bluuebunny/crossref_metadata_2025 huggingface dataset:
Discordances in patients’ and physicians’ perspectives on which contextual factors should be accounted for during smoking cessation
Authors: Malmartel Alexandre , Ravaud Philippe , Tran Viet-Thi
Published: August 2024

Background

Smoking cessation interventions requires attending to the circumstances and needs of individual patients. We aimed at highlighting the discordances between patients’ and physicians’ perspectives on contextual factors that should be considered during smoking cessation.

Methods

We identified 36 contextual factors identified that should be considered during smoking cessation using PubMed and interviewing general practitioners. Physicians recruited through social networks campaigns and smoker or former smoker patients from the ComPaRe cohort selected the factors they considered most relevant in two online paired comparison experiment. Bradley Terry Luce models estimated the ability of each factor (i.e. the probability to be preferred). We calculated the Pearson’s correlation and the intraclass correlation coefficients for the contextual factor from each perspective and compared the ranking of the 10 contextual factors with the highest abilities.

Results

Seven hundred and ninety-three patients’ and 795 physicians’ perspectives estimated the ability (i.e., importance) of the contextual factors in 11 963 paired comparisons. We found a high correlation between physicians’ and patients’ perspectives of the contextual factors to be considered for smoking cessation (r = 0.76, P < 0.0001). However, the agreement between the abilities of contextual factors was poor (ICC = 0.42 [−0.10; 0.75]; P = 0.09). Fine-grain analysis of participants’ answers revealed many discrepancies. For example, 40% factors ranked in the top 10 most important for physicians were not in patients’ top 10 ranking.

Conclusion

Our results highlight the importance of patient-centered care, the need to engage discussions about patients’ values, beyond what is thought to be important, to avoid overlooking their real context.
A comprehensive atlas of pig RNA editome across 23 tissues reveals RNA editing affecting interaction mRNA–miRNAs
Authors: Long Jiajia , Liu Weiwei , Fan Xinhao , Yang Yalan , Yang Xiaogan , Tang Zhonglin
Published: August 2024

RNA editing is a co-transcriptional/post-transcriptional modification that is mediated by the ADAR enzyme family. Profiling of RNA editing is very limited in pigs. In this study, we collated 3813 RNA-seq data from the public repositories across 23 tissues and carried out comprehensive profiling of RNA editing in pigs. In total, 127,927 A-to-I RNA-editing sites were detected. Our analysis showed that 98.2% of RNA-editing sites were located within repeat regions, primarily within the pig-specific SINE retrotransposon PRE-1/Pre0_SS elements. Subsequently, we focused on analyzing specific RNA-editing sites (SESs) in skeletal muscle tissues. Functional enrichment analyses suggested that they were enriched in signaling pathways associated with muscle cell differentiation, including DMD, MYOD1, and CAV1 genes. Furthermore, we discovered that RNA editing event in the 3′UTR of CFLAR mRNA influenced miR-708-5p binding in this region. In this study, the panoramic RNA-editing landscape of different tissues of pigs was systematically mapped, and RNA-editing sites and genes involved in muscle cell differentiation were identified. In summary, we identified modifications to pig RNA-editing sites and provided candidate targets for further validation.
Tdh3 and Rom2 are functional modulators of a conserved condensate-resident RNA-binding protein, Scd6, in Saccharomyces cerevisiae
Authors: Togra Chitra , Dhage Riya , Rajyaguru Purusharth I
Published: August 2024

Arginine–glycine–glycine motif proteins play a crucial role in determining mRNA fate. Suppressor of clathrin deficiency 6 (Scd6) is a conserved arginine–glycine–glycine motif containing ribonucleoprotein (RNP) condensate–resident, translation repressor, and decapping activator protein in Saccharomyces cerevisiae. Identifying protein factors that can modulate Scd6 function is critical to understanding the regulation of mRNA fate by Scd6. In this study, using an approach that combined mRNA tethering assay with flow cytometry, we screened 50 genes for their role in modulating the translation repression activity of Scd6. We identified 8 conserved modulators with human homologs. Of these, we further characterized in detail guanine nucleotide exchange factor Rho1 multicopy suppressor 2 (Rom2) and glycolytic enzyme triose phosphate dehydrogenase 3 (Tdh3), which, respectively, impede and promote translation repression activity of Scd6. Our study reveals that Rom2 negatively regulates the arginine methylation of Scd6 and antagonizes its localization to P-bodies. Tdh3, on the other hand, promotes Scd6 interaction with Hmt1, thereby promoting the arginine methylation of Scd6 and enhanced eIF4G1 interaction, which is known to promote its repression activity. Identifying these novel modulators provides exciting new insights into the role of a metabolic enzyme of the glycolytic pathway and guanine nucleotide exchange factor implicated in the cell wall integrity pathway in regulating Scd6 function and, thereby, cytoplasmic mRNA fate.
Religiosity and Spirituality Development: An Accelerated Longitudinal Design
Authors: Nelson Niccole A , Joiner Raquael J , Martinez Brandy S , Bergeman Cindy S
Published: August 2024

Background and Objectives

The central aim of the present study was to model developmental trends in communal and independent religious practices, spirituality, positive and negative religious/spiritual coping, as well as their confluence, across ages 45–80.

