bluuebunny/crossref_metadata_2025 huggingface dataset:
Considerations for legal, ethical, and effective practice in dementia research
Authors: David Michael C B , Del Giovane Martina , Wilson Danielle , Truman Trevor , Huntley Jonathan D , Suleman Mehrunisha , Ruck Keene Alexander , Parker Michael , Sharp David J , Malhotra Paresh A
Published: June 2024

Dementia represents a potentially overwhelming health burden, both for the UK and worldwide. Addressing this fast-growing issue is a key priority for the government, health service and the public. Advances in care including the development of efficacious disease-modifying, and eventually curative, treatments can only be achieved through effective dementia research. Specifically, research directly involving participants with dementia is essential to further understanding. However, working with cognitively impaired participants with and without capacity to consent to research presents unique ethical and legal challenges. For clinicians and scientists on the frontline of dementia research, scenarios frequently arise that pose such challenges. A lack of guidance for a consistent approach in navigating these scenarios limits researchers’ ability to proceed with confidence. This represents a threat to the rights and wishes of research participants as well as the field at large, as it may lead to studies being unnecessarily terminated or, worse, poor practice. In this article, we take a multiprofessional approach, informed by carer input, to these issues. We review the relevant ethical and legal literature relating to the conduct of non-interventional research studies in patients with dementia. This includes a thorough recap of the Mental Capacity Act (2005), which provides a legal framework in England and Wales for conducting research with participants who lack capacity to consent. We also discuss the important, but sometimes incomplete, role of research ethics committees in guiding researchers. We then present and discuss a series of case vignettes designed to highlight areas of incomplete coverage by existing governance. These vignettes describe theoretical scenarios informed by our own real-word experiences of encountering ethical issues when conducting dementia research. They include scenarios in which participants demonstrate varying degrees of understanding of the research they are involved in and ability to communicate their wishes and feelings. Building on these vignettes, we then provide a checklist for researchers to work through when presented with similar scenarios. This checklist covers the key ethical, legal and practical considerations that we have argued for. Taken together, this article can act as a guide, previously lacking in the literature, for colleagues in the field to enable much needed ethical, legal and effective research.
Development of a small animal model replicating core characteristics of takotsubo syndrome in humans
Authors: Zulfaj Ermir , Nejat Amirali , Espinosa Aaron Shekka , Hussain Shafaat , Haamid Abdulhussain , Soliman Ahmed Elmahdy , Kakaei Yalda , Jha Abhishek , Redfors Björn , Omerovic Elmir
Published: June 2024

Aims

Adequate animal models are necessary to understand human conditions, such as takotsubo syndrome (TS) characterized by the heart's transient regional wall motion abnormalities. This study aims to develop a reproducible, low-mortality TS model that closely mimics the human condition and addresses the limitations of existing models.

Methods and results

We conducted six experiments using 309 Sprague Dawley rats, each approximately 300 g and aged 7–8 weeks. Initially, we replicated an established model using intraperitoneal isoprenaline injections. Subsequent experiments varied the doses and infusion durations of intravenous isoprenaline and assessed the effects of sex, strain, and breeder on the development of reversible akinetic segments. High-resolution echocardiography monitored the regional wall motion over 30 days to correlate with histological changes. Increasing the isoprenaline dose and the infusion time significantly enhanced akinesia (P < 0.01), resulting in pronounced apical ballooning observed in three-dimensional imaging. Akinesia peaked at 6 h post-infusion, with recovery observed at 24 h; most rats recovered from akinetic segments within 48–72 h. Optimizing the mode of administration, dose, and duration achieved a TS-like phenotype in 90% of cases, with a 16.7% mortality rate. Histological examinations confirmed that myocardial injury occurred, independent of apical ballooning.

Conclusion

This study presents a refined TS model that reliably replicates the syndrome's key features, including morphological and electrocardiographic changes, demonstrating its transient nature with high fidelity and reduced mortality. The model's reproducibility, evidenced by consistent results across trials, suggests its potential for broader application pending further validation.
Body mass index and pulmonary vein isolation: real-world data on outcomes and quality of life
Authors: Vermeer Jasper , Houterman Saskia , Medendorp Niki , van der Voort Pepijn , Dekker Lukas ,   Ablation Registration Committee of the Netherlands Heart Registration, Kuijt W , Driessen A H G , Kemme M J B , van der Voort P H , Bhagwandien R E , van der Heijden J , Adiyaman A , Trines S A I P , Luermans J G L M , Schoonderwoerd B A , van Dessel P F H M , de Jong J S S G , Westra S W , Balt J C , Hassink R J , Blaauw Y
Published: June 2024

Aims

Increasing numbers of overweight and obese patients undergo pulmonary vein isolation (PVI), despite the association between higher body mass index (BMI) and adverse PVI outcomes. Evidence on complications and quality of life in different bodyweight groups is limited. This study aims to clarify the impact of BMI on repeat ablations, periprocedural complications, and changes in quality of life.

Methods and results

This multi-centre study analysed prospectively collected data from 15 ablation centres, covering all first-time PVI patients in the Netherlands from 2015 to 2021. Patients were categorized by BMI: normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obesity (≥30 kg/m2). Quality of life was assessed using the Atrial Fibrillation Effect on QualiTy-of-life questionnaire at baseline and 1-year post-PVI. Among 20 725 patients, 30% were of normal weight, 47% overweight, and 23% obese. Within the first year after PVI, obese patients had a higher incidence of repeat ablations than normal-weighing and overweight patients (17.8 vs. 15.6 and 16.1%, P < 0.05). Obesity was independently associated with repeat ablations (odds ratio 1.15; 95% confidence interval 1.01–1.31, P = 0.03). This association remained apparent after 3 years. Complication rates were 3.8% in normal weight, 3.0% in overweight, and 4.6% in obese, with weight class not being an independent predictor. Quality of life improved in all weight groups post-PVI but remained lowest in obese patients.

