bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful Long-Term Aspirin Desensitization in a Pilot With Aspirin-Exacerbated Respiratory Disease
Authors: Pacheco Curtis S , Brooks Robert M , White Kevin M
Published: November 2022

Aspirin-exacerbated respiratory disease (AERD) is a triad of asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and adverse respiratory reactions to the ingestion of aspirin/non-steroidal anti-inflammatory drugs.1 Patients with AERD are frequently plagued with CRSwNP that is difficult to manage with systemic steroids, nasal steroids, and surgical polypectomy, often requiring multiple endoscopic sinus surgeries and frequent otolaryngology follow-up.2,3 There are an abundance of therapies to treat CRSwNP in the setting of AERD, all with varying costs, efficacies, and indications for treatment.4 While limited by side effect profile, aspirin desensitization remains an effective, low-cost treatment for patients with CRSwNP and non-steroidal anti-inflammatory drug sensitivity.5 We describe a case of an active duty U.S. Air Force pilot with AERD whose CRSwNP was successfully treated with aspirin desensitization without detrimental effect on his flying status.
Towards optimal foreground mitigation strategies for interferometric H i intensity mapping in the low-redshift Universe
Authors: Chen Zhaoting , Wolz Laura , Battye Richard
Published: November 2022

We conduct the first case study towards developing optimal foreground mitigation strategies for neutral hydrogen (H i) intensity mapping using radio interferometers at low redshifts. A pipeline for simulation, foreground mitigation, and power spectrum estimation is built, which can be used for ongoing and future surveys using MeerKAT and Square Kilometre Array Observatory. It simulates realistic sky signals to generate visibility data-given instrument and observation specifications, which is subsequently used to perform foreground mitigation and power spectrum estimation. A quadratic estimator formalism is developed to estimate the temperature power spectrum in visibility space. Using MeerKAT telescope specifications for observations in the redshift range, $z$ ∼ 0.25–0.30, corresponding to the MeerKAT International GHz Tiered Extragalactic Exploration (MIGHTEE) survey, we present a case study, where we compare different approaches of foreground mitigation. We find that component separation in visibility space provides a more accurate estimation of H i clustering when compared with foreground avoidance, with the uncertainties being 30 per cent smaller. Power spectrum estimation from image is found to be less robust with larger bias and more information loss when compared with estimation in visibility. We conclude that for the considered sub-band of $z$ ∼ 0.25–0.30, the MIGHTEE survey will be capable of measuring the H i power spectrum from $k\sim 0.5$ to $k\sim 10\, {\rm Mpc^{-1}}$ with signal-to-noise ratio being ∼3. We are the first to show that, at low redshift, component separation in visibility space suppresses foreground contamination at large line-of-sight scales, allowing measurement of H i power spectrum closer to the foreground wedge, crucial for data analysis towards future detections.
Data mining techniques on astronomical spectra data – II. Classification analysis
Authors: Yang Haifeng , Zhou Lichan , Cai Jianghui , Shi Chenhui , Yang Yuqing , Zhao Xujun , Duan Juncheng , Yin Xiaona
Published: November 2022

Classification is valuable and necessary in spectral analysis, especially for data-driven mining. Along with the rapid development of spectral surveys, a variety of classification techniques have been successfully applied to astronomical data processing. However, it is difficult to select an appropriate classification method in practical scenarios due to the different algorithmic ideas and data characteristics. Here, we present the second work in the data mining series – a review of spectral classification techniques. This work also consists of three parts: a systematic overview of current literature, experimental analyses of commonly used classification algorithms, and source codes used in this paper. First, we carefully investigate the current classification methods in astronomical literature and organize these methods into ten types based on their algorithmic ideas. For each type of algorithm, the analysis is organized from the following three perspectives. (1) their current applications and usage frequencies in spectral classification are summarized; (2) their basic ideas are introduced and preliminarily analysed; (3) the advantages and caveats of each type of algorithm are discussed. Secondly, the classification performance of different algorithms on the unified data sets is analysed. Experimental data are selected from the LAMOST survey and SDSS survey. Six groups of spectral data sets are designed from data characteristics, data qualities, and data volumes to examine the performance of these algorithms. Then the scores of nine basic algorithms are shown and discussed in the experimental analysis. Finally, nine basic algorithms source codes written in python and manuals for usage and improvement are provided.
Gaia white dwarfs within 40 pc – III. Spectroscopic observations of new candidates in the Southern hemisphere
Authors: O’Brien Mairi W , Tremblay P-E , Gentile Fusillo N P , Hollands M A , Gänsicke B T , Koester D , Pelisoli I , Cukanovaite E , Cunningham T , Doyle A E , Elms A , Farihi J , Hermes J J , Holberg J , Jordan S , Klein B L , Kleinman S J , Manser C J , De Martino D , Marsh T R , McCleery J , Melis C , Nitta A , Parsons S G , Raddi R , Rebassa-Mansergas A , Schreiber M R , Silvotti R , Steeghs D , Toloza O , Toonen S , Torres S , Weinberger A J , Zuckerman B
Published: November 2022

