Strained Silicon Technology: Non-Destructive High-Lateral-Resolution Characterization Through Tip-Enhanced Raman Spectroscopy.

The semiconductor industry is undergoing a transformative phase, marked by the relentless drive for miniaturization and a constant demand for higher performance and energy efficiency. However, the reduction of metal-oxide-semiconductor field-effect transistor sizes for advanced technology nodes below 10 nm presents several challenges. In response, strained silicon technology has emerged as a key player, exploiting strain induction in the silicon crystal lattice to improve device performance. At the same time, there has been a growing need for characterization techniques that allow in-line monitoring of sample conditions during semiconductor manufacturing, as an alternative to traditional methods such as transmission electron microscopy or high-resolution X-ray diffraction, which have several limitations in terms of measurement time and sample destructiveness. This paper explores the application of advanced spectroscopic characterization techniques, in particular µ-Raman spectroscopy and tip-enhanced Raman spectroscopy (TERS), to meet the evolving needs of the semiconductor industry for quality control and failure analysis, increasingly requiring faster and non-destructive characterization techniques. µ-Raman provides insight into strain values and distributions of strained layers with different thicknesses and germanium concentrations, but its lateral resolution is constrained by the Abbe diffraction limit. TERS, on the other hand, emerges as a powerful non-destructive technique capable of overcoming diffraction limits by exploiting the combination of an atomic force microscope with a Raman spectrometer. This breakthrough makes it possible to estimate the chemical composition and induced strain in the lattice by evaluating the Raman peak position shifts in strained and unstrained silicon layers, providing crucial insights for nanoscale strain control. In particular, this paper focuses on the TERS characterization of Si0.7Ge0.3 epitaxial layers grown on a silicon-on-insulator device, demonstrating the effectiveness of this technique and the high lateral resolution that can be achieved.

Toward the nanoscale chemical and physical probing of milk-derived extracellular vesicles using Raman and tip-enhanced Raman spectroscopy.

Tip-enhanced Raman spectroscopy (TERS) is an advanced technique to perform local chemical analysis of the surface of a sample through the improvement of the sensitivity and the spatial resolution of Raman spectroscopy by plasmonic enhancement of the electromagnetic signal in correspondence with the nanometer-sized tip of an atomic force microscope (AFM). In this work, TERS is demonstrated to represent an innovative and powerful approach for studying extracellular vesicles, in particular bovine milk-derived extracellular vesicles (mEVs), which are nanostructures with considerable potential in drug delivery and therapeutic applications. Raman spectroscopy has been used to analyze mEVs at the micrometric and sub-micrometric scales to obtain a detailed Raman spectrum in order to identify the 'signature' of mEVs in terms of their characteristic molecular vibrations and, therefore, their chemical compositions. With the ability to improve lateral resolution, TERS has been used to study individual mEVs, demonstrating the possibility of investigating a single mEV selected on the surface of the sample and, moreover, analyzing specific locations on the selected mEV with nanometer lateral resolution. TERS potentially allows one to reveal local differences in the composition of mEVs providing new insights into their structure. Also, thanks to the intrinsic properties of TERS to acquire the signal from only the first few nanometers of the surface, chemical investigation of the lipid membrane in correspondence with the various locations of the selected mEV could be performed by analyzing the peaks of the Raman shift in the relevant range of the spectrum (2800-3000 cm-1). Despite being limited to mEVs, this work demonstrates the potential of TERS in the analysis of extracellular vesicles.

Probe chip nanofabrication enabled reverse tip sample scanning probe microscopy concept and measurements.

We introduce a new scanning probe microscopy (SPM) concept called reverse tip sample scanning probe microscopy (RTS SPM), where the tip and sample positions are reversed as compared to traditional SPM. The main benefit of RTS SPM over the standard SPM configuration is that it allows for simple and fast tip changes. This overcomes two major limitations of SPM which are slow data acquisition and a strong dependency of the data on the tip condition. A probe chip with thousands of sharp integrated tips is the basis of our concept. We have developed a nanofabrication protocol for Si based probe chips and their functionalization with metal and diamond coatings, evaluated our probe chips for various RTS SPM applications (multi-tip imaging, SPM tomography, and correlative SPM), and showed the high potential of the RTS SPM concept.

