bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans.
Authors: Horner R L , Innes J A , Morrell M J , Shea S A , Guz A
Published: October 2023

The present study was designed to determine the effect of sleep on reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in human subjects. Intra‐oral bipolar surface electrodes were used to record genioglossus electromyogram (EMG) responses to 500 ms duration pressure stimuli of 0 and ‐25 cmH2O applied, via a face‐mask, in four normal subjects. Stimuli were applied during early inspiration in wakefulness and in periods of non‐rapid‐eye‐movement (non‐REM) sleep, defined by electroencephalographic (EEG) criteria. The rectified and integrated EMG responses to repeated interventions were bin averaged for the 0 and ‐25 cmH2O stimuli applied in wakefulness and sleep. Response latency was defined as the time when the EMG activity significantly increased above prestimulus levels. Response magnitude was quantified as the in ratio of the EMG activity for an 80 ms post‐stimulus period to an 80 ms prestimulus period; data from after the subject's voluntary reaction time for tongue protrusion (range, 150‐230 ms) were not analysed. Application of the ‐25 cmH2O stimuli caused genioglossus muscle activation in wakefulness and sleep, but in all subjects response magnitude was reduced in sleep (mean decrease, 61%; range, 52‐82%; P = 0.011, Student's paired t test). In addition, response latency was increased in sleep in each subject (mean latency awake, 38 ms; range, 30‐50 ms; mean latency asleep, 75 ms; range, 40‐110 ms; P = 0.072, Student's paired t test). Application of the ‐25 cmH2O stimuli caused arousal from sleep on 90% occasions, but in all cases the reflex genioglossus muscle responses (maximum latency, 110 ms) always proceeded any sign of EEG arousal (mean time to arousal, 643 ms; range, 424‐760 ms). These results show that non‐REM sleep attenuates reflex genioglossus muscle activation by stimuli of negative airway pressure. Attenuation of this reflex by sleep may impair the ability of the upper airway to defend itself from suction collapse by negative pressures generated during inspiration; this may have implications for the pathogenesis of obstructive sleep apnoea.
A Project-Led Framework for Coach Development in English Men’s Professional Football: A Premier League Case Study
Authors: McCarthy Liam , Roberts Claire-Marie
Published: October 2023

Coach education and development programmes are central to the professional development experiences of sport coaches. Typically, these programmes are structured and sequenced in a linear pathway, and present an opportunity for certification which can be a prerequisite to practice and/or employment. Increasingly, as learning becomes viewed as part of a coach’s lifeworld, versus simply as a means to an end, education and development provision is beginning to reflect this. This article introduces and explores the Coach Development Institute Programme, part of the Premier League’s Elite Coaching Plan, which seeks to improve the quality of football coaching in English boys’/men’s football by engaging coaches in a 2-year work-based learning opportunity. Built around a core of project-based learning and assessment, coaches are supported as they examine a series of meaningful performance problems in their unique practice environments. Through this work, we demonstrate how theories, concepts, and principles from the adult education and assessment as learning literature might work as they are applied in a coach education and development context. With such sparsity of case-based examples like this within the peer-reviewed literature, we intend that our contribution could inform, promote dialogue, and raise questions about authentically supporting coaches beyond a minimum standard of practice.
The Effect of an Overhead External Load Lifting and Lowering on Dynamic Postural Control in Subgroups of Low Back Pain
Authors: Shahbazi Majid , Sarrafzadeh Javad , Ebrahimi Takamjani Ismail , Negahban Hossein
Published: October 2023

Background: Understanding postural control in low back pain (LBP) subgroups can help develop targeted interventions to improve postural control. The studies on this topic are limited. Therefore, the primary purpose of this study was to compare the postural control of LBP subgroups with healthy individuals during overhead load lifting and lowering. Methods: In this cross-sectional study, the participants were 52 with LBP and 20 healthy. The LBP patients were classified based on the O’Sullivan classification system into 21 flexion patterns and 31 active extension patterns. The participants lifted the box from their waists to their overheads and lowered it to their waists. Changes in postural control parameters were measured with a force plate system. Results: The results of the analysis of variance showed that during load lifting, the mediolateral phase plane (p = .044) and the mean total velocity (p = .029) had significant differences between flexion patterns and healthy. Also, the load-lowering results showed that active extension patterns, compared with healthy, had significant differences in the anteroposterior–mediolateral phase plane (p = .042). The patients showed less postural sway than the healthy. Conclusions: The results in this work highlight the importance of identifying the homogenous subgroups in LBP and support the classification of heterogeneous LBP. Different subgroups exhibit different postural control behaviors. These behaviors can be due to the loading of various tissues during different tasks.
Resident regulatory T cells reflect the immune history of individual lymph nodes
Authors: Kaminski Anne , Hager Fabian Tobias , Kopplin Lydia , Ticconi Fabio , Leufgen Andrea , Vendelova Emilia , Rüttger Lennart , Gasteiger Georg , Cerovic Vuk , Kastenmüller Wolfgang , Pabst Oliver , Ugur Milas
Published: October 2023

