bluuebunny/crossref_metadata_2025 huggingface dataset:
Diel flight activity in response to attractants in the predatory beetle, Cathartus quadricollis (Coleoptera: Silvanidae) in macadamia nut in Hawaii
Authors: Acebes-Doria Angelita , Hamilton Lindsey J , Follett Peter A
Published: March 2024

The diel flight activity in Cathartus quadricollis (Guerin-Meneville) (Coleoptera: Silvanidae), a predator of two important pests in Hawaii, coffee berry borer, Hypothenemus hampei (Ferrari) and tropical nut borer, Hypothenemus obscurus (F.) (Coleoptera: Curculionidae: Scolytinae) was studied in a macadamia nut orchard using yellow sticky traps baited with pheromone and fungal volatile attractants. The study was conducted at different months throughout the year and at different times during the lunar cycle (new moon and full moon). Flight activity peaked in the late hours of the photophase into the early hours of the scotophase, between 1830 and 2000 h; flight activity also occurred but to a lesser extent in the early morning hours between 0700 and 1030 h. Numbers of captured C. quadricollis during periods of flight activity were negatively correlated with wind speed. The implications of these findings for the development of optimal pest management strategies including biological control are discussed.
A-Bomb for the People? When Leaders Cue the Public in Nuclear Decision-Making
Authors: Gibbons Rebecca Davis , Petrovics Ariel
Published: March 2024

In building indigenous nuclear weapon programs, leaders have incentives to keep their plans secret, and several have. Domestic populations may limit the flexibility of the program, and international scrutiny could lead to sanctions or even military strikes. And yet, many leaders have cued the public to their nuclear ambitions. Why do leaders cue these audiences to their nuclear intentions when doing so could lead to both internal and external constraints from public awareness and foreign pressure? Using qualitative evidence from past cases of elite cueing, this article offers a theoretical examination of why some leaders choose to involve the public despite—or sometimes because of—the constraints that attention can impose. We describe six types of cueing logics based on the level of development of the nuclear program and the intended audience. Understanding the rationales behind such cues is not just of historical significance; these cues remain relevant as several states continue to pursue nuclear technologies—capabilities that can be used for peaceful purposes or repurposed for nuclear weapons. In other words, nuclear cueing is an important and overlooked aspect of research on nuclear proliferation.
How proton therapy fits into the management of adult intracranial tumors
Authors: Kotecha Rupesh , La Rosa Alonso , Mehta Minesh P
Published: March 2024

Intracranial tumors include a challenging array of primary and secondary parenchymal and extra-axial tumors which cause neurologic morbidity consequential to location, disease extent, and proximity to critical neurologic structures. Radiotherapy can be used in the definitive, adjuvant, or salvage setting either with curative or palliative intent. Proton therapy (PT) is a promising advance due to dosimetric advantages compared to conventional photon radiotherapy with regards to normal tissue sparing, as well as distinct physical properties, which yield radiobiologic benefits. In this review, the principles of efficacy and safety of PT for a variety of intracranial tumors are discussed, drawing upon case series, retrospective and prospective cohort studies, and randomized clinical trials. This manuscript explores the potential advantages of PT, including reduced acute and late treatment-related side effects and improved quality of life. The objective is to provide a comprehensive review of the current evidence and clinical outcomes of PT. Given the lack of consensus and directives for its utilization in patients with intracranial tumors, we aim to provide a guide for its judicious use in clinical practice.
Evolving concepts in margin strategies and adaptive radiotherapy for glioblastoma: A new future is on the horizon
Authors: Tseng Chia-Lin , Zeng K Liang , Mellon Eric A , Soltys Scott G , Ruschin Mark , Lau Angus Z , Lutsik Natalia S , Chan Rachel W , Detsky Jay , Stewart James , Maralani Pejman J , Sahgal Arjun
Published: March 2024

Chemoradiotherapy is the standard treatment after maximal safe resection for glioblastoma (GBM). Despite advances in molecular profiling, surgical techniques, and neuro-imaging, there have been no major breakthroughs in radiotherapy (RT) volumes in decades. Although the majority of recurrences occur within the original gross tumor volume (GTV), treatment of a clinical target volume (CTV) ranging from 1.5 to 3.0 cm beyond the GTV remains the standard of care. Over the past 15 years, the incorporation of standard and functional MRI sequences into the treatment workflow has become a routine practice with increasing adoption of MR simulators, and new integrated MR-Linac technologies allowing for daily pre-, intra- and post-treatment MR imaging. There is now unprecedented ability to understand the tumor dynamics and biology of GBM during RT, and safe CTV margin reduction is being investigated with the goal of improving the therapeutic ratio. The purpose of this review is to discuss margin strategies and the potential for adaptive RT for GBM, with a focus on the challenges and opportunities associated with both online and offline adaptive workflows. Lastly, opportunities to biologically guide adaptive RT using non-invasive imaging biomarkers and the potential to define appropriate volumes for dose modification will be discussed.
Graftless Syndactyly Release
Authors: Choong Jia , Hadjiandreou Michalis , McGee Pauline , Lam Wee Leon
Published: March 2024

