bluuebunny/crossref_metadata_2025 huggingface dataset:
Portraying political theatre: parody and caricature, ancient and modern
Authors: Davies Malcolm
Published: November 2024

This article builds on observations made in its author’s book The Hero’s Life-Choice (2023) and examines four nineteenth-century cartoons by John Doyle and his son Richard. It shows how the concetto underlying their title ‘a famous actor between Tragedy and Comedy’ descends from an eighteenth-century painting by Joshua Reynolds of the Shakespearean actor Garrick between the same two female personifications. This painting itself parodied the parable ‘Heracles at the Crossroads’ or ‘The Choice of Heracles between Virtue and Pleasure’, by the fifth-century bc Greek sophist Prodicus. The three earliest cartoons show two politicians on either side of, respectively, a personification of England, a king of England, and a Prime Minister of England. They may thus be interpreted as adumbrating the present-day conviction that politics is merely performative theatre. The appearance of Prime Minister Robert Peel in the latest of John Doyle’s cartoons chimes with the independently attested view by some contemporaries of his career as that of an actor-manager. A final section attempts to explain the unexpected reappearance of the ‘famous actor’ trope in two twentieth-century political cartoons and its definitive disappearance thereafter.
What to Expect When Switching to a Biosimilar: A US Healthcare Professional’s Perspective
Authors: Belton Juanita , D’Apice Nicholas
Published: November 2024

Lay Summary

As biosimilars become more available, many patients with inflammatory bowel disease may experience having their treatment switched from a reference product to a biosimilar. In this communication, a physician assistant and a pharmacist discuss the patient experience when switching to a biosimilar.
A case report of late vessel occlusion presenting as ST-segment elevation myocardial infarction after drug-coating balloon treatment of in-stent restenosis
Authors: Marschall Alexander , del Val David , Bastante Teresa , Rivero Fernando , Alfonso Fernando
Published: November 2024

Background

Drug-coated balloons (DCBs) offer an appealing therapeutic alternative for the treatment of patients with coronary in-stent restenosis (ISR). In-segment late lumen loss, translating into recurrent ISR and the clinical need for target lesion revascularization, represents a well-established and thoroughly investigated limitation of DCB in this setting. However, abrupt vessel occlusion, clinically presenting as ST-segment elevation myocardial infarction (STEMI), has not been previously described after DCB therapy for ISR.

Case summary

We herein present the case of a 70-year-old patient that underwent percutaneous coronary intervention (PCI) with DCB for ISR. Despite achieving an excellent acute angiographic result (with no flow-limiting dissection and minimal angiographic residual stenosis), the patient presented 3 months later with STEMI due to occlusion of the previously treated segment. After adequate lesion preparation, a drug-eluting stent was implanted with optimal final angiographic result. The patient was discharged 2 days after the PCI without any post-procedural complications and remained asymptomatic at 6-month clinical follow-up.

Discussion

This case report is the first description of an abrupt vessel occlusion presenting as STEMI following a DCB angioplasty for ISR. This exceptional presentation does not dismount the solid evidence supporting the long-term safety of DCB in these challenging patients.
On the rate of aneuploidy reversion in a wild yeast model
Authors: Hose James , Zheng Qi , Sharp Nathaniel P , Gasch Audrey P
Published: November 2024

Aneuploidy, arising from the gain or loss of chromosomes due to nondisjunction, is a special class of mutation. It can create significant phenotypic changes by altering the abundance of hundreds of genes in a single event, providing material for adaptive evolution. But it can also incur large fitness costs relative to other types of mutations. Understanding the mutational dynamics of aneuploidy is important for modeling its impact in nature, but aneuploidy rates are difficult to measure accurately. One challenge is that aneuploid karyotypes may revert back to euploidy, biasing forward mutation rate estimates—yet the rate of aneuploidy reversion is largely uncharacterized. Furthermore, current rate estimates are confounded because fitness differences between euploids and aneuploids are typically not accounted for in rate calculations. We developed a unique fluctuation assay in a wild-yeast model to measure the rate of extra-chromosome loss across 3 aneuploid chromosomes while accounting for fitness differences between aneuploid and euploid cells. We show that incorporating fitness effects is essential to obtain accurate estimates of aneuploidy rates. Furthermore, the rate of extra-chromosome loss, separate from karyotype fitness differences, varies across chromosomes. We also measured rates in a strain lacking RNA-binding protein Ssd1, important for aneuploidy tolerance and implicated in chromosome segregation. We found no role for Ssd1 in the loss of native aneuploid chromosomes, although it did impact an engineered chromosome XV with a perturbed centromeric sequence. We discuss the impacts and challenges of modeling aneuploidy dynamics in real-world situations.
Life Course Associations of Sibling Relationships and Cognitive Functioning in Late Adulthood
Authors: Kong Jooyoung , Moorman Sara M , Lee Gina , Engelman Michal
Published: November 2024

Objectives

Relying on the linked lives concept within the life course perspective, the current study examined the lifelong associations of sibling relationships and their effects on cognitive functioning in late adulthood.

