bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of Adjunctive Corticosteroid Treatment in Hypoxemic Adults Hospitalized for Mycoplasma pneumoniae Pneumonia: A Retrospective Cohort Study
Authors: Hagman Karl , Nilsson Anna C , Hedenstierna Magnus , Ursing Johan 
Published: September 2024

Abstract

Background
Corticosteroids appears to be beneficial for severe Mycoplasma pneumoniae pneumonia in children, but data in adults are limited. This study investigated effects of adjunctive corticosteroids in hypoxemic adults with M. pneumoniae pneumonia.

Methods
Adults admitted 2013–2017 with verified M. pneumoniae pneumonia and hypoxemia (SpO2 &lt; 93% or oxygen treatment) were included in a cohort. Treatment was defined as receipt of at least 1 glucocorticoid dose.
Primary outcome was time to regression of hypoxemia, analyzed with a multivariable Cox regression. Secondary outcomes included fever duration, length of stay, and complications.

Results
Corticosteroids were given to 31% (122/388) during hypoxemia. Median age was 44 (interquartile range [IQR] 34–57) years. Median time to start of corticosteroid treatment was 1.9 (IQR 0.6–3.6) days from admission. Median cumulative dose was equivalent to 15 (IQR 10–19) mg betamethasone. Treatment duration was 5 (IQR 3–6) days. Patients treated with corticosteroids had more severe respiratory disease, longer symptom duration, and were more often treated with fluoroquinolones.
Time to regression of hypoxemia (hazard ratio [HR] 0.92 [95% confidence interval {CI}: .72–1.19], P = .53) and length of stay (HR 0.91 [95% CI: .71–1.16], P = .44) were not significantly different between corticosteroid treated and controls. Corticosteroid treatment was associated to shorter fever duration (HR 1.44 [95% CI: 1.00–2.06], P = .046). Complications did not differ significantly between treatment groups.

Conclusions
Adjunctive corticosteroids were not associated with reduced time to regression of hypoxemia in adults with M. pneumoniae pneumonia. However, duration of fever was shorter and no increase in complications was seen.
Olfr2-positive macrophages originate from monocytes proliferate in situ and present a pro-inflammatory foamy-like phenotype
Authors: Armstrong Suthahar Sujit Silas , Nettersheim Felix Sebastian , Alimadadi Ahmad , Wang Erpei , Billitti Monica , Resto-Trujillo Natalya , Roy Payel , Hedrick Catherine C , Ley Klaus , Orecchioni Marco 
Published: September 2024

Abstract

Aims
Olfactory receptor 2 (Olfr2) has been identified in a minimum of 30% of vascular macrophages, and its depletion was shown to reduce atherosclerosis progression. Mononuclear phagocytes, including monocytes and macrophages within the vessel wall, are major players in atherosclerosis. Single-cell RNA sequencing studies revealed that atherosclerotic artery walls encompass several monocytes and vascular macrophages, defining at least nine distinct subsets potentially serving diverse functions in disease progression. This study investigates the functional phenotype and ontogeny of Olfr2-expressing vascular macrophages in atherosclerosis.

Methods and results
Olfr2+ macrophages rapidly increase in Apoe−/− mice’s aorta when fed a Western diet (WD). Mass cytometry showed that Olfr2+ cells are clustered within the CD64 high population and enriched for CD11c and Ccr2 markers. Olfr2+ macrophages express many pro-inflammatory cytokines, including Il1b, Il6, Il12, and Il23, and chemokines, including Ccl5, Cx3cl1, Cxcl9, and Ccl22. By extracting differentially expressed genes from bulk RNA sequencing (RNA-seq) of Olfr2+ vs. Olfr2− macrophages, we defined a signature that significantly mapped to single-cell data of plaque myeloid cells, including monocytes, subendothelial MacAir, and Trem2Gpnmb foamy macrophages. By adoptive transfer experiments, we identified that Olfr2 competent monocytes from CD45.1Apoe−/−Olfr2+/+ mice transferred into CD45.2Apoe−/−Olfr2−/− recipient mice fed WD for 12 weeks, accumulate in the atherosclerotic aorta wall already at 72 h, and differentiate in macrophages. Olfr2+ macrophages showed significantly increased BrdU incorporation compared to Olfr2− macrophages. Flow cytometry confirmed that at least 50% of aortic Olfr2+ macrophages are positive for BODIPY staining and have increased expression of both tumour necrosis factor and interleukin 6 compared to Olfr2− macrophages. Gene set enrichment analysis of the Olfr2+ macrophage signature revealed a similar enrichment pattern in human atherosclerotic plaques, particularly within foamy/TREM2hi-Mφ and monocytes.

