bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stellar atmospheric parameters from Gaia BP/RP spectra using uncertain neural networks
Authors: Fallows Connor P , Sanders Jason L 
Published: May 2024

ABSTRACT
With the plentiful information available in the Gaia BP/RP spectra, there is significant scope for applying discriminative models to extract stellar atmospheric parameters and abundances. We describe an approach to leverage an ‘Uncertain Neural Network’ model trained on APOGEE data to provide high-quality predictions with robust estimates for per-prediction uncertainty. We report median formal uncertainties of 0.068 dex, 69.1 K, 0.14 dex, 0.031 dex, 0.040 dex, and 0.029 dex for [Fe/H], Teff, log g, [C/Fe], [N/Fe], and [α/M], respectively. We validate these predictions against our APOGEE training data, LAMOST, and Gaia GSP-phot stellar parameters, and see a strong correlation between our predicted parameters and those derived from these surveys. We investigate the information content of the spectra by considering the ‘attention’ our model pays to different spectral features compared to expectations from synthetic spectra calculations. Our model’s predictions are applied to the Gaia data set, and we produce a publicly available catalogue of our model’s predictions.
Quantum refraction effects in pulsar emission
Authors: Kim Dong-Hoon , Kim Chul Min , Kim Sang Pyo 
Published: May 2024

ABSTRACT
Highly magnetized neutron stars exhibit the vacuum non-linear electrodynamics effects, which can be well-described using the one-loop effective action for quantum electrodynamics. In this context, we study the propagation and polarization of pulsar radiation, based on the post-Maxwellian Lagrangian from the Heisenberg–Euler–Schwinger action. Given the refractive index obtained from this Lagrangian, we determine the leading-order corrections to both the propagation and polarization vectors due to quantum refraction via perturbation analysis. In addition, the effects on the orthogonality between the propagation and polarization vectors and the Faraday rotation angle, all due to quantum refraction are investigated. Furthermore, from the dual refractive index and the associated polarization modes, we discuss quantum birefringence, with the optical phenomenology analogous to its classical counterpart.
Spectral study of star-forming rings in S0 galaxies of Dorado group – NGC 1533 and NGC 1543
Authors: Proshina Irina S , Sil’chenko Olga K , Kniazev Alexei Yu 
Published: May 2024

ABSTRACT
We have fulfilled a detailed long-slit spectroscopic analysis for two SB0 galaxies – NGC 1533 and NGC 1543, – belonging to the Dorado group. Our spectral data reveal asymmetric decoupled kinematics of the stars and ionized gas in these barred lenticular galaxies that give evidences for external origin of the gas in the rings. We have calculated the star formation rates in the rings by using the ultraviolet fluxes of the rings corrected for the foreground and intrinsic absorption; and we have estimated parameters of the stellar populations in the inner parts of the galaxies confirming that they are old – except the nucleus of NGC 1543, which demonstrates signatures of rejuvenation less than 5 Gyr ago.
REEV: review, evaluate and explain variants
Authors: Hramyka Dzmitry , Sczakiel Henrike Lisa , Zhao Max Xiaohang , Stolpe Oliver , Nieminen Mikko , Adam Ronja , Danyel Magdalena , Einicke Lara , Hägerling René , Knaus Alexej , Mundlos Stefan , Schwartzmann Sarina , Seelow Dominik , Ehmke Nadja , Mensah Martin Atta , Boschann Felix , Beule Dieter , Holtgrewe Manuel 
Published: May 2024

Abstract
In the era of high throughput sequencing, special software is required for the clinical evaluation of genetic variants. We developed REEV (Review, Evaluate and Explain Variants), a user-friendly platform for clinicians and researchers in the field of rare disease genetics. Supporting data was aggregated from public data sources. We compared REEV with seven other tools for clinical variant evaluation. REEV (semi-)automatically fills individual ACMG criteria facilitating variant interpretation. REEV can store disease and phenotype data related to a case to use these for phenotype similarity measures. Users can create public permanent links for individual variants that can be saved as browser bookmarks and shared. REEV may help in the fast diagnostic assessment of genetic variants in a clinical as well as in a research context. REEV (https://reev.bihealth.org/) is free and open to all users and there is no login requirement.
REME: an integrated platform for reaction enzyme mining and evaluation
Authors: Shi Zhenkun , Wang Dehang , Li Yang , Deng Rui , Lin Jiawei , Liu Cui , Li Haoran , Wang Ruoyu , Zhao Muqiang , Mao Zhitao , Yuan Qianqian , Liao Xiaoping , Ma Hongwu 
Published: May 2024

