bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglia complement signaling promotes neuronal elimination and normal brain functional connectivity
Authors: Deivasigamani Senthilkumar , Miteva Mariya T , Natale Silvia , Gutierrez-Barragan Daniel , Basilico Bernadette , Di Angelantonio Silvia , Weinhard Laetitia , Molotkov Dmitry , Deb Sukrita , Pape Constantin , Bolasco Giulia , Galbusera Alberto , Asari Hiroki , Gozzi Alessandro , Ragozzino Davide , Gross Cornelius T 
Published: September 2023

Abstract
Complement signaling is thought to serve as an opsonization signal to promote the phagocytosis of synapses by microglia. However, while its role in synaptic remodeling has been demonstrated in the retino-thalamic system, it remains unclear whether complement signaling mediates synaptic pruning in the brain more generally. Here we found that mice lacking the Complement receptor 3, the major microglia complement receptor, failed to show a deficit in either synaptic pruning or axon elimination in the developing mouse cortex. Instead, mice lacking Complement receptor 3 exhibited a deficit in the perinatal elimination of neurons in the cortex, a deficit that is associated with increased cortical thickness and enhanced functional connectivity in these regions in adulthood. These data demonstrate a role for complement in promoting neuronal elimination in the developing cortex.
Rifampin Based Therapy for Patients With Staphylococcus aureus Native Vertebral Osteomyelitis: A Systematic Review and Meta-analysis
Authors: El Zein Said , Berbari Elie F , Passerini Matteo , Petri Francesco , Maamari Julian , Murad M Hassan , Sendi Parham , Tande Aaron J 
Published: September 2023

Abstract

Background
Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO.

Methods
We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI).

Results
Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, −14%; 95% CI, −19% to −8%; P &lt; .001; I 2 = 0%; relative risk, 0.58; 95% CI, .37–.92, P = .02, I 2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low.

Conclusions
Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.
Effects of social capital on healthcare utilization among older adults in Indonesia
Authors: Ekadinata Nopryan , Hsu Hui-Chuan , Chen Ya-Mei , Chuang Kun-Yang 
Published: September 2023

Abstract
Social capital potentially affects older adults’ access to healthcare services. However, the effects of social capital on the use of various types of healthcare services using longitudinal data have yet to be explored. This study aimed to examine the effects of structural and cognitive social capital on different types of healthcare utilization by older adults in Indonesia. Data were from the Indonesian Family Life Survey (waves 4 and 5) in 2007 and 2014. The sample consisted of participants aged 60 years and older who completed both waves (n = 1374). Healthcare utilization by older adults assessed health posts (posyandu), health checkups, outpatient care and hospital admissions. Social capital consisted of neighborhood trust and community participation. Generalized estimating equation models were used for the analysis. Older adults with high community participation had a higher likelihood of using preventive care in posyandu (OR = 5.848, 95% CI = 2.585–13.232) and health checkup visits (OR = 1.621, 95% CI = 1.116–2.356). Meanwhile, neighborhood trust was related to a higher probability of hospital admissions (OR = 1.255, 95% CI = 1.046–1.505). Social capital significantly affects older adults’ preventive and treatment healthcare utilization. Maximizing the availability of social participation and removing barriers to access to preventive and medical care in an age-friendly environment are suggested.
Cardiolipin deficiency leads to the destabilization of mitochondrial magnesium channel MRS2 in Barth syndrome
Authors: Joshi Alaumy , Gohil Vishal M 
Published: September 2023

