bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoresponsive gene 1 facilitates TLR4 agonist-induced augmentation of innate antimicrobial immunity
Authors: McBride Margaret A , Caja Katherine R , Patil Tazeen K , Owen Allison M , Luan Liming , Bohannon Julia K , Hernandez Antonio , Stothers Cody L , Trenary Irina A , Rahim Mohsin , Young Jamey D , Calcutt M Wade , Stephens Victoria R , Davis Xenia , Oliver Mary A , Hao Dan , Si Clara , McRae Malik , Nguyen Kenny K , Davis Nicholas S , Wang Jingbin , Patil Naeem K , Sherwood Edward R 
Published: October 2024

Abstract
Treatment with the toll-like receptor 4 agonist monophosphoryl lipid A conditions innate immunocytes to respond robustly to subsequent infection, a phenotype termed innate immune memory. Our published studies show that metabolic reprogramming of macrophages is a prominent feature of the memory phenotype. We undertook studies to define the functional contributions of tricarboxylic acid cycle reprogramming to innate immune memory. We observed that priming of wild-type mice with monophosphoryl lipid A potently facilitated accumulation of the tricarboxylic acid cycle metabolite itaconate at sites of infection and enhanced microbial clearance. Augmentation of itaconate accumulation and microbial clearance was ablated in Irg1-deficient mice. We further observed that monophosphoryl lipid A potently induces expression of Irg1 and accumulation of itaconate in macrophages. Compared to wild-type macrophages, the ability of Irg1-deficient macrophages to kill Pseudomonas aeruginosa was impaired. We further observed that itaconate is directly antimicrobial against P. aeruginosa at pH 5, which is characteristic of the phagolysosome, and is facilitated by reactive oxygen species. Monophosphoryl lipid A–induced augmentation of glycolysis, oxidative phosphorylation, and accumulation of the tricarboxylic acid cycle metabolites succinate and malate was decreased in Irg1 knockout macrophages compared to wild-type controls. RNA sequencing revealed suppressed transcription of genes associated with phagolysosome function and increased expression of genes associated with cytokine production and chemotaxis in Irg1-deficient macrophages. This study identifies a contribution of itaconate to monophosphoryl lipid A–induced augmentation of innate antimicrobial immunity via facilitation of microbial killing as well as impact on metabolic and transcriptional adaptations.
Ad26.COV2.S COVID-19 Vaccine Safety And Immunogenicity in Adolescents 16–17 Years of Age
Authors: Ruiz-Guiñazú Javier , Le Gars Mathieu , Cárdenas Vicky , Vaissière Nathalie , Sadoff Jerald , Truyers Carla , Hendriks Jenny , Scheper Gert , de Groot A Marit , Struyf Frank , Schuitemaker Hanneke , Douoguih Macaya 
Published: September 2024

Abstract
2.5 × 1010 vp Ad26.COV2.S elicited robust SARS-CoV-2–specific antibody responses in adolescents through 6 months, with acceptable safety and reactogenicity profiles. Compared with adults immunized with 5 × 1010 vp Ad26.COV2.S, adolescents had higher antibody levels, despite being vaccinated with a lower dose.
Five earthenware Mandaic incantation bowls in Ābgīne Museum, Tehrān
Authors: Šafiʿī Ibrāhīm 
Published: September 2024

Abstract
This article presents the editio princeps of the Mandaic texts of five incantation bowls housed in Ābgīne Museum, Tehrān (627–S, 626–S, 110–S, 109–S and 108–S). Presumably dated to the 6th-7th centuries, the texts include protective formulae and name of the clients for whom they were written. The texts of 627–S and 626–S are written in a spiral manner, 110–S and 109–S are written in four segments and 108–S, which includes some of the earliest attested evidence of šapta ḏ-pišra ḏ-ainia, with the text arranged as a spoke, like sunrays.
Real-World Data Versus Probability Surveys for Estimating Health Conditions at the State Level
Authors: Marker David A , Hilton Charity , Zelko Jacob , Duke Jon , Rolka Deborah , Kaufmann Rachel , Boyd Richard 
Published: September 2024

