Miracle-dz/UniFAR-FTUs huggingface dataset:
Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease

Rationale: Persistent pulmonary sequelae are evident in many survivors of acute coronavirus disease 2019 (COVID-19) but the molecular mechanisms responsible are incompletely understood. Post-COVID radiological lung abnormalities comprise two broad categories, organising pneumonia and reticulation, interpreted as indicative of subacute inflammation and fibrosis, respectively. Whether these two patterns represent distinct pathologies, likely to require different treatment strategies is not known. Objectives: We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and fibrosis. Methods: We compared single-cell transcriptomic profiles and T cell receptor (TCR) repertoires of bronchoalveolar cells obtained from convalescent individuals with each radiological pattern of post-COVID lung disease (PCLD). Measurements and Main Results: Inflammatory and fibrotic PCLD single-cell transcriptomes closely resembled each other across all cell types. However, CD4 central memory T cells (TCM) and CD8 effector memory T cells (TEM) were significantly more abundant in inflammatory PCLD. A greater proportion of CD4 TCM also exhibited clonal expansion in inflammatory PCLD. High levels of clustering of similar TCRs from multiple donors was a striking feature of both PCLD phenotypes, consistent with tissue localised antigen-specific immune responses, but there was no enrichment for known SARS-CoV-2 reactive TCRs. Conclusions: There is no evidence that radiographic organising pneumonia and reticulation in PCLD are associated with differential immmunopathological pathways. Inflammatory radiology is characterised by greater bronchoalveolar T cell accumulation. Both groups show evidence of shared antigen-specific T cell responses, but the antigenic target for these T cells remains to be identified.
Patient engagement in research; benefits, challenges, importance, and implications

Objective Patient engagement (PE) and patient-oriented research have begun to reshape the thought process behind conducting research with the aim of maximizing the relevance of findings for patients. This study aimed to examine the perceived benefits, challenges, importance, and implications of patient engagement from the perspectives of sarcoma patient advisors and researchers. Methods This study utilized a mixed model design. Qualitative data was collected through two focus group discussions with sarcoma patients. Quantitative data was collected via a survey containing Likert scale questions completed by the Centre for Evidence-Based Orthopaedics Musculoskeletal Oncology research team at McMaster University. Results Results showed that patients value the opportunity to contribute to research and support future patients. Being a patient advisor also creates a sense of community and fosters support through building connections and communicating with other patients. Members of the research team noted that patient engagement is important for the study of patient relevant topics and provides insight into the improvement of patient care. However, an added challenge is the lack of current guidance surrounding the implementation of patient engagement. Conclusion These findings emphasize the potential value of patient engagement while also highlighting the need for further research into best practices for the implementation of patient engagement efforts. Overall, patient engagement is an essential area in need of further exploration to enhance future research and clinical trials.
Recovery of inhibitory control prefrontal cortex function in inpatients with heroin use disorder: a 15-week longitudinal fMRI study

