4th editions of the WHO Classification of Tumour of Haematopoietic and Lymphoid Tissues with the term “B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lym-phoma and classical Hodgkin lymphoma”, it was limited to tumours, which showed either morphologic features reminiscent of classical HL (CHL) but carrying a complete B-cell pheno-type or conversely provided with a PMBL morphology but revealing CHL phenotypic charac-teristics. The definition of GZL has been further revised in the recently published International Lymphoma Classification and 5th Edition of the WHO Classification of Haemato-lymphoid Tu-mours, which have limited it to mediastinal neoplasms based on emerging molecular evidences. The aim of this review is to critically discuss the issue of GZL, also in the light of the suboptimal response to current therapies.

The multidisciplinary approach in forensic science led to the development of geology and botany as predictive forensic applications (forensic geology – forensic botany) aimed at analyzing and studying the crime scene for the "solving" of the criminal hypothesis. Over the past fifteen years, the study of plant DNA has been used in forensics science to discriminate the place of origin of plant material found at a crime scene, to identify poisonous vegetable species, as a forensic marker in all cases where determining geographic origin is essential to investigative leads, missing person cases, and intelligence application (Bell et al., 2015), in the identification of Cannabis as support of law authorities in fighting drug abuse and global trafficking. These specific topics to date made it possible to: distinguish a primary crime scene from a secondary one, link a suspect to the crime scene, and determine the date of death. Findings of plant material can be examined through chemical analysis, morphological analysis, DNA analysis, PCR and electrophoresis. Comparative studies may be carried out among the plant remains collected from the victim and suspect and plant sampled on the event scene in order to trace the place where the plant transfer occurred. The analysis of the international literature presented through this review shows the importance of further developments in plant DNA analysis, growing and expanding a global database containing the plant DNA barcode, and implementing specific guidelines for the collection and sampling procedures of forensic samples.

Legal cases involving human and animal envenomizations may be encountered by the medicolegal investigator. Such cases are often difficult due to lack of physical evidence and analytical difficulty. The development and use of an interdisciplinary approach and standardized protocol involving experts in environmental and life sciences (toxicology, legal medicine, entomology, veterinary forensic science, biology, geography, geology, and meteorology) may improve the documentation, collection, and presentation of physical evidence in court. This information can be utilized to develop and optimize new protocols for toxicological screenings for application in human and animal cases. In such cases, the scientific background of coroners and police experts may not be sufficient to correctively delineate the environmental features of the territory that may be typical of certain species of venomous fauna present in the scene of the events. Therefore, protocols providing complete information concerning the environment of the scene and detail of the events together with exam protocols, sample collection, tissue preservation, and testing/analysis are needed. This holistic approach could enhance the ability to detect toxins involved in envenomizations to better manage forensic science and legal cases.

In a forensic context, the criminal case evaluation is often challenging, and the only autopsy may not be exhaustive to determine the cause and the time of death, mainly when the corpse is dismembered, charred, or putrefied. Moreover, the conditions of an altered corpse and the recovered places of the cadaver (countryside, forests, rivers, beaches, etc.), outdoors, or in burnt buildings and ruins, can raise challenges not only in terms of victim identification but also in terms of acquisition of additional information aimed at elucidating the dynamics of death, like the detection of the corpse transfer after the death, especially in cases of suspected homicides. In such complex cases, it is, therefore, of paramount importance to provide a multidisciplinary approach involving the collaboration of ultra-specialized forensic experts. In this context, experts in criminalistic disciplines, such as forensic geology, botany, and entomology, may provide their contribution, as well as the engineers applying to medicine new technologies for the 2D and 3D reconstructions of crime scenes and evidence. We consider helpful to report a court case that came to our attention, involving forensic pathology experts together with forensic biologists, geologists, botanists, naturalists, entomologists, veterinarians, physicists, computer scientists, and engineers whose collaboration based on a multidisciplinary approach contributed to the management and the solving of a suspect crime.

