bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial N-glycomics of the normal breast microenvironment reveals fucosylated and high-mannose N-glycan signatures related to BI-RADS density and ancestry
Authors: Rujchanarong Denys , Spruill Laura , Sandusky George E , Park Yeonhee , Mehta Anand S , Drake Richard R , Ford Marvella E , Nakshatri Harikrishna , Angel Peggi M 
Published: June 2024

Abstract
Higher breast cancer mortality rates continue to disproportionally affect black women (BW) compared to white women (WW). This disparity is largely due to differences in tumor aggressiveness that can be related to distinct ancestry-associated breast tumor microenvironments (TMEs). Yet, characterization of the normal microenvironment (NME) in breast tissue and how they associate with breast cancer risk factors remains unknown. N-glycans, a glucose metabolism-linked post-translational modification, has not been characterized in normal breast tissue. We hypothesized that normal female breast tissue with distinct Breast Imaging and Reporting Data Systems (BI-RADS) categories have unique microenvironments based on N-glycan signatures that varies with genetic ancestries. Profiles of N-glycans were characterized in normal breast tissue from BW (n = 20) and WW (n = 20) at risk for breast cancer using matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). A total of 176 N-glycans (32 core-fucosylated and 144 noncore-fucosylated) were identified in the NME. We found that certain core-fucosylated, outer-arm fucosylated and high-mannose N-glycan structures had specific intensity patterns and histological distributions in the breast NME dependent on BI-RADS densities and ancestry. Normal breast tissue from BW, and not WW, with heterogeneously dense breast densities followed high-mannose patterns as seen in invasive ductal and lobular carcinomas. Lastly, lifestyles factors (e.g. age, menopausal status, Gail score, BMI, BI-RADS) differentially associated with fucosylated and high-mannose N-glycans based on ancestry. This study aims to decipher the molecular signatures in the breast NME from distinct ancestries towards improving the overall disparities in breast cancer burden.
Impact of institutional variables on centre performance in long-term survival after heart transplant
Authors: McDonald Weston E , Shorbaji Khaled , Kilcoyne Maxwell , Few William , Welch Brett , Hashmi Zubair , Kilic Arman 
Published: June 2024

Abstract

OBJECTIVES
The gold standard metric for centre-level performance in orthotopic heart transplantation (OHT) is 1-year post-OHT survival. However, it is unclear whether centre performance at 1 year is predictive of longer-term outcomes. This study evaluated factors impacting longer-term centre-level performance in OHT.

METHODS
Patients who underwent OHT in the USA between 2010 and 2021 were identified using the United Network of Organ Sharing data registry. The primary outcome was 5-year survival conditional on 1-year survival following OHT. Multivariable Cox proportional hazard models assessed the impact of centre-level 1-year survival rates on 5-year survival rates. Mixed-effect models were used to evaluate between-centre variability in outcomes.

RESULTS
Centre-level risk-adjusted 5-year mortality conditional on 1-year survival was not associated with centre-level 1-year survival rates [hazard ratio: 0.99 (0.97–1.01, P = 0.198)]. Predictors of 5-year mortality conditional on 1-year survival included black recipient race, pre-OHT serum creatinine, diabetes and donor age. In mixed-effect modelling, there was substantial variability between centres in 5-year mortality rates conditional on 1-year survival, a finding that persisted after controlling for recipient, donor and institutional factors (P &lt; 0.001). In a crude analysis using Kaplan–Meier, the 5-year survival conditional on 1-year survival was: low volume: 86.5%, intermediate volume: 87.5%, high volume: 86.7% (log-rank P = 0.52). These measured variables only accounted for 21.4% of the between-centre variability in 5-year mortality conditional on 1-year survival.

CONCLUSIONS
Centre-level risk-adjusted 1-year outcomes do not correlate with outcomes in the 1- to 5-year period following OHT. Further research is needed to determine what unmeasured centre-level factors contribute to longer-term outcomes in OHT.
Linking epidemiological and genomic data in cases of enteric fever in England to inform clinical management and public health action
Authors: Buczkowska Matylda , Chattaway Marie A , Jenkins Claire , Hungerford Daniel , Katwa Parisha , Kirkbride Hilary , Hawker Jeremy 
Published: June 2024

Abstract

Objectives
To explore the feasibility of linking data from enhanced surveillance patient questionnaires from each enteric fever case in England with genome sequencing data, including antimicrobial resistance (AMR) profiles, from the corresponding isolate of typhoidal salmonellae.