Abstract
Government statistical offices worldwide are under pressure to produce statistics rapidly and for more detailed geographies, to compete with unofficial estimates available from web-based big data sources or from private companies. Commonly suggested sources of improved health information are electronic health records and medical claims data. These data sources are collectively known as real-world data (RWD) because they are generated from routine health care processes, and they are available for millions of patients. It is clear that RWD can provide estimates that are more timely and less expensive to produce—but a key question is whether or not they are very accurate. To test this, we took advantage of a unique health data source that includes a full range of sociodemographic variables and compared estimates using all of those potential weighting variables versus estimates derived when only age and sex are available for weighting (as is common with most RWD sources). We show that not accounting for other variables can produce misleading and quite inaccurate health estimates.
Sexual and reproductive health: level of knowledge and source of information in adolescence
Authors: Zamponi Virginia , Mazzilli Rossella , Nimbi Filippo Maria , Ciocca Giacomo , French Deborah , Limoncin Erika , Lombardo Francesco , Sesti Franz , Todaro Elisabetta , Tenuta Marta , Caserta Donatella , Tubaro Andrea , Gianfrilli Daniele , Faggiano Antongiulio 
Published: October 2024

Abstract

Background
To date, there is a lack of a structured national plan of sexual education in Italy, with large interregional differences and poor uniformity in the promotion and learning of sexual health.

Aim
The aim of this study was to evaluate the level of knowledge on sexuality and reproductive function among adolescents before and after a sexual education program, considering gender differences in the results.

Methods
A longitudinal and interventional study was conducted on high school students. Six sessions for each class were carried out by a multidisciplinary team. Anonymous questionnaires were administered to investigate basic knowledge of human sexuality and reproduction before and after intervention.

Outcomes
Participants were high school students who completed the questionnaires. Outcomes included pre and posttest answers on the knowledge questionnaire in study population.

Results
We obtained data from 842 high school students (mean ± SD age, 16.11 ± 1.74 years). The main informative sources on sexuality were social media in 37.9% of participants; family, school, and scientific material were the main source in 15.1%, 5.2%, and 4.4%, respectively. A total score of 12.6 ± 3.4 (range, 1-20) was obtained on the knowledge questionnaire; specifically, the score was higher in females than males (12.8 ± 3.4 vs 11.9 ± 3.4, P = .0001). In males and females, a statistically significant increase in level of knowledge was found after the multidisciplinary intervention (14.5 ± 3.6, P = .0001).

Clinical Implications
The lack of sexual education programs in schools in Italy compels adolescents to refer to frequently unreliable sources, such as social media and peers, contributing to misinformation and adoption of risky sexual behaviors.

Strengths and Limitations
This study is based on a large sample size and highlights the importance of sexual education programs. The main limitations are a greater representation of the female population and the inclusive nature of the school (ie, an artistic school), attracting students who identify with sexual minorities.

Conclusions
Adolescents have limited knowledge about sexuality and reproduction, with a notable gender disparity; sexual education programs in schools, providing information from sexuality experts, led to a substantial increase in knowledge and a reduction in the gender gap.
Simulated analogues I: apparent and physical evolution of young binary protostellar systems
Authors: Tuhtan Vito , Al-Belmpeisi Rami , Christensen Mikkel Bregning , Kuruwita Rajika , Haugbølle Troels 
Published: September 2024

ABSTRACT
Protostellar binaries harbour complex environment morphologies. Observations represent a snapshot in time, and projection and optical depth effects impair our ability to interpret them. Careful comparison with high-resolution models that include the larger star-forming region can help isolate the driving physical processes and give context in the time domain to the observations. We carry out four zoom-in simulations with au scale resolution that result in three binaries and a single star. For the first time ever, we follow the detailed evolution of a protobinary in a full molecular cloud context until a circumbinary disc forms. We investigate the gas dynamics around the young stars and extract disc sizes. Using radiative transfer, we obtain the evolutionary tracer Tbol of the binary systems. We find that the centrifugal radius in prestellar cores is a poor estimator of the resulting disc size due to angular momentum transport at all scales. For binaries, the disc sizes are regulated periodically by the binary orbit, having larger radii close to the apastron. The bolometric temperature differs systematically between edge-on and face-on views and shows a high-frequency time dependence correlated with the binary orbit and a low-frequency time dependence with larger episodic accretion events. These oscillations can cause the appearance of the system to change rapidly from class 0 to class I and, for short periods, even bring it to class II. The highly complex structure in early stages, as well as the binary orbit itself, affects the classical interpretation of protostellar classes, and the direct translation to evolutionary stages has to be done with caution and include other evolutionary indicators such as the extent of envelope material.
JWST/NIRISS and HST: Exploring the improved ability to characterize exoplanet atmospheres in the JWST era
Authors: Fisher Chloe , Taylor Jake , Parmentier Vivien , Kitzmann Daniel , Birkby Jayne L , Radica Michael , Barstow Joanna , Yang Jingxuan , Morello Giuseppe 
Published: September 2024