3D fractures analysis and conservation assessment of wrought iron javelin through advanced non-invasive techniques.

3D imaging is a powerful tool of high resolution and non-destructive imaging technology for the study of ancient weapons and military technology, which reveals the original microstructures and corrosion patterns that threaten these artefacts. Here we report quantitative analysis of the 3D distribution and the orientation of fractures, and uncorroded metal particles within a wrought iron javelin unearthed at the Phoenician-Punic site of Motya, Italy. The study aimed to gain a better understanding of the relationship between corrosion and local stresses within the artifact and to evaluate its manufacturing technology, as well as the effects of post-treatment with Paraloid B72 on concretion and mineralized layers. The cracks were quantified in terms of content, size, and orientation. The condition of artefact storage was evaluated by a multi-analytical approach, including X-ray microscopy, field emission electron microscopy and micro-Raman spectroscopy. The results indicated that a specific technique was used to create a sturdy, lightweight javelin with a central shaft for piercing or thrusting. The fractures appear elongated in the direction of the longitudinal axis of the blade, showing the forging direction of the original metallic block. The study concluded that the artifact had not yet been stabilized due to the presence of lepidocrocite.

Upscaling of Electrospinning Technology and the Application of Functionalized PVDF-HFP@TiO2 Electrospun Nanofibers for the Rapid Photocatalytic Deactivation of Bacteria on Advanced Face Masks.

In recent years, Electrospinning (ES) has been revealed to be a straightforward and innovative approach to manufacture functionalized nanofiber-based membranes with high filtering performance against fine Particulate Matter (PM) and proper bioactive properties. These qualities are useful for tackling current issues from bacterial contamination on Personal Protective Equipment (PPE) surfaces to the reusability of both disposable single-use face masks and respirator filters. Despite the fact that the conventional ES process can be upscaled to promote a high-rate nanofiber production, the number of research works on the design of hybrid materials embedded in electrospun membranes for face mask application is still low and has mainly been carried out at the laboratory scale. In this work, a multi-needle ES was employed in a continuous processing for the manufacturing of both pristine Poly (Vinylidene Fluoride-co-Hexafluoropropylene) (PVDF-HFP) nanofibers and functionalized membrane ones embedded with TiO2 Nanoparticles (NPs) (PVDF-HFP@TiO2). The nanofibers were collected on Polyethylene Terephthalate (PET) nonwoven spunbond fabric and characterized by using Scanning Electron Microscopy and Energy Dispersive X-ray (SEM-EDX), Raman spectroscopy, and Atomic Force Microscopy (AFM) analysis. The photocatalytic study performed on the electrospun membranes proved that the PVDF-HFP@TiO2 nanofibers provide a significant antibacterial activity for both Staphylococcus aureus (~94%) and Pseudomonas aeruginosa (~85%), after only 5 min of exposure to a UV-A light source. In addition, the PVDF-HFP@TiO2 nanofibers exhibit high filtration efficiency against submicron particles (~99%) and a low pressure drop (~3 mbar), in accordance with the standard required for Filtering Face Piece masks (FFPs). Therefore, these results aim to provide a real perspective on producing electrospun polymer-based nanotextiles with self-sterilizing properties for the implementation of advanced face masks on a large scale.

Red cell distribution width: A new parameter for predicting the risk of exacerbation in COPD patients.

