bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal trajectory and left ventricular ejection fraction association of eight circulating biomarkers in first acute myocardial infarction patients: a 12-month prospective cohort study
Authors: Elbaz Meyer , Grazide Marie-Hélène , Bataille Vincent , Blanc Grégoire , Cantero Anne-Valérie , Firat Hueseyin , Vindis Cécile
Published: October 2024

Aims

Our study aimed to explore the temporal trajectory of eight circulating biomarkers, measured serially over 12 months, in a prospective observational cohort of patients with acute myocardial infarction (AMI) and to investigate the association between these biomarkers and left ventricular ejection fraction (LVEF) during follow-up assessments.

Methods and results

We enrolled 155 patients admitted for a first AMI requiring percutaneous coronary intervention (PCI). Baseline characteristics, laboratory test results, and cardiac ultrasound examinations were collected at pre-PCI (H0), immediately post-PCI (H24), at discharge (D3), and at 6 months (M6) and 12 months (M12) post-PCI. Blood samples were analysed for established and emerging biomarkers described in left ventricular dysfunction: soluble suppression of tumorigenicity 2 (sST2), interleukin-6 (IL-6), osteopontin, angiopoietin-2, insulin-like growth factor-binding protein 2 (IGFBP-2), growth differentiation factor 15 (GDF-15), hepcidin, and galectin-3. Values at H24, D3, M6, and M12 were compared with value at H0. Three kinetic profiles were identified, with six biomarkers peaking during the acute MI phase. Crude relationships between clinical variables and the peak values (highest observed between H0 and D3) of each biomarker were studied. Peak levels of sST2, IL-6, osteopontin, and angiopoietin-2 demonstrated significant correlations with both baseline and follow-up LVEF values.

Conclusion

The assessment of the temporal trajectories of these biomarkers and their associations with LVEF suggests that sST2, IL-6, osteopontin, and angiopoietin-2 hold significant promise as companion biomarkers. These biomarkers may improve the identification of patients at risk for developing impaired LVEF following AMI, thereby enabling more targeted and effective management strategies.
Quality of life effects of renal artery stenting versus medical therapy for atherosclerotic renal-artery stenosis: results from the randomized CORAL trial
Authors: Arnold Suzanne V , Wang Kaijun , Kirtane Ajay J , Magnuson Elizabeth A , Chinnakondepalli Khaja M , Cooper Christopher J , Dworkin Lance D , Cohen David J
Published: October 2024

Background

Renal-artery stenosis can be associated with difficult to control hypertension, although renal-artery stenting has not been shown to improve clinical outcomes. Alternative antihypertensive medications could potentially result in quality of life benefits with renal-artery stenting.

Methods and results

We performed a pre-specified quality of life sub-study of the CORAL trial—multicenter, randomized, open-label trial of renal-artery stenting vs. medical therapy in patients with atherosclerotic renal-artery stenosis. Longitudinal growth curve models were used to compare the Physical Symptoms Distress Index (PSDI), SF-36, and EQ-5D scores over time between treatment groups. We also sought to validate the approach of assessing quality of life in hypertension studies. Among 906 patients (mean age 69.2 ± 9.1 years, 49.7% men), symptom frequency and distress due to side effects from antihypertensive medications changed minimally over time, with no significant differences between treatment groups. There were also no clinically significant differences between treatment groups for the SF-36 and its subscales or the EQ-5D. In internal validation of the quality of life measures, the PSDI correlated well with number/type of antihypertensive medications, and generic health status measures correlated with late clinical events.

Conclusions

In a large, multicenter, randomized clinical trial, we found no significant benefit of routine renal-artery stenting over medical management for the treatment of atherosclerotic renal-artery stenosis in terms of disease-specific or generic quality of life measures. As these quality of life measures are important to patients and are associated with medication compliance, future studies of antihypertensive treatments should consider including these quality of life measures as secondary outcomes.

Trial registration

ClinicalTrials.gov: NCT00081731
Do non-farmers pay more for land than farmers?
Authors: Schmidt Lorenz , Odening Martin , Ritter Matthias
Published: October 2024

The increase in farmland prices in many parts of the world over the past decade has sparked discussions about whether non-farmers pay higher prices for farmland. This study uses a causal machine learning approach with a rich data set of land transactions in Germany to quantify the potential price premium paid by non-farmers. By applying the causal forest method, we uncover the heterogeneity of price premiums and reveal moderating effects of covariates. We find that the average positive price premium by non-farmers decreases with parcel size and distance to a highway exit.
Examining health literacy in the Danish general population: a cross-sectional study on the associations between individual factors and healthcare-seeking behaviour
Authors: Sætre Lisa Maria Sele , Jarbøl Dorte Ejg , Raasthøj Isabella Pernille , Seldorf Sofie Amalie , Rasmussen Sanne , Balasubramaniam Kirubakaran
Published: October 2024

