Accurate virus identification with interpretable Raman signatures by machine learning.

Rapid identification of newly emerging or circulating viruses is an important first step toward managing the public health response to potential outbreaks. A portable virus capture device, coupled with label-free Raman spectroscopy, holds the promise of fast detection by rapidly obtaining the Raman signature of a virus followed by a machine learning (ML) approach applied to recognize the virus based on its Raman spectrum, which is used as a fingerprint. We present such an ML approach for analyzing Raman spectra of human and avian viruses. A convolutional neural network (CNN) classifier specifically designed for spectral data achieves very high accuracy for a variety of virus type or subtype identification tasks. In particular, it achieves 99% accuracy for classifying influenza virus type A versus type B, 96% accuracy for classifying four subtypes of influenza A, 95% accuracy for differentiating enveloped and nonenveloped viruses, and 99% accuracy for differentiating avian coronavirus (infectious bronchitis virus [IBV]) from other avian viruses. Furthermore, interpretation of neural net responses in the trained CNN model using a full-gradient algorithm highlights Raman spectral ranges that are most important to virus identification. By correlating ML-selected salient Raman ranges with the signature ranges of known biomolecules and chemical functional groups­for example, amide, amino acid, and carboxylic acid­we verify that our ML model effectively recognizes the Raman signatures of proteins, lipids, and other vital functional groups present in different viruses and uses a weighted combination of these signatures to identify viruses.

Multiplex real-time PCR FilmArray performance in the diagnosis of meningoencephalitis: lights and shadows.

PURPOSE: We aimed to evaluate the performance of the FilmArray (FA) meningitis/encephalitis (ME) panel. Secondarily, we analyzed the false positive (FP) and false negative (FN) results, as well as the predictive values of the technique, regarding the cerebrospinal fluid (CSF) characteristics. METHODS: FA is a multiplex real-time PCR detecting 14 of the most common ME pathogens in CSF. All FA performed at our hospital (2018-2022) were retrospectively reviewed. FA was compared to conventional techniques and its performance was assessed based on the final diagnosis of the episode. RESULTS: FA was performed in 313 patients with suspicion of ME. Most patients had altered mental status (65.2%) and fever (61%). Regarding CSF characteristics, 49.8% and 53.7% presented high CSF proteins and pleocytosis, respectively. There were 84 (26.8%) positive FA results, mainly for HSV-1 (10.9%), VZV (5.1%), Enterovirus (2.6%), and S. pneumoniae (1.9%). In the 136 cases where both FA and routine methods were performed, there was a 25.7% lack of agreement. We identified 6.6% FN results, but 28.6% FP, mainly due to HSV-1. This resulted in a high negative predictive value (NPV) of 93.4%, but a positive predictive value (PPV) of 73%. Remarkably, PPV as low as 36.9%, and 70.2%, were found in cases without pleocytosis, or lack of high CSF protein levels, respectively. CONCLUSION: FA was associated with high NPV, but frequent FP results and low PPV, particularly for HSV-1, and especially in patients without high CSF protein levels or pleocytosis.

Determining depletion interactions by contracting forces.

Depletion forces are fundamental for determining the phase behavior of a vast number of materials and colloidal dispersions and have been used for the manipulation of in- and out-of-equilibrium thermodynamic states. The entropic nature of depletion forces is well understood; however, most theoretical approaches, and also molecular simulations, work quantitatively at moderate size ratios in much diluted systems since large size asymmetries and high particle concentrations are difficult to deal with. The existing approaches for integrating out the degrees of freedom of the depletant species may fail under these extreme physical conditions. Thus, the main goal of this contribution is to introduce a general physical formulation for obtaining the depletion forces even in those cases where the concentration of all species is relevant. We show that the contraction of the bare forces uniquely determines depletion interactions. Our formulation is tested by studying depletion forces in binary and ternary colloidal mixtures. We report here results for dense systems with total packing fractions of 45% and 55%. Our results open up the possibility of finding an efficient route to determine effective interactions at a finite concentration, even under non-equilibrium thermodynamic conditions.

