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Clathrin-mediated endocytosis is an essential cellular pathway that enables signaling and recycling of transmembrane proteins and lipids. During endocytosis, dozens of cytosolic proteins come together at the plasma membrane, assembling into a highly interconnected network that drives endocytic vesicle biogenesis. Recently, multiple groups have reported that early endocytic proteins form flexible condensates, which provide a platform for efficient assembly of endocytic vesicles. Given the importance of this network in the dynamics of endocytosis, how might cells regulate its stability? Many receptors and endocytic proteins are ubiquitylated, while early endocytic proteins such as Eps15 contain ubiquitin-interacting motifs. Therefore, we examined the influence of ubiquitin on the stability of the early endocytic protein network. In vitro, we found that recruitment of small amounts of polyubiquitin dramatically increased the stability of Eps15 condensates, suggesting that ubiquitylation could nucleate endocytic assemblies. In live-cell imaging experiments, a version of Eps15 that lacked the ubiquitin-interacting motif failed to rescue defects in endocytic initiation created by Eps15 knockout. Furthermore, fusion of Eps15 to a deubiquitylase enzyme destabilized nascent endocytic sites within minutes. In both in vitro and live-cell settings, dynamic exchange of Eps15 proteins, a measure of protein network stability, was decreased by Eps15-ubiquitin interactions and increased by loss of ubiquitin. These results collectively suggest that ubiquitylation drives assembly of the flexible protein network responsible for catalyzing endocytic events. More broadly, this work illustrates a biophysical mechanism by which ubiquitylated transmembrane proteins at the plasma membrane could regulate the efficiency of endocytic internalization.

Abstract Specificity of a T cell receptor (TCR) is determined by the combination of its interactions to the peptide and human leukocyte antigen (HLA). TCR-based therapeutic molecules have to date targeted a single peptide in the context of a single HLA allele. Some peptides are presented on multiple HLA alleles, and by engineering TCRs for specific recognition of more than one allele, there is potential to expand the targetable patient population. Here, as a proof of concept, we studied two TCRs, S2 and S8, binding to the PRAME peptide antigen (ELFSYLIEK) presented by HLA alleles HLA-A*03:01 and HLA-A*11:01. By structure-guided affinity maturation targeting a specific residue on the HLA surface, we show that the affinity of the TCR can be modulated for different alleles. Using a combination of affinity maturation and functional T cell assay, we demonstrate that an engineered TCR can target the same peptide on two different HLA alleles with similar affinity and potency. This work highlights the importance of engineering alloselectivity for designing TCR based therapeutics suitable for differing global populations.

Abstract Background With the global increase in the older adults population, understanding factors that impact their quality of life is crucial. The perception of aging and self-efficacy are significant factors affecting older adults health outcomes. This descriptive cross-sectional study investigates the relationship between Aging Perception and self-efficacyamong older adults individuals in Birjand city, a demographic that is rapidly increasing but under-research. Methods This cross-sectional study was conducted from September 2022 to September 2023 on 400 older adults individuals in Birjand city. Participants were selected using a random sampling method from four regions, ensuring a representative sample. Data were collected through two main questionnaires: the Shortened Perceived Aging Questionnaire (SPAQ) and the General Self-Efficacy Questionnaire (GSE), both validated for the Persian-speaking population. Statistical analysis was performed using SPSS SOFTWARE. ARMONK, NY: IBM CORP. version 26, employing nonparametric tests due to the non-normal distribution of data. Results The study found a strong positive correlation between Aging Perception and self-efficacy (Spearman’s R = 0.79, p