ABSTRACT
The Hubble Space Telescope has been a pioneering instrument for studying the atmospheres of exoplanets, specifically its WFC3 and STIS instruments. With the launch of JWST, we are able to observe larger spectral ranges at higher precision. NIRISS/SOSS covers the range 0.6–2.8 microns, and thus, it can serve as a direct comparison to WFC3 (0.8–1.7 microns). We perform atmospheric retrievals of WFC3 and NIRISS transmission spectra of WASP-39 b in order to compare their constraining power. We find that NIRISS is able to retrieve precise $\mathrm{H_{2}O}$ abundances that do not suffer a degeneracy with the continuum level due to the coverage of multiple spectral features. We also combine these data sets with spectra from STIS and find that challenges associated with fitting the steep optical slope can bias the retrieval results. In an effort to diagnose the differences between the WFC3 and NIRISS retrievals, we perform the analysis again on the NIRISS data cut to the same wavelength range as WFC3. We find that the water abundance is in strong disagreement with both the WFC3 and full NIRISS retrievals, highlighting the importance of wide wavelength coverage. Finally, we carry out mock retrievals on the different instruments, which shows further evidence of the challenges in constraining water abundance from the WFC3 data alone. Our study demonstrates the vast information gain of JWST’s NIRISS instrument over WFC3, highlighting the insights to be obtained from our new era of space-based instruments.
Combining Nanopore direct RNA sequencing with genetics and mass spectrometry for analysis of T-loop base modifications across 42 yeast tRNA isoacceptors
Authors: Shaw Ethan A , Thomas Niki K , Jones Joshua D , Abu-Shumays Robin L , Vaaler Abigail L , Akeson Mark , Koutmou Kristin S , Jain Miten , Garcia David M 
Published: September 2024

Abstract
Transfer RNAs (tRNAs) contain dozens of chemical modifications. These modifications are critical for maintaining tRNA tertiary structure and optimizing protein synthesis. Here we advance the use of Nanopore direct RNA-sequencing (DRS) to investigate the synergy between modifications that are known to stabilize tRNA structure. We sequenced the 42 cytosolic tRNA isoacceptors from wild-type yeast and five tRNA-modifying enzyme knockout mutants. These data permitted comprehensive analysis of three neighboring and conserved modifications in T-loops: 5-methyluridine (m5U54), pseudouridine (Ψ55), and 1-methyladenosine (m1A58). Our results were validated using direct measurements of chemical modifications by mass spectrometry. We observed concerted T-loop modification circuits—the potent influence of Ψ55 for subsequent m1A58 modification on more tRNA isoacceptors than previously observed. Growing cells under nutrient depleted conditions also revealed a novel condition-specific increase in m1A58 modification on some tRNAs. A global and isoacceptor-specific classification strategy was developed to predict the status of T-loop modifications from a user-input tRNA DRS dataset, applicable to other conditions and tRNAs in other organisms. These advancements demonstrate how orthogonal technologies combined with genetics enable precise detection of modification landscapes of individual, full-length tRNAs, at transcriptome-scale.
The Swi5–Sfr1 complex regulates Dmc1- and Rad51-driven DNA strand exchange proceeding through two distinct three-stranded intermediates by different mechanisms
Authors: Ito Kentaro , Maki Takahisa , Kanamaru Shuji , Takahashi Masayuki , Iwasaki Hiroshi 
Published: September 2024

Abstract
In eukaryotes, Dmc1 and Rad51 are key proteins of homologous recombination. The Swi5–Sfr1 complex in fission yeast, a conserved auxiliary factor, stimulates DNA strand exchange driven by both Dmc1 and Rad51. Interestingly, biochemical analysis suggested that Swi5–Sfr1 regulates strand exchange activities of these recombinases differently, but the mechanisms were unclear. We previously developed a real-time system to analyze Rad51-driven DNA strand exchange and identified two topologically distinct three-stranded intermediates (complex 1 (C1) and complex 2 (C2)). Swi5–Sfr1 facilitates the C1–C2 transition and releases single-stranded DNA (ssDNA) from C2, acting as a strand exchange activator. In this study, we investigated fission yeast Dmc1-driven DNA strand exchange and the role of Swi5–Sfr1 in Dmc1 activity in real-time. Kinetic analysis revealed a three-step model for the Dmc1-driven reaction, similar to that of Rad51. Although Swi5–Sfr1 stimulated the Dmc1-driven reaction, it had a weaker impact than Rad51. Furthermore, Swi5–Sfr1 enhanced the association of Dmc1 with ssDNA by promoting filament nucleus formation, acting as a mediator, unlike its role with Rad51. This stimulation mechanism also differs from that of Ca2+ or ATP analog, AMP–PNP. Our findings suggest that Swi5–Sfr1 stimulates strand exchange activities of Dmc1 and Rad51 via different reaction steps.
Intravenous methylprednisolone for nephrotic syndrome with minimal change lesions in adults: a randomized controlled trial
Authors: Chen Jinxia , Li Ruting , Guo Hua , Zhu Tianyu , Xu Yongzhi , Yao Cuiwei , Liu Huafeng 
Published: September 2024