Research Design and Methods

Participants derived from the Notre Dame Study of Health & Well-being (NDHWB), a longitudinal study spanning 10 years in an age-heterogeneous sample. Using 2-level multilevel models, we estimated no change, linear change, quadratic change, and cubic change functions across ages 45–80 in each construct. Cohort differences were also tested.

Results

Communal and independent practices, spirituality, negative religious/spiritual coping, as well as composite religiosity/spirituality, followed cubic trajectories across mid- to later life. Communal religious practices peaked twice: once at 45 and again around age 70. Independent practices, in contrast, peaked at age 45 and then declined in a stage-like manner until age 80. Spirituality reached its nadir around age 50 and peaked in the early 70s; the reverse was true for negative religious/spiritual coping. The change trajectory in composite religiosity/spirituality most resembled that of independent religious practices. Finally, positive religious/spiritual coping followed a linear trajectory, but a cohort difference precluded its interpretation as developmental change.

Discussion and Implications

Individuals appear to engage with their faith in different ways as they age, meaning extant conclusions about age-related differences and change in global religiosity/spirituality may be distorted.
A community-based ambulance model: lessons for emergency medical services and everyday health systems resilience from South Africa
Authors: Brady Leanne , Gilson Lucy , George Asha , Vries Shaheem De , Hartley Shakira
Published: August 2024

The role of the emergency medical service (EMS) is changing globally as ambulance crews respond to a shifting burden of disease, as well as societal stressors such as violence and inequality. New ways of thinking about how to provide emergency care are required to shift EMS from a role primarily focused on clinical care and transporting patients to hospital. In this paper, we present the experience of the Philippi Project (PP), an innovative community-based model of care developed by front line ambulance crews in a low-income neighbourhood in Cape Town, South Africa. Our insights were developed through observational, interview and document review work, within an overall embedded research approach. Our analysis draws on the everyday health systems resilience (EHSR) framework, which sees resilience as an emergent process that may be stimulated through response to stress and shock. Responses take the form of absorptive, adaptive or transformative strategies and are underpinned by system capacities (cognitive, behavioural and contextual). We consider the PP as a potentially transformative resilience strategy, defined as a new way of working that offered the promise of long-term health system gains. We found that the PP’s initial development was supported by a range of system capacity attributes (such as the intentional development of relationships, a sense of collective purpose and creating spaces for constructive sense-making). However, the PP was hard to sustain over time because emergent ways of working were undermined both by other capacity attributes rooted in pre-existing organizational routines and two contextual shocks (Coronavirus and a violent incident). The paper adds a new empirical contribution to the still-small EHSR literature. In addition, the PP experience offers globally relevant lessons for developing community-based models of EMS care. It demonstrates that front line staff can develop creative solutions to their stressful daily realities, but only if space is created and protected.
Diverse Relationships between Batrachochytrium Infections and Antimicrobial Peptide Defenses Across Leopard Frog Populations
Authors: Le Sage Emily H , Reinert Laura K , Ohmer Michel E B , LaBumbard Brandon C , Altman Karie A , Brannelly Laura A , Latella Ian , McDonnell Nina B , Saenz Veronica , Walsman Jason C , Wilber Mark Q , Woodhams Douglas C , Voyles Jamie , Richards-Zawacki Corinne L , Rollins-Smith Louise A
Published: August 2024

Synopsis

Antimicrobial peptides (AMPs) play a fundamental role in the innate defense against microbial pathogens, as well as other immune and non-immune functions. Their role in amphibian skin defense against the pathogenic fungus Batrachochytrium dendrobatidis (Bd) is exemplified by experiments in which depletion of host’s stored AMPs increases mortality from infection. Yet, the question remains whether there are generalizable patterns of negative or positive correlations between stored AMP defenses and the probability of infection or infection intensity across populations and species. This study aims to expand on prior field studies of AMP quantities and compositions by correlating stored defenses with an estimated risk of Bd exposure (prevalence and mean infection intensity in each survey) in five locations across the United States and a total of three species. In all locations, known AMPs correlated with the ability of recovered secretions to inhibit Bd in vitro. We found that stored AMP defenses were generally unrelated to Bd infection except in one location where the relative intensity of known AMPs was lower in secretions from infected frogs. In all other locations, known AMP relative intensities were higher in infected frogs. Stored peptide quantity was either positively or negatively correlated with Bd exposure risk. Thus, future experiments coupled with organismal modeling can elucidate whether Bd infection affects secretion/synthesis and will provide insight into how to interpret amphibian ecoimmunology studies of AMPs. We also demonstrate that future AMP isolating and sequencing studies can focus efforts by correlating mass spectrometry peaks to inhibitory capacity using linear decomposition modeling.
Erdős Similarity Problem via Bi-Lipschitz Embedding
Authors: Feng De-Jun , Lai Chun-Kit , Xiong Ying
Published: August 2024