Importance: Heroin addiction and related mortality impose a devastating toll on society, with little known about the neurobiology of this disease or its treatment. Poor inhibitory control is a common manifestation of prefrontal cortex (PFC) impairments in addiction, and its potential recovery following treatment is largely unknown in heroin (or any drug) addiction. Objective: To study inhibitory control brain activity in iHUD and HC, before and after 15 weeks of inpatient treatment in the former. Design: A longitudinal cohort study (11/2020-03/2022) where iHUD and HC underwent baseline and follow-up fMRI scans. Average follow-up duration: 15 weeks. Setting: The iHUD and HC were recruited from treatment facilities and surrounding neighborhoods, respectively. Participants: Twenty-six iHUD [mean=40.6, sd=10.1 years; 7 (29.2%) women] and 24 age-/sex-matched HC [mean=41.1, sd=9.9 years; 9 (37.5%) women]. Intervention: Following the baseline scan, inpatient iHUD continued to participate in a medically-assisted program for an average of 15 weeks [abstinence increased from an initial 183 (sd=236) days by 65 (sd=82) days]. The HC were scanned at similar time intervals. Main Outcomes and Measures: Behavioral performance as measured by the stop-signal response time (SSRT), target detection sensitivity (d-prime, proportion of hits in go vs. false-alarms in stop trials), and brain activity (blood-oxygen level dependent signal differences) during successful vs. failed stops in the stop signal task. Results: As we previously reported, at time 1 and as compared to HC, iHUD exhibited similar SSRT but impaired d-prime [t(38.7)=2.37, p=. 023], and lower anterior and dorsolateral PFC (aPFC, dlPFC) activity (p<.001). Importantly, at time 2, there were significant gains in aPFC and dlPFC activity in the iHUD (group*session interaction, p=.002); the former significantly correlated with increases in d-prime specifically in iHUD (p=.012). Conclusions and Relevance: Compared to HC, the aPFC and dlPFC impairments in the iHUD at time 1 were normalized at time 2, which was associated with individual differences in improvements in target detection sensitivity. For the first time in any drug addiction, these results indicate a treatment-mediated inhibitory control brain activity recovery. These neurobehavioral results highlight the aPFC and dlPFC as targets for intervention with a potential to enhance self-control recovery in heroin addiction.
Risk assessment of N‐nitrosamines in food

Abstract EFSA was asked for a scientific opinion on the risks to public health related to the presence of N‐nitrosamines (N‐NAs) in food. The risk assessment was confined to those 10 carcinogenic N‐NAs occurring in food (TCNAs), i.e. NDMA, NMEA, NDEA, NDPA, NDBA, NMA, NSAR, NMOR, NPIP and NPYR. N‐NAs are genotoxic and induce liver tumours in rodents. The in vivo data available to derive potency factors are limited, and therefore, equal potency of TCNAs was assumed. The lower confidence limit of the benchmark dose at 10% (BMDL10) was 10 μg/kg body weight (bw) per day, derived from the incidence of rat liver tumours (benign and malignant) induced by NDEA and used in a margin of exposure (MOE) approach. Analytical results on the occurrence of N‐NAs were extracted from the EFSA occurrence database (n = 2,817) and the literature (n = 4,003). Occurrence data were available for five food categories across TCNAs. Dietary exposure was assessed for two scenarios, excluding (scenario 1) and including (scenario 2) cooked unprocessed meat and fish. TCNAs exposure ranged from 0 to 208.9 ng/kg bw per day across surveys, age groups and scenarios. ‘Meat and meat products’ is the main food category contributing to TCNA exposure. MOEs ranged from 3,337 to 48 at the P95 exposure excluding some infant surveys with P95 exposure equal to zero. Two major uncertainties were (i) the high number of left censored data and (ii) the lack of data on important food categories. The CONTAM Panel concluded that the MOE for TCNAs at the P95 exposure is highly likely (98–100% certain) to be less than 10,000 for all age groups, which raises a health concern.
H4C5 missense variant leads to a neurodevelopmental phenotype overlapping with Angelman syndrome

Recurrent de novo missense variants in H4 histone genes have recently been associated with a novel neurodevelopmental syndrome that is characterized by intellectual disability and developmental delay as well as more variable findings that include short stature, microcephaly, and facial dysmorphisms. A 4‐year‐old male with autism, developmental delay, microcephaly, and a happy demeanor underwent evaluation through the Undiagnosed Disease Network. He was clinically suspected to have Angelman syndrome; however, molecular testing was negative. Genome sequencing identified the H4 histone gene variant H4C5 NM_003545. 4: c.295T>C, p.Tyr99His, which parental testing confirmed to be de novo. The variant met criteria for a likely pathogenic classification and is one of the seven known disease‐causing missense variants in H4C5. A comparison of our proband's findings to the initial description of the H4‐associated neurodevelopmental syndrome demonstrates that his phenotype closely matches the spectrum of those reported among the 29 affected individuals. As such, this report corroborates the delineation of neurodevelopmental syndrome caused by de novo missense H4 gene variants. Moreover, it suggests that cases of clinically suspected Angelman syndrome without molecular confirmation should undergo exome or genome sequencing, as novel neurodevelopmental syndromes with phenotypes overlapping with Angelman continue to be discovered.
Electrically tunable terahertz wave modulator based on complementary metamaterial and graphene

