bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing diagnostic strategies for central adrenal insufficiency in pituitary disease
Authors: Haberbosch Linus , Meyer Nina M T , Lechner Lara , Jensen Marie , Soll Dominik , Kozarzewski Leonard , Hesse Linus , Blankenstein Oliver , Hubertus Vanessa , Vajkoczy Peter , Strasburger Christian J , Spranger Joachim , Maurer Lukas , Mai Knut 
Published: February 2025

Abstract

Objective
Central adrenal insufficiency (CAI) affects a significant number of patients with pituitary disease, and a missed diagnosis can be fatal. The optimal diagnostic algorithm, however, is still controversial. Here, we present a single-centre study with the systematic use of the overnight metyrapone test (OMT) and the short synacthen test (SST) in a large cohort of patients with pituitary disease.

Methods
We conducted a retrospective analysis of 161 patients with pituitary disease or after pituitary surgery and suspected CAI. Data from OMT (n = 134), SST (n = 156), and long-term clinical outcomes (n = 97) were evaluated.

Results
Validated in the sub-cohort with available clinical outcome evaluation after a mean of 2.7 years, 11-desoxycortisol (11-DOF, cut-off &gt;200 nmol/L) in the OMT achieved a sensitivity of 100% and a specificity of 94%. Adrenocorticotropic hormone measurement offered no additional diagnostic benefit. Cortisol in the SST (cut-off &gt;450 nmol/L after 30 min) showed an inferior sensitivity of 75.0% and a specificity of 80.2%. To assess the usefulness of the tests in pre-classified risk groups according to the recently proposed CAI-Score, we calculated CAI subgroup prevalence as well as positive/negative predictive value (NPV) for the SST in each risk group. In the low-risk group (CAI-Score = 0), the SST achieved a high NPV (0.99), while showing no clear benefit in the other groups.

Conclusions
This study reaffirms the value of 11-DOF in the OMT as a reliable diagnostic tool for CAI, while confirming the limitations of the SST. These data indicate to consider SST as a single test procedure for low-risk patients.
Chemical pollution drives taxonomic and functional shifts in marine sediment microbiome, influencing benthic metazoans
Authors: Xu Lin-Lin , McIlroy Shelby E , Ni Yueqiong , Guibert Isis , Chen Jiarui , Rocha Ulisses , Baker David M , Panagiotou Gianni 
Published: February 2025

Abstract
Microbial communities in marine sediments contribute significantly to the overall health and resiliency of marine ecosystems. However, increased human disturbance undermines biodiversity and, hence, natural functionality provided by marine sediments. Here, through a deep shotgun metagenomics sequencing of the sediment microbiome and COI metabarcoding of benthic metazoans, we demonstrate that &gt;50% of the microorganisms’ and metazoan’s taxonomic variation can be explained by specific chemical pollution indices. Interestingly, there was a significant correlation between the similarity in microbiome communities’ taxonomical and functional attributes and the similarity of benthic metazoans community composition. Furthermore, mediation analysis was conducted to evaluate the microbiome-mediated indirect effect, suggesting that microbial species and functions accounted for 36% and 26%, respectively, of the total effect of pollution on the benthic metazoans. Our study introduces a multi-level perspective for future studies in urbanized coastal areas to explore marine ecosystems, revealing the impact of pollution stress on microbiome communities and their critical biogeochemical functions, which in turn may influence macrofaunal composition.
Do trial benefits predict real-world gains in metastatic castration resistant prostate cancer
Authors: Axeen Sarah , Chen Alice J , Lakdawalla Darius N , Masia Neal , Niyazov Alexander , Arondekar Bhakti , Freedland Stephen J 
Published: February 2025

Abstract

Background
It is important to understand the relationship between drug efficacy measured in randomized clinical trials (RCTs) and real-world drug effectiveness. We estimate how RCT overall survival (OS) and RCT radiographic progression-free survival (rPFS) benefits predict the association between treatments and real-world OS gains for metastatic castration-resistant prostate cancer (mCRPC) drugs.

Methods
Using the National Cancer Institute list of approved cancer drugs and the National Comprehensive Cancer Network Treatment Guidelines, we identified all pharmaceutical therapies for mCRPC approved between 2010 to 2019. We obtained RCT OS and rPFS hazard ratios from the pivotal trials used for Food and Drug Administration (FDA) approval, and we estimated real-world OS hazard ratios using the Optum Clinformatics Extended DataMart Databases. We modeled real-world OS hazard ratios as a function of both RCT OS and RCT rPFS hazard ratios using Cox proportional hazard regressions, adjusted for year of diagnosis, age, race, and Elixhauser Comorbidity Index.