Syndactyly release aims to address skin deficits by resurfacing web spaces and sides of digits to allow independent digital motion while minimizing the risk of web creep and scar contractures. Conventional methods include the use of a dorsal and interdigitating flaps with full-thickness skin grafts. More recently, there have been several descriptions of “graftless” syndactyly release without skin grafts, thus avoiding a further (usually distant) donor site. However, the indications of when and when not to use these techniques remain unclear. In addition, the inevitable scarring from extra recruitment of local adjacent skin is perhaps underemphasized. In this article, we revisit the trilobed flap technique which serves to balance the amount of skin needed for resurfacing digits while minimizing local donor site scarring. The geometry and nuances of the flap inset are illustrated in detail to guide those embarking on this technique. The trilobed syndactyly release technique is a reproducible, safe, and reliable method for the release of simple syndactyly.
A Lesbian's Miscarriage
Authors: Chinloy Soraya
Published: March 2024

In my experience of caring for a lesbian couple suffering a miscarriage, I disengaged my bias about their sexual orientation and compassionately cared for their needs. After praying with the couple, I felt a deep connection with them and a palpable peace. Joy shone on their faces and they verbally expressed gratitude. God used me as a caring presence. Christian nurses are vessels for God's love to bring peace and healing.
Tailoring African American Faith Community-Based Diabetes Self-Management Education
Authors: Weeks Christine E. , Waldrop Julee , Jessup Ann
Published: March 2024

African Americans (AA) experience a disparate effect of type II diabetes (T2D). For this nurse-led pilot study, a pre-validated 6-week diabetes self-management education (DSME) program was implemented in a faith community setting and tailored to the participants' faith and culture by using short scriptural lessons, prayers, and individual sharing. Participants demonstrated improvements in fasting blood glucose (p = .042), diabetes knowledge (p = .002), and psychosocial self-efficacy (p = .001). Although generalizability of findings is limited, the structure and methods used in tailoring this DSME program could be transferable to other faith-based settings.
Christian Ethical Foundations of Modern Nursing in China
Authors: Chou Chuan Chiang , Wang Shu-Yi
Published: March 2024

The influence of Western Christian missionary nurses has been recorded in the history and development of nursing in China. The purpose of this study was to investigate the influence of Christianity on Chinese nursing ethics. This documentary research used content analysis to investigate Christian value trends over 13 years (1920-1932) as reflected in a major bilingual Chinese nursing journal.
Examining the Role of Cerebral Embolic Protection Devices in Preventing Postoperative Stroke in Patients with a History of Stroke or Transient Ischemic: Insights from the National Inpatient Sample
Authors: Desai Rupak , Mondal Avilash , Katukuri Nishanth , Pingili Adhvithi , Borra Vamsikalyan , Nayak Parth R. , Jain Akhil , Patel Harshil , Qaqish Omar , Vyas Ankit , Kondur Ashok
Published: March 2024

Cerebral embolic protection devices (CEPD) during transcatheter aortic valve replacement (TAVR) have been shown to lower the risk of stroke during the procedure. However, their long-term and clinical effects on neuro-cognition are unknown. Therefore, we hypothesized the benefit of CEPD in TAVR patients with a prior history of stroke or transient ischemic attack (TIA). National Inpatient Sample (2019) and International Classification of Diseases, 10th Revision codes were used to identify patients undergoing TAVR with prior stroke or TIA. Propensity-matched analysis was performed to adjust for baseline characteristics and comorbidities. Primary outcome measures were postoperative stroke and all-cause mortality. Length of stay and hospital cost were secondary outcomes. Of 8450 unmatched TAVR patients with prior stroke or TIA in 2019, 1095 (13%) utilized CEPD. After propensity matching previous myocardial infarction (MI), coronary artery bypass grafting, and drug abuse were higher in the TAVR-only cohort. Postoperative stroke rate (1.4% vs 2.2%; P = 0.081) and odds [adjusted odds ratio (aOR), 0.48; 95% confidence interval (CI), 0.11–2.17; P = 0.341] were lower in the CEPD group. There was no difference in all-cause in-hospital mortality between the 2 groups (0.9% vs 1.0%). Length of stay (3 vs 2 days, P <0.001) and hospital expenditure ($172,711 vs $162,284; P = 0.002) were higher for the TAVR-only cohort. CEPD in TAVR patients with prior stroke or TIA did not show statistically significant postoperative stroke benefits. However, further larger-scale prospective studies are needed to evaluate the long-term neurocognitive benefits of CEPD in these patients. As the use of TAVR continues to expand, optimizing peri-procedural strategies such as the use of CEPD remains a critical area of research to improve patient outcomes.
Steroid responsiveness in alcohol-associated hepatitis is linked to glucocorticoid metabolism, mitochondrial repair, and heat shock proteins
Authors: Hardesty Josiah , Hawthorne Meghan , Day Le , Warner Jeffrey , Warner Dennis , Gritsenko Marina , Asghar Aliya , Stolz Andrew , Morgan Timothy , McClain Craig , Jacobs Jon , Kirpich Irina A.
Published: March 2024

Background:

Alcohol-associated hepatitis (AH) is one of the clinical presentations of alcohol-associated liver disease. AH has poor prognosis, and corticosteroids remain the mainstay of drug therapy. However, ~40% of patients do not respond to this treatment, and the mechanisms underlying the altered response to corticosteroids are not understood. The current study aimed to identify changes in hepatic protein expression associated with responsiveness to corticosteroids and prognosis in patients with AH.