The Erdős similarity conjecture asserted that an infinite set of real numbers cannot be affinely embedded into every measurable set of positive Lebesgue measure. The problem is still open, in particular for all fast decaying sequences. In this paper, we relax the problem to the bi-Lipschitz embedding and obtain some sharp criteria about the bi-Lipschitz Erdős similarity problem for strictly decreasing sequences.
Shared decision-making and disease management in advanced cancer and chronic kidney disease using patient-reported outcome dashboards
Authors: Cella David , Kuharic Maja , Peipert John Devin , Bedjeti Katy , Garcia Sofia F , Yanez Betina , Hirschhorn Lisa R , Coughlin Ava , Morken Victoria , O'Connor Mary , Linder Jeffrey A , Jordan Neil , Ackermann Ronald T , Amagai Saki , Kircher Sheetal , Mohindra Nisha , Aggarwal Vikram , Weitzel Melissa , Nelson Eugene C , Elwyn Glyn , Van Citters Aricca D , Barnard Cynthia
Published: August 2024

Objectives

To assess the use of a co-designed patient-reported outcome (PRO) clinical dashboard and estimate its impact on shared decision-making (SDM) and symptomatology in adults with advanced cancer or chronic kidney disease (CKD).

Materials and Methods

We developed a clinical PRO dashboard within the Northwestern Medicine Patient-Reported Outcomes system, enhanced through co-design involving 20 diverse constituents. Using a single-group, pretest-posttest design, we evaluated the dashboard's use among patients with advanced cancer or CKD between June 2020 and January 2022. Eligible patients had a visit with a participating clinician, completed at least two dashboard-eligible visits, and consented to follow-up surveys. PROs were collected 72 h prior to visits, including measures for chronic condition management self-efficacy, health-related quality of life (PROMIS measures), and SDM (collaboRATE). Responses were integrated into the EHR dashboard and accessible to clinicians and patients.

Results

We recruited 157 participants: 66 with advanced cancer and 91 with CKD. There were significant improvements in SDM from baseline, as assessed by collaboRATE scores. The proportion of participants reporting the highest level of SDM on every collaboRATE item increased by 15 percentage points from baseline to 3 months, and 17 points between baseline and 6-month follow-up. Additionally, there was a clinically meaningful decrease in anxiety levels over study period (T-score baseline: 53; 3-month: 52; 6-month: 50; P < .001), with a standardized response mean (SRM) of −0.38 at 6 months.

Discussion

PRO clinical dashboards, developed and shared with patients, may enhance SDM and reduce anxiety among patients with advanced cancer and CKD.
Sounding out solutions: using SONAR to connect participants with relevant healthcare resources
Authors: McGruder Carla , Tangney Kelly , Erwin Deanna , Plewa Jake , Onyeneho Karyn , Moore Rhonda , Wise Anastasia , Topper Scott , Zhou Alicia Y
Published: August 2024

Objective

This article outlines a scalable system developed by the All of Us Research Program's Genetic Counseling Resource to vet a large database of healthcare resources for supporting participants with health-related DNA results.

Materials and Methods

After a literature review of established evaluation frameworks for health resources, we created SONAR, a 10-item framework and grading scale for health-related participant-facing resources. SONAR was used to review clinical resources that could be shared with participants during genetic counseling.

Results

Application of SONAR shortened resource approval time from 7 days to 1 day. About 256 resources were approved and 8 rejected through SONAR review. Most approved resources were relevant to participants nationwide (60.0%). The most common resource types were related to support groups (20%), cancer care (30.6%), and general educational resources (12.4%). All of Us genetic counselors provided 1161 approved resources during 3005 (38.6%) consults, mainly to local genetic counselors (29.9%), support groups (21.9%), and educational resources (21.0%).

Discussion

SONAR’s systematic method simplifies resource vetting for healthcare providers, easing the burden of identifying and evaluating credible resources. Compiling these resources into a user-friendly database allows providers to share these resources efficiently, better equipping participants to complete follow up actions from health-related DNA results.

Conclusion

The All of Us Genetic Counseling Resource connects participants receiving health-related DNA results with relevant follow-up resources on a high-volume, national level. This has been made possible by the creation of a novel resource database and validation system.
Glimpses of Haiti in West Africa, 1890–1920
Authors: Janzen Philip
Published: August 2024

Recent scholarship has traced the impacts of the Haitian Revolution around the Atlantic world, yet there has been almost no scholarly attention to the legacies of the Haitian Revolution in Africa. This article examines circulations of the history of the Haitian Revolution in the newspapers of Sierra Leone and Nigeria between 1890 and 1920. Influenced heavily by the narrative and poetic styles of the nineteenth century, West African intellectuals usually adhered to a Romantic emplotment of the revolution. They also drew on this history to inform their own nationalist and Pan-Africanist politics. I argue that the particular form of the newspaper allowed West African intellectuals to weave together a unique range of materials as they crafted their narratives. By combining their political ideas with works by prominent nineteenth-century writers, they reframed their pasts and imagined their futures anew.
Efficient use of penile Doppler ultrasound for investigating men with erectile dysfunction
Authors: Flores Jose M , West Michael , Mulhall John P
Published: August 2024

Background

Vasculogenic erectile dysfunction is the most common type of erectile dysfunction, and penile Doppler ultrasound (PDUS) is a useful tool to assess erectile hemodynamics in the clinician’s effort to discuss prognosis and management strategies with the patient.