Results
When we did not account for non-random real-world selection of patients into receiving a newly approved therapy (ie, “treatment selection bias”), real-world OS gains were 15% lower than associated RCT OS and RCT rPFS benefits. However, after accounting for treatment selection bias in real-world settings, real-world OS gains were almost 28% greater than RCT OS and RCT rPFS benefits. Association between treatment and OS gains increased the longer a new therapy was on the market.

Conclusions
After adjusting for treatment selection bias, RCT OS and RCT rPFS estimates serve as useful, or even conservative, predictors of RW OS gains.
Uncovering the Effects of Array Mutual Coupling in 21-cm Experiments with the SKA-Low Radio Telescope
Authors: O’Hara Oscar S D , Gueuning Quentin , de Lera Acedo Eloy , Dulwich Fred , Cumner John , Anstey Dominic , Brown Anthony , Fialkov Anastasia , Dhandha Jiten , Faulkner Andrew , Liu Yuchen 
Published: February 2025

Abstract
We investigate the impact of Mutual Coupling (MC) between antennas on the time-delay power spectrum response of the core of the SKA-Low radio telescope. Using two in-house tools - FAST (a fast full-wave electromagnetic solver) and OSKAR (a GPU-accelerated radio telescope simulator) - we simulate station beams and compute visibilities for various station layouts (regular, sunflower, and random). Simulations are conducted in an Epoch of Reionisation subband between 120â&#x80;&#x93;150 MHz, with a fine spectral resolution of 100 kHz, enabling the investigation of longer delays. Our results show that MC effects significantly increase foreground leakage into longer delays, especially for regular station layouts. For 21-cm science, foreground spill-over into the 21-cm window extends beyond k∥ ∼ 2 h−1Mpc for all station layouts and across all k⊥ modes, completely obscuring the detection window. We find that attempting to remove the foreground contribution from the visibilities using an approximated beam model - either based on the average embedded element pattern or by interpolating the embedded element patterns from a coarse channel rate of 781 kHz - results in residuals around ∼1011 mK2h−3Mpc3. This is still 7 orders of magnitude brighter than the expected level of the EoR signal (∼104 mK2h−3Mpc3). We also find that station beam models with at least 4-5 significant digits in the far-field pattern and high spectral resolution are needed for effective foreground removal. Our research provides critical insights into the role of MC in SKA-Low experiments and highlights the computational challenges of fully integrating array patterns that account for MC effects into processing pipelines.
Access to kidney transplantation and re-transplantation from childhood to adulthood: long-term data from the ERA Registry
Authors: Preka Evgenia , Bonthuis Marjolein , Marks Stephen D , Kramer Anneke , de Vries Aiko P J , Sørensen Søren S , Bakkaloğlu Sevcan A , Bistrup Claus , Jahnukainen Timo , Arévalo Olga L Rodriguez , Buchwinkler Lukas , Segelmark Mårten , Sanchez J Emilio , Arnol Miha , Ordóñez-Álvarez Flor A , de la Cerda-Ojeda Francisco , Plumb Lucy A , Methven Shona , Palsson Runolfur , Lundgren Torbjörn , Ríos Héctor , Ortiz Alberto , Stel Vianda S , Harambat Jerome , Jager Kitty J 
Published: February 2025

Abstract

Background and hypothesis
Knowledge regarding access to first kidney transplantation (KT) and subsequent KT in patients commencing kidney replacement therapy (KRT) in childhood is limited.

Methods
Using European Renal Association (ERA) Registry data, we investigated European patients who started KRT below 20 years of age between 1978 and 2019. Access and determinants to first, second and third KT were assessed using multivariable Cox regression.