Methods
After linking data we interrogated the merged dataset and assessed the utility of passive surveillance data to match and monitor antimicrobial treatment regimens in enteric fever patients with the AMR profiles of the infectious agent.

Results
A high proportion of cases were given antibiotics (n = 1230/1415; 86.9%); half of the cases stated the class of antibiotic they were given (n = 630/1239) and half were prescribed cephalosporins (n = 316/630). Reported treatment with a combination of antibiotics increased with symptom severity. Nearly half of isolates (n = 644/1415; 45.5%) had mutations conferring resistance to ciprofloxacin. Based on genome-derived AMR profiles, typhoidal salmonellae isolates inferred to be susceptible to the recommended first-line antimicrobials were twice as likely to be isolated from individuals residing in the least deprived areas compared with the most deprived (n = 26/169; 15.4% versus n = 32/442; 7.2%).

Conclusions
Due to the high proportion of missing data obtained from patient interviews, we recommend a more transparent and systematic approach to recording the antibiotic prescription details by healthcare professionals in primary and secondary care. A more robust approach to data capture at this point in the care pathway would enable us to audit inconsistencies in the prescribing algorithms across England and ensure equitable treatment across all sections of society. Integrating prescribing data with the genome-derived AMR profiles of the causative agent at the individual patient level provides an opportunity to monitor the impact of treatment on clinical outcomes, and to promote best practice in real time.
Therapeutic drug monitoring of linezolid and exploring optimal regimens and a toxicity-related nomogram in elderly patients: a multicentre, prospective, non-interventional study
Authors: Liu Tingting , Yuan Yaping , Wang Chao , Wu Jionghe , Wang Yajuan , Na Peng , Chen Xiaomin , Rao Weiqiao , Zhao Jing , Wang Dan , Wang Haiyan , Duan Zhimei , Xie Fei , Fang Xiangqun , Xie Lixin , Li Hongxia 
Published: June 2024

Abstract

Background
The concentrations of linezolid, its optimal regimen and the associated side effects in elderly patients remain unclear.

Methods
In this multicentre, prospective study, elderly patients receiving linezolid at four tertiary hospitals in Beijing between May 2021 and December 2022 were included. Linezolid concentrations and haematological toxicity were monitored dynamically. Risk factors for linezolid overexposure and moderate-to-severe linezolid-induced thrombocytopenia (M/S LIT) were analysed, and a predictive model of M/S LIT was developed.

Results
A total of 860 linezolid concentrations were measured in 313 patients. The median trough concentrations of linezolid were 24.4 (15.3, 35.8) mg/L at 36–72 h and 26.1 (17.0, 38.1) mg/L at 5–10 days (P = 0.132). Severe linezolid exposure was independently associated with age, estimated glomerular filtration rate (eGFR) and the worst SOFA score (SOFA1), and we further recommended dose regimens for elderly patients based on these findings. The incidences of linezolid-induced thrombocytopenia(LIT) and M/S LIT were 73.5% and 47.6%, respectively. M/S LIT was independently correlated with treatment duration, average trough concentration (TDMa), baseline platelet count, eGFR and baseline SOFA score (SOFA0). The developed nomogram predicted M/S LIT with an area under the curve of 0.767 (95% CI 0.715–0.820), a sensitivity of 71.1% and a specificity of 73.2%.

Conclusions
Linezolid trough concentrations increased dramatically in the elderly, by about 10 mg/L in patients aged 65–80 years, followed by a further increase of 10 mg/L for every 10 years of age. Therapeutic drug monitoring is recommended in elderly patients receiving linezolid. The developed nomogram may predict M/S LIT and guide dosage adjustments of linezolid.
Clinical trial registration number: ChiCTR2100045707
Application of multi-component seismic data in identifying dolomite reservoirs in the Sichuan Basin
Authors: Chen Kang , Zhang Guangzhi , Di Guidong , Guo Xin , Wen Long , Ran Qi , Ma Hualing , Dai Juncheng 
Published: June 2024