Knowledge about health literacy challenges among the general population is valuable for initiatives targeting social inequity in health. We investigated health literacy in various population groups and the impact of healthcare-seeking behaviour by analysing the associations between (i) lifestyle, socioeconomics, self-rated health, chronic disease, and health literacy and (ii) symptom burden, contact to general practitioner (GP), and health literacy. In total, 27 488 individuals participated in a population-based survey. Questionnaire data comprised information about symptoms, GP contact, lifestyle, self-rated health, chronic disease, and four aspects of health literacy: feeling understood and supported by healthcare providers, having sufficient information about health, having social support for health, and being able to actively engage with healthcare providers. Socioeconomics were obtained from registers. Descriptive statistics and multivariable linear regression models were applied. Individuals who smoked, lived alone, had different ethnicity than Danish, and low self-rated health had more health literacy challenges reflected in lower scores for all aspects of health literacy. Individuals with high symptom burden and those who had presented a high absolute number of symptoms to their GP were less likely to have sufficient information about health and be able to actively engage, whereas individuals reporting GP contact with a high relative percentage of their symptoms were more likely to feel understood and supported by healthcare providers. Health literacy challenges are related to healthcare-seeking behaviour and several individual factors. To address social inequity in health and society, interventions aimed at both the individual and community-based health literacy are essential.
The white gene as a transgenesis marker for the cricket Gryllus bimaculatus
Authors: Gonzalez-Sqalli Emmanuel , Caron Matthieu , Loppin Benjamin
Published: October 2024

The cricket Gryllus bimaculatus is an emerging model insect of the order Orthoptera that is used in a wide variety of biological research themes. This hemimetabolous species appears highly complementary to Drosophila and other well-established holometabolous models. To improve transgenesis applications in G. bimaculatus, we have designed a transformation marker gene inspired from the widespread Drosophila mini-white+. Using CRISPR/Cas9, we first generated a loss-of-function mutant allele of the Gb-white gene (Gb-w), which exhibits a white eye coloration at all developmental stages. We then demonstrate that transgenic insertions of a piggyBac vector containing a 3xP3-Gb-w+ cassette rescue eye pigmentation. As an application, we used this vector to generate G. bimaculatus lines expressing a centromeric histone H3 variant (CenH3.1) fused to EGFP and validated EGFP-CenH3.1 detection at cricket centromeres. Finally, we demonstrate that Minos-based germline transformation and site-specific plasmid insertion with the ΦC31 integrase system function in G. bimaculatus.
The Highly Repetitive Genome of Myxobolus rasmusseni, an Emerging Myxozoan Parasite of Fathead Minnows
Authors: Muthye Viraj R , Leon Coria Aralia , Liu Hongrui , Goater Cameron P , Finney Constance A M , Wasmuth James D
Published: October 2024

Myxozoans are a monophyletic taxon of approximately 2,400 described species of parasites from the phylum Cnidaria. The recent focus on their negative impacts on fisheries, on their evolution from free-living ancestors, and on their emergence into new fish host populations has stressed the critical need for genomic resources for this parasitic group. Here, we describe the genome assembly and annotation of Myxobolus rasmusseni, an emerging parasite of fathead minnows in Alberta, Canada. The assembly is 174.6 Mb in size, 68% of which is made up of repetitive elements, making it one of the most repetitive animal genomes sequenced to date. Through comparisons to other myxozoans, we show that widespread gene loss, a known phenomenon of this group of parasites, is consistent with closely related species. Additionally, we assembled the M. rasmusseni mitochondrial genome, which is nearly twice the size of the typical animal mitochondrial genome yet contains only five of the canonical mitochondrial protein-coding genes and open reading frames not found in other myxozoans. These results add to our understanding of the gene- and genome-level diversity observed in myxozoans.
Housing and Community Partner Views on the Benefits of Housing With Services: The Right Care, Right Place, Right Time Program
Authors: Miller Edward Alan , Nadash Pamela , Simpson Elizabeth , Cohen Marc A
Published: October 2024

Background and Objectives

Older adult-focused housing with services programs seek to improve access to supportive services, particularly among individuals residing in subsidized housing. The Right Care, Right Place, Right Time (R3) program comprises 2 on-site wellness teams responsible for 400 participants across 7 housing sites in Greater Boston. These embedded teams work directly with residents to address health-related needs and access to services. This study reports on the perceived benefits of participating in the R3 program from the perspective of housing staff and community partners.

Research Design and Methods

Data were derived from 24 semistructured interviews conducted as part of a program evaluation. Participants described resident, housing, and system-related reasons for deciding to participate in the R3 program and their experiences of their participation.

Results

In addition to positive overall assessments, housing partner interviewees reported concrete and psychosocial benefits for housing residents (e.g., connecting with resources, enabling longer stays, empowering residents, alleviating distress) and staffing and resident-related benefits. Community partners perceived more appropriate utilization of services by residents (e.g., reducing emergency transports).

Discussion and Implications

Findings elucidate why housing and community partners might be motivated to integrate housing, health, and supportive care into affordable housing for older adults using a wellness team.
The Interaction Between Indigenous Identity and Rural Residency in Dementia Prevalence Among Ecuadorian Older Adults
Authors: Amano Takashi , Gallegos-Riofrío Carlos Andres , Freire Wilma B , Waters William F
Published: October 2024

Background and Objectives

While recognizing the acknowledged difference in dementia prevalence between Indigenous and non-Indigenous populations, most previous studies were conducted in the Global North. This study aims to examine the relationship between Indigenous ethnic identity and dementia status with a special focus on urban–rural differences among older adults in Ecuador.

Research Design and Methods

Data came from Ecuador’s Survey of Health, Welfare, and Aging, derived from a probability sample of households in Ecuador. The final sample comprised 4,984 adults aged 60 or older. Dementia status was assessed through 3 indicators: low scores on a cognitive assessment, the number of difficulties in instrumental activities of daily living, and self-reported dementia diagnosis. Logistic regression and multivariate decomposition analyses were utilized.