BACKGROUND: Red cell distribution width (RDW) is a numerical measurement of the size variability of erythrocytes and is routinely reported as a component of complete blood count in the differential diagnosis of anemia. In recent years, researchers have reported high mortality and poor prognosis associated with higher RDW in populations with cardiovascular disease, cancer, pneumonia, and chronic obstructive pulmonary disease (COPD). The aim of the study is to evaluate the role of RDW in predicting the risk of COPD exacerbations and the impact of symptoms. METHODS: We designed an observational retrospective study based on patients hospitalized for acute exacerbation of COPD, between January 2015 and December 2018. RESULTS: We included 169 patients, 120 at GOLD four stage. RDW was significantly higher in COPD patients vs controls (P = .014). We found a positive correlation with c-reactive protein (r  = 0.375, P < .01), COPD assessment test (CAT) Score (R2 = 0.658, sy.x = 2.226; P < .01), number of exacerbations (R2=0.289; sy.x = 0.86; P = .002), and GOLD score (r = 0.30; P = .05). In ROC curve analysis, the area under the curve of RDW for the identification of frequent exacerbator was 1.0 (95% confidence interval, 1.0-1.0; P < .0001). CONCLUSION: Our data show that elevated RDW may be a useful tool in predicting the risk of exacerbation in COPD patients and may be a good indicator of the impact of symptoms.

Coronavirus disease 2019 infection in patients with recent cardiac surgery: does chronic anticoagulant therapy have a protective effect?

AIMS: The aim of this study was to evaluate the clinical course of COVID-19 in patients who had recently undergone a cardiac procedure and were inpatients in a cardiac rehabilitation department. METHODS: All patients hospitalized from 1 February to 15 March 2020 were included in the study (n = 35; 16 men; mean age 78 years). The overall population was divided into two groups: group 1 included 10 patients who presented with a clinical picture of COVID-19 infection and were isolated, and group 2 included 25 patients who were COVID-19-negative. In group 1, nine patients were on chronic oral anticoagulant therapy and one patient was on acetylsalicylic acid (ASA) and clopidogrel. A chest computed tomography scan revealed interstitial pneumonia in all 10 patients. RESULTS: During hospitalization, COVID-19 patients received azithromycin and hydroxychloroquine in addition to their ongoing therapy. Only the patient on ASA with clopidogrel therapy was transferred to the ICU for mechanical ventilation because of worsening respiratory failure, and subsequently died from cardiorespiratory arrest. All other patients on chronic anticoagulant therapy recovered and were discharged. CONCLUSION: Our study suggests that COVID-19 patients on chronic anticoagulant therapy may have a more favorable and less complicated clinical course. Further prospective studies are warranted to confirm this preliminary observation.

First report on clinical and radiological features of COVID-19 pneumonitis in a Caucasian population: Factors predicting fibrotic evolution.

BACKGROUND: At the end of February, the Lombardy region (Northern Italy) was involved in the pandemic spread of the new COVID-19. We here summarize the clinical and radiological characteristics of 90 confirmed cases and analyze their role in predicting the evolution of fibrosis. METHODS: We retrospectively analyzed the clinical and radiological data of 90 patients with COVID-19 pneumonitis. All subjects underwent an HRCT study on the day of admission and eight weeks later, and were treated with lopinavir + ritonavir (Kaletra) 400/100 mg two times a day or darunavir + ritonavir two times a day, and Hydroxychloroquine 200 mg two times a day. Pulmonary fibrosis was defined according to the Fleischner Society glossary of terms for thoracic imaging. RESULTS: Twenty-three patients developed pulmonary fibrosis (25.5%): 15 were males, whose mean age was 75 ± 15. The majority were active smokers (60.8%) and had comorbidities (78.2%), above all, hypertension (47.8%), and diabetes (34.7%). Interestingly, in our series of cases, the "reversed halo sign" is frequent (63%) and seems to be a typical COVID-19 pneumonitis pattern. The patients showing fibrosis had a higher grade of systemic inflammation (ESR and PCR) and appeared to have bone marrow inhibition with a significant reduction in platelets, leukocytes, and hemoglobin. CONCLUSIONS: To conclude, our data showed that the reversed halo sign associated with a ground-glass pattern may be a typical HRCT pattern of COVID-19 pneumonitis. The evolution to pulmonary fibrosis is frequent in older males and patients with comorbidities and bone marrow involvement.

Subclinical Nasal and Lung Lymphocytosis in Ulcerative Colitis.

