bluuebunny/crossref_metadata_2025_split huggingface dataset:
Who to Boost When: The Effect of Age and Dosing Interval on Delta and Omicron COVID-19 Incidence in the Open-label Phase of the COVE Trial
Authors: Follmann Dean , Wang Xiaowei , Baden Lindsey R , El Sahly Hana M , Essink Brandon , Gilbert Peter , Janes Holly E , Kelley Colleen F , Berman Megan A , Frank Ian , Chu Eric , Deng Weiping , Priddy Frances , Dixit Avika , Tomassini Joanne E , Das Rituparna , Miller Jacqueline , Zhou Honghong 
Published: November 2024

Abstract

Background
To help inform COVID-19 vaccination recommendations, we evaluated the impact of age and dosing interval on clinical benefit of a third dose of mRNA-1273.

Methods
Approximately 17 000 participants from the phase 3 Coronavirus Efficacy trial who previously received 2 doses of 100 µg mRNA-1273 were evaluated for COVID-19 between September 2021 and April 2022 during uptake of a third booster dose of 50 µg of mRNA-1273. Cox models assessed booster relative efficacy of a third dose.

Results
Initial booster relative efficacy against Delta COVID-19 was 83% (95% confidence interval, 60–93) 14 days postdose and 83% (67–91) 60 days later. Initial booster efficacy against Omicron COVID-19 was 56% (44–65) at 14 days postdose and 4% (−27 to 28) 120 days later. For those aged ≥65 years, initial booster efficacy against Omicron COVID-19 was 86% (69–93) compared with 50% (36–61) for those &lt;65 years. Placebo crossover to 2 doses of mRNA-1273 induced a median 5-month difference from the second to third dose between the original randomized arms. Postboost, the mRNA-1273 arm had a 24% (16%, 32%) lower risk of Omicron COVID-19 compared to the placebo-mRNA-1273 arm. Modeling predicted a 41% postboost reduction in Omicron COVID-19 for a 15- versus 7-month interval between the second and third doses.

Conclusions
Boosting reduced Delta COVID-19 risk by 83% through 2 months and reduced Omicron COVID-19 risk by 56% but declined by 4 months. A 15- versus 7-month dosing interval predicted a 41% postboost reduction in Omicron COVID-19 but increased preboost risk.

Primary Funding Source
The National Institutes of Health/National Institute of Allergy and Infectious Diseases.
Registration for the COVE Trial.  ClinicalTrials.gov ID# NCT04470427
Coronary artery microfistulae, Thebesian veins, or vessels of Wearn?
Authors: Farandzha Dzhem , Stancheva Kristina , Iliev Petar , Azis Embie , Hazarbasanov Dobri 
Published: November 2024

Abstract
We present the case of a 73-year-old woman with coronary artery-left ventricular multiple microfistulae, who was admitted with symptoms and ECG suggestive of coronary artery disease. Coronary angiography revealed tortuous coronary arteries with multiple microfistulae between the left coronary artery and the left ventricle, as well as between the right coronary artery and the left ventricle. Transthoracic echocardiography (TTE) was also able to clearly demonstrate the presence of the microfistulae with their direction of blood flow towards the left ventricle. Despite traditional reliance on coronary angiography, this case advocates for the diagnostic role of TTE due to its non-invasive nature and ability to provide crucial preliminary information, even in cases with such small structures as these microfistulae. We emphasize the importance of precise, modern terminology over historical eponyms such as Thebesian veins or vessels of Wearn, aligning medical communication with contemporary diagnostic capabilities.
Targetoid skin lesions in a newborn: a case of erythema multiforme
Authors: Awashra Ameer , Milhem Fathi , Nabresi Noor , Matar Shatha 
Published: November 2024

