bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico evidence of bitopertin’s broad interactions within the SLC6 transporter family
Authors: de Carvalho Gustavo Almeida , Tambwe Paul Magogo , Nascimento Lucas Rodrigues Couto , Campos Bruna Kelly Pedrosa , Chiareli Raphaela Almeida , Junior Guilhermino Pereira Nunes , Menegatti Ricardo , Gomez Renato Santiago , Pinto Mauro Cunha Xavier 
Published: July 2024

Abstract
The Glycine Transporter Type 1 (GlyT1) significantly impacts central nervous system functions, influencing glycinergic and glutamatergic neurotransmission. Bitopertin, the first GlyT1 inhibitor in clinical trials, was developed for schizophrenia treatment but showed limited efficacy. Despite this, bitopertin’s repositioning could advance treating various pathologies. This study aims to understand bitopertin’s mechanism of action using computational methods, exploring off-target effects, and providing a comprehensive pharmacological profile. Similarity Ensemble Approach (SEA) and SwissTargetPrediction initially predicted targets, followed by molecular modeling on SWISS-MODEL and GalaxyWeb servers. Binding sites were identified using PrankWeb, and molecular docking was performed with DockThor and GOLD software. Molecular dynamics analyses were conducted on the Visual Dynamics platform. Reverse screening on SEA and SwissTargetPrediction identified GlyT1 (SLC6A9), GlyT2 (SLC6A5), PROT (SLC6A7), and DAT (SLC6A3) as potential bitopertin targets. Homology modeling on SwissModel generated high-resolution models, optimized further on GalaxyWeb. PrankWeb identified similar binding sites in GlyT1, GlyT2, PROT, and DAT, indicating potential interaction. Docking studies suggested bitopertin’s interaction with GlyT1 and proximity to GlyT2 and PROT. Molecular dynamics confirmed docking results, highlighting bitopertin’s target stability beyond GlyT1. The study concludes that bitopertin potentially interacts with multiple SLC6 family targets, indicating a broader pharmacological property.
Overcoming drought: life traits driving tree strategies to confront drought stress
Authors: Nadal-Sala Daniel , Ruehr Nadine K , Sabaté Santiago 
Published: July 2024

Abstract
This insight article comments on:
Ziegler C, Cochard, H, Stahl C, Bastien Gérard LF, Goret J, Heuret P, Levionnois S, Maillard P, Bonal D, Coste S. 2024. Residual water losses mediate the trade-off between growth and drought survival across saplings of 12 tropical rainforest tree species with contrasting hydraulic strategies. Journal of Experimental Botany 75, 4128–4147.
Growth on Douglas fir media facilitatesCryptococcusvirulence factor production and enhances fungal survival against environmental and immune stressors
Authors: Stempinski Piotr R , Greengo Seth D , Casadevall Arturo 
Published: July 2024

AbstractThe yeasts Cryptococcus neoformans and Cryptococcus gattii are fungal pathogens that can be isolated from the environment, including the surfaces of many plants. Cryptococcus gattii caused an outbreak on Vancouver Island, British Columbia beginning in 1999 that has since spread to the Pacific Northwest of the United States. Coastal Douglas fir (Pseudotsuga menziesii) is an important lumber species and a major component of the ecosystems in this area. Previous research has explored Cryptococcus survival and mating on Douglas fir plants and plant-derived material, but no studies have been done on the production of cryptococcal virulence factors by cells grown on those media. Here, we investigated the effects of growth on Douglas fir-derived media on the production of the polysaccharide capsule and melanin, two of the most important cryptococcal virulence factors. We found that while the capsule was mostly unchanged by growth in Douglas fir media compared to cells grown in defined minimal media, Cryptococcus spp. can use substrates present in Douglas fir to synthesize functional and protective melanin. These results suggest mechanisms by which Cryptococcus species may survive in the environment and emphasize the need to explore how association with Douglas fir trees could affect its epidemiology for human cryptococcosis.
Identification and antifungal susceptibility profile of uncommon yeast species at Fattouma Bourguiba University Hospital in Tunisia
Authors: Belgacem Sameh , Chebil Wissal , Ben Salem Safa , Babba Oussama , Mastouri Maha , Babba Hamouda 
Published: July 2024