Aim

We herein describe the PDUS protocol used at our center, including indications, technique, and data interpretation.

Methods

We describe our institutional experience with PDUS and discuss it in the context of a contemporary review of the literature for this investigation.

Outcome

Our institutional PDUS protocol.

Results

To perform PDUS properly, adequate training, equipment, setting, technique, and interpretation are critical. The accuracy of PDUS is entirely predicated on achieving complete cavernosal smooth muscle relaxation. A redosing protocol optimizes the reliability and reproducibility of the hemodynamic data acquired during PDUS. A rigidity-based assessment is performed, and patients are scanned according to the erection rigidity achieved (full hardness) or by administration of maximum dose of the vasoactive agent. Peak systolic velocity is considered a measure of arterial inflow (normal, >30 cm/s), while end diastolic velocity evaluates the veno-occlusive mechanism (normal, <5 cm/s). After the procedure, the patient is evaluated to confirm detumescence. If the patient has a persistent penetration rigidity erection, intracavernosal phenylephrine is administered; however, if detumescence is not achieved with intracavernosal phenylephrine injections alone, corporal aspiration is potentially performed.

Conclusion

PDUS is a valuable minimally invasive tool for erectile hemodynamics assessment and an accurate assessment of such, provided that complete cavernosal smooth muscle relaxation is achieved.
Effect of Continuous Infusion Therapy With Low-dose Terlipressin Combined With Norepinephrine on Hemodynamics, Inflammatory Markers, and Prognosis in Patients With Severe Septic Shock
Authors: Li Wenlong , Deng Jiaqian
Published: August 2024

Objective

The present study investigated the impact of continuous infusion therapy with low-dose terlipressin (TP) combined with norepinephrine on hemodynamics, inflammatory markers, and prognosis in patients with severe septic shock.

Materials and Methods

Seventy-four patients with severe septic shock were randomly assigned to either a control group (n = 37) or an observation group (n = 37). Patients in the control group received norepinephrine alone, while those in the observation group received a continuous infusion of low-dose TP in addition to norepinephrine. To assess the effect of treatment, a set of clinical parameters was evaluated in both groups before and after treatment. These parameters included hemodynamic indicators (heart rate [HR], mean arterial pressure [MAP], central venous pressure [CVP], cardiac index [CI], and systemic vascular resistance index [SVRI]), levels of serum inflammatory markers (interleukin-8 [IL-8], tumor necrosis factor-α [TNF-α], and hypersensitivity C-reactive protein [hs-CRP]), renal function indicators (blood urea nitrogen [BUN], serum creatinine [SCr], and cystatin C [Cys-C]), serum procalcitonin (PCT), and lactate, as well as lactate clearance rate (LCR). Additionally, the acute physiology and chronic health evaluation II (APACHE II) score, 28-day mortality rate, multiple organ dysfunction syndrome (MODS) incidence rate, and adverse reaction incidence were also determined.

Results

Compared to baseline values, MAP, CVP, CI, SVRI, and LCR increased in both groups after treatment, while HR, levels of IL-8, TNF-α, hs-CRP, BUN, SCr, PCT, and lactate all decreased. Additionally, APACHE II scores also decreased. Furthermore, the observation group exhibited higher MAP, CVP, CI, SVRI, and LCR, along with lower HR, levels of IL-8, TNF-α, hs-CRP, BUN, SCr, PCT, and lactate than the control group after treatment. The observation group also had lower APACHE II score, 28-day mortality rate, MODS incidence rate, and adverse reaction incidence than the control group after treatment (P < .05).

Conclusion

Continuous infusion therapy with low-dose TP combined with norepinephrine was effective in treating patients with severe septic shock, improving hemodynamic parameters, reducing the levels of inflammatory markers, promoting renal function recovery, and reducing the mortality rate.
Visual imagery vividness correlates with afterimage conscious perception
Authors: Kronemer Sharif I , Holness Micah , Morgan A Tyler , Teves Joshua B , Gonzalez-Castillo Javier , Handwerker Daniel A , Bandettini Peter A
Published: August 2024

Afterimages are illusory, visual conscious perceptions. A widely accepted theory is that afterimages are caused by retinal signaling that continues after the physical disappearance of a light stimulus. However, afterimages have been reported without preceding visual, sensory stimulation (e.g. conditioned afterimages and afterimages induced by illusory vision). These observations suggest the role of top-down brain mechanisms in afterimage conscious perception. Therefore, some afterimages may share perceptual features with sensory-independent conscious perceptions (e.g. imagery, hallucinations, and dreams) that occur without bottom-up sensory input. In the current investigation, we tested for a link between the vividness of visual imagery and afterimage conscious perception. Participants reported their vividness of visual imagery and perceived sharpness, contrast, and duration of negative afterimages. The afterimage perceptual features were acquired using perception matching paradigms that were validated on image stimuli. Relating these perceptual reports revealed that the vividness of visual imagery positively correlated with afterimage contrast and sharpness. These behavioral results support shared neural mechanisms between visual imagery and afterimages. However, we cannot exclude alternative explanations, including demand characteristics and afterimage perception reporting inaccuracy. This study encourages future research combining neurophysiology recording methods and afterimage paradigms to directly examine the neural mechanisms of afterimage conscious perception.
BMScope: A scoping review to chart the evolving clinical study landscape in brain and leptomeningeal metastasis
Authors: Cheng Vinton W T , Heywood Richard , Zakaria Rasheed , Burger Rebecca , Zucker Kieran , Kannan Siddarth , Putra Muhammad Alifian Remifta , Fitzpatrick Amanda , Doherty Gary , Sanghera Paul , Jenkinson Michael D , Palmieri Carlo
Published: August 2024