Inversion methods play an important role in glacier models, both to calibrate and estimate parameters of interest (e.g. Glen's coefficients). However, inversions are usually made for each glacier individually, without using any global information, i.e. without deriving general laws governing the spatiotemporal variability of those parameters. The reason behind this limitation is twofold: the statistical challenge of making constrained inferences with multiple glaciers, and the computational limitation of processing massive glacier datasets. Machine learning powered with differential programming is a tool that can address both limitations. We introduce a statistical framework for functional inversion of physical processes governing global-scale glacier changes. We apply this framework to invert a prescribed function describing the spatial variability of Glen’s coefficient (A). Instead of estimating a single parameter per glacier, we learn the parameters of a regressor (i.e. a neural network) that encodes information related to each glacier (i.e. long-term air temperature) to the parameter of interest. The inversion is done by embedding a neural network inside the Shallow Ice Approximation PDE - resulting in a Universal Differential Equation - with the goal of minimizing the error on the simulated ice surface velocities. We previously had shown that this hybrid model training is possible thanks to the use of differential programming, enabling differentiation of a PDE, a numerical solver and a neural network simultaneously. In this work we upscale this approach to include larger datasets and with the goal of learning real empirical laws from observations. This framework is built inside ODINN.jl, an open-source package in the Julia programming language for global glacier evolution modelling using Universal Differential Equations. ODINN exploits the latest generation of ice surface velocities and geodetic mass balance remote sensing products, as well as many preprocessing tools from the Open Global Glacier Model (OGGM).

Sinorhizobium melilotiis a model alpha-proteobacterium for investigating microbe-host interactions, in particular nitrogen-fixing rhizobium-legume symbioses. Successful infection requires complex coordination between compatible host and endosymbiont, including bacterial production of succinoglycan, also known as exopolysaccharide-I (EPS-I). InS. melilotiEPS-I production is controlled by the conserved ExoS-ChvI two-component system. Periplasmic ExoR associates with the ExoS histidine kinase and negatively regulates ChvI-dependent expression ofexogenes, necessary for EPS-I synthesis. We show that two extracytoplasmic proteins, LppA (a lipoprotein) and JspA (a metalloprotease), jointly influence EPS-I synthesis by modulating the ExoR-ExoS-ChvI pathway and expression of genes in the ChvI regulon. Deletions ofjspAandlppAled to lower EPS-I production and competitive disadvantage during host colonization, for bothS. melilotiwithMedicago sativaandS. medicaewithM. truncatula. Overexpression ofjspAreduced steady-state levels of ExoR, suggesting that the JspA protease participates in ExoR degradation. This reduction in ExoR levels is dependent on LppA and can be replicated with ExoR, JspA, and LppA expressed exogenously inCaulobacter crescentusandEscherichia coli. Akin to signaling pathways that sense extracytoplasmic stress in other bacteria, JspA and LppA may monitor periplasmic conditions during interaction with the plant host to adjust accordingly expression of genes that contribute to efficient symbiosis. The molecular mechanisms underlying host colonization in our model system may have parallels in related alpha-proteobacteria.Author summarySymbiotic bacteria that live in the roots of legume plants produce biologically accessible nitrogen compounds, offering a more sustainable and environmentally sound alternative to industrial fertilizers generated from fossil fuels. Understanding the multitude of factors that contribute to successful interaction between such bacteria and their plant hosts can help refine strategies for improving agricultural output. In addition, because disease-causing microbes share many genes with these beneficial bacteria, unraveling the cellular mechanisms that facilitate host invasion can reveal ways to prevent and treat infectious diseases. In this report we show that two genes in the model bacteriumSinorhizobium meliloticontribute to effective symbiosis by helping the cells adapt to living in host plants. This finding furthers knowledge about genetics factors that regulate interactions between microbes and their hosts.

This single-center real-life study was conducted to evaluate the most effective combination of nutraceuticals and the most appropriate indications for the treatment of male infertile patients. Infertile patients aged 20–55 years were treated with a combination of antioxidants (Androlen®) (Group 1), with Androlen® and a mixture of fibrinolytic molecules (Lenidase®) (Group 2), or Androlen® and other molecules different from those used for the patients of the Group 2 (Group 3). Patients were also subdivided according to the presence of varicocele, mild testicular hypotrophy, idiopathic infertility, and chronic male accessory gland infection (MAGI). Forty-three patients were enrolled. In the overall analysis, only progressive motility significantly improved after therapy. Subgroup analysis showed a significant increase in progressive motility, total motile sperm count (TMSC), and in the percentage of alive spermatozoa after treatment in the Group A. Progressive motility improved significantly in patients with varicocele, while the TMSC in patients with varicocele and those with idiopathic. The percentage of alive spermatozoa increased in patients with testicular hypotrophy. Treatment with antioxidants increases progressive sperm motility. The association of fibrinolytic or other nutraceuticals does not improve the efficacy of the treatment with antioxidants alone. The treatment was effective in patients with varicocele or idiopathic infertility.