Abstract
Erythema multiforme (EM) is an immune-mediated condition that manifests as targetoid skin lesions and can be triggered by various factors, including infections and vaccinations. This case report describes a 41-day-old full-term male infant who developed widespread annular, bullseye-shaped erythematous skin lesions one week after receiving the Bacillus Calmette–Guérin (BCG) vaccination. The infant, exclusively breastfed and without a significant past medical history, presented with these lesions but no associated systemic symptoms. Physical examination revealed characteristic targetoid lesions, sparing the face, palms, soles, and mucous membranes. Laboratory tests, including a complete blood count and infection markers, were within normal ranges except for a mildly elevated C-reactive protein. The differential diagnosis ruled out other conditions and EM diagnosis is confirmed. The infant was managed conservatively with supportive care, and the lesions resolved without the need for antibiotics or any additional therapy. The patient remained stable and was discharged with instructions for monitoring and follow-up. So this case highlights the importance of distinguishing EM from other similar conditions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and urticaria.
Substrate specificities in the chlorophyll catabolism of aquatic protists determined with in vivo phagocytotic assays
Authors: Kashiyama Yuichiro , Miichi Shizuka , Imanishi Hiroki , Maruyama Moe , Ogasawara Shin , Tamiaki Hitoshi 
Published: November 2024

Abstract
Chlorophylls (Chls) are ubiquitous photosynthetic pigments with inherent potential to generate cytotoxic reactive oxygen species. Therefore, all phototrophs and any phagotrophs that attempt to digest phototrophic cells have presumably developed mechanisms to mitigate this phototoxicity. In aquatic environments, the Chls produced by the dominant producers, microalgae, are catabolized into nonphototoxic pigments, cyclopheophorbide enols (CPEs), either by microalga-feeding protists or autonomously, particularly by those carrying secondary chloroplasts during the dismantling of their chloroplasts. However, the biochemistry underpinning CPE-accumulating Chl catabolism remains largely unexamined. To characterize the reactions in the transformation pathway and identify the pivotal enzyme for the formation of the seven-membered ring distinctive to CPEs, we conducted qualitative in vivo experiments using hemisynthetically prepared Chl derivatives in the cells of a euglenozoan algivorous (phycophagic) protist, Peranema trichophorum NIES-4660. We supplied polymer beads coated with Chl-b derivatives with their food cells, a unicellular red alga, Cyanidioschyzon merolae, which exclusively contains Chl-a. After administration of Chl-b or its free base with the beads, we detected a CPE derivative with a formyl group at the C7 position [cyclopheophorbide b-enol (cPPB-bE)], clearly derived from the appended derivatives, and not from the Chl-a of the alga. In contrast, cPPB-bE was not detected when zinc- and copper-metalated Chls and C132-demethoxycarbonylated Chl-b were added, although the latter resulted in the generation of its demetalated free-base form. These results indicate that (I) pheophytins are the actual substrates of the cyclization enzyme and (II) cyclization proceeds after the enzymatic dechelation of the central magnesium of natural Chls.
Predicting attentional focus: Heartbeat-evoked responses and brain dynamics during interoceptive and exteroceptive processing
Authors: Fló Emilia , Belloli Laouen , Cabana Álvaro , Ruyant-Belabbas Alessia , Jodaitis Lise , Valente Melanie , Rohaut Benjamin , Naccache Lionel , Rosanova Mario , Comanducci Angela , Andrillon Thomas , Sitt Jacobo 
Published: November 2024

Abstract
Attention shapes our consciousness content and perception by increasing the probability of becoming aware and/or better encoding a selection of the incoming inner or outer sensory world. Engaging interoceptive and exteroceptive attention should elicit distinctive neural responses to visceral and external stimuli and could be useful in detecting covert command-following in unresponsive patients. We designed a task to engage healthy participants’ attention toward their heartbeats or auditory stimuli and investigated whether brain dynamics and the heartbeat-evoked potential (HEP) distinguished covert interoceptive–exteroceptive attention. Exteroceptive attention yielded an overall flattening of the power spectral density (PSD), whereas during interoception, there was a decrease in complexity, an increase in frontal connectivity and theta oscillations, and a modulation of the HEP. Subject-level classifiers based on HEP features classified the attentional state of 17/20 participants. Kolmogorov complexity, permutation entropy, and weighted symbolic mutual information showed comparable accuracy in classifying covert attention and exhibited a synergic behavior with the HEP features. PSD features demonstrated exceptional performance (20/20). Command-following was assessed in five brain-injured patients with a modified version of the task. An unresponsive wakefulness syndrome/vegetative state patient and a locked-in syndrome patient demonstrated a willful modulation of the HEP and together with the explored brain markers suggest that patients were complying with task instructions. Our findings underscore the importance of attentional mechanisms in shaping interoceptive and exteroceptive sensory processing and expand the framework of heart–brain interactions employed for diagnostic purposes in patients with disorders of consciousness.
The visual stimuli attributes instrumental for collective-motion-related decision-making in locusts
Authors: Bleichman Itay , Shefi Peleg , Kaminka Gal A , Ayali Amir 
Published: November 2024