Methods:

Patients with AH were enrolled based on the National Institute on Alcohol Abuse and Alcoholism inclusion criteria for acute AH and further confirmed by a diagnostic liver biopsy. Proteomic analysis was conducted on liver samples acquired from patients with AH grouped as nonresponders (AH-NR, n = 7) and responders (AH-R, n = 14) to corticosteroids, and nonalcohol-associated liver disease controls (n = 10). The definition of responders was based on the clinical prognostic model, the Lille Score, where a score < 0.45 classified patients as AH-R and a score > 0.45 as AH-NR. Primary outcomes used to assess steroid response were Lille Score (eg, improved liver function) and survival at 24 weeks.

Results:

Reduced levels of the glucocorticoid receptor and its transcriptional co-activator, glucocorticoid modulatory element-binding protein 2, were observed in the hepatic proteome of AH-NR versus AH-R. The corticosteroid metabolizing enzyme, 11-beta-hydroxysteroid dehydrogenase 1, was increased in AH-NR versus AH-R along with elevated mitochondrial DNA repair enzymes, while several proteins of the heat shock pathway were reduced. Analysis of differentially expressed proteins in AH-NR who survived 24 weeks relative to AH-NR nonsurvivors revealed several protein expression changes, including increased levels of acute phase proteins, elevated coagulation factors, and reduced mast cell markers.

Conclusions:

This study identified hepatic proteomic changes that may predict responsiveness to corticosteroids and mortality in patients with AH.
Congenital Generalized Lipodystrophy in a Division 1 Female Sprinter
Authors: Schleich Kevin T. , Novakofski Kira D. , Thomsen Timothy W. , Woodroffe Lisa , Slayman Tyler G.
Published: March 2024

A 21-year-old African American Division 1 female sprinter presented with 3-weeks history of right great toe and forefoot pain, fatigue, and a 30-day continuous menstrual cycle despite implanted etonogestrel (Nexplanon) inserted 3 years prior. An magnetic resonance imagine (MRI) identified likely stress fracture of the second metatarsal base with a diffusely low T1 signal indicating hyperactive red marrow. Due to persistent pain, a follow-up MRI was ordered 6 months later and indicated serous atrophy of the bone marrow, prompting a further metabolic workup notable for triglycerides exceeding 4000 mg/dL and a hemoglobin A1c of 10.9%. This case highlights the manifestation of a rare congenital lipodystrophy that initially presented as a relatively classic stress fracture and metrorrhagia in a female athlete.
HER2-low and Overexpression in Mucinous Ovarian Cancer: Analysis of ASCO/CAP and ToGA Immunohistochemical Scoring
Authors: Han Rachel , Madariaga Ainhoa , Gonzalez-Ochoa Eduardo , Smith Adam C. , Wang Lisa , Lheureux Stephanie , Rouzbahman Marjan
Published: March 2024

Mucinous ovarian carcinoma is an uncommon malignancy characterized by resistance to chemotherapy and poor survival in the metastatic setting. HER2 amplification is a frequent late event in carcinogenesis, yet the incidence of HER2-low in mucinous ovarian carcinoma is unknown. Further, the optimal method for determining overexpression in these tumors is not established. We sought to assess the ASCO/CAP and ToGA trial scoring methods for HER2 IHC with correlation to FISH, p53, and mismatch repair protein status and to determine the incidence of HER2-low in mucinous ovarian carcinoma. A total of 29 tumors from 23 patients were included. Immunohistochemistry for HER2, p53, MLH1, PMS2, MSH2, and MSH6 was performed. Scoring was performed according to the ASCO/CAP and ToGA trial criteria. HER2 FISH was performed and scored according to the ASCO/CAP criteria. The proportion of HER2-low, defined as 1+ or 2+ staining with negative FISH, was determined. Using ASCO/CAP, 26% demonstrated 3+ while 35% demonstrated 2+ staining. Using ToGA, 30% demonstrated 3+ while 57% demonstrated 2+ staining. By FISH, 26% were positive for HER2 amplification. Both systems captured all FISH-positive cases; the use of ASCO/CAP resulted in fewer equivocal and false-positive cases. Among HER2-negative cases, 88% were HER2-low. Aberrant p53 expression was detected in 55% of cases; mismatch repair deficiency was not identified in any cases. ASCO/CAP guidelines are accurate and resource-effective in determining HER2 overexpression in mucinous ovarian carcinoma. HER2-low is common in these tumors; further studies to determine the role of HER2-targeted therapy including antibody-drug conjugates are indicated.
Reconstruction of Extensive Maxillary Defects Using Flow-Through Fibula Free Flap With Anterolateral Thigh Free Flap
Authors: Bao Mingzhe , Paka Lubamba Grace , Hua Yufei , Zhang Gaowei , Wang Miao , Gao Ning , Li Chunjie
Published: March 2024

Background:

The maxillary defects left unreconstructed or inadequately reconstructed often result in significant functional and esthetic impairments. Adequate reconstruction of extensive maxillary defects requires a sufficient volume of hard and soft tissues.

Methods:

A 48-year-old male presenting bilateral extensive maxillary defects underwent secondary reconstruction with a flow-through fibula free flap in combination with an anterolateral thigh free flap.

Results:

The use of flow-through technique allowed minimizing the problem of limited recipient vessels and the length of free flap vascular pedicle usually encountered in secondary reconstruction. The bilateral maxillary defects were successfully reconstructed, and the postoperative outcomes were uneventful. The patient was satisfied with the treatment outcomes. He is being followed up and was referred to the implantology department for the placement of osseointegrated dental implants.