Conclusion

Obesity is independently associated with a higher rate of repeat ablations. Pulmonary vein isolation is equally safe in all weight classes. Despite lower quality of life among obese individuals, substantial improvements occur for all weight groups after PVI.
Mathematical modelling, selection and hierarchical inference to determine the minimal dose in IFNα therapy against myeloproliferative neoplasms
Authors: Hermange Gurvan , Vainchenker William , Plo Isabelle , Cournède Paul-Henry
Published: June 2024

Myeloproliferative neoplasms (MPN) are blood cancers that appear after acquiring a driver mutation in a hematopoietic stem cell. These hematological malignancies result in the overproduction of mature blood cells and, if not treated, induce a risk of cardiovascular events and thrombosis. Pegylated IFN$\alpha $ is commonly used to treat MPN, but no clear guidelines exist concerning the dose prescribed to patients. We applied a model selection procedure and ran a hierarchical Bayesian inference method to decipher how dose variations impact the response to the therapy. We inferred that IFN$\alpha $ acts on mutated stem cells by inducing their differentiation into progenitor cells; the higher the dose, the higher the effect. We found that the treatment can induce long-term remission when a sufficient (patient-dependent) dose is reached. We determined this minimal dose for individuals in a cohort of patients and estimated the most suitable starting dose to give to a new patient to increase the chances of being cured.
Phenotypic and genomic analysis of bacteria from war wounds in Dnipro, Ukraine
Authors: Stepanskyi Dmytro , Ishchenko Oksana , Luo Ting , Lebreton Francois , Bennett Jason W , Kovalenko Iryna , McGann Patrick
Published: June 2024

Objectives

To better understand the source and potential transmission routes of antibiotic-resistant bacteria infecting injured service members in Ukraine.

Methods

Phenotypic and genomic characterizations were performed on 11 Gram-negative pathogens cultured from war wounds at an intermediate evacuation hospital in Dnipro.

Results

The analysis revealed both susceptible and extensively drug-resistant strains present in cultures, including high-risk global clones carrying carbapenemases.

Conclusions

Globally distributed carbapenemase-producing lineages are being acquired early in the medical evacuation process.
Evaluation of a Rapid Drug Test Device for Urine Fentanyl Compared to Mass Spectrometry and 2 Urine Fentanyl Assays
Authors: Laryea Erving T , Nichols James H
Published: June 2024

Background

A new Rapid Drug Test Device (RDTD) is available for analysis of urine fentanyl. With the rise in fentanyl abuse in the United States, we evaluated the analytical performance of the RDTD test strip compared to mass spectrometry and 2 urine fentanyl immunoassays.

Methods

Leftover, deidentified urine samples collected from inpatients and outpatients from our psychiatric hospital and other clinics were frozen at <−70°C, thawed at room temperature, and centrifuged. Aliquots were tested with the RDTD (CLIA Waived, Inc.) test strips and 2 urine fentanyl immunoassays: the ARK Fentanyl II assay (ARK Diagnostics Inc.) and the Immunalysis SEFRIA Fentanyl assay (Immunalysis Corporation). Both assays were conducted on the Abbott Alinity c chemistry analyzer (Abbott Laboratories). Mass spectrometry analysis was performed at ARUP Laboratories. All assays had a 1 ng/mL positive cutoff.

Results

A total of 142 urine samples included 70 positive and 72 negative samples. The RDTD strips had lower sensitivity (84.3%) and efficiency (85.9%) and showed a specificity of 87.5% compared to the other assays. The ARK Fentanyl II assay showed identical sensitivity (95.7%) to the Immunalysis SEFRIA Fentanyl assay but had higher specificity (94.4% vs 81.9%) and overall efficiency (95.1% vs 88.7%).

Conclusions

Differences were noted in the number of false negatives and positives among the assays. The RDTD demonstrated acceptable performance in detecting urine fentanyl in our patient population and would provide faster test results at point-of-care testing sites in our healthcare enterprise.
Collagen structures of demineralized bone paper direct mineral metabolism
Authors: Yoon Hyejin , Park Yongkuk , Kwak Jun-Goo , Lee Jungwoo
Published: June 2024

