bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and evaluation of an ovarian hormone profile classification tool for female athletes: step one of a two-step process to determine ovarian hormone profiles
Authors: Elliott-Sale Kirsty J , Birdsey Laurence P , Burden Richard J , Cable Nigel T , Clausen Emma , D'Souza Alysha C , Dos’Santos Thomas , Field Adam , Flood Tessa R , Harris Rachel , McCall Alan , McNulty Kelly L , Ní Chéilleachair Niamh , O'Catháin Ciaran , Phillips Stuart M , Sherwin Glenn , Stebbings Georgina K , Taim Bernadette C , Van Every Derrick W , Więckowska Joanna , Minahan Clare 
Published: December 2024

ObjectiveThis study aimed to develop a reliable, comprehensive and fit-for-purpose tool for classifying ovarian hormone profiles (OHPs) (step one of a two-step process) in postmenarcheal to perimenopausal female athletes.MethodsThe OHP classification tool was designed by a team of sport scientists, practitioners and medics and is intended for use by sport practitioners. It incorporates self-reported data and guides subsequent verification methods. Written feedback was received from practitioners currently working with elite female athletes (n=5), ensuring its applicability in an applied sport setting. In addition, inter-user (n=2) and intra-user (n=30) repeatability was assessed.ResultsAll practitioners agreed that the online tool was user-friendly. Four (out of five) practitioners stated they would include the tool in their practice, with the fifth stating that they did not have the capacity to incorporate it in their practice at present. The OHP classification tool showed excellent test–retest reliability with Cronbach’s alpha values exceeding 0.9.ConclusionThis tool facilitates the classification of OHPs and promotes discussions between athletes and practitioners, enhancing understanding and management of ovarian hormone health in sportswomen.
Age-stratified comparison of heart age and predicted cardiovascular risk in 370 000 primary care patients
Authors: Stjernholm Kathrine , Kerr Andrew , Poppe Katrina K , Jensen Anders Elkær , Mehta Suneela , Nielsen Jesper Bo , Jackson Rod , Wells Susan 
Published: December 2024

BackgroundCardiovascular disease (CVD) preventive medications are recommended for patients at high short-term CVD risk. As most younger people with multiple raised CVD risk factors levels have low short-term risk, they could be falsely reassured to take no action. Heart age—the chronological age of a hypothetical person with the same short-term absolute CVD risk as the patient being assessed, but with an ‘ideal’ risk profile—is a complementary relative CVD risk metric developed to encourage these younger patients to make long-term lifestyle changes. However, clinicians sometimes use heart age to inform medication decisions. We assessed the appropriateness of this practice by comparing heart age and short-term CVD risk.MethodsNew Zealand primary care patients are recruited to the PREDICT cohort when their CVD risk is assessed. PREDICT is an ongoing prospective study in one-third of New Zealand general practices, designed to derive CVD risk prediction algorithms. Five-year CVD risk was calculated for 35–74-year-old PREDICT participants using published equations. Heart age was calculated using non-smoking, systolic blood pressure of 120 mm Hg and total cholesterol/high-density lipoprotein ratio of 3.5, as the ‘ideal’ risk profile. CVD risk and heart age gaps (difference between chronological age and heart age) were compared.ResultsAmong 371 676 PREDICT participants, 5-year CVD risk increased with age, approximately doubling every 10 years, whereas heart age gaps decreased with increasing age, approximately halving between 35 and 44-year olds and 65–74-year olds. There were 5–40-year heart age gap differences between groups with similar 5-year CVD risks, but different ages.ConclusionShort-term CVD risk and heart age are not interchangeable risk metrics. Short-term risk increases with increasing age whereas heart age gaps generally decline, with major differences between younger and older people with similar short-term risk. If heart age is used to inform medication decisions rather than encourage long-term lifestyle changes, older people at high short-term risk could be undertreated and younger people at low short-term risk could be unnecessarily medicated.
Contribution of rare chromosome 22q11.2 copy number variants to non-syndromic bicuspid aortic valve
Authors: DiGregorio Helene , Mansoorshahi Sara , Carlisle Steven G , Tovar Pensa Catherina , Watts Abi , McNeely Courtney , Sabate-Rotes Anna , Yetman Anji , Michelena Hector I , De Backer Julie F A , Mosquera Laura Muiño , Bissell Malenka M , Andreassi Maria Grazia , Foffa Ilenia , Hui Dawn S , Caffarelli Anthony , Kim Yuli Y , Citro Rodolfo , De Marco Margot , Tretter Justin T , McBride Kim L , Body Simon C , Milewicz Dianna M , Prakash Siddharth K 
Published: December 2024