Conclusions:

The flow-through fibula free flap, in combination with the anterolateral thigh free flap, was found reliable and feasible for this case of secondary reconstruction of bilateral maxillary defects. This technique has provided satisfactory functional and esthetic outcomes and effectively improved the patient’s self-esteem.
A novel cell communication method reveals that grik4 and gabrd may be critical for inducing death in RGNNV-infected groupers
Authors: He Tengfei , Yu Yepin
Published: March 2024

To investigate the infectious mechanism of RGNNV, we adopted multi-omics methods to study the precise cellular interactions. We combined proteomic, bulk-RNA seq and sc-RNA seq to search for the secret of RGNNV’s influence on the nervous system in grouper. Besides, we created a sc-RNA seq workflow for cell communication analysis that can be applied to those non-model organisms with a reference for the first time, which usually been done by comparing homologous genes in humans or mice in the past (Cheng, Chen et al. 2023), but we use stringdb database to predict interactions at the whole proteomic level (Szklarczyk, Kirsch et al. 2023), and we also build a R package of this procedure to help achieving this goal in other non-model organisms. The results shows that grik4 and gabrd might be the direct causes of death in RGNNV-infected groupers. We also present a mechanistic picture of RGNNV attacking the nervous system of grouper and causing nerve necrosis.
Multi-view graph learning for deciphering the dominant cell communication assembly of downstream functional events from single-cell RNA-seq data
Authors: Ji Boya , Wang Xiaoqi , Wang Xiang , Xu Liwen , Peng Shaoliang
Published: March 2024

Cell-cell communications (CCCs) from multiple sender cells collaboratively affect downstream functional events in receiver cells, thus influencing cell phenotype and function. How to rank the importance of these CCCs and find the dominant ones in a specific downstream functional event has great significance for deciphering various physiological and pathogenic processes. To date, several computational methods have been developed to focus on the identification of cell types that communicate with enriched ligand-receptor interactions from single-cell RNA-seq (scRNA-seq) data, but to the best of our knowledge, all of them lack the ability to identify the communicating cell type pairs that play a major role in a specific downstream functional event, which we call it “dominant cell communication assembly (DCA)”. Here, we proposed scDCA, a multi-view graph learning method for deciphering DCA from scRNA-seq data. scDCA is based on a multi-view CCC network by constructing different cell type combinations at single-cell resolution. Multi-view graph convolution network was further employed to reconstruct the expression pattern of target genes or the functional states of receiver cells. The DCA was subsequently identified by interpreting the model with the attention mechanism. scDCA was verified in a real scRNA-seq cohort of advanced renal cell carcinoma, accurately deciphering the DCA that affect the expression patterns of the critical immune genes and functional states of malignant cells. Furthermore, scDCA also accurately explored the alteration in cell communication under clinical intervention by comparing the DCA for certain cytotoxic factors between patients with and without immunotherapy. scDCA is free available at:https://github.com/pengsl-lab/scDCA.git.
Metabolic Deficiencies Underlie Plasmacytoid Dendritic Cell Exhaustion After Viral Infection
Authors: Greene Trever T. , Jo Yeara , Macal Monica , Fang Ziyan , Khatri Fawziyah S. , Codrington Alicia L. , Kazane Katelynn R. , Chiale Carolina , Akbulut Elizabeth , Swaminathan Shobha , Fujita Yu , Fitzgerald-Bocarsly Patricia , Cordes Thekla , Metallo Christian , Scott David A. , Zuniga Elina I.
Published: March 2024

Type I Interferons (IFN-I) are central to host protection against viral infections1. While any cell can produce IFN-I, Plasmacytoid Dendritic Cells (pDCs) make greater quantities and more varieties of these cytokines than any other cell type2. However, following an initial burst of IFN- I, pDCs lose their exceptional IFN-I production capacity and become “exhausted”, a phenotype that associates with enhanced susceptibility to secondary infections3–5. Despite this apparent cost for the host, pDC exhaustion is conserved across multiple species and viral infections, but the underlying mechanisms and the potential evolutionary advantages are not well understood. Here we characterize pDC exhaustion and demonstrate that it is associated with a reduced capacity of pDCs to engage both oxidative and glycolytic metabolism. Mechanistically, we identify lactate dehydrogenase B (LDHB) as a novel positive regulator of pDC IFN-I production in mice and humans, show that LDHB deficiency is associated with suppressed IFN-I production, pDC metabolic capacity, and viral control following a viral infection, and demonstrate that preservation of LDHB expression is sufficient to partially restore exhausted pDC functionin vitroandin vivo. Furthermore, restoring LDHBin vivoin exhausted pDCs increased IFNAR dependent infection- associated pathology. Therefore, our work identifies a novel and conserved mechanism for balancing immunity and pathology during viral infections, while also providing insight into the highly preserved but previously unexplained phenomenon of pDC exhaustion.
Learning to Choose: Behavioral Dynamics Underlying the Initial Acquisition of Decision Making
Authors: White Samantha R. , Preston Michael W. , Swanson Kyra , Laubach Mark
Published: March 2024