In this paper, we design and numerically demonstrate an electrically controllable light-matter interaction in a hybrid material/metamaterial system consisting of an artificially constructed cross cut-wire complementary metamaterial and an atomically thin graphene layer to realize terahertz (THz) wave modulator. By applying a bias voltage between the metamaterial and the graphene layer, this modulator can dynamically control the amplitude and phase of the transmitted wave near 1.43 THz. Moreover, the distributions of current density show that this large modulation depth can be attributed to the resonant electric field parallel to the graphene sheet. Therefore, the modulator performance indicates the enormous potential of graphene for developing sophisticated THz communication systems.
Implementation of Lung-Protective Ventilation in Patients With Acute Respiratory Failure*

OBJECTIVES: We implemented a computerized protocol for low tidal volume ventilation (LTVV) to improve management and outcomes of mechanically ventilated patients with, and without, the acute respiratory distress syndrome (ARDS). DESIGN: Pragmatic, nonrandomized stepped wedge type II hybrid implementation/effectiveness trial. SETTING: Twelve hospitals in an integrated healthcare system over a 2-year period. PATIENTS: Patients greater than or equal to 18 years old who had initiation of mechanical ventilation in the emergency department or ICU. We excluded patients who died or transitioned to comfort care on the day of admission to the ICU. We defined a subgroup of patients with ARDS for analysis. INTERVENTIONS: Implementation of ventilator protocols for LTVV in the ICU. MEASUREMENTS AND MAIN RESULTS: Our primary clinical outcome was ventilator-free days (VFDs) to day 28. Our primary process outcome was median initial set tidal volume. We included 8,692 mechanically ventilated patients, 3,282 (38%) of whom had ARDS. After implementation, set tidal volume reported as mL/kg predicted body weight decreased from median 6.1 mL/kg (interquartile range [IQR], 6.0–6.8 mL/kg) to 6.0 mL/kg (IQR, 6.0–6.6 mL/kg) (p = 0.009). The percent of patients receiving LTVV (tidal volume ≤ 6.5 mL/kg) increased from 69.8% (n = 1,721) to 72.5% (n = 1,846) (p = 0.036) after implementation. The percent of patients receiving greater than 8 mL/kg initial set tidal volume was reduced from 9.0% (n = 222) to 6.7% (n = 174) (p = 0.005) after implementation. Among patients with ARDS, day 1 positive end-expiratory pressure increased from 6.7 to 8.0 cm H2O (p < 0.001). We observed no difference in VFD (adjusted odds ratio, 1.06; 95% CI, 0.91–1.24; p = 0.44), or in secondary outcomes of length of stay or mortality, either within the main cohort or the subgroup of patients with ARDS. CONCLUSIONS: We observed improved adherence to optimal ventilator management with implementation of a computerized protocol and reduction in the number of patients receiving tidal volumes greater than 8 mL/kg. We did not observe improvement in clinical outcomes.
Wavelet denoising and evaluation of electromyogram signal using statistical algorithm

In this study, wavelet analysis has been exercised to understand the quality of surface electromyogram signal for class separability. The surface electromyogram signals were estimated with the following steps. First, the obtained signal was decomposed using wavelet transform. The decomposed coefficients were then analysed with threshold methods. With the appropriate choice of wavelet, it is possible to remove interference noise effectively in order to analyse the signal. This paper presents a comparative study of different Daubechies wavelets (db2-db14) family for analysis of arm motions. From the analysed results, it was inferred that wavelet db4 performs denoising the best among the wavelets and is suitable for accurate classification of surface electromyogram signal. Further, one-way repeated factorial Analysis of Variance (ANOVA) statistical technique was also implemented to investigate the voluntary muscular contraction relationship for different arm movements.
Marvellous moths! pollen deposition rate of bramble (Rubus futicosus L. agg.) is greater at night than day