BackgroundBicuspid aortic valve (BAV) is the most common congenital heart defect in adults, often leading to complications such as thoracic aortic aneurysms and aortic stenosis. While BAV is frequently associated with 22q11.2 deletion syndrome (22q11.2DS), the contribution of rare copy number variants (CNVs) in this region to non-syndromic BAV is less clear. This study is aimed to assess the role of rare 22q11.2 CNVs in patients with early-onset BAV (EBAV) and to determine whether these variants are linked to an increased risk of complications.MethodsWhole genome microarray genotyping was conducted on 272 patients with BAV with early onset valve or aortic disease (EBAV) and 272 biological relatives. CNVs were detected using three independent algorithms, focusing on the 22q11.2 region (18–24 Mb). CNV burden in the EBAV cohort was compared with unselected European ancestry controls.ResultsRare duplications and deletions within the 22q11.2 region, particularly involving genes associated with cardiac development, were identified in 7.4% of EBAV probands. These CNVs were significantly enriched compared with the general population and segregated with BAV in families. Individuals carrying rare 22q11.2 CNVs had a higher prevalence of psychiatric diagnoses and learning difficulties, although they did not exhibit the typical features of 22q11.2DS. Importantly, these CNVs were associated with early onset or complex BAV cases, underscoring their potential clinical relevance.ConclusionsRare 22q11.2 CNVs play a role in non-syndromic BAV, particularly in cases with early onset or complex presentations. CNV screening could be considered as part of risk stratification for patients with BAV, helping to predict complications and guide management.Trial registration numberNCT01823432.
CAR T cells secreting NGF-neutralizing scFv enhance efficacy in clear cell renal cell carcinoma by relieving immunosuppression through immunosympathectomy
Authors: Yang Peiwei , Chen Xi , Yu Fan , Wang Lan , Li Meng , Bai Zongke , Xu Hanmei 
Published: December 2024

BackgroundChimeric antigen receptor (CAR) T cells have demonstrated remarkable breakthroughs in treating hematologic malignancies, yet their efficacy in solid tumors is limited by the immunosuppressive microenvironment. Sympathetic nerves significantly contribute to this immunosuppressive milieu in solid tumors. However, the impact of tumor sympathetic denervation on enhancing CAR T-cell antitumor efficacy remains unclear.MethodsWe screened for sympathetic gene sets in various types of cancers and investigated the association of sympathetic nerves with immunosuppression in renal clear cell carcinoma. Using antibodies to block the nerve growth factor (NGF) pathway, we explored sympathetic nerve distribution in tumor tissues and tumor progression. Additionally, we engineered CAR T cells to secrete NGF single chain fragment variable (scFv) to achieve tumor immunosympathectomy and assessed their antitumor efficacy. Bulk RNA sequencing and single-cell RNA sequencing analyses were conducted to evaluate changes in immune cell phenotypes within the tumor microenvironment.ResultsBlocking the NGF pathway with antibodies effectively reduced sympathetic nerve distribution in tumor tissues and delayed tumor progression. CAR T cells engineered to secrete NGF scFv achieved a similar tumor immunosympathectomy and exhibited enhanced tumor suppression. RNA sequencing analyses revealed that this augmented effect was primarily due to the inhibition of the terminal exhaustion phenotype in tumor-infiltrating CD8 T cells and the prevention of macrophage polarization from M1 to M2. This approach maintained a stronger antitumor immune state at the tumor site. Additionally, splenic T cells also exhibited a more potent immune effector phenotype following the infusion of NGF scFv-secreting CAR T cells.ConclusionsOur results suggest that immunosympathectomy is a novel approach to weaken tumor microenvironment immunosuppression and synergistically enhance CAR T-cell efficacy against solid tumors.
Anomaly induced inflation in the minimal quartic extension of Einstein’s gravity
Authors: Demirel Kerim , Tekin Bayram 
Published: December 2024