Results
12 623, 4077, and 1186 patients were included while awaiting first, second and third KT, at median ages of 13.8 (IQR: 7.5–17.4), 20.9 (IQR: 16.5–26.1) and 26.6 (IQR: 20.3–32.8) years, respectively. During the study period, overall access was 87.8%, 72.7% and 60.5% for first, second and third KT, respectively, and median time to each KT was 0.9 (IQR: 0.2–2.1), 1.9 (0.6–4.5) and 2.6 (IQR: 1.0–5.3) years. Younger age at KRT initiation (aHR 0-4 vs. 10–14 years: 0.54; 95%CI: 0.51–0.57) and female sex (HR: 0.94; 95%CI: 0.90–0.98) were associated with lower access to first KT. KT candidates between 15–19 years had lower access to first and second KT (aHR: 0.69; 95%CI: 0.66–0.73, and aHR: 0.70; 95%CI: 0.61–0.81) compared to 10–14 year-olds. Compared to CAKUT, glomerulonephritis patients had lower access to KT (aHR: 0.75; 95%CI: 0.71–0.80 for first, aHR: 0.89; 95%CI: 0.81–0.98 for second and aHR: 0.80; 95%CI: 0.66–0.97 for third KT). Similarly, patients with primary renal diseases with high risk of recurrence, had lower chances of receiving a first and second KT (aHR: 0.80; 95%CI: 0.76–0.85 for first, aHR: 0.86; 95%CI: 0.78–0.95 for second KT). Access to re-transplantation was also higher with prior pre-emptive KT and previous graft survival exceeding five years.

Conclusion
Our study highlights KT access disparities particularly for females, the youngest recipients, high-risk age (15–19 years), and diseases with recurrence risk. Notably, pre-emptive transplants and enduring previous grafts offer advantages regarding re-transplantation.
Generating electron density archives using mainland EISCAT data between 2001-2021 at 10 minute and 1 hour integration
Authors: Reidy Jade A , Kavanagh A J , Häggström I , Themens D R , Wild M 
Published: February 2025

Abstract
The mesosphere/lower-thermosphere/ionosphere (MLTI) region is a critical boundary in the coupling of the atmosphere, climate and space weather, however it is one of the least understood regions, making it hard to include in whole atmosphere models. The EISCAT radars at Tromsø, Norway (UHF and VHF) have been measuring ionospheric parameters, such as electron density, since 1985 making it an excellent resource to study changes in the ionosphere over a long time period. This paper details how we have combined high elevation data from both radars between 2001-2021, re-integrated at 10 minutes and 1 hour, to look at the different sources of variability in the MLTI region between 50-200 km. Day of year climatology’s of the electron density highlight that the VHF data are more prone to contamination from Polar Mesospheric summer Echos. The magnetic local time variation of the electron density shows seasonal and altitude dependence related to solar UV illumination and electron precipitation, as expected. We compare our archives to the Empirical Canadian High Arctic Ionospheric Model (E-CHAIM) and find the biggest differences during the winter months and below 100 km, where the model does not yet include the impact of high energy electron precipitation.
Enrichment of spermatogonial stem cells and staging of the testis cycle in a dasyurid marsupial, the fat-tailed dunnart
Authors: Tarulli Gerard A , Tatt Patrick R S , Howlett Rhys , Ord Sara , Frankenberg Stephen R , Pask Andrew J 
Published: February 2025

Abstract
There is increasing interest in use of marsupial models in research, for use in next-generation conservation by improving fitness through genetic modification, and in de-extinction efforts. Specifically this includes dasyurid marsupials such as the Thylacine, Tasmanian devil, quolls and the small rodent-like dunnarts. Technologies for generating genetically modified Australian marsupials remains to be established. Given the need to advance research in this space, the fat-tailed dunnart (Sminthopsis crassicaudata) is being established as a model for marsupial spermatogonial stem cell isolation, modification and testicular transplantation. This species is small (60-90mm body size), polyovulatory (8-12 pups per birth), and can breed in standard rodent facilities when housed in a 12:12 light cycle. To develop the fat tailed dunnart as a model for next-generation marsupial conservation, this study aimed to enrich dunnart spermatogonial stem cells from whole testis digestions using a fluorescent dye technology and fluorescence-activated cell sorting. This approach is not dependent on antibodies or genetic reporter animals that are limiting factors when performing cell sorting on species separated from human and mouse by large evolutionary timescales. This study also assessed development of spermatogonia and spermatogenesis in the fat-tailed dunnart, by making the first definition of the cycle of the seminiferous epithelium in any dasyurid. Overall, this is the first detailed study to assess the cycle of dasyurid spermatogenesis and provides a valuable method to enrich marsupial spermatogonial stem cells for cellular, functional and molecular analysis.
The Correlation Analysis of Factors Affecting the Effective Optical Zone After SMILE
Authors: Wang Li , Xu Yue , Lou Jing , Wang Yun , Zhang Xiaofeng 
Published: February 2025

Objectives:
The purpose of this study was to analyze the size of the effective optical zone (EOZ) and its related influencing factors in small incision lenticule extraction.