We present a spectroscopic survey of 248 white dwarf candidates within 40 pc of the Sun; of these 244 are in the Southern hemisphere. Observations were performed mostly with the Very Large Telescope (X-Shooter) and Southern Astrophysical Research Telescope. Almost all candidates were selected from Gaia Data Release 3 (DR3). We find a total of 246 confirmed white dwarfs, 209 of which had no previously published spectra, and two main-sequence star contaminants. Of these, 100 white dwarfs display hydrogen Balmer lines, 69 have featureless spectra, and two show only neutral helium lines. Additionally, 14 white dwarfs display traces of carbon, while 37 have traces of other elements that are heavier than helium. We observe 35 magnetic white dwarfs through the detection of Zeeman splitting of their hydrogen Balmer or metal spectral lines. High spectroscopic completeness (> 97 per cent) has now been reached, such that we have 1058 confirmed Gaia DR3 white dwarfs out of 1083 candidates within 40 pc of the Sun at all declinations.
Astrometric detection of binary asteroids
Authors: Segev Noam , Ofek Eran O , Polishook David
Published: November 2022

Binary asteroids probe thermal-radiation effects on the main-belt asteroids’ evolution. We discuss the possibility of detecting binary minor planet systems by the astrometric wobble of the centre of light around the centre of mass. This method enables the exploration of the phase-space of binary asteroids, which is difficult to explore using common detection techniques. We describe a forward model that projects the centre-of-light position with respect to the centre of mass, as it is seen by the observer. We study the performance of this method using simulated Gaia-like data. We apply the astrometric method to a subset of the Gaia DR2 Solar system catalogue and find no significant evidence of binary asteroids. This is likely because the Gaia DR2 removed astrometric outliers, which in our case may be due to astrophysical signals. Applying this method to binary asteroid (4337) Arecibo, for which Gaia DR3 reported a possible astrometric signal with a period of P = 32.85 ± 0.38 h, reveals a possible 2.2σ solution with a period of 16.26 h (about half the reported period). We find a small, marginally significant, excess of astrometric noise in the known binary asteroid population from Pravec et al. relative to the entire asteroid population in the Gaia DR2 Solar system catalogue. We also discuss some caveats like precession and asteroid rotation.
Effect of honey on cardiometabolic risk factors: a systematic review and meta-analysis
Authors: Ahmed Amna , Tul-Noor Zujaja , Lee Danielle , Bajwah Shamaila , Ahmed Zara , Zafar Shanza , Syeda Maliha , Jamil Fakeha , Qureshi Faizaan , Zia Fatima , Baig Rumsha , Ahmed Saniya , Tayyiba Mobushra , Ahmad Suleman , Ramdath Dan , Tsao Rong , Cui Steve , Kendall Cyril W C , de Souza Russell J , Khan Tauseef A , Sievenpiper John L
Published: November 2022

Context

Excess calories from free sugars are implicated in the epidemics of obesity and type 2 diabetes. Honey is a free sugar but is generally regarded as healthy.

Objective

The effect of honey on cardiometabolic risk factors was assessed via a systematic review and meta-analysis of controlled trials using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.

Data Sources

MEDLINE, Embase, and the Cochrane Library databases were searched up to January 4, 2021, for controlled trials ≥1 week in duration that assessed the effect of oral honey intake on adiposity, glycemic control, lipids, blood pressure, uric acid, inflammatory markers, and markers of nonalcoholic fatty liver disease.

Data Extraction

Independent reviewers extracted data and assessed risk of bias. Data were pooled using the inverse variance method and expressed as mean differences (MDs) with 95%CIs. Certainty of evidence was assessed using GRADE.

Data Analysis

A total of 18 controlled trials (33 trial comparisons, N = 1105 participants) were included. Overall, honey reduced fasting glucose (MD = −0.20 mmol/L, 95%CI, −0.37 to −0.04 mmol/L; low certainty of evidence), total cholesterol (MD = −0.18 mmol/L, 95%CI, −0.33 to −0.04 mmol/L; low certainty), low-density lipoprotein cholesterol (MD = −0.16 mmol/L, 95%CI, −0.30 to −0.02 mmol/L; low certainty), fasting triglycerides (MD = −0.13 mmol/L, 95%CI, −0.20 to −0.07 mmol/L; low certainty), and alanine aminotransferase (MD = −9.75 U/L, 95%CI, −18.29 to −1.21 U/L; low certainty) and increased high-density lipoprotein cholesterol (MD = 0.07 mmol/L, 95%CI, 0.04–0.10 mmol/L; high certainty). There were significant subgroup differences by floral source and by honey processing, with robinia honey, clover honey, and raw honey showing beneficial effects on fasting glucose and total cholesterol.

Conclusion

Honey, especially robinia, clover, and unprocessed raw honey, may improve glycemic control and lipid levels when consumed within a healthy dietary pattern. More studies focusing on the floral source and the processing of honey are required to increase certainty of the evidence.

