Miracle-dz/UniFAR-FTUs huggingface dataset:
The Microbial Etiology of Community-Acquired Pneumonia in Adults: from Classical Bacteriology to Host Transcriptional Signatures

All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues to evolve as new techniques enable identification of already known organisms and as new organisms emerge. SUMMARY All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues to evolve as new techniques enable identification of already known organisms and as new organisms emerge. We now review the etiology of pneumonia (at present often called “community-acquired pneumonia”) beginning with classic bacteriologic techniques, which identified Streptococcus pneumoniae as the overwhelmingly common cause, to more modern bacteriologic studies, which emphasize Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Enterobacteriaceae, Pseudomonas, and normal respiratory flora. Urine antigen detection is useful in identifying Legionella and pneumococcus. The low yield of bacteria in recent studies is due to the failure to obtain valid sputum samples before antibiotics are administered. The use of high-quality sputum specimens enables identification of recognized (“typical”) bacterial pathogens as well as a role for commensal bacteria (“normal respiratory flora”). Nucleic acid amplification technology for viruses has revolutionized diagnosis, showing the importance of viral pneumonia leading to hospitalization with or without coinfecting bacterial organisms. Quantitative PCR study of sputum is in its early stages of application, but regular detection of high counts of bacterial DNA from organisms that are not seen on Gram stain or grown in quantitative culture presents a therapeutic dilemma. This finding may reflect the host microbiome of the respiratory tract, in which case treatment may not need to be given for them. Finally, host transcriptional signatures might enable clinicians to distinguish between viral and bacterial pneumonia, an important practical consideration.
Association of sleep with cognitive function during retirement transition: the Whitehall II study

Abstract Study Objectives Sleep duration and difficulties have been shown to associate with cognitive function. This study examined how changes in sleep and in cognitive function are associated during retirement transition. Methods The study population consisted of 2980 Whitehall II study participants, who retired during the follow-up, whose sleep was queried, and cognitive function measured (inductive reasoning and verbal memory) before and after retirement (follow-up 16 years). Using the last information on sleep before and the first after retirement, participants were categorized into constantly without (59%), increasing (13%), decreasing (11%), and constantly with (18%) sleep difficulties; and constantly short (26%), increasing (19%), decreasing (8.5%), and constantly mid-range (47%) sleep duration. Change in cognitive function during retirement transition was examined by sleep change groups using linear regression analyses with generalized estimating equations. Results More pronounced decline in inductive reasoning during retirement transition was observed among participants with increasing sleep difficulties (−1.96, 95% CI −2.52 to −1.41) compared to those constantly without sleep difficulties (−1.25, 95% CI −1.52 to −0.98) and constantly with sleep difficulties (−1.26, 95% CI −1.75 to −0.92). Decreasing sleep difficulties (−0.64, 95% CI −0.86 to −0.43) were associated with a more pronounced decline in verbal memory when compared to constantly without sleep difficulties (−0.42, 95% CI −0.52 to −0.32) in post-retirement period. No statistically significant differences across sleep duration groups in cognitive function were observed. Conclusions Increasing and decreasing sleep difficulties may be associated with accelerated decline in cognitive function during retirement transition and post-retirement.
Blue Light Signaling Regulates Escherichia coli W1688 Biofilm Formation and l-Threonine Production