Abstract
Despite the severe impact of uncommon yeast fungal infections and the pressing need for more research on the topic, there are still few studies available on the identification, epidemiology, and susceptibility profile of those pathogens. The aims of the current study were to define the profile of uncommon yeast species at Fattouma Bourguiba University Hospital using phenotypic, molecular, and proteomic methods and to study their antifungal susceptibility profile. Pre-identified uncommon yeast species were collected from 2018 to 2021. These isolates were further identified using phenotypic methods (ID32C® system and Vitek2® YST), matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), and sequencing. The antifungal susceptibility profile was studied using the reference CLSI broth microdilution method. In total, 30 strains were collected during the study period. Referring to the sequencing, the most isolated uncommon species were Saprochaete capitata, Candida lusitaniae, Candida kefyr, Candida inconspicua, and Candida guilliermondii. A total of 90% of isolates were correctly identified by MALDI-TOF MS compared to 76.7% and 63.3% by ID32® C and VITEK® 2 YST, respectively. The isolated species showed variable responses to antifungals. Candida guilliermondii showed increased azole minimum inhibitory concentrations. Misidentification of uncommon yeast species was common using commercial phenotypic methods. The high percentage of concordance of MALDI-TOF results with sequencing highlights its high performance and usefulness as a routine diagnosis tool.
Extended GeV γ-ray emission around the massive star forming region of the W3 complex
Authors: Wu Qi-Hang , Sun Xiao-Na , Yang Rui-Zhi , Ge Ting-Ting , Liang Yun-Feng , Liang En-Wei 
Published: July 2024

ABSTRACT
We analyse the GeV γ-ray emission from the W3 complex using about 14 years of Pass 8 data recorded by the Fermi Large Area Telescope (Fermi-LAT). We resolve the γ-ray emissions around W3 into two components: an elliptical Gaussian overlapping with the molecular gas and a point-like source near the cluster W3 Main. The pion-bump feature of SED for the elliptical Gaussian together with the better fitting result of pion decay model favour the hadronic origin. We further argue that the cosmic rays (CRs) could originate from the interactions between cluster winds and the shock produced by the SNR HB3. The point-like source positionally coincident with the star cluster W3 Main indicates it may be directly powered by near clusters, while its fainter γ-ray emissions below 10 GeV are possibly due to the shelter from dense gas making the low-energy CRs incapable of penetrating the dense materials. Meanwhile, we cannot rule out that the γ-ray emissions originate from the interaction of accelerated protons in SNR with the ambient gas.
Entrainment of hot gas into cold streams: the origin of excessive star formation rates at cosmic noon
Authors: Aung Han , Mandelker Nir , Dekel Avishai , Nagai Daisuke , Semenov Vadim , van den Bosch Frank C 
Published: July 2024

ABSTRACT
We explore the evolution of cold streams from the cosmic web that feed galaxies through their shock-heated circumgalactic medium (CGM) at cosmic noon, $z\simeq 1-5$. In addition to the hydrodynamical instabilities and radiative cooling that we have incorporated in earlier works, we embed the stream and the hot CGM in the gravitational potential of the host dark matter halo, deriving equilibrium profiles for both. Self-gravity within the stream is tentatively ignored. We find that the cold streams gradually entrain a large mass of initially hot CGM gas that cools in the mixing layer and condenses onto the stream. This entrainment, combined with the acceleration down the gravitational potential well, typically triples the inward cold inflow rate into the central galaxy, compared to the original rate at the virial radius, which makes the entrained gas the dominant source of gas supply to the galaxy. The potential sources for the hot gas to be entrained are recycled enriched gas that has been previously ejected from the galaxy, and fresh virial-shock-heated gas that has accumulated in the CGM. This can naturally elevate the star formation rate in the galaxy by a factor of $\sim 3$ compared to the gas accretion rate onto the halo, thus explaining the otherwise puzzling observed excess of star formation at cosmic noon. When accounting for self-shielding of dense gas from the ultraviolet background, we find that the energy radiated from the streams, originating predominantly from the cooling of the entrained gas, is consistent with observed Lyman-$\alpha$ blobs around galaxies.
The Thousand-Pulsar-Array programme on MeerKAT – XV. A comparison of the radio emission properties of slow and millisecond pulsars
Authors: Karastergiou A , Johnston S , Posselt B , Oswald L S , Kramer M , Weltevrede P 
Published: July 2024