Results

Indigenous participants, even after adjusting for sociodemographic and health-related factors, exhibited a higher likelihood of having dementia compared to their non-Indigenous counterparts. Among Indigenous participants, those residing in rural areas had a higher likelihood of having dementia status, while there was no significant urban–rural difference observed among non-Indigenous participants. Rural residency and covariates explain 91.0% of the observed difference in dementia prevalence between Indigenous and non-Indigenous older adults.

Discussion and Implications

Indigenous older adults who are living in rural areas are at particularly high risk of having dementia largely because they have presently recognized modifiable risk factors. These findings underscore the urgent need to prioritize provisions of appropriate and equitable service related to dementia for Indigenous people living in rural areas outside high-income countries.
End-of-Life Doulas: A Systematic Integrative Review and Redirection
Authors: Thompson Amber D , Utz Rebecca L
Published: October 2024

Background and Objectives

End-of-life (EOL) doulas (EOLD) are an emerging role providing nonmedical support and advocacy for the dying and their families. Research about EOLD is new and currently highlights a need for more clarity in role definition and application. This review aims to comprehensively analyze existing knowledge regarding EOLD and their role in EOL care.

Research Design and Methods

A systematic and comprehensive search of 9 bibliographic databases identified all published academic articles related to EOLD (as named, self-identified, and/or trained) research from inception to June 2023. This review utilized an integrative approach and textual narrative synthesis to summarize the existing body of research findings related to EOLD.

Results

25 articles were identified, representing multiple disciplines including health and medicine, public health, social/behavioral sciences, and humanities. Research on EOLD has rapidly increased in recent years and is showing signs of maturation. The review focuses specifically on summarizing the breadth and depth of identified research on EOLD and critically analyzes emergent themes from the review: Application, Perception, Identity, and Future Research Directions.

Discussion and Implications

This review provides the most comprehensive review of the research literature on EOLD to date. Thematic findings for future research directions have provided the basis of a redirected research agenda to guide the field going forward. There is still a need to clarify who EOLD are and how they are being conceptualized by multiple stakeholders. Future research must address these missing voices to fully grasp the value and unique role that EOLD contribute to EOL care.
Performance of the Washington Group questions in measuring blindness and deafness
Authors: Landes Scott D , Swenor Bonnielin K , Hall Jean P
Published: October 2024

The Washington Group Short Set (WGSS) questions are intended to measure the severity of disability and disability status in US federal surveys. We used data from the 2010–2018 National Health Interview Survey to examine the performance of the WGSS visual disability and hearing disability questions in capturing blindness and deafness. We found that the WGSS questions failed to capture 35.7% of blind adults and 43.7% of deaf respondents as having a severe disability, or, per their recommended cut point, as being disabled. Coupled with evidence demonstrating the poor performance of the WGSS questions in estimating the size of the overall disability population, we contend that results from this study necessitate a halt in the use of the WGSS questions to measure disability in US federal surveys.
Hybrid repair of complicated acute aortic arch intramural haematoma with the Castor single-branch stent graft
Authors: Rizza Antonio , Palmieri Cataldo , Di Sibio Silvia , Murzi Michele
Published: October 2024

We report the off-label application of the Castor single-branch stent graft for a complicated acute intramural haematoma involving the aortic arch. The endograft was deployed in zone 1 with the single branch in the left common carotid artery through a surgical left carotid and percutaneous right femoral artery access. The procedure was completed with the construction of a left carotid-subclavian bypass followed by plug embolization of the left subclavian artery.
Relative Effectiveness and Waning of a Third Dose of mRNA COVID-19 Vaccine in Medicare Beneficiaries Aged 65 Years and Older during the BA.1/BA.2 Omicron Period
Authors: Lu Yun , Matuska Kathryn , McEvoy Rowan , Izurieta Hector S , Hervol Jessica Rose , Menis Mikhail , Lindaas Arnstein , Steele Whitney R , Chillarige Yoganand , Wernecke Michael , Kelman Jeffrey A , Forshee Richard A
Published: October 2024

Background

We assessed the added benefit and waning effectiveness of a third COVID-19 vaccine dose (original formula) for preventing COVID-19-related outcomes.

Methods

We used Medicare claims data to conduct a retrospective cohort study in U.S. community-dwelling Medicare Fee-for-Service beneficiaries aged ≥65 years during the BA.1/BA.2 Omicron period (December 19, 2021 – March 26, 2022). We estimated relative vaccine effectiveness (RVE) of 3 versus 2 doses of mRNA COVID-19 vaccines using marginal structural Cox regression models.

Results

Among 8,135,020 eligible beneficiaries, 73.3% were 3-dose vaccinated by March 26, 2022. At 14-60 days since vaccination, a third dose provided significant added benefit against COVID-19-related hospitalization for Moderna (RVE: 77.2%; 95% confidence interval (CI): 76.0%, 78.4%) and Pfizer-BioNTech (RVE: 72.5%; 95% CI: 70.8%, 74.0%). Added benefit was lower >120 days. For those with prior medically attended COVID-19 diagnoses, Pfizer-BioNTech provided an added benefit for 120 days, while Moderna provided some added benefit >120 days. Added benefit for either vaccine was higher against death compared to less severe outcomes, which still decreased >120 days.