Regulatory T cells (T
regs
) are present in lymphoid and nonlymphoid tissues where they restrict immune activation, prevent autoimmunity, and regulate inflammation. T
regs
in nonlymphoid tissues are typically resident, whereas those in lymph nodes (LNs) are considered to recirculate. However, T
regs
in LNs are not a homogenous population, and circulation kinetics of different T
reg
subsets are poorly characterized. Furthermore, whether T
regs
can acquire memory T cell properties and persist for extended periods after their activation in LNs is unclear. Here, we used in situ labeling with a stabilized photoconvertible protein to uncover turnover rates of T
regs
in LNs in vivo. We found that, whereas most T
regs
in LNs recirculate, 10 to 20% are memory-like resident cells that remain in their respective LNs for weeks to months. Single-cell RNA sequencing revealed that LN-resident cells are a functionally and ontogenetically heterogeneous population and share the same core residency gene signature with conventional CD4
+
and CD8
+
T cells. Resident cells in LNs did not actively proliferate and did not require continuous T cell receptor (TCR) signaling for their residency. However, resident and circulating T
regs
had distinct TCR repertoires, and each LN contained exclusive clonal subpopulations of resident T
regs
. Our results demonstrate that, similar to conventional T cells, T
regs
can form resident memory-like populations in LNs after adaptive immune responses. Specific and local suppression of immune responses by resident T
regs
in draining LNs might provide previously unidentified therapeutic opportunities for the treatment of local chronic inflammatory conditions.
Restraining neuroinflammation in Alzheimer’s disease
Authors: Foley John F.
Published: October 2023

CD8
+
T cells recruited to the brain in a mouse model of Alzheimer's disease limit disease pathology.
The directed evolution of NDM-1
Authors: Thomas Caitlyn A. , Cheng Zishuo , Bethel Christopher R. , Hujer Andrea M. , Sturgill Aidan M. , Onuoha Kelechi , Page Richard C. , Bonomo Robert A. , Crowder Michael W.
Published: October 2023

β-Lactam antibiotics are among the most frequently prescribed therapeutic agents. A common mechanism of resistance toward β-lactam antibiotics is the production of β-lactamases. These enzymes are capable of hydrolyzing the β-lactam bond, rendering the drug inactive. Among the four described classes, the metallo- β-lactamases (MBLs, class B) employ one or two zinc ions in the active site for catalysis. One of the three most clinically relevant MBLs is New Delhi Metallo- β-Lactamase (NDM-1). The current study sought to investigate the
in vitro
protein evolution of NDM-1 β-lactamase using error-prone polymerase chain reaction. Evaluation revealed that variants were not found to confer higher levels of resistance toward meropenem based on amino acid substitutions. Thus, we postulate that increases in transcription or changes in zinc transport may be clinically more relevant to meropenem resistance than amino acid substitutions.
Acid adaptation increased the resistance of
Escherichia coli
O157:H7 in bok choy (
Brassica rapa
subsp.
chinensis
) juice to high-pressure processing
Authors: Koo Andrea , Ghate Vinayak , Zhou Weibiao
Published: October 2023

The adaptive response of
Escherichia coli
O157:H7 to acid stress, a major stressor in juice processing environments, has been shown to confer cross-resistance against pasteurization methods such as heat and X-ray. However, whether acid adaptation confers resistance against high-pressure processing (HPP) has not been explored. This study aimed to investigate the effect of acid adaptation on the pressure resistance of
E. coli
O157:H7 in a bok choy vegetable juice matrix. Acid adaptation was performed in tryptone soya broth without dextrose adjusted to pH 5.0 at 37°C for 24 h, while non-adapted cells were prepared in similar conditions, without the pH adjustment (pH 7.3). The C7927 strain was used as it exhibited the greatest increase in pressure resistance after acid adaptation among the three strains tested. Acid adaptation increased the
D
-value at 400 MPa from 0.8 ± 0.1 min in non-adapted cells to 1.2 ± 0.1 min in acid-adapted cells (
P
< 0.05). Furthermore, significantly lower reductions in total viable counts were observed after 72 h of post-HPP refrigerated storage for acid-adapted cells (3.4 ± 0.2 log CFU/mL) as compared to non-adapted cells (5.0 ± 0.1 log CFU/mL). Sublethally injured populations were measured via plating on selective media, as well as differential fluorescent staining and flow cytometry. The levels of damages to membrane, DNA, proteins, and peptidoglycan were significantly lower in acid-adapted cells, suggesting that the acid adaptive response of
E. coli
O157:H7 may protect it against HPP-induced inactivation and injury by modulating the pressure resistance of these cellular targets.

IMPORTANCE

Based on the U.S. Food and Drug Administration regulations,
E. coli
O157:H7 is a pertinent pathogen in high acid juices that needs to be inactivated during the pasteurization process. The results of this study suggest that the effect of acid adaptation should be considered in the selection of HPP parameters for
E. coli
O157:H7 inactivation to ensure that pasteurization objectives are achieved.
Student perceptions of inclusive pedagogy in undergraduate STEM classrooms
Authors: Valdez Caley J. , Kelp Nicole C.
Published: October 2023