Abstract
Barth syndrome (BTHS) is a debilitating X-linked cardio-skeletal myopathy caused by loss-of-function mutations in TAFAZZIN, a cardiolipin (CL)-remodeling enzyme required for the maintenance of normal levels of CL species in mitochondrial membranes. At present, how perturbations in CL abundance and composition lead to many debilitating clinical presentations in BTHS patients have not been fully elucidated. Inspired by our recent findings that CL is essential for optimal mitochondrial calcium uptake, we measured the levels of other biologically important metal ions in BTHS mitochondria and found that in addition to calcium, magnesium levels are significantly reduced. Consistent with this observation, we report a decreased abundance of the mitochondrial magnesium influx channel MRS2 in multiple models of BTHS including yeast, murine myoblast, and BTHS patient cells and cardiac tissue. Mechanistically, we attribute reduced steady-state levels of MRS2 to its increased turnover in CL-deficient BTHS models. By expressing Mrs2 in well-characterized yeast mutants of the phospholipid biosynthetic pathways, we demonstrate a specific requirement of CL for Mrs2 abundance and assembly. Finally, we provide in vitro evidence for the direct binding of CL with human MRS2. Together, our study has identified a critical requirement of CL for MRS2 stability and suggests perturbation of mitochondrial magnesium homeostasis as a novel contributing factor to BTHS pathology.
Sex Differences in Plasma, Adipose Tissue, and Central Accumulation of Cannabinoids, and Behavioral Effects of Oral Cannabis Consumption in Male and Female C57BL/6 Mice
Authors: Sallam Nada A , Peterson Colleen S , Baglot Samantha L , Kohro Yuta , Trang Tuan , Hill Matthew N , Borgland Stephanie L 
Published: September 2023

Abstract

Background
Cannabis edibles are an increasingly popular form of cannabis consumption. Oral consumption of cannabis has distinct physiological and behavioral effects compared with injection or inhalation. An animal model is needed to understand the pharmacokinetics and physiological effects of oral cannabis consumption in rodents as a model for human cannabis edible use.

Methods
Adult male and female C57BL/6 mice received a single dose of commercially available cannabis oil (5 mg/kg Δ⁹-tetrahydrocannabinol [THC]) by oral gavage. At 0.5, 1, 2, 3, and 6 hours post exposure, plasma, hippocampus, and adipose tissue were collected for THC, 11-OH-THC, and THC-COOH measures.

Results
We report delayed time to peak THC and 11-OH-THC concentrations in plasma, brain, and adipose tissue, which is consistent with human pharmacokinetics studies. We also found sex differences in the cannabis tetrad: (1) female mice had a delayed hypothermic effect 6 hours post consumption, which was not present in males; (2) females had stronger catalepsy than males; (3) males were less mobile following cannabis exposure, whereas female mice showed no difference in locomotion but an anxiogenic effect at 3 hours post exposure; and (4) male mice displayed a longer-lasting antinociceptive effect of oral cannabis.

Conclusions
Oral cannabis consumption is a translationally relevant form of administration that produces similar physiological effects as injection or vaping administration and thus should be considered as a viable approach for examining the physiological effects of cannabis moving forward. Furthermore, given the strong sex differences in metabolism of oral cannabis, these factors should be carefully considered when designing animal studies on the effects of cannabis.
New Directions in the Study of Populism in International Relations
Authors: Chryssogelos Angelos , Jenne Erin K , LaRoche Christopher David , Verbeek Bertjan , Zaslove Andrej , Destradi Sandra , Cadier David , Coticchia Fabrizio , Donelli Federico , Lequesne Christian 
Published: September 2023

Abstract
In recent years, there has been a growing interest in the international dimensions of populism, by now a major political phenomenon around the world. This interest, however, has been confined largely to the state level, especially the influence of populism on foreign policy. In this Forum, we argue that it is important for analysis to move beyond the state level and view populism as a concept and phenomenon of international relations (IR) rather than simply a factor of foreign policy. The Forum discusses implications of the rise of populism for IR theory, the role of international systemic change in the emergence of populism in national arenas, and the ways that regime type, state structure and institutions, ideational content, and the political strategies of populists condition the impact of populism on world politics. In this way, the Forum identifies specific directions for the study of populism in IR that scholars can follow in the future.
Human papillomavirus vaccination and anal high-grade precancerous lesions and cancer—a real-world effectiveness study
Authors: Baandrup Louise , Maltesen Thomas , Dehlendorff Christian , Kjaer Susanne K 
Published: September 2023

Abstract

Background
Human papillomavirus (HPV) vaccination has shown high efficacy against anal HPV infection and lesions in clinical trials, and the HPV prevalence and type distribution in anal precancers and cancer predict a high preventable potential for HPV vaccination. However, the real-world effectiveness of HPV vaccination against anal high-grade lesions and cancer is yet to be shown.