Effect of intravenous iron on functional outcomes in hip fracture: a randomised controlled trial.

OBJECTIVES: to determine the safety and effect of intravenous iron sucrose on functional outcomes, delirium, nosocomial infections and transfusion requirements in older patients with hip fracture. DESIGN: single-centre randomised, double-blind, placebo-controlled clinical trial. SETTING AND PARTICIPANTS: orthogeriatric share care service at an academic tertiary care hospital. A total of 253 patients were recruited: 126 patients were assigned to intravenous iron and 127 to placebo. METHODS: on days 1, 3 and 5 after admission, the iron group received 200 mg Venofer® (iron sucrose) in 100 ml saline and the placebo group 100 ml saline. The primary outcome was absolute functional gain, considered as Barthel index (BI) at discharge minus BI on admission. Secondary outcomes included incidence of postoperative delirium according to the confusion assessment method, proportion of patients recovering prior functional status at 3 months, postoperative transfusion requirements, haemoglobin at 3 months, incidence of nosocomial infections and safety. RESULTS: the median participant age was 87 (interquartile range, 82.5-91.5) years. Most patients were female (72.7%), and the median previous BI was 81(59-95). No significant effect of intravenous iron was observed for the primary outcome: the median AFG score was 17.1 points (4.8-23.3) in the intravenous iron group and 16 points (6-26) in the placebo group (P = 0.369). No significant treatment effects were observed for other functional outcomes or secondary end points. CONCLUSION: while we found no impact of intravenous iron sucrose on functional recovery, incidence of postoperative delirium, transfusion requirements, haemoglobin at 3 months, mortality and nosocomial infections rates in older patients with hip fracture, we did find that the intervention was safe.

Competing interactions in the depletion forces of ternary colloidal mixtures.

Depletion interactions between colloidal particles surrounded by smaller depletants are typically characterized by a strong attraction at contact and a moderately repulsive barrier in front of it that extends at distances similar to the size of the depletants; the appearance and height of the barrier basically depend on the concentration and, therefore, the correlation between depletants. From a thermodynamic point of view, the former can drive the system to phase separation or toward non-equilibrium states, such as gel-like states, but its effects on both local and global properties may be controlled by the latter, which acts as a kind of entropic gate. However, the latter has not been entirely analyzed and understood within the context of colloidal mixtures mainly driven by entropy. In this contribution, we present a systematic study of depletion forces in ternary mixtures of hard spherical particles with two species of depletants, in two and three dimensions. We focus the discussion on how the composition of the depletants becomes the main physical parameter that drives the competition between the attractive well and the repulsive barrier. Our results are obtained by means of the integral equation theory of depletion forces and techniques of contraction of the description adapted to molecular dynamics computer simulations.

Angstrom-Size Defect Creation and Ionic Transport through Pores in Single-Layer MoS2.

Atomic-defect engineering in thin membranes provides opportunities for ionic and molecular filtration and analysis. While molecular-dynamics (MD) calculations have been used to model conductance through atomic vacancies, corresponding experiments are lacking. We create sub-nanometer vacancies in suspended single-layer molybdenum disulfide (MoS2) via Ga+ ion irradiation, producing membranes containing ∼300 to 1200 pores with average and maximum diameters of ∼0.5 and ∼1 nm, respectively. Vacancies exhibit missing Mo and S atoms, as shown by aberration-corrected scanning transmission electron microscopy (AC-STEM). The longitudinal acoustic band and defect-related photoluminescence were observed in Raman and photoluminescence spectroscopy, respectively. As the irradiation dose is increased, the median vacancy area remains roughly constant, while the number of vacancies (pores) increases. Ionic current versus voltage is nonlinear and conductance is comparable to that of ∼1 nm diameter single MoS2 pores, proving that the smaller pores in the distribution display negligible conductance. Consistently, MD simulations show that pores with diameters <0.6 nm are almost impermeable to ionic flow. Atomic pore structure and geometry, studied by AC-STEM, are critical in the sub-nanometer regime in which the pores are not circular and the diameter is not well-defined. This study lays the foundation for future experiments to probe transport in large distributions of angstrom-size pores.