Methods

Using data from the sibling cohort of the Wisconsin Longitudinal Study, we estimated a mediational model, examining the effects of childhood sibling interactions and adverse childhood experiences (ACEs), as proxy measures for the parent–child relationship, on cognitive functioning in late adulthood through adult sibling closeness and contact. Respondents’ cognitive functioning was assessed using the Telephone Interview for Cognitive Status-modified (TICS-m) when they were in their early 80s, on average. We conducted multilevel structural equation modeling.

Results

Positive childhood sibling interactions (e.g., hugging, helping) were associated with increased adult sibling closeness and contact, whereas higher cumulative ACEs were associated with decreased adult sibling closeness and contact. We found significant indirect associations: (a) positive sibling interactions during childhood were associated with more frequent sibling contact across respondents’ mid-50s through early 70s, which was in turn associated with higher TICS-m scores in their early 80s; (b) higher cumulative ACEs were associated with less frequent sibling contact, which was in turn associated with lower TICS-m scores.

Discussion

The results suggest that childhood experiences within the family of origin may have lasting effects on adult sibling relationships and the cognitive functioning of older adults. This study highlights the potential cognitive benefits of frequent contact with adult siblings, underscoring the importance of nurturing sibling relationships throughout one’s life.
iMFP-LG: Identification of Novel Multi-Functional Peptides by Using Protein Language Models and Graph-Based Deep Learning
Authors: Luo Jiawei , Zhao Kejuan , Chen Junjie , Yang Caihua , Qu Fuchuan , Liu Yumeng , Jin Xiaopeng , Yan Ke , Zhang Yang , Liu Bin
Published: November 2024

Functional peptides are short amino acid fragments that have a wide range of beneficial functions for living organisms. The majority of previous research focused on mono-functional peptides, but a growing number of multi-functional peptides have been discovered. Although there have been enormous experimental efforts to assay multi-functional peptides, only a small fraction of millions of known peptides have been explored. Effective and precise techniques for identifying multi-functional peptides can facilitate their discovery and mechanistic understanding. In this article, we presented a method iMFP-LG for identifying multi-functional peptides based on protein language models (pLMs) and graph attention networks (GATs). Comparison results showed that iMFP-LG outperforms state-of-the-art methods on both multi-functional bioactive peptides and multi-functional therapeutic peptides datasets. The interpretability of iMFP-LG was also illustrated by visualizing attention patterns in pLMs and GATs. Regarding the outstanding performance of iMFP-LG on the identification of multi-functional peptides, we employed iMFP-LG to screen novel candidate peptides with both ACP and AMP functions from millions of known peptides in the UniRef90. As a result, 8 candidate peptides were identified, and 1 candidate that exhibits both antibacterial and anticancer effects was confirmed through molecular structure alignment and biological experiments. We anticipate that iMFP-LG can assist in the discovery of multi-functional peptides and contribute to the advancement of peptide drug design.
Secession or Sense of Belonging? Marginalization in the Context of Transnationality
Authors: Idler Annette , McGill Dáire
Published: November 2024

How does a state’s marginalization of borderland communities influence their sense of belonging? We argue that, in unstable regions in the Global South, such marginalization reinforces people’s sense of belonging to a transnational community. As we demonstrate, two causal mechanisms account for this process: the marginalization enhances (i) the border’s “disguising” quality that muddies diverse forms of insecurity and (ii) the border’s “facilitating” quality that permits certain actors and activities to cross borders while stopping others. Consolidation of people’s sense of belonging to a transnational community has implications for the state, as losing part of its citizenry to this transnational community undermines its own authority and the state–society relationship. Drawing on the case of the Colombian–Venezuelan borderlands, we substantiate our argument through evidence collected during in-depth fieldwork, including interviews and focus groups with peasants and other residents from remote borderland regions as well as with state and civil society stakeholders. We contribute to scholarship on identity and sense of belonging by theorizing its link to marginalization in the context of international borders. We further contribute empirically by documenting little-known cross-border practices and activities of residents of the shared border region of the Colombian department of Cesar and the Venezuelan state of Zulia.
Anopheles inthanonensis, formal name for An. baileyi species D of the Baileyi Complex (Diptera: Culicidae: Anophelinae) in Thailand
Authors: Phanitchakun Thanari , Wilai Parinya , Saingamsook Jassada , Harbach Ralph E , Somboon Pradya
Published: November 2024