Current theories of decision making propose that decisions arise through competition between choice options. Computational models of the decision process estimate how quickly information about choice options is integrated and how much information is needed to trigger a choice. Experiments using this approach typically report data from well-trained participants. As such, we do not know how the decision process evolves as a decision-making task is learned for the first time. To address this gap, we used a behavioral design separating learning the value of choice options from learning to make choices. We trained male rats to respond to single visual stimuli with different reward values. Then, we trained them to make choices between pairs of stimuli. Initially, the rats responded more slowly when presented with choices. However, as they gained experience in making choices, this slowing reduced. Response slowing on choice trials persisted throughout the testing period. We found that it was specifically associated with increased exponential variability when the rats chose the higher value stimulus. Additionally, our analysis using drift diffusion modeling revealed that the rats required less information to make choices over time. Surprisingly, we observed reductions in the decision threshold after just a single session of choice learning. These findings provide new insights into the learning process of decision-making tasks. They suggest that the value of choice options and the ability to make choices are learned separately, and that experience plays a crucial role in improving decision-making performance.
Corticothalamic modelling of sleep neurophysiology with applications to mobile EEG
Authors: Morshedzadeh Taha , Kadak Kevin , Bastiaens Sorenza P. , Oveisi M. Parsa , Momi Davide , Wang Zheng , Harita Shreyas , Abou Jaude Maurice , Aimone Christopher A. , Mann Steve , Hill Sean L. , Griffiths John D.
Published: March 2024

Abstract

Recent developments in mathematical modelling of EEG enable the tracking of otherwise-inaccessible neurophysiological parameters throughout sleep. Likewise, advancements in wearable electronics have enabled easy & affordable collection of sleep EEG at home. The convergence of these two advances, namely neurophysiological modelling for mobile sleep EEG, can boost preclinical and clinical assessments of sleep. However, this subject area has received limited attention in existing literature. To address this, we used an established model of the corticothalamic system to analyze EEG power spectra from 5 datasets, spanning from research-grade systems to at-home mobile EEG. In the present work, we compare the convergent and divergent features of the data and the estimated physiological model parameters. While data quality and characteristics differ considerably, key patterns consistent with previous theoretical and empirical work are observed. During the transition from lighter to deeper NREM, i) exponent of the aperiodic (1/f) spectral component is increased, ii) bottom-up thalamocortical drive is reduced, iii) corticocortical connection strengths are increased. This effect is observed in healthy subjects but is interestingly absent when taking SSRI antidepressants, suggesting possible effects of ascending neuromodulation on corticothalamic oscillations. We further show a month-long increase in REM% in one mobile EEG subject, associated with boosted high-frequency activity in spectra and higher thalamothalamic gains in the model, pointing to possible changes of thalamic inhibition in REM parasomnias. Our results provide a proof-of-principle for the utility and feasibility of this physiological modelling-based approach to analyzing mobile EEG data, providing a mechanistic measure of brain physiology during sleep.

Statement of significance

We employ a physiological model of the corticothalamic circuitry to model the EEG power spectra in sleep. We fit this model to 5 EEG datasets, and demonstrate that while mobile and non-mobile EEG recordings differ in their characteristics and quality, they can both robustly represent the changes along sleep stages using the aperiodic (1/f) component. We observe an increased corticocortical connection strength and decreased corticothalamic connection strength as the subject goes into deeper stages of NREM sleep; an effect that is, importantly, not observed in subjects taking SSRIs. This work provides a proof-of-concept for using mathematical modelling, working well for large mobile and non-mobile datasets providing valuable insight into the mechanisms generating sleep EEG.
The widely used cymoxanil fungicide impairs respiration inSaccharomyces cerevisiaevia cytochromecoxidase inhibition
Authors: Mendes Filipa , Santos-Pereira Cátia , Vieira Tatiana F. , Pinto Mélanie Martins , Castro Bruno B. , Sousa Sérgio F. , Sousa Maria João , Devin Anne , Chaves Susana R.
Published: March 2024

Cymoxanil (CYM) is a synthetic acetamide fungicide that has been widely used to combat downy mildew diseases in grapevine cultures and late blight diseases in tomato and potato caused by the oomycetesPlasmopara viticolaandPhytophthora infestans, respectively. Despite its extensive application, the biochemical mode of action of CYM remains elusive. Previous reports indicate that CYM affects growth, DNA and RNA synthesis inPhytophthoraand inhibits cell growth, biomass production and respiration rate in the well-characterized fungal modelSaccharomyces cerevisiae. We therefore used this model to further characterize the effect of CYM on mitochondria. We found that CYM inhibits oxygen consumption in whole cells after 3 h of exposure, which persists over time. Using isolated mitochondria, we demonstrated that CYM specifically inhibits cytochromecoxidase (CcO) activity during oxidative phosphorylation. Based on molecular docking algorithms, we propose that CYM acts by blocking the interaction of cytochromec(cytc) with CcO, hampering electron transfer and inhibiting CcO catalytic activity. Although other targets cannot be excluded, our data offer valuable insights into the mode of action of CYM that can be instrumental to drive informed management of the use of this fungicide.
Increasing the vitamin C transporter SVCT2 in microglia improves synaptic plasticity and restrains memory impairments in Alzheimer’s disease models
Authors: Portugal Camila C. , Santos Evelyn C. S. , Pacheco Ana M. , Costa-Pinto Sara , Almeida Tiago O. , Tedim-Moreira Joana , Gavin Dora , Canedo Teresa , Oliveira Fabiana , Summavielle Teresa , Vaz Sandra H. , Socodato Renato , Relvas João B.
Published: March 2024