Ultrasensitive gas detection of large-area boron-doped graphene.

Heteroatom doping is an efficient way to modify the chemical and electronic properties of graphene. In particular, boron doping is expected to induce a p-type (boron)-conducting behavior to pristine (nondoped) graphene, which could lead to diverse applications. However, the experimental progress on atomic scale visualization and sensing properties of large-area boron-doped graphene (BG) sheets is still very scarce. This work describes the controlled growth of centimeter size, high-crystallinity BG sheets. Scanning tunneling microscopy and spectroscopy are used to visualize the atomic structure and the local density of states around boron dopants. It is confirmed that BG behaves as a p-type conductor and a unique croissant-like feature is frequently observed within the BG lattice, which is caused by the presence of boron-carbon trimers embedded within the hexagonal lattice. More interestingly, it is demonstrated for the first time that BG exhibits unique sensing capabilities when detecting toxic gases, such as NO2 and NH3, being able to detect extremely low concentrations (e.g., parts per trillion, parts per billion). This work envisions that other attractive applications could now be explored based on as-synthesized BG.

Effect of periodontal treatment on preterm birth rate: a systematic review of meta-analyses.

Preterm birth is a major cause of neonatal morbidity and mortality in both developed and developing countries. Preterm birth is a highly complex syndrome that includes distinct clinical subtypes in which many different causes may be involved. The results of epidemiological, molecular, microbiological and animal-model studies support a positive association between maternal periodontal disease and preterm birth. However, the results of intervention studies carried out to determine the effect of periodontal treatment on reducing the risk of preterm birth are controversial. This systematic review critically analyzes the methodological issues of meta-analyses of the studies to determine the effect of periodontal treatment to reduce preterm birth. The quality of the individual randomized clinical trials selected is of highest relevance for a systematic review. This article describes the methodological features that should be identified a priori and assessed individually to determine the quality of a randomized controlled trial performed to evaluate the effect of periodontal treatment on pregnancy outcomes. The AMSTAR and the PRISMA checklist tools were used to assess the quality of the six meta-analyses selected, and the bias domain of the Cochrane Collaboration's Tool was applied to evaluate each of the trials included in the meta-analyses. In addition, the methodological characteristics of each clinical trial were assessed. The majority of the trials included in the meta-analyses have significant methodological flaws that threaten their internal validity. The lack of effect of periodontal treatment on preterm birth rate concluded by four meta-analyses, and the positive effect of treatment for reducing preterm birth risk concluded by the remaining two meta-analyses are not based on consistent scientific evidence. Well-conducted randomized controlled trials using rigorous methodology, including appropriate definition of the exposure, adequate control of confounders for preterm birth and application of effective periodontal interventions to eliminate periodontal infection, are needed to confirm the positive association between periodontal disease and preterm birth.

Ultrashort optical pulse characterization using WS2 monolayers.

We demonstrate the application of two-dimensional materials for ultrashort optical pulse characterization. Monolayer transition metal dichalcogenides, such as tungsten disulfide (WS2), possess extraordinarily large second-order nonlinear susceptibility, and due to their atomic thickness, have relaxed phase-matching requirements and, hence, an inherently wide bandwidth. Synthesized monolayer WS2 triangular islands were used to characterize ultrashort optical pulses at the focal point of an objective lens through second-harmonic generation collinear frequency-resolved optical gating.

Extraordinary room-temperature photoluminescence in triangular WS2 monolayers.

Individual monolayers of metal dichalcogenides are atomically thin two-dimensional crystals with attractive physical properties different from those of their bulk counterparts. Here we describe the direct synthesis of WS2 monolayers with triangular morphologies and strong room-temperature photoluminescence (PL). The Raman response as well as the luminescence as a function of the number of S-W-S layers is also reported. The PL weakens with increasing number of layers due to a transition from direct band gap in a monolayer to indirect gap in multilayers. The edges of WS2 monolayers exhibit PL signals with extraordinary intensity, around 25 times stronger than that at the platelet's center. The structure and chemical composition of the platelet edges appear to be critical for PL enhancement.