Systematic Review Registration

PROSPERO registration number CRD42015023580.
Effect of strobe lights on catches and length distributions of euphausiids collected by Bongo nets
Authors: Gislason Astthor , Petursdottir Hildur , Reynisson Pall
Published: November 2022

Euphausiids are difficult to catch quantitatively with most net sampling systems due to avoidance of the nets. Previous studies have shown that bright lights may reduce euphausiid net avoidance from relatively large net sampling systems. This study describes experiments where strobe lights were mounted on the smaller Bongo net frame, and net avoidance evaluated by repeated towing through layers of euphausiids, as evidenced from acoustic backscattering data, with the strobe lights either on or off. The study was conducted both in fjord and offshore environments. The results show that the use of strobe lights significantly increases the catches of Thysanoessa raschii, T. inermis and Meganyctiphanes norvegica, and that the increase is mainly due to increased catches of the older components of the populations, whereas juveniles of the spring generations are relatively unaffected. The results for T. longicaudata are less conclusive although they indicate that the catches of this species are also positively affected by the strobe lights. The results lend support to the hypothesis that the use of the strobe lights increases catches by reducing net avoidance behavior of the euphausiids rather than by attracting them, and the catches therefore better representing the composition of the stock than if the lights were not used.
2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria sets for three types of antineutrophilic cytoplasmic antibody-associated vasculitis
Authors: Yazici Hasan , Tascilar Koray , Yazici Yusuf
Published: November 2022

Purpose of review

A critique of the recently published classification criteria for three main types of antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis.

Recent findings

An ACR and EULAR joint task force recently published classification criteria for three main types of ANCA-associated vasculitis. The criteria were based on patient histories and findings in nearly 7000 patients from 136 sites in 32 countries. As such the study represented hitherto the most intensive attempt to prepare classification criteria vasculitis. We propose, this truly intensive effort was, unfortunately, unsuccessful. There were two main mishaps. The first one was that the proposed criteria were not validated in an independent cohort. This is curious in that the sponsors, ACR and EULAR, require such independent cohorts for validation. The second mishap is that the concept that disease classification criteria need to be 100% sensitive and specific for a diagnosis is unrealistic. Moreover, all-purpose disease classification criteria are not respectful to scientific research and to the probabilistic nature of the art and the science of medicine.

The new ACR/EULAR ANCA-associated vasculitis guidelines have not been validated in independent cohorts. We propose replacing the term disease criteria with disease guidelines.
Construct Validity and Internal Consistency of the Physical Therapist Student Evaluation of Clinical Experience and Clinical Instruction
Authors: Gallivan Sean
Published: November 2022

Introduction.

The purpose of this research was to assess the construct validity and internal consistency of the Physical Therapist Student Evaluation of Clinical Experience and Clinical Instruction Section II: Physical Therapist Student Evaluation of Clinical Instruction (PTSE).

Review of the Literature.

Physical therapy lacks a psychometrically sound student assessment of the performance of clinical instructor (CI), providing a basis for assessing the PTSE's internal consistency and construct validity.

Subjects.

A nonprobability convenience sample of 5,077 students from 29 physical therapist education programs (PTEPs) completed 6,851 PTSEs using a third-party clinical education management platform.

Methods.

To assess the construct validity of the PTSE, the researcher conducted exploratory factor analysis with principal axis factor extraction and promax oblique rotation on 3 PTSE data subsets. The researcher conducted internal consistency analyses on the 21-item PTSE and on each factor identified in the factor analyses.

Results.

For each PTSE subset, factor analysis identified one factor of 17 items, CI Effectiveness, which accounted for 48.5%, 54.1%, and 53.8% of the variance of the 3 data subsets, respectively. Factor analysis did not identify a factor solution that included all 21 Likert scale–rated items of Section 2 of the PTSE. Resultant Cronbach's alpha values met minimum levels of acceptable internal consistency while exceeding the 0.90 level that raises the concern of item redundancy.

Discussion and Conclusion.

Factor analysis results find plausible explanations for their degree of alignment with assessment tool item writing construction and scaling standards, although a one-factor PTSE is inconsistent with historical and prevailing multiple constructs of CI effectiveness. Individual factor and all-item internal consistency results raise concerns regarding the number and the redundancy of the questions. Factor analysis and internal consistency analyses of PTSEs completed by students from a nonprobability convenience sample of PTEPs suggest that PTEPs need a more psychometrically sound tool to assess CI performance.
Physical Therapy Education Through the Lens of the Master Adaptive Learner 24th Pauline Cerasoli Lecture
Authors: Jensen Gail M.
Published: November 2022

Background and Purpose.

The Dr. Pauline Cerasoli Lecture is both an honor and an opportunity to learn from the past and look to the future of physical therapy education. This 24th Cerasoli lecture does just that in taking a reflective look at the question—What would excellence and innovation look like in physical therapy education if we were looking outward to what society needs from us?

Position and Rationale.

While the concepts associated with the master adaptive learner (MAL) have been applied primarily at the level of individual learners, the model provides a useful framework for this reflective look at physical therapy education. Grounded in the robust concepts of learning sciences and adaptive expertise, application of this model to physical therapy education is a lens for identifying our greatest challenges and envisioning drivers for transformative change.

Discussion and Conclusion.

The question of what could or should we be doing in physical therapy education to meet societal needs is used in the reflective analysis of three major areas: 1) Reimagining the role of curriculum, 2) Learning for a lifetime of learning, and 3) Education research: needed and wanted. Together, analysis of these three areas identify opportunities for all educators (clinical and academic) to be provocative (disruptive), innovative, and adaptive!
Clinical and prognostic features of CCI/PICS patients: A prospective observational clinical study
Authors: Zhou Qingqing , Qian Hebu , Yang Aixiang , Lu Jian , Liu Jun
Published: November 2022

Objective

To investigate and compare the clinical features and prognosis of chronic critical illness (CCI)/ persistent inflammation immunosuppression and catabolism (PICS).