BACKGROUND: Extraintestinal manifestations are common in ulcerative colitis (UC). Data regarding pulmonary and nasal mucosa involvement are sparse. OBJECTIVES: The aim of the study was to evaluate, by using induced sputum (IS) and nasal cytology (NC), the cytological pattern of the lung and nose in patients with UC. MATERIALS AND METHODS: We enrolled 15 consecutive subjects from the outpatient department with a recent diagnosis of UC. On the same day of enrollment, we performed a global spirometry, including a lung diffusing capacity test, IS analysis, and evaluation of NC. RESULTS: IS analysis showed an increase in lymphocytes in UC patients when compared to those of controls (2.8 ± 0.9 vs. 0.2 ± 0.4%; p < 0.01). NC showed a similar increase in lymphocytes (12.5 ± 5.30 vs. 3.5 ± 4.0%; p < 0.01). We found a positive correlation between lymphocyte counts in IS and NC (r = 0.775; p < 0.001) and between lymphocytes in IS and NC and grade of intestinal inflammation (r = 0.603, p = 0.015; r = 0.60, p = 0.013). CONCLUSIONS: Our data demonstrated that UC patients may have a subclinical nasal and lung lymphocytosis.

A "Crazy Paving" Pattern on CT Scan in a Patient Treated with Pembrolizumab.

BACKGROUND: Programmed cell death protein 1 (PD-1) and its ligand, PD-L1, have shown great promise in clinical practice and have been incorporated into standard management of NSCLC. Pneumonitis is a serious autoimmune toxicity associated with the use of anti-PD-1/PD-L1 antibodies, resulting in significant morbidity and mortality. METHODS: We described the case of a 73-year-old woman with no history of smoking developing exertional dyspnea four months after taking Pembrolizumab. RESULTS: High resolution contrast CT scan (HRCT) presented a unilateral "crazy paving" pattern, and bronchoalveolar lavage (BAL) an important lymphocytosis (20% of total cell count). The patient reached clinical stability after the administration of systemic steroids (2mg\Kg\die) and was discharged with long term oxygen therapy. DISCUSSION: Pulmonary toxicity is frequent when using PD-1 inhibitors, resulting in significant morbidity and mortality, often leading to the discontinuation of therapy. Clinical presentation is usually protean and HRCT pattern is nonspecific. This is the first case presenting a "crazy paving" pattern associated with BAL lymphocytosis. CONCLUSION: Oncologists, pulmonologists, radiologists and general practitioners have to consider PD-1 and PD-L1 inhibitor pneumonitis as a potentially disabling and fatal event.

Erratum: Joining smallholder farmers' traditional knowledge with metric traits to select better varieties of Ethiopian wheat.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Genome Wide Association Study to Identify the Genetic Base of Smallholder Farmer Preferences of Durum Wheat Traits.

Smallholder agriculture involves millions of farmers worldwide. A methodical utilization of their traditional knowledge in modern breeding efforts may help the production of locally adapted varieties better addressing their needs. In this study, a combination of participatory approaches, genomics, and quantitative genetics is used to trace the genetic basis of smallholder farmer preferences of durum wheat traits. Two smallholder communities evaluated 400 Ethiopian wheat varieties, mostly landraces, for traits of local interest in two locations in the Ethiopian highlands. For each wheat variety, farmers provided quantitative evaluations of their preference for flowering time, spike morphology, tillering capacity, and overall quality. Ten agronomic and phenology traits were simultaneously measured on the same varieties, providing the means to compare them with farmer traits. The analysis of farmer traits showed that they were partially influenced by gender and location but were repeatable and heritable, in some cases more than metric traits. The durum wheat varieties were genotyped for more than 80,000 SNP markers, and the resulting data was used in a genome wide association (GWA) study providing the molecular dissection of smallholder farmers' choice criteria. We found 124 putative quantitative trait loci (QTL) controlling farmer traits and 30 putative QTL controlling metric traits. Twenty of such QTL were jointly identified by farmer and metric traits. QTL derived from farmer traits were in some cases dependent on gender and location, but were consistent throughout. The results of the GWA study show that smallholder farmers' traditional knowledge can yield QTL eluding metric measurements of phenotypes. We discuss the potential of including farmer evaluations based on traditional knowledge in crop breeding, arguing for the utilization of this untapped resource to develop better adapted genetic materials for local agriculture.