Effective plant virus enrichment using carbon nanotubes and microfluidics.

Plant virus detection and identification in crops is a pillar for disease management, import of crop material, production of clean stock plants and basic plant virology studies. In this report, we present a platform for the enrichment and isolation of known or unknown viruses. This platform is based on carbon nanotube arrays inside a microfluidic device that can be a solution for the identification of low titer viruses from plants. Using our microfluidic devices, we achieved enrichment of two economically important viruses, the orthotospovirus, tomato spotted wilt orthotospovirus (TSWV) and the potyvirus, zucchini yellow mosaic virus (ZYMV). The carbon nanotube arrays integrated in these microfluidic devices are capable of trapping viruses discriminated by their size; the virus rich arrays can be then analyzed by common downstream techniques including immunoassays, PCR, HTS and electron microscopy. This procedure offers a simple to operate and portable sample preparation device capable of trapping viruses from raw plant extracts while reducing the host contamination.

Comparison of inferior vena cava filter use and outcomes between cancer and non-cancer patients in a tertiary hospital.

BACKGROUND: While accepted indications for the use of inferior vena cava filter (IVCF) in patients with a venous thromboembolism (VTE) have remained stable, their use continues to be frequent. Retrieval rates are still low, being particularly notable in the population with cancer. This study aims to review the rate of adherence to guidelines recommendation and to compare retrieval rates and complications in both cancer and non-cancer patients. METHODS: A retrospective study was performed including 185 patients in whom an IVCF was placed in Hospital Clinic of Barcelona. Baseline characteristics, clinical outcomes, and IVCF-related outcomes were analyzed. A strongly recommended indication (SRI) was considered if it was included in all the revised clinical guidelines and non-strongly if it was included in only some. RESULTS: Overall, 47 % of the patients had a SRI, without differences between groups. IVCF placement after 29 days from the VTE event was more frequent in the cancer group (46.1 vs. 17.7 %). Patients with cancer (48.1 % of the cohort) were older, with higher co-morbidity and bleeding risk. Anticoagulation resumption (75.3 % vs. 92.7 %) and IVCF retrieval (50.6 % vs. 66.7 %) were significantly less frequent in cancer patients. No significant differences were found regarding IVCF-related complications, hemorrhagic events and VTE recurrence. CONCLUSIONS: SRI of IVCF placement was found in less than half of the patients. Cancer patients had higher rates of IVCF placement without indication and lower anticoagulation resumption and IVCF retrieval ratios, despite complications were similar in both groups.

Inferior Vena Cava Filters: Adherence to Clinical Practice Guidelines Recommendations, Retrieval Rates, and Filter Complications in a Tertiary Hospital.

The present study evaluated the adherence to guideline recommendations regarding the indication for inferior vena cava filter (IVCF) placement, retrieval rates, complications, thrombotic recurrences, and mortality. Patients in whom an IVCF was placed between 2015 and 2020 in a tertiary hospital were retrospectively included. We considered absolute indication of IVCF placement if all the guidelines evaluated agreed on the indication, relative indication if only some guidelines recommended it and without indication if none of the evaluated guidelines recommended it. From the 185 patients included; 47% had an absolute indication, 15% a relative indication, and 38% had no indication. Filter-associated complications and non-removal rates were 12.4% and 41%, respectively. Venous thromboembolism recurrence rate was 17.8%, being filter-associated complications (24.2 vs 9.8%, P = .02) and thrombosis of the inferior cava or iliac veins (12.1 vs 2.6%, P = .03) more frequent in this group. The mortality rate was 40%, with higher mortality risk in patients with co-existing cancer. Previous major bleeding, filter-associated complications, and mortality were associated with a major risk of non-removal. In conclusion, the adherence to guidelines regarding the indication of IVCF placement is still low and IVCF complications are not negligible. This fact is of special concern in the elderly, comorbid, and cancer patients.