In university STEM classrooms, the incorporation of inclusive practices improves student performance, decreases disparities in the academic success of underrepresented students, and increases student retention and persistence in Science, Technology, Engineering, and Mathematics (STEM) programs. Inclusive pedagogical practices include effective instructional choices like active learning, providing rubrics, and other strategies that have been shown to support students from disadvantaged backgrounds. Additionally, explicitly inclusive practices such as addressing microaggressions and sharing pronouns can promote a sense of belonging for students. While a plethora of literature has shown these impacts and faculty have access to resources and training about inclusive pedagogy, we were interested in whether students are noticing these practices and how student identities impact their observations of instructional practices. We surveyed undergraduates (
n
= 74) from diverse STEM disciplines at a large land-grant university regarding their observation of 11 different inclusive pedagogical practices. Overall, students observed inclusive instructional practices more often than they observed explicitly diversity, equity, and inclusion (DEI)-related practices. For explicitly DEI-related practices, white students observed more practices than Students of Color. This suggests that more work needs to be done to train faculty in explicit DEI-related practices, especially with the goal of supporting Students of Color who have been historically excluded from STEM.
Targeted mutations in IFNα2 improve its antiviral activity against various viruses
Authors: Karakoese Zehra , Le-Trilling Vu-Thuy Khanh , Schuhenn Jonas , Francois Sandra , Lu Mengji , Liu Jia , Trilling Mirko , Hoffmann Daniel , Dittmer Ulf , Sutter Kathrin
Published: October 2023

During viral infections, type I interferons (IFN) are induced and play a key role in counteracting initial viral spread. Twelve different human IFNα subtypes exist that bind the same receptor; however, they elicit unique host responses and display distinct potencies of antiviral activities. Our previous studies on human immunodeficiency virus (HIV) and hepatitis B virus (HBV) demonstrated that the clinically used IFNα2 is not the most effective one among the IFNα subtypes. By sequence modeling, we identified a region in helix B with mainly conserved residues at the outside facing IFNAR1, but variable residues at the inside facing the core of IFNα, potentially representing a putative tunable anchor to tune pleiotropic IFN responses. Using site-directed mutagenesis, various mutations were introduced into the IFNα2b backbone targeting sites which are important for binding to IFNAR1 and IFNAR2, the putative tunable anchor, or outside these three regions. Selected mutations were based on sequence differences to high antiviral subtypes IFNα6 and IFNα14. Treatment assays against HBV and HIV identified several critical residues for the antiviral activity of IFNα mainly in the IFNAR1 binding region. Combined mutations of the IFNα2 IFNAR1/2 binding sites or the IFNAR1 binding region plus the putative tunable anchor by those of IFNα14 further augmented activation of different downstream signaling cascades providing a molecular correlate for the enhanced antiviral activity. We describe here important functional residues within IFNα subtype molecules, which enabled us to design novel and innovative drugs that may have the potential to be used in clinical trials against a variety of different viral infections.

IMPORTANCE

The potency of interferon (IFN)α to restrict viruses was already discovered in 1957. However, until today, only IFNα2 out of the 12 distinct human IFNα subtypes has been therapeutically used against chronic viral infections. There is convincing evidence that other IFNα subtypes are far more efficient than IFNα2 against many viruses. In order to identify critical antiviral residues within the IFNα subtype sequence, we designed hybrid molecules based on the IFNα2 backbone with individual sequence motifs from the more potent subtypes IFNα6 and IFNα14. In different antiviral assays with HIV or HBV, residues binding to IFNAR1 as well as combinations of residues in the IFNAR1 binding region, the putative tunable anchor, and residues outside these regions were identified to be crucial for the antiviral activity of IFNα. Thus, we designed artificial IFNα molecules, based on the clinically approved IFNα2 backbone, but with highly improved antiviral activity against several viruses.
Targeted metagenomic assessment reflects critical colonization in battlefield injuries
Authors: Kok Car Reen , Mulakken Nisha , Thissen James B. , Grey Scott F. , Avila-Herrera Aram , Upadhyay Meenu M. , Lisboa Felipe A. , Mabery Shalini , Elster Eric A. , Schobel Seth A. , Be Nicholas A.
Published: October 2023

Current diagnostics and clinical management strategies for combat wounds are based on decisions made by expert clinicians. However, even in the hands of experienced surgeons, wounds from combat injuries can exhibit failed healing and complications related to limitations in the rapid and comprehensive generation of diagnostic information. Previous studies have demonstrated the possible use of genomic sequencing approaches to detect microbial signatures involved in combat casualty care. While effective, whole metagenome sequencing is limited by the depth required to confidently detect all relevant signatures. To address this, we developed a targeted capture sequencing panel to detect microbial signatures relevant to wound healing. These targets include known microbial nosocomial pathogens, wound colonizers, and genes involved in virulence and antimicrobial resistance. A bioinformatics pipeline was built to identify genomic regions of interest and over 8,000 oligonucleotide probes were designed for capture. The panel was synthesized and validated using control reference genomes in human background and on wound-effluent samples from a cohort of combat-injured U.S. service members. Our panel was sensitive against wound-colonizing species,
Acinetobacter baumannii
and
Pseudomonas aeruginosa
, and was specific in detecting corresponding virulence and antimicrobial-resistance genes as well as other pathogenic species present in microflora mixtures. Random forest feature permutation confirmed the prevalence of
Acinetobacter
and
Pseudomonas
in critically colonized wounds and wounds that failed to heal, respectively. Our results demonstrate the capability of targeted sequencing tools and analysis platforms to profile and deliver information on pathogenic factors influencing wound progression, thereby guiding therapeutic intervention.