Methods

This is a prospective observational clinical study. During this study period, we collect ICU patients’ data from Suzhou Municipal Hospital and Suzhou Ninth People’s Hospital. All patients older than 18 years of age were included and according to the corresponding exclusion and diagnostic criteria, they were divided into four groups: PICS group, CCI group, CCI and PICS group (CCI + PICS), nor CCI and nor PICS group (NCCI+NPICS), collected and recorded age, sex, hospital time, hospital diagnosis, acute physiological and chronic health status score II (APACHEII), sequential organ failure detection score(SOFA), c-reactive protein (CRP), absolute value lymphocyte count (L), serum albumin (Alb), white cells count (WBC), absolute value neutrophils count (N), secondary infection and 28-day case fatality rate separately.

Results

A total of 687 patients were admitted to the ICU during the study period. The hospitalization time less than 14 days were excluded, and 168 patients were eventually included. There are 17 in the PICS group, 71 in the CCI group, 50 in the CCI + PICS group, and 30 in the NCCI+NPICS group. Baseline characteristics showed statistically significant differences in SOFA, length of hospital stay, 28-day mortality among four groups. Baseline main indicator, and multiple comparisons showed that the CCI + PICS group had longer hospital stay, worse prognosis and more adverse outcomes. Multivariate analysis showed that final age, CRP on day 14 and 21, serum albumin on day 1 and 21 had an impact on the prognosis (P<0.05).

Conclusion

The clinical prognosis of the four groups decreased in order of NCCI+NPICS, CCI, PICS, CCI + PICS. Our finding of clinically isolated PICS may indicate that PICS acts as a inducement or independent factor to worsen the prognosis of CCI.
Updates in neuro-otology
Authors: Murphy Olwen C. , Hac Nicholas E.F. , Gold Daniel R.
Published: November 2022

Purpose of review

Recent updates with clinical implications in the field of neuro-otology are reviewed.

Recent findings

Important updates relating to several neuro-otologic disorders have been reported in recent years. For benign positional paroxysmal vertigo (BPPV), we provide updates on the characteristics and features of the short arm variant of posterior canal BPPV. For the acute vestibular syndrome, we report important updates on the use of video-oculography in clinical diagnosis. For autoimmune causes of neuro-otologic symptoms, we describe the clinical and paraclinical features of kelch-like protein 11 encephalitis, a newly-identified antibody associated disorder. For cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we report recent genetic insights into this condition.

This review summarizes important recent updates relating to four hot topics in neuro-otology.
Systematic Review of Treatment of Patients with Achalasia: Heller Myotomy, Pneumatic Dilation, and Peroral Endoscopic Myotomy (POEM)
Authors: Ciomperlik Hailie , Dhanani Naila H , Mohr Cassandra , Hannon Craig , Olavarria Oscar A , Holihan Julie L , Liang Mike K
Published: November 2022

Background:

The aim of this systematic review is to assess all comparative randomized controlled trials (RCTs) evaluating Heller myotomy, pneumatic dilation and per endoscopic oral myotomy (POEM).

Study Design:

Achalasia is an esophageal motility disorder associated with degeneration of the myenteric plexus, it causes significant symptoms and impacts patient quality of life (QOL). It remains unclear on the optimal treatment for patients with achalasia and the impact of these interventions on QOL. PubMed, Embase, Scopus and Cochrane were searched from inception to April 2020. RCTs that compared the three interventions were included. Primary outcome was QOL at 12-36 months post-operative. Secondary outcomes included reintervention, dysphagia, leak/perforation, and GERD recurrence.

Results:

9 publications of 6 studies were included. Of the 9 publications there was no significant difference in QOL at 12-36 months except for one study in in which QOL was significantly higher in patients who underwent Heller myotomy as opposed to pneumatic dilation at 3 years; however, at 5 years there was no difference. Pneumatic dilation was associated with the highest rates of dysphagia recurrence and reintervention while POEM had the lowest.

Conclusions:

The treatment of achalasia should be chosen in accordance with patient goals. After any of the three interventions, QOL appears to be similar. However, POEM may be associated with the lowest rates of perforation/leak, dysphagia, and reintervention and may be the lowest risk option. However, there are barriers to widespread utilization due to challenges in training and adoption.
The origin of modern patterns of continental diversity in Mauritiinae palms: the Neotropical museum and the Afrotropical graveyard
Authors: Bacon Christine D. , Silvestro Daniele , Hoorn Carina , Bogotá-Ángel Giovanni , Antonelli Alexandre , Chazot Nicolas
Published: November 2022