Hospital at home treatment with remdesivir for patients with COVID-19: real-life experience.

OBJECTIVES: Access and appropriateness of therapeutics for COVID-19 vary because of access or regulatory barriers, the severity of the disease, and for some therapies, the stage of the pandemic and circulating variants. Remdesivir has shown benefits in clinical recovery and is the treatment of choice for selected patients, both hospitalized and nonhospitalized, in main international guidelines. The use of remdesivir in alternatives to conventional hospitalization such as hospital at home (HaH) units remains incompletely explored. In this study, we aim to describe the real-life experience of outpatient remdesivir infusion for COVID-19 in a HaH unit. METHODS: We selected all the consecutive patients receiving remdesivir from a prospective cohort of 507 COVID-19 patients admitted at a HaH unit. Admission criteria included COVID-19 with a fraction of inspired oxygen requirement under 0.35 and respiratory rate under 22 rpm. Patients were daily assessed in person by a nurse and a physician. RESULTS: A total of 236 patients admitted at the HaH unit received remdesivir, 172 of whom were treated at home. Only 2% presented any adverse event related to the infusion, all of them mild. HaH saved 1416 day-beds, with only 5% of the patients requiring transfer back to the hospital. CONCLUSION: Remdesivir infusion in HaH units seems to be a safe and efficient alternative to conventional hospitalization for treating patients with nonsevere COVID-19.

Substrate-Induced Changes on the Optical Properties of Single-Layer WS2.

Among the most studied semiconducting transition metal dichalcogenides (TMDCs), WS2 showed several advantages in comparison to their counterparts, such as a higher quantum yield, which is an important feature for quantum emission and lasing purposes. We studied transferred monolayers of WS2 on a drilled Si3N4 substrate in order to have insights about on how such heterostructure behaves from the Raman and photoluminescence (PL) measurements point of view. Our experimental findings showed that the Si3N4 substrate influences the optical properties of single-layer WS2. Beyond that, seeking to shed light on the causes of the PL quenching observed experimentally, we developed density functional theory (DFT) based calculations to study the thermodynamic stability of the heterojunction through quantum molecular dynamics (QMD) simulations as well as the electronic alignment of the energy levels in both materials. Our analysis showed that along with strain, a charge transfer mechanism plays an important role for the PL decrease.

Engineering Vacancies for the Creation of Antisite Defects in Chemical Vapor Deposition Grown Monolayer MoS2 and WS2 via Proton Irradiation.

It is critical to understand the laws of quantum mechanics in transformative technologies for computation and quantum information science applications to enable the ongoing second quantum revolution calls. Recently, spin qubits based on point defects have gained great attention, since these qubits can be initiated, selectively controlled, and read out with high precision at ambient temperature. The major challenge in these systems is controllably generating multiqubit systems while properly coupling the defects. To address this issue, we began by tackling the engineering challenges these systems present and understanding the fundamentals of defects. In this regard, we controllably generate defects in MoS2 and WS2 monolayers and tune their physicochemical properties via proton irradiation. We quantitatively discovered that the proton energy could modulate the defects' density and nature; higher defect densities were seen with lower proton irradiation energies. Three distinct defect types were observed: vacancies, antisites, and adatoms. In particular, the creation and manipulation of antisite defects provides an alternative way to create and pattern spin qubits based on point defects. Our results demonstrate that altering the particle irradiation energy can regulate the formation of defects, which can be utilized to modify the properties of 2D materials and create reliable electronic devices.

Understanding the Excitation Wavelength Dependence and Thermal Stability of the SARS-CoV-2 Receptor-Binding Domain Using Surface-Enhanced Raman Scattering and Machine Learning.