Abstract Background The St. George’s Respiratory Questionnaire (SGRQ) and its idiopathic pulmonary fibrosis (IPF) version (SGRQ-I) are widely used to assess health-related quality of life in IPF. However, the psychometric properties of these questionnaires in the IPF population have not been thoroughly evaluated. This systematic review assessed and summarized the available evidence on the psychometric properties of the SGRQ and SGRQ-I in IPF patients. Methods Seven electronic databases were searched to identify relevant studies. The eligibility criteria included full-text studies focusing on the psychometric properties of the SGRQ and SGRQ-I in patients with IPF. The risk of bias, criteria for good measurement properties, and strength of evidence were assessed based on the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). The inverse-variance heterogeneity (IVhet) model was used to pool results for construct validity. Results A total of 24 studies were included; 19 assessed the psychometric properties of the SGRQ, and seven evaluated the SGRQ-I. Structural validity was assessed in one study for the SGRQ-I. Most domains of the SGRQ and SGRQ-I, except for the symptom domain of the SGRQ, had acceptable internal consistency. Both questionnaires demonstrated adequate test–retest reliability, known-groups validity, and responsiveness. Regarding construct validity, there were moderate to strong correlations with respiratory-specific measures, yet weaker correlations were observed with pulmonary function tests. Interpretability analysis revealed minor floor and ceiling effects. Conclusion The SGRQ and SGRQ-I have the potential to capture essential dimensions of health-related quality of life (HRQoL) in IPF. However, further research should focus on ensuring that the items and domains of these questionnaires truly reflect the unique challenges and experiences faced by patients with IPF through content validity studies.

Membrane curvature is essential to diverse cellular functions. While classically attributed to structured domains, recent work illustrates that intrinsically disordered proteins are also potent drivers of membrane bending. Specifically, repulsive interactions among disordered domains drive convex bending, while attractive interactions drive concave bending, creating membrane-bound, liquid-like condensates. How might disordered domains that contain both repulsive and attractive domains affect curvature? Here, we examined chimeras that combined attractive and repulsive interactions. When the attractive domain was closer to the membrane, its condensation amplified steric pressure among repulsive domains, leading to convex curvature. In contrast, when the repulsive domain was closer to the membrane, attractive interactions dominated, resulting in concave curvature. Further, a transition from convex to concave curvature occurred with increasing ionic strength, which reduced repulsion while enhancing condensation. In agreement with a simple mechanical model, these results illustrate a set of design rules for membrane bending by disordered proteins.

Abstract Due to its involvement in physiological and pathological processes, histone deacetylase 6 (HDAC6) is considered a promising pharmaceutical target for several neurological manifestations. However, the exact regulatory role of HDAC6 in the central nervous system (CNS) is still not fully understood. Hence, using a semi-automated literature screening technique, we systematically collected HDAC6-protein interactions that are experimentally validated and reported in the CNS. The resulting HDAC6 network encompassed 115 HDAC6-protein interactions divided over five subnetworks: (de)acetylation, phosphorylation, protein complexes, regulatory, and aggresome-autophagy subnetworks. In addition, 132 indirect interactions identified through HDAC6 inhibition were collected and categorized. Finally, to display the application of our HDAC6 network, we mapped transcriptomics data of Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis on the network and highlighted that in the case of Alzheimer’s disease, alterations predominantly affect the HDAC6 phosphorylation subnetwork, whereas differential expression within the deacetylation subnetwork is observed across all three neurological disorders. In conclusion, the HDAC6 network created in the present study is a novel and valuable resource for the understanding of the HDAC6 regulatory mechanisms, thereby providing a framework for the integration and interpretation of omics data from neurological disorders and pharmacodynamic assessments.

Aneurysms rarely present with features of ischemic stroke. The data on treatment of such strokes is limited. We present a case of multiple aneurysms and an ischemic stroke caused by distal anterior cerebral artery (DACA) aneurysm treated with flow diverter placement, the first case of endovascular treatment of DACA aneurysmal ischemic stroke reported to our knowledge.

Food deserts in low-income and underserved communities pose a significant challenge to ac- cessing healthy, affordable food, leading to poor health outcomes for residents. This project aimed to address this issue by examining the benefits and barriers that arise from connect- ing a student-run community garden (SRCG) with student-run free health clinics (SRFCs) to provide low-income patients with access to sustainable food and nutritional education. Using a case study research model, the study focused on investigating the organizational structure and potential mismatches between the two kinds of student-run systems. Birnbaum’s Higher Education Organization Framework (1992) was utilized to analyze how loosely and tightly coupled organizations can affect the success of collaboration. Vignettes were developed based on participants' observational experiences, and lessons were derived from fields and discussions with participants. The study identified several organizational barriers that complicated the re- lationships between student-run organic gardens and student-run free clinics. The SRCG was a loosely coupled organization with little centralized cybernetic control, and the lack of orga- nizational structure in SRCGs made it challenging to use SRFCs as outlets for providing fresh food to patients in the free clinics. Although connecting SRCGs and SRFCs shows promise for increasing food access and promoting health, the study found that it remains challeng- ing to use gardens as food production systems without creating a more cybernetically con- trolled structure in the SRCGs. By analyzing the benefits and barriers that arise from connecting these two organizations, this project sheds light on the potential of student-led initiatives to address health disparities and promote sustainable food systems in underserved communities.