Methods:
Calculation of the horizontal EOZ (Y1: H-EOZ), vertical EOZ (Y2: V-EOZ), and average EOZ (Y3: A-EOZ) using corneal topographic difference maps. Multivariate linear regression analysis was used to establish a multivariate linear equation for the dependent variable EOZ. Receiver operating characteristic (ROC) curves were constructed based on the experimental cohort and were validated in the validation cohort.

Results:
The EOZ was smaller than the programmed optical zone (POZ) (p<0.001), and the spherical (Sp) and astigmatism (As) were positively correlated with H-EOZ (pSp<0.001, pAs<0.001), whereas average K-value (Km) and horizontal corneal diameter (WTW) were negatively correlated with H-EOZ (pKm<0.001, pWTW<0.002). The corresponding multivariate linear regression equation was Y1=5.246+0.168X1−0.278X2+0.027X3−0.131X4. Spherical, As, the asphericity of cornea (Q-value), and POZ were positively correlated with V-EOZ (pAs<0.000, pQ<0.001, and pPOZ<0.05, respectively) and Y2=3.032+0.102X1+0.175X2+0.642X5+0.415X6. Spherical, astigmatism, and POZ were positively correlated with A-EOZ (pSp<0.000, pAs<0.05, pPOZ<0.05, respectively), whereas WTW was negatively correlated with A-EOZ (pWTW<0.004) as follows: Y3=4.384+0.132X1+0.023X3−0.117X4+0.294X6. The H-EOZ model had the largest area under the ROC curve, 0.853 (95% confidence interval: 0.807–0.767).

Conclusions:
The preoperative intended correction of spherical lesions may be the main factor affecting the size of the postoperative EOZ, and this study has strong predictability for the horizontal EOZ.
Correlation Between Different Shapes of Major Papilla With Outcomes of Endoscopic Retrograde Cholangiopancreatography in a Prospective Study
Authors: Fahimi Amirhossein , Langari Alale , Roshandel Gholamreza , Hasani Fatemeh , Kherad Mohammad Ebrahim , Aghaei Fatemeh , Norouzi Alireza 
Published: February 2025

Introduction:
Several factors affect the difficulty, clinical success, and side effects related to endoscopic retrograde cholangiopancreatography (ERCP), of which the endoscopic appearance of the major papilla is one of the most important. This study aimed to investigate the outcomes related to ERCP in relation to major papilla morphology.

Methods:
This study was performed prospectively on 581 patients undergoing ERCP. During ERCP, the endoscopist determined the morphology of the major papilla before the cannulation. Primary outcomes included overall operative success rate and post-ERCP pancreatitis (PEP) at 30 days. Secondary outcomes included clinically significant bleeding, perforation, cholangitis or sepsis, difficult cannulation, number of cannulation attempts, and duration of cannulation.

Results:
Papilla type 2 (OR=2.36, 95% CI: 1.07-5.20) and type 3b (OR=3.19, 95% CI: 1.16-8.73) were associated with decreased odds of procedure success. PEP was directly associated with type 4 papilla (OR=3.30, 95% CI: 1.21-8.98). There were direct correlation between difficult cannulation and types 3a (OR=1.89, 95% CI: 1.20-2.98) and 3b (OR=5.05, 95% CI: 1.98-12.86), cannulation duration more than 10 minutes and types 2 (OR=2.66, 95% CI: 1.31-5.39), 3a (OR=2.18, 95% CI:1.30-3.64), and 3b (OR=4.97, 95% CI: 1.94-12.71), and attempted cannulation more than 5 times and types 3a (OR=1.64, 95% CI: 1.01-2.69), and 3b (OR=4.40, 95% CI: 1.75-11.09).

Conclusion:
The findings of this study showed that ERCP failure is associated with types 2 and 3b papilla, and papilla type 4 is an independent risk factor for PEP.
How do we increase deceased donor kidney utilization and reduce discard?
Authors: Ariyamuthu Venkatesh K. , Qannus Abd A. , Tanriover Bekir 
Published: February 2025

Purpose of review
This review aims to address the critical issue of expanding deceased donor kidney pool and reducing the discard rates of viable kidneys in the United States. It highlights advances in organ preservation techniques and explores strategies for expanding the donor pool by leveraging suboptimal and high-risk nonuse kidneys, including those affected by acute kidney injury (AKI), hepatitis C virus (HCV), and hepatitis B virus (HBV).