Conclusions

A third dose COVID-19 vaccine provided significant added benefit against COVID-19-related hospitalization and death, even for beneficiaries with prior medically attended COVID-19 diagnoses. This added benefit decreased after 4 months.
Improved Methods for Vaccine Effectiveness Studies
Authors: Okoli George N , Cowling Benjamin J
Published: October 2024

Evaluating the impact of public health investments in vaccination programs is crucial for ensuring their efficiency and effectiveness. Vaccine effectiveness (VE) studies, such as those using the test-negative design, are commonly used to confirm the impact of vaccines and guide future improvements. The test-negative design, favored for its simplicity and cost efficiency, mitigates biases common in other epidemiologic study designs. However, its validity can be compromised by inconsistent symptom definitions and retrospective data application. Here we summarize recent findings that (1) highlight the need to address correlated vaccination behaviors when estimating VE, (2) suggest using negative control variables to reduce confounding, and (3) recommend accounting for infection history in VE studies to improve accuracy and reliability. These insights are important for refining VE estimation methods.
Gut microbiota carbon and sulfur metabolisms support Salmonella infections
Authors: Leleiwi Ikaia , Kokkinias Katherine , Kim Yongseok , Baniasad Maryam , Shaffer Michael , Sabag-Daigle Anice , Daly Rebecca A , Flynn Rory M , Wysocki Vicki H , Ahmer Brian M M , Borton Mikayla A , Wrighton Kelly C
Published: October 2024

Salmonella enterica serovar Typhimurium is a pervasive enteric pathogen and ongoing global threat to public health. Ecological studies in the Salmonella impacted gut remain underrepresented in the literature, discounting microbiome mediated interactions that may inform Salmonella physiology during colonization and infection. To understand the microbial ecology of Salmonella remodeling of the gut microbiome, we performed multi-omics on fecal microbial communities from untreated and Salmonella-infected mice. Reconstructed genomes recruited metatranscriptomic and metabolomic data providing a strain-resolved view of the expressed metabolisms of the microbiome during Salmonella infection. These data informed possible Salmonella interactions with members of the gut microbiome that were previously uncharacterized. Salmonella-induced inflammation significantly reduced the diversity of genomes that recruited transcripts in the gut microbiome, yet increased transcript mapping was observed for seven members, among which Luxibacter and Ligilactobacillus transcript read recruitment was most prevalent. Metatranscriptomic insights from Salmonella and other persistent taxa in the inflamed microbiome further expounded the necessity for oxidative tolerance mechanisms to endure the host inflammatory responses to infection. In the inflamed gut lactate was a key metabolite, with microbiota production and consumption reported amongst members with detected transcript recruitment. We also showed that organic sulfur sources could be converted by gut microbiota to yield inorganic sulfur pools that become oxidized in the inflamed gut, resulting in thiosulfate and tetrathionate that support Salmonella respiration. This research advances physiological microbiome insights beyond prior amplicon-based approaches, with the transcriptionally active organismal and metabolic pathways outlined here offering intriguing intervention targets in the Salmonella-infected intestine.
The Emerging Role of GLP-1 Agonists in Burn Care: What Do We Know?
Authors: Manasyan Artur , Cannata Brigette , Ross Erin , Lasky Sasha , Stanton Eloise W , Malkoff Nicolas , Collier Zachary , Johnson Maxwell B , Gillenwater Timothy Justin
Published: October 2024

Glucagon-like peptide-1 (GLP-1) agonists mimic the action of GLP-1, a hormone that regulates blood glucose levels via stimulation of insulin release and inhibition of glucagon secretion. After the burn, the current literature suggests that the use of GLP-1 agonists results in less insulin dependence with similar glucose control and hypoglycemic events to patients receiving a basal-bolus insulin regimen. Glucagon-like peptide-1 agonists may also promote wound healing through various mechanisms including angiogenesis and improved keratinocyte migration. Despite the potential benefits, GLP-1 agonists reduce gastrointestinal motility which impacts their widespread adoption in burn care. This dysmotility can result in inadequate nutrition delivery, unintentional weight loss, and is a potential aspiration risk. The net impact of these medications on patients with burns is unclear. Given their potential to demonstrate the safety, efficacy, and optimal dosing of various GLP-1 agonists in acute burn management.
Pre-stack seismic inversion based on one-dimensional GRU combined with two-dimensional improved ASPP
Authors: Chen Xiao , Li Shu , Wei Zong , Ning Juan , Yang Xi
Published: October 2024

Pre-stack seismic inversion is essential to detailed stratigraphic interpretation of seismic data. Recently, various deep learning methods have been introduced into pre-stack inversion, effectively capturing the vertical correlations of seismic data. However, existing deep learning methods face challenges such as insufficient feature extraction, poor lateral continuity, and unclear inversion details. We introduce the atrous spatial pyramid pooling (ASPP) module into the pre-stack inversion process, modifying the connection order and mode of its three components. Additionally, we incorporate a triplet attention module to extract features at different scales and utilize a gate recurrent unit (GRU) module to extract global information. During the network training stage, we employ a multi-gather simultaneous inversion method, combining one- and two-dimensional inversions. The proposed method is named IGIT (I for improved ASPP, G for GRU, I for initial model, and T for triplet attention). To verify the feasibility of this network model, we evaluate it using the Marmousi2 model, SEAM model, and field data, comparing the results with other deep learning methods. Experimental results demonstrate that the IGIT not only improves lateral continuity but also delivers accurate and clear inversion details. Notably, the inversion effect for density parameters shows significant enhancement.
Acceptance characterization of electron detector in SEM using stainless steel sphere
Authors: Sekiguchi Takashi , Yao Yuanzhao , Sonoda Ryosuke , Sohda Yasunari
Published: October 2024