While the latitudinal diversity gradient has received much attention, biodiversity and species richness also vary between continents across similar latitudes. Fossil information can be used to understand the evolutionary mechanisms that generated such variation between continents of similar latitudes. We integrated fossil data into a phylogenetic analysis of the Mauritiinae palms, whose extant diversity is restricted to the Neotropics, but extended across Africa and India during most of the Cenozoic. Mauritiinae diverged from its sister lineage Raphiinaeca106 Ma. Using ancestral state estimation and a lineage through time analysis, we found that diversity arose globally during the late Cretaceous and Palaeocene across South America, Africa and India. The Palaeocene–Eocene transition (ca56 Ma) marked the end of global Mauritiinae expansion, and the beginning of their decline in both Africa and India. Mauritiinae disappeared from the Indian subcontinent and Africa at the end of the Eocene and the Miocene, respectively. By contrast, Neotropical diversity steadily increased over the last 80 Myr. Taken together, our results suggest that the Neotropics functioned as a continental-scale refuge for Mauritiinae palms, where lineages survived and diversified while global climatic changes that drastically reduced rainforests led to their demise on other continents.
Variation in symbiont density is linked to changes in constitutive immunity in the facultatively symbiotic coral,
Astrangia poculata
Authors: Changsut Isabella , Womack Haley R. , Shickle Alicia , Sharp Koty H. , Fuess Lauren E.
Published: November 2022

Scleractinian corals are essential ecosystem engineers, forming the basis of coral reef ecosystems. However, these organisms are in decline globally, in part due to rising disease prevalence. Most corals are dependent on symbiotic interactions with single-celled algae from the family Symbiodiniaceae to meet their nutritional needs, however, suppression of host immunity may be essential to this relationship. To explore immunological consequences of algal symbioses in scleractinian corals, we investigated constitutive immune activity in the facultatively symbiotic coral,
Astrangia poculata
. We compared immune metrics (melanin synthesis, antioxidant production and antibacterial activity) between coral colonies of varying symbiont density. Symbiont density was positively correlated to both antioxidant activity and melanin concentration, likely as a result of the dual roles of these pathways in immunity and symbiosis regulation. Our results confirm the complex nature of relationships between algal symbiosis and host immunity and highlight the need for nuanced approaches when considering these relationships.
Associations between indoor relative humidity and global COVID-19 outcomes
Authors: Verheyen C. A. , Bourouiba L.
Published: November 2022

Globally, the spread and severity of COVID-19 have been distinctly non-uniform. Seasonality was suggested as a contributor to regional variability, but the relationship between weather and COVID-19 remains unclear and the focus of attention has been on outdoor conditions. Because humans spend most of their time indoors and because most transmission occurs indoors, we here, instead, investigate the hypothesis that
indoor
climate—particularly
indoor
relative humidity (RH)—may be the more relevant modulator of outbreaks. To study this association, we combined population-based COVID-19 statistics and meteorological measurements from 121 countries. We rigorously processed epidemiological data to reduce bias, then developed and experimentally validated a computational workflow to estimate indoor conditions based on outdoor weather data and standard indoor comfort conditions. Our comprehensive analysis shows robust and systematic relationships between regional outbreaks and indoor RH. In particular, we found intermediate RH (40–60%) to be robustly associated with better COVID-19 outbreak outcomes (versus RH < 40% or >60%). Together, these results suggest that indoor conditions, particularly indoor RH, modulate the spread and severity of COVID-19 outbreaks.
Long-term experience operating CDC recommended 5 air changes per hour in a K-5 elementary school using HEPA and MERV 16 Do-It-Yourself (DIY) portable air cleaners
Authors: Srikrishna Devabhaktuni
Published: November 2022

On May 12, 2023 CDC recommended 5 air changes per hour (5 ACH) and in July 2021 California (CDPH) recommended 6 to 12 ACH to reduce long-range, aerosol transmission of COVID-19 and other pathogens in classrooms. EPA recommends MERV 13+ DIY air cleaners for temporary use during wildfires, and a recent EPA study reported inconsistent usage in homes due to excessive noise generated by the DIY air cleaners. Questions also remain about wear and tear including how long filters retain their filtration properties and need to be replaced. Herein we report real-world experience from daily usage of 47 HEPA and 60 MERV 16 DIY air cleaners in a California elementary school during two academic school years from spring 2021 through fall of 2023 across 16 classrooms, a library, an auditorium, a lunchroom, and in a hallway. Three to six purifiers were needed in classrooms to meet 6 to 12 ACH. Teachers reported noise generated by MERV 16 DIY purifiers on lowest fan speed as acceptable for classroom use. Filtration efficiency at 0.3 μm (most penetrating particle size) for DIY air cleaners with 5” MERV 16 filters used in the classrooms averaged 77% after six months (1st batch in February 2022) compared to 92% for newly installed filters (2nd batch in October 2022). Follow up testing on both batches of filters after an additional academic year (June 2023) showed only slight changes in average filtration efficiency. Portable air cleaners (HEPA and DIY) averaged and estimated 10 ACH (6-15 ACH) across the 16 classrooms demonstrating feasibility and unit economics of meeting CDPH targets per classroom for $200-$650 with DIY versus $600-$12,000 with the HEPA models used. In one 9000 cubic foot classroom with 7 air purifiers, air exchange rate was measured using ambient aerosols at 18 ACH from air purifiers (within 20% of ACH estimated based on CADR of purifiers) and 7 ACH from HVAC for a combined total of 25 ACH. Based on this long-term experience, specific recommendations for enhancing and improving CDC’s web page “Ventilation in Buildings” include: (1) recommended operation of MERV 13+ DIY at their low speed for low noise, cost-effective air cleaning (2) electro-mechanical safety especially in relation to power outlets (3) an open-source procedure known as the “spike test” using ambient aerosols to verify ACH in a room, like the Portacount for mask fit testing. Spike testing can become the basis for ACH certification or verification in any room without generating aerosol contaminants (e.g. salt water, smoke, tracers which may be unsafe or disallowed indoors).
DETECT: Feature extraction method for disease trajectory modeling
Authors: Singhal Pankhuri , Guare Lindsay , Morse Colleen , Byrska-Bishop Marta , Guerraty Marie A. , Kim Dokyoon , Ritchie Marylyn D. , Verma Anurag
Published: November 2022