Abstract The high mortality rate of colon cancer indicates the insufficient efficacy of current chemotherapy. Thus, the discussion on engineered metal nanoparticles in the treatment of the disease has been considered. In this study, silver nanoparticles were functionalized with glutamine and conjugated with thiosemiccarbazide. Then, anticancer mechanism of Ag@Gln-TSC NPs in a colon cancer cell line (SW480) was investigated. Characterizing Ag@Gln-TSC NPs by FT-IR, XRD, EDS-mapping, DLS, zeta potential, and SEM and TEM microscopy revealed that the Ag@Gln-TSC NPs were correctly synthesized, the particles were spherical, with surface charge of − 27.3 mV, high thermal stability and low agglomeration level. Using MTT assay we found that Ag@Gln-TSC NPs were significantly more toxic for colon cancer cells than normal fibroblast cells with IC50 of 88 and 186 µg/mL, respectively. Flow cytometry analysis showed that treating colon cancer cells with Ag@Gln-TSC NPs leads to a considerable increase in the frequency of apoptotic cells (85.9% of the cells) and increased cell cycle arrest at the S phase. Also, several apoptotic features, including hyperactivity of caspase-3 (5.15 folds), increased expression of CASP8 gene (3.8 folds), and apoptotic nuclear alterations were noticed in the nanoparticle treated cells. Furthermore, treating colon cancer cells with Ag@Gln-TSC NPs caused significant down-regulation of the HULC Lnc-RNA and PPFIA4 oncogene by 0.3 and 0.6 folds, respectively. Overall, this work showed that Ag@Gln-TSC NPs can effectively inhibit colon cancer cells through the activation of apoptotic pathways, a feature that can be considered more in studies in the field of colon cancer treatment.

IntroductionCataract is the leading cause of blindness among the elderly worldwide. Twin and family studies support an important role for genetic factors in cataract susceptibility with heritability estimates up to 58%. To date, 55 loci for cataract have been identified by genome-wide association studies (GWAS), however, much work remains to identify the causal genes. Here, we conducted a transcriptome-wide association study (TWAS) of cataract to prioritize causal genes and identify novel ones, and examine the impact of their expression.MethodsWe performed tissue-specific and multi-tissue TWAS analyses to assess associations between imputed gene expression from 54 tissues (including 49 from the Genotype Tissue Expression (GTEx) Project v8) with cataract using FUSION software. Meta-analyzed GWAS summary statistics from 59,944 cataract cases and 478,571 controls, all of European ancestry and from two cohorts (GERA and UK Biobank) were used. We then examined the expression of the novel genes in the lens tissue using the iSyTE database.ResultsAcross tissue-specific and multi-tissue analyses, we identified 99 genes for which genetically predicted gene expression was associated with cataract after correcting for multiple testing. Of these 99 genes, 20 (AC007773.1, ANKH, ASIP, ATP13A2, CAPZB, CEP95, COQ6, CREB1, CROCC, DDX5, EFEMP1, EIF2S2, ESRRB, GOSR2, HERC4, INSRR, NIPSNAP2, PICALM, SENP3, and SH3YL1) did not overlap with previously reported cataract-associated loci. Tissue-specific analysis identified 202 significant gene-tissue associations for cataract, of which 166 (82.2%), representing 9 unique genes, were attributed to the previously reported 11q13.3 locus. Tissue-enrichment analysis revealed that gastrointestinal tissues represented one of the highest proportions of the Bonferroni-significant gene-tissue associations (21.3%). Moreover, this gastrointestinal tissue type was the only anatomical category significantly enriched in our results, after correcting for the number of tissue donors and imputable genes for each reference panel. Finally, most of the novel cataract genes (e.g., Capzb) were robustly expressed in iSyTE lens data.DiscussionOur results provide evidence of the utility of imputation-based TWAS approaches to characterize known GWAS risk loci and identify novel candidate genes that may increase our understanding of cataract etiology. Our findings also highlight the fact that expression of genes associated with cataract susceptibility is not necessarily restricted to lens tissue.