Conclusions
In summary, we conclude that Olfr2+ macrophages in the aorta originate from monocytes and can accumulate at the early stages of disease progression. These cells can undergo differentiation into MacAir and Trem2Gpnmb foamy macrophages, exhibiting proliferative and pro-inflammatory potentials. This dynamic behaviour positions them as key influencers in shaping the myeloid landscape within the atherosclerotic plaque.
Bradycardia-induced heart failure with preserved ejection fraction successfully treated with empagliflozin and theophylline: a case report
Authors: Miric Dino , Juric Paic Marina , Borovac Josip Andelo 
Published: September 2024

Abstract

Background
The SGLT2 inhibitor empagliflozin has recently gained approval for treating heart failure (HF) across the entire spectrum of ejection fractions including heart failure with preserved ejection fraction (HFpEF). Bradycardia-induced HF, previously described in the literature as bradycardiomyopathy, is an uncommon cause of HFpEF.

Case summary
Herein, we describe a case of a young, 32-year-old woman with no prior medical history who was referred to the hospital due to progressive fatigue and exercise intolerance. She exhibited junctional bradycardia and sinus node dysfunction on electrocardiographic examination, was hypotensive, and had significantly elevated NT-proBNP levels at admission. Transthoracic echocardiographic examination (TTE) revealed preserved systolic function of the left ventricle with segmental abnormalities of contractility and reduced global longitudinal strain, indicative of HFpEF. Cardiac magnetic resonance imaging showed hypertrabeculations, suggesting noncompaction cardiomyopathy (NCCM), even though the definitive diagnostic criteria for NCCM were not met. The patient reported no recent episodes of fever and no chest pain. A comprehensive panel for cardiotropic viruses and Lyme disease were negative while infiltrative diseases such as sarcoidosis were clinically ruled out. Coronary angiography excluded coronary artery disease. Due to profound hypotension and bradycardia, we prescribed empagliflozin and theophylline. At the subsequent follow-up visit within 1 month, the patient reported that she was asymptomatic, with restored sinus rhythm, and complete normalization of NT-proBNP values.

Discussion
Bradycardia-induced HFpEF is a rare entity that can limit the use of most cardiovascular pharmacotherapies but can be successfully treated with empagliflozin and theophylline as demonstrated in our case.
Prognostic value of Borg scale following 6-min walk test in hospitalized older patients with heart failure
Authors: Saito Hiroshi , Maeda Daichi , Kagiyama Nobuyuki , Sunayama Tsutomu , Dotare Taishi , Fujimoto Yudai , Nakade Taisuke , Jujo Kentaro , Saito Kazuya , Kamiya Kentaro , Ogasahara Yuki , Maekawa Emi , Konishi Masaaki , Kitai Takeshi , Iwata Kentaro , Wada Hiroshi , Kasai Takatoshi , Nagamatsu Hirofumi , Momomura Shin-ichi , Matsue Yuya 
Published: September 2024

Abstract

Aims
The 6-min walk test (6MWT) is a widely accepted tool for evaluating exercise tolerance and physical capacity, and the 6-min walk distance (6MWD) is an established prognostic factor in patients with heart failure (HF). However, the prognostic implications of post-6MWT dyspnoea remain unknown. We aimed to investigate the prognostic value of Borg scores after the 6MWT in patients with HF.

Methods and results
Patients hospitalized for HF who underwent the 6MWT before discharge were included. Post-test dyspnoea was assessed using the Borg scale. Patients were stratified into low and high Borg score groups based on the median Borg score. The primary outcome was 2-year mortality. Among 1185 patients analysed, the median Borg score was 12. The 6MWD was significantly shorter in the high Borg score group than in the low Borg score group. The 2-year mortality rate was 20.2%. In the Kaplan–Meier analysis, the high Borg score group demonstrated an association with 2-year mortality, which remained significant even after adjustment for conventional risk factors, including the 6MWD. Furthermore, the Borg scale provided significant net reclassification improvement to the conventional risk model incorporating 6MWD.