Abstract
A particular extension of Einstein’s General Relativity up to and including quartic terms in the curvature tensor is minimal in the sense that it has a unique maximally symmetric vacuum and only a massless spin-2 excitation in its spectrum around the vacuum. We study the inflation phase of the universe in this minimal quartic extension of Einstein’s gravity in the presence of trace anomaly terms coming from the Standard Model fields and the fields of the Minimal Supersymmetric Standard Model. We show that the theory allows a quasi-de Sitter phase with sufficient e-foldings.
Variant of Uncertain Significance Patterns among Patients with Early-Onset Colorectal Cancer
Authors: Francis Rachel A. , Tavtigian Sean , Horton Carolyn , Holowatyj Andreana N. 
Published: December 2024

Abstract
The increasing burden of colorectal cancer among adults younger than age 50 years (early-onset colorectal cancer) and new National Comprehensive Cancer Network guidelines recommending universal genetic testing in early-onset colorectal cancer emphasize the need for accurate and timely variant classification in clinical care. In this study, we investigated germline variant of uncertain significance (VUS) patterns among diverse individuals with early-onset colorectal cancer. A total of 3,980 individuals ages 15 to 49 years when diagnosed with a first primary colorectal cancer, including 1,001 cases identifying as non-White, who underwent genetic testing for 14 colorectal cancer susceptibility genes performed by a clinical testing laboratory were included. A five-tier classification system was applied to all alterations to classify VUSs and was updated in March 2024. Disparities in variant reclassification rates emerged by self-identified race/ethnicity (P &lt; 0.0001). A total of 4.8% of Ashkenazi Jewish, 18.2% of Asian, 12.2% of Black, 7.6% of Hispanic, and 6.7% of White individuals had at least one reclassified VUS. After reclassification, 356 individuals (8.9%) presented with 1+ VUSs. VUSs significantly varied by self-identified race/ethnicity (P = 0.008). Young individuals identifying as Black and Hispanic had significantly higher odds of presenting with a VUS compared with those identifying as White in multivariable logistic regression models. Individuals who identified as Black and Asian were significantly more likely to present with a VUS in PMS2 (OR = 3.59; 95% confidence interval, 1.73–7.48; P = 0.0006) and MSH2 (OR = 3.14; 95% confidence interval, 1.17–8.45; P = 0.02), respectively, compared with those identifying as White. These findings define unique VUS patterns in early-onset colorectal cancer by race and ethnicity, pointing to distinct germline variant spectra and to the potential for the discovery of novel ancestry-specific variants associated with early-onset colorectal cancer that will guide efforts to reduce clinical uncertainty and improve equitable care.

Significance:
Among individuals with early-onset colorectal cancer, germline VUS reclassification as well as rates of VUSs in cancer susceptibility genes differed by self-identified race/ethnicity. These findings point to the importance of VUS reclassification as this may alter clinical management and to distinct germline variant spectra among diverse patients with early-onset colorectal cancer.
Elevated Donor-Derived Cell-Free DNA Levels Are Associated With Reduced Myocardial Blood Flow but Not Angiographic Cardiac Allograft Vasculopathy: The EVIDENT Study
Authors: Moeller Cathrine M. , Oren Daniel , Fernandez Valledor Andrea , Rubinstein Gal , DeFilippis Ersilia M. , Rahman Salwa , Mehlman Yonatan , Donald Elena M. , Lotan Dor , Lin Edward , Oh Kyung T. , Lee Sun H. , Raikhelkar Jayant K. , Fried Justin A. , Majure David , Latif Farhana , Sayer Gabriel T. , Uriel Nir , Clerkin Kevin J. 
Published: December 2024

BACKGROUND:
Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA.