We confirmed the mechanism underlying the inhibitory effects of blue light signaling on E. coli biofilm formation and constructed a strain lacking a blue light-sensing protein; this mitigated the aforementioned effects of blue light signaling and ensured normal fermentation performance. Furthermore, this study elucidated that the blue light signaling-induced optogenetic system Magnet effectively regulates E. coli biofilm formation and contributes to l-threonine production. ABSTRACT Escherichia coli biofilm may form naturally on biotic and abiotic surfaces; this represents a promising approach for efficient biochemical production in industrial fermentation. Recently, industrial exploitation of the advantages of optogenetics, such as simple operation, high spatiotemporal control, and programmability, for regulation of biofilm formation has garnered considerable attention. In this study, we used the blue light signaling-induced optogenetic system Magnet in an E. coli biofilm-based immobilized fermentation system to produce l-threonine in sufficient quantity. Blue light signaling significantly affected the phenotype of E. coli W1688. A series of biofilm-related experiments confirmed the inhibitory effect of blue light signaling on E. coli W1688 biofilm. Subsequently, a strain lacking a blue light-sensing protein (YcgF) was constructed via genetic engineering, which substantially reduced the inhibitory effect of blue light signaling on biofilm. A high-efficiency biofilm-forming system, Magnet, was constructed, which enhanced bacterial aggregation and biofilm formation. Furthermore, l-threonine production was increased from 10.12 to 16.57 g/L during immobilized fermentation, and the fermentation period was shortened by 6 h. IMPORTANCE We confirmed the mechanism underlying the inhibitory effects of blue light signaling on E. coli biofilm formation and constructed a strain lacking a blue light-sensing protein; this mitigated the aforementioned effects of blue light signaling and ensured normal fermentation performance. Furthermore, this study elucidated that the blue light signaling-induced optogenetic system Magnet effectively regulates E. coli biofilm formation and contributes to l-threonine production. This study not only enriches the mechanism of blue light signaling to regulate E. coli biofilm formation but also provides a theoretical basis and feasibility reference for the application of optogenetics technology in biofilm-based immobilized fermentation systems.
Equations of state of magnesium perovskite and postperovskite: diagnostics from ab initio simulations

The isothermal compression of magnesium perovskite and postperovskite is examined through the F-f plot and the diagnostic plot of Vinet universal model theoretically from the ab initio quantum-mechanical calculations at the hybrid Hartree-Fock / Density Functional Theory level. A purely numerical approach, rst time applied in this paper, shows that the discrepancies largely observed between studies on the perovskite and criticized in geophysical applications are due to the inadequate choice of the Birch-Murnaghan equation of state; meanwhile the Vinet model is found utterly appropriate for the mineral and infers consistent estimations of the bulk modulus and its pressure derivative. The diagnostics of the postperovskite suggest similar conclusions.
Overview of the GLAST Mission and Opportunities

The Gamma‐ray Large Area Space Telescope, GLAST, is a mission to measure the cosmic gamma‐ray flux in the energy range 20 MeV to > 300 GeV, with supporting measurements for gamma‐ray bursts from 8 keV to 30 MeV. With its launch in late 2007, GLAST will open a new and important window on a wide variety of high‐energy phenomena, including black holes and active galactic nuclei, gamma‐ray bursts, the origin of cosmic rays and studies of supernova remnants, and searches for hypothetical new phenomena. Along with the major science questions for GLAST, this talk will include the mission status, operations plans, and the opportunities for Guest Investigators.
SARS-CoV-2 Variants Infection in Relationship to Imaging-based Pneumonia and Clinical Outcomes

Background Few reports have evaluated the effect of the SARS-CoV-2 variant and vaccination on the clinical and imaging features of COVID-19. Purpose To evaluate and compare the effect of vaccination and variant prevalence on the clinical and imaging features of infections by the SARS-CoV-2. Materials and Methods Consecutive adults hospitalized for confirmed COVID-19 at three centers (two academic medical centers and one community hospital) and registered in a nationwide open data repository for COVID-19 between August 2021 and March 2022 were retrospectively included. All patients had available chest radiographs or CT images. Patients were divided into two groups according to predominant variant type over the study period. Differences between clinical and imaging features were analyzed with use of the Pearson χ2 test, Fisher exact test, or the independent t test. Multivariable logistic regression analyses were used to evaluate the effect of variant predominance and vaccination status on imaging features of pneumonia and clinical severity. Results Of the 2180 patients (mean age, 57 years ± 21; 1171 women), 1022 patients (47%) were treated during the Delta variant predominant period and 1158 (53%) during the Omicron period. The Omicron variant prevalence was associated with lower pneumonia severity based on CT scores (odds ratio [OR], 0.71 [95% CI: 0.51, 0.99; P = .04]) and lower clinical severity based on intensive care unit (ICU) admission or in-hospital death (OR, 0.43 [95% CI: 0.24, 0.77; P = .004]) than the Delta variant prevalence. Vaccination was associated with the lowest odds of severe pneumonia based on CT scores (OR, 0.05 [95% CI: 0.03, 0.13; P < .001]) and clinical severity based on ICU admission or in-hospital death (OR, 0.15 [95% CI: 0.07, 0.31; P < .001]) relative to no vaccination. Conclusion The SARS-CoV-2 Omicron variant prevalence and vaccination were associated with better clinical outcomes and lower severe pneumonia risk relative to Delta variant prevalence. © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Little in this issue.
Multimodality for improved CNN photometric redshifts