Modeling with longitudinal electronic health record (EHR) data proves challenging given the high dimensionality, redundancy, and noise captured in EHR. In order to improve precision medicine strategies and identify predictors of disease risk in advance, evaluating meaningful patient disease trajectories is essential. In this study, we develop the algorithmDiseasE Trajectory fEature extraCTion (DETECT)for feature extraction and trajectory generation in high-throughput temporal EHR data. This algorithm can 1) simulate longitudinal individual-level EHR data, specified to user parameters of scale, complexity, and noise and 2) use a convergent relative risk framework to test intermediate codes occurring between a specified index code(s) and outcome code(s) to determine if they are predictive features of the outcome. We benchmarked our method on simulated data and generated real-world disease trajectories using DETECT in a cohort of 145,575 individuals diagnosed with hypertension in Penn Medicine EHR for severe cardiometabolic outcomes.
SIR analytical model applied to 2020 Covid-19 data in Italy
Authors: Simeone Roberto
Published: November 2022

A simple analytical Susceptible-Infectious-Recovered (SIR) model without vital dynamics is developed from basic assumptions. Based on the data available for the spread of the Covid 19 virus in Italy in 2020, the characteristic parameters of the model are estimated.
West Nile Virus spread in Europe - phylogeographic pattern analysis and key drivers
Authors: Lu Lu , Zhang Feifei , Oude Munnink Bas B. , Munger Emmanuelle , Sikkema Reina S. , Pappa Styliani , Tsioka Katerina , Sinigaglia Alessandro , Dal Molin Emanuela , Shih Barbara B. , Günther Anne , Pohlmann Anne , Beer Martin , Taylor Rachel A. , Bartumeus Frederic , Woolhouse Mark , Aarestrup Frank M. , Barzon Luisa , Papa Anna , Lycett Samantha , Koopmans Marion P. G.
Published: November 2022

Spread and emergence of West Nile virus (WNV) in Europe have been very different from those observed in North America. Here, we describe key drivers by combining viral genome sequences with epidemiological data and possible factors of spread into phylodynamic models. WNV in Europe has greater lineage diversity than other regions of the world, suggesting repeated introductions and local amplification. Among the six lineages found in Europe, WNV-2a is predominant, has spread to at least 14 countries and evolved into two major co-circulating clusters (A and B). Both of these seem to originate from regions of Central Europe. Viruses of Cluster A emerged earlier and have spread towards the west of Europe with higher genetic diversity. Amongst multiple drivers, high agriculture activities were associated with both spread direction and velocity. Our study suggests future surveillance activities should be strengthened in Central Europe and Southeast European countries, and enhanced monitoring should be targeted to areas with high agriculture activities.
Thermal phenotypic plasticity of pre- and post-copulatory male harm buffers sexual conflict in wildDrosophila melanogaster
Authors: Londoño-Nieto Claudia , García-Roa Roberto , Garcia-Co Clara , González Paula , Carazo Pau
Published: November 2022

Strong sexual selection frequently leads to sexual conflict and ensuing male harm, whereby males increase their reproductive success at the expense of harming females. Male harm is a widespread evolutionary phenomenon with a strong bearing on population viability. Thus, understanding how it unfolds in the wild is a current priority. Here, we sampled a wildDrosophila melanogasterpopulation and studied male harm across the normal range of temperatures under which it reproduces optimally in nature by comparing female lifetime reproductive success and underlying male harm mechanisms under monogamy (i.e., low male competition/harm) vs. polyandry (i.e., high male competition/harm). While females had equal lifetime reproductive success across temperatures under monogamy, polyandry resulted in a maximum decrease of female fitness at 24°C (35%), reducing its impact at both 20°C (22%), and 28°C (10%). Furthermore, female fitness components and pre- (i.e., harassment) and post-copulatory (i.e., ejaculate toxicity) mechanisms of male harm were asymmetrically affected by temperature. At 20°C, male harassment of females was reduced, and polyandry accelerated female actuarial ageing. In contrast, the effect of mating on female receptivity (a component of ejaculate toxicity) was affected at 28°C, where the mating costs for females decreased and polyandry mostly resulted in accelerated reproductive ageing. We thus show that, across a natural thermal range, sexual conflict processes and their effects on female fitness components are plastic and complex. As a result, the net effect of male harm on overall population viability is likely to be lower than previously surmised. We discuss how such plasticity may affect selection, adaptation and, ultimately, evolutionary rescue under a warming climate.
Selectivity and ranking of tight-binding JAK-STAT inhibitors using Markovian milestoning with Voronoi tessellations
Authors: Ojha Anupam Anand , Srivastava Ambuj , Votapka Lane William , Amaro Rommie E.
Published: November 2022