Methods
We investigated HPV vaccine effectiveness against anal high-grade squamous intraepithelial lesion (HSIL) or worse in a nationwide cohort including all Danish women aged 17-32 years during October 2006 to December 2021 (n = 968 881). HPV vaccinations and first occurrence of anal HSIL or worse were retrieved from nationwide registries. Women were considered vaccinated after first dose and classified by age at vaccination. Using Cox regression, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for anal HSIL or worse according to vaccination status.

Results
During follow-up, the number of incident histological anal HSIL or worse cases was 37 in unvaccinated women, and less than 5 and 26 in women vaccinated at ages younger than 17 years and 17-32 years, respectively. The overall number of cancers was less than 5. Compared with unvaccinated women, the risk of histological anal HSIL or worse was reduced for women vaccinated at age younger than 17 years (HR = 0.30, 95% CI = 0.10 to 0.87). For women vaccinated at age 17-32 years, the hazard rate of anal HSIL or worse was 1.21 (95% CI = 0.73 to 2.03).

Conclusion
This is the first study to demonstrate that HPV vaccination at a younger age is associated with substantially reduced risk of anal HSIL or worse in the general population.
Reconstructing the Antarctic ice-sheet shape at the Last Glacial Maximum using ice-core data
Authors: Turner Fiona E , Buck Caitlin E , Jones Julie M , Sime Louise C , Vallet Irene Malmierca , Wilkinson Richard D 
Published: September 2023

Abstract
The Antarctic ice sheet (AIS) is the Earth’s largest store of frozen water; understanding how it changed in the past allows us to improve projections of how it, and sea levels, may change. Here, we use previous AIS reconstructions, water isotope ratios from ice cores, and simulator predictions of the relationship between the ice-sheet shape and isotope ratios to create a model of the AIS at the Last Glacial Maximum. We develop a prior distribution that captures expert opinion about the AIS, generate a designed ensemble of potential shapes, run these through the climate model HadCM3, and train a Gaussian process emulator of the link between ice-sheet shape and isotope ratios. To make the analysis computationally tractable, we develop a preferential principal component method that allows us to reduce the dimension of the problem in a way that accounts for the differing importance we place in reconstructions, allowing us to create a basis that reflects prior uncertainty. We use Markov chain Monte Carlo to sample from the posterior distribution, finding shapes for which HadCM3 predicts isotope ratios closely matching observations from ice cores. The posterior distribution allows us to quantify the uncertainty in the reconstructed shape, a feature missing in other analyses.
Diagnosis of mucormycosis using a simple duplex PCR assay: Analysis of 160 clinical samples from COVID-19 patients
Authors: Aboutalebian Shima , Erami Mahzad , Ahsaniarani Amir Hossein , Momen-Heravi Mansooreh , Sharif Alireza , Hadipour Mahboubeh , Mirhendi Hossein 
Published: September 2023

Abstract
Early diagnosis of mucormycosis, a severe and potentially fatal complication in immunocompromised and COVID-19 patients, is crucial for initiating timely antifungal therapy and reducing infection mortality. In this study, the diagnostic performance of a duplex polymerase chain reaction (PCR) assay was evaluated to detect Mucorales-specific and Rhizopus oryzae-specific targets in 160 clinical samples collected from 112 COVID-19 patients suspected of invasive fungal rhinosinusitis (IFRS). During potassium hydroxide (KOH) direct microscopy, non-septate hyphae were observed in 73 out of 160 samples (45.63%); however, using duplex PCR, 82 out of 160 specimens (51.25%) tested positive. Among the positive PCR samples, 67 (81.71%) exhibited a double band (both 175 and 450 base pairs [bp]) indicating the presence of R. oryzae, and 15 (18.29%) showed only a single band (175 bp), suggesting the presence of non-R. oryzae Mucorales. DNAs from 10 microscopically negative samples and 4 samples with septate hyphae in microscopy were successfully amplified in PCR. Considering Calcofluor white fluorescence microscopy as the gold standard for laboratory diagnosis of mucormycosis, the duplex PCR assay utilized in this study exhibited a sensitivity of 93.88%, a specificity of 100%, a negative predictive value of 91.18%, and a positive predictive value of 100% for detecting mucormycosis in IFRS specimens. The duplex PCR assay demonstrated higher sensitivity compared to direct examination with KOH (82 vs. 73) and culture (82 vs. 41), enabling rapid detection/identification of Mucorales even in samples with negative culture or in biopsies with only a few hyphal elements.
Selection of Compton-thick AGN from a hard photometric sample using XMM–Newton observations
Authors: Mostafa Reham , Guainazzi Matteo , Ibrahim Alaa 
Published: September 2023