IMPORTANCE

Microbial contamination in combat wounds can lead to opportunistic infections and adverse outcomes. However, current microbiological detection has a limited ability to capture microbial functional genes. This work describes the application of targeted metagenomic sequencing to profile wound bioburden and capture relevant wound-associated signatures for clinical utility. Ultimately, the ability to detect such signatures will help guide clinical decisions regarding wound care and management and aid in the prediction of wound outcomes.
Developing an implementation intervention for managing acute vertigo in the emergency department
Authors: Herdman David , Ahmad Hena , Antoniades George , Bailur Gokul , Pajaniappane Arun , Moss Phil
Published: October 2023

Background

There are evidence-based bedside tests for diagnosing acute vertigo, but no evidence-based strategies to support clinicians in implementing them. The purpose of this study was to design an implementation strategy for treating acute vertigo by examining current facilitators and barriers to using these tests in the ED using the principles of implementation science.

Methods

A survey was developed using the Theoretical Domains Framework and Consolidated Framework for Implementation Research to examine barriers and facilitators for using HINTS+ (head impulse, nystagmus, test of skew, plus hearing) and Dix-Hallpike tests. The survey was sent to emergency clinicians (ECs) in a teaching hospital in London, UK, between May and September 2022. Semistructured interviews were conducted simultaneously, and data examined using direct content analysis. Implementation strategies were then selected based on the Expert Recommendations for Implementing Change framework.

Results

Fifty-one ECs responded to the survey and six ECs volunteered for interview. Less than half reported using the bedside tests to make a diagnosis. The most common barriers were beliefs about complexity, a lack of supporting materials, memory, lack of skills and negative experiences. The interview data revealed negative beliefs about the necessity, validity, safety and practicality. There were also barriers in the ED environment (eg, lack of space). There was a strong perception that the current approach to managing acute vertigo needed to change and ECs view this as part of their professional role and responsibility. Based on clinician input, the authors selected strategies to improve diagnostic efforts, which included guidelines for training, developing vertigo champions, protocols, memory aids, audit and feedback.

Conclusion

This study found several barriers to managing acute vertigo such as memory constraints, and inadequate supporting materials and training, although a robust desire for change. The implementation strategy’s initial phase is described, which must now be tested.
Developing a generic business case for an advanced chronic liver disease support service
Authors: Wright Mark , Willmore Sarah , Verma Sumita , Omasta-Martin Anita , Sahota Humraj , Prentice Wendy , Stockley Amelia Jane , Finlay Fiona , Verne Julia , Hudson Ben
Published: October 2023

Introduction

Liver disease deaths are rising, but specialist palliative care services for hepatology are limited. Expansion across the NHS is required.

Methods

We surveyed clinicians, patients and carers to design an ‘ideal’ service. Using standard NHS tariffs, we calculated the cost of this service. In hospitals where specialist palliative care was available for liver disease, patient-level costs and bed utilisation in last year of life (LYOL) were compared between those seen by specialist palliative care before death and those not.

Results

The ‘ideal’ service was described. Costs were calculated as whole time equivalent for a minimal service, which could be scaled up. From a hospital with an existing service, patients seen by specialist palliative care had associated costs of £14 728 in LYOL, compared with £18 558 for those dying without. Savings more than balanced the costs of introducing the service. Average bed days per patient in LYOL were reduced (19.4 vs 25.7) also intensive care unit bed days (1.1 vs 1.8). Despite this, time from first admission in LYOL to death was similar in both groups (6 months for the specialist palliative care group vs 5 for those not referred).

Conclusions

We have produced a template business case for an ‘ideal’ advanced liver disease support service, which self-funds and saves many bed days. The model can be easily adapted for local use in other trusts. We describe the methodology for calculating patient-level costs and the required service size. We present a financially compelling argument to expand a service to meet a growing need.
Municipal social expenditures and maternal health disparities: a study of linked birth and hospitalisation records
Authors: Muchomba Felix M , Teitler Julien O , Reichman Nancy E
Published: October 2023

Background

Local government expenditures provide services and benefits that can affect health but the extent to which they are associated with narrowing or widening of racial/ethnic and socioeconomic disparities in health is unknown. We examined race/ethnicity-stratified and education-stratified associations between municipal social expenditures—those on housing, transportation, education, and other society-wide needs—and serious life-threatening maternal health conditions in a large US state.

Methods

In this cross-sectional study, we used individual birth records for 1 003 974 births in the state of New Jersey from 1 January 2008 to 31 December 2018 linked to individual maternal hospital discharge records and municipality-level characteristics for 564 municipalities. Severe maternal morbidity (SMM) was identified in the discharge records using a measure developed by the US Centers for Disease Control and Prevention. Associations between municipal-level social expenditures per capita and SMM were estimated using multilevel logistic models.

Results

Residing in a municipality with higher social expenditures was associated with lower odds of SMM across all racial/ethnic groups and education levels. Overall, 1% higher annual social expenditures per capita was associated with 0.21% (95% CI −0.29 to –0.13) lower odds of SMM. The associations were greater for individuals with less than a high school education than for those in the other educational groups in both relative (lnOR −0.53; 95% CI −0.74 to –0.31) and absolute (β −0.013; 95% CI −0.019 to –0.008) terms.