Bone is a dynamic mineralized tissue that undergoes continuous turnover throughout life. While the general mechanism of bone mineral metabolism is documented, the role of underlying collagen structures in regulating osteoblastic mineral deposition and osteoclastic mineral resorption remains an active research area, partly due to the lack of biomaterial platforms supporting accurate and analytical investigation. The recently introduced osteoid-inspired demineralized bone paper (DBP), prepared by 20-μm thin sectioning of demineralized bovine compact bone, holds promise in addressing this challenge as it preserves the intrinsic bony collagen structure and retains semi-transparency. Here, we report on the impact of collagen structures on modulating osteoblast and osteoclast-driven bone mineral metabolism using vertical and transversal DBPs that exhibit a uniaxially aligned and a concentric ring collagen structure, respectively. Translucent DBP reveals these collagen structures and facilitates longitudinal tracking of mineral deposition and resorption under brightfield microscopy for at least 3 wk. Genetically labeled primary osteogenic cells allow fluorescent monitoring of these cellular processes. Osteoblasts adhere and proliferate following the underlying collagen structures of DBPs. Osteoblastic mineral deposition is significantly higher in vertical DBP than in transversal DBP. Spatiotemporal analysis reveals notably more osteoblast adhesion and faster mineral deposition in vascular regions than in bone regions. Subsequent osteoclastic resorption follows these mineralized collagen structures, directing distinct trench and pit-type resorption patterns. In vertical DBP, trench-type resorption occurs at an 80% frequency, whereas transversal DBP shows 35% trench-type and 65% pit-type resorption. Our studies substantiate the importance of collagen structures in regulating mineral metabolism by osteogenic cells. DBP is expected to serve as an enabling biomaterial platform for studying various aspects of cellular and extracellular bone remodeling biology.
Carboxylesterase 1 directs the metabolic profile of dendritic cells to a reduced inflammatory phenotype
Authors: Elfiky Ahmed M I , Canñizares Jessica López , Li Jiarong , Li Yim Andrew Y F , Verhoeven Arthur J , Ghiboub Mohammed , de Jonge Wouter J
Published: June 2024

The metabolic profile of dendritic cells (DCs) shapes their phenotype and functions. The carboxylesterase 1 (CES1) enzyme is highly expressed in mononuclear myeloid cells; however, its exact role in DCs is elusive. We used a CES1 inhibitor (WWL113) and genetic overexpression to explore the role of CES1 in DC differentiation in inflammatory models. CES1 expression was analyzed during CD14+ monocytes differentiation to DCs (MoDCs) using quantitative polymerase chain reaction. A CES1 inhibitor (WWL113) was applied during MoDC differentiation. Surface markers, secreted cytokines, lactic acid production, and phagocytic and T cell polarization capacity were analyzed. The transcriptomic and metabolic profiles were assessed with RNA sequencing and mass spectrometry, respectively. Cellular respiration was assessed using seahorse respirometry. Transgenic mice were used to assess the effect of CES1 overexpression in DCs in inflammatory models. CES1 expression peaked early during MoDC differentiation. Pharmacological inhibition of CES1 led to higher expression of CD209, CD86 and MHCII. WWL113 treated MoDCs secreted higher quantities of interleukin (IL)-6, IL-8, tumor necrosis factor, and IL-10 and demonstrated stronger phagocytic ability and a higher capacity to polarize T helper 17 differentiation in an autologous DC-T cell coculture model. Transcriptomic profiling revealed enrichment of multiple inflammatory and metabolic pathways. Functional metabolic analysis showed impaired maximal mitochondrial respiration capacity, increased lactate production, and decreased intracellular amino acids and tricarboxylic acid cycle intermediates. Transgenic human CES1 overexpression in murine DCs generated a less inflammatory phenotype and increased resistance to T cell–mediated colitis. In conclusion, CES1 inhibition directs DC differentiation toward a more inflammatory phenotype that shows a stronger phagocytic capacity and supports T helper 17 skewing. This is associated with a disrupted mitochondrial respiration and amino acid depletion.
(273) PIEZO TYPE-ESWT ALLEVIATES INFLAMMATION IN THE RAT MODEL OF CHRONIC PROSTATITIS
Authors: Shin Dongho , Piao JunJie , Oh Jin Sik , Kim Sae Woong
Published: June 2024

Objectives

To evaluate the anti-inflammatory effect of piezo type extracorporeal shock wave therapy (ESWT) in the rat model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Methods

For the in vivo experiments, SD male rats were randomly divided into 3 groups: (1) normal group, (2) CP/CPPS group, and (3) ESWT group (n=6 for each group). Prostatitis was induced with 17 beta-estradiol. After 4 weeks of piezo type ESWT, prostate tissues were harvested for histopathological analysis and western blotting assay.

Results

A previous study in our laboratory found that the optimal energy flux density of ESWT is 0.2 mJ/mm2, so we used this energy flux in this in vivo experiment and found that piezo type ESWT improved the inflammatory symptoms of prostatitis masters. H&E staining of prostate tissues revealed that the inflammatory symptoms of piezo type ESWT were significantly improved relative to the CP/CPPS group. Inflammation-related cytokines such as TNF-α, IL-6 and IL-8 were significantly reduced after piezo type ESWT as derived by western blotting.

Conclusions

In a rat model, piezo type ESWT effectively reduced the inflammatory factors TNF-α, IL-6 and IL-8, and also showed significant improvement in histopathology, and we found that piezo type ESWT may be a potential in the treatment of CP/CPPS.

Conflicts of Interest

None.
(234) TEMPORAL EVOLUTION IN TESTOSTERONE MEASUREMENTS AND DOSES OF TESTOSTERONE REPLACEMENT THERAPY REIMBURSED BY THE BELGIAN HEALTHCARE SYSTEM BETWEEN 2013 AND 2019
Authors: Narinx Nick , Walravens Joeri , Fiers Tom , Lapauw Prof Bruno , Antonio Prof Leen
Published: June 2024

Objectives

There are large regional and international differences in prescription patterns of testosterone replacement therapy (TRT) and testosterone measurements, with increases in testosterone prescriptions reported in several countries. We investigated temporal changes in testosterone testing and reimbursed doses of TRT covered by the Belgian healthcare system.

