Lung ultrasound is a promising screening tool to rule out interstitial lung disease in patients with rheumatoid arthritis.

BACKGROUND AND OBJECTIVE: It is still controversial how to screen for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). We aimed to evaluate the performance of lung ultrasound (LUS) as a screening tool for RA-ILD and to compare it with the performance of chest auscultation, chest x-ray and pulmonary function tests (PFTs). METHODS: Cross-sectional study of consecutive RA patients evaluated at a Rheumatology Clinic in Buenos Aires between January and December 2022. High-resolution computed tomography (HRCT) was the gold standard for diagnosing ILD and was performed within 30 days of the LUS, chest x-ray and PFTs. Investigators were blinded to HRCT results and patients' clinical data. LUS was performed by exploring 14 areas and was considered positive when the sum of B lines was ≥5. Performance for the diagnosis of ILD was reported for each diagnostic test. RESULTS: One hundred and six patients were included; 87 (82%) were women. Median age was 60.9 (±9.5) years-old. A total of 32 (30.2%, 95% CI: 21.6%-39.9%) had ILD. The sensitivity and negative predictive value of LUS were 90.6% (95% CI 75.0%-98.0%) and 94.7% (95% CI 85.4%-98.9%), respectively. LUS performance was superior to that of the other evaluated diagnostic tests for screening ILD. CONCLUSIONS: Given that the US is a low-cost point-of-care tool with a high negative predictive value, it is emerging as a valuable tool for ruling out ILD in patients with RA.

Local adaptation shapes functional traits and resource allocation in black spruce.

Climate change is rapidly altering weather patterns, resulting in shifts in climatic zones. The survival of trees in specific locations depends on their functional traits. Local populations exhibit trait adaptations that ensure their survival and accomplishment of growth and reproduction processes during the growing season. Studying these traits offers valuable insights into species responses to present and future environmental conditions, aiding the implementation of measures to ensure forest resilience and productivity. This study investigates the variability in functional traits among five black spruce (Picea mariana (Mill.) B.S.P.) provenances originating from a latitudinal gradient along the boreal forest, and planted in a common garden in Quebec, Canada. We examined differences in bud phenology, growth performance, lifetime first reproduction, and the impact of a late-frost event on tree growth and phenological adjustments. The findings revealed that trees from northern sites exhibit earlier budbreak, lower growth increments, and reach reproductive maturity earlier than those from southern sites. Late-frost damage affected growth performance, but no phenological adjustment was observed in the successive year. Local adaptation in the functional traits may lead to maladaptation of black spruce under future climate conditions or serve as a potent evolutionary force promoting rapid adaptation under changing environmental conditions.

Visualizing moiré ferroelectricity via plasmons and nano-photocurrent in graphene/twisted-WSe2 structures.

Ferroelectricity, a spontaneous and reversible electric polarization, is found in certain classes of van der Waals (vdW) materials. The discovery of ferroelectricity in twisted vdW layers provides new opportunities to engineer spatially dependent electric and optical properties associated with the configuration of moiré superlattice domains and the network of domain walls. Here, we employ near-field infrared nano-imaging and nano-photocurrent measurements to study ferroelectricity in minimally twisted WSe2. The ferroelectric domains are visualized through the imaging of the plasmonic response in a graphene monolayer adjacent to the moiré WSe2 bilayers. Specifically, we find that the ferroelectric polarization in moiré domains is imprinted on the plasmonic response of the graphene. Complementary nano-photocurrent measurements demonstrate that the optoelectronic properties of graphene are also modulated by the proximal ferroelectric domains. Our approach represents an alternative strategy for studying moiré ferroelectricity at native length scales and opens promising prospects for (opto)electronic devices.

Optimizing transcranial magnetic stimulation for spaceflight applications.