Background

Recent studies have challenged the notion that patients with brain metastasis (BM) or leptomeningeal metastasis (LM) should be excluded from systemic therapy clinical trials. This scoping study summarizes the BM/LM clinical studies published between 2010 and 2023.

Methods

MEDLINE, CINAHL, CAB Abstracts, PsycINFO, Cochrane Library, HINARI, International Pharmaceutical Abstracts, PubMed, Scopus, Web of Science, and EMBASE electronic databases were searched on June 21, 2021. An updated search was performed on February 21, 2023. Eligible studies investigated a therapeutic intervention in solid tumor patients with BM and/or LM and reported a patient outcome. Extracted study-level data, including study type, publication date, geographical location, number of BM/LM patients in the study, primary tumor type, and type of therapeutic intervention, were collected.

Results

4921 unique studies were eligible for analysis. The key finding is that BM/LM clinical research is expanding globally, both in observational studies and clinical trials. Despite the shift over time toward a higher proportion of systemic therapy trials, the majority still do not include patients with symptomatic disease and lack reporting of BM/LM-specific endpoints. Globally, there has been a trend to more international collaboration in BM/LM clinical studies.

Conclusions

Our analysis of the BM/LM literature charts the evolving landscape of studies involving this previously excluded population. Given the increasing clinical research activity, particularly involving late-stage systemic therapy trials, it is imperative that due consideration is given to the intracranial activity of new investigational agents. Wider adoption of standardized reporting of intracranial-specific endpoints will facilitate the evaluation of relative intracranial efficacy.
A low level of tumor necrosis factor α in tumor microenvironment maintains the self-renewal of glioma stem cells by Vasorin-mediated glycolysis
Authors: Zhang Yang , Kang Tianxu , Wang Yuxi , Song Chao , Li Huan , Mi Hailong , Li Yachao , Dong Minhai , Ma Xiaoyu , Zhu Hongtao , Cheng Lidong , Zhang Po , Chen Zhiye , Zhou Lin , Wu Qiulian , Mao Feng , Wang Baofeng , Zhang Suojun , Shu Kai , Wan Feng , Zhou Wenchao , Rich Jeremy N , Shen Jianying , Xiao Qungen , Yu Xingjiang
Published: August 2024

Background

Self-renewal of glioma stem cells (GSCs) is responsible for glioblastoma (GBM) therapy resistance and recurrence. Tumor necrosis factor α (TNFα) and TNF signaling pathway display an antitumor activity in preclinical models and in tumor patients. However, TNFα exhibits no significance for glioma clinical prognosis based on the Glioma Genome Atlas database. This study aimed to explore whether TNFα of tumor microenvironment maintains self-renewal of GSCs and promotes worse prognosis in glioma patients.

Methods

Spatial transcriptomics, immunoblotting, sphere formation assay, extreme limiting dilution, and gene expression analysis were used to determine the role of TNFα on GSC’s self-renewal. Mass spectrometry, RNA-sequencing detection, bioinformatic analyses, qRT-RNA, immunofluorescence, immunohistochemistry, single-cell RNA sequencing, in vitro and in vivo models were used to uncover the mechanism of TNFα-induced GSC self-renewal.

Results

A low level of TNFα displays a promoting effect on GSC self-renewal and worse glioma prognosis. Mechanistically, Vasorin (VASN) mediated TNFα-induced self-renewal by potentiating glycolysis. Lactate produced by glycolysis inhibits the TNFα secretion of tumor-associated macrophages (TAMs) and maintains TNFα at a low level.

Conclusions

TNFα-induced GSC self-renewal mediated by VASN provides a possible explanation for the failures of endogenous TNFα effect on GBM. A combination of targeting VASN and TNFα antitumor effect may be an effective approach for treating GBM.
Developmental pluripotency-associated 4 increases aggressiveness of pituitary neuroendocrine tumors by enhancing cell stemness
Authors: Chaudhary Shaista , Das Ujjal , Jabbar Shaima , Gangisetty Omkaram , Rousseau Bénédicte , Hanft Simon , Sarkar Dipak K
Published: August 2024

Background

Pituitary neuroendocrine tumors, PitNETs, are often aggressive and precipitate in distant metastases that are refractory to current therapies. However, the molecular mechanism in PitNETs’ aggressiveness is not well understood. Developmental pluripotency-associated 4 (DPPA4) is known as a stem cell regulatory gene and overexpressed in certain cancers, but its function in the context of PitNETs’ aggressiveness is not known.