Methods

Anonymous data on serum total testosterone measurements (number of analyses and amount spent in euro) in men 17 years or older, were requested from the government (RIZIV) for 2012-2022. Data on TRT were requested from the government (Farmanet) from 1-2013 until 11-2019 (requested results for 12-2019 – 12-2022 pending). This covers pharmaceutical preparations reimbursed in Belgium, prescribed by a physician and provided to the patient via public pharmacies. In Belgium, only Sustanon® is reimbursed, so this dataset does not comprise transdermal preparations or testosterone undecanoate. Data were provided as number of delivered packages and amount spent. Since 2012, one package of Sustanon® on the Belgian market contains one dose of 250 mg testosterone esters.

Results

In 2013, total testosterone was measured 105.060 times in Belgian adult men. This increased to 138.570 in 2019 (+32% over a 7-year time period). The amount spent by the healthcare system for testosterone testing increased from €379.394 in 2013 to €487.645 in 2019 (+29%). In 2013, 38.695 doses of Sustanon® were sold. In 2019, this increased to 56.789 doses (+47%), corresponding to a cost of €380.403 in 2013 and €496.390 (+30%). From 2013 till 2019, the population of Belgian adult men increased by 4.3%.

Conclusions

The number of testosterone measurements increased by 32% in Belgium between 2013 and 2019. Remarkably, the number of doses of the only reimbursed testosterone replacement therapy showed an increase of 47% over a 7-year time period, showing a similar trend of prescription pattern increases as reported in other European countries.

Conflicts of Interest

This work was funded by an Applied Biomedical Research with a Primary Societal finality (TBM) project-grant from the Flanders Research Foundation (FWO-TBM T004321N). Leen Antonio participated in advisory boards for Galapagos, Merck and Androlabs.
(257) CYSTOSCOPY AND ITS POTENTIAL ASSOCIATION WITH PEYRONIE’S DISEASE: A RETROSPECTIVE COHORT STUDY
Authors: Durukan Dr Emil , Jensen Christian FS , Østergren Peter B , Frandsen Dr Rasmus , Fode Prof Mikkel
Published: June 2024

Objectives

Patients may present with Peyronie's disease (PD) following cystoscopy. The potential link between the two remains uncertain. We aimed to investigate the potential association.

Methods

We retrospectively analyzed electronic health records from the Capital and Zealand regions of Denmark to study men diagnosed with PD between January 2018 and October 2022. Initially, we identified men diagnosed with PD between January 2018 and October 2022 and calculated their interquartile age range. We then focused on men who underwent cystoscopy within the same time frame and whose age fell within the same interquartile range (IQR). We collected data on PD risk factors (diabetes, hypertension, ischemic heart disease, erectile dysfunction, Dupuytren’s contracture) and determined the number of men diagnosed with PD within a year after their cystoscopy. We included similar-aged men who had scrotal ultrasound or thoracic x-ray for comparison, representing urological and non-urological examinations.

Results

The IQR for PD patients was 52-66 years. During the timeframe, 6,210 men within this age range underwent cystoscopies, 6,691 underwent scrotal ultrasound, and 70,927 underwent thoracic x-ray. Risk factors for PD were present in 23% in the cystoscopy group, 17% of the ultrasound group, and 22% in the x-ray group. Within the following year of their respective procedures, PD were diagnosed in 0.97%, 1.85%, and 0.16% in the three groups, respectively. The adjusted odds ratios for PD were 0.369 (95% CI 0.268 – 0.507, p <0.0001) for cystoscopy vs. ultrasound and 6.258 (95% CI 4.547 – 8.612, p <0.0001) for cystoscopy vs. x-ray.

Conclusions

As there is no plausible mechanism for scrotal ultrasound to cause PD, our analysis implies that having an examination of the male genitals leads to a higher chance of being diagnosed with PD, while cystoscopy is not a specific risk factor. Prospective studies are needed to further address the topic.

Conflicts of Interest

No conflict of interests.
(210) EXPRESSION OF POTENTIAL FUNCTIONAL SIGNIFICANCE OF ARGINASE ISOENZYMES (L-ARGININE-AMINIDOHYDROLASES) IN THE HUMAN PROSTATE
Authors: Ückert Prof Stefan , Kedia Priv-Doz George T , Tsikas Prof Dimitrios , Märker Dr Viktoria , Kuczyk Prof Markus A
Published: June 2024

Objectives

There is evidence that the nitric oxide (NO)/cyclic GMP pathway contributes mainly to the control of the normal function of smooth musculature in the human prostate. The activity of nitric oxide synthases (NOS) is in part regulated by arginase enzymes (L-arginine-aminidohydrolases, Arg), known to hydrolyse the amino acid L-arginine (the common substrate of NOS and Arg) to L-ornithineand urea. We have investigated in the transition zone of the human prostate the expression and potential functional significance of arginase enzymes type I and type II (Arg I, Arg II).

Methods

Human prostate tissue was obtained from male subjects who had undergone pelvic surgery (prostatectomy/cystectomy). The expression of Arg I and Arg II was investigated by means of Western blot analysis. Using the tissue bath technique, the effects were assessed of the cumulative administration of arginase inhibitors (DFMO, H-Orn-OH.HCl, H-Ile-OH, nor-NOHA, 1 nM - 10 μM each) on the tension induced by the alpha-adrenergic agonist norepinephrine (NE) of isolated prostate tissue. The production of cyclic GMP in the tissue strips in response to exposure to the compounds was measured also.