Janus kinases (JAK) are a group of proteins in the non-receptor tyrosine kinase (NRTKs) family that play a crucial role in growth, survival, and angiogenesis. They are activated by cytokines through the Janus kinase - signal transducer and activator of transcription (JAK-STAT) signaling pathway. JAK-STAT signaling pathways have significant roles in the regulation of cell division, apoptosis, and immunity. Identification of the V617F mutation in the Janus homology 2 (JH2) domain of JAK2 leading to myeloproliferative disorders has stimulated great interest in the drug discovery community to develop JAK2-specific inhibitors. However, such inhibitors should be selective towards JAK2 over other JAKs and display an extended residence time. Recently, novel JAK2/STAT5 axis inhibitors (N-(1H-pyrazol-3-yl)pyrimidin-2-amino derivatives) have displayed extended residence times (hours or longer) on target and adequate selectivity excluding JAK3. To facilitate a deeper understanding of the kinase-inhibitor interactions and advance the development of such inhibitors, we utilize a multiscale Markovian milestoning with Voronoi tessellations (MMVT) approach within the Simulation-Enabled Estimation of Kinetic Rates v.2 (SEEKR2) program to rank-order these inhibitors based on their kinetic properties and further explain the selectivity of JAK2 inhibitors over JAK3. Our approach investigates the kinetic and thermodynamic properties of JAK-inhibitor complexes in a user-friendly, fast, efficient, and accurate manner compared to other brute force and hybrid enhanced sampling approaches.
Wastewater as a back door to serology?
Authors: Agan Marie LittleFawn , Taylor William R. , Young Isaiah , Willis William A. , New Gari D. , Lair Halee , Murphy Anastasia , Marinelli Anna , Juel Md Ariful Islam , Munir Mariya , Dornburg Alex , Schlueter Jessica , Gibas Cynthia
Published: November 2022

Wastewater surveillance is a powerful tool for monitoring the prevalence of infectious disease. Systems for wastewater monitoring were put in place throughout the world during the COVID-19 pandemic. These systems use viral RNA copies as the basis of estimates of COVID-19 cases in the sewershed area, thereby providing data critical for public health responses. However, the potential to measure other biomarkers in wastewater during outbreaks has not been fully explored. Here we report a novel approach for detecting specific human antibodies from wastewater. We measured the abundance of anti-SARS-CoV-2 spike IgG and IgA from fresh samples of community wastewater and from archived frozen samples dating from 2020-22. The assay described can be performed with readily available reagents, at a moderate per-sample cost. Our findings demonstrate the feasibility of noninvasive serological surveillance via wastewater, enabling a new approach to immunity-based monitoring of populations.
Metabolic Sensing of Extra-cytoplasmic Copper Availability via Translational Control by a Nascent Exported Protein
Authors: Öztürk Yavuz , Andrei Andreea , Blaby-Haas Crysten E. , Daum Noel , Daldal Fevzi , Koch Hans-Georg
Published: November 2022

Metabolic sensing is a crucial prerequisite for cells to adjust their physiology to rapidly changing environments. In bacteria, the response to intra- and extra-cellular ligands is primarily controlled by transcriptional regulators, which activate or repress gene expression to ensure metabolic acclimation. Translational control, such as ribosomal stalling can also contribute to cellular acclimation and has been shown to mediate responses to changing intracellular molecules. In the current study, we demonstrate that co-translational export of the protein CutF regulates translation of the down-streamcutO-encoded multi-copper oxidase CutO in response to extracellular copper (Cu). Our data show that CutF, acting as a Cu sensor, is co-translationally exported by the signal recognition particle pathway. Binding of Cu to the periplasmically exposed Cu-binding motif of CutF delays its co-translational export via its C-terminal ribosome stalling-like motif. This allows the unfolding of an mRNA stem-loop sequence that shields the ribosome-binding site ofcutO,which favors its subsequent translation. Bioinformatic analyses reveal that CutF-like proteins are widely distributed in bacteria and often, are located upstream of genes involved in transition metal homeostasis. Our overall findings illustrate a highly conserved control mechanism using co-translational export of a protein acting as a sensor to integrate the changing availability of extracellular nutrients into metabolic acclimation.

Importance

Metabolite sensing is a fundamental biological process, and the perception of dynamic changes in the extracellular environment is of paramount importance for the survival of organisms. Bacteria usually adjust their metabolism to changing environments by transcriptional regulation. Here, we describe an alternative translational mechanism that controls the bacterial response to the presence of copper, a toxic micronutrient. This mechanism involves a co-translationally secreted protein that, in the presence of copper, undergoes a process resembling ribosomal stalling. This allows the unfolding of a downstream mRNA stem-loop and enables translation of the adjacent Cu-detoxifying multicopper oxidase. Bioinformatic analyses reveal that such proteins are widespread, suggesting that metabolic sensing using ribosome-arrested nascent secreted proteins acting as sensors may be a common strategy for integrating environmental signals into metabolic adaptation.
Iron deficiency modulates metabolic landscape of Bacteroidetes promoting its resilience during inflammation
Authors: Lewis Janina P. , Gui Qin
Published: November 2022