As space agencies aim to reach and build installations on Mars, the crews will face longer exposure to extreme environments that may compromise their health and performance. Transcranial magnetic stimulation (TMS) is a painless non-invasive brain stimulation technique that could support space exploration in multiple ways. However, changes in brain morphology previously observed after long-term space missions may impact the efficacy of this intervention. We investigated how to optimize TMS for spaceflight-associated brain changes. Magnetic resonance imaging T1-weighted scans were collected from 15 Roscosmos cosmonauts and 14 non-flyer participants before, after 6 months on the International Space Station, and at a 7-month follow-up. Using biophysical modeling, we show that TMS generates different modeled responses in specific brain regions after spaceflight in cosmonauts compared to the control group. Differences are related to spaceflight-induced structural brain changes, such as those impacting cerebrospinal fluid volume and distribution. We suggest solutions to individualize TMS to enhance its efficacy and precision for potential applications in long-duration space missions.

Thermal response analysis and compilation of cardinal temperatures for 424 strains of microalgae, cyanobacteria, diatoms and other species.

Microalgae and other phototrophic microorganisms can be cultivated to produce food and valuable bioproducts, also allowing to remove nutrients from wastewater and CO2 from biogas or polluted gas streams. Among other environmental and physico-chemical parameters, microalgal productivity is strongly influenced by the cultivation temperature. In this review, cardinal temperatures identifying the thermal response, i.e., the optimal growth condition (TOPT), and the lower and upper limits for microalgae cultivation (TMIN and TMAX), have been included in a structured and harmonized database. Literature data for 424 strains belonging to 148 genera of green algae, cyanobacteria, diatoms, and other phototrophs were tabulated and analysed, with a focus on the most relevant genera that are currently cultivated at the industrial scale in Europe. The dataset creation aimed at facilitating the comparison of different strain performances for different operational temperatures and assisting in the process of thermal and biological modelling, to reduce energy consumption and biomass production costs. A case study was presented, to illustrate the effect of temperature control on the energetic expenditure for cultivating different Chorella sp. strains under a greenhouse located in different European sites.

Targeting neural correlates of placebo effects.

Harnessing the placebo effects would prompt critical ramifications for research and clinical practice. Noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation and multifocal transcranial electric stimulation, could manipulate the placebo response by modulating the activity and excitability of its neural correlates. To identify potential stimulation targets, we conducted a meta-analysis to investigate placebo-associated regions in healthy volunteers, including studies with emotional components and painful stimuli. Using biophysical modeling, we identified NIBS solutions to manipulate placebo effects by targeting either a single key region or multiple connected areas. Moving to a network-oriented approach, we then ran a quantitative network mapping analysis on the functional connectivity profile of clusters emerging from the meta-analysis. As a result, we suggest a multielectrode optimized montage engaging the connectivity patterns of placebo-associated functional brain networks. These NIBS solutions hope to provide a starting point to actively control, modulate or enhance placebo effects in future clinical studies and cognitive enhancement studies.

Late diagnosis of CHD and its associated factors in Kenya: an analytic cross-sectional study.

INTRODUCTION: Burden of CHD in Africa is generally underestimated mainly due to significant under-reporting and early-related fetal and neonatal mortality. OBJECTIVES: Determine the prevalence and factors associated with late diagnosis of CHD seen at three tertiary care hospitals in Kenya. DESIGN: A cross-sectional study on paediatric patients with CHDs, aged 0-18 years, seen over a 5-year period, between January, 2011 and December, 2016. SETTING: Aga Khan University Hospital Nairobi, Mater Hospital, and Kenyatta National Hospital. METHODS: Patients were stratified into those diagnosed late (>1 year of age) and those diagnosed early (<1 year of age). Multiple logistic regression analysis was done to determine factors associated with late diagnosis. RESULTS: The study enrolled 411 patients, with equal gender distribution. Prevalence of late diagnosis (>1 year of age) of CHD was 60.6% (95% CI 55.7-65.3). Median age at diagnosis was 15 (IQR 5-48) months. Presence of a cardiac murmur (OR = 0.87; 95% CI 0.72-0.92, p-value = 0.016) and level of parental education (OR = 4.99; 95% CI 2.25-11.40, p-value <0001) were associated with a decreased odds of late diagnosis. Other factors like cyanosis, an increase in the number of healthcare workers and healthcare facilities per 10,000 population showed some association with decreased odds of late diagnosis of CHD, but these were not statistically significant. CONCLUSION: Late diagnosis of CHD remains alarmingly high in our setting. Initiatives to enhance early detection and screening of CHD should be adopted to reduce related mortality and morbidity.