Abstract
A comprehensive drilling of wells has been conducted in the Permian Qixia Formation in the central Sichuan Basin, revealing a significant number of dolomite reservoirs. High- and medium-porosity dolomite reservoirs are the main gas-producing reservoirs in the Qixia Formation. Seismic PP-wave data show a “bright spot” for high-porosity dolomite reservoir formations but weak responses for medium-porosity dolomite reservoir formations, which is attributed to the inability of P waves to distinguish between medium-porosity reservoirs and limestone. However, medium-porosity dolomite and limestone have different S-wave velocities. Therefore, in this study, the identification of different-porosity dolomite reservoirs using multi-component seismic data was investigated. A comprehensive analysis of the elastic waves by forward modeling shows that the PS-wave amplitude is more sensitive to medium-porosity dolomite than the PP-wave amplitude. Therefore, medium-porosity dolomite reservoirs can be predicted using the amplitude attributes of the PS-wave, and high-porosity dolomite reservoirs can be characterized using the PP-wave. Meanwhile, the elastic parameter λρ (the product of Lame constant λ and density ρ), which is highly correlated with the dolomite content, can be used as an indicator of dolomite formations. Furthermore, compared to the results of PP-wave inversion, the elastic parameters derived from the joint inversion of PP- and PS-waves exhibited a better correspondence with the well-logging results. The comprehensive use of the seismic amplitude responses of PP- and PS-waves and multi-component seismic joint inversion can effectively predict high- and medium-porosity dolomite reservoirs. The predicted results can support the exploration and development of the Qixia Formation.
SPC manufacturing and stockpiling waiver—part 1
Authors: Stief Marco 
Published: June 2024

Abstract
This two-part article analyzes and discusses the legal requirements of, as well as the opportunities and risks associated with the SPC Manufacturing and Stockpiling Waiver as introduced by EU Regulation 2019/933. The introduction of the SPC Manufacturing/Stockpiling Waiver on July 1, 2019 opened up opportunities for generics and biosimilars companies established in the EU to manufacture and stockpile medicinal products before expiry of the respective SPC, either for export to third countries or for timely Day-1 market entry in the EU. But unlike, for example, the bolar exemption, application of the SPC Waiver is dependent upon compliance with specific notification, due diligence and labeling obligations. Although introduced more than four years ago, there is still considerable legal uncertainty surrounding the application of the SPC Waiver, something recent court decisions in Germany and The Netherlands have exacerbated rather than clarified. In this first part, the policy background of the Regulation is explained and the territorial and temporal scope of the SPC Waiver is examined. In the second part of the article, to be published in the next edition of the Journal of Intellectual Property Law and Practice Vol.(…) Issue (…) I will take a close look at the material scope and core components of the waiver, particularly as it relates to privileged acts and the conditions under which the waiver is applicable
Metabolic Dysregulation and Cancer Risk Program (MeDOC): a transdisciplinary approach to obesity-associated cancers
Authors: Lam Tram Kim , Daschner Phil , Ishibe Naoko , Wali Anil , Hall Kara , Czajkowski Susan , Mahabir Somdat , Watson Joanna M , Nebeling Linda , Ross Sharon , Sauter Edward 
Published: June 2024

Abstract
With the escalating prevalence of obesity, the association between obesity and cancer is a growing public health concern. Obesity will soon surpass tobacco smoking as the most important preventable cause of cancer. Obesity-driven mechanisms can alter cell functions to induce metabolic changes, chronic inflammation, and insulin resistance that are believed to contribute to cancer risk and development; yet the specific underlying biological mechanisms of obesity-related cancer development are largely unknown. The Metabolic Dysregulation and Cancer Risk Program: a transdisciplinary approach to obesity-associated cancers (MeDOC) is a trans–National Cancer Institute research initiative supported by the Division of Cancer Control and Population Sciences, the Division of Cancer Biology, the Division of Cancer Prevention, and the Center to Reduce Cancer Health Disparities. The overall purpose of the MeDOC Program is to advance our understanding of the underlying mechanisms that connect obesity, metabolic dysregulation, and increased obesity cancer risk as well as identify markers that will enhance cancer risk prediction, improve screening for high-risk individuals, and identify targets for preventive and therapeutic interventions for cancer interception or treatment. This report describes the funded research projects, the Coordinating Center, and the goals of the MeDOC program.
Body image and psychosocial outcomes in youth and young adults with differences of sex development: a multi-method study
Authors: Crerand Canice E , Shehata Ayah , Umbaugh Hailey , Kapa Hillary M , Hansen-Moore Jennifer , Nahata Leena , Buchanan Cindy , Chen Diane , Rausch Joseph , Udaipuria Shivika , Jayanthi Venkata R , Chan Yee-Ming , Pratt Keeley J , Buschur Elizabeth , Indyk Justin , Tishelman Amy C 
Published: June 2024

Abstract

Objective
Differences of sex development (DSD) can affect the physical health, appearance, and psychosocial functioning of affected individuals, but little is known about how subjective appearance perceptions (body image) impact psychosocial outcomes. This study evaluated body image and its associations with psychosocial outcomes including quality of life, resilience, and psychosocial adjustment.