Risk assessment is utilized to prioritize preventive measures based on the probability of dispersal success of pests. A main part of the risk assessment procedure is to determine the effects of environmental variables on the current and potential geographical distributions. In the present study, the spatial distribution of the Mediterranean pine engraver, Orthotomicus erosus (Wollaston), was mapped and predicted using MaxEnt. Presence records of O. erosus (north, northeast, west and centre of Iran), environmental and topographic variables, with the lowest correlations among themselves and the highest effects on the pest distribution were used. A total of 76 presence records of O. erosus were collected. The results of the distribution prediction modelling revealed that the northern part of Iran and the areas along the Zagros are the most suitable habitats for this species. Examining environmental variable importance on the distribution of O. erosus showed that the variables related to temperature and precipitation had more contribution in the MaxEnt model, respectively than the altitude. Furthermore, the high accuracy of the model (0.928) indicated that the MaxEnt had an acceptable performance for the prediction of O. erosus distribution. These findings would provide primary and critical information about the potential distribution of O. erosus in Iran, which could be effective for the stable population regulation of this destructive pest.

Background: Augmenting auditory feedback through an error-augmentation paradigm could facilitate the perception and correction of gait asymmetry in stroke survivors, but how such a paradigm should be tailored to individual asymmetry profiles remains unclear. Before implementing the paradigm in rehabilitation, we need to investigate the instantaneous effects of distorted footstep sound feedback on gait symmetry in healthy young adults. Methods: Participants (n = 12) walked on a self-paced treadmill while listening to their footstep sounds, which were distorted unilaterally according to five conditions presented randomly: small delay; small advance; large delay; large advance; or unmodified (control). The primary outcomes were swing time ratio (SWR) and step length ratio (SLR). Secondary outcomes included walking speed, bilateral swing time, step length, and maximum toe height, as well as hip, knee, and ankle angle excursions. Results: SWR (p < 0.001) but not SLR (p ≥ 0.05) was increased in all distorted feedback conditions compared to the control condition. Increased swing time on the perturbed side ipsilateral to feedback distortion was observed in the advanced conditions (p < 0.001), while swing time increased bilaterally in the delayed conditions (p < 0.001) but to a larger extent on the unperturbed side contralateral to feedback distortion. Increases in swing time were accompanied by larger maximum toe height as well as larger hip and knee joint excursions (p < 0.05 to p < 0.001). No differences in any outcomes were observed between small and large feedback distortion magnitudes. Conclusions: Distorted footstep sound feedback successfully elicits adaptation in temporal gait symmetry (SWR), with distinct modulation patterns for advanced vs. delayed footstep sounds. Spatial symmetry (SLR) remains unaltered, likely because auditory feedback primarily conveys temporal information. This research lays the groundwork to implement personalized augmented auditory feedback in neurorehabilitation.

Abstract This study presents the optimization of the heat transfer coefficient of a micro bare tube heat exchanger. A physical and mathematical model of a micro bare tube heat exchanger was built in Matlab using the simplified ε‐number of transfer unit method. Using a temperature of minus 30°C and a 0.5–1.0 mm tube outer diameter, a 1.7–8.0 mm longitudinal tube pitch, a 1.7–5 mm transverse tube pitch, and a 1.0–5.0 m/s velocity at minimum free flow area, with carbon dioxide as the refrigerant, a comparative variation analysis was performed to optimize the heat transfer coefficient of a micro‐bare‐tube heat exchanger. The results demonstrate that the heat transfer coefficient increases as the inlet air velocity is increased from 1.0 to 5.0 m/s, with a final gain of 93.17%. The growth rate of the heat transfer coefficient steadily decreases with increasing inlet air velocity and gradually approaches zero. The effect of the gradual decrease of the tube outer diameter from 1.0 to 0.5 mm on the heat transfer coefficient is 22.52% greater than that of the gradual decrease of the transverse tube pitch from 2.2 to 1.7 mm. The study also carried out an optimization analysis on the distribution of four different variables in the heat exchanger. With the use of a genetic algorithm, the study found an optimal distribution to maximize the heat transfer coefficient. The following parameter values resulted in the maximum heat transfer coefficient: a maximum inlet air velocity of 5.0 m/s, a minimum tube outer diameter of 0.5 mm, a 1.7 mm longitudinal tube pitch, and a 1.7 mm transverse tube pitch.