Widespread concerns about declines of wild pollinating insects has attracted considerable research interest, largely directed towards identifying key nectar sources and assessing the contribution of pollinators towards ecosystem services. However, previous work has almost exclusively focussed on bees and other diurnal invertebrate taxa. This study aimed to assess the relative contribution of diurnal and nocturnal insects to the pollination of bramble (Rubus fruticosus agg.), a common and widespread species aggregate across Europe, which has been identified as a key source of pollen and nectar for diurnal pollinators. Bramble flower visitation rates by diurnal and nocturnal insects were quantified by analysing over 380,000 interval photographs taken over a 3-day period across 10 sites. A pollinator exclusion experiment was also undertaken to assess the importance of diurnal and nocturnal insects for pollination by analysing pollen deposition on 480 bramble stigmas of nocturnally exposed, diurnally exposed and unvisited control flowers across all sites. Flower visitation was significantly higher during the day, comprising 83% of all visits made by a range of taxa. Nocturnal visitation was almost exclusively by moths. Crucially, pollen deposition rates of bramble were significantly higher during the night compared with the day. No relationship was detected between pollen counts and flower visitation rates, suggesting that moths are more efficient pollinators of bramble compared with diurnal insects. Overall, this work provides further evidence of the value of bramble as a resource for pollinators and demonstrates that moths likely play an important role in bramble pollination.
The Scattering of Sound from the Sea Surface

It is assumed that the equation of the sea surface is z = ζ(xyt), and that the time average Φ = 〈ζ(x′y′t)ζ(x″y″t)〉 is a function only of ξ = x″ − x′, η = y″ − y′. The scattering coefficient of long‐wave sound is calculated and shown to be σ = (c2k2/4π)2∫∫Φ(ξη) exp[−ik(aξ+bη)]dξdη, where 2π/k is the wavelength of the sound, and a, b, c are, respectively, the sum of the x, y, z direction cosines of the incident and scattered rays. For short‐wave sound, the formula is more complicated, but independent of the wavelength of the sound, as it should be. However, it is shown that experiments with short waves yield much less information about the sea surface than do those with long waves. This is unfortunate, since the latter experiments are much more difficult than the former.
CircularSTAR3D: a stack-based RNA 3D structural alignment tool for circular matching

Abstract The functions of non-coding RNAs usually depend on their 3D structures. Therefore, comparing RNA 3D structures is critical in analyzing their functions. We noticed an interesting phenomenon that two non-coding RNAs may share similar substructures when rotating their sequence order. To the best of our knowledge, no existing RNA 3D structural alignment tools can detect this type of matching. In this article, we defined the RNA 3D structure circular matching problem and developed a software tool named CircularSTAR3D to solve this problem. CircularSTAR3D first uses the conserved stacks (consecutive base pairs with similar 3D structures) in the input RNAs to identify the circular matched internal loops and multiloops. Then it performs a local extension iteratively to obtain the whole circular matched substructures. The computational experiments conducted on a non-redundant RNA structure dataset show that circular matching is ubiquitous. Furthermore, we demonstrated the utility of CircularSTAR3D by detecting the conserved substructures missed by regular alignment tools, including structural motifs and conserved structures between riboswitches and ribozymes from different classes. We anticipate CircularSTAR3D to be a valuable supplement to the existing RNA 3D structural analysis techniques.
Correcting the negativity of high-order kernel density estimators

Two methods are suggested for removing the problem of negativity of high-order kernel density estimators. It is shown that, provided the underlying density has at least moderately light tails, each method has the same asymptotic integrated squared error (ISE) as the original kernel estimator. For example, if the tails of the density decrease like a power of x-1, as x increases, then a necessary and sufficient condition for ISEs to be asymptotically equivalent is that a moment of order 1 + [epsilon] be finite for some [epsilon] > 0. The important practical conclusion to be drawn from these results is that in most circumstances, the bandwidth of the original kernel estimator may be used to good effect in the new, nonnegative estimator. A numerical study verifies that this is indeed the case, for a variety of different distributions.
CT‐guided indocyanine green and lipiodol marking of ground glass opacity before robotic‐assisted lung resection