Conclusion
In hospitalized patients with HF, post-6MWT Borg scores were associated with 2-year mortality independent of the 6MWD, providing incremental prognostic value to the 6MWD. Even if patients are able to walk long distances for 6 min, it is essential to closely observe dyspnoea immediately thereafter.
Autonomic modulation impacts conduction velocity dynamics and wavefront propagation in the left atrium
Authors: Honarbakhsh Shohreh , Roney Caroline , Horrach Caterina Vidal , Lambiase Pier D , Hunter Ross J 
Published: September 2024

Abstract

Aims
Atrial fibrosis and autonomic remodelling are proposed pathophysiological mechanisms in atrial fibrillation (AF). Their impact on conduction velocity (CV) dynamics and wavefront propagation was evaluated.

Methods and results
Local activation times (LATs), voltage, and geometry data were obtained from patients undergoing ablation for persistent AF. LATs were obtained at three pacing intervals (PIs) in sinus rhythm (SR). LATs were used to determine CV dynamics and their relationship to local voltage amplitude. The impact of autonomic modulation- pharmacologically and with ganglionated plexi (GP) stimulation, on CV dynamics, wavefront propagation, and pivot points (change in wavefront propagation of ≥90°) was determined in SR. Fifty-four patients were included. Voltage impacted CV dynamics whereby at non-low voltage zones (LVZs) (≥0.5 mV) the CV restitution curves are steeper [0.03 ± 0.03 m/s ΔCV PI 600–400 ms (PI1), 0.54 ± 0.09 m/s ΔCV PI 400–250 ms (PI2)], broader at LVZ (0.2–0.49 mV) (0.17 ± 0.09 m/s ΔCV PI1, 0.25 ± 0.11 m/s ΔCV PI2), and flat at very LVZ (&lt;0.2 mV) (0.03 ± 0.01 m/s ΔCV PI1, 0.04 ± 0.02 m/s ΔCV PI2). Atropine did not change CV dynamics, while isoprenaline and GP stimulation resulted in greater CV slowing with rate. Isoprenaline (2.7 ± 1.1 increase/patient) and GP stimulation (2.8 ± 1.3 increase/patient) promoted CV heterogeneity, i.e. rate-dependent CV (RDCV) slowing sites. Most pivot points co-located to RDCV slowing sites (80.2%). Isoprenaline (1.3 ± 1.1 pivot increase/patient) and GP stimulation (1.5 ± 1.1 increase/patient) also enhanced the number of pivot points identified.

Conclusion
Atrial CV dynamics is affected by fibrosis burden and influenced by autonomic modulation which enhances CV heterogeneity and distribution of pivot points. This study provides further insight into the impact of autonomic remodelling in AF.
Accuracy of Whitebark Pine and Limber Pine Identification by Forest Inventory and Analysis Field Crews
Authors: Williams Shayla R , Steed James E , Morrone Jeremy , Goeking Sara A , Lavin Matt , Dodson Erich Kyle , Simons Rachel E 
Published: September 2024

Abstract
Accurate identification of whitebark and limber pine has become increasingly important following the 2022 listing of whitebark pine as a threatened species under the Endangered Species Act. However, morphological similarities make identification of the two species difficult where ranges overlap. Using a genetic test that differentiates whitebark and limber pine, we compared field identification by Forest Inventory and Analysis field crews with genetic identification for needle samples from 371 trees. Field identifications were 100% correct for the 76 samples collected from outside regions of species’ range overlap. A total of 83% of the field identifications were correct in regions of range overlap (89% for large trees, 88% for saplings, and 78% for seedlings). Field-identified samples were correct 60% of the time for limber pine and &gt;99% for whitebark pine. Random forests analysis revealed that identification accuracy is influenced by crew experience, large (≥ 12.7cm diameter) limber or whitebark pines recorded by field crews on the plot, elevation, Julian day of sample collection, and habitat type. We found that whitebark pine has likely been underestimated, and limber pine overestimated, within their overlapping ranges. We provide insights on improving accuracy of future monitoring where these species overlap.
Study Implications: Accurate identification of whitebark pine is critical for monitoring this threatened species, yet distinguishing whitebark from limber pine can be difficult. Genetic analysis determined accuracy of field identification by Forest Inventory and Analysis (FIA) crews was 83% where the species’ ranges overlap. Virtually all individuals identified as whitebark pine were genetically confirmed to be whitebark pine, although nearly 40% of individuals identified as limber pine were actually whitebark pine. Thus, previous data underestimated whitebark and overestimated limber pine abundance in the species’ range overlap. These results quantify reliability of FIA data for whitebark pine assessments and identify areas for improvement.
The Gongora gibba genome assembly provides new insights into the evolution of floral scent in male euglossine bee–pollinated orchids
Authors: Guizar Amador Maria Fernanda , Darragh Kathy , Liu Jasen W , Dean Cheryl , Bogarín Diego , Pérez-Escobar Oscar A , Serracín Zuleika , Pupulin Franco , Ramírez Santiago R 
Published: September 2024