Objective: To determine whether a resident's medical school ranking predicts their scholarship during residency. Design: The authors stratified ophthalmology residents in ACGME accredited programs into tiers based off their medical school background's US News & World Report ranking: T1 (schools 1–20), T2 (21–50), and T3 (51–90). Investigators queried PubMed and Scopus for number of total publications, first/second author publications, publications in the top 10 impact factor journals in ophthalmology, and publications with the senior author affiliated with the resident's residency program/medical school. Authors collected data from start of ophthalmology residency to December 5th, 2021, and performed Pearson chi squared, ANOVA, Eta squared, Tukey, and multivariable logistic regression tests. Results: 1054 residents were included for analysis, with 370 from T1 schools, 296 from T2 schools, and 388 from T3 schools. T3 residents had a significantly decreased likelihood of publishing at least one (OR = 0.659;95%CI = 0.481,0.905;p = .010), two (OR = 0.643;95%CI = 0.436,0.949;p = .026), or five (OR = 0.407;95%CI = 0.187,0.886;p = .024) total publications compared to T1 residents. T3 residents also were partially predicted to publish fewer first author works, high impact journal articles, and articles with senior authors affiliated with their medical school. T2 residents were more likely to publish at least one second author work than T1 residents (OR = 1.604;95%CI = 1.101,2.337;p = .014). There was no significant difference between tiers in publications with senior authors affiliated with the same residency program. Conclusions: The authors observed little difference in scholarship between residents from T1 and T2 schools, but some differences may exist between T3 and T1/T2 residents. Merit of rankings should be further explored.

Abstract Background The significant role of red blood cell distribution width (RDW) and D‐Dimer as prognostic factors in patients with some blood malignancies has been reported recently. Aim We designed and performed a meta‐analysis to investigate the prognostic roles of RDW and D‐Dimer in subjects with diffuse large B‐cell lymphoma (DLBCL). Materials and Methods We systematically reviewed PubMed‐Medline, SCOPUS, EMBASE, Web of Science Core Collection, and Google Scholar up to the present to look for publications on prognostic effects of RDW and D‐Dimer in DLBCL patients. For investigation of the associations between RDW and D‐Dimer with the overall survival (OS) and progression‐free survival (PFS) of the DLBCL cases, hazard ratio (HR) with 95% confidence intervals (CIs) was used. Results We included 13 eligible studies in the present meta‐analysis. The results of pooled analysis showed that increased levels of RDW was related to poor OS (HR = 2.01, 95% CI: 1.62–2.48, p value

The Mediterranean pine engraver, Orthotomicus erosus (Wollaston) (Col.: Curculionidae: Scolytinae), is a destructive bark beetle in pine forests worldwide. Regarding the recent outbreak of O. erosus in Iran, its flight activity and population density were monitored in four contaminated sites in western Tehran. These four sampling sites included Tabiat Park, Khargush Darreh Forest Park, Chitgar Park behind Bam Riding Club as well as Chitgar Park 9th Aghaghiya Street (western Tehran). Two pheromone traps (ECONEX ORTHOTOMICUS EROSUS 60 DAYS pheromone, Spain) were installed in each sampling site at the height of 2.5 m in the south direction of the pine trees. The number of trapped adults was recorded at 10-day intervals from April 2019 to March 2020. In total, 8514 adults of O. erosus were collected using pheromone traps during the sampling period. The results showed that the adult flight started from April in four sampling sites. The flight periods of adults continued until November in Tabiat Park, Khargush Darreh Forest Park, and Chitgar Park, behind Bam Riding Club. Differently, the last adults were collected in October in Chitgar Park, 9th Aghaghiya Street. In addition, the flight peaks of O. erosus occurred in August in Tabiat Park, Khargush Darreh Forest Park, and Chitgar Park, behind Bam Riding Club. However, the highest number of adults were trapped in July in Chitgar Park, 9th Aghaghiya Street. Based on our results, the number of trapped adults was significantly different in sampling sites. The mean number of trapped adults was the highest (183.25 ± 0.11) in Chitgar Park, 9th Aghaghiya Street and lowest (106.32 ± 0.07) in Tabiat Park during the whole monitoring experiment. These findings on flight activity and population fluctuation of O. erosus in local conditions could be helpful to establish an efficient and successful management program for this destructive pest.