Alzheimer’s Disease (AD) is characterized by progressive cognitive decline and synaptic dysfunction, often associated with amyloid-beta accumulation and microglial alterations. Here, we investigate the role of the Sodium-dependent Vitamin C Transporter 2 (SVCT2) in microglia to modulate AD-like pathology in mice. Using a combination of RNA sequencing, advanced quantitative proteomics, electrophysiology, behavioral tests, high-throughput imaging, and microglial viral gene delivery, we explore the interplay between SVCT2 expression in microglia, amyloid-beta load, synaptic proteome changes, and synaptic plasticity. Our results demonstrate that SVCT2 expression in microglia decreases with age in the 5xFAD mice, correlating with memory deficits and alterations in synaptic mitochondrial proteome. Importantly, overexpression of SVCT2 in microglia leads to enhanced clearance of amyloid plaques and reconfiguration of the mitochondrial proteome landscape in the synapses, improving synaptic long-term plasticity (LTP) and memory performance. Our findings underscore the SVCT2 overexpression in microglia as a potent strategy to simultaneously decrease amyloid pathology and enhance synaptic plasticity and memory performance, offering new avenues for therapeutic interventions in AD.
miR-155-5p/miR-674-3p presence in peripheral blood leukocytes and relative proportion of white blood cell types as biomarkers of asymptomatic and symptomatic phases of temporal lobe epilepsy
Authors: Szydłowska Kinga , Chrościcki Piotr , Olszewski Maciej , Nizińska Karolina , Piwocka Katarzyna , Łukasiuk Katarzyna
Published: March 2024

Epilepsy frequently develops as a result of brain insult, for example, brain injury or stroke. Currently, there are no tools allowing us to predict which trauma patients will eventually develop epilepsy. There is evidence that microRNAs levels are altered in the blood, making them attractive candidates for peripheral biomarkers of epilepsy. We analyzed white blood cell subpopulations containing miR-155-5p and miR-674-3p, in control and stimulated animals and in control and symptomatic or asymptomatic animals in the amygdala stimulation model. The first proposed early biomarker of epilepsy is the relative proportion of CD45RA+B cells containing miR-155-5p and/or miR-674-3p. Others are increased number of CD45RA+B cells containing either miR-155-5p or miR-155-5p and miR-674-3p together or decreased number of CD161+NK cells not containing miR-155-5p nor miR-674-3p. Additionally, we found that the decreased number of CD4+T cells can be used as a potential biomarker for identifying epileptic animals with symptomatic epilepsy.
Cell-type specific effects ofFusariummycotoxins on primary neuronal and astroglial cells
Authors: Szentgyörgyi Viktória , Bencsik Norbert , Micska Brigitta , Rátkai Anikó , Schlett Katalin , Tárnok Krisztián
Published: March 2024

Fumonisin B1, deoxynivalenol (DON) and zearalenone (ZEA) are toxic secondary metabolites produced byFusariummolds. These mycotoxins are common food and feed pollutants and represent a risk for human and animal health. Although the mycotoxins produced by this genus can cross the blood-brain-barrier (BBB) in many species, their effect on neuronal function remains unclear. We investigated cell viability effects of these toxins on specified neural cell types, including mouse primary neuronal, astroglial and mixed cell cultures 24 or 48 hours after mycotoxin administration. Cell viability assay revealed that DON decreased cell viability in a dose-dependent manner, independently from the culture’s type. Fumonisin B1 increased cell viability significantly on astroglial and mixed cell cultures in lower doses, while it exerted a highly toxic effect in 50 µM. ZEA had significant effects on all culture type in 10 nM by increasing the cell viability. Since ZEA is a mycoestrogen, we analyzed the effects of ZEA on the expression of estrogen receptor isotypes ERα and ERβ and mitochondrial voltage-dependent anion channel (VDAC1) by qRT-PCR. In neuronal and mixed cultures, ZEA administration decreased ERα expression, while in astroglial cultures, it induced the opposite effect. ERβ and VDAC1 expression was not altered by ZEA in either culture types. ZEA also affected the firing pattern of neurons by enhancing the burst frequency. Our results demonstrate thatFusariummycotoxins are acting on a cell specific manner in the brain tissue.
High-resolution fleezers reveal duplex opening and stepwise assembly by an oligomer of the DEAD-box helicase Ded1p
Authors: Patrick Eric M. , Yadav Rajeev , Senanayake Kasun , Cotter Kyle , Putnam Andrea A. , Jankowsky Eckhard , Comstock Matthew J.
Published: March 2024

DEAD-box RNA helicases are ubiquitous in all domains of life where they bind and remodel RNA and RNA-protein complexes. DEAD-box helicases unwind RNA duplexes by local opening of helical regions without directional movement through the duplexes and some of these enzymes, including Ded1p from Saccharomyces cerevisiae, oligomerize to effectively unwind RNA duplexes. Whether and how DEAD-box helicases coordinate oligomerization and unwinding is not known and it is unclear how many base pairs are actively opened. Using high-resolution optical tweezers and fluorescence, we reveal a highly dynamic and stochastic process of multiple Ded1p protomers assembling on and unwinding an RNA duplex. One Ded1p protomer binds to a duplex-adjacent ssRNA tail and promotes binding and subsequent unwinding of the duplex by additional Ded1p protomers in 4-6 bp steps. The data also reveal rapid duplex unwinding and rezipping linked with binding and dissociation of individual protomers and coordinated with the ATP hydrolysis cycle.
A novel model-free feature selection method with FDR control for omics-wide association analysis
Authors: Lu Zi-tong , Song Xue-ting , Gao Yu-fan , Xiao Jian
Published: March 2024