Numerous optical phenomena and applications have been enabled by nanophotonic structures. Their current fabrication from high refractive index dielectrics, such as silicon or gallium phosphide, pose restricting fabrication challenges, while metals, relying on plasmons and thus exhibiting high ohmic losses, limit the achievable applications. Here, we present an emerging class of layered so-called van der Waals (vdW) crystals as a viable nanophotonics platform. We extract the dielectric response of 11 mechanically exfoliated thin-film (20-200 nm) van der Waals crystals, revealing high refractive indices up to n = 5, pronounced birefringence up to $\Delta$n = 3, sharp absorption resonances, and a range of transparency windows from ultraviolet to near-infrared. We then fabricate nanoantennas on SiO$_2$ and gold utilizing the compatibility of vdW thin films with a variety of substrates. We observe pronounced Mie resonances due to the high refractive index contrast on SiO$_2$ leading to a strong exciton-photon coupling regime as well as largely unexplored high-quality-factor, hybrid Mie-plasmon modes on gold. We demonstrate further vdW-material-specific degrees of freedom in fabrication by realizing nanoantennas from stacked twisted crystalline thin-films, enabling control of nonlinear optical properties, and post-fabrication nanostructure transfer, important for nano-optics with sensitive materials.

Background: Knowledge of vascular anatomy and its possible variations is essential for performing embolization or revascularization procedures and complex surgery in the pelvis. The obturator artery (OA) is a branch of the anterior division of the internal iliac artery (IIA), and it has the highest frequency of variation between branches of the internal iliac artery. Possible anomalies of the origin of the obturator artery (OA) should be known when performing pelvic and groin surgery, where its control or ligation may be required. The purpose of this systematic review and meta-analysis, based on Sanudo’s classification, is to analyse the origin of the obturator artery (OA) and its variants. Methods: Thirteen articles, published between 1952 and 2020, were included in this systematic review and meta-analysis. Results: The obturator artery (OA) was present in almost all cases (99.8%): the pooled prevalence estimate for internal iliac artery (IIA) was 77.7% (95% CI 71.8% – 83.1%) vs 22.3% (95% CI 16.9% – 28.2%) for the external iliac artery (EIA). In most cases, the obturator artery (OA) originated from the anterior division trunk of the internal iliac artery (IIA) (61.6%). Conclusion: Performing preoperative radiological studies to know the pelvic vascular pattern and having awareness to evaluate possible changes in the obturator artery can reduce the risk of iatrogenic injury and complications

Aim The aim of this retrospective study was to compare open small- and medium-sized ventral hernia repair with flat patch mesh versus three-dimensional mesh (plug) in terms of recurrence and complication rates. Methods The medical records of 300 patients who underwent ventral hernia repair using flat mesh versus plug between January 2010 to December 2015 were reviewed. All patients were followed up after 1 month, 3 month and 1 year. The rate of recurrence, and short-term postoperative complications such as incidence of Surgical Site Infections (SSIs), hematoma and seroma were evaluated. Results Short-term follow-up data were available for all patients. The first group was composed of 150 patients that were treated with plug (60% presented umbilical hernia and 40% presented epigastric hernia). The second group was composed of 150 patients that were treated with flat mesh (68% presened umbilical hernia and 32% presented epigastric hernia). The majority of postoperative complications were wound related, representing superficial SSI or seroma. Our results showed a statistically significant reduction of SSIs [3 (2%) vs 13 (8.6%); p = 0.038] and seroma [2 (1.3%) vs 12 (8%); p = 0.030] in the group of patients treated with plugs. There was no statistically significant difference in hernia recurrences. Conclusions Usage of plugs represents a feasible and safe technique that significantly lowers the incidence of complications. Furthermore, compared to flat mesh, plugs displayed non-inferiority in terms recurrence. Further, well-designed clinical trials could be realized to investigate possible applications of plugs for umbilical and epigastric hernias repair.