Joining smallholder farmers' traditional knowledge with metric traits to select better varieties of Ethiopian wheat.

Smallholder farming communities face highly variable climatic conditions that threaten locally adapted, low-input agriculture. The benefits of modern crop breeding may fail to reach their fields when broadly adapted genetic materials do not address local requirements. To date, participatory methods only scratched the surface of the exploitability of farmers' traditional knowledge in breeding. In this study, 30 smallholder farmers in each of two locations in Ethiopia provided quantitative evaluations of earliness, spike morphology, tillering capacity and overall quality on 400 wheat genotypes, mostly traditional varieties, yielding altogether 192,000 data points. Metric measurements of ten agronomic traits were simultaneously collected, allowing to systematically break down farmers' preferences on quantitative phenotypes. Results showed that the relative importance of wheat traits differed by gender and location. Farmer traits were variously contributed by metric traits, and could only partially be explained by them. Eventually, farmer trait values were used to produce a ranking of the 400 wheat varieties identifying the trait combinations most desired by farmers. The study scale and methods lead to a better understanding of the quantitative basis of Ethiopian smallholder farmer preference in wheat, broadening the discussion for the future of local, sustainable breeding efforts accommodating farmers' knowledge.

Sellar and Suprasellar Anaplastic Hemangiopericytoma in a 34-Year Old Man.

Central nervous system hemangiopericytomas are rare, representing <1% of all primary central nervous system tumors. Hemangiopericytomas of the sellar region are exceptionally rare. Here we present a case of a sellar/suprasellar anaplastic hemangiopericytoma.The patient is a 34 year old man with a history of a resected pituitary tumor, diagnosed as a pituitary adenoma per the patient, who presented with bitemporal hemianopsia. Radiology revealed a 3.7 cm enhancing sellar/suprasellar mass with local mass effect, consistent with a pituitary adenoma. On resection, the mass was diagnosed as anaplastic hemangiopericytoma, WHO grade III. The patient experienced residual tumor with two further resections before expiring of a pulmonary embolus seven months later.There are only 10 previously documented cases of sellar/suprasellar hemangiopericytoma in the English-speaking world literature. This is the third case of anaplastic hemangiopericytoma in this region. These cases should be recorded until meaningful conclusions about therapy and prognosis can be established.

Continuous positive airways pressure and uvulopalatopharyngoplasty improves pulmonary hypertension in patients with obstructive sleep apnoea.

OBJECTIVE: Data are sparse regarding the prevalence of pulmonary hypertension (PH) in obstructive sleep apnoea (OSA) patients without COPD and clinically manifest cardiac diseases and the role of continuous positive airway pressure (CPAP) and Uvulopalatopharyngoplasty (UPPP) in normalizing this parameter. PATIENTS/METHODS: We studied 75 consecutive OSA patients, 55 of them men, using transthoracic echocardiography. A mild PH [pulmonary artery pressure (PAPs) 38.2 ± 6.8] was found in 25 subjects (prevalence 33%). These patients were divided into two groups: group 1A (n = 17), those treated with CPAP, and group 1B (n = 8), those who have the indication for a UPPP. We scheduled a follow-up at 3, 6 and 9 months. During follow-up, we performed echocardiography, measurement of anthropometric parameters (BMI, neck and waist-hip circumference), and of biochemical parameters (uric acid, fasting glucose, cholesterol, triglycerides) and blood pressure. RESULTS: Patients with PH had a higher BMI: 32 ± 6 versus 29 ± 4 (p < 0.001) and NC: 39.8 ± 4.76 versus 37.14 ± 3.49 (p = 0.003), were predominantly men (72%) and older: 64 ± 20 versus 55 ± 16 (p = 0.025) and had a significantly higher value of uric acid: 7.91 ± 2.35 versus 6.56 ± 1.31 (p = 0.003). We found a positive correlation between PH and BMI (r = 0.456; p < 0.001) and between uric acidic and PH (r = 0.636; p < 0.001). PAPs significantly changed, from 39.8 ± 4.1 to 27.1 ± 4, to 25.2 ± 3.1 and to 22.2 ± 3 mmHg (CI 95%; 15.09-20.11; p < 0.001) in group 1A and from 39.5 ± 5.1 to 23.4 ± 3.2, to 23.0 ± 3.1 and to 21.9 ± 2.9 mmHg (CI 95%; 13.15-22.05; p < 0.001) in group 1B (difference between the groups p = 0.12). CONCLUSIONS: PH was frequent in OSA patients and normalized after 6 months with both CPAP and UPPP. A similar trend was noted in diastolic blood pressure.