Abstract
A key challenge in pathway design is finding proper enzymes that can be engineered to catalyze a non-natural reaction. Although existing tools can identify potential enzymes based on similar reactions, these tools encounter several issues. Firstly, the calculated similar reactions may not even have the same reaction type. Secondly, the associated enzymes are often numerous and identifying the most promising candidate enzymes is difficult due to the lack of data for evaluation. Thirdly, existing web tools do not provide interactive functions that enable users to fine-tune results based on their expertise. Here, we present REME (https://reme.biodesign.ac.cn/), the first integrated web platform for reaction enzyme mining and evaluation. Combining atom-to-atom mapping, atom type change identification, and reaction similarity calculation enables quick ranking and visualization of reactions similar to an objective non-natural reaction. Additional functionality enables users to filter similar reactions by their specified functional groups and candidate enzymes can be further filtered (e.g. by organisms) or expanded by Enzyme Commission number (EC) or sequence homology. Afterward, enzyme attributes (such as kcat, Km, optimal temperature and pH) can be assessed with deep learning-based methods, facilitating the swift identification of potential enzymes that can catalyze the non-natural reaction.
Proscan: a structure-based proline design web server
Authors: Felbinger Nathaniel , Ribeiro-Filho Helder V , Pierce Brian G 
Published: May 2024

Abstract
The ability to control protein conformations and dynamics through structure-based design has been useful in various scenarios, including engineering of viral antigens for vaccines. One effective design strategy is the substitution of residues to proline amino acids, which due to its unique cyclic side chain can favor and rigidify key backbone conformations. To provide the community with a means to readily identify and explore proline designs for target proteins of interest, we developed the Proscan web server. Proscan provides assessment of backbone angles, energetic and deep learning-based favorability scores, and other parameters for proline substitutions at each position of an input structure, along with interactive visualization of backbone angles and candidate substitution sites on structures. It identifies known favorable proline substitutions for viral antigens, and was benchmarked against datasets of proline substitution stability effects from deep mutational scanning and thermodynamic measurements. This tool can enable researchers to identify and prioritize designs for prospective vaccine antigen targets, or other designs to favor stability of key protein conformations. Proscan is available at: https://proscan.ibbr.umd.edu.
Comparing evidence use in parliaments: the interplay of beliefs, traditions, and practices in the UK and Germany
Authors: Geddes Marc 
Published: May 2024

Abstract
This article draws on rich qualitative data from two national parliaments—the UK House of Commons and the German Bundestag—to examine knowledge practices in political institutions. This is an important topic, not only because parliaments play a significant role in democratic decision-making, but because it sheds light on debates about how such decision-making is based on and interacts with knowledge and evidence. By adopting an interpretive analytical approach, I analyze the ways in which those practices are shaped by the beliefs and values of parliamentary actors. Indeed, in better understanding everyday practices, beliefs, and ideational traditions, it also contributes to better explaining how components of political and parliamentary cultures contribute to knowledge use more broadly. In the House of Commons, MPs draw on a highly trusted and independent parliamentary administration; meanwhile, committees have become fruitful avenues for MPs to develop policy expertise and engage with knowledge and evidence in a non-partisan way. In the German Bundestag, MPs also develop policy expertise—in fact, they interpret their role as specialists in a “working” parliament—but their knowledge practices are more openly partisan through the structuring role of parliamentary party groups and the skepticism of “neutral” advice from research services. Consequently, committees tend to be sites of political bargaining and conflict, rather than evidence-gathering. In both cases, parliaments’ knowledge practices are shaped by wider webs of beliefs about the role of MPs within the institutions. This suggests that knowledge use in political and policy settings is shaped by broader cultural factors.
Religious Leaders’ Compliance with State Authority: Experimental Evidence from COVID-19 in Pakistan
Authors: Vyborny Kate 
Published: May 2024

AbstractA randomized controlled trial in Pakistan tests whether one-on-one engagement with community religious leaders can encourage them to instruct congregants to follow government regulations. Treated religious leaders are 25 percent more likely to comply with government requirements to tell congregants they should wear a mask to prevent COVID transmission when attending prayers. Treatment effects do not depend on the religious content of the message. Effects are driven by respondents who already understand the mechanics of COVID transmission at baseline, suggesting the treatment does not work by correcting basic knowledge about the disease, but rather through a mechanism of persuasion.
Safety and Efficacy of 177Lu-DOTATATE in Children and Young Adult Population
Authors: Aggarwal Piyush , Satapathy Swayamjeet , Sood Ashwani , Singh Harmandeep , Mittal Bhagwant Rai , Lal Sadhna , Gupta Rajesh , Das Chandan Krushna , Yadav Thakur Deen , Walia Rama 
Published: May 2024

Purpose
This single-center retrospective study explores the safety and efficacy of 177Lu-DOTATATE in children and young adult population with metastatic/inoperable neuroendocrine tumors (NETs).