Surgical site infections after simultaneous pancreas kidney and pancreas transplantation in the Swiss Transplant Cohort Study.

BACKGROUND: Among hospital-acquired infections, surgical site infections (SSIs) are frequent. SSI in the early post-transplant course poses a relevant threat to transplant recipients. AIM: To determine incidence, risk factors for SSI and its association with post-transplant outcomes and pancreas transplant (P-Tx) recipients. METHODS: Adult simultaneous kidney-pancreas transplantation (SPK-T) and P-Tx recipients with a follow-up of at least 90 days were identified in the Swiss Transplant Cohort Study (STCS) dataset. Except for the categorization of SSIs according to Centers for Disease Control and Prevention (CDC) criteria, all other data were prospectively collected. Risk factors for SSI were investigated with logistic regression. A Weibull accelerated failure-time model was applied to address the impact of SSI on length of stay, correcting for transplant-related complications and delayed graft function. FINDINGS: Of 130 transplant recipients, 108 SPK-Tx and 22 P-Tx, 18 (14%) individuals developed SSI within the first 90 days after transplantation. Deep incisional (seven, 38.9%) and organ/space infections (eight, 44.4%) predominated. In the majority of SSIs (11, 61.1%; two SSIs with simultaneous identification of fungal pathogens) bacteria were detected with Enterococcus spp. being most frequent. The median duration of hospitalization after transplantation was significantly longer in recipients with SSI (median: 26 days; interquartile range (IQR): 19-44) than in patients without SSI (median: 17 days; IQR: 12-25; P = 0.002). In multivariate analysis, SSI was significantly associated with increased length of stay and prolonged the duration of hospitalization by 36% (95% confidence interval: 4-79). CONCLUSION: SSI after SPK-Tx and P-Tx occurred at a frequency of 14%. Among pathogens, Enterococcus spp. predominated. SSI was independently associated with a longer hospitalization after transplantation.

Respirometric assessment of bacterial kinetics in algae-bacteria and activated sludge processes.

Algae-bacteria (AB) consortia can be exploited for effective wastewater treatment, based on photosynthetic oxygenation to reduce energy requirements for aeration. While algal kinetics have been extensively evaluated, bacterial kinetics in AB systems are still based on parameters taken from the activated sludge models, lacking an experimental validation for AB consortia. A respirometric procedure was therefore proposed, to estimate bacterial kinetics in both activated sludge and AB, under different conditions of temperature, pH, dissolved oxygen, and substrate availability. Bacterial activities were differently influenced by operational/environmental conditions, suggesting that the adoption of typical activated sludge parameters could be inadequate for AB modelling. Indeed, respirometric results show that bacteria in AB consortia were adapted to a wider range of conditions, compared to activated sludge, confirming that a dedicated calibration of bacterial kinetics is essential for effectively modelling AB systems, and respirometry was proven to be a powerful and reliable tool to this purpose.

Piggery wastewater treatment with algae-bacteria consortia: Pilot-scale validation and techno-economic evaluation at farm level.

The efficiency of an outdoor pilot-scale raceway pond treating the wastewaters generated by a large-scale piggery farm in Northern Italy was evaluated. The biomass productivity over 208 days of experimentation was 10.7 ± 6.5 g TSS·m-2·d-1, and ammoniacal nitrogen, orthophosphate, and COD average removal efficiencies were 90%, 90%, and 59%, respectively. Results were used to perform a comprehensive techno-economic analysis for integrating algae-based processes in farms of different sizes (100-10000 pigs). The amount of N disposed of on agricultural land could be reduced from 91% to 21%, increasing the fraction returned to the atmosphere from 2.4% to 63%, and the fraction in the biomass from 6.2% to 16%. For intensive farming, the release of 110 t N·ha-1·y-1 contained in the digestate could be avoided by including algae-bacteria processes. The biomass production cost was as low as 1.9 €·kg-1, while the cost for nitrogen removal was 4.3 €·kg N-1.

Long term mortality and morbidity of Italian soldiers after deployment in Iraq as related to biomarkers assessment: Results of the SIGNUM study.