Omics-wide association analysis is a very important tool for medicine and human health study. However, the modern omics data sets collected often exhibit the high-dimensionality, unknown distribution response, unknown distribution features and unknown complex associated relationships between the response and its explanatory features. Reliable association analysis results depend on an accurate modeling for such data sets. Most of the existing association analysis methods rely on the specific model assumptions and lack effective false discovery rate (FDR) control so that they may not work well. To address these limitations, we firstly apply a single index model for omics data. This model is free in performance of allowing the relationships between the response variable and linear combination of covariates can be connected by any unknown monotonic link function, and both the random error and the covariates can follow any unknown distribution. Then based on this model, we combine rank-based approach and symmetrized data aggregation approach to develop a novel and model-free feature selection method for achieving fine-mapping of risk features while controlling the false positive rate of selection. The analysis results of simulated data show our method possesses effective and robust performance for all the scenarios. The proposed method is also used to analyze a real ocean microbiome data and identifies some casual taxa unreported by the existing finds.
Heterogeneous hybrid immunity against Omicron variant JN.1 at 11 months following breakthrough infection
Authors: He Xuan , Jiang Jiajing , Li Guo , Liu Jinyuan , Gan Jiadi , Zhou Linlin , Bai Chunyang , Zi Qiong , Mou Xiaoli , Zeng Shan , Yuan Junjie , Zhou Chuanjie , Li Yangqian , Zhu Guonian , Zhao Renjie , Yang Lan , Wu Jiaxuan , Zhang Huohuo , Xian Jinghong , Wang Zhoufeng , Qi Qi , Liu Yu , Yu Jingyou , Liu Dan , Li Weimin
Published: March 2024

A highly transmissible SARS-CoV-2 variant JN.1 is rapidly spreading throughout the nation, becoming the predominant strain in China and worldwide. However, the current immunity against the circulating JN.1 at population level has yet to be fully evaluated. We recruited representative cohorts with stratified age groups and diverse combinations of vaccination and/or infection in recent months, and promptly assessed humoral immunity for these subjects predominantly exhibiting hybrid immunity. We report that at 11 months following BA.5-wave breakthrough infection (BTI), these vaccinated individuals generally showed above-the-threshold yet low level of neutralizing activity against JN.1, with slightly greater potency observed in children and adolescents compared to adults and seniors. Meanwhile, XBB/EG.5-wave reinfection post-BTI significantly boosted the neutralizing antibodies against Omicron variants, including JN.1 in both adults (13.4-fold increase) and seniors (24.9-fold increase). To better understand respiratory mucosal protection against JN.1 over an extended period of months post-BTI, we profiled the humoral immunity in bronchoalveolar lavage samples obtained from vaccinated subjects with or without BTI, and revealed increased potency of neutralizing activity against the BA.5 and JN.1 variants in the respiratory mucosa through natural infection. Notably, at 11 months post-BTI, memory B cell responses against prototype and JN.1 were detectable in both blood and respiratory mucosa, displaying distinct memory features in the circulation and airway compartments. XBB/EG.5-wave reinfection drove the expansion of JN.1-specific B cells, along with the back-boosting of B cells responding to the ancestral viral strain, suggesting the involvement of immune imprinting. Together, this study indicates heterogeneous hybrid immunity over 11 months post-BTI, and underscores the vulnerability of individuals, particularly high-risk seniors, to JN.1 breakthrough infection. An additional booster with XBB-containing vaccine may greatly alleviate the onward transmission of immune-evasive SARS-CoV-2 variants.
Resistive cooling of ions' center-of-mass energy in a Penning trap on millisecond time scales
Authors: Kiffer Markus , Ringleb Stefan , Stöhlker Thomas , Vogel Manuel
Published: March 2024

We have performed systematic measurements of the resistive cooling behavior of bunches of highly charged ions in a Penning trap after injection from an external source. In particular, we have been able to measure the exponential cooling rate of the axial center-of-mass motion and experimentally show its linear dependence on the ion number within the bunch, as expected from theory. The common center-of-mass energy of the ions is reduced by more than four orders of magnitude on the time scale of milliseconds while the single-ion cooling occurs on the scale of seconds, representing a highly effective way to remove the dominating part of the ion kinetic energy.

Published by the American Physical Society
2024
Unitary model analysis of
f0(500)
pole positions by continuously varying
mπ
: Comparison with discrete lattice predictions
Authors: Rupp George
Published: March 2024

Resonance, bound-state, and virtual-state pole positions of the f0(500) scalar meson are computed as a continuous function of pion mass in the framework of a unitarized and analytic coupled-channel model for scalar mesons, described as dynamical quark-antiquark states. The f0(500) is modeled with both light and strange qq¯ seeds, mixing with each other through the common S-wave ππ, KK¯, and ηη meson-meson decay channels. The few model parameters are fitted to experimental S-wave ππ phase shifts up to 1 GeV. In the case of the physical π± mass of 139.57 MeV, resonance poles at (460−i222)  MeV and (978−i37.2)  MeV are found for the f0(500) and f0(980), respectively. Resonance, bound-state, and virtual-state pole trajectories are computed and plotted as a function of pion masses up to 500 MeV, both in the complex-energy and complex-momentum planes. The results are discussed and compared to the most advanced lattice QCD computations employing interpolators that correspond to the qq¯ and meson-meson channels in the present model, that is, for a few discrete values of the unphysical pion mass in those lattice calculations.