ABSTRACT

Background
Patients with minimal change nephrotic syndrome (MCNS) usually experience severe oedema, which can affect the absorption of oral corticosteroid during the first 2 weeks. We conducted a randomized controlled trial (RCT) to compare the efficacy of intravenous (IV) isovalent methylprednisolone induction followed by oral prednisone therapy with conventional oral prednisone therapy in highly oedematous MCNS patients, aiming to provide a better therapy for MCNS patients.

Methods
A single-centre, open-label, parallel-arm RCT was performed in the Nephrology Department of the Affiliated Hospital of Guangdong Medical University. Patients who met the inclusion criteria were enrolled in our study from May 2015 to October 2020 and were randomized to receive conventional oral steroid or 2 weeks of IV methylprednisolone followed by oral prednisone.

Results
A total of 117 patients were enrolled and randomly assigned to either the sequential group (n = 57) or the oral group (n = 60). The total remission rate in the sequential group was higher than in the oral group after treatment for 2 weeks and 4 weeks (P = .032, P = .027). The complete remission (CR) rate was higher in the sequential group than in the oral group (63.3% versus 41.5%; P = .031) after treatment for 2 weeks. The time to achieve CR was shorter in the sequential group than in the oral group, with a statistically significant difference {14.0 days [95% confidence interval (CI) 13.5–14.5] versus 16.0 days [95% CI 12.7–19.3], P = .024}. There were no significant differences in relapse rate (24.5% versus 28.3%; P = .823) and time to relapse (155 ± 103 days versus 150.7 ± 103.7 days; P = .916) between two groups.

Conclusion
This study suggested that highly oedematous MCNS patients who received IV isovalent methylprednisolone induction therapy followed by oral prednisone achieved earlier remission than the conventional oral prednisone regimen without differences in relapse rates or adverse effects. Short-term IV methylprednisolone followed by oral prednisone may be a better choice for MCNS patients with severe oedema.
Targeted radionuclide therapy for patients with central nervous system metastasis: Overlooked potential?
Authors: Le Rhun Emilie , Albert Nathalie L , Hüllner Martin , Franceschi Enrico , Galldiks Norbert , Karschnia Philipp , Minniti Giuseppe , Weiss Tobias , Preusser Matthias , Ellingson Benjamin M , Weller Michael 
Published: October 2024

Abstract
Targeted radionuclide therapy is an emerging therapeutic concept for metastatic cancer that can be considered if a tumor can be delineated by nuclear medicine imaging and also targeted based on the expression of a particular target (thera-nostics). This mode of treatment can also compete with or supplement conventional radiotherapy, for example, if MRI does not fully capture the extent of the disease, including microscopic metastases. Targeted radionuclide therapy for patients with thyroid cancer, with certain somatostatin receptor 2-expressing tumors and with prostate-specific membrane antigen-expressing prostate cancer is approved, and numerous approaches of targeted radionuclide therapy for patients with metastatic cancer are in development (eg, using fibroblast activation protein as a target). Although brain metastases are rare in cancers with approved targeted radionuclide therapies, there is no a priori reason to assume that such treatments would not be effective against brain metastases if the targets are expressed and not shielded by the blood-brain barrier. Here, we discuss the current state of the art and opportunities of targeted radionuclide therapies for patients with brain and leptomeningeal metastases.
Current views on mechanisms of the FLASH effect in cancer radiotherapy
Authors: Ma Yuqi , Zhang Wenkang , Zhao Ziming , Lv Jianfeng , Chen Junyi , Yan Xueqin , Lin XiaoJi , Zhang Junlong , Wang Bingwu , Gao Song , Xiao Jie , Yang Gen 
Published: October 2024