Rahul G Sangani,1 Vishal Deepak,1 Javeria Anwar,1 Zalak Patel,2 Andrew J Ghio3 1Section of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, West Virginia University, Morgantown, WV, USA; 2Department of Radiology, West Virginia University, Morgantown, WV, USA; 3US EPA, Chapel Hill, NC, USACorrespondence: Rahul G Sangani, Section of Pulmonary, Critical Care, and Sleep Medicine, West Virginia University School of Medicine, 1 Medical Center Dr, PO BOX 9166, Morgantown, WV, 26506, USA, Tel +1 304 293-4661 option &num;2, Fax +1 304-293-3724, Email rgsangani@hsc.wvu.eduBackground: Cigarette smoking (CS)-related monocytosis contributes to the development of chronic lung injuries via complex mechanisms. We aim to determine correlations between measures of CS and monocytes, their capacities to predict chronic lung diseases, and their associations with mortality.Methods: A single-center retrospective study of patients undergoing surgical resection for suspected lung nodules/masses was performed. CS was quantified as cigarettes smoked per day (CPD), duration of smoking, composite pack years (CPY), current smoking status, and smoking cessation years. A multivariate logistic regression analysis was performed.Results: Of 382 eligible patients, 88% were ever smokers. In this group, 45% were current smokers with mean CPD of 27.2± 40.0. CPY and duration of smoking showed positive linear correlations with percentage monocyte count. Physiologically, CPY was associated with progressive obstruction, hyperinflation, and reduced diffusion capacity (DLCO). Across the quartiles of smoking, there was an accumulation of radiologic and histologic abnormalities. Anthracosis and emphysema were associated with CPD, while lung cancer, respiratory bronchiolitis (RB), emphysema, and honeycombing were statistically related to duration of smoking. Analysis using consecutive CPY showed associations with lung cancer (≥ 10 and < 30), fibrosis (≥ 20 and < 40), RB (≥ 50), anthracosis and emphysema (≥ 10 and onwards). Percentage monocytes correlated with organizing pneumonia (OP), fibrosis, and emphysema. The greater CPY increased mortality across the groups. Significant predictors of mortality included percentage monocyte, anemia, GERD, and reduced DLCO.Conclusion: Indices of CS and greater monocyte numbers were associated with endpoints of chronic lung disease suggesting a participation in pathogenesis. Application of these easily available metrics may support a chronology of CS-induced chronic lung injuries. While a relative lesser amount of smoking can be associated with lung cancer and fibrosis, greater CPY increases the risk for emphysema. Monocytosis predicted lung fibrosis and mortality. Duration of smoking may serve as a better marker of monocytosis and associated chronic lung diseases.Keywords: smoking, monocyte, pulmonary fibrosis, lung cancer, mortality, emphysema