Published by the American Physical Society
2024
Transformation of a skyrmionium to a skyrmion through the thermal annihilation of the inner skyrmion
Authors: Jiang Anjie , Zhou Yan , Zhang Xichao , Mochizuki Masahito
Published: March 2024

Skyrmioniums are doughnutlike topological spin textures in chiral magnets, which are able to move with zero skyrmion Hall effect. The annihilation of a skyrmionium involves the topological transition through singularity formation at the continuum level. Here we analytically and numerically study a type of thermal annihilation of a skyrmionium under the framework of micromagnetism. The skyrmionium initially exists in an ultrathin ferromagnetic film in the exchange-dominated regime and is stabilized under a uniform perpendicular magnetic field. The thermal annihilation of the “skyrmion” inside the skyrmionium results in the transformation of the skyrmionium to a skyrmion. We derive an analytical formula in the Arrhenius form describing the annihilation rate of this process. We find that the analytical solutions agree well with the micromagnetic simulation results. Besides, from the large deviation point of view, we derive the dynamical path for the collapse of a skyrmionium. Our results are useful for understanding the thermal stability of skyrmioniums and may lead to spintronic applications based on the thermal manipulation of skyrmioniums.

Published by the American Physical Society
2024
Elastic precursor softening in proper ferroelastic materials: A molecular dynamics study
Authors: Lu Guangming , Cordero Francesco , Hideo Kimura , Ding Xiangdong , Xu Zhijun , Chu Ruiqing , Howard Christopher J. , Carpenter Michael A. , Salje Ekhard K. H.
Published: March 2024

Precursor elastic effects are investigated in a displacive anharmonic spring model and shown to extend greatly into the paraelastic phase. Weak precursor effects can be detected near 2Ttr, where Ttr is the ferroelastic transition temperature. The precursor effects become strong at T<1.7Ttr. Two effects were identified in our two-dimensional model: the symmetry-breaking strain e3 (ɛxy) leads to softening of the elastic modulus C33, while the nonsymmetry-breaking strain e1+e2 (ɛxx+ɛyy) leads to hardening of C11. The strain e3 is proportional to the order parameter and scales as |e1+e2|
∼e32. The temperature evolutions of the elastic moduli are surprisingly well described by power laws and Vogel-Fulcher equations. The power-law exponents are ∼−0.5 for ΔC33 and ∼−1 for ΔC11, Δ(

C

11

+

C

12

) and Δ(C11−C12). The Vogel-Fulcher temperatures are very similar, while the Vogel-Fulcher energies differ between the excess elastic moduli. The origin of the precursor effect is the evolution of short-range order in the paraelastic phase which gives rise to a characteristic local nanostructure. In the case of the symmetry-breaking strain, this microstructure resembles dynamical twinning patterns corresponding to the ferroelastic nanostructure, which weakens the material. In the case of the nonsymmetry-breaking strain, we find density fluctuations which make the material harder.

Published by the American Physical Society
2024
Experimental demonstration of a high-fidelity virtual two-qubit gate
Authors: Singh Akhil Pratap , Mitarai Kosuke , Suzuki Yasunari , Heya Kentaro , Tabuchi Yutaka , Fujii Keisuke , Nakamura Yasunobu
Published: March 2024

We experimentally demonstrate a virtual two-qubit gate and characterize it using quantum process tomography (QPT). The virtual two-qubit gate decomposes an actual two-qubit gate into single-qubit unitary gates and projection gates in quantum circuits for expectation-value estimation. We implement projection gates via midcircuit measurements. The deterministic sampling scheme reduces the number of experimental circuit evaluations required for decomposing a virtual two-qubit gate. We also apply quantum error mitigation to suppress the effect of measurement errors and improve the average gate fidelity of a virtual controlled-Z (CZ) gate to fav=0.9938±0.0002. Our results highlight a practical approach to implement virtual two-qubit gates with high fidelities, which are useful for simulating quantum circuits using fewer qubits and implementing two-qubit gates on a distant pair of qubits.

Published by the American Physical Society
2024
Determinants of mobile health (M-Health) application adoption, usage and discontinuity among corporate workers diagnosed with hypertension and diabetes
Authors: Liashiedzi Gabriel Kojovi , Eto Florence Elorm , Atinga Roger Ayimbillah , Abor Patience Aseweh
Published: March 2024

Purpose

This study examined the determinants of mobile health (M-Health) application, adoption, usage and discontinuation among corporate workers diagnosed with hypertension and diabetes in Ghana.

Design/methodology/approach

The diffusion innovation and reasoned action theories were employed using an exploratory design. Three hundred corporate workers diagnosed with diabetes and hypertension from three health facilities for the past six months were sampled for the study using a multi-stage sampling technique and administered questionnaires. Descriptive statistics and logistic regression tools were employed in the analysis of data.

Findings

The study found a significant number of factors influencing m-health applications adoption, usage and discontinuity. These factors include nature and demand of job, perceived advantage, compatibility, complexity, triability, aesthetics and trust. Aesthetics emerged as the strongest predictive factor for the adoption, usage and discontinuity of use among diabetic and hypertensive corporate workers. With the adoption of M-Health applications, compatibility, as well as nature and demand of job, were significant predictors. With the usage of M-Health applications, complexity, triability, aesthetics and trust were significant predictors. Moreover, perceived advantage, compatibility, complexity and triability influenced significantly the choice to discontinue using M-Health applications. The study concluded that M-Health application functionalities play a valuable role in patients’ intention to adopt, use and discontinue the use of an M-Health application in Ghana.

Originality/value

This exploratory study offers in-depth insight into how major M-Health application features affect its adoption, usage and discontinuity, providing crucial information for future research and the improvement of chronic condition healthcare delivery.