Methods
This cross-sectional, multi-method study assessed body image and psychosocial outcomes including quality of life, adjustment, and resilience in 97 youth and young adults with DSD (mean age = 17 ± 3.7 years; 56% assigned female in infancy) using psychometrically sound instruments. A subsample (n = 40) completed qualitative interviews.

Results
Quantitative results indicated that overall, participants were satisfied with their physical appearance, although less so with their primary sex characteristics. Body image dissatisfaction was associated with poorer psychosocial adjustment, quality of life, and resilience. Qualitatively, youth and young adults reported a variety of perceptions, both positive and negative, related to their body image and the impact of living with a DSD condition. Themes identified included appearance management; effects of DSD on body image; diagnostic factors and features; attitudes about diagnosis; and treatment.

Conclusions
Body image is significantly associated with psychosocial outcomes in youth and young adults with DSD, with qualitative findings highlighting both positive and negative body image experiences. Results have implications for clinical care including screening for appearance concerns, normalization of appearance variations, and intervention development to better support healthy body image and psychosocial functioning in youth and young adults with DSD.
Diagnosis of Coccidioidomycosis with the Second-Generation Miravista IgG and IgM Enzyme Immunoassay and the Role of Adding Miravista Coccidioides Antigen Detection to Immunodiagnostic Assays
Authors: Kassis Christelle , Eric Holbrook , Nicolas Barros , John Witt , Christopher Dailey , Cody Banks , Kendra Carlson , Shanna Noveroske , Mary Murlow , Joseph Wheat L 
Published: June 2024

Abstract
In the present study, we validate and compare the second-generation Miravista Coccidioides IgG and IgM enzyme immunoassays (EIA) (MiraVista Diagnostics [MVD] Ab EIA) to Meridian Diagnostics Coccidioides IgG and IgM EIA (Meridian Ab EIA), immunodiffusion (ID) and complement fixation (CF). We also evaluated whether the addition of Coccidioides antigen testing to anti-Coccidioides antibody testing increased the sensitivity for the diagnosis of currently active coccidioidomycosis. We retrospectively studied 555 patients evaluated at Valleywise Health Medical Center between January 2013 and May 2017 for whom coccidioidomycosis was suspected and samples were submitted to MVD for testing. Specimens were tested for antigen in the MVD antigen enzyme immunoassay (MVD Ag EIA) and for IgG and IgM antibodies with MVD and Meridian Diagnostics EIAs. ID and CF were obtained from medical records. Sensitivity and specificity were 83.0% and 91.1% or MVD Ab EIA, 69.3% and 99.7% for Meridian Ab EIA, 85.4% and 100% for ID and 65.5% and 100% for CF. Combined MVD antigen and antibody detection by EIA and ID resulted in increased sensitivity in disseminated and pulmonary disease (MVD Ag/MVD Ab: 100%, 88.3%; MVD Ag/Meridian Ab: 98.2%, 78.6%; and MVD Ag/ID: 100%, 91.7%). The detection of antibodies by MVD EIA was more sensitive than Meridian EIA or CF but similar to ID. This study supports the use of antigen testing in immunocompromised patients and those with suspected disseminated disease. Furthermore, the addition of antigen detection by EIA to antibody detection resulted in higher sensitivity of all serological tests.
A strong blend in the morning: studying the circumgalactic medium before cosmic noon with strong, blended Ly α forest systems
Authors: Morrison Sean , Som Debopam , Pieri Matthew M , Pérez-Ràfols Ignasi , Blomqvist Michael 
Published: June 2024