A fatal case of acute interstitial pneumonia (AIP) in a woman affected by glioblastoma.

This report presents the case of a 67-year-old woman affected by glioblastoma. After a few days of adjuvant therapy with temozolomide and prophylaxis with trimetrophin-sulfamethoxazolo to prevent Pneumocystis Jiroveci, she had progressive and rapid worsening of symptoms with weakness, dyspnea and orthopnea. She had peripheral edema and proximal hyposthenia of the lower limbs. Chest CT showed bilateral ground-glass opacities and laboratory exams revealed hypoxemia and hypocapnia, an initial reduction in platelet and white blood cells, and an elevation of LDH, AST, ALT, and active urinary sediment. Blood cultures, bronchoalveolar lavage (BAL) data and transbronchial biopsy showed no infections, and in particular no evidence of Pneumocystis Jiroveci pneumonia. Histological examination revealed a typical pattern of AIP. She was treated with broad-spectrum antibiotics and high-dose steroids. The symptoms worsened and respiratory failure required mechanical ventilation. The pneumonia was not responsive to medical or invasive care. She died after ten days of hospitalization. At present very little can be found in the literature about lung toxicity caused by temozolomide. This case can be added as a new report describing this risk. The combination therapy with temozolamide and trimetophin-sulfamethoxazolo could have a synergistic action inducing various forms of pulmonary toxicity. ESTABLISHED FACTS: Acute interstitial pneumonia is a common manifestation of lung toxicity caused by drugs. The clinical course is favorable with a good response to corticosteroids. NOVEL INSIGHT: This is the first fatal case of lung toxicity caused by Temozolomide. Clinicians must be aware that a combination therapy including trimetophin-sulfamethoxazolo could have a synergistic action in inducing pulmonary toxicity.

[Osteoporosis associated with chronic obstructive pulmonary disease and other respiratory diseases]. / Osteoporosi associata a broncopneumopatia cronica ostruttiva e ad altre patologie respiratorie.

Chronic obstructive pulmonary disease (COPD) and osteoporosis are associated because of common risk factors. In addition, COPD enhance systemic inflammation, vitamin D deficiency, and above all the use of systemic steroids induce bone destruction. Early prevention and treatment of osteoporosis is useful in COPD and in other chronic lung diseases.

Structure and function of an ADP-ribose-dependent transcriptional regulator of NAD metabolism.

Besides its function as an essential redox cofactor, nicotinamide adenine dinucleotide (NAD) also serves as a consumable substrate for several reactions with broad impact on many cellular processes. NAD homeostasis appears to be tightly controlled, but the mechanism of its regulation is little understood. Here we demonstrate that a previously predicted bacterial transcriptional regulator, NrtR, represses the transcription of NAD biosynthetic genes in vitro. The NAD metabolite ADP-ribose functions as an activator suppressing NrtR repressor activity. The presence of high ADP-ribose levels in the cell is indicative of active NAD turnover in bacteria, which could signal the activation of NAD biosynthetic gene expression via inhibiting the repressor function of NrtR. By comparing the crystal structures of NrtR in complex with DNA and with ADP-ribose, we identified a "Nudix switch" element that likely plays a critical role in the allosteric regulation of DNA binding and repressor function of NrtR.