Photometric redshift estimation plays a crucial role in modern cosmological surveys for studying the universe's large-scale structures and the evolution of galaxies. Deep learning has emerged as a powerful method to produce accurate photometric redshift estimates from multiband images of galaxies. Here, we introduce a multimodal approach consisting of processing several subsets of image bands in parallel , the outputs are then merged for further processing through a convolutional neural network (CNN). We evaluate the performance of our method using three surveys: the Sloan Digital Sky Survey (SDSS), the Canada-France-Hawaii Telescope Legacy Survey (CFHTLS), and the Hyper Suprime-Cam (HSC). By improving the model's ability to capture information embedded in the correlation between different bands, our technique surpasses state-of-the-art photometric redshift precision. We find that the positive gain does not depend on the specific architecture of the CNN and that it increases with the number of photometric filters available.
How Applicable Is the Single-Dose AMBITION Regimen for Human Immunodeficiency Virus–Associated Cryptococcal Meningitis to High-Income Settings?

Abstract The AmBisome Therapy Induction Optimization (AMBITION-cm) trial, conducted in eastern and southern Africa, showed that a single, high dose (10 mg/kg) of liposomal amphotericin B, given with an oral backbone of fluconazole and flucytosine, was noninferior to the World Health Organization (WHO)–recommended regimen of 7 days of amphotericin B deoxycholate plus flucytosine for treatment of human immunodeficiency virus (HIV)–associated cryptococcal meningitis and has been incorporated into WHO treatment guidelines. We believe that the trial also has important implications for the treatment of HIV-associated cryptococcal meningitis in high-income settings. We advance the arguments, supported by evidence where available, that the AMBITION-cm trial regimen is likely to be as fungicidal as the currently recommended 14-day liposomal amphotericin–based treatments, better tolerated with fewer adverse effects, and confer significant economic and practical benefits and, therefore, should be included as a treatment option in guidance for HIV-associated cryptococcal treatment in high-income settings.
Description of Joyeuxiella pasqualei (Cestoda: Dipylidiidae) from an Italian domestic dog, with a call for further research on its first intermediate host

Abstract Abstract Although Joyeuxiella pasqualei is frequently detected in cats from Mediterranean Europe, information on its biology is still scarce. This cestode is relatively less frequently reported in dogs, possibly because it is often misdiagnosed with the better-known Dipylidium caninum. The occurrence of J. pasqualei proglottids in a dog living in a closed environment triggered us to delve into the biology of this cestode by collecting biological samples from lizards and a road-killed cat. Two reptile species, Podarcis siculus (Lacertidae), and Tarentola mauritanica (Geckonidae) were also collected in the garden and its surroundings. In addition, experimental infections with eggs obtained from gravid proglottids were performed in laboratory mice, and Tenebrio molitor (Coleoptera: Tenebrionidae) beetles. Proglottids from the dog's feces and adult cestodes detected at necroscopy of a cat were morphologically identified as J. pasqualei. Two out of 13 T. mauritanica collected in the garden had natural infections of J. pasqualei cysts in the liver and attached to the intestine. All P. siculus lizards and experimentally infected rodents and beetles were negative. DNA sequences obtained from J. pasqualei showed the highest nucleotide similarities with Versteria sp. , Echinococcus sp. , Raillietina sonini, Taenia polyacantha and D. caninum. Data herein provided show the inability of rodents to become infected by direct ingestion of gravid proglottids, suggesting a need for an invertebrate first intermediate host in the life cycle. Thus, more research study is advocated to better understand the biology of J. pasqualei such as its first intermediate host and its mechanism of transmission in reptiles and rodents.
“Not about us without us” – the feelings and hopes of climate-concerned young people around the world