Conclusion

Municipal-level spending on social services is associated with narrowing socioeconomic disparities in SMM. Narrowing racial/ethnic disparities in maternal health will likely require intervening beyond the provision of services to addressing historical and ongoing structural factors.
Comprehensive analysis of the impact of procedure time and the ‘golden hour’ in subpopulations of stroke thrombectomy patients
Authors: Ash Makenna , Dimisko Laurie , Chalhoub Reda M , Howard Brian M , Cawley C Michael , Matouk Charles , Pabaney Aqueel , Spiotta Alejandro M , Jabbour Pascal , Maier Ilko , Wolfe Stacey Q , Rai Ansaar T , Kim Joon-tae , Psychogios Marios-Nikos , Mascitelli Justin R , Starke Robert M , Shaban Amir , Yoshimura Shinichi , De Leacy Reade , Kan Peter , Fragata Isabel , Polifka Adam J , Arthur Adam S , Park Min S , Crosa Roberto Javier , Williamson Richard , Dumont Travis M , Levitt Michael R , Al Kasab Sami , Tjoumakaris Stavropoula I , Liman Jan , Saad Hassan , Samaniego Edgar A , Fargen Kyle M , Grossberg Jonathan A , Alawieh Ali
Published: October 2023

Objective

To evaluate the effect of procedure time on thrombectomy outcomes in different subpopulations of patients undergoing endovascular thrombectomy (EVT), given the recently expanded indications for EVT.

Methods

This multicenter study included patients undergoing EVT for acute ischemic stroke at 35 centers globally. Procedure time was defined as time from groin puncture to successful recanalization (Thrombolysis in Cerebral Infarction score ≥2b) or abortion of procedure. Patients were stratified based on stroke location, use of IV tissue plasminogen activator (tPA), Alberta Stroke Program Early CT score, age group, and onset-to-groin time. Primary outcome was the 90-day modified Rankin Scale (mRS) score, with scores 0–2 designating good outcome. Secondary outcome was postprocedural symptomatic intracranial hemorrhage (sICH). Multivariate analyses were performed using generalized linear models to study the impact of procedure time on outcomes in each subpopulation.

Results

Among 8961 patients included in the study, a longer procedure time was associated with higher odds of poor outcome (mRS score 3–6), with 10% increase in odds for each 10 min increment. When procedure time exceeded the ‘golden hour’, poor outcome was twice as likely. The golden hour effect was consistent in patients with anterior and posterior circulation strokes, proximal or distal occlusions, in patients with large core infarcts, with or without IV tPA treatment, and across age groups. Procedures exceeding 1 hour were associated with a 40% higher sICH rate. Posterior circulation strokes, delayed presentation, and old age were the variables most sensitive to procedure time.

Conclusions

In this work we demonstrate the universality of the golden hour effect, in which procedures lasting more than 1 hour are associated with worse clinical outcomes and higher rates of sICH across different subpopulations of patients undergoing EVT.
Coil embolization of distal vascular lesion using a 1.5 Fr Marathon microcatheter and ‘free-running’ technique
Authors: Ou Chang-Hsien , Cheng Chiu-Shih , Winardi William , Lin Pei-Ling , Lee Cheng-Lung , Lin Wan-Ching
Published: October 2023

In distal vascular lesions, such as the distal anterior inferior cerebellar artery or posterior inferior cerebellar artery (PICA) dissecting aneurysm, and dural arteriovenous fistula (dAVF) and arteriovenous malformation (AVM), super-selective catheterization and embolization using liquid agents, such as NBCA or Onyx liquid embolic system, is the preferred treatment.1 2 We used a flow-directed 1.5 Fr Marathon microcatheter (Medtronic, Minneapolis, MN, USA) for embolization because commonly used detachable coil-compatible microcatheters can be too short or rigid for superselection.3–6 We designed an in vitro coil compatibility test for the Marathon microcatheter and developed a ‘free-running’ technique (video 1). Using this technique, we trapped the distal PICA dissecting aneurysm and embolized the fistula points of dAVF precisely and safely without affecting adjacent normal structures, which can occur when applying liquid embolizing agents.1–3 After reviewing the case, we determined that this technique can also potentially be applied for implementing the pressure cooker technique7 and combining the management of AVM.4

Video 1

Free-running technique via 1.5 Fr Marathon microcatheter
Superior hypophyseal arteries: angiographic re-discovery, comprehensive assessment, and embryologic implications
Authors: Shapiro Maksim , Sharashidze Vera , Nossek Erez , Sen Chandra , Rutledge Caleb , Chung Charlotte , Khawaja Ayaz , Kvint Svetlana , Riina Howard , Nelson Peter Kim , Raz Eytan
Published: October 2023

The superior hypophyseal arteries (SHAs) are well known in anatomical and surgical literature, with a well-established role in supply of the anterior hypophysis and superjacent optic apparatus. However, due to small size and overlap with other vessels, in vivo imaging by any modality has been essentially non-existent. Advances in high resolution cone beam CT angiography (CBCTA) now enables this deficiency to be addressed. This paper presents, to the best of our knowledge, the first comprehensive in vivo imaging evaluation of the SHAs.

Methods

Twenty-five CBCTA studies of common or internal carotid arteries were obtained for a variety of clinical reasons. Dedicated secondary reconstructions of the siphon were performed, recording the presence, number, and supply territory of SHAs. A spectrum approach, emphasizing balance with adjacent territories (inferior hypophyseal, ophthalmic, posterior and communicating region arteries) was investigated.

Results

The SHAs were present in all cases. Supply of the anterior pituitary was nearly universal (96%) and almost half (44%) originated from the ‘cave’ region, in excellent agreement with surgical literature. Optic apparatus supply was more difficult to adjudicate, but appeared present in most cases. The relationship with superior hypophyseal aneurysms was consistent. Patency following flow diverter placement was typical, despite a presumably rich collateral network. Embryologic implications with respect to the ophthalmic artery and infraoptic course of the anterior cerebral artery are intriguing.