Although modern scanning electron microscope (SEM) possesses several electron detectors, it is not clear what kind of information is contained in a SEM image taken by a certain detector. Specifically, the detectors installed in the objective lens are difficult to know their characters. Thus, we propose a simple method to assess the acceptance of electron detector using a stainless steel sphere. After taking images under certain conditions, say electron beam energy, working distance (WD), etc., the image intensity of each pixel point, which is characterized by coordinate (θ, φ), is evaluated. The advantage of this method is the ease of implementation and the whole information of electron emission from the tilted surfaces is contained in the image. Using this information, the acceptance of the detector can be analyzed systematically. In this paper, the traditional Everhart–Thornley (ET) detector is analyzed with this method. It is demonstrated how the sphere image changes according to the measurement condition. The ET image quality is strongly governed by WD but not so much by the electron beam energy. We propose an alternative method to avoid the ambiguity of WD. Using a needle-type specimen stage, the ET image does not vary so much with WD and the reliability of ET image significantly improves.
Improvement of primary Sjögren’s syndrome salivary gland function by Xinfeng capsule and its effect on EGR1-STAT3 signaling pathway
Authors: Zhu Ling , Wang Beijia , Li Pingping , Cheng Gangli , Bu Su , Bian Sijie , Qiu Xiaoting , Liu Jian , Huo Xingxing
Published: October 2024

Objectives

The study was aimed to investigate the effects of Xinfeng capsule (XFC) on tissue morphology, and gland function of the salivary gland (SG) in a primary Sjögren’s syndrome (pSS) mouse model.

Methods

An animal model of pSS was established by inducing SG protein in C57BL/6 mice. SG tissues were collected for tissue sequencing and subsequent experiments to detect the expression of cholinergic receptor muscarinic 3(M3R), early growth response factor 1 (EGR1) and target genes in the SG before and after XFC intervention, with in vitro validation.

Results

Downstream targets of the EGR1 gene were predicted and analyzed using data analysis. EGR1 showed high expression and was selected for subsequent experiments. Administration of XFC significantly increased saliva production (P < 0.001) and reduced the extent of lymphatic infiltration observed in SG. Furthermore, the expression of EGR1 was increased in the model group with statistical significance in contrast with the control group but decreased after administration of XFC (P < 0.05). Data analysis predicted the downstream target of EGR1 as signal transducer and activator of transcription 3 (STAT3), which was validated in SG tissues of mice (P < .05).

Conclusions

XFC demonstrated a significant improvement in the salivary secretion function of the SG in pSS mice. EGR1 can serve as a biomarker and therapeutic target for pSS.
Gastric tube-preserving pancreaticoduodenectomy for ampullary adenocarcinoma after Lewis-Santy esophagectomy: a case report and literature review
Authors: Nachtergaele Sylvie , Mattart Laurine , Vindevogel Christophe , Francart David , Herman Dominique , Brescia Lionel
Published: October 2024

Pancreaticoduodenectomy after esophagectomy is a challenging procedure given the need to preserve the vascularization of the gastric plasty. We describe a case of a modified Longmire III procedure in a 68-year-old patient who underwent an esophagectomy with gastric conduit reconstruction in 2019 for esophageal adenocarcinoma. Two years later, an adenocarcinoma of the ampulla of Vater was diagnosed, necessitating pancreaticoduodenectomy with preservation of the gastric conduit. The patient presented no postoperative complications. Hepatic recurrence was observed 13 months after surgical resection. At 24 months follow-up, new liver metastases were observed. Preservation of the gastroduodenal and right gastric arteries was achieved, enabling conservation of the gastric plasty. Given the limitations of lymphadenectomy, the indication for this surgery must always be carefully considered. In the context of complex surgery, a complete preoperative workup to precisely determine the vascular anatomy as well as any anatomical variations is essential to establish the best operative strategy.
Niclosamide attenuates erectile dysfunction and corporal fibrosis via reversal of Smad signaling in diabetic rat model
Authors: Engin Seçkin , Barut Elif Nur , Kaya Yaşar Yeşim , Işık Semanur , Kerimoğlu Gökçen , Burnett Arthur L , Sezen Sena F
Published: October 2024

Background

Diabetes mellitus-induced erectile dysfunction (DMED) is a common urological complication of diabetes, and current drugs often fail to provide an effective treatment. Smad2/3 signaling-mediated corporal fibrosis has a critical role in the molecular basis of DMED.

Aim

We investigated the effect of Niclosamide (Nic), an antihelmintic drug with antifibrotic effects, on erectile function in a rat DMED model.

Methods

Male Sprague Dawley rats were injected intraperitoneally (i.p) with streptozotocin (75 mg/kg) to induce diabetes. At week 8, both diabetic and nondiabetic rats were treated with Nic (10 mg·kg−1/day; i.p) or vehicle for 4 weeks. At week 12, erectile function was evaluated as intracavernous pressure (ICP) response to the electrical stimulation of the cavernous nerve (CN). Penile tissues were harvested for Masson’s trichrome staining or western blotting to determine corporal fibrosis and Smad2/3 pathway-related protein expression, respectively.