Patients and Methods
This study is a retrospective analysis of all children and young adult patients (≤29 years) with advanced inoperable/metastatic epithelial or nonepithelial NETs who were administered a median of 4 cycles of 177Lu-DOTATATE therapy and low-dose oral capecitabine as a radiosensitizer every 8–12 weeks, except 2 patients who received CAPTEM chemotherapy. The radiological response was assessed using RECIST 1.1 on interim and end-of-treatment 68Ga-DOTANOC PET/CT. The primary endpoint was objective response rate, whereas disease control rate, toxicity profile, progression-free survival, and overall survival were secondary endpoints.

Results
Nineteen biopsy-proven NET patients (median age, 22 ± 10 years) with 8 of them adolescents (10–18 years) and the remaining young adults (19–29 years) were included. Fourteen patients had gastroenteropancreatic neuroendocrine tumor (pancreas being most common primary site), whereas the rest had non–gastroenteropancreatic neuroendocrine tumor. A total of 65 cycles of 177Lu-DOTATATE (range, 1–6 cycles) were administered with a median cumulative activity of 600 mCi (range, 100–1000 mCi). The objective response rate and disease control rate were 41% and 94%, respectively. Grade 1 and 2 adverse events were observed in 14 (74%) and 5 (26%) of 19 patients, respectively. In a total of 8 events (42%), 4 events each of disease progression and death occurred during a median follow-up of 80.1 months with an estimated 5-year progression-free survival and overall survival of 54% (95% confidence interval, 30–78) and 63% (95% confidence interval, 39–87), respectively.

Conclusions

177Lu-DOTATATE appears safe and effective in children and young adults with metastatic/inoperable NETs. Large prospective trials are required to validate these results.
225Ac-PSMA-617 Augmentation in High-Risk mCRPC Undergoing 177Lu-PSMA-617 Radioligand Therapy
Authors: Rosar Florian , Burgard Caroline , Rohloff Luna Vanessa , Blickle Arne , Bartholomä Mark , Maus Stephan , Petto Sven , Schaefer-Schuler Andrea , Ezziddin Samer 
Published: May 2024

Purpose
This pilot study investigates the efficacy and safety profile as well as predictive biomarkers of 225Ac-PSMA-617–augmented 177Lu-PSMA-617 radioligand therapy (RLT) in a cohort of high-risk patients with metastatic castration-resistant prostate cancer (mCRPC), enrolled in a prospective registry (NCT 04833517).

Patients and Methods
A group of n = 33 high-risk mCRPC patients received 177Lu-PSMA-617 RLT, augmented by 1 or more cycles of 225Ac-PSMA-617. Response was assessed by prostate-specific antigen (PSA) serum value after 2 cycles of treatment. Overall survival (OS) and PSA-based progression-free survival were evaluated using Kaplan-Meier analysis. To assess the side effect profile, Common Terminology Criteria for Adverse Events were applied. In total, 12 potential pretherapeutic biomarkers were tested for association with OS.

Results
The median decrease in serum PSA value was −49.1%, and 16/33 (48.5%) patients experienced a partial response after 2 cycles RLT. The median PSA-based progression-free survival and median OS was 7.2 and 14.8 months, respectively. Alkaline phosphatase (P < 0.001), lactate dehydrogenase (P = 0.035), Eastern European Oncology Group Performance Score (P = 0.037), and the presence of visceral metastases (P = 0.029) revealed significant association with OS in Kaplan-Meier analysis (log-rank test). Most of the recorded adverse events were rated as mild or moderate. Higher-grade adverse events were very limited with only 1 case (3.0%) of grade 3 anemia. Treatment-related mild xerostomia was recorded in 6/33 (18.2%) patients.