Conclusions

SHAs are consistently seen with CBCTA, allowing for correlation with existing anatomical and surgical literature, laying the groundwork for future in vivo investigation.
Immediate smoking cessation support during lung cancer screening: long-term outcomes from two randomised controlled trials
Authors: Williams Parris J , Philip Keir E J , Buttery Sara C , Perkins Alexis , Chan Ley , Bartlett Emily C , Devaraj Anand , Kemp Samuel V , Addis James , Derbyshire Jane , Chen Michelle , Polkey Michael I , Laverty Anthony A , Hopkinson Nicholas S
Published: October 2023

Background

Immediate smoking cessation interventions delivered alongside targeted lung health checks (TLHCs) to screen for lung cancer increase self-reported abstinence at 3 months. The impact on longer term, objectively confirmed quit rates remains to be established.

Methods

We followed up participants from two clinical trials in people aged 55–75 years who smoked and took part in a TLHC. These randomised participants in the TLHC by day of attendance to either usual care (UC) (signposting to smoking cessation services) or an offer of immediate smoking cessation support including pharmacotherapy. In the QuLIT1 trial, this was delivered face to face and in QuLIT2, it was delivered remotely. Follow-up was conducted 12 months after the TLHC by telephone interview with subsequent biochemical verification of smoking cessation using exhaled CO.

Results

430 people were enrolled initially (115 in QuLIT1 and 315 in QuLIT2), with 4 deaths before 12 months leaving 426 (62.1±5.27 years old and 48% women) participants for analysis. At 12 months, those randomised to attend on smoking cessation support intervention days had higher quit rates compared with UC adjusted for age, gender, deprivation, and which trial they had been in; self-reported 7-day point prevalence (20.0% vs 12.8%; adjusted OR (AOR)=1.78; 95% CI 1.04 to 2.89) and CO-verified quits (12.1% vs 4.7%; AOR=2.97; 95% CI 1.38 to 6.90). Those in the intervention arm were also more likely to report having made a quit attempt (30.2% vs UC 18.5%; AOR 1.90; 95% CI 1.15 to 3.15).

Conclusion

Providing immediate smoking cessation support alongside TLHC increases long term, biochemically confirmed smoking abstinence.

Trial registration number

ISRCTN12455871.
Evaluation of carbon dioxide sequestration via interaction with peridotite and peridotite-hosted groundwaters: an experimental case study with Bay of Islands Ophiolite rocks, western Newfoundland, Canada
Authors: Gill M.J. , Poduska K.M. , Morrill P.L.
Published: October 2023

This study measured the CO2 gas flux into various aqueous media (i.e., simulated ultra-basic and basic groundwater, and deionized water) containing ultramafic rock. Basic and ultra-basic waters simulated the aqueous chemistry and ion concentrations of distinct groundwaters found within terrestrial ultramafic bodies. Experiments were performed in a closed chamber in-line with a CO2 analyzer, which measured the gaseous CO2 concentration in the chamber every second. Total inorganic carbon, as well as aqueous species Ca, Mg, and Si were monitored in the reaction fluids. All three fluid types sequestered CO2. The addition of crushed peridotite to deionized water reduced the CO2 concentration in the headspace by 70 ppm (±9 ppm, 1σ, n = 3) and had a calculated CO2 flux of −2.5 × 104 mol/m2min (±9 × 105 mol/m2min, 1σ, n = 3), while the greatest CO2 flux was observed in ultra-basic Ca-rich waters of −1.40 × 103 mol/m2min (±3 × 105 mol/m2min, 1σ, n = 3), which reduced the headspace CO2 concentration by 323 ppm (±4 ppm, 1σ, n = 3). The presence of calcite was detected using FTIR in ultra-basic waters in the presence and absence of ultramafic rock. A carbon mass balance model indicated that solid carbonates were precipitated in the ultra-basic water experiments, converting up to 59% of the CO2 removed from the chamber headspace in 4 h. Extrapolating the data collected in these experiments, it was estimated that at surface conditions, with an adequate residence time, the mass of ultramafic rock in the Bay of Islands Complex in Newfoundland could sequester up to 4 million tonnes of atmospheric CO2.
Effects of exact kinematics and the Sudakov form factor on the dipole amplitude
Authors: Goda T. , Kutak K. , Sapeta S.
Published: October 2023

We investigate the effects of exact gluon kinematics on the parameters of the Golec-Biernat–Wüsthoff, and Bartels–Golec-Biernat–Kowalski saturation models. The resulting fits show some differences, particularly, in the normalization of the dipole cross section $$\sigma _0$$

σ
0

. The refitted models are used for the dijet production process in DIS to describe HERA data and investigate the effects of the Sudakov form factor at the future Electron Ion Collider.
Age of the basal ‘Lower Old Red Sandstone’ Stonehaven Group of Scotland: the oldest reported air-breathing land animal is Silurian (late Wenlock) in age
Authors: Wellman Charles H. , Lopes Gilda , McKellar Zoë , Hartley Adrian
Published: October 2023