Colorectal cancer (CRC) is one of the most common cancers worldwide. There are several causes of a mechanical left bowel obstructive but CRC accounts for approximately 50% of cases and in 10–30% of whom it is the presenting syndrome. In most cases, the left colon is involved. At present, the range of therapeutic alternatives in the management of obstructive left CRC in emergency conditions (primary resection vs staged resection with applied self-expanding metallic stents) is broad, whereas internationally validated clinical recommendations in each condition are still lacking. This enormous variability affects the scientific evidence on both the immediate and long-term surgical and oncological outcomes. CROSCO-1 (Colonic Resection, stOma or self-expanding metal Stents for obstruCtive left cOlon cancer) study is a national, multi-center, prospective observational study intending to compare the clinical results of all these therapeutic regimens in a cohort of patients treated for obstructive left-sided CRC. The primary aim of the CROSCO-1 study is the 1-year stoma rate of patients undergoing primary emergency surgical resection (Hartmann procedure or primary resection and anastomosis) compared with patients undergoing staged resection. Secondary outcomes are 30-day and 90-day major morbidity and mortality, 1-year quality of life and the timing of chemotherapy initiation in the two groups. Future CROSCO studies will follow in which, instead, we will evaluate the long-term oncological outcomes of the two treatment strategies ClinicalTrials.Gov ID Number, NCT05801211. Date: April 13, 2023. Protocol Version V2.1.

PDF file - 663K,Supplementary Figure S1: Confirmation of the quality of RNA in microarray experiments by denaturing gel electrophoresis in 1% agarose. Supplementary Figure S2: Representative pyrograms for PDK4, SPRR2A, SPRR1A, NR1H4 and PYCARD.Supplementary Figure S3: Identification of individual genes and functional gene categories with significant expression changes between BALB/c Mthfr+/- FD and BALB/c Mthfr+/+ CD mice. Supplementary Figure S4: Effect of diet and Mthfr genotype on expression of eight genes in normal intestine of BALB/c mice.Supplementary Figure S5: Correlation of methylation results between quantitative bisulfite-pyrosequencing and the Infinium methylation array. Supplementary Figure S6: Confirmation of DNA methylation differences in normal colon between control subjects and individuals with CRC. Supplementary Table S1: Description of control subjects.Supplementary Table S2: Description of cancer patients.Supplementary Table S3: Primer pairs for qRT-PCR for the 13 genes in Figs S1 and S2, and the internal control, Gapdh.Supplementary Table S4: Taqman primers and probes for qRT-PCR of human genes.Supplementary Table S5: Oligonucleotides used for pyrosequencing (PCR primers and sequencing primers).Supplementary Table S6: List of probe sets showing significant changes comparing Mthfr+/- FD and Mthfr+/+ CD BALB/c mice.Supplementary Table S7: Relative mRNA levels for four genes related to PPAR activation (Bcmo1, Aldh1a1), oxidative stress sensitivity (Sprr2a) or oxidative response (Ugt2b36). Supplementary Table S8: Relative expression of PPAR responsive genes.

Supplementary Table from Epigenome-Wide Study Identifies Epigenetic Outliers in Normal Mucosa of Patients with Colorectal Cancer

We have validated differences in DNA methylation levels of candidate genes previously reported to discriminate between normal colon mucosa of patients with colon cancer and normal colon mucosa of individuals without cancer. Here, we report that CpG sites in 16 of the 30 candidate genes selected show significant differences in mean methylation level in normal colon mucosa of 24 patients with cancer and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs yielded an 18-gene signature, composed of ten of the validated candidate genes plus eight additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate–strong correlation (Pearson coefficients r = 0.253–0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These seven genes, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer-screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy. Cancer Prev Res; 7(7); 717–26. ©2014 AACR.

Supplementary figures 1-5, supplementary tables 1-9

Supplementary Data from Epigenome-Wide Study Identifies Epigenetic Outliers in Normal Mucosa of Patients with Colorectal Cancer

PDF - 62K, Description of Controls and Cancer Patients.

PDF - 32K, Legend for supplementary figure 1.

Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors with variable clinical, morphologic, and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared with other mesenchymal tumors, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other mesenchymal tumors and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n = 1,289) between microdissected FDCs and fibroblasts. Supervised analysis comparing FDC sarcomas with microdissected FDCs and other mesenchymal tumors identified 370 and 2,927 differentially expressed transcripts, respectively, and on the basis of pathway enrichment analysis ascribed to signal transduction, chromatin organization, and extracellular matrix organization programs. As the transcriptome of FDC sarcomas retained similarity with FDCs, the immune landscape of FDC sarcoma was investigated by applying the CIBERSORT algorithm to FDC sarcomas and non-FDC mesenchymal tumors and demonstrated that FDC sarcomas were enriched in T follicular helper (TFH) and T regulatory (TREG) cell populations, as confirmed in situ by immunohistochemistry. The enrichment in specific T-cell subsets prompted investigating the mRNA expression of the inhibitory immune receptor PD-1 and its ligands PD-L1 and PD-L2, which were found to be significantly upregulated in FDC sarcomas as compared with other mesenchymal tumors, a finding also confirmed in situ. Here, it is demonstrated for the first time the transcriptional relationship of FDC sarcomas with nonmalignant FDCs and their distinction from other mesenchymal tumors.Implications: The current study provides evidence of a peculiar immune microenvironment associated with FDC sarcomas that may have clinical utility. Mol Cancer Res; 15(5); 541–52. ©2017 AACR.