Outcomes

At the end of the experimental protocol, in vivo erectile function was assessed by measuring the ratio of ICP/ mean arterial pressure (MAP) and total ICP following CN stimulation. Smooth muscle content and collagen fibers were evaluated by Masson’s trichrome staining of the penile tissues. The expressions of fibrosis-related proteins (Smad2, Smad3, fibronectin) were determined using western blotting in the penile tissues.

Results

Erectile function, as determined by the maximum ICP/MAP and total ICP/MAP ratios, was drastically decreased in diabetic rats. Corporal tissues of diabetic rats were severely fibrotic with a significant increase in collagen fibers and a marked reduction in smooth muscle content. Also, the protein expressions of phosphorylated (p-)Smad2, p-Smad3 and fibronectin were significantly increased in the penis of diabetic rats. Both functional and molecular alterations in DMED were effectively reversed by Nic-treated diabetic rats without a glycemic alteration.

Clinical Implications

Nic could be a promising candidate for the treatment of DMED due to its antifibrotic effects.

Strengths and Limitations

The present study provides the first evidence that Nic has beneficial effect on erectile dysfunction by attenuating corporal fibrosis in a rat model of DMED. The effect of Nic on penile endothelial function and the other potential underlying mechanisms needs to be further elucidated.

Conclusions

Nic improved erectile function in DMED rats possibly suppressing penile fibrosis by inhibiting Smad2/3 signaling. These results suggest a potential therapeutic repurposing of Nic as an adjuvant treatment in DMED.
Representation of migrant workers in Chinese newspapers: combining topic modeling and critical discourse analysis
Authors: Pang Nana , Sun Meng , Zhu Haoran
Published: October 2024

Chinese migrant workers have contributed greatly to the industrialization and urbanization of China and have thus long been a popular topic in news reports. Most previous studies on the news about this group have been qualitative or quantitative analyses based on small-scale datasets, with few based on large-scale corpus data. This study combined topic modeling and critical discourse analysis (CDA) to analyze 186,180 reports of migrant workers published by 906 Chinese newspapers between 2001 and 2021. We identified seventeen topics in the news that fell into five categories: “work and labor,” “support and care,” “rights and interests,” “homecoming,” and “social emergencies.” Overall, news reports on the group have become increasingly diverse, with various diachronic changes in the proportions of topic categories and specific topics. In addition, we found three major types of representation of migrant workers: as a disadvantaged group, as outsiders, and as a group vulnerable to risks. These negative representations might be closely related to government policies, ideology, media stance, and social reality (the broader societal context in which these individuals are situated).
Nonconventional Imaging for Viable Bacteria Detection: A Review
Authors: Gimenez Yilbert , Vandenkoornhuyse Philippe
Published: October 2024

The first attempts of bacteria observation started with the use of glass lenses to generate magnified images of specimens. This technique is constrained by the principal limit to the resolution of any optical system. Besides optical microscopy, other imaging techniques emerged to reveal more levels of details. The more the achievable resolution, the more complex the imaging systems, and at the same time, the more potentially cell-killing or DNA-damaging they may become. This article provides a state of the art of nonconventional sensor techniques that have been used in applications related to bacteria imaging, for the purpose of comparing the information they provide and determine their suitability or find out if their combination can yield new results without compromising the ability to keep the cells alive.
KK is Wrong Because We Say So
Authors: Goldstein Simon , Hawthorne John
Published: October 2024

This paper offers a new argument against the KK thesis, which says that if you know p, then you know that you know p. We argue that KK is inconsistent with the fact that anyone denies the KK thesis: imagine that Dudley says he knows p but that he does not have 100 iterations of knowledge about p. If KK were true, Dudley would know that he has 100 iterations of knowledge about p, and so he wouldn’t deny that he did. We consider several epicycles, and also explore whether the argument type also challenges other structural conditions on knowledge, such as closure under deduction.
Unexpected stratification in the equivalent-duration distributions of flare stars
Authors: Yoldaş E , Dal H A
Published: October 2024

In this study, the results obtained from the statistical models of flares observed with ground-based telescopes and TESS observations for the UV Ceti-type stars AD Leo and V1005 Ori are presented. The distribution of flare equivalent duration versus total flare duration for the flares of both stars, observed with different telescopes, has been modelled using the one-phase exponential association (OPEA) model. Although no bifurcation was observed in the models derived with the flare data of V1005 Ori, the OPEA model exhibited bifurcation in almost all observation data of AD Leo. While many similar studies have shown that such models derived for a star do not vary over time and exhibit a single distribution in the same observation season, the stratification in AD Leo’s distributions and consequently in its model is an unexpected result.
Chromatin Accessibility and Gene Expression Vary Between a New and Evolved Autopolyploid of Arabidopsis arenosa
Authors: Srikant Thanvi , Gonzalo Adrián , Bomblies Kirsten
Published: October 2024