ABSTRACT
We use data from the MeerTime project on the MeerKAT telescope to ask whether the radio emission properties of millisecond pulsars (MSPs) and slowly rotating, younger pulsars (SPs) are similar or different. We show that the flux density spectra of both populations are similarly steep, and the widths of MSP profiles obey the same dependence on the rotational period as slow pulsars. We also show that the polarization of MSPs has similar properties to slow pulsars. The commonly used pseudo-luminosity of pulsars, defined as the product of the flux density and the distance squared, is not appropriate for drawing conclusions about the relative intrinsic radio luminosity of SPs and MSPs. We show that it is possible to scale the pseudo-luminosity to account for the pulse duty cycle and the solid angle of the radio beam, in such a way that MSPs and SPs do not show clear differences in intrinsic luminosity. The data therefore support common emission physics between the two populations in spite of orders of magnitude difference in their period derivatives and inferred, surface, dipole magnetic field strengths.
Deep learning insights into non-universality in the halo mass function
Authors: Guo Ningyuan , Lucie-Smith Luisa , Peiris Hiranya V , Pontzen Andrew , Piras Davide 
Published: July 2024

ABSTRACT
The abundance of dark matter haloes is a key cosmological probe in forthcoming galaxy surveys. The theoretical understanding of the halo mass function (HMF) is limited by our incomplete knowledge of the origin of non-universality and its cosmological parameter dependence. We present a deep-learning model which compresses the linear matter power spectrum into three independent factors which are necessary and sufficient to describe the $z=0$ HMF from the state-of-the-art Aemulus emulator to sub-per cent accuracy in a wCDM$+N_\mathrm{eff}$ parameter space. Additional information about growth history does not improve the accuracy of HMF predictions if the matter power spectrum is already provided as input, because required aspects of the former can be inferred from the latter. The three factors carry information about the universal and non-universal aspects of the HMF, which we interrogate via the information-theoretic measure of mutual information. We find that non-universality is captured by recent growth history after matter-dark-energy equality and $N_{\rm eff}$ for $M\sim 10^{13} \, \mathrm{M_\odot }\, h^{-1}$ haloes, and by $\Omega _{\rm m}$ for $M\sim 10^{15} \, \mathrm{M_\odot }\, h^{-1}$. The compact representation learnt by our model can inform the design of emulator training sets to achieve high emulator accuracy with fewer simulations.
Towards a holistic magnetic braking model – II: explaining several long-term internal- and surface-spin properties of solar-like stars and the Sun
Authors: Sarkar Arnab , Eggenberger Patrick , Yungelson Lev , Tout Christopher A 
Published: July 2024

ABSTRACT
We extend our model of magnetic braking (MB), driven by an α–Ω dynamo mechanism, from fully convective M-dwarfs (FCMDs) to explain the surface and internal spin $P_\mathrm{spin}$ evolution of partly convective dwarfs (PCDs) starting from the disc-dispersal stage to the main-sequence turn-off. In our model, the spin of the core is governed by shear at the core-envelope boundary while the spin of the envelope is governed by MB and shear. We show that (1) the most massive FCMDs experience a stronger spin-down than PCDs and less massive FCMDs, (2) the stalled spin-down and enhanced activity of K-dwarfs and the pile-up of G-dwarfs older than a few Gyr are stellar-structure and MB-dependent, and weakly dependent on core-envelope coupling effects, (3) our expression of the core-envelope convergence time-scale $\tau _{\text{converge}}(M_\ast , P_{\text{spin}})$ between a few 10 to 100 Myr strongly depends on stellar structure but weakly on MB strength and shear, such that fast and massive rotators achieve corotation earlier, (4) our estimates of the surface magnetic fields are in general agreement with observations and our wind mass loss evolution explains the weak winds from the solar analog $\pi ^1$ UMa, and (5) with our model the massive young Sun hypothesis as a solution to the faint young Sun problem can likely be ruled out, because the maximum mass lost by winds from our Sun with our model is about an order of magnitude smaller than required to solve the problem.
Targeting HTR2B suppresses nonfunctioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis
Authors: Lin Shaojian , Wang Liangbo , Han Changxi , Dai Yuting , Li Changsheng , Liu Yanting , Zhang Bo , Huang Ning , Zhang Anke , Zhang Tao , Wang Yu , Xie Jing , Tang Hao , Cheng Yijun , Yao Hong , Lou Meiqing , Xue Li , Wu Zhe Bao 
Published: July 2024