Methods

We employed both rat and human models of PitNETs. In the rat pituitary tumor model, we used prenatal-alcohol-exposed (PAE) female Fischer rats which developed aggressive PitNETs following estrogen treatment, while in the human pituitary tumor model, we used aggressively proliferative cells from pituitary tumors of patients undergone surgery. Various molecular, cellular, and epigenetic techniques were used to determine the role of DPPA4 in PitNETs’ aggressiveness.

Results

We show that DPPA4 is overexpressed in association with increased cell stemness factors in aggressive PitNETs of PAE rats and of human patients. Gene-editing experiments demonstrate that DPPA4 increases the expression of cell stemness and tumor aggressiveness genes and promotes proliferation, colonization, migration, and tumorigenic potential of PitNET cells. ChIP assays and receptor antagonism studies reveal that DPPA4 binds to canonical WINTs promoters and increases directly or indirectly the WNT/β-CATENIN control of cell stemness, tumor growth, and aggressiveness of PitNETs. Epigenetic studies show the involvement of histone methyltransferase in alcohol activation of DPPA4.

Conclusions

These findings support a role of DPPA4 in tumor stemness and aggressiveness and provide a preclinical rationale for modulating this stemness regulator for the treatment of PitNETs.
Effects of Single Low-Carbohydrate, High-Fat Meal Consumption on Postprandial Lipemia and Markers of Endothelial Dysfunction: A Systematic Review of Current Evidence
Authors: Wilson Megan L , Lane Katie E , Fadel Abdulmannan , Dawson Ellen A , Moore Ella , Mazidi Mohsen , Webb Richard J , Davies Ian G
Published: August 2024

Context

Postprandial lipemia (PPL) is associated with increased risk of endothelial dysfunction (ED), a precursor of atherosclerotic cardiovascular disease (ASCVD). The effects of low-carbohydrate, high-fat (LCHF) diets on ASCVD risk are uncertain; therefore, gaining a greater understanding of LCHF meals on PPL may provide valuable insights.

Objective

The current systematic review investigated the effects of single LCHF meal consumption on PPL and markers of ED.

Data Sources

CINAHL Plus, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for key terms related to endothelial function, cardiovascular disease, glycemia, lipemia, and the postprandial state with no restriction on date.

Data Extraction

Full-text articles were independently screened by 2 reviewers, of which 16 studies were eligible to be included in the current review. All trials reported a minimum analysis of postprandial triglycerides (PPTG) following consumption of an LCHF meal (<26% of energy as carbohydrate). Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Data Analysis

Single-meal macronutrient composition was found to play a key role in determining postprandial lipid and lipoprotein responses up to 8 hours post-meal. Consumption of LCHF meals increased PPTG and may contribute to ED via reduced flow-mediated dilation and increased oxidative stress; however, energy and macronutrient composition varied considerably between studies.

Conclusion

Consumption of an LCHF meal had a negative impact on PPL based on some, but not all, single-meal studies; therefore, the contribution of LCHF meals to cardiometabolic health outcomes remains unclear. Further research is needed on specific categories of LCHF diets to establish a causal relationship between postprandial modulation of lipids/lipoproteins and impaired vascular endothelial function.

Systematic Review Registration

PROSPERO registration no. CRD 42023398774.
Testing for Blastomycosis, Coccidioidomycosis, and Histoplasmosis at a Major Commercial Laboratory, United States, 2019–2024
Authors: Benedict Kaitlin , Williams Samantha L , Smith Dallas J , Lindsley Mark D , Lockhart Shawn R , Toda Mitsuru
Published: August 2024

Background

Blastomycosis, coccidioidomycosis, and histoplasmosis are environmentally acquired fungal diseases that clinically resemble bacterial and viral community-acquired pneumonia and require laboratory testing for diagnosis. Patients frequently present to primary care and experience diagnostic delays when a fungal etiology is not initially suspected. Current national-level public health surveillance for these diseases is limited and does not include laboratory data, so nationwide testing practices are unknown.

Methods

We identified laboratory tests for blastomycosis, coccidioidomycosis, and histoplasmosis ordered during 1 March 2019–29 February 2024 and performed within a major national commercial laboratory system. We analyzed test results, patient and healthcare provider features, reasons for testing, and temporal trends.

Results

Results included 5693 Blastomyces complement fixation tests (of those, 12% were positive), 71 858 immunodiffusion tests (0.1% positive), and 1186 serum enzyme immunoassay (EIA) tests (11% positive); 154 989 Coccidioides EIA immunoglobulin M results (5% positive) and 154 968 immunoglobulin G results (8% positive); and 46 346 Histoplasma complement fixation tests (30% positive), 49 062 immunodiffusion tests (1% positive), 35 506 serum EIA tests (4% positive), and 82 489 urine EIA tests (2% positive). Most histoplasmosis (58%–74%) and blastomycosis (42%–68%) tests were ordered from hospitals, whereas coccidioidomycosis tests were most frequently ordered by primary care providers (40%). A yearly average of 2727 positive tests were ordered by healthcare providers in states without public health surveillance for these diseases.