Abstract The feelings and hopes of young people around the world are often neglected in policymaking and research, with consequences for both their wellbeing and the effectiveness of humanity’s response to the climate crisis. Many of them are distressed by climate change’s impacts, the inaction of political and corporate leaders, the ways other people respond to their feelings, and the lack of support they have to share their feelings or get involved in meaningful climate-related work. This paper is written by a group of twenty-three concerned young people from fifteen countries. It provides a first-hand account of our deepest feelings, how these feelings affect our daily lives, the support we want to help us cope, and our hopes for a radically more compassionate future. The results are particularly relevant to policymakers, mental health professionals, journalists, educators, and people working with young people more widely.
The effects of citalopram, SB-334867 and orexin-1, alone or in various combinations, on the anxiogenic-like effects of REM sleep deprivation in male mice

Sleep deprivation may induce anxiety. On the other hand, anxiety disorders elicit main changes in the quality of sleep. Moreover, orexin and citalopram play a role in the modulation of insomnia and mood diseases. Thus, we planned preclinical research to evaluate the effect of combinations of orexin agents and citalopram on anxiety behavior in rapid eye movement (REM) sleep-deprived mice. For drug intracerebroventricular (i.c.v.) infusion, the guide cannula was surgically implanted in the left lateral ventricle of mice. REM sleep deprivation was conducted via water tank apparatus for 24 h. The anxiety behavior of mice was evaluated using the elevated plus maze (EPM). Our results revealed that REM sleep deprivation reduced the percentage of open arm time (%OAT) and the percentage of the open arm entries (%OAE) but not closed arm entries (locomotor activity) in the EPM test, presenting an anxiogenic response (P < 0.05). We found a sub-threshold dose of SB-334867, orexin-1 receptor antagonist, and orexin-1 which did not alter anxiety reaction in the REM sleep-deprived mice (P > 0.05). Intraperitoneal (i.p.) injections of citalopram (5 and 10 mg/kg) increased both %OAT and %OAE (P < 0.001) representing an anxiolytic effect, but not locomotor activity in the REM sleep-deprived mice. Interestingly, co-treatment of citalopram (1, 5 and 10 mg/kg; i.p.) and SB-334867 (0.1 µg/mouse; i.c.v.) potentiated the anxiolytic effect in the REM sleep-deprived mice. On the other hand, co-treatment of different dosages of citalopram along with a sub-threshold dose of orexin-1 did not alter %OAT, %OAE, and locomotor activity in the REM sleep-deprived mice. We found a synergistic anxiolytic effect of citalopram and SB-334867 in the REM sleep-deprived mice. These results suggested an interaction between citalopram and SB-334867 to prevent anxiogenic behavior in the REM sleep-deprived mice.
An objective, automated and robust scoring using fluorescence optical imaging to evaluate changes in micro-vascularisation indicating early arthritis

Fluorescence optical imaging technique (FOI) is a well-established and valid method for visualization of changes in micro vascularization at different organ systems. As increased vascularization is an early feature of joint inflammation, FOI is a promising method to assess arthritis of the hands. But usability of the method is limited to the assessors experience as the measurement of FOI is semi-quantitative using an individual grading system such as the fluorescence optical imaging activity score (FOIAS). The goal of the study was to automatically and thus, objectively analyze the measured fluorescence intensity generated by FOI to evaluate the amount of inflammation of each of the subject’s joints focusing on the distinction between normal joint status or arthritis in psoriatic arthritis patients compared to healthy volunteers. Due to the heterogeneity of the pathophysiological perfusion of the hands, a method to overcome the absoluteness of the data by extracting heatmaps out of the image stacks is developed. To calculate a heatmap for one patient, firstly the time series for each pixel is extracted, which is then represented by a feature value. Secondly, all feature values are clustered. The calculated cluster values represent the relativity between the different pixels and enable a comparison of multiple patients. As a metric to quantify the conspicuousness of a joint a score is calculated based on the extracted cluster values. These steps are repeated for a total number of three features. With this method a tendency towards a classification into unaffected and inflamed joints can be achieved. However, further research is necessary to transform the tendency into a robust classification model.
Combination Therapy to Kill Mycobacterium tuberculosis in Its Nonreplicating Persister Phenotype