ABSTRACT
We present a selection technique to detect Compton-thick (CT) active galactic nuclei (AGNs) in the 3XMM/SDSS-DR7 cross-correlation. A subsample of 3481 X-ray sources that are detected in the hard band (2–8 keV) and have photometric redshifts constitute our parent sample. We first applied an automated spectral-fitting procedure to select highly absorbed sources (NH &gt; 1023 cm−2). We found 184 highly absorbed candidates. Then, we performed the Bayesian Monte Carlo Markov chains (MCMCs) selection technique to find CT AGNs. We also tested the MCMC selection technique by applying Monte Carlo simulations. We found that the method is accurate at 90 per cent independently of the nature of the underlying source. Our sample contains 52 bona fide CT AGNs. The CT AGNs were selected to have a range &gt;0.75 of probability of being CT when either fitting with the two models Torus and MYTorus. About 75 per cent of CT AGNs in our sample had probabilities &gt;90 per cent. From the spectral analysis, we significantly found an anticorrelation between the equivalent width of the neutral Fe K α line and the X-ray luminosity at 2–10 keV, the so-called X-ray Baldwin effect.
Contributions of histone tail clipping and acetylation in nucleosome transcription by RNA polymerase II
Authors: Oishi Takumi , Hatazawa Suguru , Kujirai Tomoya , Kato Junko , Kobayashi Yuki , Ogasawara Mitsuo , Akatsu Munetaka , Ehara Haruhiko , Sekine Shun-ichi , Hayashi Gosuke , Takizawa Yoshimasa , Kurumizaka Hitoshi 
Published: September 2023

Abstract
The N-terminal tails of histones protrude from the nucleosome core and are target sites for histone modifications, such as acetylation and methylation. Histone acetylation is considered to enhance transcription in chromatin. However, the contribution of the histone N-terminal tail to the nucleosome transcription by RNA polymerase II (RNAPII) has not been clarified. In the present study, we reconstituted nucleosomes lacking the N-terminal tail of each histone, H2A, H2B, H3 or H4, and performed RNAPII transcription assays. We found that the N-terminal tail of H3, but not H2A, H2B and H4, functions in RNAPII pausing at the SHL(-5) position of the nucleosome. Consistently, the RNAPII transcription assay also revealed that the nucleosome containing N-terminally acetylated H3 drastically alleviates RNAPII pausing at the SHL(-5) position. In addition, the H3 acetylated nucleosome produced increased amounts of the run-off transcript. These results provide important evidence that the H3 N-terminal tail plays a role in RNAPII pausing at the SHL(-5) position of the nucleosome, and its acetylation directly alleviates this nucleosome barrier.
Golden Standard: a complete standard, portable, and interoperative MoClo tool for model and non-model proteobacteria
Authors: Blázquez Blas , León David San , Torres-Bacete Jesús , Gómez-Luengo Álvaro , Kniewel Ryan , Martínez Igor , Sordon Sandra , Wilczak Aleksandra , Salgado Sergio , Huszcza Ewa , Popłoński Jarosław , Prieto Auxiliadora , Nogales Juan 
Published: September 2023

Abstract
Modular cloning has become a benchmark technology in synthetic biology. However, a notable disparity exists between its remarkable development and the need for standardization to facilitate seamless interoperability among systems. The field is thus impeded by an overwhelming proliferation of organism-specific systems that frequently lack compatibility. To overcome these issues, we present Golden Standard (GS), a Type IIS assembly method underpinned by the Standard European Vector Architecture. GS unlocks modular cloning applications for most bacteria, and delivers combinatorial multi-part assembly to create genetic circuits of up to twenty transcription units (TUs). Reliance on MoClo syntax renders GS fully compatible with many existing tools and it sets the path towards efficient reusability of available part libraries and assembled TUs. GS was validated in terms of DNA assembly, portability, interoperability and phenotype engineering in α-, β-, γ- and δ-proteobacteria. Furthermore, we provide a computational pipeline for parts characterization that was used to assess the performance of GS parts. To promote community-driven development of GS, we provide a dedicated web-portal including a repository of parts, vectors, and Wizard and Setup tools that guide users in designing constructs. Overall, GS establishes an open, standardized framework propelling the progress of synthetic biology as a whole.
DO GENOMIC ALTERATIONS INflUENCE THE DEVELOPMENT OF BRAIN METASTASES IN ADVANCED AND METASTATIC NON-SMALL CELL LUNG CANCER? A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Gillespie Conor , Mustafa Mohammad , Richardson George , Alam Ali , Lee Keng Siang , Hughes David , Escriu Carles , Zakaria Rasheed 
Published: September 2023