ABSTRACT
FLASH radiotherapy (FLASH-RT) is a new modality of radiotherapy that delivers doses with ultra-high dose rates. The FLASH effect was defined as the ability of FLASH-RT to suppress tumor growth while sparing normal tissues. Although the FLASH effect has been proven to be valid in various models by different modalities of irradiation and clinical trials of FLASH-RT have achieved promising initial success, the exact underlying mechanism is still unclear. This article summarizes mainstream hypotheses of the FLASH effect at physicochemical and biological levels, including oxygen depletion and free radical reactions, nuclear and mitochondria damage, as well as immune response. These hypotheses contribute reasonable explanations to the FLASH effect and are interconnected according to the chronological order of the organism's response to ionizing radiation. By collating the existing consensus, evidence and hypotheses, this article provides a comprehensive overview of potential mechanisms of the FLASH effect and practical guidance for future investigation in the field of FLASH-RT.
Ivermectin-Based Mass Drug Administration for Scabies in Northern India: A Single-Arm Community Intervention Trial
Authors: Engelman Daniel , Singh Rajesh , Woodall Hannah J , O’Brien Howard , Singh Raj Kumari , Zhu Xilin , Grobler Anneke C , Thomas Molly , Steer Andrew C , Grills Nathan 
Published: October 2024

Abstract

Background
Scabies and impetigo cause direct health effects and contribute to severe infectious and immune-mediated complications. Ivermectin-based mass drug administration can reduce scabies and impetigo prevalence in island settings with high prevalence, but the effectiveness in moderate-prevalence settings is not known.

Methods
We conducted a single-arm, before–after community intervention trial. Mass drug administration was offered to the entire population of 4 villages in Uttarakhand, India. The treatment consisted of 2 doses, given 7 days apart, of oral ivermectin (∼200 μg/kg), or topical 5% permethrin if ivermectin was contraindicated. The primary outcome was the prevalence of scabies at 12 months compared with baseline, as diagnosed using clinical assessment and the 2020 International Alliance for the Control of Scabies criteria. Secondary outcomes included the prevalence of impetigo at each time point. The trial was registered with the Australian and New Zealand Trials Registry (ACTRN12619001712190).

Results
In January 2020, 1211 participants were enrolled (100% of the estimated village population). Treatment coverage was high—1204 (99.4%) and 1177 (97.2%) received 1 and 2 doses, respectively. Scabies was diagnosed in 91 participants (7.5%) and impetigo in 15 (1.2%). In February 2021, 1190 (98.3% of baseline) participants re-enrolled, and of these 11 had scabies (0.9%; relative risk reduction, 87.7%; 95% CI, 77.1%–93.4%) and 5 had impetigo (0.4%; relative risk reduction, 66.1%; 95% CI, 7.0%–87.6%).

Conclusions
A single round of ivermectin-based mass drug administration substantially reduced the prevalence of scabies and impetigo in this setting with moderate scabies prevalence in northern India.
Meta-analysis of platinum chemotherapy combinations with immunotherapy in metastatic urothelial carcinoma
Authors: Bolek Hatice , Yazgan Satı Coskun , Yekedüz Emre , Ürün Yüksel 
Published: September 2024

Abstract
The therapeutic landscape for metastatic urothelial carcinoma (mUC) has evolved significantly due to the development of innovative combination treatments, including enfortumab vedotin-pembrolizumab (EVP). Despite these advancements, the limited availability of EVP means that platinum-based chemotherapy regimens continue to serve as the primary treatment modality for many patients with mUC. We evaluated the effect of the type of platinum chemotherapy used in combination with immunotherapy (IO) on treatment outcomes in mUC. The meta-analysis showed that cisplatin-gemcitabine plus IO combination and carboplatin-gemcitabine plus IO combination improve progression-free survival compared to platinum-gemcitabine therapy (hazard ratio [HR] = 0.71, 95% CI: 0.62-0.82; P &lt; .0001 and HR = 0.85, 95% CI: 0.73-0.98; P &lt; .03, respectively). However, only the cisplatin-gemcitabine plus IO combination showed overall survival (OS) benefit (HR = 0.80, 95% CI: 0.69-0.93; P &lt; .003). In comparison to the platinum-gemcitabine combination, neither the cisplatin-gemcitabine plus IO nor the carboplatin-gemcitabine plus IO combinations demonstrated an objective response rate (ORR) benefit. In summary, combining cisplatin-gemcitabine with immunotherapy offers significant overall survival benefits in mUC. The exact mechanisms—whether cisplatin’s immunomodulatory effects or patient demographic differences—are yet to be determined, necessitating further research to understand these outcomes better.