Abstract
Orchidaceae is one of the most prominent flowering plant families, with many species exhibiting highly specialized reproductive and ecological adaptations. An estimated 10% of orchid species in the American tropics are pollinated by scent-collecting male euglossine bees; however, to date, there are no published genomes of species within this pollination syndrome. In this study, we present the first draft genome of an epiphytic orchid from the genus Gongora, a representative of the male euglossine bee–pollinated subtribe Stanhopeinae. The 1.83-Gb de novo genome with a scaffold N50 of 1.7 Mb was assembled using short- and long-read sequencing and chromosome capture (Hi-C) information. Over 17,000 genes were annotated, and 82.95% of the genome was identified as repetitive content. Furthermore, we identified and manually annotated 26 terpene synthase genes linked to floral scent biosynthesis and performed a phylogenetic analysis with other published orchid terpene synthase genes. The Gongora gibba genome assembly will serve as the foundation for future research to understand the genetic basis of floral scent biosynthesis and diversification in orchids.
Finding the Balance to Quiet the Striving: The Difference Between Successful Aging and Wise Aging
Authors: Glück Judith , Jäger Luisa , Auer-Spath Irina , Harbig Imke Alenka 
Published: September 2024

Abstract
This paper draws on wisdom and lifespan development research to propose a conception of “wise aging,” which may become particularly relevant in very old age as people’s capacities for successful aging decline. We propose that 3 types of balance distinguish wise aging from successful aging. First, wisdom balances one’s own interest with the greater good, emphasizing self-transcendence and compassion. Second, wisdom balances control striving with acceptance of uncontrollability. Wise aging involves a realistic awareness of one’s decreasing levels of control and one’s interconnectedness to and dependence on other people. Third, wisdom acknowledges, regulates, and balances positive and negative affect. Wise aging involves the ability to appreciate and relish the joys of life, but also to accept and embrace more negative emotions and to support others going through different times.
A new mouse model for PRPH2 pattern dystrophy exhibits functional compensation prior and subsequent to retinal degeneration
Authors: Cavanaugh Breyanna L , Milstein Michelle L , Boucher R Casey , Tan Sharon X , Hanna Mario W , Seidel Adam , Frederiksen Rikard , Saunders Thomas L , Sampath Alapakkam P , Mitton Kenneth P , Zhang Dao-Qi , Goldberg Andrew F X 
Published: September 2024

Abstract
Mutations in PRPH2 are a relatively common cause of sight-robbing inherited retinal degenerations (IRDs). Peripherin-2 (PRPH2) is a photoreceptor-specific tetraspanin protein that structures the disk rim membranes of rod and cone outer segment (OS) organelles, and is required for OS morphogenesis. PRPH2 is noteworthy for its broad spectrum of disease phenotypes; both inter- and intra-familial heterogeneity have been widely observed and this variability in disease expression and penetrance confounds efforts to understand genotype–phenotype correlations and pathophysiology. Here we report the generation and initial characterization of a gene-edited animal model for PRPH2 disease associated with a nonsense mutation (c.1095:C&gt;A, p.Y285X), which is predicted to truncate the peripherin-2 C-terminal domain. Young (P21) Prph2Y285X/WT mice developed near-normal photoreceptor numbers; however, OS membrane architecture was disrupted, OS protein levels were reduced, and in vivo and ex vivo electroretinography (ERG) analyses found that rod and cone photoreceptor function were each severely reduced. Interestingly, ERG studies also revealed that rod-mediated downstream signaling (b-waves) were functionally compensated in the young animals. This resiliency in retinal function was retained at P90, by which time substantial IRD-related photoreceptor loss had occurred. Altogether, the current studies validate a new mouse model for investigating PRPH2 disease pathophysiology, and demonstrate that rod and cone photoreceptor function and structure are each directly and substantially impaired by the Y285X mutation. They also reveal that Prph2 mutations can induce a functional compensation that resembles homeostatic plasticity, which can stabilize rod-derived signaling, and potentially dampen retinal dysfunction during some PRPH2-associated IRDs.
Denitrification genotypes of endospore-forming Bacillota
Authors: Bell Emma , Chen Jianwei , Richardson William D L , Fustic Milovan , Hubert Casey R J 
Published: September 2024