ABSTRACT
We study of the properties of a new class of circumgalactic medium absorbers identified in the Ly α forest: ‘Strong, Blended Lyman-α’ (or SBLA) absorption systems. We study SBLAs at 2.4 &lt; z &lt; 3.1 in SDSS-IV/eBOSS spectra by their strong extended Ly α absorption complexes covering 138 $\, \, {\rm km}\, {\rm s}^{-1}$ with an integrated $\log (N_{\rm H\, {\small I}}/\mathrm{cm}^{-2}) =16.04$$\substack{+0.05 \\ -0.06}$ and Doppler parameter b = 18.1$\substack{+0.7 \\ -0.4}$$\, \, {\rm km}\, {\rm s}^{-1}$. Clustering with the Ly α forest provides a large-scale structure bias of b = 2.34 ± 0.06 and halo mass estimate of $M_h \approx 10^{12}\, h^{-1}\, {\rm M_{\odot }}$ for our SBLA sample. We measure the ensemble mean column densities of 22 metal features in the SBLA composite spectrum and find that no single-population multiphase model for them is viable. We therefore explore the underlying SBLA population by forward modelling the SBLA absorption distribution. Based on covariance measurements and favoured populations we find that ≈25 per cent of our SBLAs have stronger metals. Using silicon only we find that our strong metal SBLAs trace gas with a log (nH/cm−3) &gt; −2.40 for T = 103.5 K and show gas clumping on &lt;210 parsec scales. We fit multiphase models to this strong subpopulation and find a low ionization phase with nH = 1 cm−3, T = 103.5 K, and [X/H] = 0.8, an intermediate ionization phase with log (nH/cm−3) = −3.05, T = 103.5 K and [X/H] = −0.8, and a poorly constrained higher ionization phase. We find that the low ionization phase favours cold, dense super-solar metallicity gas with a clumping scale of just 0.009 parsecs.
Unveiling the 3D structure of magnetosheath jets
Authors: Fatemi S , Hamrin M , Krämer E , Gunell H , Nordin G , Karlsson T , Goncharov O 
Published: June 2024

ABSTRACTMagnetosheath jets represent localized enhancements in dynamic pressure observed within the magnetosheath. These energetic entities, carrying excess energy and momentum, can impact the magnetopause and disrupt the magnetosphere. Therefore, they play a vital role in coupling the solar wind and terrestrial magnetosphere. However, our understanding of the morphology and formation of these complex, transient events remains incomplete over two decades after their initial observation. Previous studies have relied on oversimplified assumptions, considering jets as elongated cylinders with dimensions ranging from $0.1\, R_{\rm E}$ to $5\, R_{\rm E}$ (Earth radii). In this study, we present simulation results obtained from Amitis, a high-performance hybrid-kinetic plasma framework (particle ions and fluid electrons) running in parallel on graphics processing units (GPUs) for fast and more environmentally friendly computation compared to CPU-based models. Considering realistic scales, we present the first global, three-dimensional (3D in both configuration and velocity spaces) hybrid-kinetic simulation results of the interaction between solar wind plasma and the Earth. Our high-resolution kinetic simulations reveal the 3D structure of magnetosheath jets, showing that jets are far from being simple cylinders. Instead, they exhibit intricate and highly interconnected structures with dynamic 3D characteristics. As they move through the magnetosheath, they wrinkle, fold, merge, and split in complex ways before a subset reaches the magnetopause.
Orbital evolution of LIGO/Virgo binaries in stellar clusters driven by cluster tides, stellar encounters, and general relativity
Authors: Rasskazov Alexander , Rafikov Roman R 
Published: June 2024

ABSTRACT
Origin of LIGO/Virgo gravitational wave events may involve production of binaries with relativistic components in dense stellar systems – globular or nuclear star clusters – and their subsequent evolution towards merger. Orbital parameters of these binaries (the inner orbit) and their motion inside the cluster (the outer orbit) evolve due to both external agents – random encounters with cluster stars and cluster tides due to the smooth cluster potential – and the internal ones – various sources of dissipation and precession within the binary. We present a numerical framework – binary evolution in stellar clusters (besc) – that follows the evolution of the binary inner and outer orbits accounting for all these effects simultaneously, enabling efficient Monte Carlo studies. The secular effect of cluster tides is computed in the singly averaged approximation, without averaging over the outer binary orbit. As to stellar encounters, we include the effects of both close and distant flybys on the inner and outer orbits of the binary, respectively. Also, given our focus on the LIGO/Virgo sources, we include the general relativistic precession (which suppresses cluster tides at high eccentricities) and the gravitational wave emission (shrinking the binary orbit). We use besc to illustrate a number of characteristic binary evolutionary outcomes and discuss relative contributions of different physical processes. In particular, we find that stellar encounters often dominate over the cluster tides in the evolution of compact binaries. besc can also be used to study other objects in clusters, e.g. blue stragglers, hot Jupiters, X-ray binaries, etc.