METHODS:
A retrospective review was conducted on HT recipients at a high-volume center who underwent dd-cfDNA testing between September 2019 and November 2022. Inclusion criteria included undergoing CAV screening with cardiac positron emission tomography scans and coronary angiograms. Patients were grouped by the presence of angiographic CAV diagnosis and MBF reserve evaluated through cardiac positron emission tomography. The latter was subdivided into normal MBF or RMBF, with RMBF defined as an MBF reserve ≤2. Elevated dd-cfDNA was defined as ≥0.12%.

RESULTS:

Two hundred fifty-six HT recipients were included (median age, 55 years; 27.6% female; median, 8 years [interquartile range (IQR), 5–14] post-HT). Ischemic etiology of heart failure was more prevalent in the RMBF group (36%) compared with the normal MBF group (20%;
P
=0.02). The prevalence and magnitude of a positive dd-cfDNA test with angiographic CAV (29%; median, 0.26% [IQR, 0.15%–0.62%]) were not significantly different from those without CAV (30%;
P
=0.94; median, 0.31% [IQR, 0.17%–0.71%];
P
=0.38). However, RMBF patients exhibited significantly higher dd-cfDNA prevalence and levels (51%; median, 0.81% [IQR, 0.48%–1.11%]) compared with normal MBF patients (27%;
P
<0.001; median, 0.25% [IQR, 0.15%–0.52%];
P
<0.001).

CONCLUSIONS:
HT recipients with angiographic CAV had similar dd-cfDNA levels and rates as those without. Notably, dd-cfDNA levels and rates were significantly elevated in patients with RMBF assessed by positron emission tomography compared with those with normal MBF.
Electrophysiology Reveals That Intuitive Physics Guides Visual Tracking and Working Memory
Authors: Balaban Halely , Smith Kevin A. , Tenenbaum Joshua B. , Ullman Tomer D. 
Published: December 2024

Abstract
Starting in early infancy, our perception and predictions are rooted in strong expectations about the behavior of everyday objects. These intuitive physics expectations have been demonstrated in numerous behavioral experiments, showing that even pre-verbal infants are surprised when something impossible happens (e.g., when objects magically appear or disappear). However, it remains unclear whether and how physical expectations shape different aspects of moment-by-moment online visual scene processing, unrelated to explicit physical reasoning. In two EEG experiments, people watched short videos like those used in behavioral studies with adults and infants, and more recently in AI benchmarks. Objects moved on a stage, and were briefly hidden behind an occluder, with the scene either unfolding as expected, or violating object permanence (adding or removing an object). We measured the contralateral delay activity, an electrophysiological marker of online processing, to examine participants’ working memory (WM) representations, as well as their ability to continuously track the objects in the scene. We found that both types of object permanence violations disrupted tracking, even though violations involved perceptually non-salient events (magical vanishing) or new objects that weren’t previously tracked (magical creation). Physical violations caused WM to reset, i.e., to discard the original scene representation before it could recover and represent the updated number of items. Providing a physical explanation for the violations (a hole behind the occluder) restored object tracking, and we found evidence that WM continued to represent items that disappeared ‘down the hole’. Our results show how intuitive physical expectations shape online representations, and form the basis of dynamic object tracking.
“Voir cette merveille et la faire voir”
Authors: Ruellet Aurélien 
Published: December 2024

Abstract
This article examines the early circulations of the Drebbelian microscope between France and Italy in 1622–1624 and maps the material and personal links that connected these territories. It addresses the question of the value of those new microscopes for the learned community and the way they could serve as gifts as well as means of introduction or of gaining reputation. The microscope was seen as a curiosity likely to bestow credit on the person who “makes one see,” which explained the attempts to control information about it, until its value declined because of the difficulties to operate the device properly or the absence of persuasive scientific or philosophic uses.
A Celestial Prodigy
Authors: Dall’Aglio Stefano 
Published: December 2024