Abstract
Denitrification is a key metabolic process in the global nitrogen cycle and is performed by taxonomically diverse microorganisms. Despite the widespread importance of this metabolism, challenges remain in identifying denitrifying populations and predicting their metabolic end-products based on their genotype. Here, genome-resolved metagenomics was used to explore the denitrification genotype of Bacillota enriched in nitrate-amended high temperature incubations with confirmed N2O and N2 production. A set of 12 hidden Markov models (HMMs) was created to target the diversity of denitrification genes in members of the phylum Bacillota. Genomic potential for complete denitrification was found in five metagenome-assembled genomes from nitrate-amended enrichments, including two novel members of the Brevibacillaceae family. Genomes of complete denitrifiers encode N2O reductase gene clusters with clade II-type nosZ and often include multiple variants of the nitric oxide reductase gene. The HMM set applied to all genomes of Bacillota from the Genome Taxonomy Database identified 17 genera inferred to contain complete denitrifiers based on their gene content. Among complete denitrifiers it was common for three distinct nitric oxide reductases to be present (qNOR, bNOR, and sNOR) that may reflect the metabolic adaptability of Bacillota in environments with variable redox conditions.
Using a Data Analysis Project to Increase Knowledge of International Politics
Authors: Hendrickson Petra 
Published: September 2024

Abstract
In international politics classes, it can be challenging to develop course materials that will both cover a wide breadth of thematic issues as well as substantially increase student knowledge of specific countries’ political systems and experiences. Using an International Politics Data Analysis Project where students select a slate of 16 countries and complete four unit check-ins where they aggregate data, identify trends, and develop case studies related to the data, I demonstrate that students can gain more knowledge about a diverse set of countries than they might otherwise. Across two semesters, students reported gains in knowledge about all world regions from the beginning of the semester to the end of the semester. Students completing the project for the first time also reported significant gains in comfort with the practical skills associated with political science. Students who had already completed the 4 × 3 Project in a companion course reported knowledge gains in five of seven world regions. Paired data of the first and last unit check-in of the semester indicates increased competence with data manipulation, trend identification, and case study writing, providing objective data to support the students’ own impressions of their development as a result of the project.
Increased mortality in hospital- compared to community-onset carbapenem-resistant enterobacterales infections
Authors: Boutzoukas Angelique E , Mackow Natalie , Giri Abhigya , Komarow Lauren , Hill Carol , Chen Liang , Doi Yohei , Satlin Michael J , Arias Cesar , Wang Minggui , Mora Moreo Laura , Herc Erica , Cober Eric , Weston Gregory , Patel Robin , Bonomo Robert A , Fowler Vance , van Duin David 
Published: September 2024

Abstract

Background
The CDC reported a 35% increase in hospital-onset (HO) carbapenem-resistant Enterobacterales (CRE) infections during the COVID-19 pandemic. We evaluated patient outcomes following HO and community-onset (CO) CRE bloodstream infections (BSI).

Methods
Patients prospectively enrolled in CRACKLE-2 from 56 hospitals in 10 countries between 30 April 2016 and 30 November 2019 with a CRE BSI were eligible. Infections were defined as CO or HO by CDC guidelines, and clinical characteristics and outcomes were compared. The primary outcome was desirability of outcome ranking (DOOR) 30 days after index culture. Difference in 30-day mortality was calculated with 95% CI.

Results
Among 891 patients with CRE BSI, 65% were HO (582/891). Compared to those with CO CRE, patients with HO CRE were younger [median 60 (Q1 42, Q3 70) years versus 65 (52, 74); P &lt; 0.001], had fewer comorbidities [median Charlson comorbidity index 2 (1, 4) versus 3 (1, 5); P = 0.002] and were more acutely ill (Pitt bacteraemia score ≥4: 47% versus 32%; P &lt; 0.001). The probability of a better DOOR outcome in a randomly selected patient with CO BSI compared to a patient with HO BSI was 60.6% (95% CI: 56.8%–64.3%). Mortality at 30-days was 12% higher in HO BSI (192/582; 33%) than CO BSI [66/309 (21%); P &lt; 0.001].

Conclusion
We found a disproportionately greater impact on patient outcomes with HO compared to CO CRE BSIs; thus, the recently reported increases in HO CRE infections by CDC requires rigorous surveillance and infection prevention methods to prevent added mortality.