INTRODUCTION: The health profile of military veterans deployed in foreign operative theatres was assessed by several international studies because of potential exposure to depleted uranium and other pollutants. Here we reported results of 15-year epidemiological surveillance assessing long-term health effects in a cohort of Italian soldiers deployed in Iraq in 2004-2005 and participating in a biomonitoring campaign to identify potential genotoxic exposure to environmental xenobiotics before and after deployment (n = 981, SIGNUM cohort). METHODS: We evaluated mortality and hospitalization risks of the SIGNUM cohort retrospectively until 2016 and 2018 respectively. A wide cohort of military personnel never deployed abroad (n = 114,260) and the general Italian population were used as control populations in risk assessment. Causes of death and diagnoses of hospitalization were derived through deterministic record linkage with official national databases of mortality and hospital discharge. Standardized Mortality Ratio (SMR) and Standardized Hospitalization Ratio (SHR) were computed adjusting according to sex, age, area of birth, and calendar year. Differential pre-post deployment in xenobiotics concentrations and early effect biomarkers (oxidative DNA alterations and micronuclei) measured in blood serum were analysed in relation to cancer hospitalization. RESULTS: Mortality risk due to pathologies was more than halved compared to the general population (SMR = 0.41, 95% CI 0.11-1.05) and not significantly different compared to soldiers never deployed abroad (SMR = 0.69, 95% CI 0.19-1.68). Similarly overall hospitalization risk due to pathologies was decreased with respect to the general population (SHR = 0.86, 95% CI 0.80-0.92) and comparable to the control military group (SHR = 0.99, 95% CI: 0.93-1.06). For haematological cancers a decreased hospitalization risk compared to the Italian general population was observed (SHR = 0.38, 95% CI 0-0.92). No statistically significant differences emerged in the patterns of biomarkers in association with cancer hospitalization. CONCLUSION: The study confirms the so called 'healthy warrior' effect for the SIGNUM veterans and showed no correlation between cancer occurrence and biomonitoring markers measured on field.

Treating disease progression with osimertinib in EGFR-mutated non-small-cell lung cancer: novel targeted agents and combination strategies.

A precision medicine approach has been successfully applied in medical oncology for the treatment of non-small-cell lung cancer (NSCLC) through the identification of targetable driver molecular aberrations; activating mutations of epidermal growth factor receptor (EGFR) are the most common. Osimertinib, a third-generation, wild-type sparing, irreversible EGFR tyrosine kinase inhibitor (TKI), originally showed a striking activity after progression to first- and second-generation EGFR-TKIs when T790M resistance mutation was identified. Thereafter, upfront use of osimertinib became the standard of care based on overall survival benefit over first-generation TKIs erlotinib and gefitinib as reported in the FLAURA trial. For patients progressing on osimertinib, identification of resistance mechanisms is crucial to develop novel targeted therapeutic approaches. Moreover, innovative drugs or combination therapies are being developed for cases in which a specific resistance mechanism is not identifiable. In this review, the post-osimertinib treatment options for EGFR-mutated NSCLC are analyzed, with an outlook to ongoing clinical trials. An algorithm to guide clinicians in managing progression on osimertinib is proposed.

Nanoscale lattice dynamics in hexagonal boron nitride moiré superlattices.

Twisted two-dimensional van der Waals (vdW) heterostructures have unlocked a new means for manipulating the properties of quantum materials. The resulting mesoscopic moiré superlattices are accessible to a wide variety of scanning probes. To date, spatially-resolved techniques have prioritized electronic structure visualization, with lattice response experiments only in their infancy. Here, we therefore investigate lattice dynamics in twisted layers of hexagonal boron nitride (hBN), formed by a minute twist angle between two hBN monolayers assembled on a graphite substrate. Nano-infrared (nano-IR) spectroscopy reveals systematic variations of the in-plane optical phonon frequencies amongst the triangular domains and domain walls in the hBN moiré superlattices. Our first-principles calculations unveil a local and stacking-dependent interaction with the underlying graphite, prompting symmetry-breaking between the otherwise identical neighboring moiré domains of twisted hBN.