To the Editor, We read with particular interest the article by Udelsman et al. regarding a the management of the multiple ground glass opacities (GGOs) with robotic surgery and the preoperative marking techniques. In the last few years, given the spreading of robotic surgery for the treatment of early stage non‐small cell lung cancer, the identification of the lung nodules, especially GGOs, that do not surface on the visceral pleura could be challenging. The author well reported the main techniques to mark the lesions using a single tracer. We want report a case of our CT‐guided technique of lung nodule marking using a mixture of indocyanine green (ICG) and lipiodol that could be useful during robotic surgery. The patient with a right lower pure GGO was referred to our unit in the morning and a CT‐guided dye marking was scheduled. The mixture dye marker used was composed of ICG (1cc) and lipiodol (2cc). After a local anesthesia with lidocaine, a percutaneous CT‐guided puncture of the lung nodule using a CHIBA 21 gauge needle (Biopsy Needles; M.l. Tech) was performed. Then, 1cc syringe with the marking solution was connected to the needle and it was injected around the nodule. After 10min another thoracic CT scan was repeated to visualize the marker solution around the lung nodule and to detect possible post‐procedural complications such as pneumothorax and embolism. The dye marker has remained around the nodule without evident spreading (Figure 1A). The length of the procedure was around 25min. After 2 h from the marking procedure the patient underwent surgery. Therefore, a robotic wedge resection using the Da Vinci Robotic Xi System (Intuitive Surgical Inc) followed by frozen section on the nodule was performed (Figure 1B). The frozen section showed a lepidic adenocarcinoma of the lung, then, we proceeded to the right lower lobectomy and the systematic lymphadenectomy. The main benefit of this techniques is represented by the combined use of lipiodol and ICG. The use of ICG does not cause physical problems to the patient such as dislodgement, pneumothorax and radiation exposure, and seems to be the best tracer in relation to the tissue penetration (<1 cm) compared to methylene blu. Adding the lipiodol solution, an oil‐based radiopaque contrast agent, to the ICG, reduces the diffusion of the solution into the adjacent tissue, and thereby facilitating accurate nodule localization. Besides, the use of lipiodol can facilitate the control of the marking with an additional CT scan after the injection as demonstrated by our procedure. Radiotracers could be a valid method to identify small lung nodules that do not surface the visceral pleura, as demonstrated by the authors, but during robotic surgery, the use of a probe could be troublesome. Other studies should be performed to validate this technique, but, in our opinion, could be a valid alternative to easily identify the GGO during robotic surgery.
A broad-line region origin for the iron Kα line in NGC 7213

The X-ray spectrum of NGC 7213 is known to present no evidence for Compton reflection, a unique result among bright Seyfert 1s. The observed neutral iron Kα line, therefore, cannot be associated with a Compton-thick material, like the disc or the torus, but is due to Compton-thin gas, with the broad-line region (BLR) as the most likely candidate. To check this hypothesis, a long Chandra High-Energy Transmission Grating observation, together with a quasi-simultaneous optical spectroscopic observation at the ESO NTT EMMI were performed. We found that the iron line is resolved with a full width at half-maximum (FWHM) = 2400 +1100 −600 km s −1 , in perfect agreement with the value measured for the broad component of the Hα, 2640 +110 −90 km s −1 . Therefore, NGC 7213 is the only Seyfert 1 galaxy whose iron Kα line is unambiguously produced in the BLR. We also confirmed the presence of two ionized iron lines and studied them in greater detail than before. The resonant line is the dominant component in the Fe XXV triplet, therefore suggesting an origin in collisionally ionized gas. If this is the case, the blueshift of around 1000 km s −1 of the two ionized iron lines could be the first measure of the velocity of a starburst wind from its X-ray emission.