Results

Western blot analysis revealed the expression of Arg I and Arg II in the transition zone of the prostate. The tension induced by NE was antagonized by the arginase inhibitors with the following rank order of efficacy: H-Orn-OH.HCl ≥ H-Ile-OH ≥ DFMO > nor-NOHA (in a range from -13% to -25%). The enhancement in cyclic GMP production registered in the presence of the arginase inhibitors was 4-fold to 14-fold.

Conclusions

Arg I and Arg II are expressed in the human prostate. Isometric tension studies and measurement of cyclic GMP showed that inhibition of arginase can reverse, to a certain degree, the tension of prostate smooth muscle induced by the activation of alpha-adrenoceptors and enhance the accumulation of cyclic GMP.

Conflicts of Interest

The authors have no conflicts of interest to declare.
(299) THE ROLE OF ATTACHMENT IN PORNOGRAPHY USE AND PROBLEMATIC PORNOGRAPHY USE: A SYSTEMATIC REVIEW
Authors: Ghinassi Simon , Fioravanti Giulia , Casale Silva , Benucci Sara Bocci
Published: June 2024

Objectives

Pornography Use (PU) is a widespread and socially accepted behavior in most parts of the world. However, its uncontrolled use, i.e., Problematic Pornography Use (PPU), can have negative consequences for the health of the individual. Among the factors associated with such behavior, attachment appears to play a significant role. However, the evidence on the association between attachment-related phenomena and PU/PPU has not yet been systematized in the literature. Therefore, the present systematic review aims to fill this gap.

Methods

Following the updated PRISMA 2020 guidelines, the research process of the studies through four electronic scientific databases (Scopus, PubMed, ScienceDirect and Web of Science) has led to the identification of 160 records. Subsequently, duplicates (n = 83) were removed, and the titles and abstracts of the remaining 77 were screened. After this preliminary screening, 37 full-text records were examined for eligibility assessment, and 10 articles met the eligibility criteria and were selected for the present systematic review.

Results

Findings from these studies have shown the significant role played by attachment-related phenomena in PU and PPU, highlighting some differences according to the type of attachment considered. While anxious attachment has emerged to be associated with both PU and PPU, the results regarding avoidant attachment were mixed. Moreover, the secure attachment indicators were considered only in PU, and the results obtained were not consistent.

Conclusions

Overall, the results suggest that individuals with insecure attachment are more likely to use pornography, also in a problematic way. Specifically, the findings suggest that people with high levels of attachment anxiety may tend to use pornography to cope with their fear of being abandoned and rejected by significant others, such as their romantic or sexual partner. Limitations, strengths, and implications of the present systematic review will be discussed.

Conflicts of Interest

No conflicts of interest to declare.
Optimizing liquid fermentation for Wolfiporia cocos: gene expression and biosynthesis of pachymic acid and mycelial biomass
Authors: Noushahi Hamza Armghan , Khan Aamir Hamid , Khan Hamza Ali , Kiedrzyński Marcin , Akbar Adnan , Shahzad Raheel , Koerniati Sri , Alrefaei Abdulwahed Fahad , Shu Shaohua
Published: June 2024

Wolfiporia cocos, a versatile fungus acclaimed for its nutritional and therapeutic benefits in Traditional Chinese Medicine, holds immense potential for pharmaceutical and industrial applications. In this study, we aimed to optimize liquid fermentation techniques and culture medium composition to maximize mycelial biomass (MB) yield, pachymic acid (PA) concentration, and overall PA production. Additionally, we investigated the molecular basis of our findings by quantifying the expression levels of genes associated with PA and MB biosynthesis using quantitative real-time polymerase chain reaction. Under the optimized fermentation conditions, significant results were achieved, with maximum MB reaching 6.68 g l−1, PA content peaking at 1.25 mg g−1, and a total PA yield of 4.76 g l−1. Notably, among the four examined genes, squalene monooxygenase, exhibited enhanced expression at 0.06 ratio under the optimized conditions. Furthermore, within the realm of carbohydrate-active enzymes, the glycoside hydrolases 16 family displayed elevated expression levels at 21 ratios, particularly during MB production. This study enhances understanding of genetic mechanism governing MB and PA production in W. cocos, highlighting the roles of squalene monooxygenase and glycoside hydrolases 16 carbohydrate-active enzymes.
WISE2MBH: a scaling-based algorithm for probing supermassive black hole masses through WISE catalogues
Authors: Hernández-Yévenes J , Nagar N , Arratia V , Jarrett T H
Published: June 2024

Supermassive Black Holes (SMBHs) are commonly found at the centres of massive galaxies. Estimating their masses (MBH) is crucial for understanding galaxy-SMBH co-evolution. We present WISE2MBH, an efficient algorithm that uses cataloged Wide-field Infrared Survey Explorer (WISE) magnitudes to estimate total stellar mass (M*) and scale this to bulge mass (MBulge), and MBH, estimating the morphological type (TType) and bulge fraction (B/T) in the process. WISE2MBH uses scaling relations from the literature or developed in this work, providing a streamlined approach to derive these parameters. It also distinguishes QSOs from galaxies and estimates the galaxy TType using WISE colours with a relation trained with galaxies from the 2MASS Redshift Survey. WISE2MBH performs well up to z ∼ 0.5 thanks to K-corrections in magnitudes and colours. WISE2MBH MBH estimates agree very well with those of a selected sample of local galaxies with MBH measurements or reliable estimates: a Spearman score of ∼0.8 and a RMSE of ∼0.63 were obtained. When applied to the ETHER sample at z ≤ 0.5, WISE2MBH provides ∼1.9 million MBH estimates (78.5 per cent new) and ∼100 thousand upper limits. The derived local black hole mass function (BHMF) is in good agreement with existing literature BHMFs. Galaxy demographic projects, including target selection for the Event Horizon Telescope, can benefit from WISE2MBH for up-to-date galaxy parameters and MBH estimates. The WISE2MBH algorithm is publicly available on GitHub.
Simultaneous retrieval of orbital phase resolved JWST/MIRI emission spectra of the hot Jupiter WASP-43b: evidence of water, ammonia, and carbon monoxide
Authors: Yang Jingxuan , Hammond Mark , Piette Anjali A A , Blecic Jasmina , Bell Taylor J , Irwin Patrick G J , Parmentier Vivien , Tsai Shang-Min , Barstow Joanna K , Crouzet Nicolas , Kreidberg Laura , Mendonça João M , Taylor Jake , Baeyens Robin , Ohno Kazumasa , Teinturier Lucas , Nixon Matthew C
Published: June 2024