COVID-19 has cost millions of lives worldwide. The constant mutation of SARS-CoV-2 calls for thorough research to facilitate the development of variant surveillance. In this work, we studied the fundamental properties related to the optical identification of the receptor-binding domain (RBD) of SARS-CoV-2 spike protein, a key component of viral infection. The Raman modes of the SARS-CoV-2 RBD were captured by surface-enhanced Raman spectroscopy (SERS) using gold nanoparticles (AuNPs). The observed Raman enhancement strongly depends on the excitation wavelength as a result of the aggregation of AuNPs. The characteristic Raman spectra of RBDs from SARS-CoV-2 and MERS-CoV were analyzed by principal component analysis that reveals the role of secondary structures in the SERS process, which is corroborated with the thermal stability under laser heating. We can easily distinguish the Raman spectra of two RBDs using machine learning algorithms with accuracy, precision, recall, and F1 scores all over 95%. Our work provides an in-depth understanding of the SARS-CoV-2 RBD and paves the way toward rapid analysis and discrimination of complex proteins of infectious viruses and other biomolecules.

[Association between atherosclerosis and periodontitis]. / Aterosclerosis en sujetos con periodontitis.

BACKGROUND: Chronic inflammation and infections are involved in the development and progression of atherosclerotic vascular disease. AIM: To evaluate the association between periodontitis and early atherosclerosis. MATERIAL AND METHODS: Fifty-three subjects who received periodontal treatment and regular maintenance for at least 10 years, and 55 subjects with periodontitis but without a history of periodontal treatment were studied. Carotid artery intima-media wall thickness (CIMT) was measured with high-resolution B-mode ultrasonography. A blood sample was obtained to measure high sensitivity C-reactive protein, fibrinogen, lipoprotein cholesterol, leukocyte count and erythrocyte sedimentation rate. Covariates included age, gender, smoking, level of education, body mass index and physical activity. The benzoyl-DL-arginine-naphthylamide (BANA) test was used to determine the number of periodontal sites with periodontal pathogens. RESULTS: CIMT value was significantly higher in subjects with periodontitis than those without it (0.775 ± 0.268 and 0.683 ± 0.131 mm respectively, p = 0.027). C-reactive protein, leukocyte count and percentage of sites with periodontal pathogens were also significantly higher in subjects with periodontitis. Regression analysis identified age, periodontitis, and smoking as independent predictors of CIMT. CONCLUSIONS: These results suggest that untreated periodontitis is associated with early atherosclerotic carotid lesions and higher levels of inflammatory markers.

Interaction of gases with monolayer WS2: an in situ spectroscopy study.

The optical and electronic properties of two-dimensional (2D) materials can be tuned through physical and chemical adsorption of gases. They are also ideal sensor platforms, where charge transfer from the adsorbate can induce a measurable change in the electrical resistance within a device configuration. While 2D materials-based gas sensors exhibit high sensitivity, questions exist regarding the direction of charge transfer and the role of lattice defects during sensing. Here we measured the dynamics of adsorption of NO2 and NH3 on monolayer WS2 using in situ photoluminescence (PL) and resonance Raman spectroscopy. Experiments were conducted across a temperature range of 25-250 °C and gas concentrations between 5-650 ppm. The PL emission energies blue- and red-shifted when exposed to NO2 and NH3, respectively, and the magnitude of the shift depended on the gas concentration as well as the temperature down to the lowest concentration of 5 ppm. Analysis of the adsorption kinetics revealed an exponential increase in the intensities of the trion peaks with temperature, with apparent activation energies similar to barriers for migration of sulfur vacancies in the WS2 lattice. The corresponding Resonance Raman spectra allowed the simultaneous measurement of the defect-induced LA mode. A positive correlation between the defect densities and the shifts in the PL emission energies establish lattice defects such as sulfur vacancies as the preferential sites for gas adsorption. Moreover, an increase in defect densities with temperature in the presence of NO2 and NH3 suggests that these gases may also play a role in the creation of lattice defects. Our study provides key mechanistic insights into gas adsorption on monolayer WS2, and highlights the potential for future development of spectroscopy-based gas sensors based on 2D materials.