Abstract
On 16 June 1666 a rare celestial event occurred: a horizontal eclipse, also known as a selenelion, in which the Sun and Moon are aligned at 180 degrees on opposite sides of the Earth and are both briefly visible at the same time. The eyes of all Europe’s astronomers were gazing skywards on that day but adverse weather conditions prevented nearly everybody from observing the phenomenon. The only one who succeeded was the young mathematician Donato Rossetti, sent by Leopoldo de’ Medici to the isle of Gorgona in the Tuscan archipelago. Drawing on a new source, this article retraces the history of that observation and highlights the pivotal role Leopoldo played, initially as promoter of observations in different places and later as reference point of the subsequent debate.
On a Modified Definition of a Derecho. Part I: Construction of the Definition and Quantitative Criteria for Identifying Future Derechos over the Contiguous United States
Authors: Squitieri Brian Joseph , Wade Andrew R. , Jirak Israel L. 
Published: December 2024

Abstract
The definition of a derecho has been modified to require hurricane-force (33+ m s−1) gusts, a staple for destructive wind events in earlier derecho studies. The new proposed definition states that the derecho is a widespread severe windstorm characterized by a family of destructive downbursts containing hurricane-force gusts and is associated with an extratropical, cold-pool-driven mesoscale convective system. Derecho identification is performed with the use of an algorithm, rendering this study among the first to identify derechos objectively. Through sensitivity tests and qualitative analyses, we propose that the term derecho be used for thunderstorm wind swaths that have pathlengths of at least 400 km, with no more than 1-h or 200-km (temporal or spatial, respectively) gaps allowed between wind reports, with at least five reports of 33+ m s−1 wind gusts, separated by 80 km, required for derecho identification. To account for possible overestimation of wind speeds, at least three 33+ m s−1 thunderstorm wind gust reports, separated by 80 km, need to be measured.
The Influence of Tropical Cyclones on Mixed-Population Flood Frequency Analysis
Authors: Wang Liangyi , Gu Xihui , Slater Louise J. , Li Jianfeng , Lai Yangchen , Zhang Xiang , Dai Juan , Chen Ying 
Published: December 2024

Abstract
Floods induced by tropical cyclones (TCs) and their frequency analysis have received much attention at the regional scale, but little is known about the role of TCs in the mixed flood frequency analysis at the global scale, which is the key for hazard management. Here, we investigated the influence of TCs on the upper tail of flood frequency estimates using discharge observations at 3883 stations influenced by TCs alongside global discharge simulations from the second phase of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP2a). Our results show that TC-induced floods in inland areas are not always found along the TC path but can be located about 1000 km ahead, which is linked to TC-induced predecessor rain events. Extreme floods associated with TCs are generally larger in coastal areas compared to those in inland areas, whereas TC-induced floods in some inland areas tend to be more extreme relative to their local flood magnitude. The flood peaks generated by TCs and other mechanisms compose a mixed population flood series. However, the largest flood peaks in coastal areas are usually affected by TCs. These large TC-induced flood peaks play an important role in making the upper tail of the flood frequency curve heavier. In regions affected by TCs, the flood magnitude with an n-yr return period is greater when estimated from TC-induced floods only. Therefore, regions (especially inland regions) should thoroughly consider the extremity of TC-induced flooding when improving hydraulic infrastructures to ensure a more conservative design, thereby enhancing the safety of these hydraulic projects.

Significance Statement
Tropical cyclones (TCs) are responsible for extreme floods in coastal and inland areas influenced by TCs, which may play an important role in the flood frequency analysis and flood risk management. In this study, we investigated how TCs affect the upper tail of flood frequency estimates at the global scale. We find that extreme floods associated with TCs are generally higher in coastal areas, whereas TC-induced floods in some inland areas tend to be more extreme relative to their regional flood magnitude. These anomalously large TC-induced flood peaks control the upper tail of the flood frequency curve in coastal and inland areas and make the upper tail heavier. Globally, the flood magnitude once in n years is generally greater, estimated from only TC-induced flood peaks than that estimated from all flood peaks. Therefore, regions (especially inland regions) should thoroughly consider the extremity of TC-induced flooding when improving hydraulic infrastructures to ensure a more conservative design, thereby enhancing the safety of these hydraulic projects.