Spectroscopic phase curves of hot Jupiters measure their emission spectra at multiple orbital phases, thus enabling detailed characterization of their atmospheres. Precise constraints on the atmospheric composition of these exoplanets offer insights into their formation and evolution. We analyse four phase-resolved emission spectra of the hot Jupiter WASP-43b, generated from a phase curve observed with the Mid-Infrared Instrument/Low Resolution Spectrometer onboard the JWST, to retrieve its atmospheric properties. Using a parametric 2D temperature model and assuming a chemically homogeneous atmosphere within the observed pressure region, we simultaneously fit the four spectra to constrain the abundances of atmospheric constituents, thereby yielding more precise constraints than previous work that analysed each spectrum independently. Our analysis reveals statistically significant evidence of NH$_3$ (4$\sigma$) in a hot Jupiter’s emission spectra for the first time, along with evidence of H$_2$O (6.5$\sigma$), CO (3.1$\sigma$), and a non-detection of CH$_4$. With our abundance constraints, we tentatively estimate the metallicity of WASP-43b at 0.6$-6.5\times$ solar and its C/O ratio at 0.6$-$0.9. Our findings offer vital insights into the atmospheric conditions and formation history of WASP-43b by simultaneously constraining the abundances of carbon, oxygen, and nitrogen-bearing species.
The FLAMINGO project: galaxy clusters in comparison to X-ray observations
Authors: Braspenning Joey , Schaye Joop , Schaller Matthieu , McCarthy Ian G , Kay Scott T , Helly John C , Kugel Roi , Elbers Willem , Frenk Carlos S , Kwan Juliana , Salcido Jaime , van Daalen Marcel P , Vandenbroucke Bert
Published: June 2024

Galaxy clusters are important probes for both cosmology and galaxy formation physics. We test the cosmological, hydrodynamical FLAMINGO (Full-hydro large-scale structure simulations with all-sky mapping for the interpretation of next generation observations) simulations by comparing to observations of the gaseous properties of clusters measured from X-ray observations. FLAMINGO contains unprecedented numbers of massive galaxy groups ($\gt 10^6$) and clusters ($\gt 10^5$) and includes variations in both cosmology and galaxy formation physics. We predict the evolution of cluster scaling relations as well as radial profiles of the temperature, density, pressure, entropy, and metallicity for different masses and redshifts. We show that the differences between volume-, and X-ray-weighting of particles in the simulations, and between cool- and non-cool-core samples, are similar in size as the differences between simulations for which the stellar and AGN (active galactic nucleus) feedback has been calibrated to produce significantly different gas fractions. Compared to thermally driven AGN feedback, kinetic jet feedback calibrated to produce the same gas fraction at $R_{\rm 500c}$ yields a hotter core with higher entropies and lower densities, which translates into a smaller fraction of cool-core clusters. Stronger feedback, calibrated to produce lower gas fractions and hence lower gas densities, results in higher temperatures, entropies, and metallicities, but lower pressures. The scaling relations and thermodynamic profiles show almost no evolution with respect to self-similar expectations, except for the metallicity decreasing with redshift. We find that the temperature, density, pressure, and entropy profiles of clusters in the fiducial FLAMINGO simulation are in excellent agreement with observations, while the metallicities in the core are too high.
Radio continuum emission from a tidal dwarf galaxy
Authors: Moncada-Cuadri Blanca M , Lisenfeld Ute , Querejeta Miguel , Mundell Carole
Published: June 2024

Tidal dwarf galaxies (TDGs) form in the debris of galaxy mergers, making them ideal testbeds for investigating star formation in an extreme environment. We present radio continuum EVLA observations spanning 1–2 GHz of the interacting system Arp 94, which contains the TDG J1023+1952. We detect extended radio continuum emission from the disc of the TDG’s putative parent galaxy, the spiral NGC 3227. The TDG lies in front of the spiral disc, partially overlapping in projection. This challenging alignment complicates the separation of the respective contributions of radio emission from the TDG and disc. However, we show that the radio continuum appears more prominent around the TDG’s location, suggesting the detection of emission from the TDG. Quantifying this argument, we derive an upper limit of 2.2 mJy for the whole TDG’s emission. Our derived inband spectral index map of the system generally shows the expected behaviour of combined thermal and synchrotron radio emission in a galaxy disc, except for a region at the periphery of the disc and the TDG with a flat spectrum (spectral index $\sim$−0.4) unrelated to regions with high H $\alpha$ emission. We speculate that at this location – which coincides with the intersection of faint tidal tails – the collision of gas clouds produces shocks which re-accelerate cosmic ray electrons, and thereby enhance the radio emission. Overall, this study provides new insights about the Arp 94 system and expands the sample of TDGs studied at radio frequencies, with only two confirmed detections so far.
Extension of semi-analytic kilonova model and the application in multicolour light curves fitting
Authors: Gong Hong-Yu , Wei Da-Ming , Jin Zhi-Ping , Fan Yi-Zhong
Published: June 2024