Bacteria have to persist in low iron conditions in order to adapt to host’s nutritional immunity. Since the knowledge of iron stimulon of Bacteroidetes is sparse, we examined oral (Porphyromonas gingivalisandPrevotella intermedia) and gut (Bacteroides thataiotaomicron) representatives for their ability to adapt to iron deplete and iron replete conditions. Our transcriptomics and comparative genomics analysis shows that many iron-regulated mechanisms are conserved within the phylum. Those include genes upregulated in low iron:fldA(flavodoxin), hmu(hemin uptake operon) and loci encoding ABC transporters. Downregulated were:frd(ferredoxin),rbr(rubrerythrin), sdh(succinate dehydrogenase/fumarate reductase),vor(oxoglutarate oxidoreductase/dehydrogenase), andpfor(pyruvate:ferredoxin/ flavodoxin oxidoreductase). Some genus-specific mechanisms, such as theB. thetaiotaomicron’ssuscoding for carbohydrate metabolism and thexusABCcoding for xenosiderophore utilization, were also identified. While all bacteria tested in our study had thenrfAHoperon coding for nitrite reduction and were able to reduce nitrite levels present in culture media, the expression of the operon was iron dependent only inB. thetaiotaomicron.It is noteworthy that we identified a significant overlap between regulated genes found in our study and theB. thetaiotaomicroncolitis study (Zhu et al; Cell Host Microbe 27: 376-388). Many of those commonly regulated genes were also iron regulated in the oral bacterial genera. Overall, this work points to iron being the master regulator enabling bacterial persistence in the host and paves the way for more generalized investigation of the molecular mechanisms of iron homeostasis in Bacteroidetes.
Human and murine neutrophils share core transcriptional programs in both homeostatic and inflamed contexts
Authors: Hackert Nicolaj S. , Radtke Felix A. , Exner Tarik , Lorenz Hanns-Martin , Müller-Tidow Carsten , Nigrovic Peter A. , Wabnitz Guido , Grieshaber-Bouyer Ricardo
Published: November 2022

Neutrophils are frequently studied in murine models, but the extent to which findings translate to humans remains poorly defined. Here, we performed an integrative transcriptomic analysis of 11 murine and 13 human datasets. In homeostasis, neutrophils exhibited the highest number of lineage-specific genes and the greatest degree of correlated expression among genes with one-to-one orthologs (r= 0.79,P< 2.2 × 10−16) compared to other leukocytes. In inflammation, neutrophils displayed considerable transcriptional diversity, but shared a core inflammation program across a broad range of conditions which was conserved between species. This core program included genes encoding IL-1 family members, CD14, IL-4R, CD69 and PD-L1. Chromatin accessibility of core inflammation genes increased significantly in blood compared to bone marrow and further with migration from blood to tissue. Transcription factor enrichment analysis nominated members of the NF-κB family and AP-1 complex as important drivers of the core inflammation program, and HoxB8 neutrophils with JUNB knockout showed a significantly reduced expression of core inflammation genes at baseline and upon stimulation. In vitro perturbations confirmed surface protein upregulation of core inflammation members in both species. Together, we demonstrate substantial transcriptional conservation in neutrophils in homeostasis and identify a core inflammation program conserved across species. This systems biology approach can be leveraged to improve transitions between the murine and human context.

Key Points

The transcriptome of resting neutrophils is substantially conserved between humans and mice

A core inflammation program in neutrophils is shared across a broad range of conditions and conserved across humans and mice

Graphical Abstract
Plethora of QTLs found inArabidopsis thalianareveals complexity of genetic variation for photosynthesis in dynamic light conditions
Authors: Theeuwen Tom P.J.M. , Logie Louise L. , Put Sanne , Bagheri Hedayat , Łosiński Konrad , Drouault Justine , Flood Pádraic J. , Hanhart Corrie , Becker Frank F.M. , Wijfjes Raúl , Hall David , Kramer David M. , Harbinson Jeremy , Aarts Mark G.M.
Published: November 2022

The environments in which plant species evolved are now generally understood to be dynamic rather than static. Photosynthesis has to operate within these dynamic environments, such as sudden changes to light intensities. Plants have evolved photoprotection mechanisms that prevent damage caused by sudden changes to high light intensities. The extent of genetic variation within plants species to deal with these dynamic light conditions remains largely unexplored. Here we show that one accession ofA. thalianahas a more efficient photoprotection mechanism in dynamic light conditions, compared to six other accessions. The construction of a doubled haploid population and subsequent phenotyping in a dynamically controlled high-throughput system reveals up to 15 QTLs for photoprotection. Identifying the causal gene underlying one of the major QTLs shows that an allelic variant ofcpFtsYresults in more efficient photoprotection under high and fluctuating light intensities. Further analyses reveal this allelic variant to be overprotecting, reducing biomass in a range of dynamic environmental conditions. This suggests that within nature, adaptation can occur to more stressful environments and that revealing the causal genes and mechanisms can help improve the general understanding of photosynthetic functioning. The other QTLs possess different photosynthetic properties, and thus together they show how there is ample intraspecific genetic variation for photosynthetic functioning in dynamic environments. With photosynthesis being one of the last unimproved components of crop yield, this amount of genetic variation for photosynthesis forms excellent input for breeding approaches. In these breeding approaches, the interactions with the environmental conditions should however be precisely assessed. Doing so correctly, allows us to tap into nature’s solution to challenging environmental conditions.