Anopheles baileyi species D of the Baileyi Complex, subgenus Anopheles (Diptera: Culicidae) in Thailand is diagnosed and formally named An. inthanonensis Somboon & Harbach, n. sp. Morphological characters of the adults, and the pupal and larval stages with their chaetotaxy, are provided and compared with other species of the complex. Phylogenetic analysis of COI sequences revealed that An. inthanonensis appears to be more closely related to An. monticola in Bhutan and China than it is to other members of the Baileyi Complex.
Big Ideas That Percolate into Clinical Ethics
Authors: Parker J Clint
Published: November 2024

Philosophers throughout history have long been drawn to big, important ideas that bubble up to the surface in interesting ways in myriads of disparate contexts. Following this tradition, authors in this issue engage with big ideas that percolate into clinical ethics, such as hope in healthcare, empathy in genetic counseling, the ramifications of Western cultural assumptions in clinical ethics, the proper aims of palliative hospice and palliative medicine, and the proper role of the public in pharmacovigilance.
Cancer clinical trial participation: a qualitative study of Black/African American communities’ and patient/survivors’ recommendations
Authors: Kaljee Linda , Antwi Sylvester , Dankerlui Doreen , Harris Donna , Israel Barbara , White-Perkins Denise , Ofori Aboah Valerie , Aduse-Poku Livingstone , Larrious-Lartey Harriet , Brush Barbara , Coombe Chris , Patman La’Toshia , Cawthorne Nayomi , Chue Sophia , Rowe Zachary , Mills Cassandra , Fernando Kurt , Daniels Gwendolyn , Walker Eleanor M , Jiagge Evelyn
Published: November 2024

Background

Black/African Americans experience disproportionate cancer burden and mortality rates. Racial and ethnic variation in cancer burden reflects systemic and health-care inequities, cancer risk factors, and heredity and genomic diversity. Multiple systemic, sociocultural, economic, and individual factors also contribute to disproportionately low Black/African American participation in cancer clinical trials.

Methods

The Participatory Action for Access to Clinical Trials project used a community-based participatory research approach inclusive of Black/African American community-based organizations, Henry Ford Health, and the University of Michigan Urban Research Center. The project aims were to understand Black/African Americans’ behavioral intentions to participate in cancer clinical trials and to obtain recommendations for improving participation. Audio-recorded focus group data were transcribed and coded, and searches were conducted to identify themes and subthemes. Representative text was extracted from the transcripts.

Results

Six community focus group discussions (70 participants) and 6 Henry Ford Health patient/survivor focus group discussions (29 participants) were completed. General themes related to trial participation were identified, including (1) systemic issues related to racism, health disparities, and trust in government, health systems, and clinical research; (2) firsthand experiences with health care and health systems; (3) perceived and experienced advantages and disadvantages of clinical trial participation; and (4) recruitment procedures and personal decision-making processes. Specific recommendations on how to address barriers were obtained.

Conclusions

Community-based participatory research is effective in bringing communities equitably to the table. To build trust, health systems must provide opportunities for patients and communities to jointly identify factors affecting cancer clinical trial participation, implement recommendations, and address health disparities.
Staggered Difference-in-Differences Estimation for Antitrust Analysis: A Review of Literature and Recommendations for Practitioners
Authors: Faghani Hassan , VanOmmeren Steven
Published: November 2024