Abstract

Background
Managing nonfunctioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline’s (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential.

Methods
We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays.

Results
Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066.

Conclusions
HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.
Pan-cancer integrative analyses dissect the remodeling of endothelial cells in human cancers
Authors: Li Jinhu , Wang Dongfang , Tang Fei , Ling Xinnan , Zhang Wenjie , Zhang Zemin 
Published: July 2024

ABSTRACT
Therapeutics targeting tumor endothelial cells (TECs) have been explored for decades, with only suboptimal efficacy achieved, partly due to an insufficient understanding of the TEC heterogeneity across cancer patients. We integrated single-cell RNA-seq data of 575 cancer patients from 19 solid tumor types, comprehensively charting the TEC phenotypic diversities. Our analyses uncovered underappreciated compositional and functional heterogeneity in TECs from a pan-cancer perspective. Two subsets, CXCR4+ tip cells and SELE+ veins, represented the prominent angiogenic and proinflammatory phenotypes of TECs, respectively. They exhibited distinct spatial organization patterns, and compared to adjacent non-tumor tissues, tumor tissue showed an increased prevalence of CXCR4+ tip cells, yet with SELE+ veins depleted. Such functional and spatial characteristics underlie their differential associations with the response of anti-angiogenic therapies and immunotherapies. Our integrative resources and findings open new avenues to understand and clinically intervene in the tumor vasculature.
Implementation of an Approach to Equitable Allocation of SARS-CoV-2 Monoclonal Antibodies for Preexposure Prophylaxis: Experience From a Single Medical Center
Authors: Hamilton Keith W , Hua Elvis , Dutcher Lauren , Fernandez Lynch Holly , Junker Paul , Doucette Abigail G , Werner Danielle , Kannel Ethan Z , Civitello Thomas , Gabriel Peter , Ahya Vivek N , Jacobs Dina A , Garfall Alfred , Pratz Keith , Degnan Kathleen O , Blumberg Emily A , Capozzi Donna , Craig Ethan , Takach Patricia , Payne Aimee S , Geara Abdallah , Koenig Helen , Holzman Lawrence , Tebas Pablo 
Published: July 2024

Abstract

Background
During the COVID-19 pandemic, SARS-CoV-2 monoclonal antibodies for preexposure prophylaxis (SMA-PrEP) offered patients who were immunocompromised another option for protection. However, SMA-PrEP posed administrative, operational, and ethical challenges for health care facilities, resulting in few patients receiving them. Although the first SMA-PrEP medication, tixagevimab and cilgavimab, had its authorization revoked due to compromised in vitro efficacy, new SMA-PrEP medications are currently completing clinical trials. This article provides an operational framework for administrative organization, patient identification and prioritization, equitable medication allocation, medication ordering and administration, and patient tracking.

Methods
A retrospective cohort study evaluating our hospital's SMA-PrEP administration strategy was performed. Multivariable logistic regression was used to examine factors associated with receipt of SMA-PrEP.

Results
Despite the barriers in administering this medication and the scarcity of resources, our hospital was able to administer at least 1 dose of SMA-PrEP to 1359 of 5902 (23.0%) eligible patients. Even with the steps taken to promote equitable allocation, multivariable logistic regression demonstrated that there were still differences by race, ethnicity, and socioeconomic status. As compared with patients who identified as Black, patients who identified as White (odds ratio [OR], 1.85; 95% CI, 1.46–2.33), Asian (OR, 1.59; 95% CI, 1.03–2.46), and Hispanic (OR, 1.53; 95% CI, 1.02–2.44) were more likely to receive SMA-PrEP. When compared with patients with low socioeconomic status, patients with high socioeconomic status (OR, 1.37; 95% CI, 1.05–1.78) were more likely to be allocated SMA-PrEP.