Background: Peribronchiolar metaplasia (PBM) is considered a reaction to injury characterized by the proliferation of bronchiolar epithelium into immediately adjacent alveolar walls. While an association of PBM with diffuse interstitial lung diseases has been recognized, the clinical significance of PBM remains uncertain. Methods: A cohort (n = 352) undergoing surgical resection of a lung nodule/mass in a rural area was retrospectively reviewed. Multivariate logistic regression analysis was performed to determine the association of PBM with clinical, physiological, radiographic, and histologic endpoints. Results: In the total study cohort, 9.1% were observed to have PBM as a histologic finding in resected lung tissue (n = 32). All but one of these patients with PBM were ever-smokers with a median of 42 pack years. Clinical COPD was diagnosed in two-thirds of patients with PBM. Comorbid gastroesophageal reflux disease (GERD) was significantly associated with PBM. All patients with PBM demonstrated radiologic and histologic evidence of emphysema. Measures of pulmonary function were not impacted by PBM. Mortality was not associated with the histologic observation of PBM. In a logistic regression model, centrilobular-ground glass opacity interstitial lung abnormality and traction bronchiectasis on the CT scan of the chest and histologic evidence of fibrosis, desquamative interstitial pneumonia and anthracosis all strongly predicted PBM in the cohort. Conclusion: A constellation of radiologic and histologic smoking-related abnormalities predicted PBM in study cohort. This confirms a co-existence of lung tissue responses to smoking including PBM, emphysema, and fibrosis. Acknowledging the physiologically “silent” nature of small airway dysfunction on pulmonary function testing, our findings support PBM as a histologic marker of small-airway injury associated with cigarette smoking.

Raven's advanced progressive matrices (APM) comprise two types of representational codes, namely visuo-spatial and verbal-analytical, that are used to solve APM puzzles. Studies using analytical, behavioral, and imaging methods have supported the multidimensional perspectives of APM puzzles. The visuo-spatial code is expected to recruit operations more responsive to the visual perception tasks. In contrast, the verbal-analytical code is expected to use operations more responsive to the logical reasoning task and may entail different cognitive strategies. Acknowledging different representational codes used in APM puzzle-solving is critical for a better understanding of APM's performance and their relationship with other tasks, especially creative reasoning. We used the eye-tracking method to investigate the role of two representational codes, visuo-spatial and verbal-analytical, in strategies involved in solving APM puzzles and in generating an APM-like puzzle by using a creative-reasoning task (CRT). Participants took longer time to complete the verbal-analytical than visuo-spatial puzzles. In addition, visuo-analytical than visual-spatial puzzles showed higher progressive and regressive saccade counts, suggesting the use of more response elimination than constructive matching strategies employed while solving verbal-analytical than visuo-spatial puzzles. We observed higher CRT scores when it followed verbal-analytical (Mdn = 84) than visuo-spatial (Mdn = 73) APM puzzles, suggesting puzzle-solving specific strategies affect puzzle-creating task performance. The advantage of verbal-analytical over visuo-spatial puzzle-solving has been discussed in light of shared cognitive processing between APM puzzle-solving and APM-like puzzle-creating task performance.

Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.

Background and Objectives: Alveolar rupture following increased transalveolar pressure on positive pressure ventilation is associated with pulmonary barotrauma (PB). The spectrum varies from pneumothorax, pneumomediastinum, pneumopericardium, pneumoperitoneum, retro-pneumoperitoneum and subcutaneous emphysema. We studied the incidence of PB and their clinical characteristics in patients with coronavirus disease 19 (COVID-19)-associated acute respiratory failure. Methods: Patients aged >18 years with COVID-19-associated acute respiratory distress syndrome were included in the study. We recorded demographics (age, gender, comorbidities), severity scores (APACHE II on admission, SOFA on the day of barotrauma), type of PB and outcomes at discharge from the hospital. Patient characteristics are descriptively reported. Survival analysis was done using Kaplan–Meier survival tests after classifying by various factors. Survival was compared using the log-rank test. Results: Thirty-five patients experienced PB. Eighty per cent of patients in this cohort were males with mean age of 55.89 years. The commonest comorbidities were diabetes mellitus and hypertension. Twelve spontaneously breathing patients developed barotrauma. Eight patients experienced sequential events. In all, 18 patients required insertion of pigtail catheters. The median survival time in patients was 37 days (95% CI: 25–49 days). The overall survival rate was 34.3%. Mean serum ferritin levels were six times upper limit of normal in deceased, reflecting the severity of lung involvement. Conclusion: A high incidence of PB was noted following severe acute respiratory syndrome coronavirus (SARS CoV-2) infection even in the non-ventilated patients, a consequence of SARS CoV-2 effects on the pulmonary parenchyma causing widespread lung injury.

Moiré superlattices offer a rich platform fort the study of correlated and topological phases. Here, by using low-temperature magneto-transport measurements, the authors demonstrate electric-field induced switching between Chern states in twisted double-layer graphene in the Hofstadter regime.