PDF - 55K, Support Vector Machine 39 CpG/16 gene signature selected from the 66 CpGs interrogated in the 18 genes in our original study (13).

Supplementary Figure from Epigenome-Wide Study Identifies Epigenetic Outliers in Normal Mucosa of Patients with Colorectal Cancer

PDF file - 403K, Bisulfite pyrosequence validation of INS (A), SLC16A3 (B), VAV1 (C) and ZNF512 (D).

PDF - 72K, Support Vector Machine analysis on multiple CpGs compare to single unique CpGs.

Nongenetic predisposition to colorectal cancer continues to be difficult to measure precisely, hampering efforts in targeted prevention and screening. Epigenetic changes in the normal mucosa of patients with colorectal cancer can serve as a tool in predicting colorectal cancer outcomes. We identified epigenetic changes affecting the normal mucosa of patients with colorectal cancer. DNA methylation profiling on normal colon mucosa from 77 patients with colorectal cancer and 68 controls identified a distinct subgroup of normally-appearing mucosa with markedly disrupted DNA methylation at a large number of CpGs, termed as “Outlier Methylation Phenotype” (OMP) and are present in 15 of 77 patients with cancer versus 0 of 68 controls (P < 0.001). Similar findings were also seen in publicly available datasets. Comparison of normal colon mucosa transcription profiles of patients with OMP cancer with those of patients with non-OMP cancer indicates genes whose promoters are hypermethylated in the OMP patients are also transcriptionally downregulated, and that many of the genes most affected are involved in interactions between epithelial cells, the mucus layer, and the microbiome. Analysis of 16S rRNA profiles suggests that normal colon mucosa of OMPs are enriched in bacterial genera associated with colorectal cancer risk, advanced tumor stage, chronic intestinal inflammation, malignant transformation, nosocomial infections, and KRAS mutations. In conclusion, our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Prospective studies are needed to determine whether OMP could serve as a biomarker for an elevated epigenetic risk for colorectal cancer development.Prevention Relevance:Our study identifies an epigenetically distinct OMP group in the normal mucosa of patients with colorectal cancer that is characterized by a disrupted methylome, altered gene expression, and microbial dysbiosis. Identification of OMPs in healthy controls and patients with colorectal cancer will lead to prevention and better prognosis, respectively.

This paper seeks to analyze the rules related to safeguarding and maintaining employment issued by Brazil and Italy during the SARS-COV-2 pandemic. Both countries adopted legislation to strengthen social safety and introduced measures restricting layoffs. The results show that, on different levels, both countries have restricted the freedom of enterprise in favor of the protection of workers.

Big data and Machine learning Techniques are reshaping the way in which food safety risk assessment is conducted. The ongoing ‘datafication’ of food safety risk assessment activities and the progressive deployment of probabilistic models in their practices requires a discussion on the advantages and disadvantages of these advances. In particular, the low level of trust in EU food safety risk assessment framework highlighted in 2019 by an EU-funded survey could be exacerbated by novel methods of analysis. The variety of processed data raises unique questions regarding the interplay of multiple regulatory systems alongside food safety legislation. Provisions aiming to preserve the confidentiality of data and protect personal information are juxtaposed to norms prescribing the public disclosure of scientific information. This research is intended to provide guidance for data governance and data ownership issues that unfold from the ongoing transformation of the technical and legal domains of food safety risk assessment. Following the reconstruction of technological advances in data collection and analysis and the description of recent amendments to food safety legislation, emerging concerns are discussed in light of the individual, collective and social implications of the deployment of cutting-edge Big Data collection and analysis techniques. Then, a set of principle-based recommendations is proposed by adapting high-level principles enshrined in institutional documents about Artificial Intelligence to the realm of food safety risk assessment. The proposed set of recommendations adopts Safety, Accountability, Fairness, Explainability, Transparency as core principles (SAFETY), whereas Privacy and data protection are used as a meta-principle. ispartof: AI and Society vol:36 issue:1 pages:1-16 status: Published online