The aim of this paper is twofold: first, we discuss literature developments surrounding difference-in-differences (DiD) methods with staggered treatment mechanisms. Second, we provide a resource for sound DiD analysis in antitrust expert testimony in light of these developments. We review relevant papers and their most important conclusions. We then discuss the antitrust implications of three important topics: parallel trends, the not-yet-treated group, and data with customer entry and exit. We supplement this discussion with Monte Carlo analysis, in which we compare the performance of DiD estimators and quantify certain types of bias. Finally, we discuss the sensitivity and robustness checks that should underlay expert testimony going forward. DiD theory has come a long way in the academic literature since the 2010s, and we distill that knowledge into what we consider to be the standards for robust DiD results going forward.
The hydrodynamic analysis of the fully appended DARPA SUBOFF model in the SPMM tests integrating the LES model with the dynamic mesh method
Authors: Lin Yu-Hsien , Lee Meng-Chun , Hasan Ahmad Darori
Published: November 2024

To investigate the hydrodynamic coefficients of the fully appended DARPA SUBOFF model under various motion modes, this study develops user-defined functions within a computational fluid dynamics (CFD) model to simulate sting-supported planar motion mechanism tests. A dimensionless yawing velocity (r′) is proposed to evaluate the influence of motion periods and amplitudes on the hydrodynamic coefficients. Taking advantage of high-resolution turbulence simulation, reduced model dependency and applicability to complex geometries, this study integrates large eddy simulation and the dynamic mesh method to simulate each motion mode. Discrepancies between simulation results and experimental data for some velocity-dependent force derivatives in oblique towing tests may be linked to the rotational centers of the planar motion mechanism (PMM) supports. Variations in PMM devices affect some acceleration-dependent moment derivatives in pure sway and heave tests. Finally, turning circle maneuvers were conducted to verify the effectiveness of the simulated hydrodynamic coefficients.
Mature cystic teratoma mimicking a tailgut cyst in an adolescent female: a case report
Authors: Abatli Safaa , AlHabil Yazan , Hamad Mohammed Shawkat , Abulibdeh Yousef
Published: November 2024

Presacral tumors are uncommon, particularly in the pediatric population, and can arise from various germ cell types during embryologic development. Tailgut cysts, or retrorectal cystic hamartomas, represent rare congenital anomalies resulting from defective regression of hindgut remnants. We present a unique case of a 13-year-old female with pelvic symptoms, initially suspected to have a tailgut cyst based on imaging findings. However, surgical exploration revealed a mature cystic teratoma, a rare occurrence in this age group. Surgical excision was performed using an anterior approach, revealing adhesions and necessitating meticulous dissection for complete removal. Histopathological examination of the mass unexpectedly confirmed a mature cystic teratoma, characterized by a fibrovascular cyst wall containing smooth muscle and lobules resembling salivary acini, the cyst’s surface exhibited squamous and respiratory-type epithelium. The accurate diagnosis of presacral masses, rather than relying solely on diagnostic measures, underscores the importance of prioritizing surgical exploration for definitive assessment and management.
Spontaneous sigmoid perforation and subsequent ruptured hepatic aneurysms in suspected vascular type Ehlers–Danlos syndrome: a case report and comprehensive literature review
Authors: Oh SaeRam , Hudnall Aaron D , Fitzgerald Caitlin A
Published: November 2024

Ehlers–Danlos syndrome (EDS) is an inherited disorder of collagen creation and function which can affect many organs. Surgical management of EDS spectrum remains a significant challenge for surgeons, including the vascular type of EDS (vEDS). There do not exist specific guidelines for the management of vEDS, which proves difficulty given the devastating pathology and potential outcomes. This case report emphasizes the need for further research in many areas including the need for certain screenings to identify any vascular aneurysms or dissections prior to rupture, as well as asking should there be a screen for this gene mutation in COL3A1 included at birth. Our case report is one of few reports that link the spontaneous colonic rupture that may trigger the subsequent vascular catastrophe leading to devastating mortality.
A rare account of incidentally discovered anal melanoma
Authors: Khan Nawal , Irving Dondre , O’Connor Lynn
Published: November 2024

Anal melanoma is a rare and highly aggressive malignancy that carries a poor prognosis. Due to its variable and ambiguous presentation, it is often misdiagnosed as a hemorrhoid, polyp, or an ulcer with a concomitant rectal prolapse. Clinicians usually have a low suspicion of anal melanoma due to its rarity and most people present with metastatic disease at the time of diagnosis. We report a case of a patient incidentally found to have anal melanoma. Prompt surgical resection with wide local excision versus abdominoperineal resection remains the mainstay of treatment as the added benefit of adjuvant chemoradiation or immunotherapy has been controversial.
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

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 <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

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

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

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

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

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

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

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 <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 < .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

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 < 0.001), bedtimes advanced by 1.40 (95% CI = –1.75, –1.06; p < 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 > 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

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.