Abstract

AIMS
Establish prevalence at diagnosis, and incidence of BM in patients with advanced and metastatic non-small cell lung cancer (NSCLC), stratified by genomic alterations.

METHOD
A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO ID CRD42022315915). Three databases were searched (Search date 30th April 2022). Prevalence at diagnosis, and per-patient year incidence of brain metastases were obtained, including patients with EGFR, ALK, KRAS, ROS1, RET, and other genomic alterations. Pooled incidence rates were calculated using random effects models.

RESULTS
Of 960 articles identified, 65 were included (24,784 patients). The combined BM prevalence at diagnosis was 28.6% (45 studies, 95% Confidence Interval [CI] 26.1-31.0). Median follow-up was 24 months (Interquartile range [IQR] 16-36 months). The combined incidence of BM development was 10.8% per year (40 studies, 95% CI 9.2- 12.6). The per-year incidence of new BM was 15.6%/year in the EGFR +ve group (16 studies, 95% CI 11.4-21.2), 17.0% in the ALK+ve group (7 studies, 95% CI 11.3-25.8), 9.8% in the KRAS +ve group (4 studies, 95% CI 5.5-17.5), 12.5% in the ROS1 +ve group (3 studies, 95% CI 5.7-27.6), and 11.8% in the RET +ve group (2 studies, 95% CI 8.0-17.5). Combined overall prevalence was 55.0% (21 studies, IQR 44.2-67.8).

CONCLUSIONS
This systematic review indicates a high rate of brain metastases in NSCLC and is the first and only study to describe incidence, stratified by genomic alterations. This will have a major clinical impact by stratifying brain imaging at staging and follow-up by patient subgroup, particularly in ALK and EGFR mutations.
SYSTEMATIC IDENTIfiCATION OF CONTEXT-DEPENDENT GENE-ESSENTIALITY IN GLIOBLASTOMA: THE GBM-CODE PLATFORM
Authors: Foster Mitchell , Ewing Ailith , Frame Margaret , Brennan Paul , Khamseh Ava , Beentjes Sjoerd , Carragher Neil , Semple Colin 
Published: September 2023

Abstract

AIMS
Glioblastoma (GBM) is a heterogeneous and aggressive brain tumour that is invariably fatal despite maximal treatment. GBM-relevant ‘biomarkers’ (such as known driver-mutations or cell-states) could be used to stratify patients for treatments. However, pairing biomarkers with appropriate therapeutic ‘targets’ is challenging. If a gene is more essential in GBM cells which contain such a biomarker, inhibiting the gene product may be therapeutically useful in GBM tumours where that biomarker is present.

METHOD
We describe a novel computational tool which distils new translational insights from existing disparate large- scale biological data (genomics, transcriptomics and functional genomics data from 60 distinct patient-derived, IDH-wildtype, adult GBM cell lines) using Targeted Learning (a subfield of mathematics and causal machine learning) to systematically identify context-dependent gene essentiality in Glioblastoma (GBM-CoDE).

RESULTS
We derived multiple target-biomarker pair hypotheses, two of which (WWTR1 is more essential in EGFR- mutated/amplified GBM, and VRK1 is more essential in VRK2-methylated GBM) have recently been published by external groups, implying that our additional novel findings may be valid. We developed an interactive plat- form to make our findings accessible to other researchers to prioritise pairs for experimental validation and subsequent translation.

CONCLUSIONS
GBM-CoDE represents a potent new approach to solving the problem of developing patient-tailored therapeutics in GBM, made possible with recent innovations in computational biology. While the majority of these target- biomarker hypotheses have yet to be experimentally validated, our results may in time accelerate effective translation to biomarker stratified clinical trials in GBM. Our method is translatable to other cancers of unmet need.