Observations of AT2017gfo, the counterpart of the double neutron star merger, confirmed the existence of kilonovae that are suggested to originate from the decay of the very heavy elements. However, the different simplified assumptions used in analytical and semi-analytical models can lead to a variety of fitting results. Previous semi-analytical models have assumed a grey body because of the challenge in calculating the detailed opacity of ejecta and to save the calculation time. However, the variation of opacity with wavelength cannot be ignored when calculating the multicolour flux. Though numerical simulations can calculate kilonova details, they require an excessive amount of time for data modelling. In this work, we propose an extension of previous semi-analytical models by not assuming the grey-body opacity and constant thermalization efficiency assumptions. We demonstrate that the impact of opacity changing with wavelength is non-negligible and then introduce an empirical analytical opacity in optical and near-infrared bands to calculate multicolour light curves of kilonovae with a three-dimensional, three-component model. Additionally, we consider the evolution of thermalization efficiency at later times, enabling application of our model to both the early and later phases of kilonovae. To enable efficient fitting of models with many parameters (23 parameters in the case of double neutron star merger), a quick method based on the greedy algorithm is developed. We can well reproduce the infrared/optical/ultraviolet observations of AT2017gfo. This model can also be extended to black-hole and neutron star mergers as well.
Chemical compositions of semiregular variable red giants
Authors: Pozhath Ramya , Lambert David L
Published: June 2024

A sample of warm, low-level semiregular variables chosen from the General Catalogue of Variable Stars is studied for their chemical compositions by analysing high-resolution optical spectra. The abundance ratios from Na/Fe to Eu/Fe displayed by these and previously analysed semiregular variables are quite similar to ratios displayed by normal red giants across the Galactic thin and thick discs and halo populations in the solar neighbourhood, suggesting from this perspective that the variables may be among the more photometrically active red giants.
Empirical calibration for helium abundance determinations in active galactic nuclei
Authors: Dors O L , Almeida G C , Oliveira C B , Flury S R , Riffel R , Riffel R A , Cardaci M V , Hägele G F , Ilha G S , Krabbe A C , Arellano-Córdova K Z , Santos P C , Morais I N
Published: June 2024

For the first time, a calibration between the He i$\lambda 5876$/H $\beta$ emission line ratio and the helium abundance y = 12 + log(He/H) for Narrow line regions of Seyfert 2 Active Galactic Nuclei is proposed. In this context, observational data (taken from the SDSS-DR15 and from the literature) and direct abundance estimates (via the $T_{\rm e}$-method) for a sample of 65 local ($z \: \lt \: 0.2$) Seyfert 2 nuclei are considered. The resulting calibration estimates the y abundance with an average uncertainty of 0.02 dex. Applying our calibration to spectroscopic data containing only strong emission lines, it yields a helium abundance distribution similar to that obtained via the $T_{\rm e}$-method. Some cautions must be considered to apply our calibration for Seyfert 2 nuclei with high values of electron temperature (${\gtrsim} 20\, 000$ K) or ionization parameter ($\log U \ \gt\ {-}2.0$).
Engineering spacer specificity of the Cre/loxP system
Authors: Hoersten Jenna , Ruiz-Gómez Gloria , Paszkowski-Rogacz Maciej , Gilioli Giorgio , Guillem-Gloria Pedro Manuel , Lansing Felix , Pisabarro M Teresa , Buchholz Frank
Published: June 2024

Translational research on the Cre/loxP recombination system focuses on enhancing its specificity by modifying Cre/DNA interactions. Despite extensive efforts, the exact mechanisms governing Cre discrimination between substrates remains elusive. Cre recognizes 13 bp inverted repeats, initiating recombination in the 8 bp spacer region. While literature suggests that efficient recombination proceeds between lox sites with non-loxP spacer sequences when both lox sites have matching spacers, experimental validation for this assumption is lacking. To fill this gap, we investigated target site variations of identical pairs of the loxP 8 bp spacer region, screening 6000 unique loxP-like sequences. Approximately 84% of these sites exhibited efficient recombination, affirming the plasticity of spacer sequences for catalysis. However, certain spacers negatively impacted recombination, emphasizing sequence dependence. Directed evolution of Cre on inefficiently recombined spacers not only yielded recombinases with enhanced activity but also mutants with reprogrammed selective activity. Mutations altering spacer specificity were identified, and molecular modelling and dynamics simulations were used to investigate the possible mechanisms behind the specificity switch. Our findings highlight the potential to fine-tune site-specific recombinases for spacer sequence specificity, offering a novel concept to enhance the applied properties of designer-recombinases for genome engineering applications.
Concerted action of ataxin-2 and PABPC1-bound mRNA poly(A) tail in the formation of stress granules
Authors: Yamagishi Ryota , Inagaki Hiroto , Suzuki Jun , Hosoda Nao , Sugiyama Haruka , Tomita Kazunori , Hotta Takashi , Hoshino Shin-ichi
Published: June 2024