The basal upper Silurian–Lower Devonian ‘Lower Old Red Sandstone’ deposits of the Midland Valley of Scotland contain several important fossil biotas, including that from the Cowie Harbour Fish Bed. This biota is of great significance because it represents one of the oldest known examples of a fossilized terrestrial ecosystem and includes the oldest reported air-breathing land animal (the myriapod
Pneumodesmus newmani
Wilson and Anderson, 2004
). Based on biostratigraphical evidence from dispersed spores this biota is dated as late Wenlock (late Silurian) in age. Recently, however, this age constraint was challenged, based on
238
U–
206
Pb radiometric analysis of zircons, and it was proposed that these deposits are much younger (Early Devonian: Lochkovian). This proposal has serious implications regarding (1) the composition and nature of early terrestrial ecosystems and (2) the geological setting with respect to the timing of terrane accretion and the onset of ‘Lower Old Red Sandstone’ sedimentation. We report on newly discovered dispersed spore assemblages and additional zircon data that confirm a late Wenlock (late Silurian) age. This age designation establishes the importance of the biota of the Cowie Harbour Fish Bed and is more compatible with both its biotic composition and the regional geological setting.
DFT Calculations of Half-Metallic Ferromagnetism and Transport Properties of Cubic KCrX3 (X = Cl, Br, I) Halides for Spintronics and Energy Conversion Applications
Authors: Alburaih Huda A. , Nazir Sadia , Noor N. A. , Laref A. , Sharma Ramesh
Published: October 2023

This paper investigates the properties of cubic halides KCrX3 (X = Cl, Br, I) compounds focusing on their half-metallic (HM) ferromagnetic and thermoelectric characteristics. The analysis is performed using the Wien2k and BoltzTrap coding. The stability of our compounds in the ferromagnetic (FM) phase is established by the higher energy release compared to the antiferromagnetic (AFM) phase. The calculated value of Poisson ratio and Pugh ratio greater than their cutoff limit (0.26 and 1.75) reveal that our examined materials are ductile in nature. To examine the electronic structure, the Trans-Bhala modified Becke Johnson potential (TB- mBJ) is employed to investigate half-metallic nature. The density of states (DDS) analysis indicates significant contributions from X-p states in the valence band and Cr 3d-states in the conduction band. A comparative analysis of crystal field (

Δ

E

c
r
y
s
t
a
l

) and exchange (indirect

Δ

x

(Pd) and direct

Δ

x

(d)) energies provides insights into the primary role of electronic spin in the ferromagnetic behavior. The observed value (4 μ
B) of total magnetic moment of the investigated halide perovskites suggest that they could be promising candidates for spintronic materials. Lastly, we compute the thermoelectric parameters within a temperature range of 200 K to 800 K to explore the potential application in renewable energy devices.
Metal transporter SLC39A14/ZIP14 modulates regulation between the gut microbiome and host metabolism
Authors: Mitchell Samuel B. , Thorn Trista L. , Lee Min-Ting , Kim Yongeun , Comrie Janine M. C. , Bai Zi Shang , Johnson Elizabeth L. , Aydemir Tolunay B.
Published: October 2023

Metal dyshomeostasis, intestinal permeability, and gut dysbiosis are emerging signatures of chronic disorders, including inflammatory bowel diseases, type-2 diabetes, and obesity. Studies in reciprocal regulations between host intestinal metal transporters genes and gut microbiome are scarce. Our research revealed a potential predisease microbial susceptibility state dependent on the host metal transporter gene, Slc39a14/Zip14, that contributes to intestinal permeability providing new insight into understanding host metal transporter gene-microbiome interactions in developing chronic disease.
Respiratory exposure to agricultural dust extract promotes increased intestinal Tnfα expression, gut barrier dysfunction, and endotoxemia in mice
Authors: Crawford Meli’sa S. , Ulu Arzu , Ramirez Briana M. , Santos Alina N. , Chatterjee Pritha , Canale Vinicius , Manz Salomon , Lei Hillmin , Nordgren Tara M. , McCole Declan F.
Published: October 2023

Agricultural workers have a higher prevalence of occupational respiratory symptoms and are at greater risk of developing respiratory diseases. However, gastrointestinal complications have also been reported, yet the intestinal pathophysiology is understudied. This work is novel because it emphasizes the role of an inhaled environmental pollutant on the development of intestinal pathophysiological outcomes. This work will provide foundation for other studies evaluating how agricultural dusts disrupts host physiology and promotes debilitating gastrointestinal and systemic disorders.
Exercise ventilatory response after COVID-19: comparison between ambulatory and hospitalized patients
Authors: Guerreiro Ivan , Bringard Aurélien , Nehme Mayssam , Guessous Idris , Benzakour Lamyae , Juillet De Saint Lager-Lucas Alix , Taboni Anna , Lador Frédéric
Published: October 2023

We evaluated the exercise ventilatory response in patients with persisting dyspnea after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. We found that despite similar peak power and peak absolute O2 uptake, tidal volume as a function of ventilation was lower in ambulatory than in hospitalized patients toward the end of exercise, reflecting ventilatory inefficiency. We call for evaluation of minute ventilation with the exploration of data throughout the exercise and not only peak data to better unveil ventilatory inefficiency.
Endothelium-Derived Dopamine and 6-Nitrodopamine in the Cardiovascular System
Authors: Zatz Roberto , De Nucci Gilberto
Published: October 2023