Conclusions

225Ac-PSMA-617 augmentation in high-risk mCRPC undergoing 177Lu-PSMA-617 RLT appears to be an effective treatment option with a favorable safety profile. The pretherapeutic values of alkaline phosphatase, lactate dehydrogenase, the Eastern European Oncology Group Performance Score, and the presence of visceral metastases may be appropriate biomarkers predicting survival outcome of this treatment regimen.
Drop-by-drop Addition of Reagents to a Double Emulsion
Authors: Cowell Thomas W. , Jing Wenyang , Han Hee-Sun 
Published: May 2024

AbstractDevelopments in droplet microfluidic assays have facilitated an era of high-throughput, sensitive single-cell, or single-molecule measurements capable of tackling the heterogeneity present in biological systems. Relying on single emulsion (SE) compartments, droplet assays achieve absolute quantification of nucleic acids, massively parallel single-cell profiling, identification of rare variants, and more. Double emulsions (DEs) have seen new interest in recent years for their potential to enable new droplet assays and build upon SE techniques. DEs are compatible with flow cytometry enabling high-throughput multi-parameter drop screening and eliminate content mixing due to coalescence during lengthy workflows, addressing inherent limitations of SEs. Despite these strengths, DEs lack important technical functions that exist in SEs such as picoinjection or any other method for adding reagents to droplets on demand. Consequently, DEs cannot be used for multistep workflows which has limited their adoption in assay development. Here, we report a simple device achieving picoinjection of DEs. We developed strategies to enable active manipulations on DEs by converting DE inputs to SEs on chip. The released aqueous cores of the DE can be manipulated using existing SE techniques, such as reagent addition, before reforming a DE at the outlet. We identified device designs and operation conditions achieving drop-by-drop reagent addition to DEs and used it as part of a muti-step aptamer screening assay performed entirely in DE drops. This work enables the further development of multistep DE droplet assays.
Pattern of Alcohol tolerance and Adh gene Frequencies in Northern and Southern Populations of two Drosophila species from India
Authors: Shamina  
Published: May 2024

AbstractIn this study, we collected four geographical populations of Drosophila melanogaster and Drosophila ananassae from the southern and northern axes of India, spanning latitudes ranging from 13.04°N to 29.58°N. We observed significant clinal variation at the alcohol dehydrogenase (Adh) locus, with the frequency of the Adh F allele increasing by 3% and 1.5% per degree latitude in D. melanogaster and D. ananassae, respectively.Adult populations of D. melanogaster were found to tolerate ethanol concentrations ranging from 10% to 14.75%, while D. ananassae exhibited tolerance levels between 2.4% and 4.0%. These patterns of interspecific divergence in ethanol tolerance levels corresponded with their natural habitats: D. ananassae primarily utilizes fermented organic matter and fruits in the wild, while D. melanogaster exploits ethanol-rich resources found indoors. Ethanol serves as a resource at low concentrations but becomes a stressor at higher concentrations for D. ananassae. Both traits exhibited a clinal pattern that is increase in ethanol tolerance and of the frequency of Adh-F allele with latitude.Our observations suggest that D. ananassae exhibits adaptive characteristics for ethanol utilization, while D. melanogaster populations demonstrate both ethanol utilization and detoxification abilities. The observed latitudinal variation in Adh F frequency and ethanol tolerance in these two Drosophilids may be maintained by the interplay of balancing natural selection and climatic factors that vary spatially along the south-north axis of the Indian subcontinent.
Coarse-graining the recognition of a glycolipid by the C-type lectin Mincle receptor
Authors: Noriega Maxime , Corey Robin A. , Haanappel Evert , Demange Pascal , Czaplicki Georges , Atkinson R. Andrew , Chavent Matthieu 
Published: May 2024

AbstractMacrophage inducible Ca2+-dependent lectin (Mincle) receptor recognizesMycobacterium tuberculosisglycolipids to trigger an immune response. This host membrane receptor is thus a key player in the modulation of the immune response to infection byM. tuberculosis, and has emerged as a promising target for the development of new vaccines for tuberculosis. The recent development of the Martini 3 force field for coarse-grained (CG) molecular modeling allow the study of interactions of soluble proteins with small ligands but its use for the study of interactions with lipids remains less explored. Here, we present a refined approach detailing a protocol for modeling such interactions at a CG level using the Martini 3 force field. Using this approach, we studied Mincle and identified critical parameters governing ligand recognition, such as loop flexibility and the regulation of hydrophobic groove formation by calcium ions. In addition, we assessed ligand affinity using free energy perturbation calculations. Our results offer mechanistic insight into the interactions between Mincle and glycolipids, providing a basis for rational design of molecules targeting this type of membrane receptors.
Mechanical state of pre-tumoral epithelia dictates subsequent tumour aggressiveness
Authors: Montemurro Marianne , Monier Bruno , Suzanne Magali 
Published: May 2024