Stress induces global stabilization of the mRNA poly(A) tail (PAT) and the assembly of untranslated poly(A)-tailed mRNA into mRNPs that accumulate in stress granules (SGs). While the mechanism behind stress-induced global PAT stabilization has recently emerged, the biological significance of PAT stabilization under stress remains elusive. Here, we demonstrate that stress-induced PAT stabilization is a prerequisite for SG formation. Perturbations in PAT length impact SG formation; PAT shortening, achieved by overexpressing mRNA deadenylases, inhibits SG formation, whereas PAT lengthening, achieved by overexpressing their dominant negative mutants or downregulating deadenylases, promotes it. PABPC1, which specifically binds to the PAT, is crucial for SG formation. Complementation analyses reveal that the PABC/MLLE domain of PABPC1, responsible for binding PAM2 motif-containing proteins, plays a key role. Among them, ataxin-2 is a known SG component. A dominant-negative approach reveals that the PAM2 motif of ataxin-2 is essential for SG formation. Notably, ataxin-2 increases stress sensitivity, lowering the threshold for SG formation, probably by promoting the aggregation of PABPC1-bound mRNA. The C-terminal region is responsible for the self-aggregation of ataxin-2. These findings underscore the critical roles of mRNA PAT, PABPC1 and ataxin-2 in SG formation and provide mechanistic insights into this process.
YY1 is involved in homologous recombination inhibition at guanine quadruplex sites in human cells
Authors: Cui Xinyu , Zhang Chengwen , Fu Chunqing , Hu Jinglei , Li Tengjiao , Li Lin
Published: June 2024

Homologous recombination (HR) is a key process for repairing DNA double strand breaks and for promoting genetic diversity. However, HR occurs unevenly across the genome, and certain genomic features can influence its activity. One such feature is the presence of guanine quadruplexes (G4s), stable secondary structures widely distributed throughout the genome. These G4s play essential roles in gene transcription and genome stability regulation. Especially, elevated G4 levels in cells deficient in the Bloom syndrome helicase (BLM) significantly enhance HR at G4 sites, potentially threatening genome stability. Here, we investigated the role of G4-binding protein Yin Yang-1 (YY1) in modulating HR at G4 sites in human cells. Our results show that YY1’s binding to G4 structures suppresses sister chromatid exchange after BLM knockdown, and YY1’s chromatin occupancy negatively correlates with the overall HR rate observed across the genome. By limiting RAD51 homolog 1 (RAD51) access, YY1 preferentially binds to essential genomic regions, shielding them from excessive HR. Our findings unveil a novel role of YY1–G4 interaction, revealing novel insights into cellular mechanisms involved in HR regulation.
Are non-practising entities opportunistic? Evidence from litigation of standard essential patents
Authors: Love Brian J , Helmers Christian
Published: June 2024

Are non-practising entities (NPEs)—firms that specialize in the enforcement of patent rights rather than the commercialization of patented technologies—more likely than other patent enforcers to behave opportunistically? To explore this question, we construct measures of opportunistic conduct by patent enforcers and document the presence or absence of these behaviours in a subset of US patent cases in which opportunism is especially likely to occur: cases that assert standard essential patents (SEPs). Our results suggest heterogeneity across different opportunistic behaviours. NPEs are more likely to exploit the SEP-declaration process and the SEP market’s lack of transparency, while practising entities (PEs) are more likely to pursue bans on the sale and importation of their products. We additionally present evidence that opportunism can affect case outcomes. Declaration and market-related opportunism are associated with a higher rate of settlement in NPE cases relative to PE cases.
Guideline-Concordant Therapy for Community-Acquired Pneumonia in the Hospitalized Population: A Systematic Review and Meta-analysis
Authors: Seo Chanhee , Corrado Mario , Lim Rachel , Thornton Christina S
Published: June 2024

Background

A commonly used guideline for community-acquired pneumonia (CAP) is the joint American Thoracic Society and Infectious Diseases Society of America practice guideline. We aimed to investigate the effect of guideline-concordant therapy in the treatment of CAP.

Methods

We systematically searched MEDLINE, Embase, CENTRAL, Web of Science, and Scopus from 2007 to December 2023. We screened citations, extracted data, and assessed risk of bias in duplicate. Primary outcomes were mortality rates, intensive care unit (ICU) admission, and length of stay. Secondary outcomes were guideline adherence, readmission, clinical cure rate, and adverse complications. We performed random-effect meta-analysis to estimate the overall effect size and assessed heterogeneity using the I2 statistics.

Results

We included 17 observational studies and 82 240 patients, of which 10 studies were comparative and pooled in meta-analysis. Overall guideline adherence rate was 65.2%. Guideline-concordant therapy was associated with a statistically significant reduction in 30-day mortality rate (crude odds ratio [OR], 0.49 [95% confidence interval .34–.70; I2 = 60%]; adjusted OR, 0.49 [.37–.65; I2 = 52%]) and in-hospital mortality rate (crude OR, 0.63 [.43–.92]; I2 = 61%). Due to significant heterogeneity, we could not assess the effect of guideline-concordant therapy on length of stay, ICU admission, readmission, clinical cure rate, and adverse complications.

Conclusions

In hospitalized patients with CAP, guideline-concordant therapy was associated with a significant reduction in mortality rate compared with nonconcordant therapy; however, there was limited evidence to support guideline-concordant therapy for other clinical outcomes. Future studies are needed to assess the clinical efficacy and safety of current guideline recommendations.