Polyploids arise from whole-genome duplication (WGD) events, which have played important roles in genome evolution across eukaryotes. WGD can increase genome complexity, yield phenotypic novelty, and influence adaptation. Neo-polyploids have been reported to often show seemingly stochastic epigenetic and transcriptional changes, but this leaves open the question whether these changes persist in evolved polyploids. A powerful approach to address this is to compare diploids, neo-polyploids, and evolved polyploids of the same species. Arabidopsis arenosa is a species that allows us to do this—natural diploid and autotetraploid populations exist, while neo-tetraploids can be artificially generated. Here, we use ATAC-seq to assay local chromatin accessibility, and RNA-seq to study gene expression on matched leaf and petal samples from diploid, neo-tetraploid and evolved tetraploid A. arenosa. We found over 8,000 differentially accessible chromatin regions across all samples. These are largely tissue specific and show distinct trends across cytotypes, with roughly 70% arising upon WGD. Interestingly, only a small proportion is associated with expression changes in nearby genes. However, accessibility variation across cytotypes associates strongly with the number of nearby transposable elements. Relatively few genes were differentially expressed upon genome duplication, and ∼60% of these reverted to near-diploid levels in the evolved tetraploid, suggesting that most initial perturbations do not last. Our results provide new insights into how epigenomic and transcriptional mechanisms jointly respond to genome duplication and subsequent evolution of autopolyploids, and importantly, show that one cannot be directly predicted from the other.
A symbiotic oyster in a shrimp burrow: phylogenetic position of Anomiostrea within the Ostreidae (Bivalvia)
Authors: Goto Ryutaro , Garzia Matteo , Oliver P Graham , Paulay Gustav , Salvi Daniele
Published: October 2024

The ostreid genus Anomiostrea Habe & Kosuge, 1966, is monotypic for A. coralliophila Habe, 1975, which is known as a symbiont inhabiting the burrow of the ghost shrimp Neocallichirus jousseaumei (Nobili, 1904), but despite this unusual habit among oysters its phylogenetic position within the Ostreidae remained unknown. Using specimens collected from two distant localities of the Indo-Pacific, Oman and Japan, we compared shell morphology of these specimens with the holotype and assessed their phylogenetic relationships based on DNA sequence data from two mitochondrial and two nuclear genes. The genetic distance in cytochrome c oxidase subunit I between the specimens from Japan and Oman was 5.5%, indicating substantial geographic differentiation. Our molecular phylogenetic results suggest that A. coralliophila is sister to Ostrea algoensis G. B. Sowerby II, 1871, an oyster from rocky shores in South Africa, and both are closely related to other Ostrea species. This confirms assignment of Anomiostrea to Ostreinae and suggests that this burrow-wall symbiont evolved from typical rocky-shore oysters. Moreover, A. coralliophila was not monophyletic with another symbiotic ostreid Ostrea permollis G. B. Sowerby II, 1871, nor with other symbiotic oysters, indicating that the symbiotic habit evolved multiple times in the Ostreinae.
Evolution of left–right asymmetry in side-resting (pleurothetic) bivalves: a test of genes as leaders or followers
Authors: Palmer A Richard
Published: October 2024

Side-resting (pleurothetic) lifestyles evolved independently many times across the Bivalvia in free-lying, byssally attached and cementing lineages. Within some species individuals lie indifferently on either their right or left side (randomly pleurothetic), whereas in others they lie consistently on one side (left-pleurothetic or right-pleurothetic). Morphological differences between valves (asymmetries) typically accompany this behaviour, so it can be studied widely across living and fossil bivalves. Because direction of asymmetry is rarely inherited in cases of random asymmetry, any evolutionary transition from randomly pleurothetic to fixed (left or right) qualifies as a case of ‘genes as followers’. Origins of left-pleurothetic or right-pleurothetic taxa directly from upright (orthothetic) ancestors would represent examples of ‘genes as leaders’. I therefore surveyed pleurothetic lifestyles across the Bivalvia. By mapping pleurothetic states onto a comprehensive phylogenetic tree that included both living and fossil families, I assessed the prevalence of these alternate modes of evolution. Various lines of evidence were also used to hypothesize phylogenetic relations within the Chamidae—the only living bivalve family exhibiting all three pleurothetic states. Randomly pleurothetic forms (direction not inherited) arose from orthothetic ancestors about half as often as fixed pleurothetic forms (direction is inherited). Unlike many other animal groups, fixed pleurothetic forms rarely arose from randomly pleurothetic ancestors, suggesting a ‘genes as leaders’ mode of evolution was most prevalent. However, many fascinating examples of randomly pleurothetic forms among Upper Ordovician and Silurian bivalves suggest that evolutionary transitions from random to fixed may have been more common. Also, randomly pleurothetic forms were short-lived in some fossil lineages, which would reduce the likelihood of them being detected. Hopefully, this preliminary analysis will motivate further study of (1) phylogenetic relations of key groups like the Chamidae, and basal Limida, Ostreida and Pterioidea, and (2) morphological variation among early members of other pleurothetic bivalve groups.
CELL-INTRINSIC METABOLIC PHENOTYPES IDENTIﬁED IN GLIOBLASTOMA PATIENTS USING MASS SPECTROMETRY IMAGING OF 13C-LABELED GLUCOSE METABOLISM
Authors: Tsyben Dr Anastasia , Dannhorn Dr Andreas , Hamm Dr Gregory , Couturier Dr Dominique Laurent , Briggs Dr Mayen , Mair Mr Richard , Brindle Prof Kevin
Published: October 2024

AIMS

Glioblastoma (GB) is an inherently heterogenous and invasive primary brain tumour. Genetic and transcriptomic studies have attempted to classify GB into subtypes that can identify therapeutic vulnerabilities and predict survival. An outstanding question and technical challenge is to visualise the metabolism of a tumour within its native microenvironment and understand to what extent its metabolism is driven by the microenvironment.