Abstract
Visual interactions play an instrumental role in collective-motion-related decision-making. However, our understanding of the various tentative mechanisms that can serve the visual-based decision-making is limited. We investigated the role that different attributes of the visual stimuli play in the collective-motion-related motor response of locust nymphs. We monitored and analyzed the behavioral responses of individual locusts tethered in a natural-like walking posture over an airflow-suspended trackball to carefully selected stimuli comprising various black rectangular shapes. The experimental findings together with a prediction model relating the level of behavioral response to the visual stimuli attributes indicate a major role of the number of objects in the visual field, and a further important effect of the object's vertical moving edges. While the object's horizontal edges can be utilized in the estimation of conspecifics' heading, the overall area or visual angle subtended by the stimuli do not seem to play any role in inducing the response. Our results offer important novel insights regarding the fundamental visual-based mechanisms underlying animal collective motion and can be useful also in swarm robotics.
A matter of culture? Conceptualizing and investigating “Evidence Cultures” within research on evidence-informed policymaking
Authors: Bandola-Gill Justyna , Andersen Niklas A , Leng Rhodri , Pattyn Valérie , Smith Katherine E 
Published: November 2024

Abstract
This paper conceptualizes the notion of “evidence culture” in evidence-informed policymaking by surveying existing literature that either specifically employs the term or uses adjacent terms such as “epistemic” or “research culture”. It employs mixed-methods scoping review, combining citation analysis using Web of Science data used to identify the key clusters of scholarship with a qualitative thematic analysis of key papers across these clusters. This analysis identifies seven distinct approaches to “evidence cultures” across disciplinary communities. The key points of divergence across the clusters include the meanings of evidence, the underlying understanding of the evidence–policy interplay, the conceptualization of culture, and its implications for evidence use in policy. Building on these insights, we offer a framework for analyzing evidence cultures, arguing for the conceptual and empirical utility of this term in advancing scholarship on evidence use in policy settings.
Fractional flow reserve measurement using dynamic CT perfusion imaging in patients with coronary artery disease
Authors: So Aaron , Choo Ki Seok , Lee Ji Won , Kim Yun-Hyeon , Haider Mustafa , Hasan Mahmud , El-Ganga Serag , Goela Akshaye , Teefy Patrick , Choe Yeon Hyeon 
Published: November 2024

Abstract

Purposes
The objective was to evaluate the accuracy of a novel CT dynamic angiographic imaging (CT-DAI) algorithm for rapid fractional flow reserve (FFR) measurement in patients with coronary artery disease (CAD).

Materials and Methods
This retrospective study included 14 patients (age 58.5 ± 10.6 years, 11 males) with CAD who underwent stress dynamic CT myocardial perfusion scanning with a dual-source CT scanner. The included patients had analyzable proximal and distal coronary artery segments adjacent to the stenosis in the perfusion images and had corresponding invasive catheter-based FFR measurements for that stenosis. An in-house software based on the CT-DAI algorithm was used to compute FFR using the pre- and post- lesion coronary time-enhancement curves obtained from the stress myocardial perfusion images. The CT-DAI derived FFR values were then compared to the corresponding catheter-based invasive FFR values. A coronary artery stenosis was considered functionally significant for FFR value &lt;0.8.

Results
The CT-DAI derived FFR values were in agreement with the invasive FFR values in all 15 coronary arteries in 14 patients, resulting in 100% per-vessel and per-patient diagnostic accuracy. FFR derived using CT-DAI (M = 0.768, SD = 0.156) showed an excellent linear correlation (R = 0.910, P &lt; .001) and statistical indifference (P= .655) with that measured using invasive catheter-based method (M = 0.796, SD = 0.149). Bland-Altman analysis showed no significant proportional bias.