Conclusions

Blastomycosis, coccidioidomycosis, and histoplasmosis are likely underdetected in primary care settings or by public health surveillance. Increased testing by primary care providers and expanded surveillance are needed to reduce disease burden.
Probing Bilin–Protein Interaction in the Protochromic Photocycle of Cyanobacteriochrome RcaE by Site-Directed Mutagenesis
Authors: Kamo Takanari , Matsushita Takaaki , Hamada Masako , Fujisawa Tomotsumi , Eki Toshihiko , Unno Masashi , Hirose Yuu
Published: August 2024

Cyanobacteriochromes (CBCRs) are members of the phytochrome superfamily of photosensor proteins that bind a bilin chromophore. CBCRs exhibit substantial diversity in their absorption wavelengths through a variety of bilin–protein interactions. RcaE is the first discovered CBCR as a regulator of chromatic acclimation, where cyanobacteria optimize the absorption wavelength of their photosynthetic antenna. RcaE undergoes a reversible photoconversion between green-absorbing (Pg) and red-absorbing (Pr) states, where the bilin chromophore adopts a deprotonated C15-Z,anti and a protonated C15-E,syn structures, respectively. This photocycle is designated as the ‘protochromic photocycle’ as the change in the bilin protonation state is responsible for the large absorption shift. With the guidance of recently determined Pg and Pr structures of RcaE, in this study, we investigated bilin–protein interaction by site-directed mutagenesis on three key residues referred to as a protochromic triad and also other conserved residues interacting with the bilin. Among the protochromic triad residues, Glu217 and Lys261 are critical for the formation of the Pr state, while Leu249 is critical for the formation of both Pg and Pr states. Substitution in other conserved residues, including Val218, Phe219 and Pro220 in the wind-up helix and Phe252, Phe214 and Leu209 in a part of the bilin-binding pocket, had less substantial effects on the spectral sensitivity in RcaE. These data provide insights into our understanding of the bilin–protein interaction in the protochromic photocycle and also its evolution in the CBCRs.
Thermodynamic Topology of Topological Black Hole in F(R)-ModMax Gravity’s Rainbow
Authors: Eslam Panah B , Hazarika B , Phukon P
Published: August 2024

In order to include the effect of high energy and topological parameters on black holes in $\mathrm{ F}(R)$ gravity, we consider two corrections to this gravity: energy-dependent spacetime with different topological constants, and a nonlinear electrodynamics field. In other words, we combine $\mathrm{ F}(R)$ gravity’s rainbow with ModMax nonlinear electrodynamics theory to see the effects of high energy and topological parameters on the physics of black holes. For this purpose, we first extract topological black hole solutions in $\mathrm{ F}(R)$-ModMax gravity’s rainbow. Then, by considering black holes as thermodynamic systems, we obtain thermodynamic quantities and check the first law of thermodynamics. The effect of the topological parameter on the Hawking temperature and the total mass of black holes is obvious. We also discuss the thermodynamic topology of topological black holes in $\mathrm{ F}(R)$-ModMax gravity’s rainbow using the off-shell free energy method. In this formalism, black holes are assumed to be equivalent to defects in their thermodynamic spaces. For our analysis, we consider two different types of thermodynamic ensembles. These are: fixed q ensemble and fixed $\phi$ ensemble. We take into account all the different types of curvature hypersurfaces that can be constructed in these black holes. The local and global topology of these black holes are studied by computing the topological charges at the defects in their thermodynamic spaces. Finally, in accordance with their topological charges, we classify the black holes into three topological classes with total winding numbers corresponding to $-1, 0$, and 1. We observe that the topological classes of these black holes are dependent on the value of the rainbow function, the sign of the scalar curvature, and the choice of ensembles.
The National Front and environmental politics, 1967–90
Authors: Bhargava Beth
Published: August 2024

The green entanglements of the inter-war British far right are well-documented. Martin Pugh has drawn attention to the predominantly rural, agricultural support base of the British Union of Fascists. We know that the aspiration to go ‘back to the land’ was deeply enmeshed with a politics of racial hygiene, which equated the urban with miscegenation and the rural with purity. However, in the post-war world, British far-right ecologism has typically been interpreted as a curious anomaly driven by cynical realpolitik. This article contends environmental themes as an intellectual staple of British fascism—running from the interwar far right, through the NF, and into the latter’s largest successor organization, the Flag Group. The Front’s preoccupation with the environment, and its racism, were mutually reinforcing, central pillars of its politics. Its environmentalism was alternately revolutionary and conservative, nostalgic and future oriented.
The use of modelling in the learning of differential equations in an economics course
Authors: Trigueros María , Martínez-Planell Rafael
Published: August 2024