Recent findings
Innovations in organ preservation, including hypothermic and normothermic machine perfusion, have demonstrated efficacy in improving outcomes for marginal and extended-criteria kidneys. The integration of normothermic regional perfusion (NRP) for donation after cardiac death (DCD) donors has enhanced organ utilization and graft viability. Additionally, research confirms that kidneys from AKI and HCV-positive donors, when managed with appropriate protocols, yield comparable long-term outcomes to standard transplants. Emerging data on HBV-positive donor kidneys further underscore their potential to safely expand transplant access with targeted antiviral prophylaxis.

Summary
Optimizing deceased donor kidney utilization requires a multi-faceted approach, including advancements in preservation technologies, evidence-based decision-making for high-risk organs, and policy innovations. Leveraging these strategies can help address the growing organ shortage, enhance transplant outcomes, and ensure broader access to life-saving kidney transplants.
Assessing the Readability, Quality, and Characteristics of Online Patient Educational Materials Pertaining to Gender-Affirming Surgery
Authors: Bajaj Anitesh , Sylla Fatoumata , Sriram Nikhil , Soltani Hannah , Marzouk Sammer , Sparks Payton J. , Uryga Abigail , Sebree Becca , Li Rena A. , Galiano Robert D. 
Published: February 2025

Background
Patients access online resources for information about various treatment modalities, including gender-affirming surgery (GAS) patient populations. The present study provides a readability, content quality, technical quality, and qualitative characteristic assessment of online patient educational materials (OPEM) related to GAS.

Methods
An online search using search phrases related to GAS was performed. The first 20 unique search results for each search term were further assessed if identified as an OPEM. The readability, content quality, and technical quality were assessed. Characteristics including mention of World Professional Association for Transgender Health (WPATH) guidelines and discussion of insurance coverage were recorded. Statistical analyses included analysis of variance, chi-squared tests, and 2-sample t tests.

Results
Overall, 231 OPEM were identified (academic/hospital: 124, private practice: 47, online health reference: 43, other: 17). The average consensus grade level was 12.7, which was significantly higher than the National Institutes of Health/American Medical Association–recommended sixth-grade level (P < 0.001). With regard to content quality, academic/hospital websites had a significantly higher DISCERN score than private practice websites (P = 0.01). Notably, only 35% of OPEM mentioned WPATH guidelines. Academic/hospital websites mentioned WPATH guidelines at a significantly higher frequency than nonacademic/hospital websites (P < 0.001). Private practice websites had a significantly higher technical quality score than academic/hospital websites (P < 0.001).

Conclusions
A significant discrepancy in readability was identified between analyzed websites and the National Institutes of Health/American Medical Association recommendation of a sixth-grade level. Further efforts are necessary to ensure accessible and accurate information is available for patients seeking OPEM related to GAS.
Manifesto: challenging the standard cosmological model
Authors: Binney James , Mohayaee Roya , Peacock John , Sarkar Subir 
Published: February 2025

We outline the rationale for holding a Discussion Meeting thus titled at the Royal Society, London during 15 and 16 April 2024, and summarize what we learnt there.
This article is part of the discussion meeting issue ‘Challenging the standard cosmological model’.
Development of a BiAD sensor for locus-specific detection of cellular histone acetylation dynamics by fluorescence microscopy
Authors: Köhler Anja R. , Gutekunst Nicole , Harsch Annika , Bashtrykov Pavel , Jeltsch Albert 
Published: February 2025

SummaryDynamic changes in histone acetylation play crucial roles during cellular differentiation and disease development. Here, we developed a Bimolecular Anchor Detector (BiAD) sensor for the detection of locus-specific changes in histone acetylation in living cells by fluorescence microscopy. For this, we used the BRD9 bromodomain cloned as tandem double-domain (2xBRD9-BD) as reader of histone acetylation. It was integrated it into a dual-color BiAD chassis that was previously described [Köhler et al., 2024, Cell Rep Methods 4(4):100739]. We identified the gene body of TTC34 as potential target for our sensor, because it contains dense histone acetylation and 392 local sequence repeats. Using a binding deficient mutant of 2xBRD9-BD as negative control, we established successful readout of histone acetylation at the TTC34 locus. A single domain reader did not function indicating the requirement for the double reader to enhance affinity and specificity of the chromatin interaction via avidity effects. With this sensor, we could detect dynamic changes of histone acetylation at the TTC34 locus after treatment of cells with the histone deacetylase inhibitor Trichostatin A for 6 hours indicating the applicability of this sensor for single-cell epigenome studies.