The review deals with the release of endothelium-derived dopamine and 6-nitrodopamine (6-ND) and its effects on isolated vascular tissues and isolated hearts. Basal release of both dopamine and 6-ND is present in human isolated umbilical cord vessels, human popliteal vessels, nonhuman primate vessels, and reptilia aortas. The 6-ND basal release was significantly reduced when the tissues were treated with Nω-nitro-l-arginine methyl ester and virtually abolished when the endothelium was mechanically removed. 6-Nitrodopamine is a potent vasodilator, and the mechanism of action responsible for this effect is the antagonism of dopamine D2-like receptors. As a vasodilator, 6-ND constitutes a novel mechanism by which nitric oxide modulates vascular tone. The basal release of 6-ND was substantially decreased in endothelial nitric oxide synthase knockout (eNOS−/−) mice and not altered in neuronal nitric oxide synthase knockout (nNOS−/−) mice, indicating a nonneurogenic source for 6-ND in the heart. Indeed, in rat isolated right atrium, the release of 6-ND was not affected when the atria were treated with tetrodotoxin. In the rat isolated right atrium, 6-ND is the most potent endogenous positive chronotropic agent, and in Langendorff’s heart preparation, it is the most potent endogenous positive inotropic agent. The positive chronotropic and inotropic effects of 6-ND are antagonized by β1-adrenoceptor antagonists at concentrations that do not affect the effects induced by noradrenaline, adrenaline, and dopamine, indicating that blockade of the 6-ND receptor is the major modulator of heart chronotropism and inotropism. The review proposes that endothelium-derived catecholamines may constitute a major mechanism for control of vascular tone and heart functions, in contrast to the overrated role attributed to the autonomic nervous system.
Cell State of Origin Impacts Development of Distinct Endometriosis-Related Ovarian Carcinoma Histotypes
Authors: Beddows Ian , Fan Huihui , Heinze Karolin , Johnson Benjamin K. , Leonova Anna , Senz Janine , Djirackor Svetlana , Cho Kathleen R. , Pearce Celeste Leigh , Huntsman David G. , Anglesio Michael S. , Shen Hui
Published: October 2023

Clear cell ovarian carcinoma (CCOC) and endometrioid ovarian carcinoma (ENOC) are ovarian carcinoma histotypes, which are both thought to arise from ectopic endometrial (or endometrial-like) cells through an endometriosis intermediate. How the same cell type of origin gives rise to two morphologically and biologically different histotypes has been perplexing, particularly given that recurrent genetic mutations are common to both and present in nonmalignant precursors. We used RNA transcription analysis to show that the expression profiles of CCOC and ENOC resemble those of normal endometrium at secretory and proliferative phases of the menstrual cycle, respectively. DNA methylation at the promoter of the estrogen receptor (ER) gene (ESR1) was enriched in CCOC, which could potentially lock the cells in the secretory state. Compared with normal secretory-type endometrium, CCOC was further defined by increased expression of cysteine and glutathione synthesis pathway genes and downregulation of the iron antiporter, suggesting iron addiction and highlighting ferroptosis as a potential therapeutic target. Overall, these findings suggest that while CCOC and ENOC arise from the same cell type, these histotypes likely originate from different cell states. This “cell state of origin” model may help to explain the presence of histologic and molecular cancer subtypes arising in other organs.

Significance:

Two cancer histotypes diverge from a common cell of origin epigenetically locked in different cell states, highlighting the importance of considering cell state to better understand the cell of origin of cancer.
SKP2 Knockout in Rb1/p53–Deficient Mouse Models of Osteosarcoma Induces Immune Infiltration and Drives a Transcriptional Program with a Favorable Prognosis
Authors: Ferrena Alexander , Wang Jichuan , Zhang Ranxin , Karadal-Ferrena Burcu , Al-Hardan Waleed , Singh Swapnil , Borjihan Hasibagan , Schwartz Edward L. , Zhao Hongling , Oktay Maja H. , Yang Rui , Geller David S. , Hoang Bang H. , Zheng Deyou
Published: October 2023

Osteosarcoma is an aggressive bone malignancy with a poor prognosis. One putative proto-oncogene in osteosarcoma is SKP2, encoding a substrate recognition factor of the SCF E3 ubiquitin ligase. We previously demonstrated that Skp2 knockout in murine osteosarcoma improved survival and delayed tumorigenesis. Here, we performed RNA sequencing (RNA-seq) on tumors from a transgenic osteosarcoma mouse model with conditional Trp53 and Rb1 knockouts in the osteoblast lineage (“DKO”: Osx1-Cre;Rb1lox/lox;p53lox/lox) and a triple-knockout model with additional Skp2 germline knockout (“TKO”: Osx1-Cre;Rb1lox/lox;p53lox/lox;Skp2−/−), followed by qPCR and immunohistochemistry validation. To investigate the clinical implications of our results, we analyzed a human osteosarcoma patient cohort (“NCI-TARGET OS”) with RNA-seq and clinical data. We found large differences in gene expression after SKP2 knockout. Surprisingly, we observed increased expression of genes related to immune microenvironment infiltration in TKO tumors, especially the signature genes for macrophages and to a lesser extent, T cells, B cells, and vascular cells. We also uncovered a set of relevant transcription factors that may mediate these changes. In osteosarcoma patient cohorts, high expression of genes upregulated in TKO was correlated with favorable overall survival, which was largely explained by the macrophage gene signatures. This relationship was further supported by our finding that SKP2 expression was negatively correlated with macrophage infiltration in the NCI-TARGET osteosarcoma and the TCGA Sarcoma cohorts. Overall, our findings indicate that SKP2 may mediate immune exclusion from the osteosarcoma tumor microenvironment, suggesting that SKP2 modulation in osteosarcoma may induce antitumor immune activation.