SUMMARYTumours evolve through the acquisition of increasingly aggressive traits associated with dysplasia. This progression is accompanied by the alteration of tumour mechanical properties, especially through extracellular matrix remodelling. However, the contribution of intrinsic tumour cells mechanics to tumour aggressiveness remains unknownin vivo.Here we show that adherens junction tension in pre-tumoral tissues dictates subsequent tumour evolution. Increased cell contractility, observed in aggressive tumours before any sign of tissue overgrowth, proved sufficient to trigger dysplasia in normally hyperplastic tumours. Unexpectedly, high contractility contributes to tumour evolution through cell death induction which favours cell-cell junctions weakening. Overall, our results highlight the need to re-evaluate the roles of tumoral cell death, and identify pre-tumour cell mechanics as an unsuspected early marker and key trigger of tumour aggressiveness.GRAPHICAL ABSTRACT
Accounting for heterogeneity due to environmental sources in meta-analysis of genome-wide association studies
Authors: Wang Siru , Ojewunmi Oyesola O. , Kamiza Abram , Ramsay Michele , Morris Andrew P , Chikowore Tinashe , Fatumo Segun , Asimit Jennifer L 
Published: May 2024

AbstractMeta-analysis of genome-wide association studies (GWAS) across diverse populations offers power gains to identify loci associated with complex traits and diseases. Often heterogeneity in effect sizes across populations will be correlated with genetic ancestry and environmental exposures (e.g. lifestyle factors). We present an environment-adjusted meta-regression model (env-MR-MEGA) to detect genetic associations by adjusting for and quantifying environmental and ancestral heterogeneity between populations. In simulations, env-MR-MEGA had similar or greater association power than MR-MEGA, with notable gains when the environmental factor had a greater correlation with the trait than ancestry. In our analysis of low-density lipoprotein cholesterol in ∼19,000 individuals across twelve sex-stratified GWAS from Africa, adjusting for sex, BMI, and urban status, we identified additional heterogeneity beyond ancestral effects for nine variants. Env-MR-MEGA provides an approach to account for environmental effects using summary-level data, making it a useful tool for meta-analyses without the need to share individual-level data.
Disruptors of sestrin-MAPK interactions rejuvenate T cells and expand TCR specificity
Authors: Lanna Alessio , D’Ambra Clara , Rinaldi Federica , Chocarro Luisa , Delpero Manuel , Capitani Melania , Karin Michael 
Published: May 2024

SummaryWhereas treatments that reactivate exhausted T cells are available, strategies to rejuvenate terminally differentiated senescent lymphocytes are yet to be developed. Senescent T cells, with short telomeres and inactive telomerase, are different from exhausted cells, and may form due to defective telomere transfer reactions upon contact with antigen presenting cells (APCs). Senescent T cells are characterized by presence of sestrin-MAPK kinase activation complexes (sMACs), large immune-inhibitory protein assemblies of sestrins bound to a stress/energy sensing kinase (AMPK) and three functional effector kinases (ERK, JNK and p38 MAPKs). Here we described first in class Disruptors of the Sestrin-MAPK immune-inhibitory Complex (DOS), which target sMAC to ubiquitin-dependent proteasomal degradation, resulting in long-term sestrin transcriptional inhibition, increased T cell fitness, and generation of long-lived stem like memory features. Strikingly, the DOS generated stem T cells presentde novoantigen-specific T-cell receptor DNA rearrangements that precede their future expansion. Although largely senescent at the point of treatment, the DOS regenerated T cells, with stem features and new TCRs, initiated immune-protective rejuvenation-dependent responses to new challenges, with or without vaccination. Therefore, it is possible to generate new T cell clones from formerly senescent cells and expand immune specificity.HighlightsDOS are the first sestrin-MAPK binding disruptorsDOS rejuvenate T cells (DOS-juvenation)DOS-juvenated T cells protect old mice from lethal infections, with or without vaccinationDOS-juvenated T cells exist as stem-like cells that undergo antigen-specific TCR revisions