Conclusion
The novel CT-DAI algorithm can reliably compute FFR across a coronary artery stenosis directly from dynamic CT myocardial perfusion images, facilitating rapid on-site hemodynamic assessment of the epicardial coronary artery stenosis in patients with CAD.
Changes in circadian timing following a 1-week in-home sleep extension manipulation in habitually short-sleeping adolescents
Authors: Holtman Sydney , Cooper Emily , Brinton John T , Bowen Anne E , Hawkins Stephen , Cree Melanie G , Nadeau Kristen J , Wright Kenneth P , Simon Stacey L 
Published: November 2024

Abstract

Study Objectives
Evaluate objectively measured circadian rhythms following 1-week of at-home sleep extension in habitually short-sleeping adolescents.

Methods
Twenty-six participants (16.1 ± 1.2 years, 69% female, and 65% White non-Hispanic) with insufficient sleep (≤7 h on school nights) were randomized to 1 week of typical sleep (TS; usual school schedule) and sleep extension (EXT; ≥1-h additional time in bed) in counterbalanced order with a 1-month washout between conditions. Home monitoring of actigraphy-estimated sleep and light exposure was assessed during both weeks. Hourly in-laboratory evening/morning dim-light salivary melatonin samples were obtained and onset (DLMOn) and offset (DLMOff) were calculated following each condition.

Results
Sleep duration increased by 1.37 h (95% CI = 1.09, 1.66; p &lt; 0.001), bedtimes advanced by 1.40 (95% CI = –1.75, –1.06; p &lt; 0.001), and waketimes did not significantly change (p = 0.055) during EXT compared to TS. There was no change in DLMOn or DLMOff following EXT (both p &gt; 0.05). The DLMOn-sleep onset phase angle narrowed by 0.72 h (95% CI = –1.39, –0.07; p = 0.04) during EXT. Light exposure within 2-h of bedtime was significantly higher during EXT compared to TS (23.37 vs. 7.73 lux; p = 0.048).

Conclusions
Sleep extension did not change melatonin onset or offset but may have increased circadian alignment. Further research should evaluate the addition of specific strategies to improve circadian timing such as morning bright light in combination with sleep extension.
Exposure to 2,4-Dichlorophenoxyacetic acid stimulates the calcium/ROS/CK1α pathway to trigger Hemolysis and Eryptosis in red blood cells
Authors: Alghareeb Sumiah A , Alsughayyir Jawaher , Alfhili Mohammad A 
Published: November 2024

Abstract

Objective
The agricultural herbicide 2,4-dichlorophenoxyacetic (2,4-D) is cytotoxic to human red blood cells (RBCs) by virtue of oxidative hemolysis. Nevertheless, there remains a great paucity of literature detailing the mechanisms by which 2,4-D triggers hemolysis. Also, the eryptotic effects of 2,4-D has thus far been largely overlooked. This study aims to expand current understanding of the cytotoxic properties of 2,4-D in RBCs.

Methods
Cells were exposed to 2,4-D ranging from 100 to 1,000 μM for 24 h at 37 °C under varied experimental conditions. Hemolysis, LDH, AST, and AChE activities were photometrically measured. Flow cytometry assessed eryptotic markers including cell volume by forward scatter (FSC), phosphatidylserine (PS) externalization by annexin-V positivity, reactive oxygen species by H2DCFDA, and intracellular Ca2+ levels by Fluo4/AM.

Results
2,4-D induced Ca2+-independent, concentration-responsive hemolysis paralleled by increased LDH, AST, and K+ in the supernatant, which was significantly blunted by D4476, isosmotic urea, sucrose, and polyethylene glycol 8,000 (PEG). Notably, 2,4-D caused a significant increase in cells positive for annexin-V-FITC, DCF, and Fluo4 with a concomitant decrease in AChE activity and FSC following KCl release. Furthermore, lymphocytes and reticulocytes were sensitive to 2,4-D within a whole blood milieu.

Conclusion
This work introduces novel cytotoxic mechanisms of 2,4-D in RBCs and reveals its pro-eryptotic effects. 2,4-D toxicity is neutralized by blockade of casein kinase 1α signaling and the presence of urea, sucrose, and PEG. These findings have significant implications for public health and inform future health risk assessments to develop novel preventive and therapeutic strategies.
The role of macrolides in chronic rhinosinusitis and nasal polyps
Authors: Suzaki Isao 
Published: November 2024

Purpose of review
Chronic rhinosinusitis (CRS) is a heterogeneous condition, so personalized treatment based on each patient's pathophysiology is essential, rather than a one-size-fits-all approach. Drug therapy for CRS has evolved significantly in recent years with the introduction of biologics, necessitating a reconsideration of the role of low-dose and long-term administration of a 14-membered ring macrolide (macrolide therapy) in the treatment of CRS. Recent research on the mechanisms of macrolide therapy and its proper use may assist physicians in improving patients’ quality of life and reducing disease burden.