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.

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.
Utilization of Neuromonitoring in Surgical Cervical Spondylosis Patients With the Presence or Absence of Myelopathy. Is it Standard?
Authors: Gonzalez Glenn A. , Corso Katherine , Porto Guilherme , Ruppenkamp Jill , Miao Jingya , Franco Daniel , Hines Kevin , O’Leary Matthew , Thalheimer Sara , Harrop James
Published: November 2024

Study Design:

Cross-sectional, observational study.

Objective:

Investigate the frequency of intraoperative neuromonitoring (IONM) utilization among Medicare patients diagnosed with cervical spondylosis (CS), both with and without myelopathy.

Background:

IONM is widely used as a tool in spine surgery. However, the overall prevalence of neuromonitoring utilization among CS undergoing surgical intervention is not well characterized.

Methods:

This study observed neuromonitoring usage in CS patients who had cervical spinal procedures from 2012 to 2020, using a 5% random sample of Medicare data. Logistic regression compared patient characteristics between those who received neuromonitoring and those who did not. The model included age, sex, region, Elixhauser Comorbidity Index score, year of surgery, elective status, and procedure type. Odds ratios with a 95% CI were generated for each covariate.

Results:

Of the 6224 patients who underwent cervical procedures for CS, 4053 were included in the study, with 2845 having myelopathy and 1208 without. Myelopathy patients had a higher number of hospitalizations (2884) compared with non-myelopathy patients (1229). Among myelopathy patients, the prevalence of neuromonitoring increased from 49.2% in 2012 to 56.5% in 2020. The range of utilization for each type of monitoring was: 96.4%–100% for somatosensory evoked potential, 73.2%–86.1% for electromyography, 70.0%–86.1% for motor evoked potential, and 17.6%–33.6% for other modalities. For non-myelopathy patients, neuromonitoring prevalence increased from 33.1% in 2012 to 43.3% in 2020. The range of utilization for each type of monitoring was: 93.0%–100% for somatosensory evoked potential, 68.9%–89.7% for electromyography, 55.8%–77.4% for motor evoked potential, and 17.8%–36.4% for other modalities.

Conclusions:

This study investigates the utilization of IONM during cervical spinal surgeries in Medicare patients with cervical spondylotic myelopathy or CS between 2012 and 2020. Although IONM is employed in cervical spine procedures, its adoption and standardization appear to vary across the country and different health care settings.
Time to rename the “ischemia/reperfusion injury” model to “ischemia/delayed reperfusion injury” model?
Authors: Liu Dan , Nordbeck Peter
Published: November 2024

Small animals are often used in the preclinical and translational studies. Left coronary artery ligation followed by reperfusion in rats or mice serves as an important myocardial infarction (MI) models resembling the clinical MI cases treated with revascularization. This model is typically referred to as the “ischemia/reperfusion injury (IRI) model.” However, it is not the reperfusion itself but rather the delay in reperfusion following ischemic insult that contributes most significantly to the residual myocardial damage. Therefore, it may be more accurate to rename it the “ischemia/delayed reperfusion injury (IdRI) model.”
Granulomatous Reactions From Microneedling: A Systematic Review of the Literature
Authors: Friedmann Daniel P. , Mehta Eshani , Verma Kritin K. , Harris Ryan
Published: November 2024

BACKGROUND

Microneedling is a common minimally invasive procedure for skin rejuvenation. Granulomatous reactions after microneedling have been rarely reported.

OBJECTIVE

To systematically review the literature for granulomatous reactions from microneedling.

MATERIALS AND METHODS

A systematic review of the Medline, Scopus, Google Scholar, and Cochrane databases was performed for articles describing granulomatous reactions to microneedling.

RESULTS

Thirteen studies were selected for inclusion after full-text review, which described 15 patients (26–74 years old) with non-necrotizing granulomatous inflammation postmicroneedling. Motorized microneedling pen use and topical Vitamin C application were implicated in a majority of cases. Although delayed-type hypersensitivity was commonly proposed as the underlying etiology, patch testing or further workup was rarely performed. Improvement or clearance occurred inconsistently with myriad treatment options, including topical steroids, oral antibiotics, and systemic anti-inflammatory medications.

CONCLUSION

Granulomatous reactions to microneedling and microneedling-mediated transepidermal drug delivery can rarely occur and may be treatment-resistant.