Conclusions
Despite efforts to mitigate health care disparities, differences by race/ethnicity and socioeconomic status still arose in patients receiving SMA-PrEP.
Understanding variants of unknown significance and classification of genomic alterations
Authors: Pavlick Dean C , Frampton Garrett M , Ross Jeffrey R 
Published: July 2024

Abstract
Despite recent efforts to issue clinical guidelines outlining strategies to define the pathogenicity of genomic variants, there is currently no standardized framework for which to make these assertions. This review does not present a step-by-step methodology, but rather takes a holistic approach to discuss many aspects which should be taken into consideration when determining variant pathogenicity. Categorization should be curated to reflect relevant findings within the scope of the specific medical context. Functional characterization should evaluate all available information, including results from literature reviews, different classes of genomic data repositories, and applicable computational predictive algorithms. This article further proposes a multidimensional view to infer pathogenic status from many genomic measurements across multiple axes. Notably, tumor suppressors and oncogenes exhibit fundamentally different biology which helps refine the importance of effects on splicing, mutation interactions, copy number thresholds, rearrangement annotations, germline status, and genome-wide signatures. Understanding these relevant datapoints with thoughtful perspective could aid in the reclassification of variants of unknown significance (VUS), which are ambiguously understood and currently have uncertain clinical implications. Ongoing assessments of VUS examining these relevant biological axes could lead to more accurate classification of variant pathogenicity interpretation in diagnostic oncology.
Genomic, immunologic, and prognostic associations of TROP2 (TACSTD2) expression in solid tumors
Authors: Morgenstern-Kaplan Dan , Kareff Samuel A , Trabolsi Asaad , Rodriguez Estelamari , Krause Harris , Ribeiro Jennifer R , Tan Heng , Antonarakis Emmanuel S , Lou Emil , Nagasaka Misako , Algaze Sandra , Lenz Heinz-Josef , Liu Stephen V , Halmos Balazs , Hoon Dave S B , Seeber Andreas , Ma Patrick C , El-Deiry Wafik S , Vanderwalde Ari M , Lopes Gilberto 
Published: July 2024

Abstract

Background
TROP2 (TACSTD2) expression is associated with decreased overall survival (OS) in some solid tumors, and the TROP2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan has been approved in breast and urothelial carcinomas. We aimed to explore the multi-omic landscape associated with TACSTD2 gene expression in various solid tumors to identify patients most likely to benefit from this approach.

Methods
Breast (N = 11 246), colorectal (N = 15 425), hepatocellular (N = 433), pancreatic (N = 5488), and urothelial (N = 4125) tumors were stratified into quartiles by TACSTD2 gene expression, analyzed by next-generation DNA sequencing, whole transcriptome sequencing, and immunohistochemistry at Caris Life Sciences (Phoenix, AZ). Survival data were obtained from insurance claims, and Kaplan-Meier estimates were calculated for molecularly defined cohorts.

Results
Several pathogenic mutations were associated with TACSTD2-high tumors, including TP53 in breast, colorectal (CRC), pancreatic, and hepatocellular cancers; KRAS in pancreatic and CRC cancers; ARID1A and FGFR3 in urothelial cancer; and CTNNB1 in hepatocellular cancer. TACSTD2-low breast tumors were enriched for copy number amplifications in CCND1 and FGF/R family member genes. TACSTD2 high was generally associated with more immune cell infiltration and greater T-cell inflammation scores. Patients with TACSTD2-high breast, CRC, and pancreatic cancers demonstrated a significantly shorter OS than TACSTD2-low tumors. This was restricted to CRC with microsatellite stable tumors and patients with pancreatic cancer with KRAS-mutant tumors. Patients with breast cancer with TACSTD2-high tumors also experienced significantly worse OS following immune checkpoint inhibitors.

Conclusions
TACSTD2 expression is associated with key driver alterations and a more active immune microenvironment, suggesting possible combinatorial strategies with TROP2-targeting ADCs plus immunotherapy in various solid tumors.