Recent findings
A classification of the pathogenesis of CRS based on endotype has been proposed, with type 2 inflammation playing a particularly important role as a refractory factor. Macrolide therapy improves CRS via immunomodulatory and anti-inflammatory effects rather than antimicrobial action, and it is expected to be effective in patients with neutrophil-dominant inflammation.

Summary
Understanding the effectiveness and limitations of macrolide therapy is critical for making the best treatment decisions, especially when combined with surgery and other pharmacologic therapies. Therefore, selecting appropriate patients for macrolide therapy is critical for achieving adequate therapeutic efficacy.
The autonomous nervous system and the cholinergic anti-inflammatory reflex in postoperative neurocognitive disorders
Authors: Lammers-Lietz Florian , Spies Claudia , Maggioni Martina A. 
Published: November 2024

Purpose of review
Postoperative delirium (POD) is a common and serious complication after surgery. It is associated with postoperative neurocognitive disorder (PNCD). The vagal cholinergic anti-inflammatory pathway (CAP) has been hypothesized to play a role in POD/PNCD and may be a target for interventions such as transcutaneous auricular stimulation (taVNS). We aim to review associations of heart rate variability (HRV) as an indicator of vagal function with POD and postoperative immune reaction as well as taVNS as a potential preventive intervention for POD.

Recent findings
Autonomous nervous system (ANS) dysfunction was a common finding in studies analysing HRV in POD and postoperative cognitive dysfunction, but results were heterogeneous. There was no evidence from HRV analysis that vagal activity prevents overshooting postoperative immune activation, but HRV may help to identify patients at risk for postoperative infections. Animal studies and preliminary trials suggest that taVNS may be used to prevent POD/PNCD.

Summary
Our review provides no evidence that CAP suppression is associated with POD/PNCD. Future studies should consider that high vagal tone may also mediate immunosuppression in surgical patients, yielding an increased risk for postoperative infections. Although taVNS is a promising approach to prevent POD/POCD, future studies should take these concerns into account.
Trends in Specialty Training and National Institutes of Health Funding Among Surgeon-Scientists
Authors: Velez Gabriel , Mahajan Vinit B. , Weigel Ronald J. , Lentz Steven R. 
Published: November 2024

Purpose:
To determine if dual-degree training [ie, completion of a National Institutes of Health (NIH)-funded MD/PhD program], among other professional development and demographic variables, predicted academic productivity (eg, K-to-R conversion, number of publications, etc.) among early-career surgeon-scientists.

Methods:
We analyzed publicly available data from the National MD/PhD Program Outcomes Study and the Association of American Medical Colleges Graduate Medical Education Track database to identify trends in the number and proportion of MD/PhD graduates pursuing surgical specialties. NIH Research Portfolio Online Reporting Tool Expenditures and Results was interrogated to identify a cohort of early-career academic surgeon-scientists receiving K-awards from 2011 to 2021.

Results:
The total number of MD/PhD program graduates completing Graduate Medical Education training increased each decade after the Medical Scientist Training Program was established by the National Institute of General Medical Sciences, but the proportion completing surgical specialties did not change significantly (P = 0.96) from 1965 to 2014. More recent residency match trends demonstrate an increase in both the proportion and number of MD/PhD graduates entering surgical specialties, with 21.5% entering surgical residency training in 2020. Among 476 early-career academic surgeon-scientists receiving K-awards at 70 institutions, 27% were faculty members at only 4 universities, suggesting that federally funded surgeon-scientists are concentrated at a small number of institutions. Although MD/PhD graduates represented only 2.3% of active surgical residents from 2011 to 2020, they constituted a much higher fraction of K-awardees (29%). Of 296 surgeon-scientists who completed K-awards, 35% successfully obtained an R01-equivalent award.

Conclusions:
These findings emphasize the need for comprehensive career development and institutional resources to support early-career surgeon-scientists.