This study examines the experience of using an open-ended modelling problem to introduce economics students to the mathematical subject of differential equations. We show the potential of such an approach in motivating students whilst at the same time helping them construct a new differential equations Schema that is coordinated with their developing understanding of economics. In a classroom context of collaborative group work, general class discussions and carefully chosen homework exercises, students showed that they could develop an interest in the relation between mathematics, specifically differential equations, and economics, and ‘discover’ uses of mathematics that are new to them whilst modelling the economics problem of diffusion of an innovation. Students were able to anticipate important mathematical ideas, like the phase plane qualitative analysis of dynamical systems, on their own. This was accompanied by activities that formalized the mathematical aspects of the course as students developed them.
Virome Scanning of Pear Germplasm Collections Identifies a New Velarivirus and Extends the Geographical Spread of Three Other Pear Viruses
Authors: Fontdevila Pareta Nuria , Gailly Carole , Blouin Arnaud G. , Buchmann Beatrix , Bünter Markus , Candresse Thierry , Dubuis Nathalie , Kutnjak Denis , Lateur Marc , Pecman Anja , Steyer Stéphan , Massart Sébastien
Published: August 2024

In this study, an extensive virome investigation was performed on a germplasm collection of pear trees ( Pyrus communis L.) from the Walloon Agricultural Research Centre (Gembloux, Belgium). In total, 128 pear trees samples were analyzed as pools using high-throughput sequencing techniques and/or tested individually for targeted viruses by reverse transcription PCR (RT-PCR). During the virome survey, a novel velarivirus was identified in several asymptomatic trees, and four known viruses were detected. Bioinformatics tools were used to assemble the genome of the new virus. The pear germplasm collection from Kozjanski Park (Slovenia) and a viral collection from Agroscope (Nyon, Switzerland) were also surveyed for the new pear virus and for three known viruses (citrus virus A [CiVA], apple rubbery wood virus 1 [ARWV-1], and apple rubbery wood virus 2 [ARWV-2]) to study their prevalence and geographic distribution. In Belgium, the new velarivirus was detected by RT-PCR in 6 of the 99 sampled trees (6%) and CiVA in 49 (49%) of them; in Slovenia, four of the six trees sampled (67%) were positive for CiVA; and in Switzerland, four of the nine trees sampled (44%) were positive for CiVA and 1 (11%) for ARWV-1 and -2. This study combined pooled high-throughput sequencing analyses to maximize the amount of germplasm tested and targeted RT-PCR tests on individual samples for accurate detection. It reports and describes a new velarivirus discovered in pear trees and first detections of CiVA in Belgium, Switzerland, and Slovenia, as well as ARWV-1 and -2 in Switzerland.

[Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Targeted inhibition of m6A demethylase FTO by FB23 attenuates allergic inflammation in the airway epithelium
Authors: Lian Zexuan , Chen Ruchong , Xian Mo , Huang Peiying , Xu Jiahan , Xiao Xiaojun , Ning Xiaoping , Zhao Jin , Xie Jianlei , Duan Jielin , Li Bizhou , Wang Wanjun , Shi Xu , Wang Xinru , Jia Nan , Chen Xuepeng , Li Jing , Yang Zhaowei
Published: August 2024

Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity‐associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small‐molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO‐regulated transcriptome‐wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP‐seq) and RNA‐seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue‐specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL‐4/IL‐13‐treated epithelial cells and house dust mite (HDM)‐induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF‐α signaling via NF‐κB and epithelial–mesenchymal transition‐related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23‐induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM‐induced mice, potentially through diverse cellular processes and epithelial–mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.
The Inequitable Experiences of Left-Handed Medical Students in Surgical Education
Authors: Gilbert Timothy J. , Anderson Maia S. , Byrnes Mary E. , Kim Gloria Y. , Solano Quintin P. , Wan Julian H. , Sack Bryan S.
Published: August 2024

Purpose

Left-handed medical students contend with unique educational barriers within surgery, such as lack of educational resources, lack of left-handed–specific training, and widespread stigmatization of surgical left-handedness. This study aimed to highlight the surgical experiences of left-handed medical students so educators may be empowered to act with greater care and appreciation of these students’ circumstances.

Method

In this qualitative study, the authors conducted semistructured interviews on surgical experiences during medical school between January 31, 2021, and June 20, 2021, on 31 current surgical residents and fellows from 15 U.S. institutions and 6 surgical specialties. Left-handed trainees were included regardless of their surgical hand dominance.

Results

The authors identified 3 themes related to left-handed medical students’ surgical experience: (1) disorienting advice from faculty or residents, (2) discouraging right-handed pressures and left-handed stigmatization, and (3) educational wishes of left-handed medical students. Trainees describe dialogues during medical school in which their handedness was directly addressed by residents and faculty with disorienting and nonbeneficial advice. Often trainees were explicitly told which hand to use, neglecting any preferences of the left-handed student. Participants also described possible changes in future surgical clerkships, including normalization of left-handedness, tangible mentorship, or granular and meaningful instruction.

Conclusions

Left-handed medical students encounter unique challenges during their surgical education. These students report being disoriented by the variability of advice provided by mentors, discouraged by how pressured they feel to operate right-handed, and burdened by the need to figure things out by themselves in the absence of adequate left-handed educational resources. Surgical education leadership should detail the unique problems left-handed learners face, impartially elicit the learner’s current operative hand preference, take responsibility for their left-handed students, promote acceptance and accommodation strategies of left-handed surgical trainees, and endeavor to improve the breadth of left-handed surgical resources.