METHOD

Patients with GB tumours were infused with [U-13C]glucose and intra-operative multi-regional tumour samples were rapidly snap frozen for metabolic tracing analysis using mass spectrometry imaging (MSI). Tissue microenvironment was assessed using multiplexing of antibodies on immunocytochemistry (IMC) of parallel sections. Isotope tracing in human derived neurospheres and patient derived xenografts were used to conﬁrm the presence of metabolic phenotypes detected in the human samples and to test susceptibility of each phenotype to a panel of drugs targeting cellular metabolism.

RESULTS

Three metabolic signatures were identiﬁed in patient GB tumours: glycolytic, oxidative and a mixed glycolytic/oxidative phenotype. The phenotypes did not correlate with microenvironmental features, including proliferation rate, immune cell inﬁltration, and vascularisation. The phenotypes were retained when patient derived cells were grown in vitro, or as orthotopically implanted xenografts, and were robust to changes in oxygen concentration, demonstrating their cell intrinsic nature. The spatial extent of the regions occupied by cells displaying these distinct metabolic phenotypes are large enough to be detected using clinically applicable metabolic imaging techniques. The phenotypes also demonstrate differential drug sensitivities.

CONCLUSION

This is the ﬁrst report to demonstrate high resolution imaging of metabolic ﬂuxes in a human tumour in vivo. In conjunction with studies on patient-derived neurospheres and orthotopically implanted xenografts we have demonstrated the presence of different metabolic phenotypes within GB that are tumour cell intrinsic and largely independent of the tumour microenvironment. These can be imaged clinically and used to stratify patients for personalised therapy.
MANAGEMENT OF THE OLDER PATIENT WITH GLIOBLASTOMA IN THE UK: AN INITIAL REPORT FROM THE HISTO-MOL GBM COLLABORATIVE
Authors: Robinson Dr Stephen , Ryan Dr Katherine , Black Dr Louisa , Forner Dr Sam , Hatton Dr Nathaniel Luke , Hatton Dr Rebecca , Aktar Dr Nurjahan , Lathangue Mr Haydn , Conkey Dr David , Durage Dr Praveen , de Luna Mr Paolo , Christodoulou Dr Pavlos , Hill Dr Timothy , MacArthur Ms Rachel , Teoh Dr May , Williams Dr Adenike , Golten Dr Jennifer , Aghadiuno Dr Tasia , Yogalingam Dr Kohgulakuhan , Kahan Dr Jennifer , Dixit Dr Sanjay , Guglani Dr Samir , Lewis Dr Rachel , Moleron Dr Rafael , Iqbal Dr Najmus , Wadd Dr Nick , Bhat Dr Prashanth , Giamas Prof Georgios , Mazarakis Dr Nektarios , Lorimer Dr Cressida , Chandy Dr Edward , Critchley Prof Giles
Published: October 2024

AIMS

The management of older (>70 years old) patients with glioblastoma is challenging with signiﬁcant variation in practice. Using the Histo-Mol GBM database we analysed the variation in practice across 11 UK centres.

METHOD

Biopsy conﬁrmed glioblastoma patients diagnosed between 01/01-31/12/2021 were identiﬁed. Descriptive statistics were used to compare demographic, tumour and treatment characteristics, and the Kaplan-Meier method was used to analyse survival, assessed from surgery date. Differences in treatment between centres were assessed using one way ANOVA.

RESULTS

In 2021, 81/330 (24.5%) patients with glioblastoma were >70. Compared to younger patients, the older cohort had a greater proportion of males (79.0% vs 59.0%, p<0.001), a worse performance status (66.7% vs 79.5% ECOG PS 0-1, p<0.001), and more likely to have MGMT promoter methylation (30.9% vs 22.9%, p=0.027). Most patients received biopsy only (31/81, 38.3%), followed by subtotal resection (85-94% tumour resection) (26/81, 32.1%), whilst 8/81 (9.9%) underwent debulking, 8/81 near-total resection (95-99% tumour resection), and 8/81 gross total resection, with statistically signiﬁcant variation in resection extent between centres (p=0.031). Adjuvant radiotherapy was used in 56/81 patients (69.1%) with no difference between centres (p=0.220). However, there was a statistically signiﬁcant difference in radiotherapy regime between centres (p=0.041). 6/81 (7.4%) received conventional chemoradiotherapy, 28/81 (34.6%) hypofractionated chemoradiotherapy, 16/81 (19.8%) hypofractionated radiotherapy alone, 2/81 (2.5%) temozolomide alone both with MGMT promoter methylation, and 21/81 (25.9%) received no oncological treatment. Median progression free survival was 5.9 months and median overall survival (OS) was 7.1 months with no difference between centres (p=0.199 and p=0.083 respectively). Median OS was 8.4 months with conventional fractionation chemoradiotherapy, 11.2 months with hypofractionated chemoradiotherapy, 7.3 months with hypofractionated radiotherapy alone, 1.8 months with temozolomide alone, and 2.5 months with no oncological treatment.

CONCLUSION

We identify variations in the treatment of elderly glioblastoma patients across the UK, although these do not signiﬁcantly impact survival.