Mycobacterium tuberculosis (Mtb) exists in various metabolic states, including a nonreplicating persister (NRP) phenotype which may affect response to therapy. We have adopted a model-informed strategy to accelerate discovery of effective Mtb treatment regimens and previously found pretomanid (PMD), moxifloxacin (MXF), and bedaquiline (BDQ) to readily kill logarithmic- and acid-phase Mtb. ABSTRACT Mycobacterium tuberculosis (Mtb) exists in various metabolic states, including a nonreplicating persister (NRP) phenotype which may affect response to therapy. We have adopted a model-informed strategy to accelerate discovery of effective Mtb treatment regimens and previously found pretomanid (PMD), moxifloxacin (MXF), and bedaquiline (BDQ) to readily kill logarithmic- and acid-phase Mtb. Here, we studied multiple concentrations of each drug in flask-based, time-kill studies against NRP Mtb in single-, two- and three-drug combinations, including the active M2 metabolite of BDQ. We used nonparametric population algorithms in the Pmetrics package for R to model the data and to simulate the 95% confidence interval of bacterial population decline due to the two-drug combination regimen of PMD + MXF and compared this to observed declines with three-drug regimens. PMD + MXF at concentrations equivalent to average or peak human concentrations effectively eradicated Mtb. Unlike other states for Mtb, we observed no sustained emergence of less susceptible isolates for any regimen. The addition of BDQ as a third drug significantly (P < 0.05) shortened time to total bacterial suppression by 3 days compared to the two-drug regimen, similar to our findings for Mtb in logarithmic or acid growth phases.
Increasing Daily Physical Activity and Its Effects on QTc Time in Severe to Very Severe COPD: A Secondary Analysis of a Randomised Controlled Trial

Abstract Approximately, half of COPD patients die from cardiovascular diseases. A prolongation of cardiac repolarization (measured as QTc interval) is associated with cardiovascular events or cardiovascular deaths in populations of older adults and COPD. One way to reduce the QTc could be to increase physical activity (PA). We investigated whether QTc can be reduced by an increase in PA in patients with severe COPD. This is a secondary outcome analysis from a randomized controlled trial investigating the effects of a 3 months pedometer based program to improve PA. 12-lead ECG was assessed at baseline and after 3 months. We measured PA using a validated triaxial accelerometer. Data were analyzed from 59 participants. Multiple regression modeling, including adjustment for baseline QTc, sex, QT prolonging medications, BMI, smoking status and FEV1%, showed no evidence for an association between an improvement of ≥15% PA and QTc reduction. A 15% improvement in PA according to step counts over 3 months seems not to reduce QTc interval by its MCID of 20 ms in patients with severe to very severe COPD.
Temporal Merge Tree Maps: A Topology-Based Static Visualization for Temporal Scalar Data

Creating a static visualization for a time-dependent scalar field is a non-trivial task, yet very insightful as it shows the dynamics in one picture. Existing approaches are based on a linearization of the domain or on feature tracking. Domain linearizations use space-filling curves to place all sample points into a 1D domain, thereby breaking up individual features. Feature tracking methods explicitly respect feature continuity in space and time, but generally neglect the data context in which those features live. We present a feature-based linearization of the spatial domain that keeps features together and preserves their context by involving all data samples. We use augmented merge trees to linearize the domain and show that our linearized function has the same merge tree as the original data. A greedy optimization scheme aligns the trees over time providing temporal continuity. This leads to a static 2D visualization with one temporal dimension, and all spatial dimensions compressed into one. We compare our method against other domain linearizations as well as feature-tracking approaches, and apply it to several real-world data sets.